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Abstract Adaptation in cone photoreceptors allows our visual system to effectively operate over an enormous range of light intensities. However, little is known about the properties of cone adaptation in the specialized region of the primate central retina called the fovea, which is densely packed with cones and mediates high-acuity central vision. Here we show that macaque foveal cones exhibit weaker and slower luminance adaptation compared to cones in the peripheral retina. We find that this difference in adaptive properties between foveal and peripheral cones is due to differences in the magnitude of a hyperpolarization-activated current, I h. This I h current regulates the strength and time course of luminance adaptation in peripheral cones where it is more prominent than in foveal cones. A weaker and slower adaptation in foveal cones helps maintain a higher sensitivity for a longer duration which may be well-suited for maximizing the collection of high-acuity information at the fovea during gaze fixation between rapid eye movements.

Abstract Intracranial pressure (ICP) is a physiological parameter that conventionally requires invasive monitoring for accurate measurement. Utilising multivariate predictive models, we sought to evaluate the utility of non-invasive, widely accessible MRI biomarkers in predicting ICP and their reversibility following cerebrospinal fluid (CSF) diversion. The retrospective study included 325 adult patients with suspected CSF dynamic disorders who underwent brain MRI scans within three months of elective 24-h ICP monitoring. Five MRI biomarkers were assessed: Yuh sella grade, optic nerve vertical tortuosity (VT), optic nerve sheath distension, posterior globe flattening and optic disc protrusion (ODP). The association between individual biomarkers and 24-h ICP was examined and reversibility of each following CSF diversion was assessed. Multivariate models incorporating these radiological biomarkers were utilised to predict 24-h median intracranial pressure. All five biomarkers were significantly associated with median 24-h ICP (p

Abstract Cardio‐ankle vascular index (CAVI) is an innovative indicator of large‐artery stiffness, which is evaluated by the pulse wave velocity (PWV) measurement. Mortality and morbidity due to cardiovascular diseases among the general public with high‐risk conditions such as hypertension are usually associated with arterial stiffness. CAVI modelizes the hazard of future cardiovascular events with standard risk factors. Additionally, the “European Society of Hypertension and Cardiology” included the aortic PWV assessment in managing hypertension in their updated guidelines in 2007. We conducted this systematic review to collect, summarize, and evaluate the evidence from relevant reported studies. A literature search of four databases was conducted comprehensively until February 2024. Cardiovascular events are the primary outcome of interest in this study, cardiovascular events that have been defined as major adverse cardiac events include “heart failure”, “stroke”, “myocardial infarction”, “cardiovascular deaths”, “stable angina pectoris”, “coronary revascularization”, and “unstable angina pectoris”. We included five studies with a 11 698 sample size in this systematic review. All five prospective studies investigated composite cardiovascular events as an outcome. Three of them revealed a statistically significant prediction ability of CAVI to assess Cardiovascular disease (CVD) risk. Further analysis is required. Current evidence is insufficient to confirm the predictive power of CAVI in the assessment of cardiovascular risk in hypertensive patients. CAVI is modestly associated with incidents of CVD risk. It is necessary to conduct further studies to assess CAVI concerning CVD predictor measures in the masses and nations other than Asia.

The purpose of the article is to provide a practical guide for manual and semi-automated image segmentation of common neurosurgical cranial lesions, namely meningioma, glioblastoma multiforme (GBM) and subarachnoid haemorrhage (SAH), for neurosurgical trainees and researchers. Materials and Methods: The medical images used were sourced from the Medical Image Computing and Computer Assisted Interventions Society (MICCAI) Multimodal Brain Tumour Segmentation Challenge (BRATS) image database and from the local Picture Archival and Communication System (PACS) record with consent. Image pre-processing was carried out using MRIcron software (v1.0.20190902). ITK-SNAP (v3.8.0) was used in this guideline due to its availability and powerful built-in segmentation tools, although others (Seg3D, Freesurfer and 3D Slicer) are available. Quality control was achieved by employing expert segmenters to review. Results: A pipeline was developed to demonstrate the pre-processing and manual and semi-automated segmentation of patient images for each cranial lesion, accompanied by image guidance and video recordings. Three sample segmentations were generated to illustrate potential challenges. Advice and solutions were provided within both text and video. Conclusions: Semi-automated segmentation methods enhance efficiency, increase reproducibility, and are suitable to be incorporated into future clinical practise. However, manual segmentation remains a highly effective technique in specific circumstances and provides initial training sets for the development of more advanced semi- and fully automated segmentation algorithms.

Abstract Phase Ib trials are common in oncology development but often are not powered for statistical significance. Go/no‐go decisions are largely driven by observed trends in response data. We applied a bootstrapping method to systematically compare tumor dynamic end points to historical control data to identify drugs with clinically meaningful efficacy. A proprietary mathematical model calibrated to phase Ib anti–PD‐1 therapy trial data (KEYNOTE‐001) was used to simulate thousands of phase Ib trials (n = 30) with a combination of anti–PD‐1 therapy and four novel agents with varying efficacy. A redacted bootstrapping method compared these results to a simulated phase III control arm (N = 511) while adjusting for differences in trial duration and cohort size to determine the probability that the novel agent provides clinically meaningful efficacy. Receiver operating characteristic (ROC) analysis showed strong ability to separate drugs with modest (area under ROC [AUROC] = 83%), moderate (AUROC = 96%), and considerable efficacy (AUROC = 99%) from placebo in early‐phase trials (n = 30). The method was shown to effectively move drugs with a range of efficacy through an in silico pipeline with an overall success rate of 93% and false‐positive rate of 7.5% from phase I to phase III. This model allows for effective comparisons of tumor dynamics from early clinical trials with more mature historical control data and provides a framework to predict drug efficacy in early‐phase trials. We suggest this method should be employed to improve decision making in early oncology trials.

