Kinesiophobia (fear of movement) has been recognized as a significant barrier to recovery and rehabilitation in patients after total knee arthroplasty (TKA). Our goal was to identify predictors of kinesiophobia and examine its correlation with early functional outcomes in TKA recipients. On the first and fifth postoperative days (POD1 and POD5), we evaluated pain using the International Pain Outcomes Questionnaire (IPO-Q) and created multidimensional pain composite scores (PCS). Pain Composite Score-total (PCStotal) assesses the overall impact of pain, taking into account outcomes of pain intensity, pain-related interference with function, and emotions and side effects. Functional status on POD 5 was determined by the Barthel index, 6-minute walking test, and knee range of motion. Kinesiophobia was measured on POD5 using the Tampa Scale for Kinesiophobia (TSK) and multivariable logistic regression was used to assess factors associated with kinesiophobia. Among 75 TKA patients, 27% exhibited kinesiophobia. The final regression model highlighted PCStotal on POD5 (OR=6.2, CI=1.9-19.9), PCStotal (OR=2.1, CI=1.2-3.8) on POD1, and the intensity of chronic pain before surgery (OR=1.4, CI=1.1-2.1) as significant kinesiophobia predictors. On POD5, those with kinesiophobia showed increased dependency, slower gait, and poorer knee extension recovery. This study highlights the importance of identifying and addressing kinesiophobia in TKA patients to optimize functional outcomes and improve recovery. Also, it is important to assess not only pain intensity but also the physical and emotional interference caused by pain, which can contribute to the development of kinesiophobia.

Background: Gastrointestinal stromal tumors (GIST) are rare mesenchymal neoplasms of the gastrointestinal tract (GIT) that represent approximately 1 to 2 percent of primary gastrointestinal (GI) cancers. Owing to their rarity, very little is known about the overall epidemiology and prognostic factors of the pathology. The purpose of this study is to investigate the clinical characteristics, survival outcomes, and independent prognostic factors of patients with GIST in the past decade. Methods: A total of 2,374 patients diagnosed with GIST, between 2010 and 2017, were ultimately enrolled in our study by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of GIST. Variables with a p value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Multivariate cox proportional hazard regression analyses of factors affecting all-cause mortality and GIST related mortality among US patients between 2010 and 2017 revealed higher overall mortality in Non-Hispanic Blacks (HR= 1.516, 95% CI 1.172-1.961, p= 0.002), age 80+ (HR= 9.783, 95% CI4.185-22.868, p= 0), followed by age 60-79 (HR= 3.408, 95% CI 1.488-7.807, p=0.004); male patients (HR= 1.795 , 95% CI 1.461-2.206, p=0); advanced disease with distant metastasis (HR= 3.865 , 95% CI 2.977-5.019, p=0), followed by regional involvement by both direct extension and lymph node involvement (HR= 3.853, 95% CI 1.551-9.57, p=0.004); and widowed patients (HR= 1.975, 95% CI 1.494-2.61, p= 0), followed by single patients (HR= 1.53, 95% CI 1.154-2.028, p=0.003). The highest CSM was observed in the same groups, except widowed patients and patients aged 60-79. The highest CSM was also observed among patients that underwent chemotherapy (HR= 1.687, 95% CI 1.19-2.392, p= 0.003). Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that non-Hispanic blacks, male patients, and patients older than 60 years have a higher mortality with GIST. Furthermore, patients who received chemotherapy have a higher GIST specific mortality and married patients had a lower mortality. However, we do not know to what extent these independent prognostic factors interact with each other to influence mortality. This study paves the way for future studies addressing those interactions. The results of this study may help treating clinicians to identify patient populations associated with dismal prognosis as those may require closer follow-up and more intensive therapy; furthermore, with married patients having a better survival, we hope to encourage clinicians to involve family members of the affected patients early in the disease course as the social support might impact the prognosis.

Comparing to males, females require much more morphine to produce comparable levels of analgesia, suggesting a difference in the endogenous hyperalgesia and analgesia modulation between sexes. Aside from hormones, emerging evidence suggests sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and American College of Gastroenterology (ACG), up to 25 % of the population having visceral pain at any one time, and in the United States 10-15 percent of adults suffering from irritable bowel syndrome (IBS). Here we analyzed literatures on clinical reports of sex differences in visceral pain focusing on IBS, other form of bowel dysfunction and comorbidities, and summarized animal models that provided means to investigate the underlying molecular mechanisms in sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems all contribute to sex-dependent nociception and nociplasticity in the painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.

Hip fractures are an important socio-economic problem in western countries. Over the past 60 years orthogeriatric care has improved the management of older patients admitted to hospital after suffering hip fractures. Orthogeriatric co-management units have increased quality of care, reducing adverse events during acute admission, length of stay, both in-hospital and mid-term mortality, as well as healthcare and social costs. Nevertheless, a large number of areas of controversy regarding the clinical management of older adults admitted due to hip fracture remain to be clarified. This narrative review, centered in the last 5 years, combined the search terms “hip fracture”, “geriatric assessment”, “second hip fracture”, “surgery”, “perioperative management” and “orthogeriatric care”, in order to summarise the state of the art of some questions such as the optimum analgesic protocol, the best approach for treating anemia, the surgical options recommendable for each type of fracture and the efficiency of orthogeriatric co-management and functional recovery.

Purpose: Expanded carrier screening (ECS) informs couples of their risk of having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes of at-risk couples (ARCs). We describe the impact of ECS on planned and actual pregnancy management in the largest sample of ARCs studied to date. Methods: Couples who elected ECS and were found to be at high risk of having a pregnancy affected by at least one of 176 genetic conditions were invited to complete a survey about their actions and pregnancy management. Results: Three hundred ninety-one ARCs completed the survey. Among those screened before becoming pregnant, 77% planned or pursued actions to avoid having affected offspring. Among those screened during pregnancy, 37% elected prenatal diagnostic testing (PNDx) for that pregnancy. In subsequent pregnancies that occurred in both the preconception and prenatal screening groups, PNDx was pursued in 29%. The decision to decline PNDx was most frequently based on the fear of procedure-related miscarriage, as well as the belief that termination would not be pursued in the event of a positive diagnosis. Conclusions: ECS results impacted couples’ reproductive decision-making and led to altered pregnancy management that effectively eliminates the risk of having affected offspring.

1. Background and Objective: Spontaneous Intracranial Hemorrhage (ICH) is a catastrophic medical condition associated with significant morbidity and mortality. As the accumulation of unbound iron following ICH contributes to secondary brain injury, deferoxamine, an approved chelation drug, has become the center of attention. At the same time, its therapeutic remains a matter of dispute. This double-blinded Randomized Controlled Trial (RCT) aims to investigate the therapeutic potential of deferoxamine in neurological and radiological aspects. 2. Methods and Materials: The study enrolled 42 participants diagnosed with spontaneous ICH and confirmed by CT scan, randomly assigning them to either the deferoxamine treatment group or the placebo control group. While the control group received the routine treatment plus a placebo, the treatment group received routine treatment conjugated with 7.5 mg/kg of deferoxamine per hour intravenously over the first three days. The study compared hematoma and edema volume, GCS score, and mortality rates between the two groups. Our study employed rigorous randomization and blinding procedures to ensure unbiased results. 3. Results: There was a significant (p<0.05) improvement in patients' GCS up until the fourth day, but no significant difference was noted afterward. In addition, the volume of both edema and hematoma was significantly lower in the intervention group, as well as the length of stay, intubation requirement, and mortality. 4. Discussion: Deferoxamine administration can, at least in a short timeframe, improve neurological and radiological parameters.

Aim. The analysis of incidence, clinical and morphological manifestations, and the prognosis of IgA nephropathy in the Northeastern Europe (NEE). Materials and methods. We enrolled cases with primary IgA nephropathy (IgAN) from 2005 to 2020 in the single-center retrospective study. Demographic and clinical parameters, histology data, and the treatment were analyzed. The outcomes were the occurrence of complete (PR) or partial remission (CR), renal replacement therapy (RRT), eGFR<15 ml/min/1.73m² and eGFR decrease ≥ 50%. The composite endpoint included all renal outcomes and was used to evaluate the risk of IgAN progression and associated factors. Results. The incidence of IgAN cases was 23.6% of all indication biopsies and 41.2% of primary immune glomerulopathies. At the time of the kidney biopsy, the proteinuria was 2.5 (1.5-5.0) g/24h, eGFR - 69 ± 32 ml/min/1.73 m². Proportions of cases with arterial hypertension and eGFR <60 ml / min / 1.73 m² were 75% and 36%, respectively. The prevalence of histological changes in accordance with the Oxford (MEST-C) classification was M1 - 40.5%, E1 -22.9%, S1-70.2%, T1-22%, T2 - 9%, C1-16.7%, C2 - 4.4%. In the follow-up of 27 (11; 61) months, 6 deaths occured (1.7%). The 10-year cumulative dialysis-free survival was 80% and progression-free survival was 56%. Remissions registered in 50% of cases, being more frequent in patients who received immunosuppression vs renoprotection (60% vs. 40%, p = 0.001). In multivariable Cox regression, the independent factors associated with the increased probability of IgAN progression were male gender, a younger age, higher blood pressure and hematuria, lower eGFR, interstitial fibrosis/ tubular atrophy (≥50%), the presence of peritubular capillaritis and any crescents. Compared to the cohorts of other ethnic or geographical origin, IgAN in the studied cohort were found to have more severe clinical and morphological presentations and faster progression rate. Conclusion. Being the most common glomerulopathy in the NEE population, IgAN has more pronounced clinical and morphological presentations. Considering the distinctive features of the disease, further research is warranted in order to establish approaches for enhancing risk stratification and treatment efficacy.

Nerve-sparing vs. non nerve sparing surgery (NSS vs. non-NSS) is associated with improved functional outcomes in prostatectomy patients. The aim of the present study is to compare the oncological outcomes of patients with high-risk localized prostate cancer undergoing nerve-sparing and non nerve-sparing robot-assisted radical prostatectomy (RARP). Between November 2002 and December 2018, we prospectively recorded data of patients undergoing RARP for high-risk localized prostate cancer (PCa). NSS (nerve-sparing surgery) was offered based on preoperative clinical characteristics of patients and intraoperative assessment. Patients were stratified into 2 groups according to NSS. The primary outcome was biochemical recurrence (BCR), while positive surgical margin (PSM) and cancer-specific survival (CSS) were secondary outcomes. Logistic regression was used to investigate predictive factors. A total of 779 patients were included in the study, 429 (55.1%) underwent NSS while 350 (44.9%) underwent a non-NSS. After a mean (±SD) follow-up of 192 (±14) months, 328 (42.1%) patients developed BCR, no significant difference was found between NSS and non-NSS group (156 vs. 172; p=0.09). Both univariable and multivariable analysis found that nerve-sparing approach was not a predictor of BCR (p>0.05). NSS vs. non-NSS was not associated with worse oncological outcomes in patients with high-risk PCa

The association between obesity and clinical as well as radiological outcomes in patients suffering non-traumatic intracerebral haemorrhage (ICH) remains unclear. The obesity paradox suggests a protective effect regarding in-hospital mortality. This study evaluates the impact of body mass index (BMI) on functional long-term outcome and bleeding volume in patients with non-traumatic ICH. A retrospective cohort study including all consecutive patients with spontaneous ICH treated at a tertiary referral centre between December 2017 and June 2021, aged 80 years or younger (n = 218), were included. Patients were dichotomized into overweight (OW, BMI ≥ 25 kg/m2) and normal weight (NW, BMI < 25 kg/m2). Functional outcomes were assessed by the modified Rankin scale (mRS), extended Glasgow Outcome Scale (GOS-E) and the National Institutes of Health Stroke Scale score (NIHSS) at 1, 3, 6 and 12-months follow-up. Bleeding volumes were calculated as ABC/2. Univariate and multivariate analysis were performed to assess clinical predictors of favourable outcome in the long-term. Of 218 patients (66.04 ± 15.18 years) suffering non-traumatic ICH, 115 (52.75%) were OW (29.72 ± 3.82). Female sex (p = 0.1), NIHSS (p = 0.69), cardiovascular risk factors (p = 0.55), ICH volume (p = 0.19), and presence of anticoagulation (p = 0.67) did not significantly differ between the OW and NW cohort. At discharge, functional outcome did not significantly differ between both cohorts (NW, mRS 3.92 ± 2.54 vs. OW, mRS 3.21 ± 2.43, (p = 0.28)). Multivariate analysis revealed that haemorrhage volume (p = 0.01) was the only robust risk factor to predict functional outcome after 1 year. Our data suggests that in ICH patients, neither obesity nor patient’s age are negative predictors for functional outcome in the long-term. Instead, bleeding volume is a robust risk factor predicting poor functional status after ICH. Therefore, prospective randomized trials analysing this coherence are highly warranted.

