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Redoy Ranjan,1 Gie Ken-Dror,1 Pankaj Sharma1,2 On behalf of the BEAST Collaborators1Department of Biological Sciences, Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), Egham, Greater London, UK; 2Department of Clinical Neuroscience, Imperial College Healthcare NHS Trust, London, UKCorrespondence: Pankaj Sharma, Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), Egham, Greater London, TW20 0EX, UK, Email pankaj.sharma@rhul.ac.ukIntroduction: Risk prediction models are commonly performed with logistic regression analysis but are limited by skewed datasets. We utilised neural networks (NNs) model to identify independent predictors of poor outcomes in cerebral venous thrombosis (CVT) due to the limitations of logistic regression (LR) analysis with complex datasets.Methods: We evaluated 1309 adult CVT patients from the prospective BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. The area under the receiver operating characteristic (AUROC) curve confirmed the goodness-of-fit of prediction models. The normalised importance (NI) of the NNs determines the significance of independent predictors.Results: The stepwise logistic regression model found thrombolysis (OR 32.1; 95% CI 3.6– 287.0; P=0.002), craniotomy (OR 6.9; 95% CI 1.3– 36.8; P=0.02), and cerebral haemorrhage (OR 4.5; 95% CI 1.3– 15.4; P=0.01) as predictors of poor clinical outcome with the AUROC of 0.71. Conversely, the NNs model identified major independent predictors of long-term poor clinical outcomes as cerebral haemorrhage (NI 100%) and thrombolysis (NI 98%), as well as trivial predictors of age (NI 2.8%) and altered mental status (NI 3.5%). The accuracy of the NNs model was 95.1% and 94.1% for self-learned randomly selected training and testing samples with an AUROC of 0.82. Positive and negative predictive values for poor outcomes were 13.2% and 97.1% for the LR model, compared with the NNs model of 18.8% and 98.7%, respectively.Conclusion: Cerebral haemorrhage and thrombolysis was a strong independent predictor, whereas age merely impacts the long-term poor clinical outcome in adult CVT. Integrating unorthodox neural networks risk prediction model can improve decision-making as it outperforms conventional logistic regression with complex datasets.Keywords: cerebral venous thrombosis, neural network, stroke, predictors, outcome

Redoy Ranjan,1 Md Kamrul Hasan,2 Asit Baran Adhikary1,3 1Department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 2Department of Cardiac Surgery, National Institute of Cardiovascular Diseases, Dhaka, Bangladesh; 3Department of Cardiac Surgery, Impulse Hospital & Research Centre, Dhaka, BangladeshCorrespondence: Redoy Ranjan, International Journal of General Medicine, Department of Cardiac Surgery, Bangabandhu Sheikh Mujib medical University, Dhaka, 1000, Bangladesh, Email redoy_ranjan@bsmmu.edu.bdBackground: Genetic factors contribute significantly to the risk of ischaemic heart disease (IHD), which is the leading cause of mortality in Bangladesh. The BANGABANDHU (Bangladeshi Atherosclerosis Biobank AND Hub) study will allow a hypothesis-free genome-wide association study (GWAS) to identify genetic risk factors associated with ischaemic heart disease patients undergoing coronary artery bypass graft (CABG) surgery in Bangladesh.Methods: This is a multi-centre population-based case–control study aimed to evaluate 1500 (Fifteen Hundred) adult (≥ 18 years of age) people divided into 2 study groups: Case/Proband (750 IHD patients undergoing CABG surgery) and Control (750 healthy people). Spouses or family members are preferred as healthy control subjects due to their shared geographic location and similar environmental exposure.Results: This will be the first largest DNA repository of CABG patients in Bangladesh, and identifying novel gene loci among CABG patients might help to discover novel therapeutic targets for Bangladeshi IHD patients. Further, identifying and comparing novel gene loci among CABG patients with other ancestry might help devise national guidelines for treating coronary artery disease.Conclusion: Promising current study results will encourage Bangladeshi researchers and pharmaceutical companies to conduct further studies into the genetic basis of Bangladeshi complex coronary artery disease, which might identify novel genes for therapeutic targets for Bangladeshi patients and strengthen the healthcare standards in Bangladesh.Keywords: Bangabandhu, Bangladesh, biobank, IHD, CABG

Aziz Momin,1 Redoy Ranjan,1,2 Oswaldo Valencia,1 Adam Jacques,3 Pitt Lim,4 David Fluck,3 Tuan P Chua,5 Venkatachalam Chandrasekaran1 1Department of Cardiac Surgery, St George’s University Hospitals NHS Foundation Trust, London, UK; 2Department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 3Department of Cardiology, Ashford and St Peter’s Hospitals NHS Foundation Trust, London, UK; 4Department of Cardiology, St George’s University Hospitals NHS Foundation Trust, London, UK; 5Department of Cardiology, Royal Surrey NHS Foundation Trust, London, UKCorrespondence: Aziz Momin, Consultant Cardiac Surgeon, St George’s University Hospitals NHS Foundation Trust, London, SW17 0QT, United Kingdom, Tel +447956336739, Email aziz.momin@stgeorges.nhs.ukObjective: This study determined hazard factors and long-term survival rate of total arterial coronary artery bypass graft surgery over 20 years in an extensively large, population-based cohort.Methods: A total of 2979 patients who underwent isolated CABG from April 1999 to March 2020 were studied in 4 groups- Group-A (bilateral internal mammary artery ± radial artery), Group-B (single internal mammary artery + radial artery ± saphenous vein), Group-C (single internal mammary artery ± saphenous vein; no radial artery), and Group-D (radial artery ± saphenous vein; no internal mammary artery). The study endpoints analysed the correlation between the number and types of grafts with the survival time following isolated CABG surgery.Results: The total arterial revascularization (Group A) group had an admirable mean long-term survival of ~19 years, compared to 18.6 years (Group B), 15.86 years (Group C), and 10.99 years (Group D). A Kaplan-Meier curve demonstrated confidence interval (CI) for study groups- (95% CI 18.33– 19.94), (95% CI 18.14– 19.06), (95% CI 15.40– 16.32), and (95% CI 9.61– 12.38) in Group A, B, C, D respectively. In the Holm-Sidak method analysis, significant associations existed between the number of arterial grafts and the long-term outcome. A statistically significant (P≤ 0.05) long-term survival advantage for arterial grafting was demonstrated, especially total arterial revascularisation over all other combinations except single internal mammary artery + radial artery grafting.Conclusion: In this series, over 20 years, total arterial CABG use has excellent long-term survival, achieving complete myocardial revascularisation. There is no significant difference between the BIMA group and SIMA with radial artery. However, there is a reduced survival with decreased use of arterial conduits.Keywords: coronary artery bypass graft, CABG, bilateral internal mammary artery, total arterial CABG, long term outcome, multiple arterial graft, mortality, survival benefits

