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Introduction: Kidney transplantation has emerged as a preferred method for improving survival and quality of life for patients with end-stage renal disease in comparison with dialysis. Living donation provides a better patient and allograft survival when compared with deceased-donor transplantation, specifically when the live donor transplant is accomplished before the onset of dialysis. The present study aimed to create and add data for the long-term survival, complications occurred in donor as well as in recipient both in single study in India. Materials and Methods: We performed a retrospective cohort study of all adult patients undergoing renal transplantation. Data on kidney transplantation and operative variables, as well as follow-up data, were obtained retrospectively from the Internal Medical Record Department. The primary outcomes examined were both donor and recipient and graft survival after 2 years and 5 years. Secondary outcomes included the presence of acute rejection and delayed graft function, as well as the rate of postoperative complications. Results: A total of 500 donors and 500 recipients participated in the research overall. The mean warm ischemia time was 3.1 ± 1.4 min and cold ischemia time was 44.3 ± 23.4 min. Surgical complications were encountered in 32.8% (164/500) of patients. The 2-year and 5-year graft survival rates were 90.2% and 84.8%, respectively. Conclusion: Our patients’ rate of complications was not greater than that noted in the previous publications. A thorough and meticulous medical assessment of the donor and recipient is required, as well as a rigorous and responsible evaluation of the indications.

Introduction: Traumatic hemothorax is accounted for about 20% of traumatic chest injuries. Although majority can be managed with the timely placement of intercostal tube (ICT) drainage, the remaining pose a challenge owing to high complication rates associated with retained hemothorax. Although various treatment modalities including intrapleural instillation of fibrinolytics, radioimage guided drainage, VATS guided evacuation and thoractomy do exist to address the retained hemothorax, but indications along with timing to employ a specific treatment option is still unclear and ambiguous. Methods: Patient with residual hemothorax (>200 mL) on ultrasonography after 48 h of indwelling ICT was randomized into either early video-assisted thoracic surgery (VATS) or conventional approach cohort. Early VATS cohort was subjected to video-assisted thoracoscopic evacuation of undrained blood along with normal saline irrigation and ICT placement. The conventional cohort underwent intrapleural thrombolytic instillation for 3 consecutive days. The outcome measures were the duration of indwelling ICT, removal rate of tube thoracostomy, length of hospital stay, duration of intensive care unit (ICU) monitoring, need for mechanical ventilation, incidence of pulmonary and pleural complications, and requirement of additional intervention to address undrained hemothorax and mortality rate. Results: The early VATS cohort had shorter length of hospital stay (7.50 ± 0.85 vs. 9.50 ± 3.03, P = 0.060), reduced duration of indwelling ICT (6.70 ± 1.25 vs. 8.30 ± 2.91, P = 0.127) with higher rate of tube thoracostomy removal (70% vs. 30%, P = 0.003) and lesser need of additional interventions (0% vs. 30%, P = 0.105). Thoracotomy (3 patients) and image-guided drainage (4 patients) were additional interventions to address retained hemothorax in the conventional cohort. However, similar length of ventilator assistance (0.7 ± 0.48 vs. 0.60 ± 1.08, P = 0.791) and prolonged ICU monitoring (1.30 ± 1.06 vs. 0.90 ± 1.45, P = 0.490) was observed in early VATS cohort. Both the cohorts had no mortality. Conclusion: VATS-guided early evacuation of traumatic hemothorax is associated with shorter length of hospital stay along with abbreviated indwelling ICT duration, reduced incidence of complications, lesser readmissions, and improved rate of tube thoracostomy removal. However, the duration of ventilator requirement, ICU stay, and mortality remain unchanged.

Abstract Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.

Navigating clinical guidelines can be complex for real-time health care decision making. Our study evaluates the chat generative prerained transformer (ChatGPT)-4 in improving responses to clinical questions by integrating guidelines on Clostridioides difficile infection and colon polyp surveillance. We assessed ChatGPT-4’s responses to questions before and after guideline integration, noting a clear improvement in accuracy. ChatGPT-4 provided guideline-aligned answers consistently. Further analysis showed its ability to summarize information from conflicting guidelines, highlighting its utility in complex clinical scenarios. The findings suggest that large language models such as ChatGPT-4 can enhance clinical decision making and patient education by providing quick, conversational, and accurate responses. This approach opens a path for using artificial intelligence to deliver reliable responses in health care, supporting clinicians in real-time decision making and improving patient care.

Abstract Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health. We show that in this location double negative 2 B cells interact with dendritic cells co-expressing the lupus autoantigens DNASE1L3 and C1q and microbicides. We observe that in humans, but not in mice, dendritic cells expressing DNASE1L3 are associated with sampled bacteria but not DNA derived from apoptotic cells. We propose that fundamental features of autoimmune diseases are microbiota-associated, interacting components of normal intestinal immunity.

Abstract Background Artificial intelligence (AI) that utilizes deep learning (DL) has potential for systemic disease prediction using retinal imaging. The retina’s unique features enable non-invasive visualization of the central nervous system and microvascular circulation, aiding early detection and personalized treatment plans for personalized care. This review explores the value of retinal assessment, AI-based retinal biomarkers, and the importance of longitudinal prediction models in personalized care. Main text This narrative review extensively surveys the literature for relevant studies in PubMed and Google Scholar, investigating the application of AI-based retina biomarkers in predicting systemic diseases using retinal fundus photography. The study settings, sample sizes, utilized AI models and corresponding results were extracted and analysed. This review highlights the substantial potential of AI-based retinal biomarkers in predicting neurodegenerative, cardiovascular, and chronic kidney diseases. Notably, DL algorithms have demonstrated effectiveness in identifying retinal image features associated with cognitive decline, dementia, Parkinson’s disease, and cardiovascular risk factors. Furthermore, longitudinal prediction models leveraging retinal images have shown potential in continuous disease risk assessment and early detection. AI-based retinal biomarkers are non-invasive, accurate, and efficient for disease forecasting and personalized care. Conclusion AI-based retinal imaging hold promise in transforming primary care and systemic disease management. Together, the retina’s unique features and the power of AI enable early detection, risk stratification, and help revolutionizing disease management plans. However, to fully realize the potential of AI in this domain, further research and validation in real-world settings are essential.

