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Abstract Expanding and intensifying agriculture has led to a loss of soil carbon. As agroecosystems cover over 40% of Earth’s land surface, they must be part of the solution put in action to mitigate climate change. Development of efficient management practices to maximize soil carbon retention is currently limited, in part, by a poor understanding of how plants, which input carbon to soil, and microbes, which determine its fate there, interact. Here we implement a diversity gradient by intercropping undersown species with barley in a large field trial, ranging from one to eight undersown species. We find that increasing plant diversity strengthens positive associations within the rhizosphere soil microbial community in relation to negative associations. These associations, in turn, enhance community carbon use efficiency. Jointly, our results highlight how increasing plant diversity in agriculture can be used as a management strategy to enhance carbon retention potential in agricultural soils.

Abstract Post-translational modifications (PTMs) are pivotal in modulating protein functions and influencing cellular processes like signaling, localization, and degradation. The complexity of these biological interactions necessitates efficient predictive methodologies. In this work, we introduce PTMGPT2, an interpretable protein language model that utilizes prompt-based fine-tuning to improve its accuracy in precisely predicting PTMs. Drawing inspiration from recent advancements in GPT-based architectures, PTMGPT2 adopts unsupervised learning to identify PTMs. It utilizes a custom prompt to guide the model through the subtle linguistic patterns encoded in amino acid sequences, generating tokens indicative of PTM sites. To provide interpretability, we visualize attention profiles from the model’s final decoder layer to elucidate sequence motifs essential for molecular recognition and analyze the effects of mutations at or near PTM sites to offer deeper insights into protein functionality. Comparative assessments reveal that PTMGPT2 outperforms existing methods across 19 PTM types, underscoring its potential in identifying disease associations and drug targets.

Abstract Influenza (sometimes referred to as “flu”) is a contagious viral infection of the airways in the lungs that affects a significant portion of the world's population. Clinical symptoms of influenza virus infections can range widely, from severe pneumonia to moderate or even asymptomatic sickness. If left untreated, influenza can have more severe effects on the heart, brain, and lungs than on the respiratory tract and can necessitate hospitalization. This study was aimed to investigate and characterize all types of influenza cases prevailing in Nepal and to analyze seasonal occurrence of Influenza in Nepal in the year 2019. A cross sectional, retrospective and descriptive study was carried out at National Influenza Center (NIC), National Public Health Laboratory Kathmandu Nepal for the period of one year (Jan–Dec 2019). A total of 3606 throat swab samples from various age groups and sexes were processed at the NIC. The specimens were primarily stored at 4 °C and processed using ABI 7500 RT PCR system for the identification of Influenza virus types and subtypes. Data accessed for research purpose were retrieved from National Influenza Centre (NIC) on 1st Jan 2020. Of the total 3606 patients suspected of having influenza infection, influenza viruses were isolated from 1213 (33.6%) patients with male predominance. The highest number of infection was caused by Influenza A/Pdm09 strain 739 (60.9%) followed by Influenza B 304 (25.1%) and Influenza A/H3 169 (13.9%) and most remarkable finding of this study was the detection of H5N1 in human which is the first ever case of such infection in human from Nepal. Similar to other tropical nations, influenza viruses were detected year-round in various geographical locations of Nepal. The influenza virus type and subtypes that were in circulation in Nepal were comparable to vaccine candidate viruses, which the currently available influenza vaccine may prevent.

Abstract Proline is widely known as the only proteogenic amino acid with a secondary amine. In addition to its crucial role in protein structure, the secondary amino acid modulates neurotransmission and regulates the kinetics of signaling proteins. To understand the structural basis of proline import, we solved the structure of the proline transporter SIT1 in complex with the COVID-19 viral receptor ACE2 by cryo-electron microscopy. The structure of pipecolate-bound SIT1 reveals the specific sequence requirements for proline transport in the SLC6 family and how this protein excludes amino acids with extended side chains. By comparing apo and substrate-bound SIT1 states, we also identify the structural changes that link substrate release and opening of the cytoplasmic gate and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.

