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Abstract Large mammals with general habitat needs can persist throughout mixed used landscapes, however, human-wildlife conflict frequently leads to their restriction to protected areas. Conservation efforts, especially for reducing conflicts with humans, can enhance tolerance of humans towards species like Asian elephants (Elephas maximus) in human-dominated landscapes. Here, we examine how elephant use in the Chure Terai Madhesh Landscape (CTML) covering the entire elephant range of Nepal changed between 2012 and 2020 in relationship to protection status and environmental conditions. We systematically surveyed ~ 42,000 km2 of potential habitat, by dividing the study area into 159 grid cells of 15 × 15 km2 and recorded elephant signs during the cool, dry season in three years (2012, 2018 and 2020). We analyzed the survey data in a single-species, multi-season (dynamic) occupancy modeling framework to test hypotheses regarding the influence of environmental conditions and protected area status on landscape use by elephants over time. The best-supported model included protected area effects on initial use, colonization, and detection probability as well as temporal variation in colonization and detection probability. Initial use and colonization rates were higher in protected areas, however elephants increasingly used cells located both inside and outside the protected areas, and the difference in use between protected areas and outside declined as elephants use became prevalent across most of the landscape. While elephant use was patchily distributed in the first year of surveys consistent with past descriptions of four sub-populations, elephant use consolidated into a western and eastern region in subsequent years with a gap in their distribution occurring between Chitwan and Bardiya National Parks. Our manuscript highlights the increasing landscape use by elephants in both protected areas and areas outside protected areas and suggests that management interventions that focus on reducing conflicts can promote greater use of both protected areas and areas outside of protected areas.

Context: Regarding the relationship between the size of the pharynx and several sagittal skeletal malocclusions and patterns of growth, contradictory findings have been documented. Aims: The intent of this research was to analyze the size of the pharynx in various sagittal malocclusions and growth patterns in the Nepalese population. Settings and Design: An analytic cross-sectional research was undertaken on patients who attended the Orthodontics Division of BPKIHS. Materials and Methods: A total of 135 patients’ lateral cephalometric radiographs were gathered. Medians and interquartile ranges of pharyngeal widths according to McNamara airway analysis and Arnett/Gunson FAB airway analysis adapted by Santiago et al. in different skeletal malocclusions and growth patterns were compared. Results: There was not any discernible statistically noteworthy variation within the upper pharynx size, lower pharyngeal width, nasopharyngeal width (WNP), oropharyngeal width, hypopharyngeal width (WHP), and deep pharyngeal width (WDP) in different skeletal malocclusions. A statistically significant variation was discovered in nasopharyngeal size (P = 0.010), hypopharyngeal size (P = 0.027), and deep pharyngeal size (P < 0.001) in various patterns of growth, i.e. hypodivergent versus normodivergent, and in hypodivergent versus hyperdivergent, not in normodivergent versus hyperdivergent group of patients. Conclusion: There was not anything statistically noteworthy variation in the pharyngeal widths of the participants with respect to the various skeletal malocclusions. WNP, WHP, and WDP showed a statistically significant variation between hypodivergent versus normodivergent and hypodivergent versus hyperdivergent growth patterns.

The diagnosis of adult Hirschsprung disease (HD) is rare, furthermore there are only 3 or 4 cases of adult ultrashort segment HD (USHD) reported previously in English literature to our knowledge. Herein, we present a case of a 22-year-old female presented with long standing history of constipation and abdominal distension secondary to USHD. Imaging modalities included plain abdominal X-ray, ultrasound (USG) and computed tomography (CT) scan which collectively aided in establishing the diagnosis. Through this case report, we aim to emphasize that HD should be suspected in every adult population with chronic constipation. Also, it highlights the role of CT scan as how it should be the preferred diagnostic tool for suspected adult HD, as, not only it helps correctly identify the transition zone but rule out other possible causes of chronic obstruction.