Background: The assessment of hidradenitis suppurativa (HS) severity requires detailed, and error‐prone lesion counts. This proof‐of‐concept study aimed to automatically classify HS disease severity using machine learning of clinical smartphone images. Methods: 777 ambient‐light and size‐controlled images were used to build a class‐balanced synthetic dataset (n = 7675). Convolutional neural networks (CNN) were used for automated severity classification (scale 0–3), and to assess disease‐dynamics. International Hidradenitis Suppurativa Severity Score System (IHS4) served as reference. A U‐NET algorithm was implemented for automated localization of diseased skin. Results: CNNs were able to distinguish no/mild from moderate/severe disease with an overall prediction accuracy of 78% [receiver operating curve (AUC) 0.85]. Correct IHS4 classification was achieved with an overall accuracy of 72% (AUC 0.84–0.89). In addition, disease dynamics using IHS4 numerical values aligned with CNN outputs (NRMSE 0.262). The UNET algorithm localized lesions with a pixel accuracy of 88.1% and test loss of 0.42. Limitations: Limitations in assessing tattooed and hairy skin. Limited number of patients with dark skin colour and Hurley I. Conclusion: CNNs were able to distinguish no/mild from moderate/severe disease, classify disease severity over time, and automatically identify diseased skin areas and the skin phototype. This study breaks new grounds for fast, reliable, reproducible and easy‐to‐use HS severity assessments using clinical images. [ABSTRACT FROM AUTHOR]

A fundamental necessity in advancing sustainable crop production lies in the establishment of a reliable technique for assessing soil health. Soil health assessment is a challenge considering multiple interactions among dynamic indicators within various management strategies and agroecological contexts. Hence a study was conducted to determine the soil health variables, quantify the soil health index (SHI), and validate them with the productivity of rice (Oryza sativa L.)-wheat (Triticum aestivum L.) system for the Indo Gangetic basin of Bihar, India, under four contrasting agro-climatic zones (ACZ-I, II, IIIA & IIIB). For this study, 100 soil samples (0-15 cm) from each ACZ with a total of 400 soil samples were obtained for analyzing 20 soil health variables (soil physical, chemical, and biological properties). To identify SHI and important soil health variables, principal component analysis (PCA) was employed. Apart from specific variables, soil pH, soil organic carbon (SOC), available Zn and available water capacity (AWC) were identified as common indicators for the four ACZs. Results revealed that under the rice-wheat cropping system, ACZ-IIIB soils had a higher SHI (0.19-0.70) than other ACZs. SHI of ACZ-IIIB was significantly influenced by SOC (19.32 %), available P (10.52 %), clay (10.43 %), pH (10.80 %), and soil respiration (9.8 %). The strong relationship between SHI and system productivity of the rice-wheat (R 2  = 0.79) system indicates that the selected soil health variables are representative of good soil health. It is concluded that ACZ-specific SHIs are a promising strategy for evaluating and monitoring soil health to achieve the United Nations' Sustainable Development Goal of 'zero hunger' by 2030., Competing Interests: Declaration of competing interest The authors declare that there are no known competing financial interests or personal relationships that could have influenced this paper's findings., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this paper, the work has been done to develop a cost-effective methodology, for the isolation of the potential producer of bacterial nanocellulose. No report is available in the literature, on the use of gram flour and table sugar for the screening of nanocellulose-producing isolates. Since commercially used, Hestrin-Schramm medium is expensive for the isolation of nanocellulose-producing micro-organisms, the possibility of using gram flour-table sugar medium was investigated in this work. Qualitative screening of micro-organisms was done using cost-effective medium, i.e., gram flour-table sugar medium. Qualitative analysis of various nanocellulose-producing bacteria depicted that cellulose layer production occurred on both HS medium and gram flour-table sugar medium. The yield of nanocellulose was also better on air-liquid surface in case of gram flour-table sugar medium as compared to HS medium. 16S rRNA was used for molecular characterization of bacterial strain and the best nanocellulose producer was identified as Novacetimonas hansenii BMK-3_NC240423 (isolated from rotten banana). FTIR and FE-SEM studies of nanocellulose pellicle produced on HS medium and gram flour-table sugar medium demonstrated equivalent structural, morphological, and chemical properties. The cost of newly designed medium (0.01967 $/L) is nearly 90 times lower than the Hestrin-Schramm medium (1.748 $/L), which makes the screening of nanocellulose producers very cost-effective. A strategy of using gram flour extract-table sugar medium for the screening of nanocellulose-producing micro-organisms is a novel approach, which will drastically reduce the screening associated cost of cellulose-producing micro-organisms and also motivate the researchers/industries for comprehensive screening programme for getting high cellulose-producing microbes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Neck dissection forms an important component in the surgical management of head and neck cancers. By using the conventional techniques of neck dissection, a conspicuous scar is inevitable for the patients. The development of robotic assisted neck dissection provides for a scar-free neck along with good oncological and functional outcomes., Methods: A prospective observational study was conducted in our institute from 2020 March to 2022 March, where robotic-assisted neck dissections performed via the modified bilateral axillo-breast insufflation technique., Results: Eighty-two patients underwent robotic neck dissections in our institute. Notably, 79 patients were treatment-naïve. The average docking time was 12 min and console time was 160 ± 15 min. The mean lymph node yield was 28.2. The average post-operative stay was 5.6 days. The average follow-up was noted to be 6.4 months. The mean cosmetic satisfaction score in our patients was 4.45. Only one patient presented with nodal recurrence, who was identified as a defaulter for adjuvant treatment. Robotic neck dissection gives similar functional and oncological outcomes as compared with conventional neck dissection. Patients had excellent cosmetic satisfaction following the procedure. The limitations of these techniques include high cost of procedure and longer operating time. This is a level IV evidence study., Conclusion: Although good oncological, functional, and cosmetic outcomes have been attained in robotic assisted neck dissection, further randomized controlled studies need to be conducted to justify the added costs, cosmetic advantage, and the time taken., Level of Evidence: IV Laryngoscope, 134:4045-4051, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Herein, we disclose an expedient visible-light-mediated, organophotoredox-catalyzed multicomponent synthesis of unnatural amino acids using a Katritzky salt, glyoxal derivatives, and substituted anilines. Mechanistically, an alkyl radical is generated from the Katritzky salt via a deaminative process that undergoes addition to the in situ -generated imine to furnish α-amino acids in a moderate diastereoisomeric ratio. For the first time, we have demonstrated this deaminative protocol to access substituted β-amino acids from α-amino acid-derived Katritzky salts. Furthermore, α-amino amides are also generated from the corresponding 2-oxoacetamide derivatives.

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., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

In the aftermath of the COVID-19 pandemic, opportunities to modulate biological pathways common to the lifecycles of viruses need to be carefully considered. N -linked glycosylation in humans is mediated exclusively by the oligosaccharyltransferase complex and is frequently hijacked by viruses to facilitate infection. As such, STT3A/B, the catalytic domain of the OST complex, became an intriguing drug target with broad-spectrum antiviral potential. However, due to the critical role N -linked glycosylation plays in a number of fundamental human processes, the toxicological ramifications of STT3A/B inhibition required attention commensurate to that given to antiviral efficacy. Herein, we describe how known STT3A/B inhibitor NGI-1 inspired the discovery of superior tool compounds which were evaluated in in vitro efficacy and translational safety (e.g., CNS, cardiovascular, liver) studies. The described learnings will appeal to those interested in the therapeutic utility of modulating N -linked glycosylation as well as the broader scientific community.