Abstract Glucose transporter-2 (GLUT2) monitors cellular glucose uptake. Astrocyte GLUT2 controls glucose counterregulatory hormone secretion. In vivo gene silencing and laser-catapult-microdissection tools were used here to investigate whether ventromedial hypothalamic nucleus (VMN) GLUT2 may regulate dorsomedial (VMNdm) and/or ventrolateral (VMNvl) γ-aminobutyric acid (GABA) neurotransmission to control this endocrine outflow in female rats. VMN GLUT2 gene knockdown suppressed or stimulated hypoglycemia-associated glutamate decarboxylase (GAD)1 and GAD2 mRNA expression in VMNdm versus VMNvl GABAergic neurons, respectively. GLUT2 siRNA pretreatment also modified co-expressed transmitter marker gene profiles in each cell population. VMNdm GABA neurons exhibited GLUT2 knockdown-sensitive up-regulated 5’-AMP-activated protein kinase-alpha1 (AMPKα1) and -alpha2 (AMPKα2) transcripts during hypoglycemia. Hypoglycemic augmentation of VMNvl GABA neuron AMPKα2 was refractory to GLUT2 siRNA. GLUT2 siRNA blunted (VMNdm) or exacerbated (VMNvl) hypoglycemic stimulation of GABAergic neuron steroidogenic factor-1 (SF-1) mRNA. Results infer that VMNdm and VMNvl GABA neurons may exhibit divergent, GLUT2-dependent GABA neurotransmission patterns in the hypoglycemic female rat. Data also document differential GLUT2 regulation of VMNdm versus VMNvl GABA nerve cell SF-1 gene expression. Evidence for intensification of hypoglycemic hypercorticosteronemia and -glucagonemia by GLUT2 siRNA infers that VMN GLUT2 function imposes an inhibitory tone on these hormone profiles in this sex.

Abstract Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody development following repeat CHMI. After two exposures, time to blood stage patency increases significantly and the number of reported symptoms decreases indicating the development of clinical tolerance. The time to patency correlates positively with both anti-Pf circumsporozoite protein (CSP) IgG and CD8 + CD69+ effector memory T cell levels consistent with partial pre-erythrocytic immunity. IFNγ levels decrease significantly during the participants’ second exposure to high blood stage parasitemia and could contribute to the decrease in symptoms. In contrast, CD4-CD8 + T cells expressing CXCR5 and the inhibitory receptor, PD-1, increase significantly after subsequent Pf exposures, possibly dampening the memory response and interfering with the generation of robust sterilizing immunity.

Abstract Designing ultralight conductive aerogels with tailored electrical and mechanical properties is critical for various applications. Conventional approaches rely on iterative, time-consuming experiments across a vast parameter space. Herein, an integrated workflow is developed to combine collaborative robotics with machine learning to accelerate the design of conductive aerogels with programmable properties. An automated pipetting robot is operated to prepare 264 mixtures of Ti3C2Tx MXene, cellulose, gelatin, and glutaraldehyde at different ratios/loadings. After freeze-drying, the aerogels’ structural integrity is evaluated to train a support vector machine classifier. Through 8 active learning cycles with data augmentation, 162 unique conductive aerogels are fabricated/characterized via robotics-automated platforms, enabling the construction of an artificial neural network prediction model. The prediction model conducts two-way design tasks: (1) predicting the aerogels’ physicochemical properties from fabrication parameters and (2) automating the inverse design of aerogels for specific property requirements. The combined use of model interpretation and finite element simulations validates a pronounced correlation between aerogel density and compressive strength. The model-suggested aerogels with high conductivity, customized strength, and pressure insensitivity allow for compression-stable Joule heating for wearable thermal management.