Introduction: Intrathecal adjuvants have gained favour in recent years with the goal of extending the duration of a block. Among these, Dexamethasone possesses anti-inflammatory and analgesic action and can be given as an adjuvant to local anaesthetics to enhance the efficacy of regional anaesthesia, as well as to decrease the intensity of shivering. The addition of Magnesium sulphate (MgSO4) to spinal anaesthesia helps in improving postoperative analgesia in an orthopaedic setting. Aim: To compare the effects of Intravenously (i.v.) MgSO4 and i.v. dexamethasone on intraoperative haemodynamics, the time to achieve dermatome T10 intraoperatively, and to compare postoperative Visual Analogue Scale (VAS) scores between the two groups at 1, 3, 6, 12, and 24 hours after surgery. Materials and Methods: This randomised clinical trial was conducted, and patients were randomly divided into two groups. Group M (n=40): MgSO4 40 mg/kg given 15 minutes before spinal anaesthesia in 100 mL normal saline infusion i.v. Group D (n=40): Dexamethasone 8 mg given 15 minutes before spinal anaesthesia in 100 mL normal saline infusion i.v. The parameters assessed included haemodynamic parameters, time to achieve dermatome T10 intraoperatively, postoperative VAS score at 1, 3, 6, 12, and 24 hours after surgery, and any side-effects like sedation, respiratory depression, nausea, vomiting, pruritus, urinary retention, bradycardia, and hypotension. Statistical testing was conducted using the statistical software Statistical Package for Social Sciences (SPSS) 28.0. Results: There was no significant difference in demographic variables (age and gender) between the two groups (p-value>0.05). However, the decrease in mean heart rate, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Mean Arterial Blood Pressure (MAP) was greater in group D compared to group M at different time intervals (p-value

Background: Bladder exstrophy is a complex, rare congenital malformation with an incidence of 3.3 cases in every 100000 live births and is slightly more common in males. Primary surgical repair requires many hours of surgery with fluid and blood loss. Because of wide fluctuations in hemodynamics, a longer duration of surgery, smaller age, risk of hypothermia and post-operative intensive care may be required. We evaluated the use of continuous caudal epidural infusion of bupivacaine and fentanyl under general anesthesia for urinary bladder exstrophy-epispadias surgery in children. Aims and Objectives: Aim of the study was to evaluate the postoperative analgesia in patients undergoing surgery for bladder exstrophy. The primary objective was to assess the postoperative pain using FLACC scale and sedation score after successful caudal administration. Secondary objective was to assess the hemodynamic changes after caudal administration. Materials and Methods: A total of 13 patients aged between 9months and 13 years of either sex, weighing between 5kg to 30kg, belonging to ASA grade II to IV, underwent surgery for epispadias–exstrophy complex. Initial bolus 0.75ml/kg of 0.25% bupivacaine with fentanyl 1ug/kg was given through epidural. Postoperative analgesia was maintained by continuous infusion of 0.0625% bupivacaine @0.1ml/kg/hr in young children and 0.125% bupivacaine with fentanyl 1ug/ml in older children for 4-5 days with the help of ON-Q pump or infusion pump. Baseline hemodynamic parameters including MAP, heart rate and SpO2 was recorded at various time intervals. Postoperative pain was assessed using face, legs, activity, cry and consolability (FLACC) pain scale and sedation score was assessed by using ramsay sedation score. Results: There was a statistically significant decrease in mean pulse rate in the study group from baseline to thirty minutes after reversal (p

Background and objective: Focal therapy (FT) is increasingly recognized as a promising approach for managing localized prostate cancer (PCa), notably reducing treatment-related morbidities. However, post-treatment anatomical changes present significant challenges for surveillance using current imaging techniques. This study aimed to evaluate the inter-reader agreement and efficacy of the Prostate Imaging after Focal Ablation (PI-FAB) scoring system in detecting clinically significant prostate cancer (csPCa) on post-FT multiparametric magnetic resonance imaging (mpMRI). Methods: A retrospective cohort study was conducted involving patients who underwent primary FT for localized csPCa between 2013 and 2023, followed by post-FT mpMRI and a prostate biopsy. Two expert genitourinary radiologists retrospectively evaluated post-FT mpMRI using PI-FAB. The key measures included inter-reader agreement of PI-FAB scores, assessed by quadratic weighted Cohen’s kappa (κ), and the system’s efficacy in predicting in-field recurrence of csPCa, with a PI-FAB score cutoff of 3. Additional diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were also evaluated. Key findings and limitations: Scans from 38 patients were analyzed, revealing a moderate level of agreement in PI-FAB scoring (κ = 0.56). Both radiologists achieved sensitivity of 93% in detecting csPCa, although specificity, PPVs, NPVs, and accuracy varied. Conclusions and clinical implications: The PI-FAB scoring system exhibited high sensitivity with moderate inter-reader agreement in detecting in-field recurrence of csPCa. Despite promising results, its low specificity and PPV necessitate further refinement. These findings underscore the need for larger studies to validate the clinical utility of PI-FAB, potentially aiding in standardizing post-treatment surveillance. Patient summary: Focal therapy has emerged as a promising approach for managing localized prostate cancer, but limitations in current imaging techniques present significant challenges for post-treatment surveillance. The Prostate Imaging after Focal Ablation (PI-FAB) scoring system showed high sensitivity for detecting in-field recurrence of clinically significant prostate cancer. However, its low specificity and positive predictive value necessitate further refinement. Larger, more comprehensive studies are needed to fully validate its clinical utility.

Purpose: Retinoblastoma (RB) is the most common intraocular tumor in pediatric age group. The role of genetics has been explored in predicting survival prognosis, but its role in predicting globe salvage remains largely unexplored. We hereby aim to isolate cell-free DNA (cfDNA) from aqueous humor (AH) in RB eyes and validate its use for genetic studies. Methods: AH was obtained from 26 eyes undergoing enucleation (arm A) or intravitreal chemotherapy (arm B). Isolation of cfDNA was done using QIAamp® Circulating Nucleic Acid kit, and the cfDNA was utilized for targeted sequencing of RB1 gene. Results: We could isolate cfDNA in all eyes (72% unilateral and 28% bilateral) with a distribution peak between 140 and 160 bp and a mean concentration of 27.75 ng/µl for arm A and 14 ng/µl for arm B. Targeted sequencing done on four samples showed RB1 gene mutations, namely, inframe deletion (c. 78-80del, p.Pro29del), start-loss mutation (c.1A>T, p.Met1?), nonsense mutations (c.2236G>T, p.Glu746Ter), (c.1659T>A, p.Cys553Ter), and (c.2065C>T, p.Gln689Ter), and novel missense mutations (c.672C>A, p.Asp224Glu) and c.692C>T (p.Pro231Leu). Genetic profile of cfDNA extracted from AH and genomic DNA from the tumor tissue was comparable. Conclusion: Our study supports the previous reports that AH may be used as a source of tumor-derived cfDNA. This is the first report from South Asia on isolation and genetic analysis of cfDNA from AH of RB eyes and, therefore, a big step forward in paving the role of tumor genetics in RB. Further studies are required to elucidate concordance between the tumor and AH genetic profile.