A straightforward transition-metal-free sustainable methodology for oxidative cyclopropanation of aza-1,6-enynes has been devised, enabling the synthesis of valuable, functionalized azabicyclo[4.1.0]heptane-2,4,5-triones, via four bond formation in a single step under mild conditions. Control experiments and real-time mass data monitoring using online ESI-MS spectroscopy support the pathway proposed for this reaction. The synthesized products have been utilized in diverse product transformations. Key advantages of this reaction include its operational ease, transition metal-free nature, rapid completion, and compatibility with a wide range of functional groups and substrates.

Introduction: The intersection of sexism with racism and xenophobia disproportionately exposes visible minority women to gender-based violence (GBV) at the community and systemic levels. This study aims to understand the knowledge strengths and gaps on GBV against visible minority women with an intersectional lens, revealing systemic barriers to accessing support and how these barriers intensify GBV and its effects. It will also identify effective and ineffective policies and practices in the literature to develop strategies addressing the root causes of GBV and supporting survivors., Methods and Analysis: We will conduct a mixed-methods systematic review using a convergent integrated approach to examine current literature on community- and systemic-level GBV against visible minority women. We will follow Joanna Briggs Institute's guidelines to converge data from both qualitative and quantitative studies to obtain an integrated qualitative synthesis on GBV in five countries: Canada, the USA, the UK, Australia and New Zealand. This analysis will be conducted following Thomas and Harden's thematic synthesis guidelines. Community members with lived experience of GBV will actively contribute to improving the relevance and interpretation of results, following a community-engaged research approach. Themes are expected to unveil various aspects of community- and systemic-level GBV due to the intersection of racism, xenophobia and sexism, alongside barriers in addressing GBV and research gaps., Ethics and Dissemination: Since this study does not involve primary data collection or the use of identifiable human data, no ethical approval will be needed. Results will be disseminated through integrated knowledge translation, involving collaboration with participants who have lived experience of GBV. The findings will be used to identify specific areas of policy intervention, including adopting culturally sensitive approaches, improving school and workplace policies and promoting rights of visible minority women., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Black gram (Vigna mungo L.) plants showing yellow mosaic symptoms during 2019-2022 crop seasons were collected randomly from a Dayalbagh field, Agra Region of Uttar Pradesh, India. Total genomic DNA was isolated from the infected leaf samples by the Cetyltrimethylammonium bromide (CTAB) method and subjected to PCR. After viral confirmation, the viral genome was amplified by rolling circle amplification following the standard protocol. The DNA A and DNA B subgenomes were cloned individually as a PstI and BamHI fragment in the pUC18 vector. Positive clones were subjected to DNA sequencing. The results revealed that DNA A and DNA B show the closest nucleotide identity with "mungbean yellow mosaic India virus-[Mungbean], DNA-A, the complete sequence" (GeneBank Accession No AF416742.1) with 98.14% identity, and "mungbean yellow mosaic India virus isolate Mu1-Dholi segment DNA-B, the complete sequence" (GeneBank Accession No MW814723.1) with 97.94% identity, respectively. The new isolate of mungbean yellow mosaic India virus (MYMIV) shows sequence similarity with the coat protein gene of various strains of MYMIV. In the new isolate of MYMIV, a point mutation was observed at the 2036th nucleotide of DNA B, which disrupts the reading frame to introduce a stop codon and thus leading to a decrease in the size of the movement protein gene. In the present study we are reporting the whole genome sequence of the MYMIV Dayalbagh isolate for the first time., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Doped ceria has been extensively explored as an efficient electrolyte material for intermediate to low temperature solid oxide fuel cell. Among other ceria electrolytes, gadolinia doped ceria (GDC) is one of the most extensively studied electrolyte materials for low temperature SOFC applications. Here, co-precipitation method is employed to synthesize GDC nanoparticles with stoichiometric ratio of Gd x Ce 1-x O 2-δ (with 0  ≤  x  ≤  0.20). In this process, the molecular water of the precursors has been utilized during the co-precipitation to avoid possible agglomeration caused by hydrogen bonding. The cubic phase formation was examined using X-ray diffraction (XRD) and Raman profile ascribing absence of other phases. XRD along with Reitveld refinement confirm the presence of cubic phase of ceria and Raman profile confirms the oxygen vacancies due to the non-stoichiometry created in CeO 2 lattice. The granularity of the sample was observed using field emission scanning electron microscopy (FESEM) with elemental mapping by EDS. It is observed from FESEM that the grains are compact in nature and the density observed was around 98% of the theoretical density. The electrochemical behavior was investigated using electrochemical impedance spectroscopy (EIS), which was taken between the temperature ranges of 350-700 °C. It is observed from the EIS study that ceria doped with 15 mol % Gd 3+ (Gd 0.15 Ce 0.85 O 2-δ ) is having highest grain boundary ionic conductivity of about 0.104 S cm -1 at 700 °C with an activation energy of 0.81 eV. This work demonstrates the correlation between oxygen vacancy generation and the enhancement of ionic conductivity with Gd 3+ doping in ceria., (© 2024. The Author(s).)

The nitro moiety is an indispensable functional group in organic synthesis due to its facile introduction and reduction to the corresponding amines for a plethora of organic transformations. Owing to its distinct electronegative and conventional properties, it has been used for activated aromatic nucleophilic substitution (S N Ar) reactions, Smiles reactions, Henry reactions, acyl anion equivalents, etc. Recently, the excellent photochemical properties of nitroarenes have been rediscovered by several groups, and their untapped potential in organic synthesis under UV or visible light irradiation has been exploited. Photoexcited nitroarenes can undergo facile reduction to amines, azo-coupling, metal-free reductive C-N coupling with boronic acids via a 1,2-boronate shift, hydrogen atom transfer (HAT), oxygen atom transfer for anaerobic oxidation of organic molecules, molecular editing via nitrene intermediates, denitrative coupling of β-nitrostyrene, radical α-alkylation of nitroalkanes, etc. They have also been used as a photolabile protecting group in medicinal chemistry and chemical biology applications. Here, we summarise the recent findings on visible-light-mediated transformations involving nitro-containing organic molecules.

