ARTICLE | doi:10.20944/preprints202309.0255.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: oral squamous cell carcinoma; prognosis; overall survival; disease free survival; connexin 43; EMMPRIN; E-cadherin; vimentin; metastasis; epithelial-to-mesenchymal transition
Online: 5 September 2023 (07:54:11 CEST)
Background: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations including changes caused by the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin and vimentin during the invasive metastatic process of OSCC and the possibility of using this system for prognosis prediction. Methods: The protein expression profiles of Cx43, EMMPRIN, E-cadherin and vimentin were investigated by immunohistochemistry in tissue samples from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROI) of adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). Disease-free survival (DFS) and overall survival (OS) were the primary clinical endpoints. Results: Significant changes in the expression profiles of the different marker proteins were detected between the different ROIs (all p values < 0.05). Multivariable Cox regression analysis revealed a significant effect of increased EMMPRIN expression towards IF on DFS (p = 0.019) and OS (p = 0.023). The combined predictive analysis showed a significant predictive value of the marker system for DFS (p = 0.0017) and OS (p = 0.00044). Conclusions: The combined marker system was able to significantly predict patient prognosis. An increase in EMMPRIN expression towards IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.
ARTICLE | doi:10.20944/preprints202309.1286.v1
Subject: Medicine And Pharmacology, Transplantation Keywords: Graft rejection; survival; mortality; chemotherapy
Online: 19 September 2023 (10:22:28 CEST)
Background: Systemic treatment options for hepatocellular carcinoma (HCC) after liver transplantation (LT) are limited in patients in whom sorafenib treatment was failed. The purpose of our study was to compare outcomes among sorafenib, regorafenib, and nivolumab treatment groups in patients with recurrent HCC after LT. Methods: This study retrospectively evaluated patients who received sorafenib for recurrent HCC treatment after LT at a single center from March 2007 to December 2018. Some patients received regorafenib or nivolumab after sorafenib treatment failure. Results: Fifty-six patients were treated with sorafenib due to HCC recurrence. Among these, 38 patients (67.9%) continued treatment with sorafenib only; the other 18 patients (32.1%) were converted to regorafenib treatment. Ten patients (17.9%) of these 18 were converted to nivolumab after sorafenib and regorafenib therapy failed. The disease-free survival and overall survival (OS) from LT were not different among the three groups. In addition, OS from HCC recurrence, sorafenib usage, and usage of each systemic therapeutic agent were not different among the three groups. Three cases in the nivolumab group developed acute rejection; one of these led to graft failure and death due to antibody-mediated rejection. Conclusion: Sequential regorafenib or nivolumab treatment in recurrent HCC LT patients does not improve OS compared sorafenib treatment.
ARTICLE | doi:10.20944/preprints202209.0242.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: pancreatic cancer (PC); abdominal ultrasonography (US); surveillance; prognosis; medical checkup; 5-year survival; cancer screening
Online: 16 September 2022 (08:08:33 CEST)
Recent advancements in surgical and anti-cancer therapies have provided significant hope of long survival in patients with pancreatic cancer (PC). To realize this hope, routine medical checkups of asymptomatic people should be performed to identify operable PCs. In this study, we evaluated the efficacy of medical checkups using abdominal ultrasonography (US). We retrospectively analyzed 374 patients with PC at our institute between 2010 and 2021. We divided these patients into several groups according to the diagnostic approach and compared their background and prognosis. These groups comprised PCs diagnosed through (a) symptoms, 242 cases; (b) US during medical checkup for asymptomatic individuals, 17; and other means. Of the 375 patients, 192 were men (51.3%), and the median age was 74 years (34–105). Tumors were located in the pancreatic tail in 67 patients (17.9%). Excision ratio and 5-year survival rate were significantly better in group (b) than in (a) (58.8% vs. 23.1%, P<0.01 and 42.2% vs. 9.4%, P<0.001, respectively). The prognosis of patients diagnosed using US during medical checkup was better than that of patients identified through symptomatic presentation of PC. US for asymptomatic individuals with PC might be useful for promoting better prognosis of PCs.
REVIEW | doi:10.20944/preprints202306.2252.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: nutritional assessment; oesophageal cancer; pharyngeal cancer; prognosis; survival; nutritional status; diagnosis; malnutrition; chemotherapy; radiotherapy
Online: 30 June 2023 (12:36:40 CEST)
Background: Malnutrition in oesophageal and pharyngeal cancer patients constitutes a common and serious concern, which significantly reduces patients’ prognosis. Cancers of the oesophagus and the pharynx can considerably impair feeding in patients, resulting in severe undernutrition. This is a scoping review which aims to critically summarize and scrutinize the current clinical evidence on the use and prognostic role of diverse nutritional assessment tools on the prognosis of patients with oesophageal and pharyngeal cancers. Methods: PubMed, Scopus, Web of Science and Google Scholar databases were comprehensively explored utilizing relative keywords to detect clinical studies that investigate whether nutritional status may affect disease prognosis. Results: Several assessment tools have evaluated and highlighted the prognostic role of nutritional status on patients’ survival and disease complications in both oesophageal and pharyngeal cancers. Regarding oesophageal cancer, CONUT, PNI, PG-SGA and NRS-2002 are more commonly used, while albumin is also frequently evaluated. Regarding pharyngeal cancers, fewer studies are currently available. PNI has been evaluated and its significance as a factor for shorter overall survival, distant metastasis-free survival, progression-free survival, and locoregional recurrence-free has been highlighted. Comprehensive Nutritional Index has also been evaluated with positive results, as well as NRS 2002, GPS, and body weight status. However, there is currently a lack of studies with adequate female patients. There is also a significant lack of well-designed prospective studies with well-organized methodology. Conclusion: Nutritional status may significantly affect disease progression and patients’ survival, highlighting the importance of a good nutritional status in patients with oesophageal and pharyngeal cancers. Further large-scaled and well-designed prospective clinical studies are strongly recommended to verify the potential beneficial effects of nutritional status in patients with oesophageal and pharyngeal cancers.
ARTICLE | doi:10.20944/preprints202001.0122.v1
Subject: Physical Sciences, Biophysics Keywords: cervical adenocarcinoma; immune-checkpoint inhibitor; programmed cell death-1(PD-1); programmed cell death-ligand 1(PD-L1); CD8 expression; lymphocyte; survival analysis
Online: 12 January 2020 (15:01:23 CET)
The effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. It may be possible for us to use programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of CA patients and their response to ICI therapy. The levels of the PD-1, PD-L1, and CD8 proteins were analyzed by immunohistochemical analysis from formalin-fixed, paraffin-embedded tumor samples. The correlation between the expression levels and patient prognosis was analyzed by the Kaplan–Meier method and univariate and multivariate Cox proportional hazard regression model. We observed a significant inverse-correlation between the PD-1 and CD8 expression (p=0.001, chi square test). We also found a significant inverse-correlation between the PD-L1 and CD8 expression (p=0.027). The overall survival was significantly worse in patients with positive PD-1 expression (p=0.027). Similarly, the progression-free survival was also worse (p=0.087). Our results demonstrate that a high level of PD-1 expression is associated with a poor prognosis in CA patients. Further research is necessary to identify the molecular mechanisms that mediate this association.
REVIEW | doi:10.20944/preprints202112.0278.v1
Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: systematic review; meta-analysis; dietary pattern; prospective cohort; randomized controlled trial; cancer prognosis; cancer survival; dietary intervention
Online: 16 December 2021 (15:06:33 CET)
Cancer survival continues to improve in high-income countries, partly explained by advances in screening and treatment. Previous studies have mainly examined the relationship between individual dietary components and cancer prognosis in tumours with good therapeutic response (breast, colon and prostate cancers). The aim of this review was to assess qualitatively (and quantitatively where appropriate) the associations of dietary patterns and cancer prognosis from published prospective cohort studies, as well as the effect of diet interventions by means of randomized controlled trials (RCT). A systematic search was conducted in PubMed, and a total of 35 prospective cohort studies and 14 RCT published between 2011 and 2021 were selected. Better overall diet quality was associated with improved survival among breast and colorectal cancer survivors; adherence to the Mediterranean diet was associated to lower risk of mortality in colorectal and prostate cancer survivors. A meta-analysis using a random-effects model showed that higher versus lower diet quality was associated with a 23% reduction in overall mortality in breast cancer survivors. There was evidence that dietary interventions, generally combined with physical activity, improved overall quality of life, though most studies were in breast cancer survivors. Further cohort and intervention studies in other cancers are needed to make more specific recommendations.
ARTICLE | doi:10.20944/preprints202309.1941.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: DNA repair; genetic polymorphism; head and neck cancer; radiotherapy; survival; CHEK1; MRE11; XRCC5; XRCC6; RAD51; LIG4; ATM; TP53; NBS1
Online: 28 September 2023 (17:54:16 CEST)
Radiotherapy and cisplatin-based chemotherapy belong to the main treatment modalities for head and neck squamous cell carcinoma (HNSCC), and induce cancer cell death by generating DNA damage, including the most severe double strand breaks (DSBs). Alterations in DSB response and repair genes may affect individual DNA repair capacity and treatment sensitivity, contributing to therapy resistance and poor prognosis often observed in HNSCC. In this study, we investigated the association of a panel of single nucleotide polymorphisms (SNPs) in 20 DSB signaling and repair genes with therapy results and prognosis in 505 HNSCC patients treated non-surgically with DNA damage-inducing therapies. In the multivariate analysis, there were a total of 14 variants associated with overall, locoregional recurrence-free or metastasis-free survival. Moreover, we identified 10 of these SNPs as independent predictors of therapy failure and unfavorable prognosis in the whole group or in two treatment subgroups. They were MRE11A rs2155209, XRCC5 rs828907, RAD51 rs1801321, rs12593359, LIG4 rs1805388, CHEK1 rs558351, TP53 rs1042522, ATM rs1801516, XRCC6 rs2267437 and NBS1 rs2735383. Only CHEK1 rs558351 remained statistically significant after correction for multiple testing. These results suggest that specific germline variants related to DSB response and repair may be potential genetic modifiers of therapy effects and disease progression in HNSCC treated with radiotherapy and cisplatin-based chemoradiation.
ARTICLE | doi:10.20944/preprints202303.0549.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: beraprost; feline; chronic kidney disease; progression-free survival; overall survival
Online: 31 March 2023 (11:17:14 CEST)
Background: Overall survival is the most important outcome for treatment response in feline chronic kidney disease (CKD). Beraprost has been shown to reduce the kidney function decline in cats with International Renal Interest Society (IRIS) stage 2 and 3 CKD. However, association with prolonged survival has not yet been examined. Objective: To assess the relationship between beraprost and overall survival in cats with CKD in real clinical practice. Animals: Client-owned cats with IRIS stage 3 CKD (n = 134), evaluated between 2017 and 2020. Methods: Retrospective cohort study based on data from electronic medical records of one hospital. Results: Multivariable Cox regression models on all treatment effects showed that beraprost only was related to better survival (P = 0.028). The cohort was divided into “beraprost therapy” and “no beraprost therapy” groups, and survival analyses revealed that overall survival was significantly longer in the beraprost therapy group, using Kaplan-Meier curves (P = 0.004). However, baseline phosphate is known to be an important prognostic indicator and was not well balanced between the two groups. Therefore, a subcohort of 97 cats was selected (those having baseline phosphate < 6.0 mg/dL) that allowed for this parameter to be balanced between groups. The survival data in this subcohort was consistent with that of the overall study cohort. Conclusions: In feline patients with CKD, beraprost therapy was associated with better overall survival.
ARTICLE | doi:10.20944/preprints202310.1726.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: dacomitinib; EGFR inhibitor; overall survival; pharmacokinetics; progression-free survival; proton pump inhibitors
Online: 27 October 2023 (07:06:07 CEST)
Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the treatment of patients with advanced non-small cell lung cancer (NSCLC) and EGFR-activating mutations. Proton pump inhibitors decreased dacomitinib exposure. This anal-ysis summarizes the effect of H2RA on dacomitinib exposure. A within-patient comparison of steady-state trough concentrations (Ctrough,ss) of dacomitinib and its active metabolite and active moiety with and without concomitant use of H2RA was conducted using a linear mixed effects model with pooled data from 11 clinical studies in patients with NSCLC. An oral absorption PBPK model was constructed and verified using clinical PK data after a single dose of dacomitinib in healthy volunteers to estimate the effect of gastric pH altered by an H2RA on dacomitinib PK. The adjusted geometric mean of dacomitinib Ctrough,ss of dacomitinib parent, metabolite and active moiety following co-administration with H2RA was approximately 86%, 104% and 100% relative to that following dacomitinib 45 mg administration without H2RA (P>0.05). The PBPK modeling showed negligible change in dacomitinib Cmax and AUC over 0-24 hours after H2RA administra-tion, when compared with those administered dacomitinib alone. Co-administration of an H2RA with dacomitinib is not expected to have any clinically relevant effect on dacomitinib exposure.
ARTICLE | doi:10.20944/preprints202310.0810.v1
Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: early-onset endometrial cancer; prognostic nomogram; overall survival; cancer-specific survival; SEER
Online: 13 October 2023 (03:02:06 CEST)
Background. This study aimed to establish a prognostic nomogram for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with early-onset endometrial cancer (EOEC). Methods. Patients diagnosed with EOEC during 2004-2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were performed to ascertain the independent factors impacting the prognosis of EOEC patients, while a prognostic nomogram was established. Its performance was verified by the receiver operating characteristic (ROC) curves, and calibration plots. The prediction accuracy and clinical net benefit between the model, TNM stage and SEER stage were further compared by the concordance index (C-index) and decision curve analysis (DCA). Results. A total of 4415 eligible patients with EOEC were identified and enrolled in this study. Independent prognostic factors for OS and CSS were confirmed by multivariate Cox regression, which were further incorporated to constructed a nomogram. ROC curves and calibration curves indicated an optimal accuracy of the nomogram. Meanwhile, the C-index and DCA showed the predictive capability and the clinical applicability of the nomogram was superior over the TNM stage and SEER stage. Conclusions. Nomogram based on risk factors was developed as an individualized tool to predict OS and CSS for EOEC patients. The novel tool will assist in patient counseling and selection of appropriate therapeutic regimens.
ARTICLE | doi:10.20944/preprints202307.1474.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: Hepatocellular carcinoma; Atezolizumab–bevacizumab; Hepatic artery infusion chemotherapy; Overall survival; Progression-free survival
Online: 21 July 2023 (14:00:43 CEST)
This study aimed to compare the prognosis and characteristics of patients with advanced hepatocellular carcinoma treated with first-line atezolizumab plus bevacizumab (AB) combination therapy and hepatic artery infusion chemotherapy (HAIC). We retrospectively assessed 179 and 72 patients treated with HAIC and AB combination therapy, respectively, between January 2018 and January 2023. The progression-free survival of patients treated with HAIC was significantly superior than that of patients treated with AB (P<0.05), but there was no significant difference in overall survival and objective response rate (ORR) between the two groups (P=0.1056 and P=0.137, respectively). After propensity score matching (PSM), our data revealed that there was no significant difference in PFS between patients who received AB combination therapy and HAIC therapy (P=0.8888). However, patients who received AB combination therapy had significantly better overall survival than those who received HAIC therapy (P=0.0133). In addition, after PSM, significant differences in ORR and disease control rate were not observed. In conclusion, our propensity score study reveals that patients treated with AB therapy have a significantly longer OS than those treated with HAIC.