The European Charter of Local Self-Government (ECLSG) is a cornerstone for local governance, emphasising principles such as autonomy, financial independence, and democratic processes. This article assessed the implementation of the ECLSG in Azerbaijan, focusing on legal compliance and institutional adaptation. This study aimed to assess Azerbaijan's level of compliance with the principles established in the ECLSG and to evaluate the extent to which its institutions have been modified to align with the charter's benchmarks. A qualitative research methodology relying on document analysis, legal reviews, and expert interviews was employed in the study. The analysis included a review of pertinent legal documents, reports, and scholarly articles to evaluate the degree of legal adherence and institutional flexibility in Azerbaijan. The findings indicated Azerbaijan has shown advancements in implementing the ECLSG, especially in decentralisation and forming local self-governing entities. However, there are still obstacles to guaranteeing complete legal adherence, including issues related to the autonomy of local governments, boundary protection, and financial resources. The European Charter of Local Self-Government is vital in promoting local democracy and self-government in Europe. It emphasises the autonomy of local authorities and democratic processes at the local level. In Azerbaijan, implementing the ECLSG has led to significant institutional changes, including establishing municipal councils and executive bodies. However, challenges remain, such as limited autonomy, inadequate funding, and shortcomings in the electoral process. Addressing these challenges is crucial for Azerbaijan to comply with the charter and improve local governance fully. The findings suggest that while Azerbaijan has taken steps to align its legal framework with the ECLSG, further reforms are needed to enhance local self-government. Addressing challenges such as central government interference, boundary adjustments, and budget limitations will be essential in achieving complete adherence to the charter and strengthening local governance in Azerbaijan.

Toilet cleaner containing hydrochloric acid is a common item found in households all over the world. Due to the availability of the substance, it becomes one of the main contributors to corrosive damage to the gastrointestinal system. This study reports a case of a female in her 50s with an alleged history of ingestion of toilet cleaner an empty bottle of which was found together with a suicide note at the incident site. During the autopsy, the forensic expert made an intriguing observation regarding the dispersion of ingested acid to other organs without gastric perforation. Despite the absence of gastric perforation, the corrosive effects of the ingested acid were evident in various organs, including the liver and spleen. This phenomenon suggests a unique mechanism by which the acid is able to disperse and cause damage beyond the stomach, leading to widespread organ involvement. However, through a comprehensive analysis of the detailed history, typical macroscopic autopsy findings, and chemical analysis reports, it is possible to establish that the cause of death is corrosive acid poisoning. In such cases, further investigation is warranted to gain a better understanding of the underlying mechanisms responsible for the dispersion of the acid and its clinical implications. By delving deeper into these aspects, we can enhance our knowledge and contribute to the field of forensic medicine.

Abstract The continuing emergence of new strains of antibiotic-resistant bacteria has renewed interest in phage therapy; however, there has been limited progress in applying phage therapy to multi-drug resistant Mycobacterium tuberculosis (Mtb) infections. In this study, we show that bacteriophage strains D29 and DS6A can efficiently lyse Mtb H37Rv in 7H10 agar plates. However, only phage DS6A efficiently kills H37Rv in liquid culture and in Mtb-infected human primary macrophages. We further show in subsequent experiments that, after the humanized mice were infected with aerosolized H37Rv, then treated with DS6A intravenously, the DS6A treated mice showed increased body weight and improved pulmonary function relative to control mice. Furthermore, DS6A reduces Mtb load in mouse organs with greater efficacy in the spleen. These results demonstrate the feasibility of developing phage therapy as an effective therapeutic against Mtb infection.

Abstract SARS‐CoV‐2 epidemic (severe acute respiratory corona virus 2 syndromes) has caused major impacts on a global scale. Several countries, including India, Europe, U.S.A., introduced a full state/nation lockdown to minimise the disease transmission through human interaction after the virus entered the population and to minimise the loss of human life. Millions of people have gone unemployed due to lockdown implementation, resulting in business and industry closure and leading to a national economic slowdown. Therefore, preventing the spread of the COVID‐19 virus in the world while also preserving the global economy is an essential problem requiring an effective and immediate solution. Using the compartmental epidemiology S, E, I, R or D (Susceptible, Exposed, Infectious, Recovery or Death) model extended to multiple population regions, the authors predict the evolution of the SARS‐CoV‐2 disease and construct an optimally scheduled lockdown calendar to execute lockdown over phases, using the well‐known Knapsack problem. A comparative analysis of both classical and quantum models shows that our model decreases SARS‐CoV‐2 active cases while retaining the average global economic factor, Gross Domestic Product, in contrast to the scenario with no lockdown.

Introduction: Peripheral nerve blocks have recently proven to be extremely promising in terms of patient satisfaction. In upper limb procedures, rapid and deep anaesthesia can be achieved with supraclavicular ultrasound-guided access to the brachial plexus. To improve the quality of local anaesthesia, adjuvants such as magnesium sulfate and dexmedetomidine have been added to the local anaesthetic. Aim: To evaluate the efficacy of magnesium sulfate and dexmedetomidine as adjuvants to ropivacaine in supraclavicular Brachial Plexus Blockade (BPB). Materials and Methods: A prospective randomised double-blind study was conducted in the Department of Anaesthesiology from June 2016 to November 2017 ( 1 year and 6 months) at King George's Medical University, Lucknow, Uttar Pradesh, India. A total of 60 patients were divided into two groups using a computer-generated random number for upper limb surgeries (below the mid-humerus) under supraclavicular brachial plexus block. Group A (n=30) received ropivacaine 0.5% (30 mL) plus dexmedetomidine 50 μg for the supraclavicular block, and Group B received ropivacaine 0.5% (30 mL) plus magnesium sulfate 150 mg in 1 mL Normal Saline (NS) 0.9% for the same block. A comparison of these two groups was conducted for the time of onset, duration of sensory and motor block, haemodynamic stability, postoperative analgesia, and complications. Statistical analyses such as Student’s t-test, Chi-square test, and Mann-Whitney U-test were used. Results: The mean age of Group A was 28.03±5.86 years and Group B was 31.07±7.06 years. The sensory block and motor block onset were significantly faster among patients of Group A (6.47±1.43 min and 8.50±1.46 min) compared to Group B (9.57±1.22 min and 11.77±1.19 min). The mean duration of analgesia was significantly longer (p

The fifth generation (5G) network enabled communication between devices has emerged as a state-of-the-art technology. In the era of proliferating smart devices and intelligent wireless communication networks, Reflecting Intelligent Surfaces (RIS) and Unpiloted Air Vehicles (UAV) duplet has turn out to be a trustworthy, lucrative and handy solution for various appearing real world communication issues. This article pitches into the downlink UAV communication empowered by RIS, where UAV communicates with Mobile Instruments (MI) via RIS patches installed at a tall tower. Considering the attributes like transmitted power and UAV trajectory, Deep Reinforcement Learning (DRL) based approach is recommended to maximize the overall Sum-rate. In present scenario, DRL technology has popped up as a commanding tool that allows a network to regulate itself in order to deliver optimum solution. In this article, we have proposed a novel viewpoint evolved from Deep Deterministic Policy Gradient (D-DPG) Algorithm specifically Shared Deep Deterministic Policy Gradient (SD-DPG) algorithm for downlink UAV-MI power allocation and trajectory optimization problem. Numerical outcomes manifest that our model, concerned to maximizing sum-rate, outperformed other DRL based method DD-DPG by at least 30% and D-DPG by approximately 3 folds together with optimizing power, phase-shift and UAV trajectory.