Abstract Background Governments worldwide are facing growing pressure to increase transparency, as citizens demand greater insight into decision-making processes and public spending. An example is the release of open healthcare data to researchers, as healthcare is one of the top economic sectors. Significant information systems development and computational experimentation are required to extract meaning and value from these datasets. We use a large open health dataset provided by the New York State Statewide Planning and Research Cooperative System (SPARCS) containing 2.3 million de-identified patient records. One of the fields in these records is a patient’s length of stay (LoS) in a hospital, which is crucial in estimating healthcare costs and planning hospital capacity for future needs. Hence it would be very beneficial for hospitals to be able to predict the LoS early. The area of machine learning offers a potential solution, which is the focus of the current paper. Methods We investigated multiple machine learning techniques including feature engineering, regression, and classification trees to predict the length of stay (LoS) of all the hospital procedures currently available in the dataset. Whereas many researchers focus on LoS prediction for a specific disease, a unique feature of our model is its ability to simultaneously handle 285 diagnosis codes from the Clinical Classification System (CCS). We focused on the interpretability and explainability of input features and the resulting models. We developed separate models for newborns and non-newborns. Results The study yields promising results, demonstrating the effectiveness of machine learning in predicting LoS. The best R2 scores achieved are noteworthy: 0.82 for newborns using linear regression and 0.43 for non-newborns using catboost regression. Focusing on cardiovascular disease refines the predictive capability, achieving an improved R2 score of 0.62. The models not only demonstrate high performance but also provide understandable insights. For instance, birth-weight is employed for predicting LoS in newborns, while diagnostic-related group classification proves valuable for non-newborns. Conclusion Our study showcases the practical utility of machine learning models in predicting LoS during patient admittance. The emphasis on interpretability ensures that the models can be easily comprehended and replicated by other researchers. Healthcare stakeholders, including providers, administrators, and patients, stand to benefit significantly. The findings offer valuable insights for cost estimation and capacity planning, contributing to the overall enhancement of healthcare management and delivery.

Abstract Herpes zoster (HZ) is caused by reactivation of latent infection of varicella zoster virus (VZV) in sensory (cranial, dorsal root) ganglia. Major risk factors for HZ are increasing age and immunosuppression. HZ ophthalmicus (HZO) is a subset of HZ with involvement of the ophthalmic division of the fifth cranial trigeminal nerve. Approximately 4–20% of patients with HZ develop HZO. Approximately 50% of patients with HZO develop ocular disease, among whom up to 25% develop chronic or recurrent disease. Common manifestations of ocular disease include conjunctivitis, keratitis, and uveitis, whereas optic neuropathy and retinitis are uncommon. Due to the potential for vision impairment, ocular involvement requires urgent ophthalmic consultation. Early recognition and timely treatment with antivirals may prevent ocular complications. HZO is preventable by vaccination against HZ. Vaccine efficacy/effectiveness studies have been largely conducted for HZ with few studies assessing HZO. Both the recombinant adjuvanted vaccine (RZV) and live-attenuated vaccine (ZVL) significantly reduce the incidence of HZ and HZO in older adults. RZV is more effective than ZVL. Data on the effectiveness of vaccines for prevention of recurrent disease in patients with HZO are limited; however, vaccination is recommended. Despite recommendations to vaccinate individuals likely to benefit from an HZ vaccine, coverage for adults remains suboptimal. Barriers to vaccination include patient beliefs about HZ or HZ vaccines, and factors related to healthcare providers. In particular, the lack of a recommendation from their primary care physician is often cited by patients as a reason for remaining unvaccinated. By encouraging vaccination against HZ, physicians not only prevent HZ and HZO but also potential vision loss due to HZO. Graphical abstract available for this article.

Computation in neural circuits relies on the judicious use of nonlinear circuit components. In many cases, multiple nonlinear components work collectively to control circuit outputs. Separating the contributions of these different components is difficult, and this limits our understanding of the mechanistic basis of many important computations. Here, we introduce a tool that permits the design of light stimuli that predictably alter rod and cone phototransduction currents – including stimuli that compensate for nonlinear properties such as light adaptation. This tool, based on well-established models for the rod and cone phototransduction cascade, permits the separation of nonlinearities in phototransduction from those in downstream circuits. This will allow, for example, direct tests of how adaptation in rod and cone phototransduction affects downstream visual signals and perception.

Background: The clinical characteristics and outcomes of patients who develop cardiogenic shock (CS) secondary to primary valvular dysfunction (valvular cardiogenic shock [VCS]) remain unclear. Objectives: The purpose of this study was to describe the cohort of patients with VCS and understand their outcomes compared to other forms of CS. Methods: All patients admitted to Cleveland Clinic cardiac intensive care unit between January 1, 2010, and December 31, 2021, with a diagnosis of CS were retrospectively identified. Characteristics and outcomes for shock patients with VCS were compared to those without VCS. Results: A total of 2,754 patients were admitted to our cardiac intensive care unit with CS, of which 442 (16%) had VCS. The median age of patients with VCS was higher than those with non-VCS (70 years vs 64 years, P

Abstract Background Lignin and xylan are important determinants of cell wall structure and lignocellulosic biomass digestibility. Genetic manipulations that individually modify either lignin or xylan structure improve polysaccharide digestibility. However, the effects of their simultaneous modifications have not been explored in a similar context. Here, both individual and combinatorial modification in xylan and lignin was studied by analysing the effect on plant cell wall properties, biotic stress responses and integrity sensing. Results Arabidopsis plant co-harbouring mutation in FERULATE 5-HYDROXYLASE (F5H) and overexpressing Aspergillus niger acetyl xylan esterase (35S:AnAXE1) were generated and displayed normal growth attributes with intact xylem architecture. This fah1-2/35S:AnAXE1 cross was named as hyper G lignin and hypoacetylated (HrGHypAc) line. The HrGHypAc plants showed increased crystalline cellulose content with enhanced digestibility after chemical and enzymatic pre-treatment. Moreover, both parents and HrGHypAc without and after pre-treating with glucuronyl esterase and alpha glucuronidase exhibited an increase in xylose release after xylanase digestion as compared to wild type. The de-pectinated fraction in HrGHypAc displayed elevated levels of xylan and cellulose. Furthermore, the transcriptomic analysis revealed differential expression in cell wall biosynthetic, transcription factors and wall-associated kinases genes implying the role of lignin and xylan modification on cellular regulatory processes. Conclusions Simultaneous modification in xylan and lignin enhances cellulose content with improved saccharification efficiency. These modifications loosen cell wall complexity and hence resulted in enhanced xylose and xylobiose release with or without pretreatment after xylanase digestion in both parent and HrGHypAc. This study also revealed that the disruption of xylan and lignin structure is possible without compromising either growth and development or defense responses against Pseudomonas syringae infection.