Background/Objectives:The first attempts of posterior lumbar interbody fusion can be traced back to the 1940s, where their performance was marked by animosity due to high rates of failure. Nowadays, the use of interbody fusion involves a much more complicated consideration of factors such as global alignment, disc height, fusion rates, and operative risk, all combined at once.Our study aims to examine all these effects using Flarehawk 9 as a means of interbody fusion.Materials and methods: A total of 58 patients underwent open posterior lumbar surgery using Flarehawk 9 between September 2021 and February 2023 with a mean follow up of 1 year.The mean age was 59.8 years old ( range between 33 and 79 years old), 36 of them are males while 22 of them are females. The diagnostic groups included spinal canal stenosis (n=40), failed back surgery syndrome-revision surgery (n=5),spondylolisthesis with slip percentage 25% (n=4),recurrent herniated disc (n=7) and adjacent segment disease (n=2). Results: The majority of patients demonstrated remarkable improvement based on ODI scores.The rate of union varied based on the fused levels and whether the patients had previous surgery or not.The amount of lordosis postoperatively is increased by 2±0.4 degrees.Conclusions: Even though anterior approaches become more and more popular and advanced nowadays, posterior fusion with interbody cage still remains a safe and effective method to treat various spine surgical pathologies with optimal results.

Background: Modern computational solutions enabling evaluation of the global neuronal network arrangement seem to be particularly valuable for research on neuronal disconnection in schizophrenia. However, a vast number of algorithms used in these analyzes may be an uncontrolled source of results inconsistency. Objective: Our study aimed to verify whether the comparison of schizophrenia patients with healthy controls, in terms of indexes describing the organization of the neural network, will give analogous results when these parameters are calculated using two different functional connectivity measures. Methods: Resting-state EEG recordings from schizophrenia patients and healthy controls were collected. Based on these data, Minimum Spanning Tree (MST) graphs were computed two times using two different functional connectivity measures (phase lag index, PLI, and phase locking value, PLV). Results: Two series of be-tween-group comparisons regarding MST parameters calculated based on PLI or PLV gave contradictory results, in many cases the values of a given MST index based on PLI were higher in patients, and the results based on PLV were lower in patients than in the controls. Additionally, within the patients' group, selected network measures were significantly different when calculated from PLI or PLV. Conclusions: The selection of FC measures significantly affects the parameters of MST-based neural networks and might be a source of disagreement between the results of network studies on schizophrenia.

Since the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies, we performed this meta-analysis. A systematic search of published articles was performed in PubMed and EMBASE from January-May 5, 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR). A total of 6,997 hypertensive patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). Compared to all other antihypertensives, ACEIs decreases the risk poor COVID-19 outcomes (OR=0.77, 95% CI: [0.63-0.93]) while ARBs did not (OR=1.13, 95% CI: [0.95-1.35]). The risk of poor patient outcomes from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. Unlike ARBs, ACEIs might help in decreasing the severity and mortality of COVID-19.

Obesity represents a worldwide epidemic disorder, increasing the overall morbidity and mortality rate. In this study we investigated the impact of obesity on peri-operative and long-term functional outcomes of Robotic assisted simple prostatectomy (RASP). Baseline flowmetry parameters and validated questionnaires’ scores were prospectively recorded. Follow-up assessments included Flowmetry and validated questionnaires. Composite outcomes (Trifecta) was defined as combination of: post-operative Q-max>15 ml/sec, IPSS score<8 and absence of complications. Pentafecta included also post-operative ejaculation persistence (MSHQ score>0) and the Erectile function maintenance (∆IEEF<6). Data were stratified by BMI (<30 or ≥30). 81 patients underwent RASP in our Institution. Baseline demographics and clinical features, questionnaires score and baseline flowmetry results were comparable between obese and non-obese cohorts. At follow-up, obese patients reported lower subjective improvement in IPSS (p=0.02) and OABQ scores (p<0.001) and higher incidence of stress incontinence requiring Duloxetin (p<0.001). Flowmetry outcomes, were also worse in this cohort (p=0.02 and p=0.03, respectively). At comprehensive outcomes assessment, obese patients had comparable Trifecta (67% vs 54%, p=0.39) and pentafecta achievement rate (p=0.76). Our prelimirary results proved that obesity is associated with worse functional outcomes (storage LUTS and incontinence rate) after RASP, but doesn’t affect trifecta and pentafecta achievement rate.

Comorbidities can have a cumulative effect on hospital outcomes of care, such as the length of stay (LOS), and hospital mortality. This study examines patients hospitalized with Congestive Heart Failure (CHF), a life-threatening condition, which, when it coexists with a burdened disease profile, the risk for negative hospital outcomes increases. Since coexisting conditions co-interact, with a variable effect on outcomes, clinicians should be able to recognize these joint effects. In order to study CHF comorbidities, we used medical claims data from CMS. After extracting the most frequent cluster of CHF comorbidities, we: (i) Calculated, step-by-step, the conditional probabilities for each disease combination inside this cluster (ii) Estimated the cumulative effect of each comorbidity combination on the LOS and hospital mortality (iii) Constructed (a) Bayesian, scenario-based graphs and (b) Bayes-networks to visualize results. Results show that, for CHF patients, different comorbidity constructs have variable effect on the LOS and hospital mortality. Therefore, dynamic comorbidity risk assessment methods should be implemented for informed clinical decision making in any ongoing effort for quality of care improvements.

Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials.gov - NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared intensive behavioral treatment intervention condition (IC) with control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n=88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n=88) received only the brochure. Participants were assessed at baseline and day-22 follow-up. Self-reported chewing status at day-22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Results: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p=0.0058, which met the Stage 3 criteria for significance and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Conclusion: Robust self-reported intervention effects at day-22 suggests that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

People are increasingly encouraged to reduce animal food consumption and shift towards plant-based diets, however the implications for children’s health are unclear. In this narrative review of research in high-income settings, we summarize evidence on the increasing consump-tion of plant-based diets in children, and update an earlier systematic review regarding their associations with children’s health outcomes. The evidence indicates that vegan but not vege-tarian diets can restrict growth relative to omnivorous children, and increase the risk of being stunted and underweight although the percentage affected is relatively small. Bone mineral content is reduced in vegetarian and especially vegan children, compared to omnivores. Both vegetarian and vegan children who do not use vitamin B12 supplements manifest with B12 defi-ciency, however supplementation rectifies this problem. Both vegetarians and vegans have lower concentrations of 25 (OH)D if unsupplemented, and lower body iron stores, but usually have normal iron metabolism markers. Both groups are at risk of iodine deficiency and this might affect thyroid health. Children consuming a vegan diet have more favorable lipid profile than omniv-orous children, however the results for vegetarian diet are inconsistent and vary by outcome. Based on the same scientific evidence, national and international dietary recommendations are heterogeneous, with some countries supporting plant-based diets among infants, children and adolescents, and others discouraging them. We offer a research roadmap, highlighting what is needed to provide adequate evidence to harmonize dietary recommendations for plant-based diets in children. A number of measures should urgently be introduced at international and na-tional levels to improve the safety of their use in children.

A multicenter, prospective cohort study conducted in 5 physiotherapy clinics in the UAE from January 2021 to March 2023 to assess coronal lumbar spine radiographic parameters as a predictor of conservative therapy outcomes in patients suffering from low back and leg pain due to lumbar disc herniation (HNP). Ninety patients (mean age 44 yrs., 54% male) with lumbar HNP underwent conservative therapy. All participants received lumbar spine MRI and radiography to assess spine alignment. Interventions included specific exercises, diathermy, traction, education, a home-based exercise pro-gram, and medications. Detailed demographic data was collected. Follow-up was 6-months after discharge. A successful outcome was based on a minimum of the following four outcomes: (1) reduction of pain by 17.5 points (0–100 NRS); (2) fatigue reduction by 7.5 points; (3) distress reduction by 5 points; and (4) interference reduction by 9.5 points. At 6-month follow-up it was found that patient age, education, and radio-graphic determined lumbosacral angle measures significantly affected the odds of a successful outcome. Increasing age 1-year significantly decreased the odds of success of improving pain, fatigue (OR = 0.85, p = 0.016) and interference scores (OR = 0.89, p = 0.042) by 15%, 15%, and 11% respectively. Lower education significantly increased the odds of success for improving pain, fatigue, and interference by 26.18, 26.18, and 7.5 (p = 0.006, = 0.006, and = 0.029 respectively). Increasing (worsening) the radiographic lumbosacral angle by each 1° significantly reduced the odds of success for improving pain, fatigue, distress, and interference by 3.52, 3.52, 27.99, and 2.55, respectively (p < 0.001, < 0.001, = 0.003, = 0.001). Our findings indicate that younger age, less education, and better coronal radiological lumbar spine alignment all had a substantial impact on the likelihood of success of 6-month outcomes in patients suffering from chronic lower back pain and radiculopathy due to HNP.

Background: Olecranon fractures are common injuries of the upper limb in adults. Simple dis-placed trasverse fractures are generally surgically treated with tension-band wiring (TBW) or plate fixation (PF). The purpose of this retrospective study is to compare the clinical-functional outcome, complications and reoperation rates between TBW and PF for Mayo IIA fractures. Methods: 72 patients treated with PF or TBW at our institution, completed our survey and clinical evaluation and their demographic and clinical data were recorded and analysed. The clini-cal-functional outcomes were evaluated assessing ROMs and three validated scoring systems: the Disabilities of the Arm, Shoulder, and Hand (DASH), the Mayo Elbow Performance Score (MEPS) and the Patient American Shoulder and Elbow Surgeons Standardized Elbow Assess-ment score (pASES-e). Results: 38 patients (53%) underwent TBW and 34 (47%) PF. The mean DASH, MEPS and pASES-e scores were respectively 14.5±17.2, 80.5±14.7 and 83.6±12.4 in the TBW group and 21±21.7, 75.6±15.3 and 75.1±19.2 in the PF group (p=0.16, p=0.17 and p=0.03). The mean duration of surgery and hospitalisation period were longer in the PF group (p=0.002, p=0.37) whereas the complication and reoperation rates were higher after TBW (p=0.15, p=0.24). Conclusion: According to the literature, both TBW and PF resulted comparable valid surgical op-tions for the treatment of simple isolated displaced olecranon fractures, revealing that they both provide good/excellent outcomes with no significant differences.

The FDA has concluded that a biosimilar candidate capable of demonstrating pharmacodynamic biomarkers in a healthy subject need not be tested for clinical efficacy in patients, regardless of if the biomarker correlates with clinical response. Since monoclonal antibodies (mAbs) do not trig-ger pharmacodynamic response, they can be substituted with robust functional disqualifying them for this waiver that can be overcome by allowing comparison of functional properties that eventually result in clinical response. This suggestion is based on the FDA's preference for more sensitive testing methods. However, clinical efficacy testing in patients is the least sensitive method, as confirmed by statistical modeling, a fact that regulatory agencies need to admit. In this paper, I present a logical and rational argument to establish the biosimilarity of products that do not have pharmacodynamic biomarkers based on their orthogonally proven functional bio-similarity. This understanding will significantly lower the development cost of biosimilars, a goal that the FDA outlined in all its guidance. Keywords: biosimilarity 1; biosimilars 2; pharmacodynamic biomarkers 3; monoclonal antibodies 4; FDA 5; clinical efficacy testing in healthy subjects 6; clinical efficacy testing in patients 7; functional assays 8; receptor binding 9.

Thrombosis has threatened human health in past decades. Bacillus nattokinase is a potential thrombolytic drug without side-effect and low cost and has been introduced into the consumer market as a functional food or dietary supplement. This review firstly summarizes the biodiversity sources and fermentation process of nattokinase, and systematically expounds the structure, cata-lytic mechanism and enzymatic properties of nattokinase; In view of the problems of low fermen-tation yield, insufficient activity and stability of nattokinase, this review discusses the heterologous expression of nattokinase in different microbial hosts, and summarizes the protein and genetic en-gineering progress of nattokinase-producing strains; Finally, this review summarizes the clinical application of nattokinase.

