Introduction: Parkinson’s disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Methods: Demographic and treatment data of a cohort of PD carriers of recessive genes (9 homozygous or compound heterozygous PRKN carriers, 4 Heterozygous PRKN carriers and 3 biallelic PINK1 carriers) were evaluated. Results: The average Levodopa Equivalent daily dose (LEDD) was 806.8±453.5 (range 152-1810) in PRKN carriers and 765±96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of Levodopa. The response to Dopamine Agonists (DA) was often favorable both as initial and longitudinal therapy. 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate Levodopa or DA. Conclusions: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any Levodopa treatment decades after disease initiation. DA or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments will be further discussed.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.

(1) Background: Non-surgical endodontic treatment has been repeatedly shown to be clinically successful, however, clinical data are scarce. This practice-based retrospective clinical study aimed to investigate endodontic outcome over 40 years and to identify relevant factors from clinical protocols. (2) Methods: Two experienced dental practitioners in two different private dental practices treated 174 patients with 243 teeth from 1969 to 1993. After obturation, either a new restoration (amalgam, resin composite, glass-ionomer cement), or re-cementation of pre-existing prosthetic restorations or its renewal followed. Metal posts (operator A) or screws (operator B) were inserted when indicated. The primary outcome (tooth survival) was achieved when the endodontically treated tooth was in situ, painless and in full function. Secondary outcome was to investigate the impact of potential prognostic factors on survival rates. (3) Results: Overall mean 40-years survival was 56.1% of all treated teeth after 40 years of clinical service resulting in an annual failure rate of 1.1%. Most investigated clinical factors (Jaw, tooth position, number of intracanal dressings, post/screw placement, sex) had no significant influence on survival. Among postendodontic restorations, resin composite was advantageous. (4) Conclusions: Even with materials and techniques from the 1970’s and 1980’s, successful root canal treatment was achievable. Except postendodontic restorations, most of the evaluated factors had no significant influence on clinical long-term survival of root-canal treated teeth.

Globally, gastric cancer is a major cause of cancer mortality, with a 5-year survival rate of 32% for locally advanced and metastatic gastric cancer. This systematic literature review summarized the clinical, safety, and humanistic outcomes associated with systemic regimens given as first line therapy for locally advanced and metastatic gastric cancer. The search included articles published in English in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and the American Society of Clinical Oncology meeting library, from inception to April 2022. Phase II and III randomized controlled trials conducted among western populations diagnosed with stage III and IV locally advanced and metastatic gastric cancer were included. Two investigators independently reviewed the studies, conducted data extraction, and assessed risk of bias in accordance with PRISMA guidelines. Twenty-four randomized controlled trials totaling 8,705 patients were included. Median overall survival ranged from 5.0-13.1 months, median progression-free survival ranged from 2.0-7.7 months, and objective response ranged from 13.0-64.1%. Two studies reported higher quality of life outcomes. Grade 3 and 4 adverse events were reported in most studies. Improvement in clinical outcomes can be seen in recently published randomized controlled trials for locally advanced and metastatic gastric cancer.

Abstract Kidney transplant recipients, because of a weak immune response due to the assumption of immunosuppressant are exposed to the risk of COVID-19 infection. This fact realize the problem on how to treat the severe infection without carrying the risk of acute rejection due to the reduction of the immunosuppressive drugs. The best are the prophylactic measures to be taken before transplantation as vaccination. If the patient is already transplanted, three measures may be undertaken: Vaccination, use of monoclonal antibodies, use of therapeutic antiviral small molecules. Concerning vaccination is still debated which one is the best and how many doses should be given. The surge of new virus variant is the major problem and invites to find new active vaccines. In addition, not all the transplanted patients develop antibodies. The other measure is the use of monoclonal antibodies. They may be used as prophylaxis or in the early stage of the disease. Finally, the antiviral small molecules may be used again as prophylaxis or treatment. Their major drawback are the interference with the immunosuppressive drugs and the fact that some of them cannot be administered to patients with low eGFR.

We present the AI-discovered aetiology of COVID-19, based on a precise disease model of COVID-19 built under five weeks that best matches the epidemiological characteristics, transmission dynamics, clinical features, and biological properties of COVID-19 and consistently explains the rapidly expanding COVID-19 literature. We present that SARS-CoV-2 implements a unique unbiased survival strategy of balancing viral replication with viral spread by increasing its dependence on (i) ACE2-expressing cells for viral entry and spread, (ii) PI3K signaling in ACE2-expressing cells for viral replication and egress, and (iii) viral-non-structural-and-accessory-protein-dependent immunomodulation to balance viral spread and viral replication. We further propose the combination of irinotecan (an in-market topoisomerase I inhibitor) and etoposide (an in-market topoisomerase IIinhibitor) could potentially be an exceptionally effective treatment to protect critically ill patients from death caused by COVID-19-specific cytokine storms triggered by sepsis, ARDS, and other fatal comorbidities.

Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD) patients using neuropsychological testing. The study involved 71 post-COVID patients, with matched control groups: recovered COVID-19 individuals without complications (n=18) and individuals without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, a comparison group (noPCD, n=46) included participants with neurological COVID-19 complications, excluding clinical depression. The PCD patients showed significantly less scores in the MoCA test, decreased immediate memory recall in the Word Memory Test, decreased processing speed and higher accuracy in the Trail Making Test, and near to significant worse executive control and processing speed in the Stroop task compared to controls and the noPCD patients. The number of post-COVID symptoms negatively correlated with immediate word memory recall and processing speed among all post-COVID patients. In PCD patients, negative correlations between number of post-COVID symptoms and delayed recall, between time after recovery and immediate recall, and positive correlation between the number of acute symptoms and processing speed in the incongruent condition of the Stroop task were found. No differences between groups in Sniffin’s stick olfactory test was found. Overall, our study revealed cognitive impairment in PCD patients similar to those in major depressive disorder.

Human infection caused by the SARS-CoV-2 virus, called COVID-19, is a new pandemic with devastating effects worldwide. Science seeks the rational and systematic explanation of phenomena. In pandemics, decisions on prevention and treatment of people should be consistently taken, supported by scientific knowledge and ethical principles to produce more good than harm. At first, prospective observational studies to systematically collect patient data, correlating protective or therapeutic interventions with outcomes to assess effectiveness and safety, should be prioritized as the most appropriate type of study. The proposed protocol in this article aims to provide doctors with information on the reduction of harm in early COVID-19 patients by applying individualized interventionist or expectant therapeutic strategies, respecting the autonomy and preferences of physicians and patients in clinical decision-making. The evaluation of the clinical status, besides laboratory confirmation of COVID-19, comprises an individualized symptom score for each patient, a global self-perception scale of the severity of the disease, a clinical progression scale developed by the WHO for clinical studies in COVID-19 and, at the first consultation, doctors´ overall impression on the clinical prognosis. The analysis of anonymized data should preferably use descriptive and inferential statistical resources. The case report form is available for free use in the protocol, along with examples of patient informed consent forms for the prescription of off-label medications and authorization to use the data. Their results may be useful to indicate interventions that are candidates for efficacy trials, in randomized controlled trials, with a higher chance of success. It respects the autonomy and preferences of doctors and patients to decide the best options for treatment in uncertain situations. It also allows the gathering of useful information for future more rigorous clinical trials, trying to link science, ethics, and personal clinical experience.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, re-considering the immunohistochemical negative score of 0, 1+ or score of 2+/in situ hybridization (ISH) negative phenotype. In the present review we have outlined the needed criteria to exactly distinguish HER2 low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody-drug conjugates (ADCs) in treating these group sof tumors. In particular, Trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC has been recently approved by the U.S. Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally we hope that new guidelines may help to codify HER2 low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment.

The study's objective was to assess the impact of Mediterranean diet/lifestyle interventions for weight loss on Positive airway pressure (PAP) adherence, Body mass index (ΒΜΙ), sleepiness, and blood pressure measurements (BP) in patients with obstructive sleep apnea (OSA). We designed a randomized, controlled trial, including overweight and obese patients with moderate-to-severe OSA, randomized to standard care (SCG, n=37) and Mediterranean diet group (MDG, n=37). SCG received healthy lifestyle advice, while MDG underwent a 6-month behavioral intervention aiming to enhance weight loss and adherence to Mediterranean diet. PAP adherence, BMI, Epworth Sleepiness Scale (ESS) and BP measurements were evaluated pre- and post-intervention. Post-intervention PAP use was higher in MDG compared to SCG (6.1 vs 5.4, p=0.02). Diet/lifestyle intervention was one of the most significant predictive factors for PAP adherence (OR = 5.458, 95% CI = 1.144-26.036, p=0.03). The SCG demonstrated a rise in BMI, while the MDG displayed a decline (0.41 vs -0.75, p=0.02). The MDG also demonstrated a substantial reduction in adjusted SBP (-5.5 vs 2.8, p=0.014) and DBP (-4.0 vs 2.5, p=0.01). Ultimately, incorporating a dietary/lifestyle intervention with standard care yields superior PAP adherence, BMI, and BP measurements in contrast to standard care alone, underscoring the potential benefits of allocating increased time and support within the MDG group. Trial registry: ClinicalTrials.gov; No.: NCT05881824; URL: www.clinicaltrials.gov.

This study investigates the effects of xylitol, a natural sugar alcohol, on tumor progression in syngeneic mouse cancer models. Xylitol has been known for its dental health benefits, but emerging evidence suggests broader biological roles, including potential anti-cancer properties. We explored xylitol's impact on two mouse cancer models: 4T1 mammary carcinoma and B16F10 melanoma. Xylitol's efficacy in inhibiting cancer cell lines and modulating tumor progression was assessed using immunocompetent female mice. The experiments involved intratumoral and peri-tumoral administration of a 20% xylitol solution in two mouse strains: BALB/c (4T1 mammary carcinoma) and C57BL/6 (B16F10 melanoma). Tumor volume, histopathology, and metabolomic analyses were conducted to gauge xylitol's influence. The study revealed that xylitol administration initially reduced tumor growth in the B16F10 melanoma model, accompanied by alterations in tumor metabolism. However, similar effects were not observed in the 4T1 mammary carcinoma model, and melanoma tumor growth re-commenced after stroma deterioration permitted xylitol solution leakage. These findings suggest that xylitol may have potential as an adjunct therapy in cancer treatment, specifically in melanoma. The differential response between the two cancer models underscores the complexity of cancer biology and the need for further investigation into xylitol's mechanisms of action and its role in cancer therapy.

Human displacement is on the rise globally, and the increase in the burden of tuberculosis (TB) is also attributed to migrations worldwide. A significant number of such displacement occur in regions with considerably higher areas of TB burden. Displacements may delay in TB diagnosis and treatment, which possibly will lead to TB transmission among healthy individuals. In this study, we assessed the association of existing determinants after a protracted internal displacement of people with the delay in TB diagnosis and treatment outcomes. A cross-sectional study was conducted on internally displaced TB patients registered at selected health facilities in three urban districts of Pakistan from March 2019 to February 2020. The univariate and multivariate logistic regression model was used to assess the delay in diagnosis and treatment outcomes. IDPs with delay in initiation of treatment beyond 30 days were at high possibility of unsuccessful TB treatment outcomes (adjusted odds ratio AOR,2.60; 95% CI 1.06-6.40). Analysis of factors that affect health seeker behavior and timely treatment showed a significant association (p<0.05) in-between age group 55-65 years (AOR, 2.66; 95% CI 1.00-7.07), female patients (AOR, 2.42; 95% CI 1.21-4.81), visited non-formal health provider (AOR, 8.81; 95% CI 3.99-19.46), self-medication (AOR, 2.72; 95 % CI 1.37-5.37), poor knowledge of TB (AOR, 11.39; 95% CI 3.31-39.1), and perceived stigma (AOR, 8.81; 95% CI 3.99-19.4). Prolong delay in treatment was associated with unfavorable treatment outcomes among IDPs, more specifically. As migrants and IDPs are more likely to experience an interruption in care due to overall exclusion from social and health care services. Therefore, it is imperative to understand the barriers in providing public health care services, particularly in preventing and treating TB.