Abstract Accurately building 3D atomic structures from cryo-EM density maps is a crucial step in cryo-EM-based protein structure determination. Converting density maps into 3D atomic structures for proteins lacking accurate homologous or predicted structures as templates remains a significant challenge. Here, we introduce Cryo2Struct, a fully automated de novo cryo-EM structure modeling method. Cryo2Struct utilizes a 3D transformer to identify atoms and amino acid types in cryo-EM density maps, followed by an innovative Hidden Markov Model (HMM) to connect predicted atoms and build protein backbone structures. Cryo2Struct produces substantially more accurate and complete protein structural models than the widely used ab initio method Phenix. Additionally, its performance in building atomic structural models is robust against changes in the resolution of density maps and the size of protein structures.

Abstract The advent of single-particle cryo-electron microscopy (cryo-EM) has brought forth a new era of structural biology, enabling the routine determination of large biological molecules and their complexes at atomic resolution. The high-resolution structures of biological macromolecules and their complexes significantly expedite biomedical research and drug discovery. However, automatically and accurately building atomic models from high-resolution cryo-EM density maps is still time-consuming and challenging when template-based models are unavailable. Artificial intelligence (AI) methods such as deep learning trained on limited amount of labeled cryo-EM density maps generate inaccurate atomic models. To address this issue, we created a dataset called Cryo2StructData consisting of 7,600 preprocessed cryo-EM density maps whose voxels are labelled according to their corresponding known atomic structures for training and testing AI methods to build atomic models from cryo-EM density maps. Cryo2StructData is larger than existing, publicly available datasets for training AI methods to build atomic protein structures from cryo-EM density maps. We trained and tested deep learning models on Cryo2StructData to validate its quality showing that it is ready for being used to train and test AI methods for building atomic models.

Abstract In the middle of an ever‐changing landscape of diabetes care, precision medicine, and lifestyle therapies are becoming increasingly important. Dietary polyphenols are like hidden allies found in our everyday meals. These biomolecules, found commonly in fruits, vegetables, and various plant‐based sources, hold revolutionary potential within their molecular structure in the way we approach diabetes and its intimidating consequences. There are currently numerous types of diabetes medications, but they are not appropriate for all patients due to limitations in dosages, side effects, drug resistance, a lack of efficacy, and ethnicity. Currently, there has been increased interest in practicing herbal remedies to manage diabetes and its related complications. This article aims to summarize the potential of dietary polyphenols as a foundation in the treatment of diabetes and its associated consequences. We found that most polyphenols inhibit enzymes linked to diabetes. This review outlines the potential benefits of selected molecules, including kaempferol, catechins, rosmarinic acid, apigenin, chlorogenic acid, and caffeic acid, in managing diabetes mellitus as these compounds have exhibited promising results in in vitro, in vivo, in silico, and some preclinical trials study. This encompassing exploration reveals the multifaceted impact of polyphenols not only in mitigating diabetes but also in addressing associated conditions like inflammation, obesity, and even cancer. Their mechanisms involve antioxidant functions, immune modulation, and proinflammatory enzyme regulation. Furthermore, these molecules exhibit anti‐tumor activities, influence cellular pathways, and activate AMPK pathways, offering a less toxic, cost‐effective, and sustainable approach to addressing diabetes and its complications.

Abstract Background Disability stigma in low- and middle-income countries is one of the most persistent and complex barriers limiting persons with disabilities (PwDs) from enjoying their rights and opportunities. Perceived stigma among PwDs and its impact on participation restriction is rarely assessed in Nepal. Objective This study aimed to measure the extent of perceived stigma by PwDs, identify its relationships with specific demographic factors, and assess the impact on social participation. Methods A cross-sectional survey was conducted between May and July 2022 among PwDs in Nepal, with a sample of 371. The Explanatory Model Interview Catalog (EMIC) stigma scale and P-scale suitable for people affected by stigmatized conditions were used, and the generated scores were analyzed. One-way ANOVA was performed to determine group differences for sociodemographic variables, and linear regression and correlational analysis were used to identify their association and measure the strength and direction of the relationship. Results The mean stigma score was 16.9 (SD 13.8). 42% of respondents scored higher than the mean. The scores differed significantly by disability type, caste and ethnicity, education, occupation, and household wealth. Over 56% reported participation restriction, and 38% had severe/extreme restriction. Approximately 65% of participants with intellectual disabilities, 53% with multiple disabilities, and 48.5% of persons with severe or profound disabilities experienced severe or extreme restrictions. Perceived stigma had a positive correlation with Disability type (r = 0.17, P 0.05). Conclusion All participants exhibited stigma in general; however, the severity varied based on disability type, level of education, and sociocultural circumstances. A large proportion of participants reported facing a high degree of restrictions in participation; however, no association was detected between perceived stigma and participation restriction. A significant negative linear correlation was observed between education and participation restriction. Stigma reduction programs focusing on education and empowerment would be especially important for overcoming internalized stigma and increasing the participation of PwDs.