(1) Background: The aim of this work was to systematically review existing studies on whether hysteroscopy improves the reproductive outcomes of women with infertility even in the absence of intrauterine pathologies when compared to women who did not receive a hysteroscopy. (2) Methods: We established the Participant-Intervention-Comparison-Outcome strategy and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to conduct a systematic review of 11 studies which were retrieved from 3 electronic databases: Ovid-Medline, Ovid-Embase, and the Cochrane Library. Two independent investigators extracted the data from the included studies and used the Cochrane risk-of-bias tool to assess their quality. (3) Results: The primary outcome measures were the clinical pregnancy rates (CPRs) and live birth rates (LBRs) in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Hysteroscopy in infertile women without intrauterine pathologies showed higher CPRs and LBRs than those in the same population who did not receive hysteroscopy in cases of recurrent implantation failure and IVF (odds ratio: 1.79 and 1.46, 95% confidence interval: 1.46-2.30 and 1.08-1.97 for CPR and LBR, respectively); however, the degree of significance was not as high for LBR. (4) Conclusions: Hysteroscopy before IVF/ICSI in infertile women without intrauterine pathologies may potentially be effective in improving the CPRs and LBRs in patients with RIF. Robust and high-quality randomized trials are warranted to confirm this finding.

A consistent factor in the epidemic of chronic disease is a pro-inflammatory metabolic state. The ability of clinicians to use nutrients to balance inflammation by supporting oxidant homeostasis rests on the quality of research within the field of antioxidants. Understanding the intersection of two prominent theories regarding the role of antioxidants in quelling inflammation, nutritional hormesis and oxidant scavenging, will enable the therapeutic use of antioxidants in clinical practice. This review investigates the less well-established theory, nutritional hormesis, which has not been comprehensively reviewed recently to our knowledge. To understand the state of research on the hormetic response, we conducted a comprehensive literature review describing the relationship between dietary antioxidants, hormesis, and chronic disease. We used an adaptive search strategy in PubMed and Scopus, retrieving a total of 343 articles, of which 218 were unique. Title and abstract screenings were conducted by two reviewers independently with a third as a tiebreaker, resulting in 152 articles included in this review. Most studies reviewed the hormetic response in plant and cell models (73.6%) while only 2.2% were conducted in humans. Limitations exist in translating plant/cell/animal models into the complexities of human biochemistry and physiology that warrant consideration before extrapolating such results into clinical practice. A critical hurdle in our literature review process is the lack of standardized nomenclature describing the hormetic effect in the research community that challenges the ability to comprehensively review the subject matter. Further, aA knowledge gap exists between the cell culture and animal model research that shows a biphasic, hormetic quality to the role of antioxidants and the observational human studies, which have yet to corroborate these findings. Therefore, we cannot accurately translate this research into clinical care at this time.

Optoacoustic imaging is an emerging technology that holds great promise for improving general clinical practice since it offers a unique combination of optical absorption contrast, high resolution, and high penetration depth. This combination of factors provides a distinct advantage over alternative imaging modalities in oncology, cardiology, dermatology, or endocrinology among other medical fields. Optoacoustic technology affords the medical practitioner the possibility of visualizing light-absorbing biomolecules like water, lipids, oxy/deoxy hemoglobin, or melanin in deep tissue with relatively cheap and small form factor instruments, without the need of contrast agents or ionizing radiation. Moreover, exogenous fluorescent contrast agents like indocyanine green or methylene blue can also be observed. Driven by its potential for new applications in the clinic, the field has experienced intense changes in the last 20 years. Continuous technological advancements in instrumentation, image formation methods, or acquisition geometries, have led to the development of numerous clinical devices also motivating the creation of several startup companies that aim to translate the technology from the lab to the clinic. Thus, the question arises: how far are we from clinical adoption? In this article, we aim to shed light on such question by reviewing the clinical studies that have been performed in the last 10 years. Our intention is to go beyond the classical review format by providing a brief general overview of the steps that new imaging methods undergo on their journey from the lab to clinical adoption. Then we examine the progress that optoacoustic technology has made on such a journey.

We performed electronic research for articles published in PubMed, MEDLINE, and ScienceDirect databases from January 2004 to January 2023. The systematic review of twenty (20) peer-reviewed articles about dosimetric parameters and eight (8) articles about clinical outcomes confirmed the dosimetric advantages of ART through better target coverage and Organs at Risk (OARs) sparing, with subsequent benefits on decreased toxicity and improved clinical outcome, specifically local control of the disease. ART replanning is a sustainable strategy for minimizing toxicity by improving normal tissue sparing. Furthermore, it enhances target volume coverage by correctly determining the specific amount of dose to be delivered to the tumor. In conclusion, this review confirms that ART benefits dosimetric, clinical/therapeutic, and toxicity outcomes.

Background: Good clinical practice (GCP) training is the industry standard for ensuring the quality conduct of registrational clinical trials. However, concerns have been raised about whether the current structure and delivery of GCP training sufficiently prepares clinical investigators and their delegates to conduct clinical trials. Methods: We conducted qualitative semi-structured interviews with 13 clinical investigators and 10 research sponsors to 1) examine characteristics of the quality conduct of sponsored clinical trials, including critical tasks and concerns perceived as essential for trial quality, 2) identify key knowledge and skills required to perform critical tasks, and 3) identify gaps and redundancies in GCP training and areas of improvement to ensure the quality conduct of clinical trials. We used applied thematic analysis to analyze the data. Results: The top three tasks identified as critical for the quality conduct of clinical trials were obtaining informed consent, ensuring protocol compliance, and protecting participants’ health and safety. Respondents acknowledged that GCP principles address each of these critical tasks; however, they described many challenges and burdens of GCP training, including high training frequency and repetitive content. Respondents suggested moving beyond GCP training as a mere check-box activity by making it more effective, engaging, and interactive. They also emphasized that applying GCP principles in a real-world, skills-based environment would increase the relevance of GCP training to investigators and their delegates. Conclusion: Our findings indicate that although investigators and sponsors recognize that GCP training addresses critical tasks necessary to the quality conduct of clinical trials, they articulated the need for significant improvement in the design, content, and presentation of GCP training.

Objectives: This study aims to identify, report, and analyze registered and published clinical trials and observational studies for the pharmacological treatment of COVID-19 conducted in China. Methods: A strategic search was conducted via the Chinese Clinical Trial Registry to identify and extract clinical trials and observational studies registered and conducted in China for the pharmacological treatment of COVID-2019 between January 1^st, 2020 and March 21^st, 2020. This was further supplemented by searches conducted via the China National Knowledge Infrastructure (CNKI) database, the MEDLINE database, the World Health Organization (WHO) database, and MedRxiv and BioRxiv electronic platforms for preprint articles, published up until April 8^th, 2020. Studies available in Chinese and English were included in the searches and extracted. A primary descriptive analysis was performed for registered clinical trials and observational studies identified in the Chinese Clinical Trial Registry based on the extraction of the following clinical study information: trial ID, planned date of enrollment, recruitment status, study design, population, sample size, intervention/exposure group, control /reference group, dosage, and primary outcomes. A secondary descriptive analysis was performed for published clinical trials and observational studies identified from the supplementary databases based on the extraction of the following published clinical study information: study design, population, intervention/exposure group, control /reference group and main results as appropriate. Results: A total of 221 clinical trials and observational studies were included from all databases searched. From the Chinese Clinical Trial Registry, 195 registered clinical studies including 170 clinical trials and 25 observational studies were identified and included for primary analysis. From the supplementary databases, 26 published clinical studies including 8 clinical trials and 18 observational studies were included for secondary analysis. Of these 26 published clinical studies, 18 studies, including 3 clinical trials and 15 observational studies were identified from CNKI, 2 studies including 1 clinical trial and 1 observational study from MEDLINE, 2 including 1 clinical trials and 1 observational studies from the WHO database, and 4 including 3 clinical trials and 1 observational studies from MedRxiv and BioRxiv platforms. In the primary analysis, among the 170 clinical trials included from the Chinese Clinical Trial Registry, 101 investigated western medicines (WMs), while 15 investigated Traditional Chinese Medicines (TCMs), and 54 investigated a combination of TCMs and WMs. Among the 25 included observational studies from the Chinese Clinical Trial Registry, 2 investigated WMs, 2 investigated TCMs, and 21 investigated a combination of TCMs and WMs. The total number of exposed patients in all 195 clinical studies from the Chinese Clinical Trial Registry amounted to 24,500. In the secondary analysis, treatment with Lopinavir-ritonavir and treatment with Hydroxychloroquine was not associated with a difference from standard of care in the rate of RT-PCR negativity; treatment with a combination of Lopinavir-ritonavir, interferon α, and Lian-Hua-Qing-Wen capsule was found to significantly improve the effective rate of treatment compared with Interferon α combined with Lian-Hua-Qing-Wen capsule. Conclusions: China is generating a massive source of evidence that is critical for defeating the COVID-19 pandemic. Not only the clinical experience, but also the scientific evidence should be shared with the global scientific community.

The Clinical Trials Transformation Initiative (CTTI) Investigator Qualification Project addresses the need for a more efficient and effective means of identifying qualified clinical investigators and delegates. Selection of investigators and delegates who are qualified by training and experience to conduct clinical trials is essential to safeguarding protections for study participants and ensuring data quality and integrity. Sponsors generally document investigator qualification through training on the principles of good clinical practice (GCP), as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), adopted by regulatory authorities in the US, Japan and the European Union. Although these GCP principles provide an important foundation for promoting the conduct of quality clinical trials, the industry standard “one-size-fits-all” GCP training may not fully prepare investigators and delegates for conducting quality clinical trials. Routine GCP training alone may not be sufficient to prepare an inexperienced member of a site team, while repeating such training is unlikely to enhance the qualifications of an experienced researcher. The CTTI project team used findings from qualitative research activities, as well as input from an expert meeting with multiple stakeholders, to identify gaps and redundancies in the current training of investigators and their delegates and recommend practical, action-based solutions. CTTI provides recommendations on how to implement a more efficient and effective means of qualification for investigators and delegates, determine whether a site team is a good fit for a particular protocol, and improve the quality of clinical trial conduct.

Functional somatic disorders (FSD) characterized by persistent and disabling physical symptoms are common in adolescents. Diagnostic uncertainty and insufficient illness explanations are proposed perpetuating factors that may constitute barriers for treatment engagement. This study evaluates the impact of manualized assessment and psychoeducation on diagnostic certainty and various clinical outcomes in adolescents with multi-system FSD. Ninety-one adolescents (15-19 years) included in a randomized trial testing group-based therapy (AHEAD) received systematic assessment (4 hrs.) and a subsequent psychiatric consultation (1.5 hrs.). Clinical outcomes included self-reported physical health, symptom severity, illness perception, illness related behavior, and psychological flexibility assessed before and approximately two months after assessment, prior to specialized treatment. Data were analyzed using t-tests. Immediately following assessment 71 (80.7%) adolescents out of 88 reported a higher diagnostic certainty and 74 (84.1%) reported that attending assessment gave them positive expectations for future treatment. A clinically relevant improvement of physical health was not observed at two months but considerable reductions were seen on symptom severity, illness worry, negative illness perceptions, limiting illness behavior and psychological inflexibility. The results underpin the importance of systematic assessment and psychoeducation which may be effective in their own right in specialized treatment of adolescents with severe FSD.

Multicompartment compliance aids (MCAs) are devices with each discrete section denoting a single dosing occasion. The purpose of an MCA is to maximize patient adherence and thereby optimize the treatment benefits. These devices are widely employed throughout western Europe and UK and use appears to be rapidly increasing (2) although the RPS as moved away from these devices as a means to improve adherence. We analysed MCAs from various pharmacies over a wide geographic area in England and North Wales. We concluded that most MCA users are elderly patients. Also, most of the patients suffer of combined cardiovascular disease. However, a significant proportion of patients falls in the mental/ neurological disease category. Additionally, most of the externals added to MCAs are inhalers and painkillers. Moreover, SDIs are more frequent in female patients and these SDI are mainly related with mental health medication, cardiovascular disease medication and neurological medication. In conclusion, a directive for dispensing of MCAs in pharmacies by pharmacists through an enhanced service should be elaborated having in consideration PIMs, SDIs, drug stability and use of externals and MCA design and brand.