Introduction: Sri Lanka implemented the National Programme for Elimination of Lymphatic Filariasis (NPELF) in its endemic regions in 2002. Five annual rounds of mass drug administration using the two-drug combination diethylcarbamazine (DEC) and albendazole led to sustained reductions in infection rates below threshold levels. In 2016, WHO validated that Sri Lanka eliminated lymphatic filariasis as a public health problem., Objective: To explore the impact of the NPELF on lymphatic filariasis morbidity in Sri Lanka., Methods: Passive Case Detection (PCD) data maintained in filaria clinic registries from 2006-2022 for lymphoedema and hospital admission data for managing hydroceles/spermatoceles from 2007-2022 were analyzed. The morbidity status in 2022 and trends in overall and district-wise PCD rates were assessed. Poisson log-linear models were used to assess the trends in PCD for endemic regions, including district-wise trends and hospital admissions for the management of hydroceles/spermatoceles., Results: In 2022, there were 566 new lymphoedema case visits. The mean (SD) age was 53.9 (16.0) years. The staging was done for 94% of cases, of which 79% were in the early stages (57.3% and 21.4% in stages two and one, respectively). Western Province had the highest caseload (52%), followed by the Southern (32%) and Northwestern (16%) Provinces, respectively. The reported lymphoedema PCD rate in 2022 was 0.61 per 10,000 endemic population. The overall PCD rate showed a decline of 7.6% (95%CI: 4.9% - 10.3%) per year (P < 0.0001) from 2007 to 2022. A steady decline was observed in Colombo, Gampaha and Kurunegala districts, while Kalutara remained static and other districts showed a decline in recent years. Further, admissions for inpatient management of hydroceles/spermatoceles showed a declining trend after 2015., Conclusions: The PCD rates of lymphoedema and hydroceles/spermatoceles showed a declining trend in Sri Lanka after the implementation of the NPELF., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gunaratna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Laparoscopic cholecystectomy is performed very commonly but laparoscopic common bile duct exploration (LCBDE) is performed infrequently. We aimed to determine the most significant barriers to performing LCBDE and to identify the highest yield interventions to facilitate adoption., Methods and Procedures: A national survey was designed by content experts, who regularly perform LCBDE. The survey was distributed by email to the Society of American Gastrointestinal and Endoscopic Surgeons and the American Association for the Surgery of Trauma memberships. Non-U.S. surgeon responses were excluded. Descriptive statistics were used to analyze the results., Results: Seven hundred twenty six practicing surgeons responded to the survey, 543 of which were US surgeons who perform laparoscopic cholecystectomy. Only 27% of respondents preferred to manage choledocholithiasis with LCBDE. Their technique of choice was choledochoscopy (70%). Despite this, 36% of surgeons did not have access to a choledochoscope or were unsure if they did. Seventy percent of surgeons who performed LCBDE did not have supplies readily available in a central stocking location. Only 8.5% of surgeons agreed that routine LCBDE would impact their referral relationship with gastroenterology. About half the respondents (47%) considered LCBDE worth the time, but only 25% knew about reimbursement for the procedure. Almost all (85%) of surgeons understood that LCBDE results in shorter length of stay compared to ERCP., Conclusions: Only a quarter of the surgeons performing cholecystectomy perform LCBDE. Multiple barriers contribute to low LCBDE utilization. Increasing availability of appropriate equipment, a dedicated supply cart, and teaching fluoroscopic LCBDE interventions may address limitations and increase adoption. These efforts may also increase efficiency, minimizing perceived time and skill restraints. Although many surgeons understand LCBDE decreases length of stay, they are unaware of surgeon-specific LCBDE financial benefits. Systematically addressing these barriers may increase LCBDE adoption, improve patient care, and decrease healthcare costs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Poorer baseline functioning is associated with long-term cognitive decline among Hispanic older adults, but little is known about associations of these factors with Alzheimer's disease (AD) neuroimaging biomarkers., Methods: A total of 461 Hispanic and White non-Hispanic (NHW) older adults who are cognitively normal ( n  = 76), had impaired cognition without mild cognitive impairment (MCI) ( n  = 41), or carried a diagnosis of MCI ( n  = 253) or dementia ( n  = 91) completed neuropsychological and functional assessment, genetic testing, and brain magnetic resonance imaging (MRI). Structural equation modeling (SEM) was used to examine predictive associations between functional and cognitive measures of AD neuroimaging biomarkers., Results: MRI volumes significantly predicted functional limitations in both groups. Sex and amyloid load significantly predicted functional limitations among the Hispanic group only. Years of education and MRI regional volume were the strongest predictors of cognition among both groups., Discussion: Results indicate that functional performance is associated with early AD biomarkers among Hispanic older adults. Clinical implications are discussed., Highlights: The current study addresses health disparities in Alzheimer's disease (AD) and related dementia assessment among Hispanics by identifying measures sensitive to early AD biomarkers.Associations of functional measures with AD genetic and neuroimaging biomarkers revealed that similarities in these associations exist between Hispanic and White non-Hispanic individuals, but biological sex and amyloid load significantly predicted functional limitations among the Hispanic group only.These results have clinical implications for physicians who treat Hispanic AD patients and indicate that when compared to traditional diagnostic assessments, functional assessments may better aid in AD diagnostic precision among Hispanics., Competing Interests: Authors have no conflicts of interest to declare. Author disclosures are available in the Supporting Information., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Disruption of retinal vasculature is linked to various diseases, including diabetic retinopathy and macular degeneration, leading to vision loss. We present here a novel algorithmic approach that generates highly realistic digital models of human retinal blood vessels, based on established biophysical principles, including fully-connected arterial and venous trees with a single inlet and outlet. This approach, using physics-informed generative adversarial networks (PI-GAN), enables the segmentation and reconstruction of blood vessel networks with no human input and which out-performs human labelling. Segmentation of DRIVE and STARE retina photograph datasets provided near state-of-the-art vessel segmentation, with training on only a small (n = 100) simulated dataset. Our findings highlight the potential of PI-GAN for accurate retinal vasculature characterization, with implications for improving early disease detection, monitoring disease progression, and improving patient care., (© 2024. The Author(s).)

Honey truffle sweetener (HTS), a 121 amino acid protein is identified as a high-intensity sweetener found naturally occurring in the Hungarian Sweet Truffle Mattirolomyces terfezioides , an edible mushroom used in regional diets. The protein is intensely sweet, but the truffle is difficult to cultivate; therefore, the protein was systematically characterized, and the gene coding for the protein was expressed in a commonly used host yeast Komagataella phaffii . The heterologously expressed protein maintained the structural characteristics and sweet taste of the truffle. Preliminary safety evaluations for use as a food ingredient were performed on the protein including digestibility and in silico approaches for predicting the allergenicity and toxicity of the protein. HTS is predicted to be nonallergenic, nontoxic, and readily digestible. This protein is readily produced by precision fermentation of the host yeast, making it a potential replacement for both added sugars and small molecule high-intensity sweeteners in food.