REVIEW | doi:10.20944/preprints202306.1560.v1
Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: cancer survival; hormonal menopausal treatment
Online: 21 June 2023 (13:28:48 CEST)
Objective: to create a set of eligibility criteria for the use of MHT in non-gynecological cancer patients. Methods: We searched all articles published in peer-reviewed journals up to March 2021. The PICOS standards were used and the selection criteria as follows: menopausal women of any age with non-gynecological and non-breast cancer receiving HMT, any MHT preparation (oestrogens alone or combined with a progestogen, tibolone or tissue selective oestrogen complex) or any route of administration (oral, transdermal, vaginal or intra-nasal), recurrence and mortality, randomized controlled trials, and related extension studies or follow-up reports. Results: Women colorectal cancer survivors who use MHT have a lower risk of death from any cause than those survivors who do not use MHT. Women Skin Melanoma Survivors Using MHT Have Longer Survival than Non-MHT Survivors. There is no evidence that women lung cancer survivors who use MHT have a different survival rates than those survivors who do not use MHT. Conclusion: MHT is safe in women who have suffered from colorectal, lung or skin melanoma cancers The study was registered at www.prospero.org (CRD42020166658)
ARTICLE | doi:10.20944/preprints201808.0084.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: genistein; ∆F508-CF; mouse; survival
Online: 4 August 2018 (11:24:00 CEST)
Genistein is a naturally occurring isoflavone found in soy. Mice homozygous for the ∆F508 mutation are characterized with severe intestinal disease and require constant laxative treatment for survival. This pathology mimics the intestinal obstruction (meconium ileus) seen in some cystic fibrosis (CF) patients. We therefore tested whether dietary supplementation with genistein would reduce the dependence of the ∆F508 CF mouse model on laxatives for survival, thereby improving mortality rates. At weaning (21 days), we maintained homozygous ∆F508 mice on three diet regimens for a period of up to 65 days; normal diet, normal diet + Colyte or genistein diet. Survival rates for males were as follows: standard diet (38%), standard diet plus Colyte (83%) or genistein diet (60%). Survival rates for females were as follows: standard diet (47%), standard diet plus Colyte (71%), or genistein diet (87%). Average weight of male mice fed genistein diet increased by ~2.5 g more compared to those with Colyte treatment. Genistein diet did not change final body weight of females. Expression of SGLT-1 increased 2-fold with genistein diet in females (no change in males). Expression of GLUT2 and GLUT5 was comparable between all diet groups. Genistein diet reduced the number of goblet cells per micometer of crypt depth in female, yet was without effect in males. We conclude that supplementation of diet with genistein for ~45 days increases the survival rate of female ∆F508-CF mice precluding the requirement for laxatives, and only improves weight gain in males.
ARTICLE | doi:10.20944/preprints202311.0695.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: malnutrition; ovarian cancer; overall survival; nutritional risk screening score; nutrition; phase angle; progression-free survival
Online: 13 November 2023 (08:32:41 CET)
Background: Malnutrition was associated with worse survival outcomes, impaired quality of life, and deteriorated performance status across various cancer types. We aimed to identify risk factors for malnutrition in patients with epithelial ovarian(EOC) and impact on survival. Methods: In our prospective study, we included the patients with primary and recurrent EOC, tubal or peritoneal cancer conducted. We assessed serum laboratory parameters, body mass index, nutritional risk index, nutritional risk screening score(NRS-2002), and bio-electrical impedance analysis. Results: We recruited a total of 152. Patients >65 years-old, with ascites of >500 ml, or with platinum-resistant EOC showed statistically significant increased risk of malnutrition when evaluated by NRS-2002(p-values = 0.014, 0.001, and 0.007, respectively). An NRS-2002<3 was an independent predictive factor for complete tumor resectability (p=0.009). The patients with NRS-2002≥3 had a median overall survival(OS) of seven months (95% CI=0-24 months), as compared to the patients with NRS-2002<3 where median OS was 46 months(p=0,001). Phase angle(PhAα)≤ 4.5 was the strongest predictor of OS. Conclusion: Malnutrition is an independent predictor of incomplete cytoreduction in study population. It is an independent prognostic factor for poor OS. Preoperative nutritional assessment is an effective tool in identification of high-risk groups within EOC characterized by poor clinical outcome.
REVIEW | doi:10.20944/preprints202310.1321.v1
Subject: Medicine And Pharmacology, Surgery Keywords: colorectal cancer; incidence; mortality; screening; survival
Online: 20 October 2023 (08:31:13 CEST)
Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In last years the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality and survival rate for CRC.
ARTICLE | doi:10.20944/preprints202305.1737.v1
Subject: Medicine And Pharmacology, Surgery Keywords: liver surgery; colorectal cancer; laparoscopy; survival
Online: 25 May 2023 (05:14:42 CEST)
Abstract Introduction Minimally invasive approaches to oncological liver resection is common in many hepatobiliary centres. This study aims to compare the key oncological and survival outcomes of patients with colorectal liver metastases (CRLM) undergoing laparoscopic or open resections using propensity score matching (PSM). Methods A single-centre retrospective study was performed using a prospective database of patients undergoing liver resection for CRLM between January 2016 and December 2019. Different co-variates were selected for matching using PSM. Pre-matching and post-matching analyses were compared. Surgical and survival outcomes were analysed. Results In total, 303 patients who met the inclusion criteria were identified: 214 underwent open liver resection (OLR) and 91 laparoscopic liver resection (LLR). LLR had a significantly reduced length of intensive treatment unit (ITU) and overall in-patient stay but longer pringle and operative times. In the unmatched cohort, the median overall and disease-free survival time was significantly longer in patients undergoing laparoscopic compared with open surgery. A PSM model demonstrated significantly reduced blood loss and length of hospital stay, with a significantly greater Pringle and operative time in the LLR group. Differences seen in overall and disease-free survival were lost with propensity score matching, possibly due to lack of bi-lobar disease within the minimally invasive group. Conclusion In selected patients with CRLM, LLR presents similar survival and oncological outcomes with the advantages of the short-term results associated with the laparoscopic approach.
ARTICLE | doi:10.20944/preprints202010.0025.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: β-mannanase; bacteriophage; calf, growth; survival
Online: 1 October 2020 (16:46:42 CEST)
The objective of this study was to evaluate the effects of dietary supplementation with bacteriophage and β-mannanase on health and growth performance in calves. Thirty-six pre-weaning male Holstein calves were randomly allocated to one of four dietary treatments: no supplementation, 0.1% β-mannanase, 0.1% bacteriophage, and both 0.1% bacteriophage and β-mannanase supplementation in a starter. The experiment lasted from 2 weeks before weaning to 8 weeks after weaning. Twenty-two calves survived to the end of the experiment. No interaction was observed between the two methods of supplementation. A 1-kg increase in initial BW resulted in a 1.41-fold increase in the odds ratio of survival (p < 0.01). The bacteriophage supplementation tended to increase the odds ratio of survival (p = 0.09). The number of Escherichia coli in feces significantly decreased one week after weaning. β-mannanase supplementation increased the concentrates intake (p < 0.01) and tended to increase the final BW (p = 0.08). Analysis of repeated measures indicated β-mannanase supplementation increased weekly body weight gain (p = 0.018). We conclude that bacteriophage supplementation may have a positive effect on calf survival rate, while β-mannanase supplementation may increase the growth rate and intake of a starter in calves.
ARTICLE | doi:10.20944/preprints202308.0627.v1
Subject: Medicine And Pharmacology, Otolaryngology Keywords: open partial horizontal laryngectomy; laryngeal cancer; laryngeal preservation; laryngectomy free survival; disease specific survival; total laryngectomy
Online: 8 August 2023 (10:25:24 CEST)
In recent years, the number of open preservation surgeries for treatment of laryngeal Cancer has increased. The purpose of this surgery is to avoid the highly mutilating intervention of a total laryngectomy (TL) and to maintain laryngeal function while ensuring oncological radicality. The aim of this study was to assess the oncologic results of OPHL I and II and to identify prognostic factors that could impact patient survival and local failure rates. This study was conducted on 182 patients with laryngeal squamous cell carcinoma treated with OPHLs between 2005 and 2015. The survival rates of a group of patients treated with TL between 2004 and 2014 were taken into con-sideration to compare survival outcomes. The DSS in pT2 and pT3 tumors in relation to the type of surgery showed no statistically significant difference between OPHLs and TL (p=0.54 and p=0.63 respectively). The 5-years T-recurrence free survival showed that pT4 tumors, perineural/vascular positive invasion and OPHL IIb + ARY treated tumors were associated with a higher risk of tumor recurrence (p<0.0001, p=0.0005 and p=0.016 respectively). OPHLs represent an excellent alterna-tive to TL considering the characteristics of the tumor and the general conditions of the patient.
ARTICLE | doi:10.20944/preprints202310.1339.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: mycosis fungoides; relapsed/refractory; treatment patterns; Europe; real-world data; observational study; overall survival; progression-free survival
Online: 20 October 2023 (12:08:51 CEST)
(1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lym-phoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analysed patient records (1984–2016) from 27 clinical sites in Eurpe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS), and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. Median (range) times from start of first-line therapy to first R/R MF and from first to second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radio-therapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). Median (95% confidence interval [CI]) OS from the diagnosis of first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); es-timated median PFS (95% CI) from the time of first R/R MF was 1.3 (1.0–2.1) years. (4) Conclu-sion: High rates of R/R disease were observed after second- and third-line treatments in this re-al-world cohort, with longer median OS in patients receiving non-chemotherapy versus chemo-therapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF.
ARTICLE | doi:10.20944/preprints202305.1499.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: head-and-neck cancer; chemoradiation; cisplatin; carboplatin; loco-regional control; metasta-ses-free survival; overall survival; toxicity
Online: 22 May 2023 (10:21:54 CEST)
Keywords: head-and-neck cancer; chemoradiation; cisplatin; carboplatin; loco-regional control; metastases-free survival; overall survival; toxicity.
ARTICLE | doi:10.20944/preprints201810.0152.v1
Subject: Medicine And Pharmacology, Surgery Keywords: video assisted thoracic surgery, open thoracotomy, recurrence-free survival, overall survival, positive margins, postoperative length of stay.
Online: 8 October 2018 (15:23:21 CEST)
Background: Video assisted thoracoscopic surgery (VATS) has become the recommended approach for treatment of resectable lung cancer. However, no large randomized clinical trial has been conducted formally comparing surgical resections completed by VATS to those done by open thoracotomy (OT) in low volume centers. The current study sought to assess differences in recurrence-free survival (RFS), overall survival (OS), positive margins and postoperative length of stay (LOS) between VATS and OT lobectomies in our center. Method: A single institution retrospective chart review from May 2005 through May 2015 was conducted. All patients diagnosed with stage I through III lung cancer who underwent surgical resection were selected. Patient and tumor characteristics recorded included age at diagnosis, sex, tobacco use, tumor location (side and lobe), stage, size and receipt of chemotherapy or radiotherapy. Chis-square and Wilcoxon-Mann-Whitney tests were used to compare demographics, tumor characteristics and LOS. Multiple logistic and Cox regression analyses were used to compute relative risk (RR) for positive margins and mortality hazard ratios along with 95 percent confidence intervals (95%CI), respectively. Results: Of the 235 patients, 101 subjects had VATS while OT was performed in 134 patients. Age at diagnosis, sex, tobacco use, tumor location, and size were comparable for VATS and OT. No significant difference was observed in the relative risk of positive margins for VATS versus OT, RR = 0.56 (95%CI = 0.26, 1.05). However, VATS had shorter median LOS compared to OT (4 vs. 6 days, respectively), p = 0.002. A comparison of VATS versus OT showed no significant difference in the risk of recurrence, HR = 1.21 (95%CI = 0.74, 2.00), or death, HR = 1.34 (95%CI = 0.88, 2.06), in the intent-to-treat population. Similarly, no significant differences in recurrence or mortality risk were observed between VATS versus OT for analyses conducted separately for each cancer stage group or those limited to patients with negative margins. Conclusion: Our study indicates that compared to OT, VATS leads to shorter LOS while achieving comparable margins status, recurrence-free and overall survival regardless of tumor stage at diagnosis.
REVIEW | doi:10.20944/preprints202310.0828.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Lymph Nodes; Lymphadenectomy; Diagnostic Imaging; Survival Analysis
Online: 12 October 2023 (15:39:39 CEST)
Cervical cancer (CC) continues to be a significant global public health concern, even with preventive measures in place. In women with early-stage CC, the status of lymph nodes is of paramount importance, not only for final prognosis but also for determining the best therapeutic strategy. According to main international guidelines, pelvic full lymphadenectomy (PLND) is recommended for lymph node staging. However, in these early stages of CC, Sentinel lymph node biopsy (SLNB) has emerged as a precise technique for evaluating lymph node involvement, improving its morbidity profile. We performed a literature review through PubMed articles about progress on the application of SLNB in women with early-stage CC focusing on the comparison with PET/CT and PLND in terms of oncological outcomes and diagnostic accuracy. While the superiority of SLNB is clear compared to radiologic modalities, it demonstrates no clear oncologic inferiority over PLND, given the higher detection rate of positive lymph nodes and predominance of no lymph node recurrences. However, due to a lack of prospective evidence, particularly concerning long-term oncological safety, SLNB is not the current gold standard. With careful patient selection and adherence to straightforward protocols, a low false negative rate can be ensured. The aim of the ongoing prospective trials is to address these issues.
REVIEW | doi:10.20944/preprints202309.0758.v1
Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: penile cancer; lymph node dissection; timing; survival
Online: 12 September 2023 (10:29:17 CEST)
Background: The management of penile cancer patients has some grey zones, one of them being the timing of prophylactic pelvic lymph node dissection. Here, we review the impact of timing of prophylactic inguinal and pelvic lymph node dissection on patients’ outcome. Methods: Relevant databases were searched according to recommendations by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Before the systematic review we present a narrative review on the indications for lymph node dissection and the impact of pathological anatomical considerations on the timing of prophylactic lymph node dissection and patients’ outcome. The primary research questions were disease-free and overall survival rate in patients who underwent early or late lymph node dissection after penile cancer diagnosis. Results: Four clinical trials were included in the systematic review. Conclusions: The survival rate of patients with penile cancer is strictly associated with the timing of prophylactic pelvic lymph node dissection. Even though there are no randomized controlled trials we conclude that there is evidence for a strong recommendation that lymph node dissection should be performed as soon as possible after diagnosis with3 months as a realistic cut-off time between early and late. According to the present evidence base, lymph node dissection should be offered the sooner the better to all patients at high risk of lymph node metastasis.
ARTICLE | doi:10.20944/preprints202309.0257.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: clinical features; histopathologic features; retinoblastoma; survival; children
Online: 5 September 2023 (11:25:46 CEST)
BACKGROUND: Retinoblastoma is a malignant tumour that develops from the immature cells of the retina. It is the most frequent type of paediatric intraocular cancer and is curable. Clinical and histological findings after enucleation of the affected eye dictate not only the patient's secondary care but also their prognosis. We assessed the clinical and histopathologic predictors of survival among children with retinoblastoma from two tertiary health facilities in Uganda. METHODS: This retrospective research utilized archived formalin fixed & paraffin embedded blocks of eye specimens enucleated between 2014 to 2016 at Mbarara University, pathology department and Ruharo Eye Centre. The specimens were then processed and stained with haematoxylin and eosin. The confirmation of retinoblastoma was made to include histologic stage and features of the tumor. Biographic data of the patients and the clinical features such as leukocoria, proptosis, phthisis, staphyloma, buphthalmos were retrieved from the records.RESULTS: Males (55.1%) dominated the study population (N=78). The median age was 31 months. The commonest clinical sign was leukocoria (69.2%) and the most abundant histopathological stage was stage 1 (41%). Optic nerve invasion 39.5%, choroidal invasion 29.5%, scleral invasion 7.7% and orbital extension 16.7% were seen. Flexner-Wintersteiner rosettes were seen in 24.6%. Necrosis was a prominent feature (71.2%). The two-year survival was estimated to be 62%. Leukocoria (RR 1.1), female gender (RR 1.4), intralaminar optic nerve invasion (RR 7.6) and a lack of orbital extension (RR- 7) were significant predictors of survival.CONCLUSION: Leukocoria and proptosis are noticeable clinical signs of retinoblastoma. Most patients present while in stage one although stage four presentation is also common. Leukocoria, optic nerve invasion, orbital extension, and gender are significant factors predictive of survival in patients with retinoblastoma.