This study aimed to determine clinical instructors’ perceptions of the assessments used to evaluate the clinical knowledge of undergraduate nursing students. This study uses a descriptive phenomenological approach. Purposive sampling was used to recruit sixteen clinical instructors for semi-structured interviews between August to December 2019. All interviews were audio-recorded and transcribed verbatim. Data were analyzed using Colaizzi’s seven-step method. Four criteria were used to ensure the study’s validity: credibility, transferability, dependability, and confirmability. Three themes were identified in the clinical instructors’ views on evaluating the clinical performance of student nurses: familiarity with students, patchwork clinical learning, and differing perceptions of the same scoring system. Study results suggest the need for a reliable, valid, and consistent approach to evaluating students’ clinical knowledge. If the use of patchwork clinical internships for student nurses is unavoidable, a method for assessing student nurses’ clinical performance that requires instructor consensus is necessary.

The study describes the acute and delayed time course of recovery following the CrossFit® Benchmark Workout Karen. Eight trained men (28.4±6.4 years; 1RM back squat 139.1±26.0 kg) undertook the Karen protocol. The protocol consists of 150 Wall Balls, aiming to hit a target 3 meters high. Countermovement jump height (CMJ), creatine kinase (CK), and perceived recovery status scale (PRS) (general, lower and upper limbs) were assessed pre, post-0h, 24h, 48h and 72h after the session. The CK concentration 24h after was higher than pre-exercise (338.4 U/L vs. 143.3 U/L; effect size: 0.74; p≤0.05). At 48h and 72h following exercise, CK concentration had returned to baseline levels. The PRS general and of the lower limbs were lower in the 24-hours post-exercise compared to pre-exercise (PRS general: 4.7 ±1.5 and 7.9 ±1.7 mmol/L; and PRS of the lower limbs: 4.0 ±2.5 and 7.9 ±0.8, respectively). The PRS general, lower, and upper limbs were reduced at 48-post exercise compared to 72-hours post-exercise scores. Our findings provide insights into the fatigue profile and recovery in acute CrossFit® and can be useful to coaches effectively design the daily session.

Lymphoma diagnoses in the U.S. are substantial, with an estimated 89,380 new cases in 2023, necessitating innovative treatment approaches. Phase 1 clinical trials play a pivotal role in this context. We developed a binary predictive model to assess trial adherence to expected average durations, analyzing 1,089 completed Phase 1 lymphoma trials from clinicaltrials.gov. Using machine learning, the Random Forest model demonstrated high efficacy with an accuracy of 0.7248 and ROC-AUC of 0.7701 for lymphoma trials. Importantly, this model maintained an accuracy of 0.7405 when applied to lung cancer trials, showcasing its versatility. A key insight is the correlation between higher predicted probabilities and extended trial durations, offering nuanced insights beyond binary predictions. Our research contributes to enhanced clinical research planning and potential improvements in patient outcomes in oncology.

Genome-based testing in oncology is a rapidly expanding area of health care which is the basis of the emerging area of precision medicine. Efficient and considered adoption of novel genomic medicine testing is hampered in Canada by the fragmented nature of health care oversight as well as by lack of clear and transparent processes to support rapid evaluation, assessment and implementation of genomic tests. This article provides an overview of some key barriers and proposes approaches to addressing these challenges as a potential pathway to developing a national approach to genomic medicine in oncology.

Worldwide, the cesarean section rate has steadily increased from 6.7% in 1990 to 21.1% in 2018 and is expected to rise even more. World Health Organization propose the adoption of the Robson classification system as a global standard for monitoring, evaluating, and comparing delivery rates. The purpose of the current study is to use the Robson classification system to investigate how, independently of medical factors, the day of the week and time of delivery may affect the mode of birth. In the sample analysis, we included the records of 8572 women giving birth in one private health facility in Greece. Over 60% of deliveries during the study period were performed by a cesarean section and 8.5% of deliveries were performed by operative vaginal delivery. The results of this study indicate that the lowest birth rates are observed on Monday, Saturday, and Sunday. In Robson category 1 women are 73% more likely to deliver by cesarean section between 08:00 a.m. - 03:59 p.m. compared to those who give birth between 12:00 a.m. - 07:59 a.m. Also, women in group 5.1 are 16.7 times more likely to deliver by cesarean section in the morning compared to overnight deliveries. These result point out two non-clinical variables that influences the CS rate. The Robson classification system was a useful tool for the above comparisons.

The Rényi entropy functional was optimised for the novel findings of this investigation under various conditions. Their research's findings suggest that the complete spectrum of Lévy stable distributions is covered by generalised t-distributions. Additionally, an exposition was undertaken to prove that the Lévy distribution generalizes Tsallisian distribution, rather than the reverse. The current study is a strong generalization of an existing research work in the literature.

This comprehensive review delves into the cognitive neuroscience of hypnosis and variations in hypnotizability by examining research employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG) methods. Key focus areas include functional brain imaging correlations in hypnosis, EEG band oscillations as indicators of hypnotic states, alterations in EEG functional connectivity during hypnosis and wakefulness, drawing critical conclusions, and suggesting future research directions. The reviewed functional connectivity findings support the notion that disruptions in the functional integration between different components of the executive control network during hypnosis may correspond to altered subjective appraisals of the agency during the hypnotic response, as per dissociated and cold control theories of hypnosis. Building upon existing EEG results, a promising exploration avenue involves investigating how frontal lobes' integrated functioning with other cortical regions influences hypnosis and individual differences in hypnotizability during both waking and hypnotic states. Future studies investigating the effects of hypnosis on brain function should prioritize examining distinctive activation patterns across various neural networks. A practical approach entails simultaneously analyzing the causal relationships in functional connectivity linked to cognitive, physiological, and behavioral responses.

Aim. In the current study, we aimed at identifying resting-state brain networks, which are different in patients with depression compared to healthy individuals. Moreover, we analyzed the potential for clinical use of different network measures that could discriminate the two groups and thus help the diagnostic process. Method and subjects. We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed to investigate functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were made at the functional networks level, using false discovery rate method. Independent samples t-test was performed on the network measures mean values to reveal differences between HC and MDE groups. Permutation-based statistical testing was used to test the significance of the difference between the distributions of the network measures by nodes for HC and MDE groups. Linear discriminant analysis was used to differentiate between the groups. Results and discussion. Significant differences in FC between depressed patients and healthy controls were found with the most prominent changes encompassing within-region as well as between-region connectivity of occipital lobe areas such as precuneus (PreCu), cuneus (Cu), superior occipital gyrus (SOG), lingual gyrus (LG), fusiform gyrus (FG), cerebellum, along with limbic structures including the hippocampus (Hipp) and cingulate gyrus. Linear discriminant analysis demonstrated that the full connectivity matrices, as well as those with only the significant connections identified in advance, were the most precise in differentiating between depression and health. These measures reached precision levels of 97% and 94%, respectively. Conclusion. Our study delivered further evidence about impairment of functional connectivity networks in MDE that may contribute to differentiate patients with depression from healthy subjects.

Clinical trials, by contributing to the development of diagnostics and to the search for modern, more effective, and safer therapies, have become one of the most important elements of the healthcare system. The aim of this study was to assess Poles' knowledge and beliefs about clinical trials. Methods: The survey was conducted among Poles aged 18 and over with the help of external company, Ariadna, which is an independent research panel. The questionnaire contained 22 questions, of which 13 questions concerned beliefs and attitudes towards clinical trials. Results: One thousand and seventy-nine participants took part in the study (N = 1079). The mean age of respondents was 44.96 years (SD = 16.30). Slightly more women (N = 568, 52.6%) than men (N = 511, 47.4%) took part in the study. Among the respondents, 86.5% (N = 933) were aware of clinical trials. The main sources of information about clinical trials were the media (53.8%) including the Internet (N= 355, 32.9%), TV (N = 175, 16.2%), press (N = 30, 2.8%) and radio (N = 21, 1.9%). 43.2% (N = 466) of respondents reported little knowledge of clinical trials, while more than three quarters (N = 805, 75.2%) said they would like to learn more about clinical trials. Most respondents (N = 879, 81.4%) agreed with the statement that participation in a clinical trial is completely voluntary, and more than half (N = 580, 53.7%) agreed with the statement that hospitals participating in clinical trials provide better healthcare. The statement that the results of clinical trials are made available to the public was disagreed with by 37.2% (N = 402) of participants. Only 30.3% (N = 327) of participants agreed that clinical trials should be conducted with children. Conclusions: Poles rate their knowledge of clinical trials as low and would like to learn more. To reach the largest possible group of Polish patients, parallel educational activities on multiple levels may have the best effect. Poles' knowledge of clinical trials is mainly based on commercial sources. Further studies in different groups, i.e., clinical trial patients and investigators, are needed.

Objectives: Data sharing has become a requirement of many funding bodies and is becoming a scientific standard in many disciplines. In medical research, however, data sharing can conflict with clinicians’ obligation to protect patients’ privacy. General recommendations on data sharing exist also for clinical research, but so far lack practical and Swiss-specific aspects. The objective of this document is to provide practical recommendations for all relevant aspects of data sharing in agreement with legislation in Switzerland. Methods: This document was written by members of the Swiss CTU Network, a network of academic clinical trial units. The process did not follow a formalized Delphi process. After an internal consensus round, this report is now published as pre-print for external review. A second version will incorporate external comments. We plan to publish this document as a text in progress, as we expect relevant changes in related fields such as the development of further dedicated medical repositories or methodological advances in anonymization techniques. Results: We developed principles and practical recommendations with respect to informed consent, data management plan, anonymization, data structure and format, coding of variables, metadata and documentation, version control, selection of repository, requesting and use of data. We also provide a summary of legal aspects relevant for the Swiss context. Conclusions: The intension to share data has an impact not only after a clinical trial or an observational study is completed, but also during the planning period, the conduct and the analysis phase. Clinical researchers need to be aware at the beginning of a study on how to inform patients and at least the amount of work related to preparing data for sharing, metadata, and any further documentation. This report provides details of aspects to be considered, suggests decision criteria, and provides examples and checklists, in order to support data sharing in practice.

Clinical education is a method that is applied to formal nurse education as a step to provide real and direct learning experiences in the nursing environment correctly and effectively. The success of education in a clinical setting certainly requires the support of teaching nurses (clinical instructors) who have credibility and competence in terms of knowledge, attitudes and skills and are actively involved in professional activities. The diversity of backgrounds of nurses and students, including patients, certainly contributes to a shift in paradigms and perspectives for the nursing environment both in education and in clinical settings in health services. Responding to this cultural diversity, it is important to prepare knowledge and understanding related to transcultural nursing issues, intercultural communication and clinical education which explores the socio-cultural elements in the implementation of staff, students and patients. Purpose: The purpose of this literature review is to identify the extent to which nurse educators play a role by including socio-cultural and transcultural aspects in efforts to develop the quality of education in clinical practice environments in the millennium era. Method: The method of writing this article uses 11 literature review, the publication year period 2019,2020 and 2021 with sources from 4 databases such as science Direct, Scopus, ProQues and Elsevier. The review guidelines used are based on Prisma and the Joanna Briggs Institutute. The level of eligibility is identified through the title, abstract, research methodology as well as the type of scholarly journal and full text. Results: The results of the reviews found are presented in a narrative form. The results of the review study found that there were 11 articles explaining the competence of clinical education based on the socio-cultural approach, which is an educational strategy in the clinical area that integrates transcultural elements of nursing, intercultural communication, collaboration, self-directed with the principles of openness, honesty, and mutual respect in the implementation of team interaction and collaboration. The development of interpersonal relationships is also an important role that educators must have in helping to introduce the nurse orientation process to the organizational environment and other professional teams so that the achievement of satisfaction with clinical education is able to improve the performance of nurses and students perfectly. Conclusion: Clinical education which is supported by the competence of nurse educators (clinical instructors) who have individual and professional competences has a role to play in improving clinical learning outcomes by both students and nurses with a socio-cultural and transcultural strategic approach that will create satisfaction with the achievement of clinical competence and performance effectively.