Abstract Background Violence against women (VAW) is a significant public health problem. With the emergence of the COVID-19 pandemic, the frequency and severity of VAW has escalated globally. Approximately one in four women in Nepal have been exposed to either physical, psychological, and/or sexual violence in their lifetime, with husbands or male partners being the perpetrators in most cases. VAW prevention has been under-researched in low- and middle-income countries, including Nepal. This study aims to explore the perspectives of local stakeholders, including healthcare providers and survivors of violence in Madhesh Province. The overarching goal is to provide insights for designing prevention and support programs that are acceptable to communities and cater to the needs of survivors. Methods An explorative qualitative study was conducted in Madhesh Province, southern Nepal. A total of 21 interviews, including 15 in-depth interviews (IDIs) with health care providers, three IDIs with women seeking general or maternal and child health services at health care centres, three key informant interviews with the local stakeholders working in the field of VAW, and one focus group discussion with violence survivors, were conducted in Nepali by trained field interviewers. Interviews were recorded, transcribed, translated into English, and analysed using content analysis. Results VAW, particularly physical violence, was a common experience in the study area. Sociocultural traditions such as dowry, child marriages and son preference were identifiable triggers for VAW, causing significant physical injuries and mental health problems, including suicide. Health care providers reported that violence survivors often hide their experiences of violence and do not seek any kind of help. Women feared that violence would increase in frequency and intensity if their perpetrators found out that they had disclosed their experiences of violence to health care providers. Local stakeholders emphasized the importance of engaging community leaders and garnering support from both women and men in interventions designed to reduce VAW and its impacts on mental health. Conclusions Participants reported that verbal and physical violence is often perceived as a normal part of women’s lives. Women should be made aware of available support services and empowered and supported to increase access and uptake of these services. Additionally, more individual-based counselling sessions that encourage women to escape violence and its mental health consequences while maintaining privacy and confidentiality are recommended.

Abstract Coronavirus disease 2019 (COVID-19) has had a broad impact on health services and health outcomes. During the pandemic, there were numerous reports of herpes zoster (HZ) in people with COVID-19 and in COVID-19 vaccine recipients. The aim of this review is to elucidate the global effects of the COVID-19 pandemic on HZ. It is postulated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces an immunosuppressive state that favours varicella zoster virus (VZV) reactivation. Three large cohort studies (a multinational study and studies from the USA and Spain) that excluded individuals vaccinated against HZ reported significantly increased risk of HZ following COVID-19 infection, especially in people aged ≥ 50 years. In contrast, a large study from Israel that did not consider HZ vaccination status reported no such increase. Cases of HZ following COVID-19 vaccination have been reported and may be the result of attenuated cell-mediated immunity. This phenomenon appears to vary by vaccine type. Some (but not all) large analyses have reported a significant positive relationship between receipt of mRNA vaccines for COVID-19 and development of HZ. These include analyses of health records databases in Israel and Hong Kong and of spontaneous case reports in the US Vaccine Adverse Event Reporting System (VAERS) database. Routine vaccinations, including shingles vaccine programmes, were disrupted by the COVID-19 pandemic. It is estimated that missed shingles vaccinations may have resulted in 63,117 avoidable HZ cases in the USA. Now that the World Health Organization has declared an end to the COVID-19 pandemic as a health emergency and routine vaccination services have resumed, there is a need to increase awareness of HZ and HZ vaccination. Graphical abstract available for this article. Graphical Abstract

ABSTRACTHerpes zoster (HZ) is a painful rash which typically affects older adults. This is of concern in Asia-Pacific given its aging population. As HZ epidemiology and burden are evolving, this systematic literature review aimed to update the current understanding of HZ burden and associated costs for selected Asia-Pacific locales. MEDLINE and Embase were searched for English articles of HZ studies conducted in Australia, China, Hong Kong, Japan, Korea, New Zealand, Singapore, and Taiwan. Eligible outcomes included HZ incidence and prevalence, occurrence of HZ-related complications, healthcare resource utilization, costs, and HZ-associated quality of life outcomes. This paper focused on HZ data in the general adult population (N = 90 articles). Substantial HZ-related disease and economic burden were observed in these locales, consistent with global trends. These findings reinforce the increasing burden of HZ and need for preventive strategies, which may include raising awareness and encouraging timely vaccination.

ABSTRACTHerpes zoster (HZ) is a prevalent disease characterized by a painful rash. A multi‑country study was conducted to elicit public and physician knowledge, attitude, and practice (KAP) toward HZ disease and vaccination for the assessment of local factors influencing HZ vaccine perceptions in four Asian-Pacific countries/territories One-to-one qualitative interviews were conducted in 2022, among the public (people aged ≥ 50 years, adults with parents aged ≥ 50 years, zoster vaccine live-vaccinated individuals aged ≥ 50 years in Republic of Korea, and HZ patients; n = 78) and physicians (general practitioners and specialists; n = 24). Themes surrounding KAP toward HZ and HZ vaccination were summarized using a thematic analysis. A substantial knowledge gap related to HZ was observed among the public, including its causes, long-term impacts, and the at-risk population. There was a low perceived risk of HZ and low general awareness of HZ vaccine availability, although country/territory-specific differences existed. Fear of HZ-associated pain contributed toward vaccination intent among HZ patients and adults with parents aged ≥ 50 years. HZ-naïve adults who were encouraged to receive the vaccine by others were not motivated to do so due to optimism bias. Physicians were perceived to be a reliable source of information. However, physicians did not always proactively discuss HZ vaccination due to time constraints and a perceived need to prioritize other vaccinations including influenza and pneumococcal vaccines. Initiatives are needed to improve public awareness of HZ and its complications, in terms of overall impact on individuals and society, and highlight the important role of physicians in recommending vaccination.

Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative and anti-inflammatory properties such as diosgenin (DG) and emodin (ED) can be a therapeutic intervention targeting silica-induced pulmonary inflammation and fibrosis. Hydrophobicity and low bioavailability are the barriers that restrict the therapeutic efficacy of DG and ED against pulmonary defects. Encapsulating these APCs in polymeric nanoparticles can overcome this limitation. The present study has thus explored the anti-inflammatory and anti-fibrotic effects of polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) individually loaded with DG (DGn) or ED (EDn) and in combine DG+ED [(DG+ED)n] in respirable silica dust (RSD)-induced pulmonary fibrosis silicosis rat model. Our study found that individual and combined NPs revealed physiochemical characteristics appropriate for IV administration with sustained-drug release purposes. Physiological evaluations of RSD-induced silicosis rats suggested that no treatment could improve the body weight. Still, they reduced the lung coefficient by maintaining lung moisture. Only (DG+ED)n significantly cleared free lung silica. All interventions were found to attribute the increased per cent cell viability in BALF, reduce cytotoxicity via minimizing LDH levels, and balance the oxidant-antioxidant status in silicotic rats. The expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1, and TGF-β1) were efficiently down-regulated with NPs interventions compared to pure (DG+ED) treatment. All drug treatments significantly declined, the 8-HdG and HYP productions indicate that RSD-induced oxidative DNA damage and collagen deposition were successfully repaired. Moreover, histopathological investigations proposed that individual or combined drugs NPs interventions could decrease the fibrosis and alveolitis grades in RSD-induced silicosis rats. However, (DG+ED)n intervention significantly inhibited pulmonary fibrosis and alveolitis compared to pure (DG+ED) treatment. In conclusion, the RSD can induce oxidative stress and inflammation in rats, producing reactive oxygen species (ROS)-mediated cytotoxicity to pulmonary cells and leading to silicosis development. The IV administration of combined NP suppressed lung inflammation and collagen formation by maintaining oxidant-antioxidant status and effectively interrupting the fibrosis-silicosis progression. These results may be attributed to the improved bioavailability of DG and ED through their combined nano-encapsulation-mediated targeted drug delivery.

Background: The bacteria, Achromobacter are present ubiquitously in the moist environment. Infections due to Achromobacter have mostly been reported in immunocompromised patients. However, the microorganism has also been associated with nosocomial infections even in healthy subjects. Report: We report chronic osteomyelitis caused by Achromobacter denitrificans in a 44-year-old male with a history of femoral intramedullary nail in situ. The organism was confirmed by matrix assisted laser desorption ionization-time of flight mass spectrometry (MADI-TOF MS). Clinical management: The patient was managed with implant removal, surgical debridement and culture-directed antibiotic therapy that led to clinical cure. Conclusion: Identification of implant associated infection poses a serious challenge to surgeons and clinical microbiologists. Atypical pathogens must always be considered with a history of any implant in a case of chronic osteomyelitis.

Abstract Introduction Herpes zoster (HZ; shingles) is a painful, cutaneous disease caused by reactivation of the varicella zoster virus, which causes varicella (chickenpox) typically during childhood. The considerable healthcare burden of HZ is relatively well documented, with approximately one in three individuals experiencing at least one episode during their lifetime, debilitating symptoms including neuropathic pain, and complications such as post-herpetic neuralgia, vision loss, and rarely, stroke, and increased severity in immunocompromised individuals. However, we are not aware of a comprehensive review of literature specifically examining the burden of HZ recurrence. Methods We conducted a PubMed search (1 January 2003–2 February 2023) to assess available literature on the incidence, risk factors, and clinical features of HZ recurrence. Results The incidence of HZ recurrence reported by the studies identified was wide ranging. Studies in general populations of immunocompetent or immunocompetent/immunosuppressed (mixed) populations with an initial HZ episode estimate that approximately 1.2–9.6% of individuals may experience HZ recurrence, with an incidence rate of 1.7–16.6 cases per 1000 person-years. HZ recurrence was reported in 0.0–18.2% of immunocompromised individuals with HZ, with an incidence rate of 17.0–55 cases per 1000 person-years. Incidence rates varied according to study design, follow-up, and study populations. Recognized risk factors for HZ recurrence include immunocompromised status, female sex, family history, and comorbidities such as diabetes. Other factors that may predispose individuals to recurrence include long-lasting pain after the initial HZ episode and the presence of herpes zoster ophthalmicus. Discussion Our review underlines that following an initial HZ episode, individuals remain at risk of HZ recurrence, adding to the disease burden in a population. As HZ is preventable by vaccination, national HZ vaccination recommendations should include the need for and timing of vaccination in both immunocompetent and immunocompromised individuals who have a history of HZ.

Background The aims of this study were to understand the incidence and outcomes of patients with cardiogenic shock (CS) due to severe aortic stenosis (AS), and the impact of conventional treatment strategies in this population. Methods and Results All patients admitted to the Cleveland Clinic cardiac intensive care unit between January 1, 2010 and December 31, 2021 with CS were retrospectively identified and categorized into those with CS in the setting of severe AS versus CS without AS. The impact of various treatment strategies on mortality was further assessed. We identified 2754 patients with CS during the study period, of whom 216 patients (8%) had CS in the setting of severe AS. Medical management was associated with the highest 30‐day mortality when compared with either balloon aortic valve replacement or aortic valve replacement (surgical or transcatheter aortic valve replacement) (hazard ratio, 3.69 [95% CI, 2.04–6.66]; P