In the present study, we investigate the post-editese phenomenon, i.e., the unique features that set machine translated post-edited texts apart from human-translated texts. We use two literary texts, namely, the English children's novel by Lewis Carroll Alice’s Adventures in Wonderland (AW) and Paula Hawkins' popular book The Girl on the Train (TGOTT) translated from English into Brazilian-Portuguese to investigate whether the post-editese features can be found on the surface of the post-edited (PE) texts. In addition, we examine how the features found in the PE texts differ from the features encountered in the human-translated (HT) and machine translation (MT) versions of the same source text. Results revealed evidence for post-editese for TGOTT only with PE versions being more similar to the MT output than to the HT texts.

Conventional models do not fully explain composition of the solar system – for example, the presence of p-nuclei and post-post-Fe-nuclei remains not yet understood (and is one of the great unresolved puzzles of nuclear astrophysics in general); other puzzles exist. We offer a hypothesis which can explain the appearance of non-native elements in the solar system, and a feasible scenario for its implementation. The hypothesis suggests that a nuclear-fission "event" occurred in the inner part of the solar system at the time currently defined as the birth of the system. Conventional models have never considered fission as a contributing nuclei-production mechanism. Upon examination of the existing models and factual data (presented in volumes of publications but never combined into an aggregate), we identified one plausible scenario by which a fission event (not demolishing the entire solar system) could occur: an encounter with a compact super-dense stellar "fragment" (with specific properties) and its "explosion" in fission-cascades. Such scenario also helps resolve other long-standing puzzles of the solar system. For example, it provides that the fission-produced nuclei subsequently transformed into the material that (eventually) accreted into the "rocky" objects in the system (terrestrial planets, asteroids, etc.) and enriched the pre-existed hydrogen-helium objects (the Sun and the gaseous giants) – this offers an explanation for the planets’ inner position and compositional differences within the predominantly hydrogen-helium rest of the solar system. Other implications also follow.

Background: The annual mortality of patients with untreated chronic thromboembolism pulmonary hypertension (CTEPH) is approximately 50% unless a timely diagnosis is followed by adequate treatment. In pulmonary embolism (PE) survivors with functional limitation the diagnostic work-up starts with echocardiography. It is followed by lung scintigraphy and right heart catheterization. However, noninvasive test providing diagnostic clues to CTEPH, or ascertain this diagnosis as very unlikely, would be extremely useful since the majority of post PE functional limitations is caused by deconditioning. Methods: Patients after acute PE underwent a structured clinical evaluation with electrocardiogram, routine laboratory tests including NT-proBNP and echocardiography. The aim of study was to verify whether the parameters from echocardiographic or perhaps electrocardiographic examination and NT-proBNP concentration best determine the risk of CTEPH. Results: A total (n = 261, male n = 123) patients after PE were included into the study, in group of 155 patients (59.4%) with reported functional impairment 13 patients (8.4%) had CTEPH and 7 PE survivors had chronic thromboembolic pulmonary disease (CTEPD) (4,5%). Echo parameters differed significantly between CTEPH/CTEPD cases and other symptomatic PE survivors. Patients with CTEPH/CTEPD had also higher level of NT-proBNP (p = 0.022) but concentration of NT-proBNP above 125 pg/ml did not differentiate patients with CTEPH/CTEPD (p>0.05). Additionally, proportion of patients with right bundle brunch block registered in ECG was higher in group with CTEPH/CTED (23.5% vs. 5.8%, p = 0.034) but there were no differences between other ECG characteristics of right ventricle overload. Conclusion: Screening for CTEPH/CTEPD should be performed in patients with reduced exercise tolerance compared to pre PE period, It is not effective in asymptomatic PE survivors. Patients with CTEPH/CTED had predominantly abnormalities indicatingchronic thromboembolism in the echocardiographic assessment. NT-proBNP and electrocardiographic characteristics of right ventricle overload proved to be insufficient in predicting CTEPH/CTEPD development.

Long Covid or post-acute sequelae of SARS-CoV-2 infection (PASC) can manifest as long-term symptoms in multiple organ systems, including respiratory, cardiovascular, neurological, and metabolic systems. In patients with severe COVID-19, immune dysregulation is significant, and the relationship between metabolic regulation and immune response is of great interest in determining the pathophysiological mechanisms. We aimed to characterize the metabolomic footprint for recovering severe COVID-19 patients in three consecutive time points and compare metabolite levels to controls. Our findings add proof of dysregulated amino acid metabolism in the acute phase, and dyslipidemia, glycoprotein level alterations, and energy metabolism disturbances in severe COVID-19 patients 3-4 months post hospitalization.

The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the BRCA2 gene. The second case involves a child with alveolar rhabdomyosarcoma, Xanthogranuloma Juvenile, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the NF1 gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nefroblastoma in whom a pathogenic variant in the DICER1 gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play crucial roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are crucial for improving outcomes in these individuals.

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AHE), undergoing organ-preserving treatment, was conducted. Objective of the study: to determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n=28) and AEH (n=13), willing to preserve reproductive function, were studied; 18 specimens of endometrial cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n=28), 14 patients had complete response (EC CR group) and 14 had not (non-CR). It was found that all groups had statistically significant differences in CDO1 gene methylation levels with the control group (p&lt;0.001) except for the EC CR group (p=0.21). The p-value of difference between EC CR and EC non-CR groups was &lt;0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p&lt;0.001), except for AEH group (p=0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p&lt;0.001), and the control and EC comparison groups (p=0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was &lt;0.001. Simultaneous assessment of CDO1 and CDH13 genes methylation allowed to accurately distinguish between EC CR and EC non-CR groups (AUC=0.96). Conclusion: Assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), planned for medical treatment, can predict the treatment outcome.

There is still little research on psychological wellbeing and reported problems in preadolescents and adolescents under therapy for leukemia, also comparing them with their healthy peers. The present study aims to analyze the life perceptions, psychological well-being and problems’ intensity in these patients during the first year of therapy and to compare these reports with those of matched healthy peers adopting a battery of self-report questionnaires. Mann-Whitney tests identified the younger patients more at risk than older ones in their problems’ intensity and psychological symptoms. Older patients resulted instead more vulnerable regarding past life perceptions. Wilcoxon test with 2 dependent samples analyses showed that: healthy peers have a better perception of current life and lower percentage of somatization symptoms than patients after 6-months post-diagnosis. On the other hand, healthy peers reported more problems dealing with impulsivity, mood, disorganization, concentration and memory than patients both at 6-months and 1-year from diagnosis. Healthy peers reported also more anxiety and depression symptoms than patients and worse past and future life perceptions than patients at 1-year from diagnosis. The clinical aim is to perform a psychological screening of preadolescents and adolescents in order to prepare ad hoc psychological interventions.

Endovascular techniques are currently considered as a first line treatment options for lower limb chronic limb-threatening ischemia (CLTI), defined by the presence of ischemic rest pain and severe tissue loss such as ulcers or gangrene. Although the technical success rate of endovascular revascularization is high, in specific patients with advanced infrapopliteal disease and absence of run-off tibial vessels ("desert foot"), the chance of successful revascularization is minimal. In order to avoid primary amputation several treatment option are currently being investigated, including different strategies such as gene therapy or venous arterialization techniques. This review focuses on the percutaneous deep venous arterialization technique, recently introduced in everyday clinical practice, as a promising, minimally invasive treatment option for limb salvage in CLTI patients presenting with “desert foot”.

BACKGROUNDː The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for a better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO2) are the most commonly used perfusion markers, but they are not completely reliable to identify a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO2/C(a-v)O2] can be a good index to predict the development of LCOS in the aforemen-tioned patients, so as to treat it promptly. METHODSː This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Inte-grated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analysis were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to intensive care unit, before and after extubation and at any time of instability or modification of the patient’s clinical and therapeutic conditions. RESULTSː The data analysis shows that 46.9% of the children developed a LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO2/C(a-v)O2 ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. CONCLUSIONSː This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO2 and oxygen extraction ratio-ERO2) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with he-modynamic instability before surgery.

(1) Background: Metastasis is a complex process in which the primary cancer cells spread to a distant organ or organs, creating a secondary tumour location, which in many patients leads to treatment failure and death. The aim of the present study was to assess the association of endothelial markers (i.e., sP-selectin, sE-selectin and von Willebrand factor) with the leptin-to-adiponectin ratio (LAR) and to perform an analysis of the predictive value on the survival of patients with luminal A and B invasive breast cancer (IBrC). (2) Methods: The trial included 70 previously untreated women with a median age of 54.5 years and a median tumour size of 1.5 cm. The concentrations of pre- and post-treatment endothelial markers, leptin, and adiponectin were evaluated with specific ELISA kits. The median duration of follow-up was 68.5 months (interquartile range (IQR) = 59–72 months) with a recurrence rate of 15.71%. (3) Results: Regardless of the treatment pattern, endothelial marker concentrations and the LAR increased after treatment. The follow-up showed a significantly higher relapse rate in patients with IBrC who had higher pre-treatment sP-selectin and post-treatment LAR levels. A post-treatment LAR of 0.83 ng/mL with a sensitivity of 88.9% and specificity of 57.9% was established as the optimal cut-off value for distinguishing patients with or without disease recurrence. Additionally, a higher risk of breast cancer relapse was associated with a lower post-treatment sP-selectin concentration. (4) Conclusions: Our results showed mainly that pre-treatment sP-selectin levels and post-treatment LAR may have a value as prognostic indicators and may contribute to predicting the future outcome in patients with early-stage IBrC.

Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particular vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a hard outcome to be targeted, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD however, the optimal intensity of such therapy is still topic of debate, particularly in the post-acute and long-term setting. Recent well powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and patients selection is a key issue. The aim of this review is therefore to discuss and summarize the most updated available evidences for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both type of atherosclerotic disease and comparing a higher versus a lower intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improving precision medicine.

With the outbreak of coronavirus disease 2019 (COVID-19), there is a need for efficient management of patients with mild or no symptoms, which account for the majority. The aim of this study is to introduce the structure and operation protocol of a living and treatment support centre (LTSC) operated by Seoul National University Hospital in South Korea. The existing accommodation facility was converted into a 'patient centre' where patients was isolated. A few Medical staff here performed medical tests and responded to emergencies. Another part of the LTSC was 'remote monitoring centre'. In this center, patients’ self-measured vital signs and symptoms were monitored twice a day, and the medical staff staying here provided video-consultation via a smartphone. During the 3 weeks from March 5 to March 26, 2020, 113 patients were admitted and treated. LTSC could be an efficient alternative to hospital admission in pandemic situation like COVID-19.

The aim was to identify if surface electromyography (sEMG) parameters are indicative of post-activation potentiation (PAP)/post-activation performance enhancement (PAPE), in terms of twitch potentiation and voluntary performance. Three databases were used in March 2024, with the following inclusion criteria: (a) original research, assessed in healthy human adults, (b) sEMG parameters were measured. The exclusion criteria were: (a) studies with no PAP/PAPE-protocol, (b) non-randomized control trials. The following data were extracted: study characteristics/demographics, PAP/PAPE-protocols, sEMG parameters, twitch/performance outcomes, and study findings. A modified physiotherapy evidence database (PEDro) scale was used for quality assessment. Fifteen randomized controlled trials (RCTs), with a total of 199 subjects were included. The M-wave amplitude (combined with a twitch torque outcome) was shown to generally be indicative of PAP. The sEMG amplitude (in some muscles) were found to be indicative of PAPE during ballistic movements, while a small decrease in the MdF (in certain muscles) were shown to reflect PAPE. Changes in the Hmax/Mmax ratio were found to contribute (temporally) to PAP, while the H-reflex amplitude was shown to be neither indicative of PAP nor PAPE. This review provides preliminarily findings suggesting that certain sEMG parameters could be indicative of PAP/PAPE. However, future research is warranted.