Background: In the functional data analysis (FDA), the hybrid or mixed data are scalar and functional datasets. The semi-functional partial linear regression model (SFPLR) is one of the first semiparametric models for the scalar response with hybrid covariates. Various extensions of this model are explored and summarized. Methods: Two first research articles, including “semi-functional partial linear regression model”, and “Partial functional linear regression” have more than 300 citations in Google Scholar. Finally, only 106 articles remained according to the inclusion and exclusion criteria such as 1) including the published articles in the ISI journals and excluding 2) non-English and 3) preprints, slides, and conference papers. We use the PRISMA standard for systematic review. Results: The articles are categorized into the following main topics: estimation procedures, confidence regions, time series, and panel data, Bayesian, spatial, robust, testing, quantile regression, varying Coefficient Models, Variable Selection, Single-index model, Measurement error, Multiple Functions, Missing values, Rank Method and Others. There are different applications and datasets such as the Tecator dataset, air quality, electricity consumption, and Neuroimaging, among others. Conclusions: SFPLR is one of the most famous regression modeling methods for hybrid data that has a lot of extensions among other models.

Olfactory system is a vital sensory system in mammals, giving them the ability to connect with their environment. Anosmia, or the complete loss of olfaction ability, which could be caused by injuries, is an interesting topic for inspectors with the aim of diagnosing patients. Sniffing test is currently utilized to examine if an individual is suffering from anosmia; however, functional Magnetic Resonance Imaging (fMRI) provides unique information about the structure and function of the different areas of the human brain, and therefore this noninvasive method could be used as a tool to locate the olfactory-related regions of the brain. In this study, by recruiting 31 healthy and anosmic individuals, we investigated the neural BOLD responses in the olfactory cortices following two odor stimuli, rose and eucalyptus, by using a 3T MR scanner. Comparing the two groups, we observed a network of brain areas being more active in the normal individuals when smelling the odors. In addition, a number of brain areas also showed an activation decline during the odor stimuli, which is hypothesized as a resource allocation deactivation. This study illustrated alterations in the brain activity between the normal individuals and anosmic patients when smelling odors, and could potentially help for a better anosmia diagnosis in the future.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments in targeted therapy tailored to address distinct molecular pathway alteration required for PDAC. Our review delineates the principal signaling pathways and molecular mechanisms implicated in the initiation and progression of PDAC. Subsequently, we provide an overview of prevailing guidelines, ongoing investigations, and prospective research trajectories related to targeted therapeutic interventions, drawing insights from randomized clinical trials and other pertinent studies. This review focus on a comprehensive examination of preclinical and clinical data substantiating the efficacy of these therapeutic modalities, emphasizing the potential of combinatorial regimens and novel therapies to enhance the quality of life for individuals afflicted with PDAC. Lastly, the review delves into the contemporary application and ongoing research endeavors concerning targeted therapy for PDAC. This synthesis serves to bridge the molecular elucidation of PDAC with its clinical implications, the evolution of innovative therapeutic strategies, and the changing landscape of treatment approaches.

Background The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs in patients with COVID-19 was the basis for conducting this study. Aim The objective of this study was to assess DOACs consumption and expenditures in Russian Federation during COVID-19 pandemic and to analyse domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. Methods We searched Russian databases for CPGs, published between 2020 and 2023. We identified 7 relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using a AGREE II questionnaire. We calculated DOACs DDD consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020-2022. Results 7 clinical CPGs were analyzed with the AGREE II tool, it was revealed that experts gave the highest scores for the sections scope and purpose (from 62.98% to 100%), clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections stakenholder involment (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), editory independence ( from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores - ROPNIZ (Livzan), ROPNIZ (Drapkina). The minimum score is registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020 – 26.59 DDD per patient with COVID-19; in 2021 – 15.75 DDD per patient with COVID-19), and in 2022 – 10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 – 5.48 DDD, which is 2.74 times less than recommended.

The transition from undergraduate dental student to the actual practicing dentist is a crucial phase and ensuring the preparedness of graduates for the complexity and demands of contempo-rary dental practice is a challenging task. This study aimed to evaluate the self-perceived prepar-edness of undergraduate dental students and house officers in the dental colleges of Pakistan. Cross-sectional national study was planned to collect the information from dental students and new graduates in Pakistan. The pre-validated Dental Undergraduates Preparedness Assessment Scale (DU-PAS) was used. Purposive sampling technique was utilized to recruit house officers and undergraduate dental students from 27 dental schools in Pakistan. The data analysis was car-ried out using the R statistical environment for Windows (R Core Team, 2015). The total of 862 responses with 642 females and 219 males were analyzed in the study. Overall, clinical skills score was 30.56+9.08 and score for soft skills was 30.54+10.6. The mean age of the participants was 23.42+1.28. Deficiencies were reported in various soft skills and clinical skills attributes.The results highlighted the strengths and weaknesses of dental students and new graduates in Pakistani den-tal institutions. The findings may be used to further develop and strengthen teaching and training of dental students in Pakistan.

Scientific, technical and bioinformatics advances have made it possible to establish analytics-based molecular biosimilarity for the approval of biosimilars. If the molecular structure and other product- and process-related attributes are comparable within the limits of testing then a biosimilar candidate would have safe safety and efficacy as its reference products. The current model of animal and human testing becomes redundant since all of these studies have much lower sensitivity and reproducibility in confirming biosimilarity. The recent AI-based protein structure prediction model has confirmed that the 3D structure can be predicted from the amino acid sequence, reducing the need for structural analysis; however, the new test methods based on MS are millions of times more sensitive and accurate. While the regulatory agencies have begun waiving animal testing and, in some cases, clinical efficacy testing, removing clinical pharmacology profiling brings a dramatic paradigm shift, reducing development costs without compromising safety and efficacy. Also shared is a list of 160+ products ready to enter as biosimilars. Major actions from regulatory agencies and developers are required to make this paradigm shift.

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

Conditional heteroskedastic financial time series are commonly modelled by (G)ARCH processes. ARCH(1) and GARCH were recently established in C[0,1] and L^2[0,1]. This article provides sufficient conditions for the existence of strictly stationary solutions, weak dependence and finite moments of (G)ARCH processes for any order in C[0,1] and L^p[0,1]. It deduces explicit asymptotic upper bounds of estimation errors for the shift term, the complete (G)ARCH operators and the projections of ARCH operators on finite-dimensional subspaces. The operator estimaton is based on Yule-Walker equations, and estimating the GARCH operators also involves a result estimating operators in invertible linear processes being valid beyond the scope of (G)ARCH. Moreover, our results regarding (G)ARCH can be transferred to functional AR(MA).

In this paper, I investigate Hyers-Ulam-Rassias stabilities of the general quintic functional equation and the general sextic functional equation.

Clinical pharmacists are employed at many hospital departments in Denmark, but not yet on the Faroe Islands. The purpose of this study was to test feasibility of a clinical pharmacist-led medication review service at the surgical ward of the National Hospital on the Faroe Islands. Hospitalised surgical patients were offered a medication review service by a clinical pharmacist. Identified drug related problems (DRPs) were classified according to the Pharmaceutical Care Network Europe (PCNE) model. The qualitative inputs from the ward’s staff were collected. In total, 42 patients with 171 identified DRPs were included. The majority of the DRPs concerned suboptimal effect and the safety of the drug treatment. The 49.6 % of the proposed medication changes were accepted by the ward physicians. According to the qualitative inputs, the interest for the service was greater among the younger physicians compared to the older ones, and among nurses compared to physicians. Identified barriers for the optimal service implementation were an absence of medication ordinations and poor visibility of pharmacist’s notes in electronic health records. For a successful implementation of the service, work on the physicians’ interest in an interdisciplinary cooperation and optimization of the electronic health records are warranted.

Pharmacogenomics may improve patient care by guiding drug selection and dosing, however this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe co-morbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV, and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using literature, a list of pharmacogenes vital in disposition of the top 20 drugs was constructed leading to drug-gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants and statins were frequently prescribed cholesterol lowering drugs. HIV was reported in 20.3% of the study participants with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.

In recent years, the consumption of over-the-counter probiotics used to promote health has grown rapidly worldwide and become an industry. In medicine, various studies have proven that probiotics can help improve the immune system and intestinal health. They are usually safe, but in some rare cases, they may cause concerning adverse reactions. Although the use of probiotics has been widely popularized in the public, the results of many probiotics clinical trials are contradictory. Especially for the cancer patients, the feasibility of probiotics management to provide benefits by targeting cancer and lessening anti-cancer side effects requires further investigations. And this review summarizes the interactions between probiotics and the host and current pros and cons of applying probiotics in the cancer patients.

In this work, we propose a generalized partially functional linear model, which not only models the relationship between multiple scalar and functional predictors and response, but also automatically estimates the link function. Specifically, we use the functional principal component analysis method to reduce the dimensionality of functional predictors, estimate the regression coefficients using the maximum likelihood estimation method, estimate the link function using the method of local linear regression, iteratively obtain the final estimator, and prove the asymptotic normality of the estimator. The asymptotic normality is illustrated through simulation experiments. Finally, the proposed model is applied to study the influence of environmental, economic, and medical levels on life expectancy in China. In the study functional predictors are the daily air quality index, temperature, and humidity of 58 cities in 2020 and scalar predictors are GDP and number of beds in hospitals.

This study aimed to investigate sex differences in the functional movement in the adolescent period. Seven hundred and thirty adolescents (365 boys) aged 16–17 years participated in the study. The participants performed standardized Functional Movement Screen™ (FMS™) protocol and a t-test was used to examine sex differences in the total functional movement screen score while the chi-square test was used to determine sex differences in the proportion of dysfunctional movement and movement asymmetries within the individual FMS tests. Girls demonstrated a higher total FMS™ score compared to boys (12.7 ± 2.3 and 12.2 ± 2.4, respectively; F=8.26, p=0.0054). Also, sex differences were present in several individual functional movement patterns where boys demonstrated a higher prevalence of dysfunctional movement compared to girls in patterns that challenge mobility and flexibility of the body, while girls underperformed in tests that have higher demands for upper-body strength and abdominal stabilization. Findings of this study suggest that sex dimorphism exists in functional movement patterns in the period of mid-adolescence. The results of this research need to be considered while using FMS™ as a screening tool as well as the reference standard for exercise intervention among the secondary school-aged population.

Background: Measuring vital signs has always been a central task for Critical Care Nurse´s (CCNs) and Registered Nurse Anesthetist`s (RNAs) providing care in the post-anesthesia care unit (PACU) and a prerequisite for their decision-making. Properly measuring and understanding pediatric vital signs is a challenge in younger pediatric patients up to 36 months old. Purpose: gain a greater understanding of CCNs' and RNAs' perceptions of decision-making regarding the level of vital sign monitoring children require in the PACU. Method: A qualitative study design involving the critical-incident technique was used. Interviews were carried out with a purposeful sample of CCNs and RNAs (n=17) from two different hospitals. Findings: According to the nurses' experience, grounds for decisions concerning children’s need of vital-sign monitoring were both adequate and inadequate. They used actions to adjust the monitoring of vital signs to optimise conditions for assessment and the prospects of a safe recovery for the child. Conclusions: Evidence-based care and safety are compromised when the technology has limitations and is not adapted for children. Its use means that experience and clinical assessment are relied on to a greater extent. This not only makes experience important for reliable assessment, but also means that greater risks are accepted.

Advanced food processing techniques have drastic effects on the food, mainly on the nutritional profile; furthermore, the sedentary lifestyle led by people makes the body starve for nutrients and has a negative impact on proper growth and health. Addressing those major issues, various organic and functional foods have been widely recognised in recent times. The current work intends to prepare and evaluate a functional food made out of Aloe Vera. The health claims of Aloe Vera were uncountable. From the organoleptic profiling of the milk shake up to the 5% addition of Aloe Vera, all the sensory parameters were more satisfying. Incorporating Aloe Vera in the milkshake will be an innovative novel food product while enhancing the functional properties of Aloe Vera.

In this paper, we introduce a way of representing a given mapping as the sum of odd and even mappings. Then, by using this representation, we investigate the stability of various forms for the general nonic functional equation.