Abstract Low-cost detection systems are needed for the identification of microplastics (MPs) in environmental samples. However, their rapid identification is hindered by the need for complex isolation and pre-treatment methods. This study describes a comprehensive sensing platform to identify MPs in environmental samples without requiring independent separation or pre-treatment protocols. It leverages the physicochemical properties of macroporous-mesoporous silver (Ag) substrates templated with self-assembled polymeric micelles to concurrently separate and analyze multiple MP targets using surface-enhanced Raman spectroscopy (SERS). The hydrophobic layer on Ag aids in stabilizing the nanostructures in the environment and mitigates biofouling. To monitor complex samples with multiple MPs and to demultiplex numerous overlapping patterns, we develop a neural network (NN) algorithm called SpecATNet that employs a self-attention mechanism to resolve the complex dependencies and patterns in SERS data to identify six common types of MPs: polystyrene, polyethylene, polymethylmethacrylate, polytetrafluoroethylene, nylon, and polyethylene terephthalate. SpecATNet uses multi-label classification to analyze multi-component mixtures even in the presence of various interference agents. The combination of macroporous-mesoporous Ag substrates and self-attention-based NN technology holds potential to enable field monitoring of MPs by generating rich datasets that machines can interpret and analyze.

Abstract Hematopoietic stem cell (HSC) mutations can result in clonal hematopoiesis (CH) with heterogeneous clinical outcomes. Here, we investigate how the cell state preceding Tet2 mutation impacts the pre-malignant phenotype. Using an inducible system for clonal analysis of myeloid progenitors, we find that the epigenetic features of clones at similar differentiation status are highly heterogeneous and functionally respond differently to Tet2 mutation. Cell differentiation stage also influences Tet2 mutation response indicating that the cell of origin’s epigenome modulates clone-specific behaviors in CH. Molecular features associated with higher risk outcomes include Sox4 that sensitizes cells to Tet2 inactivation, inducing dedifferentiation, altered metabolism and increasing the in vivo clonal output of mutant cells, as confirmed in primary GMP and HSC models. Our findings validate the hypothesis that epigenetic features can predispose specific clones for dominance, explaining why identical genetic mutations can result in different phenotypes.

Abstract Despite considerable advances in flood forecasting during recent decades, state-of-the-art, operational flood early warning systems (FEWS) need to be equipped with near-real-time inundation and impact forecasts and their associated uncertainties. High-resolution, impact-based flood forecasts provide insightful information for better-informed decisions and tailored emergency actions. Valuable information can now be provided to local authorities for risk-based decision-making by utilising high-resolution lead-time maps and potential impacts to buildings and infrastructures. Here, we demonstrate a comprehensive floodplain inundation hindcast of the 2021 European Summer Flood illustrating these possibilities for better disaster preparedness, offering a 17-hour lead time for informed and advisable actions.

Abstract Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5–15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

Abstract Restoring tree cover changes albedo, which is the fraction of sunlight reflected from the Earth’s surface. In most locations, these changes in albedo offset or even negate the carbon removal benefits with the latter leading to global warming. Previous efforts to quantify the global climate mitigation benefit of restoring tree cover have not accounted robustly for albedo given a lack of spatially explicit data. Here we produce maps that show that carbon-only estimates may be up to 81% too high. While dryland and boreal settings have especially severe albedo offsets, it is possible to find places that provide net-positive climate mitigation benefits in all biomes. We further find that on-the-ground projects are concentrated in these more climate-positive locations, but that the majority still face at least a 20% albedo offset. Thus, strategically deploying restoration of tree cover for maximum climate benefit requires accounting for albedo change and we provide the tools to do so.