Post-ovulatory aging (POA) is an inevitable factor during some assisted reproduction technology procedures, and results in poor fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and in vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte(A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte(A_vitro) were intersected to explore the co-effects of POA. It was found that "organelles", especially "mitochondria", were significantly enriched GO terms. The expression of genes related to the “electron transport chain” and “cell redox homeostasis” pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. WGCNA analysis to explore gene expression modules specific to A_vivo. Trait-modules association analysis showed that the red modules were most associated with in vivo aging. There are a total of 959 genes in the red module, which are mainly enriched in “RNA binding”, “mRNA metabolic process”, etc. GO terms, and “spliceosome” and “nucleotide excision repair” pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. And these genes were all expressed higher in A_vivo. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study helps us understand the detailed mechanism of POA and provides strategies for researching oocyte aging.

Open pit mining is a common activity in the Yucatan peninsula for the extraction of limestone. This mining is known under the generic name of quarries, and regionally as sascaberas (sascab=white soil in Mayan language). These areas are characterized by the total removal of the natural vegetation cover and soil in order to have access to the calcareous material. The present study shows the composition and structure of the vegetation in five quarries after approximately ten years of abandonment, and the conserved vegetation near to each one of the quarries in southeastern Quintana Roo. Using a canonical correspondence analysis (CCA), the distribution of the species was determined in relation to the edaphic variables: soil depth, percentage of organic matter (OM), cationic exchange capacity (CEC), pH and texture. 26 families, 46 genera and 50 species were recorded in the quarries and 25 families, 45 genera and 47 species were recorded in the conserved areas. The dominant species in the quarries belong to the families Poaceae, Fabaceae, Rubiaceae and Anacardiaceae. The quarries with higher values of OM (1.63%), CEC (24.05 Cmol/kg), depth (11 cm) and sand percentage (31.33%) include the following species like Lysiloma latisiliquum, Metopium brownei and Bursera simaruba which are commonly found in secondary forests. On the other hand, quarries with lower values of OM (0.39%), CEC (16.58 Cmol/kg) and depth (5.02), and higher percentage of silt (42.44%) were dominated by herbaceous species belonging to the Poaceae family and by Borreria verticillata, which are typical in disturbed areas of southeastern Mexico. In all cases, the pH was slightly alkaline due to the content of calcium carbonate (CaCO3), characteristic of the soils of the region. The edaphic variables are significantly correlated with the development and distribution of vegetation, and with the structure of the communities.

Abstract: Cervical cancer, which is the fourth most common malignancy and the fourth greatest cause of cancer-related deaths in women globally, continues to be a serious issue for global health. Despite advancements in treatment techniques, particularly the implementation of concomitant chemoradiation therapy, predicting the prognosis of locally advanced cervical cancer, especially for stage III, remains challenging. In recent years, neoadjuvant chemotherapy (NACT) has gained interest as a viable treatment strategy. The objective of this review paper is to scrutinize the clinical data and outcomes associated with NACT in the management of stage 3 cervical cancer. Electronic databases were used to perform a comprehensive literature search, and research up to 2023 were included. The findings suggest that NACT followed by irradiation may have advantages such as lowering tumor size, pelvic architectural distortion, and subclinical distant metastases, therefore enhancing radiation delivery. However, several studies have produced conflicting findings, raising questions regarding toxicity and finding no appreciable survival benefit over radiation alone. NACT followed by radical surgery has demonstrated more promising outcomes compared to surgery alone in terms of increasing rates of overall survival (OS) and progression-free survival (PFS). Additionally, NACT has been associated with decreased tumor growth, parametrial infiltration, nodal, metastases, and vascular space invasion. These findings suggest adjuvant radiation treatment. Although the overall survival rate has been markedly increased by concomitant chemoradiation treatment, metastatic disease continues to be a major factor in the death rate from cervical cancer. Therefore, improving outcomes in locally advanced cervical cancer requires investigating novel systemic treatments, such as NACT. The study also emphasizes how crucial it is to research factors like cisplatin dose-intensity and cycle lengths in order to maximize NACT's efficacy. To prevent the need for subsequent treatments and cumulative toxicity, more study should concentrate on patient selection for NACT followed by surgery.

Low back pain (LBP) is a pandemic and costly musculoskeletal condition in the United States. Patients with LBP may endure surgery, injections, and expensive visits to emergency departments. Some suggest that using physical therapy or chiropractic in the earlier stage of LBP reduces the utilization of expensive health services and lowers the treatment costs. Nevertheless, there is no consistent evidence to declare which one of these methods is a cost-effective treatment within a short (less than a year) period of time. The purpose of this study was to investigate the cost-effectiveness of chiropractic versus physical therapy in the United States. A decision tree analytic model was used for estimating the economic outcomes. The findings showed that in the chiropractic group, the total average cost was $48.56 lower than the physical therapy group, and daily adjusted life years (DALY) was 0.0043 higher than the physical therapy group. Chiropractic care was shown to be a cost-effective alternative compared with physical therapy for adults with at least three weeks of low back pain over six months.

Non-Small Cell Lung Cancer (NSCLC) is the most common pulmonary malignancy, most frequently diagnosed at an advanced stage (III/IV). Patients in the Locally-Advanced Stage Subgroup (IIIA) are relatively few, yet compose of heterogenic phenotypes posing a diagnostic and treating challenge, leading to lack of clinical guidelines regarding the optimal standard of care. Several approaches exist, with a general agreement that a combined oncological and surgical modality approach is required. In this current retrospective descriptive study, operable Stage IIIA NSCLC patients who underwent surgery between 2013-2020 were evaluated on several aspects, including initial diagnosis, neoadjuvant regimens, outcomes of surgical intervention, overall survival at 2-years and 5-years following treatment. A total of 35 patients had neoadjuvant oncological treatment (mostly chemoradiation therapy) prior to surgery, out of which 28 patients were diagnosed with Stage IIIA NSCLC. In post-operative assessment of pathological staging, downstaging was reported in 20 patients, of which 7 (25%) cases were defined as complete pathological response. The 2-years overall survival rate was 65% and the 5-years overall survival rate was 60%. The main pattern of disease recurrence was distant metastasis.

Complete pathologic response (pCR) predicts the long-term outcome of neoadjuvant treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers able to guide adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether shifts in the serum concentration of thymidine kinase 1 (sTK1) during NAC could be utilized as a biomarker. In the PROMIX trial, women with localized HER2- BC received neoadjuvant epirubicin/docetaxel in six cycles. sTK1 was measured with an ELISA in 54 patients at cycles 1-4 and in a total of 131 patients before and 48h after cycle 1. The prognostic significance of the results was evaluated by log-rank tests of Kaplan–Meier estimates. Treatment resulted in a 2-fold increase of sTK1 before and 3-fold increase 48h after the cycles, except for the first cycle, where half of patients reacted with a decrease (post/pre sTK1- ratio <1.12) and the other half reacted with an increase (ratio >1.12). OS rates in ER+ patients with ratios of >1.12 and <1.12 were 97.7% and 78% (p=0.005), respectively, and DFS rates were 90.7% and 68% (p=0.006), respectively. Thus, response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy.

This study presents a novel technique utilizing high frequency vibration to shorten treatment time and preserve alveolar bone in challenging orthodontic cases treated with Invisalign® clear aligners. Four non-growing orthodontic patients (age range 14-47 years old) with Class II skeletal patterns (convex profiles with retrognathic mandibles) who sought correction of their crowded teeth and non-surgical correction of their convex profiles were included in this study. These patients were treated using Invisalign clear aligners together with high frequency vibration (HFV) devices (120 Hz) (VPro5™) that were used by all patients for five minutes per day during active orthodontic treatment. Vertical control and forward rotation of the mandible for each patient was achieved through pre-programming the Invisalign to produce posterior teeth intrusion. Successful forward rotation of the mandibles achieved in all patients led to improvement of their facial convex profiles (ANB improved 2.1 + 0.5 degrees; FMA improved 1.2 +1.1 degrees). Dental decompensation was achieved by lingual tipping of the lower incisors and palatal root torque of upper incisors. The use of HFV together with Invisalign facilitated achieving these results within a 12+6 month period. In addition, more bone labial to the lower incisors after their lingual movement was noted. In conclusion, the use of HFV concurrent with SmartTrack Invisalign aligners allowed complex tooth movement and forward projection without surgery in non-growing patients with skeletal Class II relationships. The clinical impact and implications of this case series is that the use of HFV facilitates complex orthodontic tooth movement including posterior teeth intrusion and incisor decompensation in addition to increased bone formation labial to lower incisors that may minimize future gum recession due to their labial inclination.

Neuromuscular symptoms in long COVID patients are common. Since adequate diagnostics are still missing, investigating muscle function might be beneficial. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially vulnerable for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients in recovery process. AF parameters of elbow/hip flexors were assessed in 17 patients at three timepoints (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three timepoints. Symptoms intensity decreased significantly from pre to end. In conclusion, maximal holding capacity seems to be impaired in long COVID patients and increases with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process.

Hydrogen has a leading role in accomplishing a net zero green-house gas emission future. Today’s challenge is producing green hydrogen to cover the fuel demand of transportation and industry, to gain independence from fossil fuels. This review’s goal is to demonstrate critically the existing methods of biomass treatment and assess their ability to scale up. Biomass is an excellent hydrogen carrier and biomass-derived processes are the main target for hydrogen production as it is an innovative pathway to green hydrogen production. Comparing the existing processes, thermochemical treatment is found to be far more evolved than biological or electrochemical treatment especially with regard to scaling prospects.

Malignant neoplasms arising from the gastrointestinal (GI) tract are among the most common cancer types with a high mortality rate. Despite advances in treatment in a small subgroup harboring targetable mutations, the outcome remains poor, accounting for one in three cancer-related deaths observed globally. As a promising therapeutic option in various tumor types, immunotherapy with immune checkpoint inhibitors has also been evaluated in GI cancer, albeit with limited efficacy except for a small subgroup expressing microsatellite instability. In the quest for more effective treatment options, energetic efforts have been placed to evaluate the role of several immunotherapy approaches comprising of cancer vaccines, adoptive cell therapies and immune checkpoint inhibitors. In this review, we report our experience with personalized dendritic cell cancer vaccine and cytokine-induced killer cell therapy in three patients with GI cancers and summarize current clinical data on combined immunotherapy strategies.

Standard Non-Melanoma Skin Cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in case of advanced tumors. Exosomes, integral to carcinogenesis, are found in NMSC, releasing mediators impacting tumor progression. Nevertheless, the precise intercellular signaling role of NMSC-derived exosomes remains unclear. This review aims to elucidate their potential role in NMSC diagnosis and treatment. A systematic review encompassed literature searches in electronic databases from inception to September 2023, based on certain inclusion and exclusion criteria, addressing NMSC-derived exosomes, their molecular cargo and their implications in the diagnosis, prognosis, and treatment of NMSC. Key components were identified. Extracellular vesicle (EV) proteins and RNA emerged as diagnostic biomarkers in EV-based liquid biopsy. Circular RNA CYP24A1, known for its molecular stability, holds promise as a diagnostic biomarker. Long noncoding RNAs (lincRNA-PICSAR) and Desmoglein 2 (DSg2) are linked to drug resistance, serving as prognostic biomarkers. EV mediators are actively investigated for their potential role as drug delivery agents. In conclusion, this systematic review showed that NMSC-derived EVs display promise as therapeutic targets and diagnostic biomarkers. Further research is imperative to fully comprehend exosome mechanisms and explore their potential in cancer diagnosis and treatment.