Inconsistent results published in previous studies make it difficult to determine the precise effect of consumer knowledge on their acceptance of functional foods, which were developed to improve consumers’ health status by providing adequate nutrition. We conducted a systematic review and meta-analysis by identifying and collecting relevant literature from three databases. Of the 1050 studies we reviewed, we included 40 in the systematic review and 18 in meta-analysis. Based on the focus of each included study, we operationally defined knowledge as knowledge of the functional food concept, nutritional-related knowledge, and knowledge of specific functional products. Results from the systematic review indicate that most participants from the included studies had a low level of knowledge, especially nutrition-related knowledge associated with consuming functional foods, and they were generally not familiar with the concept of functional foods. It is possible that participants’ level of knowledge was influenced by their demographic characteristics (e.g., age, gender, educational level, marital status, nationality). Results from the meta-analysis generated a summary effect size (r = 0.14, 95% CI [0.05; 0.23]), measured by the correlation coefficient r, which indicates that a small positive relationship exists between consumers’ level of functional foods knowledge and their acceptance of functional foods.

Stroke is a major leading cause of chronic disability, often affecting patients’ motor and sensory functions. Functional magnetic resonance imaging (fMRI) is the most commonly used method of functional neuroimaging and allows the non-invasive study of brain activity. The time-dependent coactivation of different brain regions at rest is described as resting-state activation. As a non-invasive task-independent functional neuroimaging approach, resting-state fMRI (rs-fMRI) may provide therapeutically useful information on both the focal vascular lesion and the connectivity-based reorganization and subsequent functional recovery in stroke patients. Considering the role of prompt and accurate prognosis in stroke survivors along with the potential of rs-fMRI in identifying patterns of neuroplasticity in different post-stroke phases, this review provides a comprehensive overview of the latest literature regarding the role of rs-fMRI in stroke prognosis in terms of motor and sensory outcome. Our comprehensive review suggests that with the advancement of MRI acquisition and data analysis methods, rs-fMRI emerges as a promising tool to study the motor and sensory outcome in stroke patients and evaluate the effect of different interventions.

Lung cancer is the leading cause of global cancer-related mortality resulting in ~1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or biobanked sections/biopsy of lung tumors, PDXs, and pleural affusion. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and immune therapy agents. PDOs mainly recapitulated the genomic alterations, transcriptomic landscape and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remained, PDOs showed promise to screen novel therapy drugs. With the technical advance of high throughput, tumor-on-chip, combined microenvironment, and air-liquid interface (ALI), the drug screening using PDOs would serve better for precision care of lung cancer patients.

Ketamine as an old - new drug has variety of clinical implications. In the last 30 years, ketamine has become popular for acute use in humans. Ketamine at standard doses is principally utilized for the induction and maintenance in surgical procedures. Beside its use in anesthesia and analgesia, recently studies had shown that ketamine find the place in the treatment of asthma, epilepsy, depression, bipolar affective disorders, alcohol and heroin addiction. Its mechanism of action is complex, but it mostly acts as a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. Ketamine is generally considered relatively secure and does not result in serious adverse effects when used at low doses and for short periods- Also, ketamine is known as a powerful psychostimulant. During the past decade, ketamine has been one of the commonly abused drug.

Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancers, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development [1]. Therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options [1-4]. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection [5-7]. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy and targeted agents are occurring.

Background: Transient Hypogammaglobulinemia of Infancy (THI) is a primary immunodeficiency caused by a temporary decline of serum levels of immunoglobulin G (IgG) greater than 2 standard deviations below the mean age-specific reference values in an infant between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as, in the third trimester of pregnancy, IgG is transferred across the placenta from mother to infant.Objective: To systematically review the diagnostic criteria of Transient Hypogammaglobulinemia of infants.Design & Methods: Systematic Review. Manual searching of 3 electronic databases (PubMed, Medline, & Google Scholar) from September 2021 – April 2022. Abstracts were screened to assess fit to the inclusion criteria. Data was extracted from the selected studies by using an adapted extraction tool from Cochrane.org. Studies were then assessed for bias by using an assessment tool also adapted from Cochrane.org.Results: Of the 215 articles identified, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in 6 domains. 5 studies (31%) had a low risk of bias, while 4 studies (25%) had a high risk of bias, & 7 studies (44%) were unclear for bias.Conclusion: We can conclude that THI is only definitively diagnosed after the abnormal IgG levels have normalized, hence THI is mostly a benign condition, but must be monitored for subsequent recurrent infections. The diagnostic criterion also includes vaccine & isohaemagglutinin responses to differentiate against other immunological disorders in infants.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

Background: Mucormycosis is a worldwide angio-invasive fungal infection that is associated with high morbidity and mortality. A few European studies have focused on the epidemiology. Methodology: A retrospective longitudinal descriptive study was performed with inpatients diagnosed with mucormycosis (ICD-9-CM, code 117.7, cases 1997-2015; and ICD-10, code B46, cases 2016-2018; along with length of hospital stay) in Spanish public hospitals between 1 January 1997 and 31 December 2018. Data were obtained from the Minimum Basic Data Set (CMBD in Spanish). Principal findings: A total of 962 patients were recorded; 665 were men. The mean age (±SD) was 55±18.8 years. The annual incidence rate increased from 0.74 to 1.24 cases per million person-years. The lethality rate was 31.3%. Renal failure (41.6%) and hematological malignancy (36.3%) were the main factors involved. Conclusions: Mucormycosis is a rare infectious disease in Spain, but it has had a significantly increased incidence in the last two decades. Being an adult male and having diabetes, neoplasm or renal failure are the main factors associated. High mortality is usually associated mainly with hematological malignancy and renal failure. CMBD studies could be an efficient tool for assessing changes in the epidemiology of mucormycosis.

The treatment of peptides has played an important role in clinical practice since the discovery of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States (US and other regional mar-kets, and peptides continue to undergo drug discovery steadily. Peptide research and development has lev-eraged a wider range of structures known from other plant sources, via pharmacology and medicinal molecular biology, beyond its conventional focus on individual endogenous peptides. We build a comprehensive database of peptides that have met scientific studies with more than 150 constantly evolving peptides. Here we provide a simple overview of the peptide-based drug therapy environment, comprising evolutionary points of view, structural properties, operational thresholds, and explanation of the therapeutic area.

Background: Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed diagnosis when initial clinical symptoms do not fulfill the traditional criteria. We aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD. Method: We retrospectively enrolled a total of 83 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data. Results: In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A patient with a neutrophil to lymphocyte ratio greater than 1.33 combined with a C-reactive protein more than 33 mg/L was more likely to have KD. Conclusion: Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

Clinical training in medical schools in Spain is performed by rotations in university hospitals. During these internships, students are expected to acquire and master basic procedural skills. However, the assessment tools available rarely check whether these skills are completely acquired by the students. We have used an e-portfolio to determine the optimal number of times the students need to repeat a procedure to be able to perform it independently. The results were compared with the actual performance during the internships. An e-portfolio collected qualitative information about the internships. Quantitative information was also requested about the number of times each clinical skill was performed. Later, a survey asked these students and their teachers the optimal number of times each skill should be repeated before it could be considered fully acquired. The questionnaire was answered by 98.6% of the students and 70.3% of their teachers. Out of the 21 clinical skills and procedures selected, both students and their tutors agreed in a similar optimal value in 16 of them; only in five of them, teachers thought that students needed a greater number of times than that selected by the students. When these optimal values were compared with the actual values recorded in the portfolio during the internships, it was found that about half of the clinical skills were carried out less frequently than expected, thus providing an important feedback about the internships. Quantitative information collected in portfolios reveals a moderate mismatch between students and tutors perceptions of their training needs.

Requirements Engineering (RE) is an important step in the whole software development lifecycle. The problem in RE is to determine the class of the software requirements as functional and non-functional. Proper and early identification of these requirements is vital for the entire development cycle. On the other hand, manual government of requirement classes is a timewasting task, and it needs intensive effort. Automatic requirement classification techniques through advanced Machine Learning (ML) strategies are started to be developed to address this problem. Basically, software requirements are generated as natural language explanations and therefore requirement classification may be handled as a particular Natural Language Processing (NLP) problem. From ML point of view, classification strategies require dataset to be used in the training/learning phase. For this goal, we generated a unique Turkish dataset having collected the requiremenst from real-world software projects with 4600 samples. Of these requirements, 3000 and 1600 were labeled as functional and non-functional, respectively. The data set has been evaluated using (i) traditional machine learning algorithms, (ii) deep learning algorithms, and (iii) transformer models respectively. As a result BERTurk was found to be the most successful algorithm to discriminate functional and non-functional requirements in terms of 95% f-score metric.

Cognitive biases towards disorder-specific stimuli are suggested to be crucial in the development and maintenance of symptoms in adults with functional gastrointestinal disorders (FGID). Functional abdominal pain disorders (FAPD), a subtype of FGID, are common in children and adolescents, but the influence of cognitive biases is sparsely examined. The aim of this study was to 1) develop a new experimental design for assessing cognitive biases towards gastrointestinal stimuli in children and adolescents (age 8-17 years) and 2) test its feasibility on a healthy sample exploring potential sex- and age-related differences. The online experimental design – BY-FAP (Bias in Youth with Functional Abdominal Pain) includes a word task and a picture task. Stimuli in both tasks are related to general and gastrointestinal symptoms and the design includes three phases: 1) encoding, 2) free recall and 3) recognition. Results from 96 healthy participants (Mage = 12.3, 47.9% female) found no significant difference between sex or age groups in recall and recognition of either words or pictures. The results support that the design is feasible for children and adolescents. In the future, BY-FAP can be used to explore possible cognitive biases in children and adolescents with FAPD.

A growing number of studies focus on methods to estimate and analyze the functional connectome of the human brain. Graph theoretical measures are commonly employed to interpret and synthesize complex network-related information. While resting state functional MRI (rsfMRI) is often employed in this context, is known to exhibit poor reproducibility, a key factor which is commonly neglected in typical cohort studies using connectomics-related measures as biomarkers. We aimed to fill this gap by analyzing and comparing inter- and intra- subject variability of connectivity matrices as well as graph-theoretical measures in a large (n=1003) database of young healthy subjects which underwent four consecutive rsfMRI sessions. We analyzed both directed (Granger Causality and Transfer Entropy) and undirected (Pearson Correlation and Partial Correlation) time-series association measures and related global and local graph-theoretical measures. While matrix weights exhibit a higher reproducibility in undirected as opposed to directed methods, this difference disappears when looking at global graph metrics and, in turn, exhibits strong regional dependence in local graphs metrics. Our results warrant caution in the interpretation of connectivity studies, and serve as a benchmark for future investigations by providing quantitative estimates for the inter- and intra- subject variabilities in both directed and undirected connectomic measures.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Current drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and CSF biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of the Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are currently assessed in clinical trials. The abovementioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are consequential to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

As the global semiconductor market is growing steadily, the need for optimization of the man-ufacturing process is paramount. For example, in the process of transferring the semiconductor chips to the substrate, each chip needs to be individually separated from the dicing tape via a plunger. In this process, however, the fixed chip is not easily removed from the tape due to strong adhesion, and the chip can become damaged if it is forcibly pulled out. Therefore, the present paper reports the development of functional adhesive tapes that initially adhere strongly to the semi-conductor chip on the dicing tape but can be easily removed after transfer. The fabricated functional tape has an initial adhesion of 350 gf, which enables firm fixing of the semiconductor chip to be transferred, and a final adhesion of 0.8 gf after UV curing, thereby facilitating removal of the chip without damage after transfer. Therefore, the fabricated functional tape is expected to contribute to the optimization of the semiconductor manufacturing process and is expected to be useful in the semiconductor package manufacturing process.

In recent years, the evaluation of many plant-derived compounds as potential new drugs or functional foods has become an active research topic. The characteristics of quinces of the genera Cydonia, Chaenomeles and Pseuocydonia are largely similar, which is why these fruits are often confused. Although they have been appreciated in Asia for centuries as a valuable component of local ethnomedicine, they are less known in Western countries and scientific knowledge about their health benefits remains fragmentary. This literature review presents the bioactive compounds of these fruits with special emphasis on antioxidants. Most space has been devoted to the presentation of the biological activities and potential medical applications of the fruits due to their antioxidant, anti-inflammatory, anticancer, cardioprotective and antidiabetic effects.