Abstract Background Huntington’s disease is one of the rare neurodegenerative diseases caused because of genetic mutation of the Huntingtin gene. The major hallmarks of the condition include motor impairment, cognitive decline, and psychiatric symptoms. With no cure and only symptomatic treatments available, early detection and personalized therapy are warranted for managing the disease effectively. Artificial Intelligence has emerged as a transformational tool in healthcare, revolutionizing many parts of medical practice and research, thus holding the potential in detecting, monitoring, and managing Huntington’s disease. Main body of abstract Artificial Intelligence’s role in Huntington’s disease includes a variety of applications like medical image analysis and predictive analytics. AI-driven algorithms are utilized to analyze brain imaging data in medical image analysis. Deep learning and convolutional neural networks (CNNs) aid in the detection of subtle brain changes and the identification of illness biomarkers, allowing for the early diagnosis of the disease. Additionally, the predictive analytics capabilities of AI are used to analyze disease development and forecast clinical outcomes. AI models can identify illness patterns, estimate the rate of functional decline, and assist doctors in making educated decisions about treatment methods and care planning by analyzing patient data. Conclusions With clinical practice and research integrated with Artificial Intelligence technologies, we can significantly improve the quality of life of individuals affected with Huntington’s disease. This integration holds the potential to develop effective personalized interventions. Nevertheless, collaborative efforts among doctors, researchers, and technology sound developers would be key to the successful implementation of AI in HD. Graphical Abstract

Abstract Across four studies, we examined the how design decisions influenced the effectiveness of fact-checking articles created by CrossCheck France during the 2017 French election. We measured both memory for the article and belief in the false rumor. We saw no difference in fact check efficacy based on the type of headline (question vs negation) or the number of newsroom logos present around the article (one, four, or seven). In addition, informative design features such as an icon identifying the type of misinformation were ignored by readers. Participants failed to remember many of the details from the article, but retrieval practice was beneficial in reducing forgetting over a 1-week delay. In both US and French samples, reading the fact check decreased belief in the false information, even 1 week later. However, the articles were much more effective in the US sample, who lacked relevant prior knowledge and political beliefs. Overall, fact-checking articles can be effective at reducing belief in false information, but readers tend to forget the details and ignore peripheral information.

Abstract The correct strategy of heat management in electric machines is extremely important due to their operating costs and length of operation. In this paper, the thermal management element strategies of the induction motors are developed to assure better endurance and boost efficiency. Additionally, an extensive review of the literature was carried out in terms of cooling methods for electrical machines. As the main result, the thermal analysis of an air-cooled and large-capacity induction motor is given, considering well-known heat distribution problems. Moreover, this study also presents an integrated approach with two or more cooling strategies to be the need of the hour. A model of a 100-kW air-cooled induction motor and an improved thermal management model of the same motor were both numerically investigated, using a combination of air cooling and integrated water cooling systems to achieve a significant improvement in motor efficiency. The integrated system comprising air- and water-cooled systems are investigated using SolidWorks 2017 and ANSYS Fluent version 2021. Three different flow rates of water 5 LPM, 10 LPM and 15 LPM are analyzed and compared with a conventional air-cooled induction motor, which was validated with the available published resources. Performed analyses indicate that for different flow rates of 5 LPM, 10 LPM and 15 LPM respectively, we have obtained a reduction of temperature accordingly of 2.94%, 4.79% and 7.69%. Hence, the results indicated that an integrated induction motor is efficient in bringing down the temperature compared to air cooled induction motor.

Abstract Fact-checkers want people to both read and remember their misinformation debunks. Retrieval practice is one way to increase memory, thus multiple-choice quizzes may be a useful tool for fact-checkers. We tested whether exposure to quizzes improved people’s accuracy ratings for fact-checked claims and their memory for specific information within a fact check. Across three experiments, 1551 US-based online participants viewed fact checks (either health- or politics-related) with or without a quiz. Overall, the fact checks were effective, and participants were more accurate in rating the claims after exposure. In addition, quizzes improved participants’ memory for the details of the fact checks, even 1 week later. However, that increased memory did not lead to more accurate beliefs. Participants’ accuracy ratings were similar in the quiz and no-quiz conditions. Multiple-choice quizzes can be a useful tool for increasing memory, but there is a disconnect between memory and belief.

Background Patients who experience in-hospital ST-segment elevation myocardial infarction (iSTEMI) represent a uniquely high-risk cohort owing to delays in diagnosis, prolonged time to reperfusion and increased mortality. Quality initiatives aimed at improving the care of this vulnerable, yet understudied population are needed.Methods This study included consecutive patients with iSTEMI treated with percutaneous coronary intervention (PCI) between 1 January 2011 and 15 July 2019 at a single, tertiary referral centre. A comprehensive iSTEMI protocol (CSP) was implemented on 15 July 2014, incorporating: (1) cardiology fellow activation of the catheterisation lab using standardised criteria, (2) nursing chest pain protocol, (3) improved electronic access to electrocardiographic studies, (4) checklist for initial triage and management, (5) 24/7/365 catheterisation lab readiness and (6) radial-first PCI approach. Key metrics and clinical outcomes were compared before and after CSP implementation.Results Among 125 total subjects, the post-CSP cohort (n=81) was younger, had more males and were more likely to be hospitalised for cardiac-related reasons relative to the pre-CSP cohort (n=44) who were more likely hospitalised for operative-related aetiologies. After CSP adoption, median ECG-to-first-device-activation time decreased from 113 min to 64 min (p

Serotonin syndrome is a toxidrome consisting of autonomic instability, altered mentation, hyperreflexia, clonus, and seizures. It is suspected to be due to either elevated serotonin concentrations or overstimulation of 5-hydroxytryptamine (5-HT) receptors. There are at least seven families of serotonin or 5-HT receptors along with multiple subtypes. The 5-HT1A and 5-HT2A serotonin receptor subtypes are heavily suspected to cause the broad spectrum of symptoms seen in serotonin syndrome. We present the case of a young woman treated with multiple psychotropic medications who developed serotonin syndrome (SS) after receiving electroconvulsive therapy (ECT). She had multiple psychiatric hospitalizations, and ECT was determined to be the appropriate course of treatment due to her treatment-resistant symptoms and catatonia. The case was unique as she tolerated multiple ECT treatments over a few weeks before the acute onset of serotonin syndrome following her eighth treatment, and she did not have any medication changes after the second ECT treatment. The patient’s acute presentation of rigidity, elevated temperature, hyperreflexia, diaphoresis, confusion, and psychomotor agitation led to a diagnosis of serotonin syndrome. ECT is a neuromodulatory procedure approved for treatment-resistant depression and schizophrenia that involves electrically stimulating the brain with electrodes on the scalp to induce a seizure. The mechanism by which ECT confers therapeutic benefit for patients with neuropsychiatric conditions is not entirely understood. We discuss some of the literature on SS and ECT to better understand the potential for a causal relationship.