Diagnostic assays that are able to detect foot-and-mouth disease (FMD) virus infection in the vaccinated population are essential tools in the progressive control pathway for the FMD. However, testing of serum samples using a single diagnostic assay may not completely substantiate freedom from the virus infection. Therefore, viral non-structural proteins (NSPs)-based various serological assays have been developed for the detection of FMD infection. Nevertheless, the NSPs-based ELISAs have been developed in the indirect-ELISA format, thereby necessitating the use of species-specific conjugated secondary-antibodies for the detection of anti-NSP antibodies in various FMD-susceptible species. Therefore, this study presents a novel recombinant 2B-NSP-based indirect ELISA, employing HRP-conjugated protein-A/G detection system which can detect anti-NSPs antibodies from multiple FMD-susceptible species in a single ELISA platform. Recombinant 2B (r2B) protein was expressed as His-SUMO tagged protein in the E. Coli cells and purified using NI-NTA affinity column chromatography. Using the r2B protein and HRP-conjugated protein A/G, an indirect ELISA was developed and validated for the detection of anti-2B antibodies in serum samples collected from multiple FMD-susceptible animal species with known FMD status. Further, a resampling based statistical technique has been reported for determination of optimal cut-off value for the diagnostic assay. Through this technique, the optimal cut-off of 44 percentage of positivity value was determined for the assay. At this optimal cut-off value, the developed diagnostic assay provided diagnostic sensitivity, specificity, and accuracy, positive and negative predictive values (PPV and NPV) of 92.35 %, 98.41 %, 95.21 %, 98.58 %, and 91.67 %, respectively. The assay was validated further by analyzing random serum samples collected across multi-locations in India. The assay can be used as a single platform for testing serum samples from different species of FMDV-susceptible animals and will be useful for NSP-based serosurveillance of FMDV., Competing Interests: Declaration of competing interest The authors declare no competing financial and non-financial interest., (Copyright © 2024 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Background and aims Laryngoscopy and intubation cause an increased sympatho-adrenergic pressor response, which can be detrimental to patients with coronary artery disease, hypertension, etc. Various drugs and manoeuvres have been tried to reduce the pressor response with acceptable results but the quest for the ideal drug still continues. Hence, we planned to compare the effects of magnesium sulfate with paracetamol and fentanyl with lignocaine on attenuating the hemodynamic responses due to direct laryngoscopy and intubation and to note the complications of these drugs. Methods We studied 60 adult patients of the American Society of Anaesthesiologists (ASA) physical status I and II of either sex, scheduled for elective surgery under general anaesthesia. The patients were randomly divided into two groups. Group A received 25 mg/kg magnesium sulphate mixed with paracetamol 1 gram IV (100 ml) given over 10 minutes before induction and Group B received 2 mcg/kg fentanyl and 1.5 mg/kg lignocaine, 3 minutes before intubation. All patients were uniformly pre-medicated, induced, and intubated as per standard protocol. Heart rate (HR) and systemic arterial pressures were recorded at baseline, after study drug infusion, after induction, and 1, 3, 5, 10, and 15 mins after intubation. Hemodynamic parameters were compared using repeated measures analysis of variance (ANOVA). In the post-hoc tests, p value < 0.05 was considered statistically significant. Results We observed the mean pre-op HR (p = 0.161) and mean HR one-minute post-induction (p = 0.144). The percentage change from baseline at one-minute post-induction was 9.7 in Group A and 15.2 in Group B. We observed the mean pre-op mean arterial pressure (MAP) (p = 0.119) and mean MAP one minute post-induction (p = 0.585). The percentage change from baseline at one-minute post-induction was 3.3 in Group A and 2.8 in Group B. The percentage change from baseline was found to be within 15%, for HR in Group A and for systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP in Group B. However, there was no statistically significant difference (p > 0.05) between the mean HR, SBP, DBP, and MAP between the time points. Conclusion In our study, both the combinations of drugs, magnesium sulphate with paracetamol (Group A drugs) and fentanyl with lignocaine (Group B drugs) were found to be equally effective (i.e. neither group was superior to the other) in attenuating the hemodynamic response to laryngoscopy and intubation., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. PIMS Institute Ethics Committee (IEC) issued approval IEC: RC/19/112, CTRI/2019/12/022315, 11/12/2019. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Murugesan et al.)

Global change is associated with variable shifts in the annual production of aboveground plant biomass, suggesting localized sensitivities with unclear causal origins. Combining remotely sensed normalized difference vegetation index data since the 1980s with contemporary field data from 84 grasslands on 6 continents, we show a widening divergence in site-level biomass ranging from +51% to -34% globally. Biomass generally increased in warmer, wetter and species-rich sites with longer growing seasons and declined in species-poor arid areas. Phenological changes were widespread, revealing substantive transitions in grassland seasonal cycling. Grazing, nitrogen deposition and plant invasion were prevalent in some regions but did not predict overall trends. Grasslands are undergoing sizable changes in production, with implications for food security, biodiversity and carbon storage especially in arid regions where declines are accelerating., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Biapenem has been recently approved by the Drug Controller General of India for the treatment of complicated urinary tract infections (cUTI). However, there are no assessment studies that evaluate the in-vitro activity of biapenem against contemporary ESBL-producing Indian Enterobacterales isolates. To determine the activity of biapenem against contemporary ESBLs and/or OXA-1/ampC producing Enterobacterales and Pseudomonas aeruginosa isolates., Methodology: Isolates were tested for susceptibility to biapenem and its comparators using the broth microdilution method. Presence of ESBLs (SHV, TEM, CTX-M) genes, OXA-1, and ampC genes (ACC, ACT, DHA, CIT/CMY, FOX) using multiplex PCR., Results: Against ESBL with OXA-1 and/or ampC-producing E. coli, ESBL-K. pneumoniae, and cephalosporin-resistant P. aeruginosa, biapenem showed in-vitro activity similar to that of meropenem. Overall, a biapenem disc concentration of 10 μg provided no error rates for testing E. coli, K. pneumoniae, and P. aeruginosa isolates., Conclusion: It is more accurate to test biapenem at a 10 μg disc concentration and apply more stringent disc diffusion breakpoints for interpretation., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content submitted., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Terahertz (THz) wireless communication holds immense potential to revolutionize future 6G to XG networks with high capacity, low latency and extensive connectivity. Efficient THz beamformers are essential for energy-efficient connections, compensating path loss, optimizing resource usage and enhancing spectral efficiency. However, current beamformers face several challenges, including notable loss, limited bandwidth, constrained spatial coverage and poor integration with on-chip THz circuits. Here we present an on-chip broadband THz topological beamformer using valley vortices for waveguiding, splitting and perfect isolation in waveguide phased arrays, featuring 184 densely packed valley-locked waveguides, 54 power splitters and 136 sharp bends. Leveraging neural-network-assisted inverse design, the beamformer achieves complete 360° azimuthal beamforming with gains of up to 20 dBi, radiating THz signals into free space with customizable user-defined beams. Photoexciting the all-silicon beamformer enables reconfigurable control of THz beams. The low-loss and broadband beamformer enables a 72-Gbps chip-to-chip wireless link over 300 mm and eight simultaneous 40-Gbps wireless links. Using four of these links, we demonstrate point-to-4-point real-time HD video streaming. Our work provides a complementary metal-oxide-semiconductor-compatible THz topological photonic integrated circuit for efficient large-scale beamforming, enabling massive single-input multiple-output and multiple-input and multiple-output systems for terabit-per-second 6G to XG wireless communications., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Cervical lymph node metastasis is one of the most common clinical presentations of papillary thyroid carcinoma (PTC). Occult thyroid carcinoma is described as absence of primary tumour or with presence of microcarcinoma in thyroid with cervical lymph node metastasis. Frequency of occult thyroid cancer has decreased due to developments in imaging and improved accuracy of histological examinations. 38 year old male presented to us with complaints of swelling over the left side of neck for the past 2 months. Ultrasonography was suggestive of multiple suspicious enlarged nodes in left level II, III, IV and V and fine needle aspiration cytology showed features of metastatic PTC. He was planned for total thyroidectomy with central compartment clearance and bilateral functional neck dissection. Final histopathology staging was pT0N1b. Radioactive iodine (RAI) screening showed residual functioning thyroid and later therapeutic RAI was administered. He has been on regular follow up and disease free for 1 year post treatment. Occult thyroid carcinoma is a rare diagnosis with multiple treatment plans. Few hypothesis for this entity includes tumor regression, ectopic thyroid carcinoma or missed pathological findings., Competing Interests: Conflict of interestNo potential conflict of interest relevant to this article exist., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults., Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3., Design, Setting, and Participants: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease., Exposures: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board., Main Outcomes and Measures: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion., Results: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources)., Conclusions and Relevance: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.