Simultaneous wireless information and power transfer (SWIPT) is a method through which users can simultaneously obtain energy and receive data from the base station (BS). This allows them to charge their batteries, which have limited power capacity, and enhance the quality of service (QoS). Nevertheless, this technology encounters the double near-far issue, where users located at the edges of the cell experience insufficient energy due to energy path loss, resulting in a decrease in system performance. In this investigation, we integrate the self-energy recycling technology with a D2D communication system that enables full-duplex operation. By employing this technology, the D2D cell edge user (DCEU) can harvest energy from self-interference and utilize it to transmit data to the nearest D2D cell center user (DCCU). The DCCU combines its data with the DCEU and sends it to the BS using uplink non-orthogonal multiple access (NOMA). Both the DCCU and DCEU use a significant amount of energy when transmitting data, which negatively affects the quality of service (QoS). The goal of this research is to decrease the overall energy consumption of the DCEU and DCCU while maintaining their QoS. The defined problem is complex due to time and power limitations, as well as the presence of self and NOMA interference. To address this issue, we utilize a technique that combines time and power allocation. The numerical results demonstrated that the proposed scheme consumes 28.12% and 40.67% lesser amount of energy as compared to the baseline schemes.

Abstract Background Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients. Methods We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir’s safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample. Results After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint (P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients’ guts. Conclusions Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir’s safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU. Trial registration NCT05416814; trial registered on June 13, 2022.

Abstract To survive, cells must respond to changing environmental conditions. One way that eukaryotic cells react to harsh stimuli is by forming physiological, RNA-seeded subnuclear condensates, termed amyloid bodies (A-bodies). The molecular constituents of A-bodies induced by different stressors vary significantly, suggesting this pathway can tailor the cellular response by selectively aggregating a subset of proteins under a given condition. Here, we identify critical structural elements that regulate heat shock-specific amyloid aggregation. Our data demonstrates that manipulating structural pockets in constituent proteins can either induce or restrict their A-body targeting at elevated temperatures. We propose a model where selective aggregation within A-bodies is mediated by the thermal stability of a protein, with temperature-sensitive structural regions acting as an intrinsic form of post-translational regulation. This system would provide cells with a rapid and stress-specific response mechanism, to tightly control physiological amyloid aggregation or other cellular stress response pathways.

Introduction Eagle syndrome is a rare and an often misdiagnosed entity in otorhinolaryngology.

Objective:. To determine whether socio-demographic and preoperative clinical factors contribute to the percent total body weight loss (%TBWL) after bariatric surgery (BS). Background:. BS is the most effective long-term treatment for medically complicated obesity. More information is needed about the factors that contribute to postoperative %TBWL in large and ethnically diverse cohorts. Methods:. This retrospective study conducted in the Kaiser Permanente Northern California region included 7698 patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between January 2009 and March 2015. Trajectory analyses were conducted from 5-year follow-up data to assign patients to “low,” “average,” or “high” postoperative %TBWL groups. We then evaluated whether age, sex, race/ethnicity, neighborhood deprivation index and preoperative body mass index (BMI)/weight loss, diabetes, hypertension, and sleep apnea contributed to postoperative %TBWL using logistic regression models. Results:. Of 7698 patients (83.2% women), 48.6% underwent a RYGB and 51.4% underwent a SG. Postoperative %TBWL trajectories over 5 years were obtained in 6229 (81%) of 7698 eligible patients. About 27.8% and 29.3% of patients followed the “low” postoperative %TBWL trajectory, for RYGB and SG, respectively. Men, older patients, and Asian, Black, and Hispanic/Latino patients were more likely to be classified in the low postoperative %TBWL group. Patients showing lower postoperative %TBWL had a lower preoperative BMI (but lost less weight before surgery) and were more likely to have preoperative comorbidities. Conclusions:. This study confirms and extends prior findings of the effects of several demographic and preoperative clinical factors on postoperative weight loss. Findings could improve the support of patients to achieve desired surgical outcomes.

Abstract Background and Aim According to the European Society of Gastrointestinal Endoscopy (ESGE), gastroscopy should be conducted within 6 h for complete obstruction and 24 h for incomplete obstruction due to food bolus impaction. This study explores whether adults with acute esophageal food bolus (FB) impaction experience adverse outcomes when their time to esophagogastroduodenoscopy (EGD) deviates from the recommended guidelines. Methods A retrospective review was performed on the records of 248 patients who presented at the study site between 2015 and 2022 with symptoms of FB impaction. Results Two hundred and forty‐eight patients underwent EGD for FB impaction. Grade 1 (erosion, ulceration), Grade 2 (tear), and Grade 3 (perforation) complications were present in 31.6%, 6.9%, and 0.8% of cases, respectively. Of the 134 (54.0%) patients with complete obstruction, 51 (38.1%) received EGD within the recommended 6 h. Of the 114 (46%) patients with incomplete obstructions, 93 (81.6%) received EGD within the recommended 24 h. There was no statistically significant correlation between length of stay (LOS) post‐EGD and any of ingestion to presentation time, presentation to EGD time, or ingestion to EGD time. Age and complication level were greater predictors of longer LOS than presentation to EGD time. Patients who presented in hours were significantly more likely to receive EGD within the 6‐ and 24‐h guidelines than those who presented out of hours (50.7% vs 22.0%). Conclusion Neither time to EGD from ingestion of food bolus nor time to EGD from hospital presentation correlated with complication rate, complication severity, or length of stay post‐EGD.