Abstract Although numerous models of aerial‐robots/drones and planet landers have been demonstrated to fly autonomously in natural and manmade environments for far‐reaching scientific and technological change to help humankind, no drone flowed yet with a push‐pull dual‐head electromagnetic propulsion (EMP) system ensuring unrestricted flight endurance. The precept of EMP is eminent as it hastens an object using a flowing electrical current, either to charge a field or opposing a magnetic field for locomotive use. Here we present a proof of concept to demonstrate the capability of a newly invented variable speed propulsion and energy conversion system for uninterruptedly generating the reciprocating motion of a magnetic piston by a solar battery‐driven polarity changer timing circuit together with a laser‐based timing circuit for redundancy. The reciprocating crusade of the magnetic piston could be successfully converted into rotary motion to generate continuous power for various multidisciplinary applications on Earth and the other planets effectively in lieu of long‐lasting rechargeable batteries. The proposed concept can also be used for devising various systems and subsystems from underwater to outer space by using light weight supermalloy, which ensures high magnetic fluxes with relatively low current. Lucrative applications include nanomaterial‐enabled locomotive applications. Aerial robots regulated with the EMP system could be used for fostering pharmaceutical florae in the international space station for drug design to negate the recently discovered phenomenon of Sanal flow choking in cardiovascular system at gravity and/or microgravity conditions. This concept is originated from mind and aimed for lucrative product developments of yocto to yotta scale energy systems and beyond by discovering new magnetic materials through the fourth industrial revolution. Herein, a proof of the concept of an unrestricted solar‐battery driven push‐pull electromagnetic propulsion and energy conversion device by use of light weight high power magnetic materials is presented.

ABSTRACTThe recombinant zoster vaccine (RZV) was licensed in the US for prevention of herpes zoster (HZ) in 2017. We conducted a literature search (January 1, 2017–August 1, 2023) using PubMed, Embase, and Scopus to consolidate the real-world evidence related to RZV. Overall, RZV effectiveness against HZ was high across the studied populations in real-world settings, including adults aged ≥ 50 years and patients aged ≥ 18 years with immunodeficiency or immunosuppression. Effectiveness was higher with two doses versus one dose, especially in elderly people and immunocompromised individuals. The safety profile of RZV was broadly consistent with that established in clinical trials. RZV does not appear to increase the risk of disease flares in patients with immune-mediated diseases. Approximately two-thirds of individuals received a second RZV dose within 2–6 months after the first dose. Collectively, RZV effectiveness against HZ was high, and these real-world studies reaffirm its favorable benefit–risk profile.

Growing population, rapid urbanization, and increasing travel demand emphasize the need for reliable public transportation systems and sustainable transportation planning. A reliable bus service fosters a more significant, satisfied, and committed base of users. This research focuses on examining the association between on-time performance (OTP) and road network, demographic, socioeconomic, and land use characteristics to identify relevant external factors for proactive and reliable public transportation system planning. The analysis was conducted at a bus stop level. Bus arrival/departure data from the Charlotte Area Transit System (CATS) was obtained. The road network, demographic, socioeconomic, and land use characteristics were captured within 0.25-mile and 0.50-mile buffers. Pearson correlation analysis was conducted to understand the association between OTP and road network, demographic, socioeconomic, and land use characteristics by day of the week and time of the day. The results show that OTP is associated with external factors such as the number of signalized or cul-de-sac/dead-end intersections, number of lanes, network density, population, income (median and total), and land use types related to residential and commercial/employment purposes within the bus stop vicinity. The findings provide vital insights for transit agencies to enhance scheduling, service and maximize benefits, effectively utilize available resources, plan, and provide equitable services to all riders.

Summary: Sensitivity of primate daylight vision varies across the visual field. This is attributed to regional variations in cone photoreceptor density and synaptic connectivity of the underlying circuitry. In contrast, we have limited understanding of how synapse organization of the primate night vision pathway changes across space. Using serial electron microscopy, we reconstructed the first synapse of the night vision pathway between rod photoreceptors and second-order neurons, at multiple locations from the central part of the primate retina, fovea, to the periphery. We find that most facets of the rod synapse connectivity vary across retinal regions. However, rod synaptic divergence and convergence patterns do not change in the same manner across locations. Moreover, patterns of rod synapse organization are tightly correlated with photoreceptor density. Such regional heterogeneities revise the connectivity diagram of the primate rod synapse which will shape synapse function and sensitivity of the night vision pathway across visual space.

Problem Considered: Vitamin D deficiency is a global concern that needs significant attention. This observational study reports the impact of Vitamin D supplementation on general body aches, frequency of infection, and energy levels among Indian adults. Methods: This study included 508 adults aged 19–89 years old from low socioeconomic backgrounds who were given Vitamin D supplements for 4 months. The severity of musculoskeletal symptoms, frequency of infection or its symptoms, and perceived energy levels of the participants before and after the exposure were measured using a structured questionnaire. Data were analyzed descriptively for the frequencies, and a Chi-square and Wilcoxon signed-rank test was used to analyze the impact of Vitamin D on the variables studied. Results: The majority of the participants were female (82.3%) and were never exposed to Vitamin D supplementation earlier (84%). Nearly 65% of the participants were either homemakers, students, unemployed, or retired. Vitamin D supplementation was significantly associated with the reduction in back pain (P < 0.001), fatigue and body pain (P < 0.001), knee pain (P < 0.001), and pain in the hands and legs (P < 0.001). Vitamin D also significantly reduced the frequency of infection and/or its symptoms (P < 0.001) and improved physical work capacity (P < 0.001). Conclusion: Vitamin D supplementation for urban low socioeconomic groups may be beneficial as it can reduce the pain, frequency of infection and improve general well-being. The limitations of this study, such as the lack of a nonexposed group and data on the Vitamin D status of the participants, warrant consideration in future studies.