Abstract Over-consumption of fructose in adults and children has been linked to increased risk of non-alcoholic fatty liver disease (NAFLD). Recent studies have highlighted the effect of fructose on liver inflammation, fibrosis, and immune cell activation. However, little work summarizes the direct impact of fructose on macrophage infiltration, phenotype, and function within the liver. We demonstrate that chronic fructose diet decreased Kupffer cell populations while increasing transitioning monocytes. In addition, fructose increased fibrotic gene expression of collagen 1 alpha 1 (Col1a1) and tissue metallopeptidase inhibitor 1 (Timp1) as well as inflammatory gene expression of tumor necrosis factor alpha (Tnfa) and expression of transmembrane glycoprotein NMB (Gpnmb) in liver tissue compared to glucose and control diets. Single cell RNA sequencing (scRNAseq) revealed fructose elevated expression of matrix metallopeptidase 12 (Mmp12), interleukin 1 receptor antagonist (Il1rn), and radical S-adenosyl methionine domain (Rsad2) in liver and hepatic macrophages. In vitro studies using IMKC and J774.1 cells demonstrated decreased viability when exposed to fructose. Additionally, fructose increased Gpnmb, Tnfa, Mmp12, Il1rn, and Rsad2 in unpolarized IMKC. By mass spectrometry, C13 fructose tracing detected fructose metabolites in glycolysis and the pentose phosphate pathway (PPP). Inhibition of the PPP further increased fructose induced Il6, Gpnmb, Mmp12, Il1rn, and Rsad2 in nonpolarized IMKC. Taken together, fructose decreases cell viability while upregulating resolution and anti-inflammatory associated genes in Kupffer cells.

Abstract Postcholecystectomy syndrome (PCS) is persistent distressing symptoms which develops following a laparoscopic cholecystectomy (LC); in cases when the condition is severe, readmission may be necessary. However, research on the prevalence of PCS and potential factors associated with PCS in Nepalese patients is still limited. An observational point-prevalence, correlational predictive cross-sectional study was conducted to determine the prevalence of PCS and examine what predicting factors including preoperative anxiety, preoperative dyspepsia, smoking, alcohol consumption, and duration of preoperative symptoms are associated with PCS. A total of 127 eligible Nepalese patients who came for follow-up after 1 week of LC at outpatient department of surgery in one single university hospital, Kathmandu, Nepal, were recruited. A set of questionnaires consisting participants' information record form, Hospital Anxiety and Depression Scale (HADS), Leeds Dyspepsia Questionnaires (LDQ), Fagerstrom Test for Nicotine Dependence (FTND), and Alcohol Use Disorder Identification Test (AUDIT) was administered for data collection. The associations between influential factors and PCS were analyzed using Binary logistic regression. 43.3% of participants reported PCS after 1 week of surgery. The findings from logistic regression analysis affirmed that the patients with preoperative anxiety (OR = 6.38, 95%CI = 2.07–19.67, p

Abstract Background By resolving complicated spectra from drug combinations, chemometric techniques are valuable for multi-component investigation. The capacity to properly estimate combinations of components without separating drugs from their mixture is one of the benefits of chemometric analysis approaches over traditional analytical methods. These approaches are easy to use and sensitive even to the lowest concentrations. They are also practical, affordable, and cost-effective. In the current study, the chemometric aided spectrophotometric approach was used to evaluate the two drugs naringin and verapamil. The approach is multidimensional and based on chemometrics, which includes an orthogonal partial least square method that is a new refinement of the partial least squares regression analysis method. With this technique, no conversions are made to the spectrum that overlaps the two drugs. The tools UV-PROBE, SIMCA version 17, and excel were used to process the chemometric data. Results According to results from an orthogonal partial least square model, the mean percent recovery and relative standard deviation for the combination of verapamil with naringin were 100.80/1.19 and 100.836/1.35, respectively.The calibration model was used to predict known synthetic mixtures.This method shows good consistency in recovery ranging between 98.92 and 103.59% for VER and from 96.21 to 101.84% NAR. As saying the synthetic mixture revealed that it had a high percentage of purity. Conclusions The proposed chemometric method can estimate the quantitative amount of pharmaceuticals based on their dosage forms. This approach meets the requirements for the international conference on harmonization's (ICH) analytical criteria, such as precision and accuracy. Graphical Abstract