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

Direct and indirect effects after mine operations cease must ideally be subject to perpetual monitoring routines in order to detect possible risks or avoid adverse effects on the surrounding ecosystems at an early stage. In this contribution, mining subsidence lakes created inside the nature reserve Kirchheller Heide and Hilsfeld Forest are subjected to analysis for a long-term monitoring scheme. For this purpose, we employ high-resolution unmanned aerial system (UAS)-based multispectral and thermal mapping tools to provide a fast, non-invasive and multitemporal environmental monitoring method. Specifically, we propose to monitor vegetation evolution through multispectral analysis, biotypes identification using machine learning algorithms, and water surface extent detection, together with their thermal behavior. The aim of this contribution is to present the proposed workflow and first results to establish a baseline for future analyses and subsequent surveys for longterm multi-temporal monitoring

Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the OPN and CD44 genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also inves-tigated. Multivariate analysis showed that OPN rs11730582 CC carriers had a significantly in-creased risk of death (p = 0.029), while the CD44 rs187116 A allele correlated with reduced risk of locoregional recurrence (p = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (p = 0.016). Fur-thermore, the OPN rs1126772 G variant alone (p = 0.018) and in combination with rs11730582 CC (p = 7x10-5) was associated with poor OS in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG and rs1126772 G, as well as their respective combinations, were in-dependent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that OPN and CD44 germline variants may predict treatment effects in NSCLC.

A key step in providing management/treatment options to men with suspected prostate cancer (PCa) is categorizing the risk for the presence of benign, low risk, intermediate risk, or high-risk disease. Our novel modality brings new evidence, based on the long-known hallmark characteristic of PCa – decreased Zinc (Zn), which is the most direct metabolic sign of malignancy and its aggressiveness. To date, this approach has not been adopted for clinical use for a number of reasons that are described in this article and which have been addressed by our approach: Zn has to be measured on fresh samples, prior to fixating in formalin, therefore samples have to be scanned during the biopsy session; as Zn depletion occurs in the glands, where the tumors develop, estimation of the glands’ levels in the scanned tissue along with their compactness, are essential for accurate diagnosis. Combined with the Zn depletion, this facilitates a reliable assessment of the disease aggressiveness. Data gathered in the clinical study described here indicate that in addition to improving the biopsy quality by real-time interactive guidance, a malignancy score can now be established for the entire prostate, allowing higher granularity personalized risk stratification and more decisive treatment decisions for all PCa patients.

STUDY QUESTION: Which are the main research interests among patients of assisted reproductive technologies (ART)? SUMMARY ANSWER: Patients identified as research priorities that deserve further investigation: success rates and risks of ART, side-effects of treatments, resources to cope with infertility, effectiveness of alternative therapies, lifestyle habits to protect fertility, oocyte quality and ovarian reserve, and causes of genetic or hereditary infertility. WHAT IS KNOWN ALREADY: The involvement of patients and caregivers in setting research agendas in medicine has gathered significant momentum in the last decade. Patients’ involvement in setting research priorities offers several benefits: improved patient knowledge and awareness of their condition; greater understanding of the medical professionals of the impact of the condition on patients’ quality of life; reduced costs associated with redundant research activities. This is may be also applicable to research in infertility and ART, where patients’ interests have never been explored before. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study that consists of an anonymous online survey, which was sent up to three times to 2112 patients from 11 fertility centers in 5 countries between January-December 2018. The study design was based on the James Lind Alliance priority setting partnership model, which comprises the identification of patients groups, the exploration of the research agenda, the analysis of collected data and identification of priorities. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 2112 patients were contacted, and 945 surveys were answered (RR: 44.7%). Patients were asked to identify research questions relevant to them in the areas of infertility causes and prevention, fertility treatments (medication and ART), and the emotional aspects of infertility. Answers were categorized in topics and ranked by frequency. A long list of the top-30 research topics was extracted from the aggregate results, from which, a short list of the top-10 research topics was created. At the end, 10 research questions related to each of the 10 research topics were constructed, based on the answers given by patients. MAIN RESULTS AND THE ROLE OF CHANCE: Female (845, 89.4%) and male (100, 10.6%) patients were included. The mean age of patients was 37.8 (SD 1.74). Most of the patients did not have children at the time of the survey (523, 59%), while 51 (5.7%) were pregnant. Sixty (6.3%) patients did not start treatment, 579 (61.3%) were performing a treatment with their own gametes and 304 (32.2%) were treated through gamete donation. Patients were mainly interested in the effectiveness of ART -especially per clinical profile-, side effects of drugs, protection of fertility and prevention of infertility –especially through diet and exercise-, and psychological aspects of the infertility journey. The top-10 research questions (and weight) obtained were: 1) What are the side-effects of ART treatments? (41.6%); 2) What are the most effective methods to cope with infertility from the psychological point of view? (37.2%); 3) What effects could diet have on fertility? (25.9%); 4) What are ART success rates per clinical profile? (25.9%); 5) Are there habits and lifestyle factors that could prevent infertility? (20.0%); 6) What are the long-term risks associated to ART? (18.5%); 7) Are alternative therapies such as acupuncture, yoga, and meditation effective to treat/prevent infertility? (18.5%); 8) What is the impact of exercise on fertility? (15.4%); 9) How does oocytes quantity and quality affect fertility? (9.5%); 10) What are the genetic patterns or hereditary conditions causing/related to infertility? (9.5%). LIMITATIONS, REASONS FOR CAUTION: Although all respondents had attended a fertility center, not all of them were diagnosed as infertile (i.e. single women) and had started treatment at the time of response, while a few were pregnant; their priorities for research might have been influenced by their infertility journey. Also, all participants attended private fertility centers: areas of interest may be different in public settings. WIDER IMPLICATIONS FOR THE FINDINGS: Researchers and clinicians should keep in mind that, in addition to improvement of treatments’ success rates and side-effects, patients greatly value research on causes, prevention and emotional aspects of infertility. As their views might differ from those of medical professionals, patients’ voices should be incorporated in setting infertility research priorities.

We use a system biology approach to translate the interaction of Bacillus Calmette-Gurin (BCG) + interleukin 2 (IL-2) for the treatment of bladder cancer into a mathematical model. The model is presented as a system of differential equations with the following variables: number of tumor cells, bacterial cells, immune cells, and cytokines involved in the tumor-immune response. This work investigates the delay effect induced by the proliferation of tumor antigen-specific effector cells after the immune system destroys BCG-infected urothelium cells following BCG and IL-2 immunotherapy in the treatment of bladder cancer. For the proposed model, three equilibrium states are found analytically. The stability of all equilibria is analyzed using the method of Lyapunov functionals construction and the method of linear matrix inequalities (LMIs).

Breast cancer represents the most frequent cancer and the leading cause of cancer death among women. Thus, the prevention and early diagnosis of breast cancer appears to be of primary urgency as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor that plays a key role in the regulation of neuronal functions thought the binding to the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). Also, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin or by binding to TrkA receptors with low affinity. Both in vitro and in vivo studies showed that NGF is synthesized and released by breast cancer cells and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. Here, we comprehensively summarize and systematically review the current experimental evidence on this topic.

Prostate cancer (PCa) is a major cause of cancer-related mortality worldwide, with a rising incidence observed over the years. The androgen receptor (AR) signaling pathway plays a pivotal role in male development and maintaining masculine characteristics. Dysregulation of AR signaling in prostate cancer can lead to disease progression and resistance to standard therapies. Understanding the intricate regulation and function of AR in both healthy and diseased states is crucial for developing effective treatment strategies. This review comprehensively explores the role of androgen receptors in prostate cancer susceptibility, disease progression, and treatment response by analyzing recent literature. An extensive search of peer-reviewed publications in major databases, including PubMed, Scopus, and Web of Science, was conducted using specific keywords related to androgen receptor, prostate cancer, disease progression, and treatment resistance. Relevant conference abstracts and clinical trial reports were also included. The review presents an overview of the role of androgen receptors in prostate cancer initiation, progression, and treatment resistance. It highlights emerging biomarkers associated with AR signaling dysregulation and their potential utility for early detection and personalized treatment approaches. Additionally, recent advances in targeting the AR pathway for novel therapeutic strategies to improve patient outcomes and overcome treatment resistance in advanced prostate cancer are discussed. The findings contribute to a comprehensive understanding of the AR signaling pathway in prostate cancer and offer insights into its multifaceted role in disease development and treatment response. They may pave the way for innovative therapeutic interventions and precision medicine approaches based on specific AR signaling profiles, enhancing patient care and reducing the burden of this lethal disease.

Colorectal liver metastases (CRLM) patients combined with hepatic lymph node metastases was a negative prognostic factor associated with outcomes. Up to now, there was still lack of a reliable method to identify the status of hepatic lymph nodes. The aim of this study was to investigate the predictive ability of mono-exponential, bi-exponential, and stretched-exponential diffusion-weighted imaging (DWI) models to distinguish between benign and malignant hepatic lymph nodes in CRLM patients who underwent neoadjuvant chemotherapy prior to surgery. In total, 97 CRLM patients with pathologically proved hepatic lymph node status were included. Various quantitative parameters, including the apparent diffusion coefficient (ADC) from mono-exponential model, D, D*, and f derived from intravoxel incoherent motion (IVIM) model, as well as DDC and α from stretched-exponential model (SEM), were measured. Multivariate analysis revealed that the pre- treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes. A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients, with an area under the curve (AUC) of 0.873. Therefore, the nomogram can serve as a preoperative assessment tool for determining the status of hepatic lymph nodes and aiding in the decision-making process for surgical treatment in CRLM patients.

Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

Programmed-death-1 (PD-1) receptor plays a major physiological role in maintainance of im-mune tolerance, and, by interaction with its ligands (PD-L1 and PD-L2), prevents the develop-ment of multiple immune-mediated diseases. There is growing evidence of an important role of PD-1/PD-L1 pathway in pathogenesis of psoriasis. 84 subjects with psoriasis were included into the study, together with 29 healthy subjects as a control group. 28 of psoriatic patients were treated with biologice therapy (TNF-alpha, interleukin (IL)-12/23 or IL-17 inhibitors). Amounts of PD1 and PD-L1 positive T-cells in peripheral blood were evaluated using flow cytometry. Significantly lower levels of peripheral blood mononuclear cells (PBMCs) with the expression of PD-1 and PD-L1 were found in psoriatic patients when compared to healthy individuals, i.e. CD3/PD1, CD3/PDL1, CD4/PD1, CD4/PDL1, CD8/PDL1, CD19/PD1, CD19/PDL1 positive cells. Biologic treatment resulted in elevation of CD3/PDL1, CD8/PDL1 and decrease of CD8/PD1 posi-tive PBMCs. Our results confirm previous observations of disrupted PD-1/PD-L1 pathway in psoriasis, and that this disturbances may play an important role in development of the disease. Biologic drugs may reverse several abnormalities observed within this pathway, which may ex-plain their excellent efficacy in the treatment of psoriasis. Further research should be conducted to fully explain the results obtained.