In the present study, extraction of nutraceuticals from neem leaves (Azadirachta indica A. Juss) was optimized using different extraction methods and solvents. Nutraceuticals possessing antimicrobial activities has been studied. The maximum amount of yield of neem oil was obtained when methanol was used and the yield comes out to be 7.68±0.11% by weight. 100 µL of extracted neem oil was incorporated in three different types of hydrogels of different proportions such as Chitosan-Gelatin hydrogel (1:1. 1.67:1 and 1:5), Maltodextrin-Whey protein (1:2) and Gum Arabic hydrogel and the release behavior was determined. The neem nutraceutical release was maximum (89.99 %) in case of Chitosan-Gelatin hydrogel where chitosan and gelatin was in the ratio of 5:1 and the amount of nutraceutical present was 100 µL, whereas the amount of drug release was observed minimum (44.45 %) in Gum Arabic hydrogel.

Abstract Amplification of sea surface temperature (SST) seasonality in response to global warming is a robust feature in climate model projections but season‐dependent regional disparities in this amplification and the associated mechanisms are not well addressed. Here, by analyzing large ensemble simulations using Community Earth System Model version 2, we investigate detailed spatiotemporal characteristics of the amplification of SST seasonality focusing on the North Pacific and North Atlantic, where robust changes are projected to emerge around 2050 under SSP3‐7.0 scenario. Our results indicate that atmosphere‐ocean coupled processes shape regional changes in SST seasonality differently between warm (MAMJJAS) and cold seasons (ONDJF). During the warm season, the projected warming tendency is mainly due to increased net surface heat flux and weakening of vertical mixing. On the other hand, in the cold season, the projected cooling tendency is driven by strengthened vertical mixing over the North Pacific associated with the northward shift of storm tracks but weakened horizontal advection and mixing due to changes in ocean currents over the North Atlantic.

Summary: Retinal ganglion cell (RGC) differentiation is tightly controlled by extrinsic and intrinsic factors. Growth and differentiation factor 15 (GDF-15) promotes RGC differentiation, opposite to GDF-11 which inhibits RGC differentiation, both in the mouse retina and in human stem cells. To deepen our understanding of how these two closely related molecules confer opposing effects on retinal development, here we assess the transcriptional profiles of mouse retinal progenitors exposed to exogenous GDF-11 or -15. We find a dichotomous effect of GDF-15 on RGC differentiation, decreasing RGCs expressing residual pro-proliferative genes and increasing RGCs expressing non-proliferative genes, suggestive of greater RGC maturation. Furthermore, GDF-11 promoted the differentiation of photoreceptors and amacrine cells. These data enhance our understanding of the mechanisms underlying the differentiation of RGCs and photoreceptors from retinal progenitors and suggest new approaches to the optimization of protocols for the differentiation of these cell types.

Background Patients may prefer percutaneous coronary intervention (PCI) over coronary artery bypass graft (CABG) surgery, despite heart team recommendations. The outcomes in such patients have not been examined. We sought to examine the results of PCI in patients who were recommended for but declined CABG. Methods and Results Consecutive patients with stable ischemic heart disease and unprotected left main or 3‐vessel disease or Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score >22 who underwent PCI after heart team review between 2013 and 2020 were included. Patients were categorized into 3 groups according to heart team recommendations on the basis of appropriate use criteria: (1) PCI‐recommended; (2) CABG‐eligible but refused CABG (CABG‐refusal); and (3) CABG‐ineligible. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. The study included 3687 patients undergoing PCI (PCI‐recommended, n=1718 [46.6%]), CABG‐refusal (n=1595 [43.3%]), and CABG‐ineligible (n=374 [10.1%]). Clinical and procedural risk increased across the 3 groups, with the highest comorbidity burden in CABG‐ineligible patients. Composite events within 1 year after PCI occurred in 55 (4.1%), 91 (7.0%), and 41 (14.8%) of patients in the PCI‐recommended, CABG‐refusal, and CABG‐ineligible groups, respectively. After multivariable adjustment, the risk of the primary composite outcome was significantly higher in the CABG‐refusal (hazard ratio [HR], 1.67 [95% CI, 1.08–3.56]; P=0.02) and CABG‐ineligible patients (HR, 3.26 [95% CI, 1.28–3.65]; P=0.004) groups compared with the reference PCI‐recommended group, driven by increased death and stroke. Conclusions Cardiovascular event rates after PCI were significantly higher in patients with multivessel disease who declined or were ineligible for CABG. Our findings provide real‐world data to inform shared decision‐making discussions.

Summary: Cytotoxic T lymphocyte (CTL) and terminal exhausted T lymphocyte (ETL) activities crucially influence immune checkpoint inhibitor (ICI) response. Despite this, the efficacy of ETL and CTL transcriptomic signatures for response prediction remains limited. Investigating this across the TCGA and publicly available single-cell cohorts, we find a strong positive correlation between ETL and CTL expression signatures in most cancers. We hence posited that their limited predictability arises due to their mutually canceling effects on ICI response. Thus, we developed DETACH, a computational method to identify a gene set whose expression pinpoints to a subset of melanoma patients where the CTL and ETL correlation is low. DETACH enhances CTL’s prediction accuracy, outperforming existing signatures. DETACH signature genes activity also demonstrates a positive correlation with lymphocyte infiltration and the prevalence of reactive T cells in the tumor microenvironment (TME), advancing our understanding of the CTL cell state within the TME.

Background: Full-thickness rectal prolapse remains a challenging pathology to correct surgically with significant recurrence rates. Among perineal approaches, the proctosigmoidectomy with levatorplasty, commonly referred to as the Altemeier procedure is frequently performed. The addition of levatorplasty has been postulated to improve recurrence rates, however, its efficacy varies across studies. The aim of this study was to systematically review recurrence rates following proctosigmoidectomy with levatorplasty, and to meta-analyze pooled data comparing recurrence rates between proctosigmoidectomy with and without a levatorplasty. Methods: A search of EMBASE, OVID Medline, and CENTRAL was performed from database inception to October 2021 aimed at identifying studies investigating recurrences of rectal prolapse following proctosigmoidectomy with levatorplasty. Primary endpoint was recurrence of rectal prolapse. Articles that did not report this endpoint or did not evaluate proctosigmoidectomy with levatorplasty were excluded. A pairwise meta-analysis was performed using Mantel-Haenszel random effects. Results: From 200 citations, 14 primary studies met inclusion criteria. A total of 620 patients (88.9% female, mean age: 71 years) underwent proctosigmoidectomy with levatorplasty, and 117 without levatorplasty. Of the patients undergoing levatorplasty, 86 (13.8%) experienced a recurrence. Mean follow up was 46 months. Meta-analysis comparing recurrence rates between proctosigmoidectomy with and without levatorplasty demonstrated no significant difference (RR 0.80, 0.92, 95% CI 0.32–2.59, P = 0.87, I2 = 77%). Narrative review of postoperative quality of life metrics demonstrated decreased incontinence with levatorplasty as measured by Wexner and ICIQ-SIF scores. Discussion: The addition of a levatorplasty does not significantly reduce the risk of recurrent rectal prolapse after proctosigmoidectomy, however it may improve postoperative continence.