Abstract Folate receptor (FR) alpha (FOLR1) and beta (FOLR2) are membrane-anchored folate transporters that are expressed at low levels in normal tissues, while their expression is strongly increased in several cancers. Intriguingly, although the function of these receptors in, for example, development and cancer has been studied intensively, their role in aging is still unknown. To address this, we utilized Caenorhabditis elegans, in which FOLR-1 is the sole ortholog of folate receptors. We found that the loss of FOLR-1 does not affect reproduction, physical condition, proteostasis or lifespan, indicating that it is not required for folate transport to maintain health. Interestingly, we found that FOLR-1 is detectably expressed only in uterine-vulval cells, and that the histone-binding protein LIN-53 inhibits its expression in other tissues. Furthermore, whereas knockdown of lin-53 is known to shorten lifespan, we found that the loss of FOLR-1 partially rescues this phenotype, suggesting that elevated folr-1 expression is detrimental for health. Indeed, our data demonstrate that overexpression of folr-1 is toxic, and that this phenotype is dependent on diet. Altogether, this work could serve as a basis for further studies to elucidate the organismal effects of abnormal FR expression in diseases such as cancer.

Abstract The earth is warming, and the frequency of extreme weather events have been rapidly growing globally with unprecedented consequences to farming communities. In principle, weather and climate information services (WCIS) can help farmers better manage their activities and farm level outcomes by supporting their decision-making with relevant and usable information to address the potential impacts of expected changing climate conditions. But, in practice, can the availability and use of WCIS help improve agricultural outcomes given the weather and climate related uncertainties? To understand the use and impact of WCIS in the cotton-wheat cropping areas of Pakistan, we conducted a multistage stratified clustered random sample of 612 farm households in the provinces of Punjab and Sindh. Over 55% of the farm households in the sample indicated that they used WCIS provided by the Pakistan Meteorological Department and other sources for making their agricultural decisions. Our analysis, however, suggests that the impact of using WCIS on major farm outcomes (i.e. farm revenue, costs, profits, and input usage) is not statistically significant when compared with those farm households not using WCIS (null result). This result is robust to different estimation techniques (i.e. ordinary least squares, instrumental variable approach, and propensity score matching method). From the focus group discussions, we gathered that farmers perceived WCIS as less reliable, often unclear, and difficult to understand as this information is not translated and transmitted in local languages. Addressing these issues can help reduce the impact of climate and weather variability on farm outcomes in those provinces as well as in Pakistan more generally. Our study suggests that, under uncertainty, emphasis should be on WCIS that farmers can rely on for making farming related decisions.

First birth interval after marriage is a particularly interesting subject, because it unveils both the social behaviors and fertility patterns. Though, for a woman, who marry at an early age and get sooner childbearing can be the health threat for both mother and child. The objective of this study is to systematically investigate significant predictors associated with time to first birth after marriage. Following the PRISMA guidelines; three database Scopus, PubMed and EMBASE were used to capture relevant articles. A total of 21 articles with the thorough assessment of 326 articles published in English up to 10 January 2024 were included in final review. Thirty-nine significant predictors associated with first birth interval after marriage have been explored. Predictors, such as age at marriage, education, residence, contraceptive, religion, wealth index were observed as some of the major significant predictors. The findings indicate to take care of those factors in order to deal with time to first birth after marriage. Understanding the impact of influential factors can be considered as important reference to formulate appropriate policy to intervene effective program as well as to plan such studies based on primary data with special reference to certain country or region.

The performance of electrochemical double-layer capacitors (EDLCs) is evaluated by the capacitance of activated carbon (AC) electrodes. The capacitance of AC electrodes is influenced by many factors such as precursor type, activation method, pore structure, surface chemistry and electrolytic properties. In this paper, we present a comparative study of machine learning based prediction of surface area, mesopore volume and total pore volume of activated carbon for energy storage applications. The ML models were trained on a dataset of synthetic data that were generated from the limited number of experimental data and which included the activation temperature, methylene blue number and iodine number of the activated carbon (AC). The best performing ML model was random forest model and XG boost model. The results of this study can be used to optimize the production of activated carbon and improve its performance in energy storage applications.