Fragility scales are intended to help in therapeutic decisions. Here we asked if the fragility as-sessment in MM patients ≥75 years old qualified for treatment by the local physician correlates with the choice of treatment: a 2- or 3-drug regimen. Between 7/2018 to 12/2019 we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in com-pletely dependent. Patients with more than 3 comorbidities were 26.9% (53 patients). Thus, ac-cording to the Palumbo calculator, 43 patients were in the intermediate-fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received 3-drug regimens and 20.3% (40) received 2-drug regimens. In each ECOG group, more than 3/4 of patients received 3-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received 3-drug regimens. Out of 53 pa-tients with at least 4 comorbidities, 71.7% received 3-drug regimens, and the rest 2-drug regi-mens. Three-drugs regimens received 34 patients from the intermediate-fit group (79.0%), and 123 (79.9%) from the frail group. Early mortality occurred in 25 patients (12.7%). No one discon-tinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with tri-ple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations which questions the clinical utility of current fragility scales in everyday practice.

Water resources, especially safe, potable water, are limited for many Haitians. In areas where shallow groundwater is available, many household water needs such as laundry, bathing, and cooking are supplied by hand-dug wells. In order to better understand the water quality and prevalence of these household wells, 35 hand-dug wells were surveyed and sampled near the Hôpital Albert Schweitzer (HAS) in Deschapelles, Haiti. Water samples were collected and tested for fecal coliform and E. coli using the IDEXX Colilert-18 method. Of the samples collected, 89 percent were determined unsafe to use as a drinking water source based on the World Health Organization standard of 1.0 colony-forming unit (cfu) Escherichia Coli (E. coli) per 100 mL. 66 percent of the wells exceeded recreational/body contact standards for the state of Michigan (130 cfu/100 mL). Some of these wells were deemed suitable for conversion to a new well type called In-Situ Filtration (ISF) wells. ISF wells are installed with an internal sand filter pack, PVC casing, pump, and cap which seals the well from surface contamination and provides additional water treatment as water is pumped. Previous ISF installations have reduced E. coli to safe drinking water levels within 90 days.

Three patients with multi-year histories of relapsing and remitting Lyme disease and associated co-infections despite extended antibiotic therapy were each given double dose dapsone combination therapy (DDD CT) for a total of 7-8 weeks. At the completion of therapy, all three patients major Lyme symptoms remained in remission for a period of 25-30 months. In conclusion, Double dose dapsone therapy could represent a novel and effective anti-infective strategy in chronic Lyme disease/PTLDS, especially in those individuals who have failed regular dose dapsone combination therapy (DDS CT) or standard antibiotic protocols. A randomized, blinded, placebo-controlled trial is warranted to evaluate the efficacy of DDD CT in those individuals with chronic Lyme disease/PTLDS.

Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigation for new therapeutic approaches is necessary. Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription-quantitative polymerase chain reaction technologies. Tested at various concentrations, the half-maximal inhibitory concentrations (IC50) of IMBZC on HT29 and SW620 cell growth were determined to be 6.97 μg/mL and 4.89 μg/mL, respectively. IMBZC did not alter cell growth of normal cells HEK293. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyzes revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. In conclusion, the study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC.

Premortem clinical diagnoses and postmortem autopsy findings do not match throughout history. These clinicopathological discrepancies are expected to be raised during the coronavirus disease 2019 (COVID-19) pandemic due to increased pressure on healthcare. At the same time, autopsies and clinicopathological discrepancies accurately display the quality of the healthcare system. To assess that, we examined the relevant works of literature according to the PRISMA-based protocol. As discrepancy rate changes in the correlation to the length of stay in the hospital, we also checked whether studies with patients from the intensive care unit (ICU) differed in discrepancies significantly. We found overall risk differences pretty much alike in "pre-COVID" and "during the pandemic" groups of studies. Based on that, we concluded that healthcare quality did not drop significantly during the pandemic. Be it as it may, the pandemic exposed some shortcomings in mortem healthcare regarding consensus to the autopsy, organ retention, burial, and the postponed burial or the digitalization of post mortem healthcare. All of these issues should be addressed in the future.

The embryonic epicardium originates from the proepicardium, an extracardiac primordium constituted by a cluster of mesothelial cells. In early embryos, the embryonic epicardium is characterized by a squamous cell epithelium resting on the myocardium surface. Subsequently, it invades the subepicardial space and thereafter the embryonic myocardium by means of epithelial-mesenchymal transition. Within the myocardium, epicardial-derived cells present multilineage potential, later differentiating into smooth muscle cells and contributing both to coronary vasculature and cardiac fibroblasts in the mature heart. Over the last decades, we have progressively increased our understanding of those cellular and molecular mechanisms driving proepicardial/embryonic epicardium formation. This study provides a state-of-the-art review of the transcriptional and emerging post-transcriptional mechanisms involved in the formation and differentiation of the embryonic epicardium.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

People with severe mental illness (SMI) are often in poor physical health, resulting in higher mortality and reduced life expectancy compared to the general population. Although eating habits are one of the main predictors of physical health, few studies assess the nutritional status and eating behaviour of people with SMI. The aim of this study was to examine the nutritional status and risk of malnutrition in people with SMI and in need of intensive psychiatric treatment. The cross-sectional study included 65 inpatients and 67 outpatients with psychotic or depressive disorders from the Psychiatric Hospital of the University of Zurich. Patients’ assessments at admission included anthropometric measurements, such as weight and height, and interview data including severity of symptoms and functioning (SCL-K-9, PHQ-D, CGI, m-GAF), personal and medical data, nutrition risk screening tools (adapted NRS, MNA-SF) and laboratory values. The results showed that 32% of the inpatients (body mass index [BMI] = 25.3) and 34% of the outpatients (BMI = 27.9) were at risk of malnutrition, which was associated with higher levels of psychiatric symptoms and lower levels of functioning. These results indicate that a substantial proportion of psychiatric patients seem to be at risk of malnutrition, despite most being overweight, and hence they might benefit from nutritional support during their psychiatric treatment. Moreover, nutritional risk screening tools specifically developed for the mental healthcare setting are needed.

The Sars-Cov-2 pandemic led to several needed containing measures that conditioned the onset of depressive, anxiety and post-traumatic stress symptoms in population. These symptoms, espe-cially if not diagnosed and treated, can also occur in patients undergoing surgery with high im-pact on people’s lives, like hysterectomy. To evaluate the post-surgical distress and anx-ious-depressive symptoms following hysterectomy for benign disease focusing on the impact of COVID-19 pandemic. The prospective observational cohort study included patients undergoing hysterectomy for benign disease. Psychologic evaluation through social-demographic question-naires was obtained before surgery (T1), postoperatively (T2), and 3 months after surgery (T3). The HADS (Hospital Anxiety and Depression Scale) was used to evaluate anxious-depressive symptoms and the PCL-5 (Post-traumatic Stress Disorder Checklist for DSM-5) compared the on-set of post-surgical distress and anxiety and depressive symptoms. The pre-COVID-19 pan-demic period was compared to the post-COVID-19 pandemic phase. Patients treated after COVID-19 pandemic showed higher depressive symptoms rate compared to those treated before (p-value=0.02); conversely, pre-COVID-19 patients were more prone to develop a PTSD (p-value=0.04). A significative association between the occurrence PTSD and anxiety-depressive symptoms registered at T2 a (p-value=0.007) and T3 (p-value

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low grade inflammatory response; immune dysregulation and defective immune response; reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal dysregulation, mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; as well as cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers or their link to etiopathogenetic mechanisms, and the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on main LC symptomatology in the frame of the epidemiological and pathogenetic aspects of the syndrome, and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma &lt;10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

Validation and verification are the critical requirements in the knowledge acquisition method for the clinical decision support system (CDSS). After acquiring the medical knowledge from diverse sources, the rigorous validation and formal verification process are required before creating the final knowledge model. Previously, we have proposed a hybrid knowledge acquisition method for acquiring medical knowledge from clinical practice guidelines (CPGs) and patient data in the Smart CDSS for treatment of oral cavity cancer. The final knowledge model was created by combining knowledge models obtained from CPGs and patient data after passing through a rigorous validation process. However, detailed analysis shows that due to lack of formal verification process, it involves various inconsistencies in knowledge relevant to the formalism of knowledge, conformance to CPGs, quality of knowledge, and complexities of knowledge acquisition artifacts. Therefore, it is required to enhance a hybrid knowledge acquisition method that thwarts the inconsistencies using formal verification. This paper presents the verification process using the Z formal method and its outcome as an enhanced acquisition method – known as the refined knowledge acquisition (ReKA) method. The ReKA method adopted verification method and explored the mechanism of theorem proving using the Z notation. It enables to identify inconsistencies in the validation process used for hybrid knowledge acquisition. Additionally, it refines the hybrid knowledge acquisition method by discovering the missing steps in the current validation process at the acquisition stage. Consequently, ReKA adds a set of nine additional criteria to be used to have a final valid refined clinical knowledge model. The criteria ensure the validity of final knowledge model concerning formalism of knowledge, conformance to GPGs, quality of the knowledge, usage of stringent conditions and treatment plans, and inconsistencies possibly resulting from the complexities. Evaluation, using four medical knowledge acquisition scenarios, shows that newly added knowledge in CDSS due to the addition of criteria by ReKA method always produces a valid knowledge model. The final knowledge model was also evaluated with 1229 oral cavity patient cases, which outperformed with an accuracy of 72.57\% compared to a similar approach with an accuracy of 69.7\%. Furthermore, ReKA method identified a set of decision paths (about 47.8%) in the existing approach, which results in a final knowledge model with low quality, non-conformed from standard CPGs. In conclusion, ReKA is formally proved method which always yields valid knowledge model having high quality, supporting local practices, and influenced from standard guidelines.

Chikungunya virus is a re-emerging mosquito-borne alphavirus. Outbreaks are unpredictable and explosive in nature. Fever, arthralgia, and rash are common symptoms during the acute phase. Diagnostic tests are required to differentiate chikungunya virus from other co-circulating arboviruses, as symptoms can overlap, causing a dilemma for clinicians. Arthritis is observed during the sub-acute and chronic phases, which can flare up, resulting in increased morbidity that adversely affects activities of daily living. During the 2019 chikungunya epidemic in Thailand, cases surged in Bangkok in the last quarter of the year. Here, we demonstrate the chronic sequelae of post-chikungunya arthritis in one of our patients 1 year after the initial infection. An inflammatory process involving edema, erythema, and tenderness to palpation of her fingers' flexor surfaces was observed, with positive chikungunya IgG and negative IgM tests and antigen. The condition produced stiffness in the patient’s fingers and limited their range of motion, adversely affecting daily living activities. Resolution of symptoms was observed with a short course of an anti-inflammatory agent. More research is required to determine whether sanctuaries enable chikungunya virus to evade the host immune response and remain latent, flaring up months later and triggering an inflammatory response that causes post-chikungunya arthritis.