Attention Deficit Hyperactivity Disorder (ADHD) it is known as a neuropsychiatric disorder. Anatomicaly components with implications in this previously mentioned disorder, are the anterior cingulate gyrus and dorsolateral prefrontal cortex (DLFPC) that are are found having a role in appearing this disease. ADHD is associated with cognitive and functional deficits that relate to diffuse abnormalities in the brain. ADHD is a specific pathology in children but may persisit to youth and also not so hard to find to adults.Till now, hard to find the curative treatment knowing ADHD as a neuropsychiatric disorder with enlarge unknown scientific points. Genetic and environmental component play an important role in diagnosis. Patients life style, a relevant history of individual geneticsand environmental factors are important in diagnosisThe management of ADHD, is also an important part togeter with future trends.

Goat milk starts to be gradually the preferred milk by consumers worldwide and also in Slovakia. It is also demanded as functional and/or nutraceutical drink as it is rich in bioactive components. Goat milk contains complex of microbiota among which the phylum Firmicutes have been occurred with abundance 20.5 %. Among individual representatives of this phylum are involved also lacticaseibacilli. This study has been focused on bacteriocin-producing, beneficial strain Lacticaseibacillus paracasei LPa 12/1 isolated from raw goat milk and its potential to be additive in dairy products. Based on safety testing of bacteriocin-producing LPa 12/1 strain using BALB/c mice, it looks as safe. Even increase tendency in phagocytic activity in blood of mice was noted after LPa 12/1 strain application. Encapsulated form of LPa 12/1 strain producing thermo-stable bacteriocin seems to be a suitable to supplement dairy products. The strain colonized better ewe-goat milk yoghurt (up to 6.1 cfu/g log 10) than cow milk yoghurt (almost 5.0 cfu/g log 10). Although specific organoleptic tests were not involved, cow milk yoghurts remained in better consistency after LPa 12/1 strain supplementation in comparison with ewe-goat milk yoghurts. LPa 12/1 strain may be supposed as a new potential additive in dairy products/yoghurts.

In many previous studies, the conclusions for the effects of disturbance and environmental gradients on the diversity was remain controversial due to exclusions of trait-based diversity in their methodology. This study hypothesized trait-based indices are more likely to show monotonic and predictable relations than traditional based species diversity to guide effective restoration of tree species diversity against environmental change and anthropogenic factors. This study therefore, was initiated to access trait based functional diversity of Yayu Coffee Forest Biosphere Reserve (YCFBR), Southwest Ethiopia. Data was collected from 90 proportionally distributed plots along disturbance levels from core, buffer and transitional zones. For functional trait diversity estimation, traits relevant to plant-life strategy, competition and response to disturbances and climate change were selected. Multiple regression model was used to test the response of species diversity and functional diversity to disturbance and environmental gradients. The result revealed that, anthropogenic disturbance and elevational gradients are the most important factors influencing functional diversity in the YCFBR. Overall this study demonstrates that, trait based functional diversity is useful to predict adaptation potentials of species in heterogeneous environments. Species with low specific leaf area &amp; selective seed mass is recommended for the restoration of disturbed ecosystem.

Type 2 Diabetes (T2D) is a growing global health problem that requires new and effective prevention and management strategies. Recent research has highlighted the role of epigenetic changes in the development and progression of T2D, and the potential of functional foods as complementary therapy for the disease. This review aims to provide an overview of the current state of knowledge on the preventive epigenetic mechanisms of functional foods in T2D. We provide background information on T2D and its current treatment approaches, an explanation of the concept of epigenetics, and an overview of the different functional foods with demonstrated preventive epigenetic effects in T2D. We also discuss the epigenetic mechanisms by which these functional foods prevent or manage T2D and the studies that have investigated their preventive epigenetic effects. In addition, we revisit works on the beneficial influence of functional foods against the programming and complications of parentally-triggered offspring diabetes. We also postulate, albeit based on the scarce data, that epigenetic inheritance mechanistically mediates the impacts of functional nutrition against the metabolic risk of diabetes in the offspring. Finally, our review highlights the importance of considering the preventive epigenetic mechanisms of functional foods as a potential avenue for the development of new prevention and management strategies for T2D.

Bioactive compounds are the food constituents, providing beneficial health effects to functional foods and nutraceuticals. These compounds have antioxidants activity including anti-inflammatory, antifungal, and have additional preventative actions. Since these compounds are important constituents enhancing function of the foods, therefore, these constituents are necessary to be incorporated under the umbrella of functional foods. Functional foods provides health benefits though bioactive compounds, as these compounds target mechanisms that manage, prevent, and/or treat chronic or acute diseases. The bioactive compounds are quite essential for functional foods that are crucial for optimal health, thereby leading to the inclusion of these compounds in the most recent definition of functional foods. Some experts have defined that bioactive compounds are the chemical components that contributes and regulates in biological mechanisms. These bioactive compounds are more accurately defined by Dr. Martirosyan and Pisarski as the “primary and secondary metabolites of nutritive and non-nutritive natural components generating health benefits by preventing or managing chronic disease or its symptoms”. These compounds have potential antioxidant and anti-inflammatory activity, which provide benefits to health. Although they are a small proportion of a food source, these compounds can also trigger the mechanisms that will alter and can improve human health. Certain bioactive compounds present in foods are extremely beneficial, but if consumed in excess, they can cause toxicity. Therefore, each bioactive compound must be fully evaluated in order to establish a beneficial and a toxic threshold amount.

Salvia is a large genus in traditional Chinese medicine with hundreds of species. Tanshinones are a highly representative class of exclusive compounds found in the Salvia genus that exhibit significant biological activity. Tanshinone components have been identified in 16 species of the Salvia genus. The CYP76AH subfamily (P450) is crucial for the synthesis of tanshinone due to its catalytic generation of polyhydroxy structures. 420CYP76AH genes were obtained, clear clustering relationships. In this study 15 CYP76AH genes from 10 Salvia species were cloned and studied from the perspectives of evolution and catalytic efficiency. Structure-function relationship revealed several conserved residues which might be related to the function of CYP76AHs. Amino acids (97I, 116V, and 290T) are conserved in CYP76AH1 group, while amino acids (117G, 208S, 237Y, and 479F) are CYP76AH3 group protein sequence characteristics with unique enzyme function.This research holds significant implications for the classification of the Salvia genus and provide efficient catalytic elements for the synthetic biology production of tanshinones.Keywords: Salvia; CYP76AH; P450; biosynthesis; functional gene

In Functional Analysis as well as Topology, we frequently encounter sets, say $X$, that contain elements close to each other. These sets display a defining "finite-ness" property: for all open cover $\mathcal{O}$ of $X$, there exists a finite subcollection $\mathcal{U}\subseteq\mathcal{O}$ such that $\mathcal{U}$ covers $X$. Such spaces $X$ are called $\textbf{compact}$, and the above "finite-ness" property afford us great convenience, because we can always investigate $X$ by investigating its finite open cover $\mathcal{U}$Arzela-

Wildfires have continued to increase in frequency and severity in Southern California due in part to climate change. To gain a further understanding of microbial soil communities’ response to fire and functions that may enhance post-wildfire resilience, soil fungal and bacterial microbiomes were studied from different wildfire areas in the Gold Creek Preserve within the Angeles National Forest using 16S, FITS, 18S, 12S, PITS, and CO1 amplicon sequencing. Sequencing datasets from December 2020 and June 2021 samplings were analyzed using DNA Subway, ranacapa, stats, vcd, EZBioCloud, and mixomics. Significant differences were found among bacterial and fungal taxa associated with different fire areas in the Gold Creek Preserve. There was evidence of seasonal shifts in the alpha diversity of the bacterial communities. In the sparse partial least squares analysis, there were strong associations (r>0.8) between longitude, elevation, and a defined cluster of Amplicon Sequence Variants (ASVs). The Chi-square test revealed differences in fungi:bacteria (F:B) proportions between different trails (p=2*10^-16). sPLS results focused on a cluster of Green Trail samples with high elevation and longitude. Analysis revealed the cluster included the post-fire pioneer fungi Pyronema, and Tremella. Chlorellales algae, and pathogenic Fusarium sequences were elevated. Bacterivorous Corallococcus, which secretes antimicrobials, and bacterivorous flagellate Spumella, were associated with the cluster. There was functional redundancy in clusters that were differently composed, but shared similar ecological functions. These results implied a set of traits for post fire resiliency. These included photo-autotrophy, mineralization of pyrolyzed organic matter and aromatic/oily compounds, pathogenicity and parasitism, antimicrobials, and N-metabolism.

Evolutionary ecologists seek to understand how phenotypic evolution relates to population level traits. To document that, we quantified functional traits (escape strategy, sprint speed and predatory performance) and population density across 10 lizard species representing the acquisition of burrowing snake-like morphs (BSLM), from Brazil. We used phylogenetic mixed models to test if: a) morph and substrate affects lizards’ flight strategy and speed, b) BSLM species get more access to different potential prey types than lacertoid ones, when in syntopy, and d) morph is correlated with population abundance and habitat use in a way expected from the output of the previous experiments. We found that BSLM rigidly relied on burrowing as flight strategy, while syntopic lacertoid species changed their strategy according to the substrate. Also, sand has opposite effects on sprint speed depending on morph, making lacertoids run slower and BSLM faster. Despite BSLM were overall slower than lacertoids, they were as good hunters of challengingly fast prey, and better hunters of underground prey. Further, in the sandy habitats where these morphs are syntopic, prey is most available at superficial leaf litter under vegetation, although there is a large stock of underground prey, under the vegetation, too. These results support our observed higher importance of sand for BSLM’s populations and the higher importance of vegetation for lacertoids’ population density. Finally, although BSLM species reached the highest populational densities among the studied species, a systematic effect of morphological evolution on abundance remains elusive.

Chronic diseases (e.g., heart disease, cancer, diabetes) are of major public concern. Such chronic diseases are often caused by a dietary pattern characterized as relatively high in fat, refined sugar, salt, and cholesterol. Societal interest in consuming healthy foods and the demand for healthy food products has increased significantly. As a result, functional foods have gained significant research attention in the food health and technology innovations field. To date, many studies have investigated the factors that may predict consumer acceptance of functional foods, and a wide range of influential factors have been reported. However, studies conducted in different contexts pose challenges to gaining a clear understanding of the factors influencing consumer acceptance. This scoping review identified 75 articles published with varying populations around the globe that empirically investigated consumers’ acceptance of functional foods. We identified and categorized a wide range of determinants related to consumer acceptance of different types of functional foods. The five categories of determinants were product characteristics, socio-demographic characteristics, psychological characteristics, behavioral characteristics, and physical characteristics. Each of the determinants were more fully described by sub-determinants in our scoping review. These determinants should be considered and used by leaders and scientists in product development to aid decision making and, ultimately, the successful launch of novel functional foods.

Task fMRI has played a critical role in recognizing the specific functions of the different regions of human brain during various cognitive activities. This study aimed to investigate group analysis and functional connectivity in the Faradarmangars brain during the Faradarmani CF (FCF) connection. Using task functional MRI (task-fMRI), we attempted the identification of different activated and deactivated brain regions during the Consciousness Filed connection. Clusters that showed significant differences in peak intensity between task and rest group were selected as seeds for seed-voxel analysis. Connectivity of group differences in functional connectivity analysis was determined following each activation and deactivation network. In this study, we report the fMRI-based representation of the FCF connection at the human brain level. The group analysis of FCF connection task revealed activation of frontal lobe (BA6/BA10/BA11). Moreover, seed based functional connectivity analysis showed decreased connectivity within activated clusters and posterior Cingulate Gyrus (BA31). Moreover, we observed an increased connectivity within deactivated clusters and frontal lobe (BA11/BA47) during the FCF connection. Activation clusters as well as the increased and decreased connectivity between different regions of the brain during the FCF connection, firstly, validates the significant effect of the FCF and secondly, indicates a distinctive pattern of connection with this non-material and non-energetic field, in the brain.