Rice is one of the most important food crops in the South India. Many varieties of rice are cultivated in different regions of the India to meet the dietary needs of the ever-growing population. In spite of huge investment in terms of land, labour, raw materials and machinery, the farmers continuously face irrecoverable loss due to various reasons like climatic changes, drought situation and seed quality. In the current practice, the quality of the seeds is certified by the Seed Testing Laboratories (STL) and purity analysis is done manually by trained technicians. However, seed classification is not uniform across different labs, due to several factors like fatigue, eye-strain and personal circumstances of the technicians. Hence, automated rice seed variety identification becomes a crucial task for ensuring the quality and germination potential of rice crops. This research is focused on the application of Deep Neural Network (RiceSeedNet) combined with traditional image processing techniques to classify local rice seed varieties of southern Tamilnadu, India. The RiceSeed Image corpus is created for this purpose considering 13 local varieties. The captured RGB images of rice seed data consists of 13,000 images of local rice seed varieties, having 1000 images for each variety. To automate the rice seed varietal identification, vision transformer-based architecture RiceSeedNet is developed. The proposed RiceSeedNet is 97% accurate in classifying the 13 local varieties of rice seeds. The RiceSeedNet was also evaluated on a publicly available rice grain data set to study the performance of the proposed model across the different rice grain varieties. On this cross-data validation, RiceSeedNet is able to achieve 99% accuracy in classifying 8 varieties of rice grains on the public dataset.

Objectives Inappropriate antibiotic prescribing is a major cause of antimicrobial resistance (AMR). The aim of this study was to explore paediatric general practitioners’ (GP Peds) antibiotic prescription practice in suspected respiratory tract infections (RTIs), using the capability–opportunity–motivation–behaviour framework.Design The design is a qualitative study based on individual, semistructured telephone or virtual interviews.Setting Paediatric general practice in Hungary. We applied stratified maximum variation sampling to cover the categories of age, sex and geographical location of participants.Participants We interviewed 22 GP Peds. Nine were male and 13 were female: 2 of them were less than 40 years old, 14 were between 40 and 60 years, and 6 were above 60 years. 10 worked in low-antibiotic prescription areas, 5 in areas with medium levels of antibiotic prescription, 3 in high-antibiotic prescription areas, and 4 in and around the capital city.Results Study participants had varying antibiotic prescription preferences. Personal experience and physical examination play a central role in GP Peds’ diagnostic and treatment practice. Participants emphasised the need to treat children in their entirety, taking their personal medical record, social background and sometimes parents’ preferences into account, besides the acute clinical manifestation of RTI. Most respondents were confident they apply the most effective therapy even if, in some cases, this meant prescribing medicines with a higher chance of contributing to the development of AMR. Some participants felt antibiotic prescription frequency has decreased in recent years.Conclusions Our findings suggest that a more prudent attitude toward antibiotic prescribing may have become more common but also highlight relevant gaps in both physicians’ and public knowledge of antibiotics and AMR. To reinforce awareness and close remaining gaps, Hungary should adopt its national AMR National Action Plan and further increase its efforts towards active professional communication and feedback for primary care physicians.

Background The extent and consequences of ischemia in patients with chronic limb‐threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis‐to‐limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI. Methods and Results In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk‐adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time 30 days, each additional 10‐day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014–1.036]). There was no association between D2L time and all‐cause death. Conclusions A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.

Purpose: To evaluate the surgical outcome of porous polyethylene orbital implants in anophthalmic sockets with implant migration. Methods: A prospective interventional case series: Patients of anophthalmic sockets with implant migration were recruited, which were replaced with porous polyethylene implants. Patients were evaluated for recurrence of implant migration, ability to wear artificial eye, movement of prosthesis, complications, and satisfaction. Results: Fifteen patients with a mean age of 8.33 years were operated for implant migration. Postoperatively, recurrence of implant migration was seen in one patient. Fourteen patients were able to wear the artificial eye. The overall mean prosthetic motility at 6 months of follow-up was 26% of the contralateral eye. Enophthalmos (>2 mm) and pseudoptosis (>2 mm) were present in 2 patients each. Satisfaction was good in 10 patients and fair in 5 patients. Conclusion: The recurrence of implant migration was almost nil with the use of porous polyethylene orbital implant in a follow-up of 6 months. A majority (93%) of the patients could wear the artificial eye with good satisfaction.

Preserving human health is of utmost importance, and unrestricted availability of medications is essential for overall wellness. Pharmaceuticals, which consist of a wide range of therapeutic substances utilized to diagnose, treat, and improve various diseases and conditions, play a crucial part in healthcare. However, the drug research and development process is widely recognized for its lengthy duration, demanding nature, and substantial expenses. To enhance the effectiveness of this complex process, interdisciplinary groups have converged, giving rise to the field known as “Bioinformatics”. The emergence and future advancements of Quantum Computing (QC) technologies have the potential to significantly enhance and accelerate the complex process of drug discovery and development. This paper explores various disciplines, such as Computer-Aided Drug Design (CADD), quantum simulations, quantum chemistry, and clinical trials, that stand to gain significant advantages from the rapidly advancing field of quantum technology. This study explores a range of fundamental quantum principles, intending to facilitate a thorough understanding of this revolutionary technology.

Cloud computing offers dynamic, scalable, and virtualized computing resources to end users over the internet. Load balancing is crucial for efficient resource use, distributing workloads across multiple resources to prevent overloading. Load balancing is crucial for resource utilization and processing time reduction, but traditional algorithms are often stuck at local maxima, leading to unequal allocation and performance decline. A metaheuristic based algorithm is proposed to dynamically adjust load distribution, ensuring resilience and sensitivity to changing workloads while managing energy consumption. This research presents a Rock Hyrax-based load balancing algorithm that addresses local maxima and power efficiency issues using QoS parameters. The algorithm’s performance is evaluated qualitatively and statistically, considering both static and dynamic modes of jobs and virtual machines. Comparing it with existing scheduling algorithms, the algorithm reduces makespan by 10%–15% and total energy consumption in data centers by 8%–13%. These results demonstrate the effectiveness of the Rock Hyrax-based load balancing algorithm in improving performance and energy efficiency in data centers, highlighting its potential impact on optimizing resource allocation and enhancing overall system performance.