Venous leg ulcers still pose a significant medical problem worldwide. The complexity of the problem determines the need for further interdisciplinary activities that will improve the quality of life of treated patients. The study compared the quality of life of patients with venous leg ulcers who received local hyperbaric oxygen therapy or local ozone therapy procedures as a part of comprehensive treatment. The study included 129 patients (62 men and 57 women) with venous leg ulcers. Group I underwent local hyperbaric oxygen therapy (HBOT), group II - local ozone therapy (OZONE). In both groups, the patients' quality of life was assessed before the start of treatment cycle, as well as 10 weeks and 6 months after the completion of the treatment, by using the EQ-5D-5L questionnaire and the Polish shortened version of the SF-36 scale. After completing the respective therapeutic cycle, both groups showed a statistically significant (p<0.001) improvement the quality of life according to the EQ-5D-5L questionnaire and the SF-36 scale. Differences were noted between 1st examination (before treatment) and 2nd examination (10 weeks after treatment), as well as 3 examination (6 months after treatment). In the EQ-5D-5L assessment of anxiety and depression, self-care and activities of daily living 6 months after the end of treatment, better results were found in the group of patients treated with local hyperbaric oxygen therapy (p<0.001). In this group, 6 months after the end of the treatment, a statistically significantly higher result on the EQ-VAS scale was also obtained (73.09±19.8 points vs. 68.03±17.37 points, p=0.043). However, in the SF-36 assessment 6 months after the end of treatment better results - a statistically significantly lower value of the quality of life index - were recorded in the group of patients treated with local ozone therapy (103.13±15.76 points vs. 109.89±15.42 points, p<0.015). Hyperbaric oxygen therapy and local ozone therapy procedures have a beneficial effect on improving the quality of life of patients with venous leg ulcers.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

Breast Angiosarcoma is a rare malignancy, accounting less than 1% of all soft tissue. It comprises primitive and secondary subtypes, such as radiogenic breast angiosarcoma (RAS). Despite the multimodal treatment, angiosarcomas represent an incurable disease for many patients and represent a cause of substantial deterioration of their quality of life. Surgery represents the cornerstone in the management, but high recurrence rates are reported. Electrochemotherapy (ECT) is practicable locoregional treatment in patients with advanced angiosarcoma, in a multimodal therapeutic strategy. ECT palliative benefit includes optimal patient compliance, good local hemostasis control, and local responses. Considering that only 22 cases are described in literature, we reported a rare case of RAS treated with ECT, after a multidisciplinary approach including Next Generation Sequencing (NGS). A literature review about the feasibility of ECT in RAS management was also performed.

Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.

Our understanding of Alzheimer’s disease (AD) pathogenesis has developed with several hypotheses over the last 40 years, including the Amyloid and Tau hypotheses, respectively. More recently, the p53 protein, well-known as ‘the guardian of the genome,’ has gained attention for its role in the early evolution of AD. This is due to p53’s central role in the control of oxidative stress and potential involvement in both Amyloid and Tau pathways. p53 is commonly regulated by post-translational modifications (PTMs), which affect its conformation, increasing its capacity to adopt multiple structural and functional states, including those that can influence several processes in AD. The following review will explore the impact of p53 post-translational modifications (PTMs) on its function and consequential involvement in AD pathogenesis.

Abstract Objectives To assess the causes and risk factors of posttraumatic stress disorder (PTSD) in adult asylum seekers and refugees. To explore whether the causes and risk factors of PTSD, between male and female adult refugees/ asylum seekers is different. Study design Systematic review of current literature. Data Sources PubMed, Web of Science, Scopus and Google Scholar up until February 2019 Method A structured systematic search was conducted in the relevant databases. Papers were excluded, if they failed to meet the inclusion and exclusion criteria. Afterwards, a qualitative assessment was performed on the selected papers. Results 12 Studies were included for the final analysis. All papers were either case studies/report or cross sectional studies. The number of traumatic events experienced by refugees/asylum seekers, is the most frequently reported pre-migration causes for PTSD development. Whilst acculturative stress, is the most common post migration stressor. There were mixed reports, regarding the causes of PTSD between both genders of refugees/asylum seekers. Conclusion This reviews’ findings, have potential clinical application into helping clinicians, to risk stratify refugees/asylum seekers for PTSD development and thus aid in embarking on earlier intervention measures. However, more rigorous research similar to this one, is needed for it to be implemented into clinical practice.

Public key encryption methods are often used to create a digital signature, and where Bob has a public key and a private key. In order to prove his identity, he will encrypt something related to the message with his private key, and which can then be checked with his public key. The main current methods of public-key encryption include RSA and ECC (Elliptic Curve Cryptography), and which involve computationally difficult operations. But these operations have not been proven to be hard in an era of quantum computers. One well-known hard problem is the solving of quadratic equations with $m$ equations with $n$ variables. This is a known NP-hard problem, even in a world of quantum computers. These can be used as post-quantum signature schemes and which involve multivariate equations. In order to understand these methods, this paper outlines a simple example of implementing the oil and vinegar method, and where we have a number of unknown oil variables and a number of known vinegar variables, and where the vinegar variables help convert the hard problem into an easy one.

Biochirality is evident in the hierarchical relation of molecular and cellular physiology during organism development and aging. Chirality influences the higher levels of biological processes, such as perception, memory and cognition, through intermolecular interactions between DNA, proteins, and lipids. At the molecular level, an organism's aging is the accumulation of macro-molecules with the aberrant composition, chirality, and folding. Cellular aging is driven by the non-physiological phase transitions (PhTs) withing membrane-bound and membrane-less compartments. Genomic instability and protein aging, as the interconnected root-causes of cell and organism aging, share two essential feature – spontaneous nature and accumulation over a lifetime. Consequently, we will analyze the interaction between the enzymatic (Enz) and spontaneous (Sp) post-translational modifications (PTMs^Enz and PTMs ^Sp). Both forms of PTMs significantly contribute to the balance of L- and D-amino acids (L/D-AAs) in organisms, modulating the functions of nervous and immune systems. The most abundant form of PTM - enzymatic phosphorylation is bio-chemically associated with the spontaneous racemization (Rz^Sp). The crass talk of enzymatic phosphorylation and spontaneous racemization, as an essential determinant of protein aging and aggregation, associated with the aberrant autophagy, apoptosis, and cell signaling, is discussed in this review.

A brand-new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this Unitarian perspective based upon that the hydrogen ion (H+) dynamics of cancer, allows understanding and integrating the many dualisms, confusions, and paradoxes of the disease. The new H+-related wide range model can embrace under a unique frame of mind the many aspects of the disease and at the same time therapeutically interfere with most, if not with all, the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC here reviewed may be beneficial for all types and stages of the disease. In this vein, we have attempted a mega synthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide range approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of a pH-related drugs nowadays available for the treatment of breast cancer is advanced.

We previously reported nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes and tumors were harvested at 4-hour, 8-hour, 1-, 3-, 7-day. Additional studies were conducted over 3-month posttreatment intervals for the analysis of frequencies, death and functional markers of various immune cells in addition to suppressor function of regulatory T cells (Tregs). NPT was verified to elicit strong in situ vaccination (ISV) against breast cancer and promoted both acute and long-term T cell memory. NPT abolished immunosuppressive dominance systemically and in the TME by substantially reducing Tregs, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). NPT induced apoptosis in Tregs and TAMs. It also functionally diminished the Treg suppression capacity, likely explained by the downregulation of activation markers, particularly 4-1BB and TGFβ, and a phenotypic shift from predominantly activated (CD44+CD62L-) to naïve (CD44-CD62L+) Tregs. Importantly, NPT selectively induced apoptosis in activated Tregs and spared effector CD4+ and CD8+ T cells. These changes were followed by a concomitant rise in CD8+CD103+ tissue-resident memory T cells and TAM M1 polarization. These findings indicate that NPT effectively switches the TME and secondary lymphatic systems from an immunosuppressive to an immunostimulatory state allowing cytotoxic T-cell function and immune memory formation to eliminate cancer cells and account for the NPT in situ vaccination.

Citation: Lastname, F.; Lastname, F.; Last-name, F. Title. Phar-maceuticals 2022, 15, x. https://doi.org/10.3390/xxxxx Academic Editor: Firstname Lastname Received: date Accepted: date Published: date Publisher’s Note: MDPI stays neutral with regard to jurisdic-tional claims in pub-lished maps and insti-tutional affiliations. Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons 1Olga Gumkowska-Sroka, 2Kacper Kotyla, 3Ewa Mojs, 2Klaudia Palka, 1,2*Przemysław Kotyla 1. Department of Rheumatology and Clinical Immunology Voivodeship Hospital No5 in Sosnowiec Medical University of Silesia Katowice, Poland 2. Department of Internal Medicine Rheumatology and Clinical Immunology Medical University of Silesia Katowice , Poland 3. 3. Department of Clinical Psychology, Poznan University of Medical Sciences Poznan, Poland *Correspondence: Prof Przemysław Kotyla Department of Internal Medicine Rheumatology and Clinical Immunology Medical University of Silesia, Katowice, Poland- Summary Systemic sclerosis is a connective tissue disease of unknown origin and unpredictable course, with both cutaneous and internal organ manifestations. In spite of enormous progress in rheumatology and clinical immunology, the background of diseases is largely unknown and no specific therapy exists. The therapeutic approach to the disease is aimed to treat and preserve the function of internal organs, and this approach is commonly referred to as an organ-based treatment. However, in modern times data from the other branches of medicine may help to treat disease-related complications, making it possible to find a group of drugs to be utilized in the treatment of the disease. In this review, we present possible therapeutic options aiming to stop the progression of fibrotic processes, restore aberrant immune response, stop improper signalling from proinflammatory cytokines, and halt the production of disease-related autoantibodies.

(1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lym-phoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analysed patient records (1984–2016) from 27 clinical sites in Eurpe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS), and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. Median (range) times from start of first-line therapy to first R/R MF and from first to second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radio-therapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). Median (95% confidence interval [CI]) OS from the diagnosis of first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); es-timated median PFS (95% CI) from the time of first R/R MF was 1.3 (1.0–2.1) years. (4) Conclu-sion: High rates of R/R disease were observed after second- and third-line treatments in this re-al-world cohort, with longer median OS in patients receiving non-chemotherapy versus chemo-therapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF.

African swine fever (ASF) is a notifiable viral disease of domestic and wild suids. Despite intensive re-search efforts, the pathogenesis of the disease is still far from being understood. Analysis of biomarkers in different body fluids may supplement traditional pathogenesis studies. As reliable protocols are often es-tablished in laboratories with lower biosafety, reliable inactivation of samples is crucial. The objective of this study was to find a procedure that inactivates the virus while preserving the biomarkers for down-stream analyses. To this means, three different inactivation protocols were employed, namely Tergitol-type NP-40 (NP-40) and polyoxyethylene-p-t-octylphenol (Triton X-100), respectively, and one with 95 °C heating. It could be demonstrated that all samples treated with 0.5% (v/v) concentration of both deter-gents showed absence of virus infectivity. The same was true for heated samples. However, heated serum was not suitable for analyses. Next, the treatment impact on biomarker readouts was assessed. While all protocols had an impact on the detection of biomarkers, correlation was retained. Especially NP-40 could be the desired detergent for more accurate measurements while achieving efficient virus inactivation. Based on these studies, samples can be reliably inactivated for most biomarker analyses and thus broader interdisciplinary cooperation is possible.

PDMS samples may be used in various microfluidic applications by hydrophilizing their surfaces. This study examines the effects of air plasma jet (APJ) and dielectric barrier discharge (DBD) plasma on the surface hydrophilicity of polydimethylsiloxane. In order to increase the hydrophilicity of PDMS sample surfaces, two plasma sources including APJ and DBD were compared. Both DBD and APJ setups were measured for voltage and current, and their respective power was calculated and compared based on their characteristics. It is important to note that the electrical specifications of APJ and DBD were identical, and the source power rates for APJ and DBD plasma were 306W and 300W respectively. UV-vis spectroscopy was used to characterize the plasma, and an electrical characterization of the plasma's power supply was carried out. The effects of parameters such as the distance from the nozzle tip, the duration of the process, and the source voltage on the hydrophilicity of the surfaces during the treatment by APJ were also examined, and samples were then examined for a period of time to determine whether surface hydrophilicity was preserved. On the PDMS surface, a contact angle of about 5.1° was observed using short-term plasma treatments of 10 seconds. In the same conditions, the effect of DBD treatment was superior to that of APJ treatment.