Global food production consumes a large fraction of energy budget, land area, and freshwater; however, a larger fraction of the produce is lost or unutilized, which has potential to produce useful products for human use. The biogenic synthesis of silver nanoparticles from such waste food appears to be a promising strategy. A conservative estimate of 70–140 thousand tons of potato peels is produced annually by food-chain companies globally; however, they are primarily utilized to produce substandard feed for livestock or manure. For the formation of highly profitable compounds, enhancement of value, and the process of extraction, such as nanocomposite, organic antioxidants, and organic meal inclusions, potato peels can be used as a cheap, productive, and readily available source of raw material. In the present research, silver nanoparticles (AgNPs) were extracted from the peels of potato (Solanum tuberosum). The fabrication of potato peel-derived AgNPs was established using UV-visible spectroscopy analysis. Approaches like X-ray diffraction (XRD), attenuated total reflection-infrared (ATR-IR) spectroscopy analysis, and field emission scanning electron microscopy (FESEM) were used to determine the characteristics of the AgNPs. Additionally, strains of Gram-positive bacteria such as Staphylococcus aureus (S. aureus) (ATCC 25923) and Gram-negative bacteria such as Escherichia coli (E. coli) (ATCC 25922) were used to determine the antibacterial activity of AgNPs via the disc diffusion technique. The antibacterial properties of AgNPs could help protect food from microbial contamination. Furthermore, AgNPs were tested for their potential application in purification of industrial wastewater. The results revealed that AgNPs derived from the potato peels could be used in industrial and biomedical applications and possess excellent antibacterial activity. Our research suggests that AgNPs can be extracted from a safe and ecofriendly fabrication technique from largely unused potato peels that have a great potential for inhibiting the bacterial growth and for the in situ purification of wastewater in the upcoming years. Therefore, besides value addition to the farm produce, such recycling of potato peels is likely to reduce the burden of the solid waste volumes in agro-centers, kitchen wastes, and food industries across the globe.

Introduction: Dengue is in an increasing trend in our part of the world mostly due to global warming, It can present with various manifestations including cutaneous manifestations. The main objective of our study was to find out the prevalence of dengue fever among patients visiting the Outpatient Department of Dermatology in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among patients visiting the Outpatient Department of Dermatology in a tertiary care centre after taking ethical approval from the Institutional Review Committee (Reference number: 09092022\04). Data from 1 June 2022 to 8 September 2022 were collected between 1 December 2022 to 20 February 2023 from the hospital records. The laboratory data of individuals were analyzed to find out the prevalence of dengue fever. A Visual Analogue Scale was used to assess the severity of pruritus. Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 7442 patients, dengue fever was found to be in 202 (2.71%) (2.34-3.08, 95% Confidence Interval) patients. The mean duration of fever was 3.02±2.960 days. The mean duration of onset of rash after having a fever was 2.56±2.032 days. The most common cutaneous manifestation was maculopapular rash 70 (34.65%). Conclusions: The prevalence of dengue fever was found to be lower than in the studies done in similar settings.

The focus of this paper is on evaluating the safety effectiveness of restricted crossing U-turn (RCUT) intersections in rural and suburban areas based on prior control type. Both, unsignalized and signalized RCUT intersections were evaluated using the Empirical Bayes (EB) before-after evaluation method. The 42 RCUT intersections selected for this research were converted from a two-way stop-controlled (TWSC) intersection or signalized intersection in the rural and suburban areas. The results show a 70.63% reduction in the total number of crashes and a 76.10% reduction in the number of fatal and injury crashes at unsignalized stop-controlled RCUT intersections in the rural area. Also, an 89.25% reduction in the total number of crashes and a 94.42% reduction in the number of fatal and injury crashes was observed at offset three-legged unsignalized stop-controlled RCUT intersections converted from four-legged TWSC intersections in rural areas. In the suburban areas, a 64.86% reduction in the total number of crashes and a 73.39% reduction in the number of fatal and injury crashes was observed at unsignalized stop-controlled RCUT intersections. Further, a 10.15% and a 31.08% reduction in the total number of crashes, and an 84.26% and 41.31% reduction in the number of fatal and injury crashes was observed at a signalized RCUT intersection in the rural and suburban areas, respectively. The safety effectiveness of unsignalized RCUT intersections in the rural areas with a larger sample size was found to be higher than was observed by researchers in the past. While unsignalized RCUT intersections in the suburban areas are effective, there is not enough evidence to support the installation of signalized RCUT intersections. These findings help researchers and practitioners in making informed decisions and installing RCUT intersections from a safety perspective.

Hox genes are known to control anteroposterior patterning, including the vertebrate spine. Here Xue et al. show that maternal Smchd1 regulates Hox expression in an epigenetic manner, and that wild type offspring from heterozygous mothers show skeletal homeotic transformations as a result of this dysregulation.

The retinal neural circuit is intricately wired for efficient processing of visual signals. This is well-supported by the specialized connections between retinal neurons at both the functional and ultrastructural levels. Through 3D electron microscopic (EM) reconstructions of retinal neurons and circuits we have learnt much about the specificities of connections within the retinal layers including new insights into how retinal neurons establish connections and perform sophisticated visual computations. This mini-review will summarize the retinal circuitry and provide details about the novel insights EM connectomics has brought into our understanding of the retinal circuitry. We will also discuss unresolved questions about the retinal circuitry that can be addressed by EM connectomics in the future.