Introduction: There is limited literature on digital ischemia in systemic Lupus erythematosus (SLE). We report the prevalence, associations and outcome of digital infarcts and gangrene from the Indian SLE inception cohort (INSPIRE)., Methods: From the web-based database of INSPIRE, we extracted information for patients with 'Digital Infarct' and 'Digital gangrene' at enrolment into cohort, together considered as critical peripheral ischemia (CPI); all others were controls. We describe the associations of CPI with SLE clinical phenotype, autoantibodies, and disease activity at enrolment. We also report short term outcomes viz. Digital tissue loss and early mortality up to 6 months and recurrence of digital ischemic events in cases till date., Results: Of 2503 SLE patients enrolled into the INSPIRE cohort, we identified 75 (2.9%) patients with CPI, 72 (96%) women and 6 (8%) children. Of them, 55 (73.3%) had digital gangrene and 21 (28%) patients had digital infarcts. Majority of digital gangrene resulted in amputation distal to terminal phalanx (63.6%). Multivariable analysis showed that pulmonary hypertension AOR [6.34 (1.99, 20.2)], coexistent thrombosis AOR [27.8 (15.7, 48.7)], triple antiphospholipid antibody positivity AOR [5.36 (1.67, 16.9)] and the presence of anti-Scl-70-antibody AOR [5.59 (1.86, 16.7)] were more likely while patients with class 3 or 4 lupus nephritis AOR [0.37 (0.15, 0.95)] and anti-nucleosome antibodies AOR [0.47 (0.23, 0.99)] were less likely to be associated with CPI. SLEDAI and short-term mortality were similar between cases and controls., Conclusions: CPI occurred in a higher proportion (2.9%) of SLE patients in the INSPIRE cohort as compared to earlier reports. Both prothrombotic state and vasculopathy contribute to its occurrence., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Purpose: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT., Methods: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model., Results: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01)., Conclusions: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The present study aimed to investigate the molecular epidemiology, risk factors, and haemato-biochemical changes in anaplasmosis in Indian dromedary camels. Blood samples collected from 103 camels were analysed using blood smear examination and semi-nested PCR based on the 16s rRNA gene to diagnose anaplasmosis. The prevalence of anaplasmosis was estimated to be 42.72% (95% CI: 33.59-52.37) by PCR assay and 16.5% (95% CI: 10.47-24.95%) by blood smear examination. Phylogenetic analysis of six partial sequences of 16s rRNA gene obtained in the present study indicated the involvement of multiple Anaplasma species, including A. marginale and A. platys, showing genetic similarity with cattle strains. A novel genotype related to A. camelii/A. cinensis/A. platys group was also identified. Hemato-biochemical examination revealed mild anaemia, increased serum urea nitrogen and creatinine levels, and decreased total protein and albumin levels in Anaplasma-positive animals. The infections were largely subclinical in nature, except in one camel that revealed fever, inappetence, and pale mucous membrane and responded well to treatment with oxytetracycline. To our knowledge, this is the first molecular study on camel anaplasmosis in India, indicating a high prevalence of infection and involvement of multiple Anaplasma species with potential risk for interspecies transmission., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background/objective: To determine the prevalence of visual impairment (VI), uncorrected refractive errors (URE), and effective refractive error coverage among individuals aged 15-50 years in Koshi Province, Nepal., Methods: A population-based cross-sectional study was conducted in Koshi Province in which 4800 participants were selected from 80 clusters. The study teams visited the selected households and conducted eye examinations. This included monocular unaided (and aided) visual acuity assessment using a Snellen chart with tumbling E optotypes at a distance of 6 meters. Near vision was assessed binocularly using the N notation chart at a fixed distance of 40 cm for each individual. Torchlight examination and distance direct ophthalmoscopy was done. VI was defined as presenting visual acuity worse than 6/12 in the better eye. URE was defined as presenting visual acuity worse than 6/12 and improving to 6/12 or better on using a pinhole. Near Vision Impairment was defined as binocular presenting near vision worse than N8 among those age 35 years and older., Results: In total, 4057 were examined (84.5% response rate). The prevalence of VI was 3.52% (95% CI:2.89-4.13; n = 143). The prevalence of URE in the better eye was 1.95% (95% CI:1.54-2.42; n = 79). The Refractive Error Coverage and Effective Refractive Error Coverage were 34.8% and 31.3% respectively. The prevalence of NVI was 34.24% (95% CI: 32.1-36.40; n = 666)., Conclusion: The prevalence of VI and  URE was low, attributed to the availability and uptake of services in Koshi province in Nepal., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Dynamic terahertz devices are vital for the next generation of wireless communication, sensing, and non-destructive imaging technologies. Metasurfaces have emerged as a paradigm-shifting platform, offering varied functionalities, miniaturization, and simplified fabrication compared to their 3D counterparts. However, the presence of in-plane mirror symmetry and reduced degree of freedom impose fundamental limitations on achieving advanced chiral response, beamforming, and reconfiguration capabilities. In this work, a platform composed of electrically actuated resonators that can be colossally reconfigured between planar and 3D geometries is demonstrated. To illustrate the platform, metadevices with 3D Split Ring Resonators are fabricated, wherein two counteracting driving forces are combined: i) folding induced by stress mismatch, which enables non-volatile state design and ii) unfolding triggered by the strain associated with insulator-to-metal transition in VO 2 , which facilitates volatile structural reconfiguration. This large structural reconfiguration space allows for resonance mode switching, widely tunable magnetic and electric polarizabilities, and increased frequency agility. Moreover, the unique properties of VO 2 , such as the hysteretic nature of its phase transition is harnessed to demonstrate a multi-state memory. Therefore, these VO 2 integrated metadevices are highly attractive for the realization of 6G communication devices such as reconfigurable intelligent surfaces, holographic beam formers, and spatial light modulators., (© 2024 Wiley‐VCH GmbH.)

Aquatic invasive species (AIS) are one of the greatest threats to the functioning of aquatic ecosystems worldwide. Once an invasive species has been introduced to a new region, many governments develop management strategies to reduce further spread. Nevertheless, managing AIS in a new region is challenging because of the vast areas that need protection and limited resources. Spatial heterogeneity in invasion risk is driven by environmental suitability and propagule pressure, which can be used to prioritize locations for surveillance and intervention activities. To better understand invasion risk across aquatic landscapes, we developed a simulation model to estimate the likelihood of a waterbody becoming invaded with an AIS. The model included waterbodies connected via a multilayer network that included boater movements and hydrological connections. In a case study of Minnesota, we used zebra mussels (Dreissena polymorpha) and starry stonewort (Nitellopsis obtusa) as model species. We simulated the impacts of management scenarios developed by stakeholders and created a decision-support tool available through an online application provided as part of the AIS Explorer dashboard. Our baseline model revealed that 89% of new zebra mussel invasions and 84% of new starry stonewort invasions occurred through boater movements, establishing it as a primary pathway of spread and offering insights beyond risk estimates generated by traditional environmental suitability models alone. Our results highlight the critical role of interventions applied to boater movements to reduce AIS dispersal., (© 2024 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