ARTICLE | doi:10.20944/preprints202308.1830.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: Hepatocellular Carcinoma; survival HCC; epidemiology; NASH; Austria
Online: 28 August 2023 (09:43:05 CEST)
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths and remains a major burden on health-care systems worldwide. The incidence of HCC continues to rise globally, despite preventative efforts being made. Aims: This study aimed to investigate epidemiological changes observed in the aetiology and survival outcomes of HCC patients at Klinikum Klagenfurt am Wörthersee between 2012 and 2023. Methods: This was a retrospective, single-centre cohort observational study. Two time-periods (2012-2017 and 2018-2023) were created to enable comparison between the respective intervals. Results: More patients were diagnosed with HCC during the second time-period, proving that the incidence of HCC is rising or the referral patterns changing. The median age of diagnosis was 72.5 years (SD 8.6). Patients were on average 2 years younger in the second time-period compared to the first (p = 0.042). Alcohol remained the leading underlying aetiology of HCC and no statistically significant change was seen over time (p = 0.353). Nevertheless, a clear upward trend in the number of NASH cases was evident over time (n = 15, n = 28 respectively). Nearly half of the patient population did not have a raised AFP at the time of diagnosis. The survival time for HCC patients remained similar between time-periods, with a median overall survival time of 20.5 months (95% CI 16.8-24.2, p = 0.841), despite improvements in management strategies and the availability of new systemic treatments but more advanced stage HCC was documented in the second period. An increasing number of HCC patients without liver cirrhosis were identified during the second time-period (n = 22, n= 47 respectively, p = 0.005). NASH was the most common underlying aetiology in patients without liver cirrhosis (50%), compared to alcohol use in being the primary cause in cirrhotic patients (p < 0.001). Conclusion: HCC continues to be an important health concern in our society. The number of HCC patients without liver cirrhosis is steadily increasing, with NAFLD/ NASH, due to underlying life-style diseases playing an important aetiological role. Continued efforts should be made to prevent HCC and to screen at-risk population groups. Preventative strategies and screening techniques should be adjusted in light of the changing epidemiological landscape of HCC.
BRIEF REPORT | doi:10.20944/preprints202212.0525.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Respiratory Syncytial Virus Infections; Child; Bronchiolitis; Survival.
Online: 28 December 2022 (02:37:39 CET)
Background: The respiratory syncytial virus infection (RSV) spread has been unusually high during 2022 and increasing trends have been documented We aimed to assess the survival experience of children hospitalized due bronchiolitis by laboratory-confirmed RSV. Methods: A nationwide and retrospective cohort was conducted in Mexico and data from 436 children aged 5 years and younger, with symptoms onset from August 2021 to November 2022, were analyzed. Survivor functions and 95% confidence intervals (CI) were computed by using the Kaplan-Meier method. Results: The survival rates were high, particularly within the first three weeks of admission. The 3-day survival was 99.8% (CI 95% 98.4-99.9%) and went to 98.9% (CI 95% 96.5-99.7%), 97.5% (CI 95% 91.9-99.3%), 86.7% (95% CI 48.2-97.2%), and 69.4% (95% CI 24.2-91.0%) on days 7, 14, 21 and 28 of hospital stay, respectively. We documented 5 fatal outcomes, and the mortality rate was 2.1 per 1,000 person-days. Conclusions: We analyzed a large set of pediatric patients with bronchiolitis by RSV and the presented results contribute to achieving a better understanding of the in-hospital evolution of this disease.
ARTICLE | doi:10.20944/preprints202209.0246.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: hemoglobin; monocytes; overall survival; prostate cancer; radiotherapy
Online: 16 September 2022 (10:11:15 CEST)
The prognostic value of inflammatory indices such as absolute monocyte count (AMC) has been a subject of interest in recent prostate cancer (PCa) literature, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized disease. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data was available for all cases based on the National Cancer Registry with a median observation time of 120 months (IQR 80.9-144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox proportional hazards regression model was used for analysis. The median age was 68.8 years (IQR 63.3-73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0-19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, ISUP Grade Group, clinical T stage and maximum PSA concentration. The study demonstrated that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa.
REVIEW | doi:10.20944/preprints202109.0242.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: PDK1; breast cancer; survival; prognosis; targeted therapy
Online: 14 September 2021 (14:51:06 CEST)
Given that 3-Phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in malignant biological behaviors of a wide-range of cancers, we further review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and extensively demonstrate the interacting networks of PDK1 via PI3K-dependent/ PI3K-independent pathway. Then we enlighten the roles of PDK1 in carcinogenesis, growth and survival, metastasis, and chemoresistance in BC cells. More important, we sort the current preclinical or clinical trials of PDK1 targeted therapy in BC and find that even though at present no selective PDK1 inhibitor is available for BC therapy, but the combination trials of PDK1 targeted therapy and other agents have demonstrated some benefit. Thus, there is increasing anticipations that PDK1 targeted therapy will have its space in future therapeutic concepts of BC, and we hope to feature PDK1 in BC to the clinic and bring the new promising to patients for targeted therapies.
ARTICLE | doi:10.20944/preprints202108.0135.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Glioblastoma; biomarker; TSPO; single nucleotide polymorphism; survival.
Online: 5 August 2021 (10:22:34 CEST)
Glioblastoma (GBM) is the most common primary brain tumor in adults, with few available therapies and a 5-year survival rate of 7.2%. Hence, strategies for improving GBM prognosis are urgently needed. The translocator protein 18kDa (TSPO) plays crucial roles in essential mito-chondria-based physiological processes and is a validated biomarker of neuroinflammation, which is implicated in GBM progression. The TSPO gene has a germline single nucleotide pol-ymorphism, rs6971, which is the most common SNP in the Caucasian population. High TSPO gene expression is associated with reduced survival in GBM patients; however, the relation between the most frequent TSPO genetic variant and GBM pathogenesis is not known. The present study ret-rospectively analyzed the correlation of the TSPO polymorphic variant rs6971 with overall and progression-free survival in GBM patients using three independent cohorts. TSPO rs6971 poly-morphism was significantly associated with shorter overall survival and progression-free survival in male GBM patients but not in females in one large cohort of 441 patients. We observed similar trends in two other independent cohorts. These observations suggest that the TSPO rs6971 pol-ymorphism could be a significant predictor of poor prognosis in GBM, with a potential for use as a prognosis biomarker in GBM patients. These results reveal for the first time a biological sex-specific relation between rs6971 TSPO polymorphism and GBM.
Subject: Social Sciences, Gender And Sexuality Studies Keywords: gender-based violence, coping, abuse, survival, resilient
Online: 2 July 2021 (14:00:57 CEST)
Gender-based violence is considered a serious social and public health problem. Overcoming this situation implies a process that results in the favorable biopsychosocial rehabilitation, the resilient of women. The objective of this study was to analyze the tools, resources and personal and psychosocial mechanisms used by women survivors of gender-based violence. The design was an interpretative phenomenology. It carried out with 22 women who have overcome gender-based violence. Data was collected through personal interviews and narration. The results were grouped into four themes: "Process of violence", "Social resources for coping and overcoming GBV", "Personal tools for coping and overcoming GBV", and "Feelings identified, from the abuse stage to the survival stage". Several studies concluded that overcoming abuse is influenced by the women social network, and it can be the action of these people determining their survival to gender violence. Despite the recognized usefulness of these available resources, it would be desirable to strengthen them in order to be able to drive more women toward survival, assuming a strengthening of coping and overcoming, without forgetting the importance of other support mechanisms such as their family and group therapies.
ARTICLE | doi:10.20944/preprints202005.0057.v2
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; treatment; drug; survival; antiviral; hydroxychloroquine
Online: 9 May 2020 (04:45:37 CEST)
Background: Although no specific treatment for COVID 19 has been proven effective yet, some drugs with in vitro potential against SARS-CoV-2 virus have been proposed for clinical use. Hydroxychloroquine has in vitro anti-viral and immunomodulatory activity, but there is no current clinical evidence of its effectiveness on the outcome of the disease. Methods: We enrolled all 18-85 years old inpatients from Central Defense Hospital, Madrid, Spain, who were hospitalised due to COVID-19 and had a definitive outcome (either dead or discharged). We used a statistical survival analysis. Results: We analysed 220 medical records. 166 patients met the inclusion criteria. 48,8 % of patients not treated with HCQ died, versus 22% in the group of hydroxychloroquine (p=0,002). According to clinical picture at admission, hydroxychloroquine increased the mean cumulative survival in all groups from 1,4 to 1,8 times. This difference was statistically significant in the mild group. Conclusions: in a cohort of 166 patients between 18 to 85 years hospitalised with COVID-19, hydroxychloroquine treatment with an initial loading dose of 800mg improved patient survival when admitted in early stages of the disease. There was a non-statistically significant trend towards survival in all groups, which will need to be clarified in subsequent studies.
ARTICLE | doi:10.20944/preprints201907.0333.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: correlated response; pre-weaning; survival; weight; welfare
Online: 29 July 2019 (09:40:36 CEST)
A divergent selection experiment on environmental sensitivity was performed in rabbits. The aim of this study was to estimate the correlated response in kits’ weight and its survival, and weight distance from birth to weaning. Weight distance was calculated as the absolute values of the differences between the individual value and the mean value of its litter. Also, relationship between probability of survival at 4 d of age and weight at birth was studied. Environmental sensitivity was measured as litter size variability. A total of 2484 kits from 127 does of the low line (selected for reducing litter size variability) and 1916 kits of 114 does of the high line (selected for increasing litter size variability) of the 12th generation were weighed. Bayesian methodology was used to estimate the correlated response to selection, and LOGISTIC procedure of SAS was used to estimate the relationship between weight and probability of survival. Both lines showed similar individual weight at birth and at weaning, and similar survival at birth and at 4 d of age. Survival at weaning was higher in the low line than in the high line (0.67 and 0.62; P= 0.93). Weight distance was higher at birth but lower at weaning in the low line (47.8 g and 54.1 g; P=0.98). Kit’s weight at birth affected its survival. In conclusion, selection for environmental sensitivity showed correlated response in kits survival and in homogeneity of litter weight at weaning.
ARTICLE | doi:10.20944/preprints201805.0427.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; comorbidities; older women; radiotherapy; survival
Online: 29 May 2018 (13:01:28 CEST)
Background: Radiotherapy plays an important role in the management and survival of patients with breast cancer. The aim of this study was to examine the association between age, comorbidities and use of radiotherapy in this population. Methods: Patients diagnosed with breast cancer from 2004–2013 were identified from the American College of Surgeons National Cancer Database (NCDB). Follow-up time was measured from the date of diagnosis (baseline) to the date of death or censoring. Adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) were used as the measure of association. Results: Independently of comorbidities and other important outcome-related factors, patients >65 years of age who received radiotherapy survived significantly longer than those who did not receive radiotherapy (aHR = 0.53, 95%CI = 0.52–0.54). However, as women aged, those with comorbidities were less likely to receive RT (adjusted P-trend by age <0.0001). Conclusions: The development of decision-making tools to assist clinicians, and older women with breast cancer and comorbidities, are needed to facilitate personalized treatment plans regarding RT. This is particularly relevant as the population ages and the number of women with breast cancer is expected to increase in the near future.
ARTICLE | doi:10.20944/preprints201801.0174.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: provenances, height, root-collar-diameter, survival, growth
Online: 18 January 2018 (16:39:53 CET)
The aims of the study were to evaluate seedling growth and survival of Prunus africana provenances in awi highland based on ecological requirement of the tree. We measured survival and growth of three P.africana provenances seedlings found in Ethiopia (provenances sources namely: Gedeo, Jibat and Munnessa). Design of experiment with randomized complete block design (RCBD) with three replications. Seedlings planted at 2m, 2.5m and 3m distance between plants, plot, and blocks respectively. A plot size of 10mx10m and 25 plants are found per plot (0.01ha). We used ANOVA to test differences in survival, and growth among provenances over time. Results concluded that, provenances have no significant variation among in establishment rate, plant height and collar diameter growth. Of these provenances, Jibat was the first in establishment (56%), second in height (1.97m) and diameter (2.89cm). Gedeo was stood first in height (2.30m) but second in establishment rate (52%) and thickness(3.45cm), but Munessa with very good growth in diameter(3.59cm) might be prefreed for bark extraction followed by Gedeo, last in height (1.75m),but established second (52%). Contrary to expectations, seedlings were still at substantial risk of mortality ≥3 years after planting. Probably the plants survival rate and growth probably affected by altitude, soil water potential, light exposure, and wild animal presence in the surrounding. In steep slope sites, canopy shade, existing weed vegetation as well as wild animals such as apes is unlikely to enhance seedling survival after planting. Our results suggest that seedling mean growth increased with 0.008mm thickness and 0.41mm per day while 2.8mm thickness and 146.8mm tall increment recorded in 2560meter elevated high land or injibara with mean value of 18.5°C and rain fall is 1300mm.
ARTICLE | doi:10.20944/preprints201611.0028.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: random survival forests; ependymoma; predictors; valproic acid
Online: 3 November 2016 (11:02:12 CET)
Ependymoma is responsible for 8–10% of all pediatric brain tumors and constitutes the third most common brain tumor in children. No robust molecular markers are yet in routine clinical use. Surgical resection and adjuvant radiotherapy cure approximately 40-70% of pediatric patients with ependymoma. In our centre, we have been using prophylactic valproic acid treatment for brain tumor patients. Initial observations indicated that valproate could have a beneficial effect in the survival of patients. Recent observations by other authors have shown that patients with glioblastoma benefited from the treatment with valproic acid, a histone deacetylase inhibitor. We have used random survival forest, a novel ensemble survival modelling method to study a single- center, small number cohort of pediatric patients with ependymoma. This analysis has confirmed surgery resection extent and treatment with radiotherapy as independent predictors of overall survival. Treatment with valproic acid was also a predictor of higher survival in this cohort. These results highlight the potential usefullness of the random survival forest model in gathering information from retrospective data. More data is needed about the possible influence of histone deacetylase inhibition by valproic acid in the survival of patients with ependymoma.
ARTICLE | doi:10.20944/preprints202309.1880.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: FLAIR infiltration; brain tumors; extent of surgical resection; glioblastoma; overall survival; progression-free survival; pseudocapsule; neuro-oncology; tumor volume
Online: 28 September 2023 (03:26:09 CEST)
Background: Glioblastoma is the most common primary brain neoplasm in adults, with still a poor prognosis despite a constant effort to improve patients’ survival. Some neuroradiological volumetric parameters seem to play a predictive role on Overall Survival (OS) and Progression Free Survival (PFS). The aim of this study is to analyze the impact that the volumetric areas of contrast-enhancing tumor and perineoplastic edema have on survival of patients treated for glioblastoma; Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered as the end points of the study. For each patient a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology board. A manual and semi-automatic measurement were adopted to perform the radiological evaluation: contrast Enhancement Preoperative (CE-PTV) and Postoperative Tumor Volume (CE-RTV), Edema/Infiltration Preoperative (T2/FLAIR-PV) and Postoperative Volume (T2/FLAIR-RV); necrosis volume inside the tumor (NV); total tumor volume, including necrosis (TV); Results: The median OS value was 9 months and the median PFS value was 4 m; the mean values were respectively 12,3 m and 6,9 m. Multivariate analysis showed that the OS related factors were: adjuvant chemo-radiotherapy (p < 0,0001), CE-PTV < 15 cm³ (p=0,03), surgical resection > 95% (p=0,004) and the presence of a “pseudo-capsulated” radiological morphology (p=0,04); Conclusions: maximal safe resection is one of the most relevant predictive factors for patients’ survival. The semi-automatic pre-operative MRI evaluation could play a key role in prognostically categorizing these tumors.
REVIEW | doi:10.20944/preprints202311.1369.v1
Subject: Biology And Life Sciences, Other Keywords: VBNC state; stress; beneficial bacteria; rhizosphere; latency; survival
Online: 24 November 2023 (04:11:22 CET)
Many bacteria have the ability to survive in challenging environments; however, they cannot grow on standard culture media, a phenomenon known as the Viable but Non-Culturable (VBNC) state. Bacteria commonly go into the VBNC state under nutrient-poor environments or under stressful conditions. This review explores the concept of the VBNC state, providing insights into the beneficial bacteria known to employ this strategy. The investigation covers different chemical and physical factors that can induce the latency state, cell features, and gene expression observed in cells in the VBNC state. The revision also covered the significance and applications of beneficial bacteria, methods for evaluating bacterial viability, the ability of bacteria to persist in environments associated with higher organisms, and the factors that facilitate the return to the culturable state. Knowledge about beneficial bacteria capable of entering the VBNC state remains limited, however, beneficial bacteria in this state could face adverse environmental conditions, and return to culturable state when conditions become suitable and continue to exert their beneficial effects. Likewise, this unique feature positions them as potential candidates for healthcare applications, such as the use of probiotic bacteria to enhance human health, applications in industrial microbiology for the production of prebiotics, functional foods, and in the beer and wine industry. Moreover, their use in formulations to increase crop yield and for bacterial bioremediation offers an alternative pathway to harness their beneficial attributes.