Objectives: The primary objective was to investigate the correlation of musculoskeletal pain (MSP) intensity with Vitamin D status and glycemic control in patients of type II diabetes mellitus. The secondary objective was to monitor the anxiety and depression levels with Vitamin D supplementation. Methods: A prospective observational cohort study was conducted over a period of 18 months where 100 patients of type II diabetes mellitus with MSP were screened for Vitamin D status and glycemic levels in terms of HbA1c, anxiety, and depression. MSP was assessed by Visual Analog Scale (VAS) score. The patients who were found with Vitamin D levels (

Multimodal video analysis is a complex and time-consuming process for a researcher; it entails capturing, watching, and re-watching video data to identify which segments best inform or address the questions that drive the research. Modern AI applications can alleviate the challenges that arise during the fine-grained analysis of learners' multimodal interactions captured through video. In this study, we present a supervised approach to training a deep neural network to analyze children's computational thinking (CT) captured through multimodal video data. The approach first uses a set of images extracted from video data to train the AI to map them to labels generated using a priori theory. Confusion matrices were used to establish the performance of the AI by comparing AI predictions to human analysis on a validation set of data. The findings suggested that the AI classified several aspects of children's CT in a way that was highly consistent with human analysis, demonstrating how the AI could serve as an additional team member during multimodal analysis. Implications for using AI to ease the challenges of multimodal analysis of video data are discussed.

Introduction: Coronavirus disease-19 infection is caused by the coronavirus and has taken a toll throughout the world. The aim of this study was to find the prevalence of coronavirus disease-19 infection among patients presenting to a tertiary care centre. Methods: A descriptive cross-sectional study was conducted at the fever clinic of a tertiary care centre between January 2021 to September 2021 after receiving ethical approval from the Institutional Review Committee (Reference number: 2011202001). Convenience sampling was done. Data were collected from the records of patients diagnosed with real-time polymerase chain reaction) test in the sample group. Point estimate and 95% Confidence Interval were calculated. Results: Among 230 patients presenting to the fever clinic, 130 (56.52%) (50.11-62.93, 95% Confidence Interval) were diagnosed with coronavirus disease-19. Conclusions: Our study found that the prevalence of coronavirus disease-19 was higher when compared to similar studies conducted in similar settings.

During meiosis, recombination between homologous chromosomes (homologs) generates crossovers that promote proper segregation at the first meiotic division. Recombination is initiated by Spo11-catalyzed DNA double strand breaks (DSBs). 5' end resection of the DSBs creates 3' single strand tails that two recombinases, Rad51 and Dmc1, bind to form presynaptic filaments that search for homology, mediate strand invasion and generate displacement loops (D-loops). D-loop processing then forms crossover and non-crossover recombinants. Meiotic recombination occurs in two temporally distinct phases. During Phase 1, Rad51 is inhibited and Dmc1 mediates the interhomolog recombination that promotes homolog synapsis. In Phase 2, Rad51 becomes active and functions with Rad54 to repair residual DSBs, making increasing use of sister chromatids. The transition from Phase 1 to Phase 2 is controlled by the meiotic recombination checkpoint through the meiosis-specific effector kinase Mek1. This work shows that constitutive activation of Rad51 in Phase 1 results in a subset of DSBs being repaired by a Rad51-mediated interhomolog recombination pathway that is distinct from that of Dmc1. Strand invasion intermediates generated by Rad51 require more time to be processed into recombinants, resulting in a meiotic recombination checkpoint delay in prophase I. Without the checkpoint, Rad51-generated intermediates are more likely to involve a sister chromatid, thereby increasing Meiosis I chromosome nondisjunction. This Rad51 interhomolog recombination pathway is specifically promoted by the conserved 5'-3' helicase PIF1 and its paralog, RRM3 and requires Pif1 helicase activity and its interaction with PCNA. This work demonstrates that (1) inhibition of Rad51 during Phase 1 is important to prevent competition with Dmc1 for DSB repair, (2) Rad51-mediated meiotic recombination intermediates are initially processed differently than those made by Dmc1, and (3) the meiotic recombination checkpoint provides time during prophase 1 for processing of Rad51-generated recombination intermediates.

In India, although incidence of Herpes zoster has not been assessed, regional cases have been reported. We revisited the peer-reviewed literature on clinical cases of HZ to depict the trends in population characteristics, disease presentation, and predisposing factors for the disease in India. Systematically conducted literature search yielded 27 studies, published between January 2011 and May 2020, reporting 3124 HZ clinical cases, with high proportions in older adults (>50 years of age: 15.0–81.3%). Thoracic dermatome was consistently reported as the most frequent site affected by HZ (38.9–71.0%). Post-herpetic neuralgia and secondary bacterial infections were the two most frequent complications (10.2–54.7% and 3.5–21.0%, respectively). Despite the paucity of data and gaps in the reporting of HZ cases, available evidence indicate that the disease causes an important burden to older adults in India, suggesting that preventive strategies, along with recommendations to healthcare practitioners, can help mitigate the burden of HZ.

Abstract We are now in an era of molecular medicine, where specific DNA alterations can be used to identify patients who will respond to specific drugs. However, there are only a handful of clinically used predictive biomarkers in oncology. Herein, we describe an approach utilizing in vitro DNA and RNA sequencing and drug response data to create TreAtment Response Generalized Elastic-neT Signatures (TARGETS). We trained TARGETS drug response models using Elastic-Net regression in the publicly available Genomics of Drug Sensitivity in Cancer (GDSC) database. Models were then validated on additional in-vitro data from the Cancer Cell Line Encyclopedia (CCLE), and on clinical samples from The Cancer Genome Atlas (TCGA) and Stand Up to Cancer/Prostate Cancer Foundation West Coast Prostate Cancer Dream Team (WCDT). First, we demonstrated that all TARGETS models successfully predicted treatment response in the separate in-vitro CCLE treatment response dataset. Next, we evaluated all FDA-approved biomarker-based cancer drug indications in TCGA and demonstrated that TARGETS predictions were concordant with established clinical indications. Finally, we performed independent clinical validation in the WCDT and found that the TARGETS AR signaling inhibitors (ARSI) signature successfully predicted clinical treatment response in metastatic castration-resistant prostate cancer with a statistically significant interaction between the TARGETS score and PSA response (p = 0.0252). TARGETS represents a pan-cancer, platform-independent approach to predict response to oncologic therapies and could be used as a tool to better select patients for existing therapies as well as identify new indications for testing in prospective clinical trials.