To investigate how the fatty acid composition of brain phospholipids influences brain-specific processes, we leveraged the AdipoR2 (adiponectin receptor 2) knockout mouse model in which the brain is enlarged, and cellular membranes are excessively rich in saturated fatty acids. Lipidomics analysis of brains at 2, 7, and 18 months of age showed that phosphatidylcholines, which make up about two-thirds of all cerebrum membrane lipids, contain a gross excess of saturated fatty acids in AdipoR2 knockout mice, and that this is mostly attributed to an excess palmitic acid (C16:0) at the expense of oleic acid (C18:1), consistent with a defect in fatty acid desaturation and elongation in the mutant. Specifically, there was a ~12% increase in the overall saturated fatty acid content within phosphatidylcholines and a ~30% increase in phosphatidylcholines containing two palmitic acids. Phosphatidylethanolamines, sphingomyelins, ceramides, lactosylceramides, and dihydroceramides also showed an excess of saturated fatty acids in the AdipoR2 knockout mice while nervonic acid (C24:1) was enriched at the expense of shorter saturated fatty acids in glyceroceramides. Similar defects were found in the cerebellum and myelin sheaths. Histology showed that cell density is lower in the cerebrum of AdipoR2 knockout mice, but electron microscopy did not detect reproducible defects in the ultrastructure of cerebrum neurons, though proteomics analysis showed an enrichment of electron transport chain proteins in the cerebellum. Behavioral tests showed that older (33 weeks old) AdipoR2 knockout mice are hyperactive and anxious compared to control mice of a similar age. Also, in contrast to control mice, the AdipoR2 knockout mice do not gain weight in old age but do have normal lifespans. We conclude that an excess fatty acid saturation in brain phospholipids is accompanied by hyperactivity but seems otherwise well tolerated., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Objective: To update and add to the first report commissioned by the Blue Ribbon Committee about 20 years prior., Summary of Background Data: Following a summit in late 2022 commissioned by the American Board of Surgery regarding competency-based reforms in surgical education and via a partnership with the American College of Surgeons (ACS) and other stakeholders, a Blue Ribbon Committee (BRC-II) on surgical education was formed. The BRC-II would have seven subcommittees. This paper details the work of the Medical Student Subcommittee within the BRC- II., Methods: The subcommittee's work, supported by staff from the ACS, entailed a thorough literature review, which involved collating and aggregating the findings, identifying key challenges and opportunities, and committing to draft recommendations. These recommendations were then presented and refined via discussions with the Blue Ribbon Committee at large in multiple virtual and in-person settings., Results: The subcommittee's work is detailed below and further summarized in table format. The section below elucidates the medical student education continuum and discusses the pertinent topics of recruitment, surgical engagement in medical student training and the surgical image, training for the current surgical practice model, trainee selection for graduate medical education (GME), and optimizing the transition from undergraduate medical education (UME) to GME., Conclusions: The last two decades have shown significant changes and shifts in medical education and surgical practice. The findings of BRC-II in this manuscript help to structure the current and future necessary improvements, focusing on different aspects of medical student education., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The rearrangement and expression of the immunoglobulin μ heavy chain (Igh) gene require communication of the intragenic Eμ and 3' regulatory region (RR) enhancers with the variable (V H ) gene promoter. Eμ binding of the transcription factor YY1 has been implicated in enhancer-promoter communication, but the YY1 protein network remains obscure. By analyzing the comprehensive proteome of the 1-kb Eμ wild-type enhancer and that of Eμ lacking the YY1 binding site, we identified the male-specific lethal (MSL)/MOF complex as a component of the YY1 protein network. We found that MSL2 recruitment depends on YY1 and that gene knockout of Msl2 in primary pre-B cells reduces μ gene expression and chromatin looping of Eμ to the 3' RR enhancer and V H promoter. Moreover, Mof heterozygosity in mice impaired μ expression and early B cell differentiation. Together, these data suggest that the MSL/MOF complex regulates Igh gene expression by augmenting YY1-mediated enhancer-promoter communication., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Commercially available plasma p-tau217 biomarker tests are not well studied in ethnically diverse samples., Methods: We evaluated associations between ALZPath plasma p-tau217 and amyloid-beta positron emission tomography (Aβ-PET) in Hispanic/Latino (88% of Cuban or South American ancestry) and non-Hispanic/Latino older adults. One- and two-cutoff ranges were derived and evaluated to assess agreement with Aβ-PET., Results: A total of 239 participants underwent blood draw and Aβ-PET (age 70.8 ± 7.8, 55.2% female, education 15.6 ± 3.4 years, 48.9% Hispanic/Latino, 94.9% white). Plasma p-tau217 showed excellent discrimination of Aβ-PET positive and negative participants (visual read: AUC = 0.91 [0.87-0.95], p  < 0.001; Centiloids quantification: AUC = 0.90 [0.86-0.94]). There was a greater percent agreement between low p-tau217 and negative Aβ-PET (95.8%) than high p-tau217 and positive Aβ-PET (86.3%). Analyses within ethnicity-specific subgroups suggested similar p-tau217 performance., Discussion: Plasma p-tau217 (ALZPath) relates to brain Aβ in Hispanic/Latino and non-Hispanic/Latino older adults. Independent validation and replication are necessary to establish reference ranges and inform appropriate contexts of use across ethno-racially diverse populations., Highlights: Plasma p-tau217 (ALZPath) and Aβ-PET were measured in Hispanic/Latino and non-Hispanic/Latino older adults.Plasma p-tau217 accurately discriminated Aβ-PET positive and negative participants.Applying a two-cutoff "intermediate" plasma p-tau217 approach could reduce need for more invasive and costly testing.Plasma p-tau217 associations with Aβ-PET were strong within both Hispanic/Latino and non-Hispanic/Latino groups., Competing Interests: The authors report no disclosures relevant to the content of this work. STDeK reports being a consultant with Biogen, Prevail, Vaccinex, and Acumen Dementia. DEV reports consulting for Neuroimaging Solutions. All other authors report no disclosures. Author disclosures are available in the Supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The interferon (IFN) system protects mammals from diseases caused by virus infections. IFN synthesis is induced by pattern recognition receptor signaling pathways activated by virus infection. IFN is secreted from the infected cells and acts upon neighboring cells by binding cell surface receptors and triggering induction of hundreds of IFN-stimulated genes and proteins, many of which block different steps of virus replication. The IFN-induced tetratricopeptide repeat proteins (IFIT) are a family of RNA-binding proteins. We and others have previously reported that IFIT2 protects mice from many neurotropic RNA viruses; indeed, Ifit2-/- mice are very susceptible to intranasal or subcutaneous infections with vesicular stomatitis virus (VSV). Here, using a newly generated conditional knockout mouse, we report that ablation of Ifit2 expression only in neuronal cells was sufficient to render mice susceptible to neuropathogenesis caused by intranasal, but not subcutaneous, infection of VSV. Another genetically modified mouse line, expressing a mutant IFIT2 that cannot bind RNA, was as susceptible to VSV infection as Ifit2 -/- mice. These results demonstrated that IFIT2 RNA-binding activity is essential for protecting mice against neurological diseases caused by intranasal infection of VSV.IMPORTANCEInterferon's (IFN's) antiviral effects are mediated by the proteins encoded by the interferon-stimulated genes. IFN-stimulated genes (IFIT2) is one such protein, which inhibits replication of many RNA viruses in the mouse brain and the resultant neuropathology. Our study sheds light on how IFIT2 works. By ablating Ifit2 expression only in neuronal cells, using a newly generated conditional knockout mouse line, we showed that Ifit2 induction in the neurons of the infected mouse was necessary for antiviral function of interferon. IFIT2 has no known enzyme activity; instead, it functions by binding to cellular or viral proteins or RNAs. We engineered a new mouse line that expressed a mutant IFIT2 that cannot bind RNA. These mice were very susceptible to infection with vesicular stomatitis virus indicating that the RNA-binding property of IFIT2 was essential for its antiviral function in vivo ., Competing Interests: The authors declare no conflict of interest.