COMMUNICATION | doi:10.20944/preprints202310.0091.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Amyotrophic lateral sclerosis; neutrophils; lymphocytes; NLR; survival; prognosis
Online: 3 October 2023 (05:55:51 CEST)
Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative motor neuron disease and remains misunderstood with difficult diagnosis and prognosis. The implication of the immune system is recognized in ALS pathophysiology, hence the interest in leucocytes count as lymphocytes and neutrophils. The neutrophil to lymphocyte ratio (NLR) has recently been used as a prognosis factor to assess the progression of ALS. Thus, the aim of this study was to analyze the evolution of the NLR during disease evolution in a French cohort of ALS patients and its relation with survival. Clinical parameters and NLR were collected in ALS patients followed at the University Hospital of Tours (France). ALS patients were subdivided into three groups in regard to their NLR value at inclusion: group 1 (NLR < 2); group 2 (NLR: 2-3); group 3 (NLR > 3). Comparison of qualitative and quantitative clinical and biological variables between NLR groups was performed. Then Cox-regressions were carried out to determine the association of NLR with survival. We observed a significant correlation of NLR with ALSFRS-r score (p<0.0001) and with vital forced capacity (p=0.0004) at inclusion. We observed that increased NLR at diagnosis is associated with decreased ALS patients’ survival.
ARTICLE | doi:10.20944/preprints202308.1897.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Glioma; Prognostic markers; Autophagy; Micro-RNA; Overall Survival
Online: 29 August 2023 (03:33:04 CEST)
Abstract: Autophagy has a dual role in gliomagenesis in a microRNA-modulated environment. We investigated the potential relevance of autophagy in glioma development and survival by exploring the association of autophagy-associated genes and microRNAs in low- and high-grade gliomas. Real-time PCR (qPCR) was used to determine the expression of genes and microRNAs in 50 fresh glioma tissues while Formalin-fixed paraf-fin-embedded tissues of the same patients were used for immunohistochemistry. The Mann-Whitney U-test test, Spearman correlation test, and Kaplan-Meier survival analysis were performed to evaluate the expression, association, and overall survival in patients respectively. The expression of LC3, AKT, and miR-21 was increased in high-grade glioma compared to low-grade glioma while ULK2 expression was decreased in high-grade glioma. A strong positive correlation was observed for ULK2 with UVRAG, PTEN, miR-7, and miR-100, while the moderate correlation with mTOR, Beclin1, miR-30, miR-204, miR-374, miR-21 and miR-126 in low-grade glioma, while a moderate positive correlation between ULK2 and PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, AKT and miR-374, and between AKT and ULK1, VPS34, UVRAG, and miR-7 in high-grade gliomas. The low ULK2 and LC3 expression group was significantly associated with better overall survival in gliomas while miR-21 overexpression showed a poor prognosis in glioma patients. Therefore, miR-21, ULK2, and LC3 may serve as prognostic biomarkers for survival outcomes in glioblastoma.
ARTICLE | doi:10.20944/preprints202307.1254.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: urothelial carcinoma; GATA3; immunohistochemistry; overall survival; meta-analysis
Online: 19 July 2023 (12:44:52 CEST)
This study aimed to evaluate the diagnostic and prognostic roles of GATA3 immunohistochemistry in urothelial carcinoma (UC) through a meta-analysis. We investigated GATA3 immunohistochemical expression rates and performed a subgroup analysis based on tumor site, study location, and histological subtypes. The overall survival rates of patients with GATA3-positive and negative UC were compared. The estimated GATA3 expression rate was 0.748 (95% confidence interval [CI]: 0.704–0.787). GATA3 expression rates in the urinary bladder and urinary tract were 0.775 (95% CI: 0.727–0.818) and 0.614 (95% CI: 0.426–0.774), respectively. The GATA expression rates of noninvasive and invasive UCs were 0.965 (95% CI: 0.938–0.980) and 0.644 (95% CI: 0.581–0.702), respectively. In invasive UCs, there was a significant difference in GATA3 expression between non-muscular invasion and muscular invasion subgroups (0.937, 95% CI: 0.883–0.967 vs. 0.753, 95% CI: 0.645–0.836). GATA3 expression was the highest in the microcytic subtype among the histologic subtypes (0.952, 95% CI: 0.724–0.993). There was a significant correlation between GATA3 expression and better prognosis (hazard ratio: 0.402, 95% CI: 0.311–0.521). Taken together, GATA3 expression significantly correlated with low-stage and better prognosis in UC. GATA3 expression is highly variable across histological subtypes and it is careful interpreting GATA3 expression.
ARTICLE | doi:10.20944/preprints202307.1106.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: NICU; neonatal mortalities; survival; racial disparities; perinatal epidemiology
Online: 17 July 2023 (11:33:59 CEST)
Abstract: Objective: We aimed to look for the mortality of Black and White Neonates and compare the Black and White neonates' mortalities after stratifying the population by many significant epidemiologic and hospital factors. We utilized the National Inpatient Sample (NIS) dataset over seven years from 2012 through 2018 for all neonates ≤ 28 days of age in all hospitals in the USA. Design/Method: We utilized the National Inpatient Sample (NIS) dataset over seven years from 2012 through 2018 for all neonates ≤ 28 days of age in all hospitals in the USA. Neonatal characteristics used in the analysis included ethnicity, sex, household income, and type of healthcare insurance. Hospital characteristics were urban teaching, urban non-teaching, and rural. Hospital location was classified according to the 9 U.S. Census Division regions. Results: Neonatal mortality continues to be higher in Black: 21,975 (0.63%) and in White was: 35495 (0.28%), Government-supported health insurance was significantly more among Black populations when compared to White (68.8% vs. 35.3% p<0.001). Household income differed significantly; almost half (49.8%) of the Black population has income ≤ 25th percentile vs. 22.1% in White. There was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division (0.72%), and the lower mortality was in the New England division (0.51%), whereas in the White population, the highest mortality was in the East South-Central division (0.36%), and the lowest mortality was in the New England division (0.21%). Trend analysis showed a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by sex, types of insurance, the household income, the type of hospitals, the mortality was consistently higher in Black groups throughout the study years, Conclusions: Disparities in neonatal mortality continue to be higher in Black; There was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division, and the lower mortality was in the New England division, whereas in the White population, the highest mortality was in the East South-Central division, and the lowest mortality was in the New England division. There has been a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by many significant epidemiologic and hospital factors, the mortality was consistently higher in Black groups throughout the study years.
ARTICLE | doi:10.20944/preprints202305.0198.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: gastric fluid; urine; metabolite; GC-MS; prematurity; survival
Online: 4 May 2023 (05:21:26 CEST)
Prediction of survival in very preterm infants is very important in terms of clinical medicine and parent counseling. In this prospective study involving 96 very preterm infants, we evaluated whether metabolomic analysis of gastric fluid and urine samples obtained soon after birth could predict survival on days of life (DOL) 3 and 15 as well as overall survival up to hospital discharge. Gas chromatography-mass spectrometry (GC-MS) profiling was used. Uni- and multivariate statistical analyses were carried out to evaluate significant metabolites and their prognostic value. Differences in several metabolites were identified between survivors and non-survivors at the time-points of the study. Binary logistic regression showed that certain metabolites in the gastric fluid including arabitol as well as succinic, erythronic and threonic acids was associated with DOL 15 and overall survival. Gastric glyceric acid was also associated with DOL 15 survival. Urine glyceric acid could predict survival on DOL 3 and overall survival. In conclusion, non-surviving preterm infants showed a different metabolic profile compared survivors showing a significant discrimination with the use of GC-MS-based gastric fluid and urine analysis. Results of this study support the usefulness of metabolomics in developing survival biomarkers in very preterm infants.
ARTICLE | doi:10.20944/preprints202304.0485.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: Prostate Cancer, Survival, Disparities, Geographic, Multilevel, Healthcare Access
Online: 18 April 2023 (04:49:50 CEST)
Introduction Prostate Cancer (PCa) exhibits one of the widest racial and socioeconomic disparities. PCa disparities have also been widely linked to location as living in more deprived regions was associated with lower healthcare access and worse outcomes. This study aims to examine PCa survival across various US counties in function of different socioeconomic profiles and discuss the role of potential intermediary factors. Methods The SEER database linked to county-level SES was utilized. Five-year PCa-specific survival using the Kaplan Meier method was performed for 5 racial/ethnic categories in function of SES quintiles. Multilevel Cox proportional hazards regression was performed to assess the relationship between county-level SES and PCa survival. Multivariate regression analysis was performed to examine the role of healthcare utilization and severity. Results 279,000 PCa records were extracted, 5-year PCa-specific survival was 94%. Overall, living in counties with worst poverty/income quintile and highest proportions of foreign-born/language-isolated increased PCa mortality by 23% each. No association was observed with county-level High-School education, while Bachelor’s-level education decreased mortality risk by 23%. Associations varied considerably upon racial/ethnic stratification. Multilevel analyses showed varying contributions of individual and area-level factors to survival within minorities. The relationship between SES and PCa survival appeared to be influenced by healthcare utilization and disease stage/grade. Discussion Racial/ethnic categories responded differently under similar county-level SES and individual-level factors to the point where disparities reversed in Hispanics. The inclusion of Healthcare utilization and severity factors may provide partial early support for their role as intermediaries. Healthcare access (insurance) might not necessarily be associated with better PCa survival, through performing biopsy and or/surgery. County-level education plays an important role in PCa decision-making as it might elucidate discussions of other non-invasive management options. Conclusion Findings of this study demonstrate that interventions need to be tailored according to each group's needs. This potentially informs the focus of public health efforts in terms of planning and prioritizing. This study could also direct further research delving into pathways between area-level characteristics with PCa survival.
ARTICLE | doi:10.20944/preprints202112.0104.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: glioma; HLA-G; IL-6; polymorphism; prognosis; survival
Online: 7 December 2021 (12:55:23 CET)
HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14 bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients had also higher plasma levels of sHLA-G. Patients with methylated MGMT promoter had lower levels of sHLA-G than those with unmethylated MGMT promoter. Level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut off value 40 U/mL survived significantly longer than patients with sHLA-G above 40 U/mL. The levels of sHLA-G also negatively correlated with the level of IL-6 (P=0.0004) and positively with IL-10/IL-6 (P=0.046). Conclusion: The presence of 14 nt insert in both homozygous and heterozygous states of the HLA-G 14 bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival.
ARTICLE | doi:10.20944/preprints202010.0046.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: glioblastoma; master regulators; IGFBP2; survival; tumorigenicity; transcription factors
Online: 2 October 2020 (15:21:34 CEST)
Only 2% of Glioblastoma multiforme (GBM) patients respond to standard care and survive beyond 36 months (long-term survivors, LTS) while the majority survives less than 12 months (short-term survivors, STS). To understand the mechanism leading to poor survival, we analyzed publicly available datasets of 113 STS and 58 LTS. This analysis revealed 198 differentially expressed genes (DEGs) that co-occur with aggressive tumor growth and may be responsible for the poor prognosis. These genes belong largely to the GO-categories “epithelial to mesenchymal transition” and “response to hypoxia”. Promoter and network analysis of the DEGs identified 5 potential master regulators that may explain dysregulation of the DEGs in the STS. The following 5 important master-regulators were identified: IGFBP2, VEGFA, PDGFA, OSMR and AEBP1. It is known that IGFBP2 confers increasing malignancy leading to poor prognosis. However, the molecular mechanism by which IGFBP2 affects disease progression and patient prognosis is unclear. Here we found that IGFBP2 is highly upregulated in short survivors and significantly impact survival. Further investigation of the gene regulatory network revealed that IGFBP2 expression can be regulated by FRA-1 transcription factor via MEK2/RAF/ERK5 pathway. FRA-1 is found to be upregulated and to have significant impact on survival in GBM. It is previously reported that FRA-1 can dysregulate at-least 50 genes involved in tumor invasiveness in tumor xenografts making it a therapeutic target for GBM intervention. We propose that IGFBP2 drives dysregulated gene network responsible for short survival in GBM via FRA-1 transcription factor.
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Cherax quadricarinatus; red claw; substrate; survival; growth; molting
Online: 7 September 2020 (09:53:47 CEST)
The experiment was conducted to determine the effects of different substrate on the survival, growth and total number of moulting in juvenile red claw, Cherax quadricarinatus for aquaculture purposes. In the present study, there is a problem in culturing juvenile stage of C. quadricarinatus especially for survival and growth. Thus, a substrate was used to improve the survival and growth of C. quadricarinatus especially for the intensive system due C. quadricarinatus need a large space to survive. C. quadricarinatus with initial body weight from 1.10 to 2.90 g, total length 2.82 to 4.36 cm were placed in tanks (80 L in volume capacity) with 55L in water and there are eight juveniles in each tank. Treatment tanks were introduced with coral as treatment 2 and pipe as treatment 3. While, tank without shelters was set as control (treatment 1). Black nets were installed on top of each for circumventing foreign objects enter the tank and protect from direct sunlight. Besides, C. quadricarinatus were acclimatized for seven days before started the experiment. The experiment was done in duplicate and conducted for 60 days and C. quadricarinatus were fed twice daily (morning and evening) based on 5% of body weight. From the total of two replications, C. quadricarinatus for treatment 2 (coral) were significantly in survival (81.25±8.84%), weight gain (347.36 ±6.04%), specific growth rate (2.50±0.02%), carapace length (32.93 ± 0.93 %) and total number of moulting (55.00±2.93%) compared to other treatments. Besides, the control treatment (treatment 1) has a lower percentage in survival (37.50±8.84%) weight gain (122.60±20.51%) specific growth rate (1.33±0.15%), carapace length (25.84±0.33 %) and total number of molting (29.00±0.71%). As a conclusion, usage of coral as the substrate in the rearing tank showed improvement in survival, weight gain, specific growth rate, carapace length and total number of molting in C. quadricarinatus. The coral can use in rearing tank for increase the growth and survival for a small scale and not for commercial. In addition, in the environmental aspect, the present study showed the benefit of replacing the use of PVC pipes with the natural structure of dead coral.
ARTICLE | doi:10.20944/preprints202005.0497.v1
Subject: Business, Economics And Management, Business And Management Keywords: Product innovation; enterprise survival; competitive intensity; competitive advantage
Online: 31 May 2020 (19:45:30 CEST)
Product innovation is a crucial factor in enterprise survival. Even though there are sources from strategic theory that guides the clear comprehension towards appreciating the nexus between these two variables (product innovation and enterprise survival), there are still many lacunas that should be addressed and filled. Consequently, the need for additional empirical corroboration or support is pertinent. This study aimed at verifying the nexus between product innovation and enterprise survival, and how they are affected by the existence of antecedent variables such as competitive intensity and competitive advantage. In the methodology, this study adopts the conduct of explanatory and cross-sectional investigations through the use of structural equation modelling (SEM) to a sample of selected food and beverages enterprises in Lagos, Nigeria. Regarding the food and beverage enterprises in Lagos, Nigeria, this study discovered that competitive intensity has huge positive implication on product innovation at (0.39; t = 5.69, p < 0.05). This gives numerical evidence that, in the face of more market competition, enterprises will be pressured to adopt the model of costs reduction on products which will enhance the reduction of product prices, and will have significant impact on profit. However, the findings reveal that there is no significance between competitive advantage and product innovation at (0.002; t = 0.203, p > 0.05), and there is no significance between product innovation and enterprise survival at (-0.035; t = -1.583, p > .05). As a result, the food and beverage enterprises should concentrate more on product innovation so that they will be able to stand the intensity of competition. The results emanated from the study is germane as it make significant contribution to literature and the body of knowledge and on strategic management by enlightening that competitive intensity is a necessary inducement for product innovation.
ARTICLE | doi:10.20944/preprints202003.0425.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cancer; immune checkpoint inhibitors; survival; antibiotic; meta-analysis
Online: 29 March 2020 (06:43:23 CEST)
Antibiotics (ABs) are common medications used for treating infections. In cancer patients treated with immune checkpoint inhibitors (ICIs), concomitant exposure to ABs may impair the efficacy of ICIs and lead to a poorer outcome compared to AB non-users. We report here the results of a meta-analysis evaluating the effects of ABs on the outcome of patients with solid tumors treated with ICIs. PubMed, the Cochrane Library, and Embase were searched from inception until September 2019 for observational or prospective studies reporting prognosis of adult patients with cancer treated with ICIs and with or without ABs. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI), and an HR > 1 associated with a worse outcome in ABs users compared to no-ABs users. Fifteen publications were retrieved for a total of 2363 patients. In the main analysis (n = 15 studies reporting data), OS was reduced in patients exposed to ABs before or during treatment with ICIs (HR = 2.07, 95%CI 1.51–2.84; P<.01). Similarly, PFS was inferior in ABs users in n = 13 studies with data available (HR = 1.53, 95%CI 1.22–1.93; p<.01). In cancer patients treated with ICIs, AB use significantly reduces OS and PFS. Short duration/course of ABs may be considered in clinical situations in which they are strictly needed.