Background and Aims: Of all primary liver tumors, primary hepatic angiosarcoma (PHA) is a rare and aggressive malignant vascular tumor. The standard therapeutic care for hepatic angiosarcoma remains unclear. This study compared the survival outcomes of aggressive treatment (resection and liver transplant) and nonaggressive treatment (chemotherapy, transarterial chemoembolization [TACE], and conservative treatments) for patients with PHA and analyzed the prognostic factors influencing survival. Materials and Methods: Data of patients diagnosed as having PHA at our facility were retrospectively reviewed. The primary outcome was survival time. The secondary outcome was calculated baseline characteristics. Results: We included a total of 19 patients, who were divided into 2 treatment groups: aggressive (8 patients had undergone resection or transplants) and nonaggressive (11 patients had undergone TACE, chemotherapy, or conservative treatment). The mean survival time was 233.1 ± 189.7 days in the aggressive treatment group and 146.5 ± 115.8 days in the nonaggressive treatment group. A Kaplan-Meier plot revealed no significant difference in survival time between the 2 treatment groups (P = .3256). Conclusions: The survival time of patients receiving aggressive treatment was longer than that of those receiving nonaggressive treatment. The long term survival time in some selective cases of aggressive treatment will be achieved. Thought a difference was not significant between the groups. Because the number of patients was limited, more cases are required to confirm these findings.

This article presents a narrative review of neonatal and paediatric complications in post-dated pregnancy and covers scientific views on the aetiology, pathology, risk factors, symptoms and complications of post-dated pregnancy. A pregnancy extending beyond 42 weeks of gestation is termed as a post term pregnancy. There are multiple complications that can occur in the perinatal period, some of the most common ones are stillbirth, asphyxia, meconium aspiration syndrome, fetal distress syndrome, etc which are found to be greater in post-dated pregnancy and hence ultimately leads to increased mortality and morbidity of the new born. Studies have shown that post-term pregnancy also causes increased risk of developing behavioural and emotional problems in children of paediatric age group. It is surprising not much importance has been given to the maternal and neonatal consequences of post- term pregnancies. It is not well understood why some women experience post-dated pregnancies. It is found that factors such as hormones and genetic build up, are responsible for causing post-term pregnancy in an obese female. The treatment and management of a post-term pregnancy still poses a challenge to clinicians in determining the right choice and right time for a particular intervention so that both mother and fetus can be prevented from having complications.

Introduction: Outcome measures using telerehabilitation (TR) in the context of post-stroke rehabilitation is an area of emerging research. The current review assesses the literature related to TR for patients requiring post-stroke rehabilitation. The purpose of this study additionally is to survey the outcome measures used in TR studies and to define which parts of the International Organization of Functioning are measured in trials. Methods: TR studies were searched in Cochrane Central Register of Controlled Trials, PubMed, Embase, Scopus, Google Scholar, and Web of Science from 2016 to June 2023. Two reviewers individually assessed the full text. Disagreements about inclusion or exclusion were determined by consensus or by checking with a third reviewer. Results: A total of 24 studies were included in the current review. The results were synthesized and reported considering the implications of the results within clinical practice, areas of investigation, and strategic implementation. Conclusions: The current scoping review recognized a wide range of outcome measures used in TR studies and helped elucidate gaps in the current use of outcome measures in the literature. The scoping review also informs researchers and end users (i.e. clinicians and policymakers) regarding the most suitable outcome measures for TR.

The purpose of this study was to analyze the influence of Chitosan 0.2% in various final cleaning methods on the bond strength of fiberglass post (FP) to intrarradicular dentin. Ninety bovine incisors were sectioned to obtain root remnants measuring 18 mm in length. The roots were divided: G1: EDTA 17%; G2: EDTA 17% + PUI; G3: EDTA 17% + EA; G4: EDTA 17% + XPF; G5: Chitosan 2%; G6: Chitosan 2% + PUI; G7: Chitosan 2% + EA; G8: Chitosan 2% +XPF. After carrying out the cleaning methods, the posts were installed, and the root cleaved to to generate two disks from each root third. Bond strength values (MPa) obtained from the micro push-out test data were assessed by Kruskal-Wallis and Dwass-Steel-Critchlow-Fligner tests for multiple comparisons (α = 5%). Differences were observed in the cervical third between G1 and G8 (p=0.038), G4 and G8 (p=0.003), G6 and G8 (p=0.049), and Control and G8 (p=0.019). The final cleaning method influenced the adhesion strength of cemented FP to intrarradicular dentin. Chitosan 0.2% + XPF positively influenced adhesion strength, with the highest values in the cervical third.

Actively combating post-harvest food spoilage and waste can dramatically increase the efficiency of food utilization worldwide. In climacteric fruits, chemical treatments such as 1-MCP are an effective way of reducing post-harvest spoilage and waste by inhibiting the fruit’s ability to perceive ethylene. 1-MCP treatment is increasingly being used to explore the complex nature of ripening physiology at a fundamental level, however, differences in application and quantitation methods create difficulties in comparing conclusions across studies. Here we report an effective and reproducible method for 1-MCP application and quantitation for small-medium sized research applications. By use of surrogate alkene standards 1-butene and cis-2-butene, the highly volatile and elusive 1-MCP molecule can be identified and quantified by gas chromatography and subsequent standard curves may be developed. It is hoped that the methodology outlined here can help standardize consistent 1-MCP application for post-harvest research without excessive investment in specialized equipment.

Post-evaluation of ecological redevelopment is a good method for its achievements. The eco-engineering technologies and achievements of landscape water reconstructed from aquaculture ponds in Shanghai Chenshan Botanical Garden have been introduced in this study. The sediments and water quality were also sampled and tested for basic physicochemical parameters and heavy metal concentration. The ecological redevelopment of landscape water reconstructed from aquaculture ponds was evaluated using the Nemero comprehensive pollution index method. The results shown that nutrients including organic matter, organic nitrogen and their ratio of sediment were found to be in a state of moderate pollution, while their ecological risk of heavy metals was low. Although total nitrogen and total phosphorus of water quality was really higher than that of other indexes, the decline trends of ammonia nitrogen, total nitrogen and total phosphorus was obvious presented over time. In general, this is a good example that redevelopment of water ecosystems from aquaculture ponds using eco-engineering technologies.

Residential satisfaction with post-disaster housing is crucial for the success and sustainability of a resettlement project. However, little attention has been given to this aspect in the permanent houses developed after the 2015 Gorkha earthquake. To bridge this gap, the study examined factors affecting residential satisfaction among poor displaced households resettled in the Panipokhari Integrated Settlement of Nepal. Data were collected through a questionnaire survey, interviews, and field observation. Internal consistency and reliability were assessed using Cronbach's Alpha test, while satisfaction was measured by mean satisfaction scores. The relative importance index ranked the factors, and Spearman's rank correlation coefficient analyzed their relationship with overall residential satisfaction. The study identified several crucial fac-tors influencing residential satisfaction, including the design and layout of the house, space for modification, provision of a kitchen garden and cattle shed, thermal comfort, completeness of the house, provision of a hearth, and spaces for rituals and cultural events. These findings shed light on the resettlement decisions of affected populations and provide valuable insights for policymakers, implementers, and researchers aiming for successful and sustainable resettlement outcomes.

Background: Optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of the moderately hypofractionated post-prostatectomy radiotherapy in 16 daily fractions delivered with IMRT/VMAT. The treatment schedule selection was motivated by limited technology resources. Methods: One hundred consecutive M0 patients with post-prostatectomy radiotherapy were evaluated. Radiotherapy indication was adjuvant (ART) in 19%, early salvage (eSRT) in 46% and salvage (SRT) in 35%. The dose prescription for prostate bed PTV was 52.8 Gy in 16 fractions of 3.3 Gy. The Common Terminology Criteria v.4 for Adverse Events scale was used for toxicity grading. Results: The median follow-up was 61 months. Five-year biochemical recurrence-free survival (bRFS) was 78.6%, distant metastases-free survival was 95.7% and overall survival was 98.8%. Treatment indication was the only significant factor for 5-year bRFS in multivariate analysis which was 84.6% vs. 67.6% for ART or eSRT vs. SRT respectively (HR 0.15, 95% CI 0.05–0.47, p=0.001). Acute GI toxicity grade 2 was recorded in 24%, grade 3 in 2% and acute GU toxicity grade 2 in 10% and no grade 3. Cumulative rate of late GI toxicity grade ≥2 was observed in 9% and late GU toxicity grade ≥2 in 16%. Conclusion: Observed results confirmed efficacy and acceptable toxicity of post-prostatectomy hypofractionated radiotherapy in 16 daily fractions.

Current study was to estimation the post-harvest loss of avocado at the producer level using cross-sectional data obtained from 385 proportionately sampled respondents from Wolaita and Kembata Tembaro Zones, the SNNPR of Ethiopia. Descriptive and multiple regression analysis were used to the amount and determinant of post harvest loss of avocado fruits. Estimated total post harvest- loss of avocados was 24%; of which 5.7% unacceptable harvesting methods and 4.9% of improper storage practices. The respondent's sex, education, income, training, contact with extension agents, distance from the nearest road, and off-farm income were found to be negative determinants, whereas storage accessibility and avocado harvest techniques were found to be positive determinants of post-harvest loss of avocado fruits. Post-harvest management techniques for avocados need to be better understood and used by avocado growers if they are to minimize losses. Post-harvest losses contribute considerably to food insecurity and create a problem for the source of revenue for people and the economy of the country as well. Therefore, the use of a practical and effective post-harvest loss reduction technique could be a sustainable solution to increase food availability, eliminate hunger and improve farmers' livelihoods.

The universal chirality is the commonly accepted view of nature. Biological chirality is the distinct part of the more general phenomena. Following this view, all living organisms are characterized by the non-equilibrium state of their molecular constituents. From the thermodynamic perspective, the non-equilibrium state of biomolecular ensemble holds inevitable consequences being the substrate of spontaneous reactions directed to equilibrium (not associated with life) state. At the protein level, spontaneous biological reactions represent the natural part of proteins' post-translational modifications (PTMs). The essential contribution to the origin and maintenance of the non-equilibrium state belongs to prevalent bio-molecular chirality. Correspondently, spontaneous PTMs such as racemization and glycation, working against life-supporting prevalent chirality, are known as the significant determinants of protein misfolding, dysfunctions, and aggregation. Accumulation of aberrant protein during life-span allows consideration of time-dependent spontaneous racemization and glycation as protein aging. Spontaneous PTMs of proteins is occurring in the interaction with other forms of enzymatic and non-enzymatic PTMs. In this review, we are considering the contribution of spontaneous racemization and non-enzymatic glycosylation to protein aging.

Smoking during pregnancy remains one of the most significant risk factors for poor birth outcomes. The Loma Linda University Health Comprehensive Tobacco Treatment Program (CTTP) is the largest maternal tobacco cessation program in San Bernardino County – the largest county in the contiguous US. CTTP is an eight week, incentivized, behavioral intervention for tobacco cessation for pregnant smokers. As part of program evaluation, we used a retrospective cohort design to assess smoking abstinence and to identify predictors of relapse/smoking after enrollment. Among CTTP cohort enrollees (n=233) from 2012-2013 we found: 1) a 28.4% 8 week point prevalence abstinence (PPA), and at a median of 9 months of follow-up after the PPA, 81.6% continued to indicate tobacco cessation, and 2) a high rate of relapse or loss to follow-up (56%). Our modeling of relapse/smoking after enrollment indicated that this was higher in young mothers, non-Hispanic mothers (White, Black), first/third trimester mothers, and rural mothers. The evaluation identified efficacy of the behavioral model at 8 weeks, but that relapse/smoking was occurring in disparity populations. Formative research is needed to expand the programmatic outreach and enrollment of mothers wanting to quit smoking.