Novel therapies for heart failure with reduced ejection fraction (HFrEF) are angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose co-transporter 2 inhibitor (SGLT2i), etc. The purpose of this review is to determine the effects of ARNI and SGLT2i in heart failure (HF), compare the impact of SGLT2i with ARNI, and finally evaluate the current data regarding the combination of these two drugs in HF. Various trials on the respective medications have shown some significant reduction in all-cause mortality and cardiovascular (CV) death. The combination of these drugs has shown more CV benefits than monotherapy. There is emerging data about these two drugs in patients with heart failure with preserved ejection fraction (HFpEF). At present, there are less head-to-head comparison trials of these two drugs. This review provides insights on the current evidence, comparative efficacy, and combination therapy of ARNI and SGLT2i in managing HF, focussing on HFrEF and HFpEF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

We report herein an eosin Y/Pd(II) dual catalytic approach for regio- and chemoselective C(sp 2 )-H monoarylation of N-H unprotected 2-phenyl quinazolinone derivatives under green light irradiation with no necessity for any base/additive/external oxidant. The free N-H moiety was post-modified for quinazolinone scaffold diversification and C-H annulation.

Dysregulation of oligodendrocyte progenitor cell (OPC) recruitment and oligodendrocyte differentiation contribute to failure of remyelination in human demyelinating diseases such as multiple sclerosis (MS). Deletion of muscarinic receptor enhances OPC differentiation and remyelination. However, the role of ligand-dependent signaling versus constitutive receptor activation is unknown. We hypothesized that dysregulated acetylcholine (ACh) release upon demyelination contributes to ligand-mediated activation hindering myelin repair. Following chronic cuprizone (CPZ)-induced demyelination (male and female mice), we observed a 2.5-fold increase in ACh concentration. This increase in ACh concentration could be attributed to increased ACh synthesis or decreased acetylcholinesterase-/butyrylcholinesterase (BChE)-mediated degradation. Using choline acetyltransferase (ChAT) reporter mice, we identified increased ChAT-GFP expression following both lysolecithin and CPZ demyelination. ChAT-GFP expression was upregulated in a subset of injured and uninjured axons following intraspinal lysolecithin-induced demyelination. In CPZ-demyelinated corpus callosum, ChAT-GFP was observed in Gfap + astrocytes and axons indicating the potential for neuronal and astrocytic ACh release. BChE expression was significantly decreased in the corpus callosum following CPZ demyelination. This decrease was due to the loss of myelinating oligodendrocytes which were the primary source of BChE. To determine the role of ligand-mediated muscarinic signaling following lysolecithin injection, we administered neostigmine, a cholinesterase inhibitor, to artificially raise ACh. We identified a dose-dependent decrease in mature oligodendrocyte density with no effect on OPC recruitment. Together, these results support a functional role of ligand-mediated activation of muscarinic receptors following demyelination and suggest that dysregulation of ACh homeostasis directly contributes to failure of remyelination in MS., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Introduction: The gut microbiome's influence on weight management has gained significant interest for its potential to support better obesity therapeutics. Patient stratification leading to personalized nutritional intervention has shown benefits over one-size-fit-all diets. However, the efficacy and impact on the gut's microbiome of personalizing weight loss diets based on individual factors remains under-investigated., Methods: This study assessed the impact of Digbi Health's personalized dietary and lifestyle program on weight loss and the gut microbiome end-points in 103 individuals. Participants' weight loss patterns and gut microbiome profiles were analyzed from baseline to follow-up samples., Results: Specific microbial genera, functional pathways, and communities associated with BMI changes and the program's effectiveness were identified. 80% of participants achieved weight loss. Analysis of the gut microbiome identified genera and functional pathways associated with a reduction in BMI, including Akkermansia, Christensenella, Oscillospiraceae, Alistipes, and Sutterella, short-chain fatty acid production, and degradation of simple sugars like arabinose, sucrose, and melibiose. Network analysis identified a microbiome community associated with BMI, which includes multiple taxa known for associations with BMI and obesity., Discussion: The personalized dietary and lifestyle program positively impacted the gut microbiome and demonstrated significant associations between gut microbial changes and weight loss. These findings support the use of the gut microbiome as an endpoint in weight loss interventions, highlighting potential microbiome biomarkers for further research., Competing Interests: SK, IP, BJ, KM, SS, CI, RS and DA are employees and/or contractors of Digbi Health and may hold stocks or stock options on Digbi Health. GK was an advisor to Digbi Health and has received stock options from Digbi Health. The digital therapeutics program provided to study participants in this work is a commericially available program developed and marketed by Digbi Health. PD has received consulting and/or research support from Takeda, Pfizer, Janssen, BMS, Gilead, Novartis, Lily; and royalties from PreciDiag. RS was CEO and founder of Digbi Health. DA has received royalties from Kura Biotech. SK, IP, RS, and DA had patents pending concerning this work: US Application No. 17/817,558, Methods and systems for multi-omic interventions, and US Application No. 63/476,672, Methods and systems for longitudinal gut microbiome interventions as diagnostics for personalized care. The former conflicts of interest do not alter our adherence to policies on sharing data and materials., (Copyright © 2024 Kumbhare, Pedroso, Joshi, Muthukumar, Saravanan, Irudayanathan, Kochhar, Dulai, Sinha and Almonacid.)

An interview-based questionnaire survey was done in 2021 to assess the socio-economic conditions, farming practices adopted, and problems faced by fish farmers and to analyze the cost and benefits of fish farming in the Fish super zone area of Pachrauta Municipality, Bara district. A simple random sampling technique was used to select 60 respondents for the study and the information collected was analyzed and processed by MS-Excel and SPSS. The majority of respondents were male, belonged to the age group of 25-36 years, and had a secondary level of school education. The mean total land holding size was found to be 3.65 ± 2.57 bigha with a total pond area of 1.38 ± 1.08 bigha and a small minority (18 %) practiced contract farming. Most of the farmers were found to have experience of 6-11 years (40 %). The farming system was polyculture and mostly Intensive (60 %). While the use of modern equipment was low (25 %), the majority of farmers (>90 %) practiced regular drying and liming of ponds. Mid-April to Mid-July was the most preferred time of stocking and the big fraction of feed used was locally prepared (70 %). Fertilizer use and Multiple harvesting were also common. Fish farming in the study area was found to fetch an average annual income of 0.95 million NRs. The major problems faced by farmers were Expensive feed (0.67), Lack of quality seeds (0.60), and Lack of proper marketing channels (0.55). Despite the constraints, Economic analysis revealed fish production in the study area as a profitable business with a BC ratio of 2.20 and a high gross margin value (Rs. 1330341.6 per hectare)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Adarsha Neupane (First Author) reports financial support was provided by PMAMP-PIU Bara. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)