ARTICLE | doi:10.20944/preprints201911.0094.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: hPSCs; ROCK inhibitors; fasudil; cell survival; metabolism; differentiation
Online: 8 November 2019 (10:41:13 CET)
Poor survival of human pluripotent stem cells (hPSCs) following freezing, thawing, or passaging hinders maintenance and differentiation in stem cell research. Rho-associated kinases (ROCKs) play a crucial role in hPSC survival. To date, a typical ROCK inhibitor, Y-27632, has been the primary agent used in hPSC research. Here, we report that another ROCK inhibitor, fasudil, can be used as an alternative. Fasudil increased hPSC growth due to survival rather than proliferation following thawing and passaging, similar to Y-27632. It did not affect pluripotency and genetic integrity including mitochondrial genome (mtDNA). Notably, the genes related to metabolism, mTORC1, and TP53 have mainly displayed a faster recovery pattern with ROCK inhibitors than control. Furthermore, fasudil was confirmed as useful for the single dissociation of hPSCs and for aggregation. It also increased retinal pigment epithelium (RPE) differentiation and the survival of neural crest cells during differentiation. These findings suggest that fasudil can replace Y-27632 for use in stem cell research.
ARTICLE | doi:10.20944/preprints201910.0180.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: long term survival; Glioblastoma; IDH; EGFR; Ki67; p53
Online: 16 October 2019 (08:30:25 CEST)
Background: Glioblastomas (GBM) is generally burdened, to date, by a dismal prognosis, although Long Term Survivors have a relatively significant incidence. Our specific aim was to determine the exact impact of many surgery-, patient- and tumor-related variable on Survival parameters. Methods: The surgical, radiological and clinical outcomes of patients have been retrospectively reviewed for the present study. All the patients have been operated on in our Institution and classified according their Overall Survival in LTS (Long Term Survivors) and STS (Short Term Survivors). A thorough Review of our surgical series was conducted to compare the oncologic results of the patients in regards to 1. Surgical , 2. Molecular, and 3.Treatment related features. Results: A total of 177 patients were included in the final cohort. Extensive statistical analysis by means of univariate, multivariate and survival analyses disclosed a survival advantage for patients presenting a younger age, a smaller lesion and a better functional status at presentation. From the Histochemical point of view, Ki67(%) was the strongest predictor of better oncologic outcomes. A stepwise analysis of variance outlines the existence of 8 prognostic subgroups according to the molecular patterns of Ki67 overexpression and EGFR, p53 and IDH mutations. Conclusions: On the ground of our statistical analyses we can affirm that the following factors were significant predictors of survival advantage: KPS, Age, Volume of the lesion, Motor disorder at presentation, a Ki67 overexpression. A fine molecular profiling is feasible to precisely stratify the prognosis of GBM patients.
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: 5-hmC; ELISA; TET; HNSCC; disease-free survival
Online: 22 July 2019 (08:55:04 CEST)
Ten-eleven translocation (TET) enzymes are implicated in DNA demethylation through dioxygenase activity, which converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). However, the specific roles of TET enzymes and 5-hmC levels in head and neck squamous cell carcinoma (HNSCC) have not yet been evaluated. In this study, we analyzed 5-hmC levels and TET mRNA expression in a well-characterized dataset of 117 matched pairs of HNSCC tissues and normal tissues. 5-hmC levels and TET mRNA expression were examined via enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. 5-hmC levels were evaluated according to various clinical characteristics and prognostic implications. Notably, we found that 5-hmC levels were significantly correlated with tumor stage (P = 0.032) and recurrence (P = 0.018). Univariate analysis revealed that low levels of 5-hmC were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038). The expression of TET family genes was not associated with outcomes. In multivariate analysis, low levels of 5-hmC were evaluated as a significant independent prognostic factor of DFS (hazard ratio: 2.352, 95% confidence interval: 1.136–4.896; P = 0.021). Taken together, our findings showed that reduction of TET family gene expression and subsequent low levels of 5-hmC may affect the development of HNSCC.
ARTICLE | doi:10.20944/preprints201906.0017.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; relative survival; excess hazard; excess mortality
Online: 3 June 2019 (10:08:23 CEST)
Measurement of breast cancer burden and identification of its influencing factors help in the development of public health policy and strategy against the disease. This study aimed to examine the variability of the excess mortality of female breast cancer patients in the North East Region of Peninsular Malaysia. This retrospective cohort study was conducted using breast cancer data from the Kelantan Cancer Registry between 2007 and 2011, and Kelantan general population mortality data. The breast cancer cases were followed up for five years until 2016. Out of 598 cases, 549 cases met the study criteria and were included in the analysis. Modelling of excess mortality was conducted using Poisson regression. Excess mortality of breast cancer varied according to age group (50 years old and below vs above 50 years old, Adj. EHR: 1.47; 95% CI: 1.31, 4.09; P=0.004), ethnicity (Malay vs non-Malay, Adj. EHR: 2.31; 95% CI: 1.11, 1.96; P=0.008), and stage (stage III and IV vs. stage I and II, Adj. EHR: 5.75; 95% CI: 4.24, 7.81; P<0.001). In conclusion, public health policy and strategy aim to improve cancer survival should focus more on patients presented at age below 50 years old, Malay ethnicity, and at a later stage.
ARTICLE | doi:10.20944/preprints201902.0042.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: RNA-Seq; Oncology; DNA repair; Survival; PCNA metagene
Online: 4 February 2019 (16:55:20 CET)
Removal of the proliferation component of gene expression by PCNA adjustment has been addressed in numerous survival prediction studies for breast cancer and all cancers in the TCGA. These studies indicate that widespread co-regulation of proliferation upwardly biases survival prediction when gene selection is performed on a genome-wide basis. In addition, removal of the correlative effects of proliferation does not reduce the random bias associated with survival prediction using random gene selection. Since most cancers become addicted to DNA repair as a result of forced cellular replication, increased oxidation, and repair deficiencies from oncogenic loss or genetic polymorphisms, we pursued an investigation to remove the proliferation component of expression in DNA repair genes to determine survival prediction. This translational hypothesis-driven focus on DNA repair genes is directly amenable to finding new sets of DNA repair genes that could potentially be studied for inhibition therapy. Overall survival (OS) prediction was evaluated in 18 cancers by using normalized RNA-Seq data for 126 DNA repair genes with expression available in TCGA. Transformations for normality and adjustments for age at diagnosis, stage, and PCNA metagene expression were performed for all DNA repair genes. We also analyzed genomic event rates (GER) for somatic mutations, deletions, and amplification in driver genes and DNA repair genes. After performing empirical p-value testing with use of randomly selected gene sets, it was observed that OS could be predicted significantly by sets of DNA repair genes for 61% (11/18) of the cancers. Interestingly, PARP1 was not a significant predictor of survival for any of the 11 cancers. Results from cluster analysis of GERs indicates that the most opportunistic cancers for inhibition therapy may be AML, colorectal, and renal papillary, because of potentially less confounding due to lower GERs for mutations, deletions, and amplifications in DNA repair genes. However, the most opportunistic cancer for inhibition therapy is likely to be AML, since it showed the lowest GERs for mutations, deletions, and amplifications in DNA repair genes. In conclusion, our hypothesis-driven focus to target DNA repair gene expression adjusted for the PCNA metagene as a means of predicting OS in various cancers resulted in statistically significant sets of genes.
ARTICLE | doi:10.20944/preprints201812.0151.v1
Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: Peripatidae, conservation status, survival, urban populations, threatened species
Online: 12 December 2018 (14:07:09 CET)
ABSTRACT: Charismatic species, like the panda, play an important role in conservation, and velvet worms arguably are charismatic worms. Thanks to their extraordinary hunting mechanism, they have inspired from a female metal band in Japan, to origami worms in Russia and video game monsters in the USA. Objective: To assess their conservation status in Costa Rica. Methods: we located all collection records of the 29 known species from the Onychophora Database in the map of the Costa Rican Conservation Network. Results: We found that seven species are protected inside forest reserves, five in Protected Zones, four in Wildlife Refuges, two in National Parks and one, Principapillatus hitoyensis, in a strictly pristine Biological Reserve. The largest species in the world, Peripatus solorzanoi, occurs both inside a Forest Reserve and in protected private land. Protection inside Costa Rican nature areas is enforced year round by personnel that includes armed guards, and is supported by educational programs in surrounding communities. Twelve species have not been found in protected areas, but in Costa Rica, all biological species, named and unnamed, are protected by law and cannot be legally collected, or exported, without technically issued permits. Conclusion: Like in the only other country with similar information (New Zealand), the conservation of onychophorans seems to be of least concern for at least two thirds of the known species. Epiperipatus isthmicola, recently rediscovered after a century of absence in collections, can be considered Threatened because nearly all of its natural habitat has now been covered by a city.
ARTICLE | doi:10.20944/preprints201810.0383.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Biologic subtypes; diagnosis; inflammatory breast cancer; pCR; survival
Online: 17 October 2018 (11:08:56 CEST)
The aim of this study was to examine pathologic complete response (pCR) and overall survival (OS) of patients diagnosed with non-metastatic inflammatory breast cancer (IBC). A total of N=8,550 cases undergoing surgery were identified between 2004-2013, using the National Cancer Database (NCDB). Patients were grouped into 4 biologic subtypes (HR+/HER2-, HR+/HER2+, HR-/HER2+, HR-/HER2-). The median age at diagnosis was 56 years. On average, women were followed for 3.7 years [interquartile range=3.0]. The majority were white (80%), had private health insurance (50%), and presented with poorly differentiated tumors (57%). Approximately 46% of the cancers were >5cm. Most patients underwent mastectomy (94%) and received radiotherapy (71%). Differences by biologic subtypes were observed for grade, lymph node invasion, race, and tumor size (p<.0001). Compared with non-pCR (54%), patients experiencing pCR had superior 5-year survival (77%) (p<.0001). Survival was poor for triple-negative (TN) tumors (37%) vs. other biologic subtypes (60%) (p<.0001). On multivariable analysis, TN-IBC, positive margins, and not receiving either chemotherapy, hormonal therapy or radiotherapy were independently associated with poor 5-year survival (p<.0001). In this large multicentric analysis of IBC, categorized by biologic subtypes, we observed significant differential tumor, patient and treatment characteristics, and OS.
ARTICLE | doi:10.20944/preprints201806.0490.v1
Subject: Arts And Humanities, Humanities Keywords: The Uncanny, Deadly Premonition, Twin Peaks, Survival Horror
Online: 29 June 2018 (15:33:39 CEST)
The influence of the cult television series Twin Peaks (1990-91) can be detected in a wide range of videogames, from adventure, to roleplaying to survival horror titles. While many games variously draw upon the narrative, setting and imagery of the series for inspiration, certain element of the distinctive uncanniness of Twin Peaks are difficult to translate into gameplay, particularly its ability consistently disrupt the expectations and emotional responses of its audience. This paper examines the ways in which the 2010 survival horror title Deadly Premonition attempts to replicate the uncanniness of Twin Peaks in both its narrative and gameplay, noting how it expands upon conceptualisations of the gamerly uncanny (Hoeger and Huber 2007). It contends that Deadly Premonition's awkward and uncanny recombination of seemingly inconsistent and excessive gameplay features mirrors the ways in which David Lynch and Mark Frost draw upon and subvert audience expectations for police procedurals and soap operas in the original Twin Peaks, while also providing a similarly disorienting excess of “realistic” detail. Furthermore its exploration of the theme of possession – a central element of the television series – offers a diegetic exploration of the uncanny relationship between the player and their onscreen avatar.
ARTICLE | doi:10.20944/preprints202311.0809.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: colic syndrome; equine; prognostic; survival; outcome; physiological; parameters; biochemical
Online: 14 November 2023 (05:34:17 CET)
Colic, a primary cause of illness and death in horses, necessitates improved prognostic tools. We assessed the predictive value of physiological parameters in colic prognosis. A comprehensive clinical evaluation encompassed heart rate, mucous membranes, capillary refill time, rectal temperature, respiratory rate, gut motility, reflux, and limb pulse strength. Results reveal key predictors of fatal outcomes in colic-affected horses. Stomach reflux, absence of gut noises, and increased heart rate (mean increase of 12 bpm) strongly correlate with a poor prognosis. Prolonged capillary refill (mean increase of 3 seconds), elevated packed cell volume (mean increase of 4%), and blood lactate levels (mean increase of 5 mmol/L) underscore the significance of these markers. Notably, blood lactate (p < 0.001), gut noises (p < 0.05), and heart rate (p < 0.001) exhibit the highest predictive significance based on statistical analysis. Future research should explore the prognostic potential of additional parameters and assess the impact of recommended treatments on colic prognosis. This data-driven study emphasizes the critical role of early recognition and thorough assessment in colic cases, offering vital insights into improving equine healthcare and mitigating mortality rates.
ARTICLE | doi:10.20944/preprints202310.1012.v1
Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: Minimally invasive surgery, Type II endometrial cancer, overall survival
Online: 18 October 2023 (03:05:50 CEST)
Objective: To compare the overall survival (OS) and surgical outcomes between open and minimally invasive surgery (MIS) in a large cohort of women with Type II endometrial cancer. Methods: Using the National Cancer Database, we identified a cohort of women who underwent hysterectomy for type II endometrial cancer (serous, clear cell, carcinosarcoma) between January 2010 and December 2014. Primary outcome was the comparison of OS between MIS and the open approach. Secondary outcomes included the length of hospital stay, readmission rate, 30- and 90-day mortality. Multivariable logistic regression and inverse propensity weighting analyses were performed. Results: A total of 12,905 patients with Type II, Stage I-III endometrial cancer who underwent hysterectomy were identified. Among these patients, 7,123 (55.2%) underwent MIS. The utilization of MIS increased from 39% to 64% over the four-year period. In propensity-score-weighted analysis, MIS was associated with superior OS (101.7 vs. 86.7 months, p=0.0003 by the log-rank test), with a hazard ratio of 0.9 (CI 0.857-0.954, p=0.0002). MIS was also associated with improved perioperative outcomes, including a shorter length of stay (1 vs. 4 days, p<0.001), lower 30-day readmission rate (2.5% vs. 5%), and lower 30- and 90-day postoperative mortality (0.5% vs. 1.3% and 1.5% vs. 3.6%, respectively; p<0.001). The time interval between surgery and initiation of chemotherapy was shorter in the MIS group (38 vs. 41 days, p<0.001).The increase in MIS adoption correlated with a decrease in 90-day postoperative mortality (2.8% to 2.2%, r=-0.89; p=0.003) and 12-month overall mortality (51% to 38%, r=-0.95, p=0.006). Conclusions: In an epidemiologic study, MIS is associated with improved overall survival and superior perioperative outcomes compared to open surgery in women with Type II endometrial cancer.
ARTICLE | doi:10.20944/preprints202306.1590.v1
Subject: Computer Science And Mathematics, Probability And Statistics Keywords: survival distribution; right-skewed distribution; EM algorithm; simulated annealing
Online: 22 June 2023 (10:29:31 CEST)
In recent decades, there have been numerous endeavors to develop a novel category of survival distributions possessing enhanced flexibility through the extension of existing distributions. This article constructs and validates the statistical properties of a novel survival distribution in order to obtain an alternative distribution that is suitable for analyzing survival data by presenting the novel mixture of the Fréchet distribution along with statistical properties such as the probability density function (PDF), cumulative distribution function (CDF), rth ordinary moment, skewness, kurtosis, moment-generating function, mean, variance, mode, survival function, hazard function, and asymptotic behavior, as well as constructing the estimators of the unknown parameter by employing the expectation-maximization (EM) algorithm, and simulated annealing. Additionally, the performance of the proposed estimators was compared with bias, mean squared errors (MSE), and simulated variances, and given an illustrative example of the proposed distribution to the survival data set in order to show that the proposed distribution is appropriate for the right-skewed data. This will be extremely advantageous in survival analysis.