Objective: This study used spectrophotometry to examine how staining beverages affect the color stability of three commercial composite materials (nanohybrid composite (A), bulk fill composite (B), and flowable composite (C)) over time. Materials and Methods: Composite discs were randomly divided into groups. The specimens were kept in coffee, tea, red wine, and cola for 14 days at 37°C in the dark. At baseline, 7 days, and 14 days, spectrophotometers measured color. Calculated and analyzed color differences (E). Results: Staining beverages changed the color of all composites. Composite material A had the best color stability, whereas material C stained beverages the most. Red wine and coffee discolored composites most. Discoloration increased over the 14-day immersion period. Conclusion: Composite materials with better color stability were material A. Red wine and coffee discolored composites most. When choosing restorative materials, dentists should consider composite materials' color stability for long-lasting, visually acceptable results.

Introduction: Overall wellness depends on oral health. Epidemiological, clinical, and laboratory studies have linked periodontitis to some systemic diseases. Pregnancy labor, contractions, and delivery are controlled by prostaglandin (PGE 2) levels rise during pregnancy, and labor begins when a critical threshold is reached. These associations support the underlying cause of maternal periodontal disease. Materials and Methods: In the study, 3,885 pregnant women aged 18–40 had singleton babies. All mother participants were clinically evaluated by the primary investigator. The periodontal disease is defined using a few parameters. Based on that the prevalence rate will be evaluated. Result: The prevalence of preterm babies' mothers affected with periodontitis was 0.5% and low-birth weight babies' mothers affected with periodontitis was 1.6%. So, there was a significant result is there. Conclusion: Periodontal health and preterm LBW newborns are highly associated with periodontitis in research. It may modify preterm birth and LBW risk factors. Thus, dentists detect and treat this sickness early, preventing pregnancy difficulties in sensitive mothers.

Background: Sepsis is a severe and life-threatening condition triggered by a dysregulated response to infection, leading to organ failure and, often, death. The syndrome is expensive to treat, with survivors frequently experiencing reduced quality of life and enduring various long-term disabilities. The increasing understanding of RNA, RNA biology, and therapeutic potential offers an unprecedented opportunity to develop innovative therapy. Objective: This study is a scoping review focusing on pre-clinical studies of microRNA (miRNA)-based therapies for sepsis. Methodology: A scoping review. The search strategy identified papers published in PubMed until 15 October 2023, using the keywords (microRNA) AND (sepsis) AND (animal model). Inclusion criteria included papers that used either gain- or loss-of-function approaches, excluding papers that did not focus on microRNAs as therapy targets, did not include animal models, did not show organ failure-specific assessments, and focused on microRNAs as biomarkers. The PRISMA-ScR guideline was used in this study. Results: A total of 199 articles were identified that featured the terms “microRNA/miRNA/miR”, “Sepsis”, and “animal model”. Of these, 51 articles (25.6%) employed miRNA-based therapeutic interventions in animal models of sepsis. Of these, 15 studies extended their inquiry to include or reference human clinical data. Key microRNAs of interest and their putative mechanisms of action in sepsis are highlighted. Conclusions: The body of work examined herein predominantly addresses various dimensions of sepsis-induced organ dysfunction, supporting the emerging role of miRNAs as potential therapeutic candidates. However, nearly 5% of papers on miR-based therapy have been retracted over the past 5 years, raising important concerns regarding the quality and complexity of the biology and models for assessing therapeutic potential.

Selective laser trabeculoplasty (SLT) has experienced a resurgence in interest, primarily driven by promising findings from the Laser in Glaucoma and Ocular Hypertension Trial. By offering SLT as an initial drug-free treatment option, we may be able to thwart issues such as adherence and persistence that plague our current medical management protocols. In this comprehensive narrative review, we delve into the current body of literature that explores the utility of SLT across a wide spectrum of scenarios and glaucoma subtypes. We present evidence that provides valuable insight into the efficacy and benefits of SLT, positioning it as a viable option in the management of glaucoma. Careful consideration of the associated risks and challenges is also necessary for successful adoption into clinical practice. Despite the ample evidence supporting SLT's efficacy, some questions remain regarding its long-term effects and the potential need for retreatment. This review aims to shed light on these aspects to guide clinicians in making informed decisions and tailoring treatment plans to individual patient needs. This review also provides the readers with a bird's eye view of the potential impact of SLT and adds clarity to the various therapeutic protocols that one can follow to ensure optimal clinical outcomes for our patients.

Purpose: To quantifiably assess the diagnostic accuracy of Adven-I, a proprietary artificial intelligence (AI)-driven diagnostic system that automatically detects diseases from fundus images. The purpose is to quantify the performance of Adven-i in differentiating a nonreferable (within normal limits) image from a referable (diseased fundus) image and further segregating diabetic retinopathy (DR) from the rest of the abnormalities (non-DR) encompassing the wide spectrum of abnormal pathologies. The assessment is carried out in comparison to manual reading as the reference gold standard. Adven-i is the only AI system classifying retinal abnormalities into DR and non-DR classes separately, apart from predicting nonreferable fundus, while most existing systems classify fundus images into referable and nonreferable DR. Methods: The double-blinded study was conducted on retrospective data collected over the course of a year in the ophthalmology outpatient department (OPD) at a top Tier II eyecare hospital in Chandigarh, India. Three vitreoretina specialists who were blinded to one another read the images. The ground-truth was generated on the basis of majority agreement among the readers. An arbitrator's decision was regarded final if all three readers disagreed. Results: 2261 fundus images were analyzed by Adven-i. The sensitivity and specificity of Adven-i in diagnosing images with abnormalities were 95.12% and 85.77%, respectively, and for segregating DR from rest of the retinal abnormalities were 91.87% and 85.12%, respectively. Conclusions and Relevance: Adven-i shows definite promise in automated screening for early diagnosis of referable fundus images including DR. Adven-i can be adopted to scale for mass screening in resource-limited settings.