Synchronous existence of hepatic, splenic, and skeletal hemangiomas has not been reported previously in the English literature to our knowledge. In this case report, we present a case of coexistence of hepatic, splenic, and skeletal hemangiomas in a 30-year-old woman with on and off bilateral lumbar region pain and no significant past medical history. Radiological investigations, including ultrasound and computed tomography and magnetic resonance imaging helped identify the synchronous existence of hepatic, splenic, and skeletal hemangiomas. The patient improved with conservative management and was kept on follow-ups. Although there have been reports of coexistence of splenic and hepatic hemangiomas in the literature, to our knowledge, this is the first report of synchronous existence of hepatic, splenic, and skeletal hemangiomas.

At the onset of egg production, physiological changes governing calcium and phosphorus utilization must occur to meet demands for medullary bone formation and eggshell mineralization. The objective of this study was to identify these changes and determine if they are influenced by dietary supplementation with 1α-hydroxycholecalciferol (AlphaD3™, Iluma Alliance). Commercial laying hens fed either a control or AlphaD3-supplemented diet beginning at 18 weeks of age were sampled at 18 (n = 8) and 31 weeks (n = 8/diet) to evaluate mRNA expression associated with calcium and phosphorus utilization in kidney, shell gland, ileum, and liver, circulating vitamin D3 metabolites, and bone quality parameters in humerus, tibia, and keel bone. Though diet did not heavily influence gene expression at 31 weeks, several significant differences were observed between 18- and 31-week-old hens. Heightened sensitivity to hormones regulating calcium and phosphorus homeostasis was observed at 31 weeks, indicated by increased parathyroid hormone receptor 1, calcium-sensing receptor, calcitonin receptor, and fibroblast growth factor 23 receptors in several tissues. Increased renal expression of 25-hydroxylase and vitamin D binding protein (DBP) at 31 weeks suggests kidney participates in local vitamin D3 25-hydroxylation and DBP synthesis after egg production begins. Biologically active 1,25(OH)2D3 was higher at 31 weeks, with correspondingly lower inactive 24,25(OH)2D3. Increased expression of plasma membrane calcium ATPase 1 and calbindin in kidney, shell gland, and ileum suggests these are key facilitators of calcium uptake. Elevated renal inorganic phosphorus transporter 1 and 2 and sodium-dependent phosphate transporter IIa at 31 weeks suggests increased phosphorus excretion following hyperphosphatemia due to bone breakdown for eggshell formation. Diet did influence bone quality parameters. Bone mineral density in both humerus and tibia was higher in AlphaD3-supplemented hens at 31 weeks. Tibial bone mineral content increased between 18 and 31 weeks, with AlphaD3-supplemented hens increasing more than control hens. Moreover, control hens exhibited diminished tibial breaking strength at 31 weeks compared to hens at 18 weeks, while AlphaD3-supplemented hens did not. Together, these results indicate supplementation with AlphaD3 enhanced bone mineralization during the medullary bone formation period and elucidate the adaptive pathways regulating calcium and phosphorus utilization after the onset of lay.