REVIEW | doi:10.20944/preprints202302.0134.v1
Subject: Biology And Life Sciences, Forestry Keywords: planting depth; drought; freeze injury; herbivory; mortality; survival; insects
Online: 7 February 2023 (14:01:52 CET)
Artificial regeneration is successful when high performing seedlings are transported with care to the planting site, stored for a short period in an environment without desiccation or fungal growth, and are planted in a deep hole so roots are in contact with moist soil. One of the requirements for success is the ability to avoid common planting mistakes. Due, in part, to use of container stock plus an increase in rainfall, average 1st year survival of pine seedlings (89%) in the southern United States is about 15% greater now than 45 years ago. However, when survival is less than 50% six months after planting, some landowners seek reimbursement for their loss. Some assume poor seedling quality was the cause without realizing that anaerobic soils or sudden freeze events or shallow planting holes or pruning roots, a lack of rain, or underground insects can kill pines. With a focus on pines planted in the southern United States, we list non-nursery factors that have killed seedlings in North America, Africa and Europe.
ARTICLE | doi:10.20944/preprints202105.0093.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Breast neoplasms; neoplasm metastasis; inflammatory breast neoplasms; survival analysis
Online: 6 May 2021 (14:56:00 CEST)
The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype, and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. Median OS was significantly longer in patients with non-inflammatory breast cancer (P = .02) and in patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all P <.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.
ARTICLE | doi:10.20944/preprints202104.0529.v1
Subject: Computer Science And Mathematics, Algebra And Number Theory Keywords: censored data; machine learning; deep learning; DNNSurv; survival analysis
Online: 20 April 2021 (11:15:02 CEST)
As the development of high-throughput technologies, more and more high-dimensional or ultra high-dimensional genomic data are generated. Therefore, how to make effective analysis of such data becomes a challenge. Machine learning (ML) algorithms have been widely applied for modelling nonlinear and complicated interactions in a variety of practical fields such as high-dimensional survival data. Recently, the multilayer deep neural network (DNN) models have made remarkable achievements. Thus, a Cox-based DNN prediction survival model (DNNSurv model) , which was built with Keras and Tensorflow, was developed. However, its results were only evaluated to the survival datasets with high-dimensional or large sample sizes. In this paper, we evaluate the prediction performance of the DNNSurv model using ultra high-dimensional and high-dimensional survival datasets, and compare it with three popular ML survival prediction models (i.e., random survival forest and Cox-based LASSO and Ridge models). For this purpose we also present the optimal setting of several hyper-parameters including selection of tuning parameter. The proposed method demonstrates via data analysis that the DNNSurv model performs overall well as compared with the ML models, in terms of three main evaluation measures (i.e., concordance index, time-dependent Brier score and time-dependent AUC) for survival prediction performance.
ARTICLE | doi:10.20944/preprints202101.0244.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: DPP9; SNPs; Hepatocellular carcinoma; Survival; TCGA; DPP4 gene family
Online: 13 January 2021 (12:13:37 CET)
Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases including The Cancer Genome Atlas (TCGA) were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 LoF variants were most often associated with uterine carcinoma. Two DPP9 intronic SNPs that have been associated with lung fibrosis and COVID-19 were not associated with liver fibrosis or cancer. All four DPP4-like genes were overexpressed in liver tumours and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients.. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is essential for human survival and the DPP4 protease family is important in cancer pathogenesis.
ARTICLE | doi:10.20944/preprints202012.0476.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Ovarian cancer; mapping-based; mapping-free; SNVs; survival prognosis
Online: 18 December 2020 (15:15:50 CET)
Ovarian cancer is the most frequent cause of deaths in gynecologic malignancies. Many possible mechanisms have been proposed via RNAseq and DNAseq technique recently. However, the driving factors are still obscure. The possible reasons are attributed to the incomplete human reference. This study integrated the canonical mapping-based and mapping-free protocols to extract reliable variations and novel events. We eventually obtained 450 reliable SNVs from the WES data and novel events from the RNAseq data, including 154 SNVs, 462 intron events, two repeats and six splice events. We identified six differentially expressed genes and six contigs that are significantly related to survival prognosis. The recurrent SNVs in significantly differentially expressed genes can be validated in an independent cohort of 20 Chinese ovarian cancer patients.
ARTICLE | doi:10.20944/preprints202010.0624.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: medical record systems; cutaneous malignant melanoma; survival analysis; immunotherapy
Online: 29 October 2020 (16:02:44 CET)
Background: Cutaneous malignant melanoma (CMM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice for the treatment of metastatic CMM. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CMM in several Italian centers which are part of the Clinical National Melanoma Registry (CNMR), and the oncological outcomes obtained. Methods: CNMR collects data of patients with a histologically confirmed diagnosis of primary CMM treated in one of the 38 Italian institutions (hospitals, research institutes, etc.) participating in the network. Melanoma-specific survival and Overall survival were calculated. Kaplan-Meier curves and medians of OS and 95% CI are presented overall and by immunotherapy and target treatments. The Log-rank test compared curves by treatments. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. Results: The median follow-up time was 36 months (range 1.2-185.1). 787 CMM were included in the analysis with completed information about therapies.Global immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by nivolumab/pembrolizumab immunotherapy (anti-PD1 HR=0.25 95% CI 0.14-0.42), globally immunotherapy was significantly associated with improved survival, either for anti-CTL A4 monotherapy or combined with anti-PD1 (HR=0.47;95% CI 0.33-0.66 and HR=0.26; 95% CI 0.15-0.46, respectively). Conclusions: The nivolumab/pembrolizumab and the combination of ipilimumab can be considered the best therapy to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.
ARTICLE | doi:10.20944/preprints202007.0277.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: colorectal cancer; survival; KRAS; median; codon; metastasis; sided; tumour
Online: 13 July 2020 (03:03:23 CEST)
Colorectal cancer (CRC) is the third most common cancer, with rising incidence due to lifestyle and diet. 40% of CRC cases are found to have KRAS mutations. In this study, we investigate the survival outcome of metastatic Colorectal cancer mCRC) patients in Brunei Darussalam restrospectively. Chi-squared test was used to compare the survival outcomes of mCRC patients, and Mann-Whitney U test was used to compare the median ages of both groups. Kaplan-Meier survival curves were drawn and logrank test was used to compare the survival outcome between two groups. There was a total of 105 patients with stage IV CRC being treated during the study period. 81.6% (n=62) of mCRC patients were found to have the primary tumours on the left side of the colon. 19 of these 26 (73.1%) mutant KRAS mCRC patients died, while 23 of 50 (46.0%) wild-type KRAS mCRC patients died at the end of the study period, contributing to death rates of 45.2% and 54.8%, correspondingly. 30.3% (n=23) of the study population had a single metastatic site detected (either liver, or lung or any other organs), while 69.7% (n=53) of the 76 mCRC patients had two (double) or more metastatic sites. 69.2% (n=18) and 30.8% (n=8) of the mutant KRAS mCRC patients had mutations within codons 12 and 13, respectively. To our knowledge, this is the first study in Brunei Darussalam to analyse both the survival outcomes of metastatic CRC patients and those of mutant KRAS mCRC patients. Chi-squared analysis showed a significant difference between the survival outcomes of wild-type KRAS and mutant KRAS mCRC patients (p-value = 0.024). There was a significant difference in the survival outcome between the mutant KRAS mCRC patients with RCC and mutant KRAS mCRC with LCC patients. There was no significant difference between the survival outcomes of mutant KRAS patients with mutations in either codon 12 or 13 of the KRAS gene (Table 3). However, there is a significant difference in the median survival periods between the mutant KRAS mCRC patients with mutations in codon 12 and those with mutation in codon 13 of the KRAS gene (p-value = 0.003). In conclusion, we found that mutant KRAS mCRC patients had a significantly poorer OS, which was shown to be worse when the primary tumours were found at the left side of the colon. Mutant KRAS mCRC patients with mutations in codon 12 were found to have shorter survival median periods than those with mutations within codon 13.
ARTICLE | doi:10.20944/preprints202005.0110.v1
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; intervention; growth curve; survival; doubling time; correlation
Online: 7 May 2020 (08:24:00 CEST)
COVID-19 is fast spreading around the globe in a highly contagious manner. In this article we have described that after prolonged interventions the percentage growth curve for COVID-19 cases showed a flattened nature, after prolonged volatility in number of COVID-19 cases. The stability in the growth curve was continuously maintained from 18 April, 2020 to 29 April, 2020. The significance of this sustained stable curve on survival & doubling time has been discussed. One significant part of the study reflected that the doubling time of COVID-19 cases showed a negative correlation with the percent increase in COVID-19 cases (R=0.301). It is plausible that if such negative correlation is maintained with further flattening of the growth curve at a lower level, it may influence the infective ability of nCoV-19 & ultimately have a positive evolutionary implication on the spread of COVID-19 among the population.
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: glioblastoma; miRNA; MGMT; survival; radiotherapy; chemotherapy; temozolomide; translational medicine
Online: 9 April 2020 (08:27:12 CEST)
Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than 3% and an average survival rate of 12 months after diagnosis, GBM has become a focus of current research to urgently develop new therapeutic approaches in order to prolong survival of GBM patients. The methylation status of the promoter region of the O6-methylguanine–DNA methyltransferase (MGMT) is nowadays routinely analyzed, since a methylated promoter region is beneficial for an effective response to temozolomide-based chemotherapy. Furthermore, several miRNAs were identified regulating MGMT expression, apart from promoter methylation, by degrading MGMT mRNA before protein translation. These miRNAs could be a promising innovative treatment approach to enhance Temozolomide (TMZ) sensitivity in MGMT unmethylated patients and to increase progression-free survival as well as long-term survival. In this review, the relevant miRNAs are systematically reviewed.
ARTICLE | doi:10.20944/preprints202311.0688.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: melanoma; metastasis; overall survival; progression-free survival; side effects; Nivolumab; Ipilimumab; anti-programmed death-1 antibodies; anti-cytotoxic T-lymphocyte antigen-4 antibodies.
Online: 10 November 2023 (11:05:56 CET)
Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.
ARTICLE | doi:10.20944/preprints202310.0681.v1
Subject: Biology And Life Sciences, Aquatic Science Keywords: Aspalathus linearis; Oreochromis mossambicus; feed supplements; growth performance; survival rate
Online: 11 October 2023 (08:53:42 CEST)
Supplements in fish nutrition can help alleviate pressure on the wild stock; however, there is limited information on the benefits of rooibos tea extract in aquafeed. This study aimed to determine the effect of rooibos tea extract inclusion in the commercial diet on the growth performance of larval fish. Fish were reared on three diets: a commercial diet with 30% fermented or green rooibos extract and a commercial tilapia diet (control). Fish (initial weight of 0.54 ± 0.008 g and length of 2.22 ± 0.01 cm) were randomly distributed into recirculating aquaculture systems in triplicates at 100 fish per tank. Fish was hand-fed thrice daily for eight weeks at 2% body weight. After that, samples were withdrawn to measure growth parameters. Fish-fed fermented, and green tea extracts exhibited a significantly (p ˂ 0.05) higher weight gain than the controls. The feed conversion ratio was higher in the control group, fermented (1.50 ± 0.25 cm) and green tea (1.41 ± 0.07 cm). Similarly, the control group exhibited the highest condition factor (K=13.14 ± 4.87). The two treatment groups were comparable (p >0.05) in growth performance. Overall, the evidence indicates that adding rooibos tea extracts to the basal diet can improve fish growth.
ARTICLE | doi:10.20944/preprints202304.0151.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Ovarian clear cell carcinoma; residual disease; recurrence; survival; endometriosis- associated
Online: 10 April 2023 (05:14:42 CEST)
A retrospective study including 49 women with ovarian clear cell carcinoma between January 2009 and December 2021 at Oxford cancer centre was done. The mean age was 63 years, with 78% post-menopausal. All women underwent cytoreductive surgery with no residual disease (R0) in 39 women. The follow-up time ranged between 12-144 months, with mean of 105.5 months. The 3-year OS was 73.4%, and 3-year PFS was 81.3%, with a mean of 101.7months (95%CI, 84.63-118.93). As expected, women with stage 1 disease had the best outcome. In comparing OS in respect to absence or presence of residual disease, the 3-year OS was 88.6% (95% CI 108.6-141.8), compared to 12.5% (95% CI 4.48-32.11) respectively (P<0.001). In multivariant analysis the variables included were CA 125 (< or >200 IU/ml), Hb (< or >115 g/L), albumin (< or >40 g/L), associated endometriosis, ascites, residual disease, and FIGO staging. FIGO stage was the only independent prognostic indicator of OS with (p<0.05). Surgery to achieve no residual tumour is necessary to improve the prognosis in advanced OCCC. At present, the true challenge is to predict which patients with early-stage disease are at higher risk of recurrence and would most benefit from adjuvant treatments.
ARTICLE | doi:10.20944/preprints202303.0060.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Neuroendocrine tumors; survival; meta-analysis; NET; gastropancreatic NET; systemic review
Online: 3 March 2023 (06:59:20 CET)
Background: Neuroendocrine tumors (NET) are a rare group of epithelial neoplasm present in gastrointestinal tract (GI) (67.5%), bronchopulmonary tree (25.3-30%), and in 15% of cases, the primary sites cannot be identified. Although endoscopic screening, improvement in pathological techniques, and early detection have shown improvement in NET survival rates, the prognosis of advanced, metastatic, and poorly differentiated NET is very poor. In this study, we aimed to evaluate the effect of Gastrointestinal and pancreatic (GEPs) NETs grade on overall survival. Method: We searched observational studies describing the overall survival or prognostic factors of primary GEP NETs from May 2011 -May 2021 following PRISMA guidelines. Studies describing the effect of primary grade 3 GEP NETs on overall survival were included. Meta-analysis was performed, and pooled hazard ratio and their 95% confidence interval (95% CI) were obtained. The forest plots were created using random-effects models and sensitivity analysis was performed to account for the heterogeneity. Results: Seven studies with 7692 confirmed patients were included. In our meta-analysis grade 3 GEP NET were associated with higher odds of poor survival (pooled HR: 2.73; 95% CI: 1.36–5.47; p = 0.005), with 92% heterogeneity between studies (p < 0.0001). To account for heterogeneity, sensitivity analysis was performed by removing two outlying studies (Fathi et al. and Foubert et al.) on funnel plots. The results after sensitivity analysis did not change and still showed significant association of grade 3 with poor survival (pooled HR: 4.53; 95% CI: 3.54–5.78; p < 0.00001), with no heterogeneity between studies (p = 0.72; I2 = 0%). Conclusion: Our meta-analysis found that grade 3 GEP NETs are associated with poor survival and additional future studies are needed to identify other risk factors associated with poor survival in GEP NETs to improve mortality.
REVIEW | doi:10.20944/preprints202207.0251.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: adenovirus infection; adenovirus disease; cidofovir; preemptive therapy; risk factors; survival
Online: 18 July 2022 (08:13:46 CEST)
Human Adenovirus (HAdV) infection occurs in 14-16% of patients in the early months after pediatric hematopoietic cell transplantation (HCT) and this correlates with a higher risk to develop HAdV disease and overall 6-month mortality. The main risk factors for HAdV infection are T-cell depletion of the graft by ex vivo CD34+ selection or in vivo use of alemtuzumab or anti-thymocyte serum, the development of grade III-IV graft versus host disease (GVHD), the type of donor (unrelated donor, cord blood, haploidentical or HLA mismatched parent) and severe lymphopenia (< 0.2 x 109/L). The prevention of HAdV disease is based on early intervention with antivirals in the asymptomatic patient when the permitted viral load threshold on blood (> 102-3 copies/ml) and/or on the stool (109 copies/g stool) is exceeded. Cidofovir, a monophosphate nucleotide analog of cytosine, is the primary drug for preemptive therapy, used at 5 mg/kg/week for 2 weeks followed by 3-5 mg/kg every 2 weeks. The alternative schedule is 1 mg/kg every other day (three times/week). Enhancing virus-specific T-cell immunity in the first months post-HCT by donor-derived or third-party-derived virus-specific T cells represents an innovative and promising way of intervention applicable both in prevention and therapeutic setting.