Abstract Introduction Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients’ health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3. Methods This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea within 8 weeks post-treatment) was analyzed adjusting for baseline patient characteristics. HRQL was measured using the Clostridioides difficile Quality of Life Survey (Cdiff32); absolute scores and change from baseline in total and domain (physical, mental, and social) scores were summarized and compared between arms. Analyses were conducted for the trial’s blinded phase only. Results Among 86 eligible patients (32.8% of the overall trial population, RBL 53 [61.6%], placebo 33 [38.4%]), RBL-treated patients had significantly lower odds of recurrence (i.e., greater probability of treatment success) at week 8 vs. placebo (odds ratio 0.35 [95% confidence interval 0.13, 0.98]). Probability of treatment success at week 8 was 81% for RBL and 60% for placebo, representing 21% absolute and 35% relative increases for RBL (crude proportions 79.2% vs. 60.6%; relative risk 0.53, p = 0.06). Additionally, RBL was associated with significantly higher Cdiff32 total (change score difference 13.5 [standard deviation 5.7], p

Abstract Background: Suicide is the second leading cause of death for adolescents in the United States. However, relatively little is known about the forms of atypical neuro-cognitive function that are correlates of suicidal ideation (SI). One form of cognitive/affective function that, when dysfunctional, is associated with SI is emotion regulation. However, very little work has investigated the neural correlates of emotion dysregulation in adolescents with SI. Methods: Participants (N = 111 aged 12-18, 32 females, 31 [27.9%] reporting SI) were recruited shortly after their arrival at a residential care facility where they had been referred for behavioral and mental health problems. Daily reports of SI were collected during the participants’ first 90-days in residential care. Participants were presented with a task-fMRI measure of emotion regulation – the Affective Number Stroop task shortly after recruitment. Participants were divided into two groups matched for age, sex and IQ based on whether they demonstrated SI. Results: Participants who demonstrated SI showed increased recruitment of regions including dorsomedial prefrontal cortex/supplemental motor area and parietal cortex during task (congruent and incongruent) relative to view trials in the context of emotional relative to neutral distracters. Conclusions: Participants with SI showed increased recruitment of regions implicated in executive control during the performance of a task indexing automatic emotion regulation. Such data might suggest a relative inefficiency in the recruitment of these regions in individuals with SI.

The introduction of pre-trained large language models (LLMs) has transformed NLP by fine-tuning task-specific datasets, enabling notable advancements in news classification, language translation, and sentiment analysis. This has revolutionized the field, driving remarkable breakthroughs and progress. However, the growing recognition of bias in textual data has emerged as a critical focus in the NLP community, revealing the inherent limitations of models trained on specific datasets. LLMs exploit these dataset biases and artifacts as expedient shortcuts for prediction. The reliance of LLMs on dataset bias and artifacts as shortcuts for prediction has hindered their generalizability and adversarial robustness. Addressing this issue is crucial to enhance the reliability and resilience of LLMs in various contexts. This survey provides a comprehensive overview of the rapidly growing body of research on shortcut learning in language models, classifying the research into four main areas: the factors of shortcut learning, the origin of bias, the detection methods of dataset biases, and understanding mitigation strategies to address data biases. The goal of this study is to offer a contextualized, in-depth look at the state of learning models, highlighting the major areas of attention and suggesting possible directions for further research.

The medical field is witnessing rapid adoption of artificial intelligence (AI) and machine learning (ML), revolutionizing disease diagnosis and treatment management. Researchers explore how AI and ML can optimize medical decision-making, promising to transform healthcare. Feed Forward Neural Networks (FNN) are widely used to create predictive disease models, cross-validated by medical experts. However, complex medical data like diabetes leads to multi-modal search spaces prone to local minima, affecting optimal solutions. In this study, we focus on optimizing a diabetes dataset from the Pima Indian community, evaluating decision-making performance in diabetes management. Employing multimodal datasets, we compare various optimization algorithms, including the Whale Optimization Algorithm (WOA) and Particle Swarm Optimization (PSO). The test results encompass essential metrics like best-fit value, mean, median, and standard deviation to assess the impact of different optimization techniques. The findings highlight the superiority of the Oppositional Whale Optimization Algorithm (OWOA) over other methods employed in our research setup. This study demonstrates the immense potential of AI and metaheuristic algorithms to revolutionize medical diagnosis and treatment approaches, paving the way for future advancements in the healthcare landscape. Results reveal the superiority of OWOA over other methods. AI and metaheuristics show tremendous potential in transforming medical diagnosis and treatment, driving future healthcare advancements.

Abstract Background The pro-inflammatory ATP-gated P2X7 receptor is widely expressed by immune and non-immune cells. Nanobodies targeting P2X7, with potentiating or antagonistic effects, have been developed. Adeno-associated virus (AAV)-mediated gene transfer represents an efficient approach to achieve long-term in vivo expression of selected nanobody-based biologics. This approach (AAVnano) was used to validate the relevance of P2X7 as a target in dextran sodium sulfate (DSS)-induced colitis in mice. Results Mice received an intramuscular injection of AAV vectors coding for potentiating (14D5-dimHLE) or antagonistic (13A7-Fc) nanobody-based biologics targeting P2X7. Long-term modulation of P2X7 activity was evaluated ex vivo from blood samples. Colitis was induced with DSS in mice injected with AAV vectors coding for nanobody-based biologics. Severity of colitis, colon histopathology and expression of chemokines and cytokines were determined to evaluate the impact of P2X7 modulation. A single injection of an AAV vector coding for 13A7-Fc or 14D5-dimHLE efficiently modulated P2X7 function in vivo from day 15 up to day 120 post-injection in a dose-dependent manner. An AAV vector coding for 13A7-Fc significantly ameliorated DSS-induced colitis and significantly reduced immune cell infiltration and expression of chemokines and proinflammatory cytokines in colonic tissue. Conclusions We have demonstrated the validity of AAVnano methodology to modulate P2X7 functions in vivo. Applying this methodological approach to a DSS-induced colitis model, we have shown that P2X7 blockade reduces inflammation and disease severity. Hence, this study confirms the importance of P2X7 as a pharmacological target and suggests the use of nanobody-based biologics as potential therapeutics in inflammatory bowel disease. Graphical Abstract

The exponential proliferation of wearable medical apparatus and healthcare information within the framework of the Internet of Medical Things (IoMT) introduces supplementary complexities pertaining to the elevated Quality of Service (QoS) of intelligent healthcare in the forthcoming 6G era. Healthcare services and applications need ultra-reliable data transfer and processing with ultra-low latency and energy usage. Wireless Body Area Network (WBAN) and Mobile Edge Computing (MEC) technologies enabled IoMT to handle large amounts of data sensing, transmission, and processing while maintaining good QoS. Traditional frame aggregation (FA) systems in WBAN, on the other hand, create an excessive number of control frames during data transmission, resulting in significant latency and energy consumption, as well as a lack of flexibility. A Federated Reinforcement Learning (FRL) based TO Approach is recommended in this research. In the beginning, different types of service-related information were separated into queues with equal QoS needs. The duration of the FA was then automatically determined by the aggregation vertex based on energy consumption, latency, and throughput using FRL. Finally, based on the existing status, the amount of tasks offloaded was determined. The simulation results demonstrate that, as compared to the baseline schemes, the suggested FRLTO efficiently reduces energy consumption and latency while enhancing throughput and total WBAN utilization. Numerical results show that the proposed scheme improves the throughput by 37.06% and reduced the energy consumption by around 69.84% and time delay by about 6.23%, as compared to the state-of-the-art existing baseline schemes.