Postpartum depression (PPD), a condition that affects up to the 15% of mothers in high-income countries, reduces attention toward the needs of the child and it is among the first causes of infanticide. PPD is usually identified using self-report measures and therefore the diagnosis may not always be valid. Previous studies highlighted the presence of significant differences in the acoustical properties of the vocalizations of children of depressed and healthy mothers. In this study, cry episodes of infants of depressed and non-depressed mothers are analyzed to investigate the possibility that a machine learning model can identify PPD in mothers from the acoustical properties of infants' vocalizations. Acoustic features (F0, F1-4, Intensity) are first extracted from recordings of crying infants, then novel cloud-based artificial intelligence models are employed to identify maternal depression versus non depression from estimated features. Trained model shows that commonly adopted acoustical features can be successfully used to individuate Post-Partum Depressed mothers with very high accuracy (89.5%).

Background: Paracetamol may be use as antipyretic agent for the treatment of fever, as well as an analgesic in the treatment of mild to moderate pain on post vaccination in infants. The use of Paracetamol during fever may be or may not be recommended since it may alter natural human body immune response although it may reduce pain. Objectives: This study described the relevancy of Paracetamol use post infants vaccination based on data collection systematic review analyses. This study aims to describe the effectiveness of breastfeeding in reducing pain and Paracetamol in reducing fever and pain post infants vaccination. Data Sources and Study Selection: Electronic literature search by hand searching six (6) databases which include Ovid LWW Total Access Collection and Medline, CINAHL (Cumulative Index to Nursing and Alled Health Literature) Plus with Fulltext, Science Direct, Proquest Dissertations and Theses, Proquest Education Journal and Proquest Health and Medical Complete. Additionally, manual reference checks of all articles on Paracetamol and breastfeeding post infants vaccination published in English Language between 1978 and 2017. Two level of screening were used on 9614 citations which include screening of abstracts and titles followed by full text screening. Data Synthesis: Data synthesis were tabulated into study characteristics, quality and effects. Authors of trials were not contacted for further details or provision of original data if the published report contained insufficient information. The study findings, as reported by the authors, were included in this review. The data in this research cannot be pool due to not enough data regarding odd ratio or relative risk as well as confidence interval in each study. Results: Systematic review of breastfeeding included three (3) studies from 9614 of database searching. The reviews of all these three (3) studies found significant benefit from breastfed in pain score and duration of crying as well as behavioral changes. None study stated the unbeneficial of breastfeeding before, during and after immunization. Meanwhile, systematic review of Paracetamol effectiveness included four (4) studies from 1177 of database searching. The reviews of two (2) studies found significant benefit from prophylaxis Paracetamol in fever and only one (1) study found significant benefit from prophylaxis Paracetamol in fussiness. On the other hand, there was one (1) study found not signifiant benefit from prophylaxis Paracetamol in fever. Other than that, there were two (2) studies evaluate the safety of prophylactic Paracetamol which revealed different outcomes, in which study by Prymula et. al. in 2009 found that antibody responses to several antigens were reduced significantly, and the other study by Uhari et. al. in 1988 found that antibody titres to DTP bacteria of placebo and PCM not differ significantly. Thus, Paracetamol seems to be not relevant post infants vaccination and breastfeeding was found to be beneficial post infants vaccination. Conclusions: The relevancy of giving Paracetamol post all types of vaccination may be questionable since the safety issue of this intervention may be arised. Breastfeeding before, during and after immunization are recommended for pain reduction as it was proved effectively. Finally, in deciding Paracetamol to be of rational use following infants immunization, it may need for further research which include in depth quantitative and qualitative studies to identify specific problem and causes regarding this issue.

Experimental quantification of retention factors related to post-fire strength as well as post-fire ductility of intentionally selected stainless steel grades applied in construction is the objective of research presented here. These steel grades are characterized by a two-phase austenitic-ferritic microstructure of the duplex type. In this context two mutually corresponding chromium-nickel-molybdenum steel grades have been subjected to analysis, namely X2CrNiMoN22-5-3 steel belonging to the standard duplex group (DSS 22% Cr) and X2CrMnNiN21-5-1 steel belonging to the lean duplex group (LDSS). The similarities and differences in the mechanical properties exhibited by these steel grades after effective cooling, following more or less prolonged simulated fire action conforming to several development scenarios, have been identified and indicated. The resistance of given steel grade to permanent structural changes induced by the heating program proved to be the critical factor determining these properties and resulting in many cases in increased susceptibility to brittle fracture.

Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

Arsenic is naturally present in many geological formations around the world and is a major source of groundwater contamination. Bolivia is not exempt from this problem. Physical-chemical studies of water quality in deep and shallow wells have determined the presence of arsenic in some areas of the Bolivian Altiplano, valleys, and plains. In the Lake Poopó basin, water from shallow wells (up to 30 m) has arsenic concentrations that exceed the Bolivian drinking water standard and the WHO recommendation of 10 μg-As/l by up to 25 times. In peri-urban areas of Cochabamba, the arsenic content in groundwater is up to 113 μg-As/l. chronic exposure to arsenic is associated with neurological and dermatological problems and carcinogenic effects. To date, no measures have been taken to mitigate the arsenic problem for the rural population, who often rely on arsenic-contaminated water as their only source of drinking water. This contamination represents a serious threat to the health and economic well-being of the inhabitants and ecosystem in these areas. In this work, for arsenic removal, iron and iron oxide nanoparticles obtained from recycling metal chips by top-down and bottom-up technology have been used for arsenic adsorption in an experimental filter combined with other artisanal filtering materials in the form of layers. The results have shown that water contaminated with arsenic after passing through the filter reduces the concentration of total arsenic filtered from 83, 52 ppb to less than 5 ppb, less than the Bolivian standard 512 of 10 ppb for drinking water.

The aim of this research involves investigating the elimination of nitrogen ions from groundwater through the application of dynamic permeable reactive barriers (PRB) utilizing A400-nZVI. The aim also implyies determining barrier parameters, as well as assessing the overall retention capacity of nitrogen ions through percolation with a potassium nitrate solution. The research involves obtaining zero valent iron nanoparticles (nZVI), which were synthesized and doped onto an anionic resin support material (A400) through the reduction reaction of ferrous ions with sodium borohydride (NaBH4). This was achieved by preparing a ferrous sulfate solution, contacting it with the ion exchange resin at various solid-liquid mass ratios, and gradually adding sodium borohydride under continuous stirring in an oxygen-free environment to create the A400-nZVI barrier. The outcomes of this study, focusing on the development of permeable reactive barriers composed of nanovalent iron and ion exchangers, demonstrate significant potential in purification processes when appropriately dimensioned. The research specifically evaluated the efficacy of NO3- removal using the A400-nZVI permeable reactive barrier, conducting laboratory tests that simulated a naturally stratified aquifer with high nitrate contamination.

Abstract: Female pelvic floor dysfunction (FPFD) is a series of conditions caused by the displacement or dysfunction of the patient's pelvic organs due to defects, injuries, and deterioration of the pelvic floor supportive structures, with stress urinary incontinence and pelvic organ prolapse being the most common. The mechanism of pelvic floor dysfunction is complex and not yet fully understood, and is often related to one or more functional abnormalities of muscles, connective tissues, fascia, nerves and blood vessels. Specialized clinicians are often unable to cover the comprehensive medical professional information of various specialties such as gynecology and obstetrics, urology, anus and intestines, imaging, etc., and the systematic and comprehensive diagnosis and treatment of the disease will be limited. The application of artificial intelligence concepts in the medical field not only improves the diagnostic efficiency of physicians, but also provides reference and basis for the development of comprehensive treatment programs. This article follows and draws on the diagnosis and treatment process of pelvic floor dysfunction recommended in various guidelines, incorporates physical therapy techniques into the conventional non-surgical treatment of pelvic floor dysfunction, provides guidance for the diagnosis and treatment of pelvic floor dysfunction, and briefly introduces the clinical application and value of pelvic floor intelligent diagnosis and treatment in pelvic floor dysfunction.

.Celiac disease (CeD) is a chronic, autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environ-mental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist de-spite apparent compliance with a GFD. That could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on GFD who expe-rience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This re-view will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.

Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.

VarroMed® is a soft acaricide registered for honey bees on the European Union market since 2017 for Varroa control. Researchers involved were partners of different countries of the Varroa control task force of COLOSS Association. Our goal was to evaluate performances (acaricide efficacy and toxic effects on honey bees) of VarroMed® in different climatic conditions. Our results in the tested apiaries showed an efficacy ranging from 71.2 to 89.3 % in summer/autumn, and from 71.8 % to 95.6 % in winter. No toxic effects on bees were observed, except in one apiary, where severe cold climatic conditions played a crucial role. The treatment could be efficiently applied in brood right as well as in broodless colonies. Integrated pest management (IPM) recommendations for bee-keepers are provided in order to apply the best Varroa control protocol.

Large-span post-tensioned (PT) beams play a crucial role in maximizing the benefits of post-tensioning techniques. Bonded and unbonded systems are prevalent, with the latter being more widespread in the United States. While bonded systems are advantageous for creating long spans when multiple tendons are grouped in ducts, limited literature exists on their demolition. In a case study, this paper addresses the unique challenge of demolishing large-span bonded post-tensioned beams due to a building's functional change. Emphasizing insights for engineers, it explores the use of cutting and dismantling methods, considering the presence of prestressed cables. The demolition process is distinctive due to the presence of numerous pre-stressed cables along the beams, necessitating a specialized and cautious cutting approach. This is accomplished through the use of a drilling technique that selectively distresses the tendons, ensuring they are not all affected simultaneously. An intriguing observation discussed in this paper pertains to the occurrence of horizontal cracks accompanied by loud sounds following the drilling process, offering insights from the design perspective of PT systems. The paper details an innovative method for safely demolishing large-span bonded PT beams, using ground-penetrating radar and computer models to navigate structural complexities and ensure nearby structures' safety.

The pandemic was an enormous experience all over the world. The type of living, working and study were changed irreversibly. Facing the opportunity to establish old frames of education in universities is impossible. The adoption of new ways of teaching and assessments reveal their convenience and in the same way their weak points. In response to that stage, on 14 December 2022, the EU parliament accepted the "Digital Decade Policy Programme 2030", for the establishment of a digital transformation community (EU 2022). Trakia University had an online assessment system, quizzes for self-training, and final exams, developed in 2008 on Moodle virtual learning environment. During the pandemic, online exams and lectures were conducted using platforms like BigBlueButton in Moodle or Google Meets. The article gives the results of online exams before, during, and after the pandemic. The outcome, without doubt, displays the lowering knowledge level or performance during the social isolation due to COVID-19, and after, and the reasons are discussed. During the second year of the pandemic was mentioned also a high dropout of students. Now the situation is returning to the previous levels, before the pandemic, but the quality of education is not yet reached. The article values the grades results of session exams and has the intention to clarify the influence of the pandemic period on the excellence of high institution education.

The study aimed to evaluate the after-effects of the COVID-19 pandemic on the sleep quality and patterns of women across different cultural settings within Iraq, spanning the period of 2022. A cross-sectional survey was administered to a diverse cohort of women from multiple provinces in Iraq. The survey measured various parameters, including sleep duration, onset latency, and disturbances. The post-pandemic period has seen a notable decline in sleep quality among the female population. Contributing factors include psychological stress, lifestyle changes due to the pandemic, and ongoing socio-economic challenges. The impact on sleep quality exhibited variation across different cultural groups, indicating a significant cultural influence on the pandemic's psychological aftermath. The study concludes that the post-pandemic phase has adversely affected the sleep health of women in Iraq, with cultural factors playing a critical role in these changes. There is a pressing need for culturally sensitive public health strategies to address sleep disturbances and mitigate their long-term effects on women's health. Public health initiatives should be tailored to address the specific cultural contexts within Iraq to improve sleep health among women. Further research is warranted to explore the long-term consequences of disturbed sleep patterns and the effectiveness of different intervention strategies.