ARTICLE | doi:10.20944/preprints202202.0051.v1
Subject: Computer Science And Mathematics, Mathematical And Computational Biology Keywords: Glioblastoma; survival prediction; Machine Learning; biomarkers; HumanPSDTM; Long-term survivor
Online: 3 February 2022 (12:00:23 CET)
Glioblastoma (GBM) is a very aggressive malignant brain tumor with the vast majority of patients surviving less than 12 months (Short-term survivors [STS]). Only around 2% of patients survive more than 36 months (Long-term survivors [LTS]). Studying these extreme survival groups might help in better understanding GBM biology. This work aims at exploring application of machine learning methods in predicting survival groups(STS, LTS). We used age and gene expression profiles belonging to 249 samples from publicly available datasets. 10 Machine learning methods have been implemented and compared for their performances. Hyperparameter tuned random forest model performed best with accuracy of 80% (AUC of 74% and F1_score of 85%). The performance of this model is validated on external test data of 16 samples. The model predicted the true survival group for 15 samples achieving an accuracy of 93.75%. This classification model is deployed as a web tool GlioSurvML. The top 1500 features which retained classification efficiency (Accuracy of 80%, AUC of 74%) were studied for enriched pathways and disease-causal biomarker associations using the HumanPSDTM database. We identified 199 genes as possible biomarkers of GBM and/or similar diseases (like Glioma, astrocytoma, and others). 57 of these genes are shown to be differentially expressed across survival groups and/or have impact on survival. This work demonstrates the application of machine learning methods in predicting survival groups of GBM.
ARTICLE | doi:10.20944/preprints202201.0426.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Sinonasal squamous cell carcinoma; Head and neck; HPV; p16; Survival
Online: 28 January 2022 (07:20:10 CET)
Background: Sinonasal squamous cell carcinoma (SNSCC) is rare in the general population. No clear and consistent etiologic correlation between human papillomavirus and SNSCC has yet been delineated in literature. p16 is a tumour suppressor protein used as a surrogate marker for HPV. This study aims to evaluate the relationship between p16 overexpression in SNSCC and its role in prognosis and survival. Methods: A population-based retrospective analysis was performed using prospectively collected data from the Northern Alberta Head and Neck Tumour Board, Alberta Cancer Registry, and Alberta Cancer Research Biobank. p16 overexpression was analyzed from pathologic sample of patients meeting study criteria, and participants were dichotomized by status. Subsequently, nonparametric analysis of demographics, initial staging, and initial treatment were performed, and a Kapan-Meier curve was developed to assess differences in survival. Results: 16 patients were included in analysis. p16 overexpression was seen in 68.8% of patients. p16 positive and negative groups were comparable for age, gender, smoking status, stage, and treatment. A statistically significant five-year survival advantage was observed in patients with p16 positive SNSCC (p = 0.013). Conclusions: This is the first Canadian study to demonstrate a high prevalence of p16 positivity in SNSCC and its presence denoting a statistically significant survival advantage. Results demonstrate a previously unconfirmed role of oncogenic HPV in SNSCC.
ARTICLE | doi:10.20944/preprints202108.0289.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: bortezomib; cMAF; MAFb; multiple myeloma; POMP; prognosis; PFS; survival; OS
Online: 13 August 2021 (08:43:42 CEST)
While multiple myeloma (MM) treatment with proteasome inhibitors and other agents yields encouraging results, primary and secondary resistance remains an emerging problem. An important factor in such treatment resistance is the overexpression of several proteins. The present study comprehensively evaluates the expression of POMP, PSMB5, NRF2, XBP1, cMAF and MAFb proteins in plasma cells isolated from the bone marrow of 39 MM patients treated with bortezomib-based regimens using enzyme-linked immunosorbent assay (ELISA). The proteins were selected on the basis of previous laboratory and clinical studies in bortezomib treated MM patients. It was found that the expression of the investigated proteins did not significantly differ between bortezomib-sensitive and bortezomib-refractory patients. However, the expression of some proteins correlated with overall survival (OS); this was significantly shorter in patients with higher POMP expression (HR 2.8, 95% CI: 1.1-7.0, p = 0.0277) and longer in those with higher MAFB expression (HR 0.32, 95% CI: 0.13-0.80, p = 0.0147). Our results indicate that high expression of POMP and MAFB in MM plasma cells may serve as predictors of OS in MM patients treated with bortezomib-based regimens. However, further studies are needed to determine the role of these factors in effective strategies for improving anti-myeloma therapy.
ARTICLE | doi:10.20944/preprints202106.0330.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Chemotherapy; Radiotherapy; Cognitive dysfunction; Big data; Cohort studies; Survival analysis
Online: 14 June 2021 (07:51:57 CEST)
Background: We aimed to assess the risk of chemotherapy- and radiotherapy-related cognitive impairment in colorectal cancer patients. Methods: We randomly selected 40% of colorectal cancer patients from Korean National Health Insurance Database (NHID), 2004-2018 (N=148,848). Patients with one or more ICD-10 diagnostic codes for dementia or mild cognitive impairment was defined as cognitive impairment cases. Patients who were aged 18 or younger, diagnosed with cognitive impairment before colorectal cancer (N=8,225) and did not receive primary resection (N=45,320) were excluded. The effects of each chemotherapy agent on cognitive impairment were estimated. We additionally estimated the effect of radiotherapy in rectal cancer patients. Time-dependent competing risk Cox regression was conducted to estimate overall and age-specific hazard ratios (HR) separately for colon and rectal cancer. Results: In colon cancer, capecitabine and irinotecan was associated with higher cognitive im-pairment, while 5-fluorouracil was not. In rectal cancer, no chemotherapy agents increased the risk of cognitive impairment, nor did radiotherapy. Hazardous association of irinotecan was estimated larger in elderly patients compared with younger counterparts. Conclusion: Heterogeneous associations between various chemotherapy agents and cognitive impairment were observed. Elderly patients were more vulnerable to possible adverse cognitive effects. Radiotherapy did not increase the risk of cognitive impairment.
ARTICLE | doi:10.20944/preprints202102.0002.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Acute Toxicity, Oropharyngeal Cancer; Proton Beam Therapy; Radiation Therapy; Survival
Online: 1 February 2021 (08:57:08 CET)
Purpose: To report the early clinical outcomes of combining intensity‐modulated radiation therapy (IMRT) and intensity‐modulated proton therapy (IMPT) in comparison with IMRT alone in treating the oropharynx cancer (OPC) patients. Materials and Methods: The medical records of 148 OPC patients were retrospectively reviewed, who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center. During the 5.5 weeks’ RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity‐score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. Results: With the median follow‐up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, IMRT/IMPT combination group experienced grade ≥3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p<0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p=0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p=0.021); and AQA in 47.4% and 21.1% (p=0.016), respectively. In multivariate logistic regression, grade ≥3 mucositis was significantly less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.027 and 0.024, respectively). AQA score ≥3 was also less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.085 and 0.018, respectively). Conclusions: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.
REVIEW | doi:10.20944/preprints202010.0243.v1
Subject: Business, Economics And Management, Accounting And Taxation Keywords: distance education; open and distance education; student retention; survival analysis
Online: 12 October 2020 (13:22:55 CEST)
Student retention is one indicator of accountability in the implementation of educational programs. Achievement of student retention rates indicates the performance of the quality objectives of an institution or college. To get an accurate picture of the factors related to retention, we need to do modeling. The retention variable is the time response variable measured in semester units. One of the statistical analyzes that can be used to analyze response data in time is survival analysis. The selection of an accurate analytical method in modeling will produce valid conclusions and impact making policies that are right and on target. This paper presents alternative modeling of student retention in distance education using survival analysis. The method used is a literature review. This paper also briefly describes distance education, open and distance education, distance education students' characteristics, distance education student retention, and survival models for modeling student retention in distance education.
CASE REPORT | doi:10.20944/preprints201908.0278.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: FOLFIRINOX; pancreatic ductal adenocarcinoma; surgery; liver metastases; long term survival
Online: 27 August 2019 (05:16:03 CEST)
Metastatic pancreatic ductal adenocarcinoma pancreatic (PDAC) is characterized by poor prognosis and short survival. Today, the use of new polytherapeutic regimens increases clinical outcome of these patients opening new clinical scenario. A crucial issue related to the actual improvement achieved with these new regimens is represented by the occasional possibility to observe a radiological complete response of metastatic lesions in patients with synchronous primary tumor. What could be the best therapeutic management of these patients? Could surgery represent an indication? Herein we reported a case of a patient with a PDAC of the head with multiple liver metastasis, who underwent first line chemotherapy with mFOLFIRINOX. After 10 cycles, he achieved a complete radiological response of liver metastases and a partial response of pancreatic lesion. A, duodenocephalopancreasectomy was performed. Due to liver a lung metastases after 8 months from surgery, a second line therapy was started with a disease free survival and overall survival of 8 months and 45 months, respectively. Improvement in the molecular characterization of PDAC could help in the selection of patients suitable for multimodal treatments.
ARTICLE | doi:10.20944/preprints201710.0086.v2
Subject: Engineering, Electrical And Electronic Engineering Keywords: cluster head; dead node; random; vicinity; modulation; index; survival; overhead
Online: 23 October 2017 (08:06:47 CEST)
As Heterogeneous Wireless Sensor Network (HWSN) fulfill the requirements of researchers in the design of real life application to resolve the issues of unattended problem. But, the main constraint face by researchers is energy source available with sensor nodes. To prolong the life of sensor nodes and hence HWSN, it is necessary to design energy efficient operational schemes. One of the most suitable routing scheme is clustering approach, which improves stability and hence enhances performance parameters of HWSN. A novel solution proposed in this article is to design energy efficient clustering protocol for HWSN, to enhance performance parameters by EECPEP-HWSN. Propose protocol is designed with three level nodes namely normal, advance and super node respectively. In clustering process, for selection of cluster head we consider three parameters available with sensor node at run time, i.e., initial energy, hop count and residual energy. This protocol enhance the energy efficiency of HWSN, it improves performance parameters in the form of enhance energy remain in the network, force to enhance stability period, prolong lifetime and hence higher throughput. It is been found that proposed protocol outperforms than LEACH, DEEC and SEP with about 188, 150 and 141 percent respectively.
ARTICLE | doi:10.20944/preprints202309.1752.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: Hepatocellular carcinoma; Transarterial radioembolization; Yttrium-90; Locoregional treatment; Portal vein tumor thrombosis; Overall survival; Progression-free survival; Skeletal muscle mass; Sarcopenia; Body mass index.
Online: 26 September 2023 (08:22:48 CEST)
Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90 loaded microspheres. This was a multicenter retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT) and 126 (36.3%) were classified as sarcopenic. The median overall survival (OS) was 28.1 months (95% CI, 24.8-35.7) and median progression-free survival was 8.0 months (95% CI, 6.4-9.4). Multivariate Cox regression analysis revealed that sarcopenia (hazard ratio [HR], 1.36; 95% CI, 1.00-1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33-2.49, p < 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04-1.92, p = 0.03), and albumin-bilirubin grade (2-3) (HR 1.74; 95% CI, 1.24-2.43, p < 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment sarcopenia independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.
REVIEW | doi:10.20944/preprints202309.1363.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Breast Cancer; Malignancy; Gulf Cooperation Council(GCC); Survival; HER2; Triple Negative
Online: 20 September 2023 (13:51:45 CEST)
Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of BC in the GCC. Most of the studies reported a consistent increase in BC incidence over the past decades, which was particularly attributed to the adoption of a westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data about BC risk factors in GCC was limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50, an advanced stage at presentation, and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed towards elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.
ARTICLE | doi:10.20944/preprints202309.0534.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: community-dwelling older individuals; comorbidity; deep learning; frailty; survival prediction model
Online: 7 September 2023 (09:30:19 CEST)
In a super-aged society, maintaining healthy aging, preventing death, and enabling a continua-tion of economic activities are crucial. This study sought to develop a model for predicting the survival time in community-dwelling older individuals by using a deep learning method, and to identify the level of influence of various risk factors on the survival period, so that older in-dividuals can manage their own health. This study used the Korean National Health Insurance Service claims data. We observed community-dwelling older people, aged 66 years, for 11 years and developed a survival time prediction model. Of the 189,697 individuals enrolled at baseline, 180,235 (95.0%) survived from 2009 to 2019, while 9,462 (5.0%) died. Using deep learning based models (C statistics = 0.7011), we identified Charlson’s comorbidity index; the frailty index; long-term care benefit grade; disability grade; income level; a combination of diabetes mellitus, hypertension, and dyslipidemia; sex; smoking status; and alcohol consumption habit as factors impacting survival. In particular, Charlson’s comorbidity index (SHAP value: 0.0445) and frailty index (SHAP value: 0.0443) were strong predictors of survival time. Older individuals should rec-ognize modifiable risk factors that affect survival period in order to manage their own health.
ARTICLE | doi:10.20944/preprints202308.0946.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SOX11; epithelial-mesenchymal; transition; E-cadherin; vimentin; ovarian; cancer; metastasis; survival
Online: 14 August 2023 (05:34:42 CEST)
Background: Ovarian cancer is the leading cause of death from gynecological malignancies with serous carcinoma being the most common histopathologic subtype. Epithelial-Mesenchymal Transition (EMT) correlates with an increased metastatic potential, whereas the transcription factor SOX11 is overexpressed in diverse malignancies. Methods: In the present study, we aim to evaluate the potential role of the immunohistochemical expression of SOX11 in 30 serous ovarian carcinomas in association with E-cadherin and Vimentin expression as well as with patients’ clinicopathological data. Results: Most of the examined cases showed concurrent expression of E-cadherin and Vimentin, whereas SOX11 was expressed in a minority of the cases (26,7%). Interestingly, the positive cases had more frequently a metastatic disease at the time of diagnosis compared to the negative cases (p=0.09), an association, however, of marginal significance. Moreover, there was a negative correlation between E-Cadherin and SOX11 expression (p=0,0077) and a positive correlation between Vimentin and SOX11 expression (p=0,0130). Conclusions: The present work, for the first time, provides preliminary evidence SOX11 overexpression alongside E-cadherin loss in the promotion of EMT in serous ovarian cancer, thereby endorsing tumor metastasis.
ARTICLE | doi:10.20944/preprints202308.0757.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: breast cancer; young patients; genomic; disease-free survival; galactose metabolism; stemness
Online: 9 August 2023 (09:35:55 CEST)
In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to the intermediate and elder patients. Therefore, it’s imperative to identify identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify prognostic factors. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.
ARTICLE | doi:10.20944/preprints202305.2227.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Biologics in UC; drug efficacy in UC; drug survival in UC
Online: 31 May 2023 (10:46:31 CEST)
Background & Aim: Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting. Methods: We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between Dec 1st, 2017, and May 1st, 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid, surgical, and hospitalization-free treatment. Results: 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks (p=0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p=0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ (p=0.593). Conclusion: VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.
ARTICLE | doi:10.20944/preprints202305.1968.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: breast cancer; deep learning; survival analysis; data dimension raising; age stratification
Online: 29 May 2023 (04:52:42 CEST)
(1) Background: Breast cancer is the second leading cause of cancer death among women. The accurate prediction of survival intervals will help physicians make informed decisions on treatment strategies or the use of palliative care for patients; (2) Methods: The gene expression is predictive and correlates to patient prognosis. To establish a reliable prediction tool, we collected the RNA-seq data of breast cancer patients, a total of 1187 RNA-seq data (median age 58 years), in FPKM format from the TCGA database. Among them, 144 RNA-seq data with date of death information was selected to establish the SaBrcada-AD dataset. We first normalized the SaBrcada-AD dataset to transcripts per million (TPM) to build survival prediction model SaBrcada. After normalization and dimension raising, the differential gene expression data were used for testing eight different deep learning architectures. Among them, GoogLeNet performed the best. Considering the effect of age on prognosis, we examined all ages between the lower and upper quartiles of patient age for a stratified random sampling test; (3) Results: Stratifying by age based on a cut-off of 61 years of age improved the accuracy of SaBrcada compared to previous findings, resulting in an accuracy of 0.798. We also built a free website tool to provide 5 kinds of predicted survival period information for clinician reference; (4) Conclusions: We established a breast cancer survival analysis prediction model, SaBrcada, and a website tool with the same name. Through this highly reliable survival analysis model and website tool, information on survival intervals will be provided for clinicians as part of precision medicine.
ARTICLE | doi:10.20944/preprints202301.0424.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: artificial incubation; captive rearing; apparent survival; hatching rate; fledging rate; conservation.