Background: Reperfusion injury, characterized by oxidative stress and inflammation, poses a significant challenge in cardiac surgery with cardiopulmonary bypass (CPB). Deferoxamine, an iron-chelating compound, has shown promise in mitigating reperfusion injury by inhibiting iron-dependent lipid peroxidation and reactive oxygen species (ROS) production. Objectives: The objective of our study was to analyze and evaluate both the efficacy and safety of a new and promising intervention, that is, deferoxamine for ischemia-reperfusion injury (I/R). Design: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines are used to perform the study. Data sources and methods: We conducted a systematic review following PRISMA guidelines to assess the efficacy and safety of deferoxamine in reducing I/R injury following CPB. A comprehensive search of electronic databases, namely, PubMed, Scopus, and Embase, yielded relevant studies published until August 18, 2023. Included studies evaluated ROS production, lipid peroxidation, cardiac performance, and morbidity outcomes. Results: (a) ROS production : Multiple studies demonstrated a statistically significant decrease in ROS production in patients treated with deferoxamine, highlighting its potential to reduce oxidative stress. (b) Lipid peroxidation : Deferoxamine was associated with decreased lipid peroxidation levels, indicating its ability to protect cardiac tissue from oxidative damage during CPB. (c) Cardiac performance : Some studies reported improvements in left ventricular ejection fraction and wall motion score index with deferoxamine. Conclusion: Our review shows that deferoxamine is an efficacious and safe drug that can be used to prevent myocardial I/R injury following CPB. It also highlights the need for trials on a larger scale to develop potential strategies and guidelines on the use of deferoxamine for I/R injury.

The sugary sap of different palm trees is fermented to create palm wine, an alcoholic beverage. This work was aimed at studying the changes that occur during the fermentation process of wine made from the sap of the wild date palm species Phoenix sylvestris. At first, the best age of the palm tree was determined by observing total soluble solid and sap yield for 24 h and was found to be middle-aged palm plants (15–40 years old). Pure wine yeast (Saccharomyces cerevisiae SC22) and a natural starter culture were added to the palm saps, adjusting the total soluble solid (TSS) to 21.5° brix (°Bx). Total titratable acidity, pH, volatile acidity, reducing sugar, non-reducing sugar, total sugar, alcohol content, ester content, and aldehyde contents were the parameters under investigation. The statistical analysis showed significant (p ≤ 0.05) changes in the physico-chemical and volatile constituents of palm sap during the fermentation process in both systems. Sensory evaluation revealed that palm wine fermented with pure yeast culture was significantly superior to natural, spontaneously fermented wine. The acceptability test showed that the ideal characteristics of palm wine are cloudy in appearance, fruity in aroma, and sweet in taste.

Chiuri (Diploknema butyracea) is a medium-sized tree indigenous to Nepal and integral to the Chepang ethnic group. The utilization of Chiuri has experienced a decline, leading to a perceptible gap between agricultural practitioners and entrepreneurial endeavors within the Chepang community. This study, conducted from January to July 2023 in the Rapti municipality of the Chitwan district, Nepal, aims to document both traditional and contemporary applications of Chiuri in the Chepang community, evaluating its market presence, economic contributions, and cultural practices. The research involved household surveys and six key informant interviews, employing structured and semi-structured questionnaires for primary data collection. The collected data underwent meticulous analysis using MS-Excel and statistical tools. Traditionally, the Chepang community employed Chiuri for diverse purposes, including the extraction of Chiuri butter, utilization of flower juice, leaf plate fabrication, liso production, and oilcake processing. However, contemporary practices have witnessed a transition towards packaged oil, various juice derivatives, and fertilizer. Historically, Chiuri butter held paramount importance as the primary source of income for the Chepang community, supplemented by revenue generated from honey, oilcake, leaf plate crafting, alcohol juice production, and liso manufacturing. Over the past two decades, a marked decline is evident, with only 36% of the population currently engaged in processing and selling Chiuri products, compared to 85% in the past. Market transactions predominantly occur in Lothar Bazaar, trailed by Bhandara and local markets, where Chiuri butter, honey, and seeds are the primary commodities. Beekeeping, honey production and butter have emerged as the predominant sources of income. Historically vital for the economic and social well-being of the Chepang community, Chiuri has seen a decline in traditional practices such as Chepuwa (Khalang) oil extraction and a diminishing prevalence of the dowry system. Adopting cost-effective treatment technology is crucial to replace traditional methods and ensure sustainable Chiuri product production.