Whey proteins have excellent nutritional characteristics due to their levels of essential amino acids with high bioavailability. However, it has a high biochemical oxygen demand (BOD) and a considerable polluting potential, thus food manufacturers have opted to add whey to food formulations. The demand for beverages containing vitamins, probiotics, prebiotics, minerals, and bioactive compounds (antioxidants) with health benefits has increased and driven market growth. Therefore, this study aimed to develop a probiotic functional carbonated beverage from cheese whey and evaluate its microbiological, and physicochemical characteristics soon after the production and during storage. The viability and stability of probiotic, the microbiological characteristics, titratable acidity and sedimentation of the beverage were monitored during refrigerated storage for a month. The probiotic to be added to the formulation was established in a preliminary step. The production of this beverage proved to be a simple technology and the product was suitable for incorporation of the probiotic Bifidobacterium animalis subsp. lactis. The probiotic showed good viability and stability during storage. The microbiological quality of the beverage met the Brazilian legal standards. The pH and titratable acidity of the probiotic carbonated beverage remained stable during storage, and slight sedimentation was observed after one week of refrigerated storage.

This study investigates the pivotal areas where Artificial Intelligence (AI) integration in healthcare warrants further exploration, leveraging insights from Boston Specialists, a forefront healthcare provider in AI adoption. Employing a qualitative case study approach, enriched by in-depth interviews and comprehensive literature reviews, we identify three main domains for potential AI expansion: scheduling efficiency, clinical documentation, and AI-driven medical research. Our results underscore the substantial enhancements AI brings to operational workflows and patient care, notably through improved scheduling systems, accuracy in medical documentation, and the facilitation of data-driven research methodologies. These findings suggest a critical need for healthcare institutions to further invest in AI technologies, focusing on these key areas to harness AI's full potential in personalizing care, optimizing efficiency, and advancing medical knowledge. The study concludes with a call for continued investigation into AI's integration within healthcare settings, emphasizing the importance of a supportive organizational infrastructure, ethical considerations, and data security in realizing AI's transformative impact on healthcare delivery and patient outcomes.

Cacipacoré virus (CPCV) was discovered in 1977 deep in the Amazon rainforest, from the blood of a black-faced ant thrush (Formicarius analis). As a member of the family Flaviviridae, genus orthoflavivirus, CPCV's intricate ecological association with vectors and hosts raises profound questions. CPCV’s transmission cycle may involve birds, rodents, equids, bovines, marsupials, non-human primates and bats as potential vertebrate hosts, whereas Culex and Aedes spp mosquitoes, have been implicated as potential vectors of transmission. The virus' isolation across diverse biomes, including urban settings suggests its adaptability as well as presents challenges for its accurate diagnosis and thus its impact on veterinary and human health. With no specific treatment or vaccine, prevention hinges on traditional arbovirus control measures. Here we provide an overview of the ecology, transmission cycles, epidemiology, pathogenesis and prevention, aiming in improving our ability to better understand this neglected arbovirus.

Blood-based biomarkers for early detection of recurrence have a significant clinical impact on the improved management of breast cancer patients, as cancer recurrence results in poor prognosis. This study aimed to investigate if the measurement of blood endocan in breast cancer patients with high ESM1 expression could be an effective tool to detect postoperative recurrence compared with existing tumor markers. Blood was collected before and after the tumor resection from the mouse models of breast cancer, and endocan levels were measured while visualizing metastatic recurrence with noninvasive luminescence imaging. In clinical settings, blood was withdrawn from 16 breast cancer patients before and after the tumor resection, and the effect of lumpectomy on blood endocan level was evaluated. Additionally, the blood endocan from 20 patients diagnosed with postoperative recurrence was measured, and their positivity rate for endocan was compared with that for serum carcinoembryonic antigen (CEA) or cancer antigen 15-3 (CA15-3). Our preclinical and clinical experiments revealed that blood endocan levels reflected tumor burden. Furthermore, over 60% of patients suffering from postoperative recurrence who tested negative for CEA or CA15-3 were positive for endocan. Our results support the clinical significance of endocan in breast cancer patients for detecting breast cancer recurrence.

Dietzia natronolimnaea C79793-74 has emerged as a potential probiotic strain with implications for managing Crohn's disease. This study evaluates the safety profile of D. natronolimnaea C79793-74 as a probiotic sup-plement. Genotypic characterization involved a 16S rRNA gene and genomic sequencing and genome an-notation. The safety assessment included interrogation of the assembled genome for antibiotic resistance genes and virulence factors, utilizing the CARD and VFDB databases. Notably, the analysis revealed an ab-sence of antibiotic resistance or virulence factors in Dietzia natronolimnaea C79793-74. The safety and tol-erability of D. natronolimnaea C79793-74 were further investigated in an 8-week double-blind, place-bo-controlled clinical trial involving healthy adult participants. A daily dose of 5 x 109 CFU of the probiotic strain was administered. This clinical trial represents the first assessment of the safety of D. natronolimnaea C79793-74 in human subjects. Results demonstrated that participants in both the Dietzia and Placebo groups maintained clinical and hematologic markers within the normal range throughout the study. More-over, the probiotic strain was well-tolerated, with nearly all participants experiencing no severe or medium adverse events. Collectively, the comprehensive data obtained in this study support the inference that Dietzia natronolimnaea C79793-74 is safe and well-tolerated as a nutritional supplement for human con-sumption

This review explores the complex interrelationships between emotion, attention, and behavior, drawing upon empirical evidence from psychological, neuroscientific, and clinical studies. It delves into the neural mechanisms that underlie these interactions, with a focus on key brain regions such as the prefrontal cortex and amygdala. Clinical cases involving stroke and attention-deficit/hyperactivity disorder (ADHD) are examined to illustrate the real-world implications of these cognitive interactions. The review also discusses the impact of effective emotion regulation strategies and the role of attention as a cognitive mechanism that influences both emotion and behavior. Neuroimaging studies, particularly functional MRI, are highlighted for their role in providing a deeper understanding of these intricate relationships. The review concludes by emphasizing the importance of this triadic relationship in adaptive functioning and its broader implications for mental health, interpersonal relationships, and quality of life.

Post operative recurrence (POR) is the rule in patients with Crohn’s disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single center randomized open label clinical study, in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 post-operatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score≥i2. We enrolled 35 patients (25 males, mean age 35±1.4 years, median disease duration 5±6.1 years) following ileocecectomy. Of these, 7(20%) were current smokers and 9(26%) biologics experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs 69%, p=0.004) and 58 (47% vs 75%), (p=0.03, HR=0.39, 95% CI=0.16-0.93). POR was associated with increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin and serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab is more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower post-operative BMI were associated with ePOR. Eighteen weeks serum hemoglobin and ALT, and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB therapy is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a serious medical and epidemic problem all over the world. We present here a series of clinical cases consist of two patients diagnosed with isoniazid resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. And the pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis1,2 via the following mutation c.947G&gt;A; p.Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons, as well as mutations in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the katG315 mutation worldwide. The second most common mutation is inhA-15, and it has been reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and katG 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.

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.

Purpose: The goal of this article was to introduce a new technique for root coverage (RC), the Mixed-Thickness Tunnel access (MiTT), approaching a full-split design, showing the results obtained in a case series and demonstrating it step-by-step. Methods: Healthy individuals, non-smokers, and non-diabetics, who were diagnosed with gingival recession (GR) type 1 or 2 (RT1 or RT2). After all necessary evaluations, prophylaxis was performed 14 days before the surgical procedure. Then, after the basics clinical conduct and anesthesia, one or two vertical incision(s) on the mucosa (around 1-2 mm apical to the MGJ), lateral to the papilla base, were done. Initial detachment of the mucosa from the muscles (split design); it was permitted (but not mandatory) to do intrasulcular incisions; from the MGJ to coronal, subperiosteal access was done to raise the full-thickness tunnel. It must communicate up to the gingival sulcus area and the papilla’s base, keeping the papilla’s tip intact. A connective tissue graft was harvested, which was inserted through the linear incision or intrasulcularly. Interrupted sutures were done and may be used as adjunctive material. Results: Nine healthy individuals (7 females and 2 males) aged 19 and 43 years were enrolled. They were treated following the MiTT steps. There were four cases with a single GR, 2 patients with 2 teeth involved, and three with 3 or 4 GR. Seven cases were RT1 and two RT2. All RT1 cases achieved 100% RC, while the mean RC obtained for RT2 was around 80%. Conclusion: MiTT can be considered a more straightforward approach for minimally invasive surgical technique, which is a feasible option to treat RC with a high success rate, predictability, and esthetic preservation. There is a technical sensitivity to performing the full-split design procedure.

Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 among healthy children to those of VarivaxTM (control). Children aged 12 months to 12 years were randomized 1:1 to receive either NBP608 or control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. A total of 499 participants (NBP608, n = 251; control, n = 248) was enrolled. The seroconversion rate (SCR) measured using FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for SCR difference (NBP608 minus control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of –15%. In assessment by gpELISA, the SCR was 99.53% in the NBP608 group; and the 95% LCL for SCR difference was 6.5%, which was higher than the specified non-inferiority margin of –15%. There were no significant differences between the NBP608 and control group with respect to proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to VarivaxTM.

ChatGPT is gaining widespread acceptance for its ability to generate natural language sentences in response to various inputs and is expected to become a supplementary tool for diagnosing and determining treatment policies in clinical settings. ChatGPT was used to evaluate its ability to perform clinical inference and accuracy in answering questions on the 117th Japanese National Medical Licensing Examination held in February 2023. The exam questions were manually inputted into ChatGPT's window, and the accuracy of ChatGPT's responses was determined based on answers provided by a preparatory school. ChatGPT provided answers for 389 out of 400 questions, and its overall correct answer rate was 55.0%. The correct answer rate for 5-choice-1, 5-choice-2, and 5-choice-3 were 57.8%, 42.9%, and 41.2%, respectively. The highest correct answer rate was for the compulsory exam (67.0%), followed by the specific knowledge exam (54.1%) and the cross category exam (47.9%). The correct answer rate for non-image questions was 56.2% and for image questions, it was 51.5%. The study suggests that ChatGPT has potential to support healthcare professionals in clinical decision-making in Japanese clinical settings, but caution should be exercised in interpreting and using the answers generated by ChatGPT due to room for improvement in performance.

Introduction: Leprosy, caused by Mycobacterium leprae is one of the oldest infectious diseases in human history and its eradication is linked to poverty control, lack of basic sanitation, the fragility of health, and education services. Objective: To evaluate the frequency of blood groups (ABO/Rh) and the sociodemographic and clinical profile of Angolan patients with Leprosy treated at the Anti-Tuberculosis and Leprosy Dispensary in Luanda, the capital city of Angola. Methodology: A descriptive, introspective, cross-sectional study with a quantitative approach was carried out with 102 patients of Luanda, in the second half of 2021. Results: Of the 102 patients included in the study, the majority belonged to the ORh+ group (51.9%), followed by the BRh+ group (27.4%) and ARh+ (18.6%), most were under 51 years of age ( 87.3%), with low education (54.9%), coming from urban areas (44.1%). As for clinical conditions, most had a multibacillary infection (93.1%), diagnosed mainly by smear microscopy (75.5%) without other infection (79.4%), some of them with complications (28.4%) and individuals with non-O blood group showed changes in the blood count. Conclusion: Leprosy seems to be common in ORh+ individuals, it continues to affect especially those residing in areas of population agglomerations and with low education, presenting itself as a multibacillary infection, where changes in the blood count are greater in non-O individuals.

Laboratory medicine is a digital science. Every large hospital produces a wealth of data each day - from simple numerical results from e.g. sodium measurements to highly complex output of “-omics” analyses, as well as quality control results and meta-data. Processing, connecting, storing, and ordering extensive parts of these individual data requires Big Data techniques. Whereas novel technologies such as artificial intelligence and machine learning have exciting application for the augmentation of laboratory medicine, the Big Data concept remains fundamental for any sophisticated data analysis in large databases. To make laboratory medicine data optimally usable for clinical and research purposes, they need to be FAIR: findable, accessible, interoperable, and reusable. This can be achieved for example by automated recording, connection of devices, efficient ETL (Extract, Transform, Load) processes, careful data governance, and modern data security solutions. Enriched with clinical data, laboratory medicine data allow a gain in pathophysiological insights, can improve patient care, or they can be used to develop reference intervals for diagnostic purposes. Nevertheless, Big Data in laboratory medicine do not come without challenges: The growing number of analyses and data derived from them is a demanding task to be taken care of. Laboratory medicine experts are and will be needed to drive this development, take an active role in the ongoing digitalization, and provide guidance for their clinical colleagues engaging with the laboratory data in research.