Online: 24 January 2023 (07:40:29 CET)
Headstarting is a conservation approach that suggests offering an advantage to a population by improving egg production, survival of embryos and/or juveniles. In this article, we are providing the quantitative data obtained during 10-years for different stages of headstarting (production of eggs per pair, hatching and fledging rates) and the resulting impact (survival to maturity, philopatry rate, sex ratio, apparent survival, growth/decline rate) on the local population of the critically endangered spoon-billed sandpiper. We have shown that headstarting gain is reduced over time from fledging to long-term recruitment to the local breeding population. The possible reasons for this reduction are suggested and discussed. The unexpected finding was a drastic difference in sex ratios of the new recruits which was about even for headstaring, but strongly male-biased for wild reared birds. We suggest that to happen due to increased mortality of female chicks in nature. We have also shown only headstarting could stop the global decline of the species, particularly once the suggested improvements are implemented and the number of pairs involved is scaled up. Headstarting also had a significant social effect due to involvement of in-creasing numbers of people both in the local communities in Chukotka and from many countries on the flyway into searching for marked birds and learning about waders, raising awareness about ecological problems on the East Asian-Australasian Flyway, thus, making the need for conservation actions on the flyway more obvious and sensible.
ARTICLE | doi:10.20944/preprints202106.0477.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Infective endocarditis; Kidney Transplantation; Survival analysis; graft failure; transplant infectious diseases
Online: 18 June 2021 (11:17:15 CEST)
Purpose: Kidney Transplant Recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation and outcome. While infective endocarditis (IE) is among such complications in KTRs, literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. Methods: We performed a retrospective case/control study which included patients from two centers. First episodes of definite or possible IE (Duke criteria), in adult KTRs from January 2007 to December 2018 were included, as well as two controls per case, and followed until December 31 2019. Clinical, biological, and microbiological data and the outcome were collected. Survival was studied using the Kaplan-Meier method. Finally, we searched for factors associated with the onset of IE in KTRs by the comparison of cases and controls. Results: Seventeen cases and 34 controls were included. IE was diagnosed after a mean delay of 78 months after KT, mostly on native valves of the left heart only. Pathogens of digestive origin were most frequently involved (six Enterococcus spp, three Streptococcus gallolyticus and one Escherichia coli), followed by Staphylococci (three cases of S. aureus and S. epidermidis each). Among the risk factors evaluated only age was significantly associated with the occurrence of IE in our study (63.8 years for cases vs. 55.6 years for controls, P=0.03) Patient and death-censored graft survival were greatly diminished five years after IE compared to controls being 50.3% vs. 80.6% (p<0.003) and 29.7% vs. 87.5% (p<0.002), respectively. Conclusion: IE in KTRs is a disease that carries significant risks both for the survival of the patient and the transplant.
REVIEW | doi:10.20944/preprints202105.0296.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: CAD/CAM; dental restoration; ceramic; all-ceramic; survival; fixed dental prosthesis
Online: 13 May 2021 (13:18:51 CEST)
Although CAD/CAM ceramics present a promising alternative to metal-ceramic fixed dental prostheses, little is known about their mid- and long-term clinical performance. This systematic review aims to estimate the survival and success rates and describes the underlying complication characteristics for CAD/CAM tooth-supported fixed dental prostheses (FDPs). We systematically searched MEDLINE and Web of Science to find relevant prospective studies with a follow-up of at least one year. We estimated pooled 1-, 5- and 10-year survival and success rates by combining the collected data in a Poisson regression model. Descriptive statistics were conducted to evaluate the distribution of failures and complications in the included studies. Risk of bias for the included studies was assessed with an adapted checklist for single-arm trials. Pooled estimated 1-, 5-, and 10-year survival rates ranged from 93.80% to 94.66%, 89.67% to 91.1%, and 79.33% to 82.20%, respectively. The corresponding success rates, excluding failures but including any other types of intervention, were 94.53% to 96.77%, 90.89% to 94.62%, and 81.78% to 89.25%. Secondary caries was the most frequent cause of failure, followed by chipping of the veneering. The most common cause of complication, excluding failures but requiring intervention, was chipping of the veneering. Risk of bias was generally acceptable for the included studies, with 7 studies associated with low risk of bias, 8 studies with a moderate risk of bias, and 3 studies with serious risk of bias. The current meta-analysis on CAD/CAM supported FDPs revealed satisfying survival and success rates for up to 10 years of exposure. More prospective studies focusing on long-term performance are needed to strengthen the evidence currently available in the literature.
ARTICLE | doi:10.20944/preprints202102.0365.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cancer subtype detection; Multi-omics data; Data integration; Autoencoder; Survival analysis
Online: 17 February 2021 (10:09:51 CET)
A heterogeneous disease like cancer is activated through multiple pathways and different perturbations. Depending upon the activated pathway(s), patients’ survival vary significantly and show different efficacy to various drugs. Therefore, cancer subtype detection using genomics level data is a significant research problem. Subtype detection is often a complex problem, and in most cases, needs multi-omics data fusion to achieve accurate subtyping. Different data fusion and subtyping approaches have been proposed, such as kernel-based fusion, matrix factorization, and deep learning autoencoders. In this paper, we compared the performance of different deep learning autoencoders for cancer subtype detection. We performed cancer subtype detection on four different cancer types from The Cancer Genome Atlas (TCGA) datasets using four autoencoder implementations. We also predicted the optimal number of subtypes in a cancer type using the silhouette score. We observed that the detected subtypes exhibit significant differences in survival profiles. Furthermore, we also compared the effect of feature selection and similarity measures for subtype detection. To evaluate the results obtained, we selected the Glioblastoma multiforme (GBM) dataset and identified the differentially expressed genes in each of the subtypes identified by the autoencoders; the obtained results coincide well with other genomic studies and can be corroborated with the involved pathways and biological functions. Thus, it shows that the results from the autoencoders, obtained through the interaction of different datatypes of cancer, can be used for the prediction and characterization of patient subgroups and survival profiles.
ARTICLE | doi:10.20944/preprints202005.0081.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Lung cancer; biomarker; gene ontology; protein-protein interaction networks; survival analysis
Online: 5 May 2020 (12:28:25 CEST)
Objective: The aim of study is to find key genes and enriched pathways associated with lung cancer. Participants and Methods: Differentially expressed genes (DEGs) data of 54674 genes based on stage, tumor and status of lung cancer was taken from 66 patients of African American (AAs) origin. 2392 DEGs were found based on stage, 13502 DEGs were found based on tumor, 2927 DEGs were found based on status having p value (p<0.05). Results: Total 33 common DEGs were found from stage, tumor and status of lung cancer. Gene ontology (GO) and KEGG pathway enrichment analysis was performed and 49 significant pathways were obtained, out of which 10 pathways were found to be exclusively involved in lung cancer development. Protein-protein interaction (PPI) network analysis found 69 nodes and 324 edges and identified 10 hub genes based on their highest degrees. Module analysis of PPI found that ‘Viral carcinogenesis’, ‘pathways in cancer’, ‘notch signaling pathway’, ‘AMPK signaling pathways’ had a close association with lung cancer. Conclusion: These identified DEGs regulate other genes which play important role in growth of lung cancer. The key genes and enriched pathways identified can thus help in better identification and prediction of lung cancer.
REVIEW | doi:10.20944/preprints201811.0511.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: coeliac disease; Crohn’s disease; dysplasia; histotype; overall survival; tumor infiltrating lymphocyte.
Online: 20 November 2018 (16:43:14 CET)
Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders, including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumor-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.
ARTICLE | doi:10.20944/preprints202311.0771.v1
Subject: Biology And Life Sciences, Insect Science Keywords: Long-lasting insecticidal net; median function survival; survivoship; attrition; fabric integrity; Tanzania
Online: 13 November 2023 (10:17:43 CET)
Long-lasting insecticidal nets (LLINs) have been the main contributor to the reduction of malaria in the past two decades in sub-Saharan Africa. Development of pyrethroid insecticide resistance threatens the effectiveness of these LLINs, especially when nets become holed and the insecticide decays. Three classes of dual active ingredient (AI) LLINs, have been assessed for their physical durability as follows: 1) Royal Guard®, combining pyriproxyfen, which is known to disrupt female reproduction and fertility of eggs, and a pyrethroid alpha-cypermethrin; 2) Interceptor® G2, two adulticides with differing modes of action; chlorfenapyr and alpha-cypermethrin; 3) OlysetTM Plus incorporates permethrin (pyrethroid) and a synergist, piperonyl butoxide, to enhance the potency of pyrethroid insecticides; all nets were compared to standard pyrethroid only net (Interceptor®). About 40,000 nets of each type were distributed in February 2019 to different villages in Misungwi. A total of 3072 LLINs were followed at 6, 12, 24, 30 and 36 months to assess survivorship and fabric integrity in a community setting. The median functional survival were less than three years with Interceptor®, Interceptor® G2 and Royal Guard® having 1.9 year each and 0.9 years for OlysetTM Plus . After 36 months, 90% of OlysetTM Plus and Royal Guard® and 87% of Interceptor® G2 were no longer present (thrown away) in the households due to wear and tear, compared to 79% for standard Interceptor®. Short life spans of all assessed LLINs were driven by material of the net, rather than social economic status and housing material. All dual AI LLINs have a poor textile durability with OlysetTM Plus being the worst of the three.
ARTICLE | doi:10.20944/preprints202307.1396.v2
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Cdkl5 KO mice; voluntary exercise; brain development; dendritic pathology; neuronal survival; neuroinflammation
Online: 7 September 2023 (11:25:05 CEST)
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene. CDD is characterized by a broad spectrum of clinical manifestations, including early-onset refractory epileptic seizures, intellectual disability, hypotonia, visual disturbances, and autism-like features. The Cdkl5 knockout (KO) mouse recapitulates several features of CDD, including autistic-like behavior, impaired learning and memory, and motor stereotypies. These behavioral alterations are accompanied by diminished neuronal maturation and survival, reduced dendritic branching and spine maturation, and marked microglia activation. There is currently no cure or effective treatment to ameliorate the symptoms of the disease. Aerobic exercise is known to exert multiple beneficial effects in the brain, not only by increasing neurogenesis, but also by improving motor and cognitive tasks. To date, no studies have analyzed the effect of physical exercise on the phenotype of a CDD mouse model. In view of the positive effects of voluntary running on the brain of mouse models of various human neurodevelopmental disorders, we sought to determine whether voluntary daily running, sustained over a month, could improve brain development and behavioral defects in Cdkl5 KO mice. Our study showed that long-term voluntary running improved hyperlocomotion and impulsivity behaviors, and memory performance of Cdkl5 KO mice. This is correlated with increased hippocampal neurogenesis, neuronal survival, spine maturation, and inhibition of microglia activation. These behavioral and structural improvements were associated with increased BDNF levels. Given the positive effects of BDNF on brain development and function, the present findings support the positive benefits of exercise as an adjuvant therapy for CDD.
ARTICLE | doi:10.20944/preprints202307.1209.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Gold fish (Carassius auratus), probiotic bacteria (Bacillus cereus), survival rate, growth performance
Online: 18 July 2023 (10:01:13 CEST)
Marine sediment sample was collected and the total aerobic population was counted and probiotic Bacillus cereus was isolated. Then it was mixed with formulated feed by spraying, while control diet was purchased from a local aquarium. 30 days of feeding experiment was conducted. Carassius auratus fishes were randomly divided into two experimental groups in rectangular tanks. The first group served as a control in which fishes were fed with commercial feed. The second group of fish were fed with probiotic incorporated feed. After 40 days, their survival and growth performance were detected. Bacillus cereus incorporated feed significantly yielded higher survival rate of the fish compared to control. Food conversion ratio (FCR) was significantly lower than the control group. The main aim of this work is to investigate the effect of a marine probiotic bacteria, Bacillus cereus on the survival and growth performance of gold fish Carassius auratus.
ARTICLE | doi:10.20944/preprints202307.0204.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: deuterium depletion; deuterium-depleted water (DDW); glioblastoma multiforme; median survival time (MST)
Online: 5 July 2023 (03:25:21 CEST)
Glioblastoma multiforme (GBM) and malignant gliomas are the most common primary malignant brain tumors. Temozolomide (TMZ) chemotherapy plus radiation therapy (RT), admi-nistered after debulking surgery, increased median survival time (MST) from 12.1 months with RT alone merely to 14.6 months. In this study, the action of deuterium-depleted water (DDW) on the survival of GBM patients who also received conventional therapies was investigated. Without changing the conventional treatment, the daily fluid intake of the patients was wholly replaced with DDW in 1.5-2 liters per day volume to reduce D concentration in their bodies. The primary endpoint was MST. The 55 patients involved, receiving conventional treatment and consuming DDW, showed longer MST (30 months) compared to the historical control (12.1-14.6 months). There was a massive difference between the two genders in the calculated MST values; it was 25 months in the male subgroup (n=33) and 42 months in the female subgroup (n=22). MST was 27 months without TMZ treatment (38 patients) and 42 months in the TMZ-treated group (17 patients). For the selected 31 patients, who consumed DDW in the correct way in addition to conventional treatments, MST was 30 months. Within this group, the 20 subjects who had relapsed before DDW treatment had 30 months of MST, but in those 10 subjects who were in remission when DDW treatment started, MST was 47 months. In the subgroup of patients who started DDW treatment parallel with radiotherapy, MST was 47 months again, and it was 25 months when DDW treatment started 8 weeks or later after the completion of radiotherapy. Altogether, survival times were substantially prolonged, compared to prospective clinical data of patients with primary GBM. Consequently, if conventional therapies are supplemented with D depletion, better survival is achieved in advanced stage of GBM than with the known targeted or combination therapies. Application of DDW is recommended in all stages of the disease, before surgery, parallel with radiotherapy, and repeated DDW courses are advised when remission has been achieved.
REVIEW | doi:10.20944/preprints202306.1650.v1
Subject: Biology And Life Sciences, Other Keywords: Esophageal cancer; Targeted drug therapies; Pathway targeting; Drug resistance; Patient survival rates
Online: 23 June 2023 (09:44:00 CEST)
Esophageal cancer is a formidable challenge in the realm of cancer treatment. Conventional methods such as surgery, chemotherapy, and immunotherapy have demonstrated limited success rates in managing this disease. In response, targeted drug therapies have emerged as a promising strategy to improve outcomes for patients. These therapies aim to disrupt specific pathways involved in the growth and development of esophageal cancer cells. This review explores various drugs used to target specific pathways, including cetuximab and monoclonal antibodies (gefitinib) that target the epidermal growth factor receptor (EGFR), trastuzumab that targets human epidermal growth factor receptor 2 (HER-2), drugs targeting the vascular endothelial growth factor receptor (VEGFR), mTOR inhibitors, and cMET inhibitors. Additionally, the article discusses the impact of drug resistance on the effectiveness of these therapies, highlighting factors such as cancer stem cells, cancer-associated fibroblasts, immune-inflammatory cells, cytokines, hypoxia, and growth factors. While drug targeting approaches do not provide a complete cure for esophageal cancer due to drug resistance and associated side effects, they offer potential for improving patient survival rates.
ARTICLE | doi:10.20944/preprints202306.1103.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: bilaterality; unilateral multifocality; papillary thyroid carcinoma; disease-free survival; propensity score matching
Online: 15 June 2023 (08:22:44 CEST)
Papillary thyroid cancer (PTC) is commonly characterized by multifocality, which is associated with aggressive features and a less favorable prognosis. The current study aimed to compare the clinicopathologic characteristics and long-term oncological outcomes of bilateral and unilateral multifocal PTC. The medical records of 1745 patients with multifocal PTC who underwent thyroid surgery at Seoul St. Mary’s Hospital were retrospectively reviewed. The clinicopathological characteristics and recurrence rates were compared based on cancer laterality. Further, 357 patients who underwent total thyroidectomy were matched to investigate the recurrence risk and disease-free survival (DFS). Before propensity score matching (PSM), there was no significant difference in the recurrence rate between the bilateral and unilateral multifocal PTC groups. Cancer laterality was not a predictor of DFS based on the Cox regression analyses. However, after PSM, unilateral multifocality was associated with a significantly high risk of recurrence. Similarly, unilateral multifocality was associated with a significantly poor DFS based on the Kaplan–Meier analysis. Compared with bilateral PTC, unilateral multifocal PTC was associated with a poor DFS. A comprehensive preoperative examination should be performed to detect multifocality before the initial surgical intervention for optimal treatment. Postoperative short-term follow-up is recommended for unilateral multifocal PTC for recurrence surveillance.