The plants Buddleja asiatica and Buddleja paniculata are two closely related species of which the former has widespread uses in traditional medicine while the latter remains relatively unexplored. The present study focused on the analysis of phytoconstituents and the estimation of different biological activities of extracts and semi-purified fractions. The ethyl acetate stem fraction and methanolic extract of the leaf of B. asiatica displayed the highest phenolic contents of 390.98 ± 5.32 and 383.72 ± 7.31 mg GAE/g. TFC content was measured as 207.33 ± 0.34 and 138.58 ± 0.53 mg QE/g for ethyl acetate leaf and stem fraction of B. asiatica. The highest antioxidant activity was displayed by crude stem extract of B. paniculata with IC50 35.65±0.61 µg/mL in DPPH assay followed by ethyl acetate stem fraction of B. asiatica with IC50 36.17±0.92 µg/mL. The DCM leaf fraction and stem fraction of B. asiatica were found active against gram-negative and gram-positive bacteria. Both plants displayed mild to no toxicity against the brine shrimp nauplii. Median lethal concentration (LC50) ranged from 346.96 ± 25.39 in hexane fraction of leaf to 2719.32 ± 706.5 µg/mL in crude methanol extract of B. paniculata. The present study showed these medicinal plants are rich in an important class of organic compounds that play a significant role in the cure of bacterial infection which ultimately supports pharmaceutical research.

Summary: Taste organs contain distinct gustatory receptors that help organisms differentiate between nourishing and potentially harmful foods. The detection of high pH levels plays a crucial role in food selection, but the specific gustatory receptors responsible for perceiving elevated pH in foods have remained unknown. By using Drosophila melanogaster as a model organism, we have uncovered the involvement of ionotropic receptors (IRs) in avoiding high-pH foods. Our study involved a combination of behavioral tests and electrophysiological analyses, which led to the identification of six Irs from bitter-sensing gustatory receptor neurons essential for rejecting food items with elevated pH levels. Using the same methodology, our study reevaluated the significance of Alka and OtopLa. The findings highlight that Alka, in conjunction with IRs, is crucial for detecting alkaline substances, whereas OtopLa does not contribute to this process. Overall, our study offers valuable insights into the intricate mechanisms governing taste perception in organisms.

The gain-of-function mutation in the TALK-1 K+ channel (p.L114P) is associated with maturity-onset diabetes of the young (MODY). TALK-1 is a key regulator of β-cell electrical activity and glucose-stimulated insulin secretion. The KCNK16 gene encoding TALK-1 is the most abundant and β-cell-restricted K+ channel transcript. To investigate the impact of KCNK16 L114P on glucose homeostasis and confirm its association with MODY, a mouse model containing the Kcnk16 L114P mutation was generated. Heterozygous and homozygous Kcnk16 L114P mice exhibit increased neonatal lethality in the C57BL/6J and the CD-1 (ICR) genetic background, respectively. Lethality is likely a result of severe hyperglycemia observed in the homozygous Kcnk16 L114P neonates due to lack of glucose-stimulated insulin secretion and can be reduced with insulin treatment. Kcnk16 L114P increased whole-cell β-cell K+ currents resulting in blunted glucose-stimulated Ca2+ entry and loss of glucose-induced Ca2+ oscillations. Thus, adult Kcnk16 L114P mice have reduced glucose-stimulated insulin secretion and plasma insulin levels, which significantly impairs glucose homeostasis. Taken together, this study shows that the MODY-associated Kcnk16 L114P mutation disrupts glucose homeostasis in adult mice resembling a MODY phenotype and causes neonatal lethality by inhibiting islet insulin secretion during development. These data suggest that TALK-1 is an islet-restricted target for the treatment for diabetes.

Salt (NaCl), is an essential nutrient for survival, while excessive salt can be detrimental. In the fruit fly, Drosophila melanogaster, internal taste organs in the pharynx are critical gatekeepers impacting the decision to accept or reject a food. Currently, our understanding of the mechanism through which pharyngeal gustatory receptor neurons (GRNs) sense high salt are rudimentary. Here, we found that a member of the ionotropic receptor family, Ir60b, is expressed exclusively in a pair of GRNs activated by high salt. Using a two-way choice assay (DrosoX) to measure ingestion volume, we demonstrate that IR60b and two co-receptors IR25a and IR76b are required to prevent high salt consumption. Mutants lacking external taste organs but retaining the internal taste organs in the pharynx exhibit much higher salt avoidance than flies with all taste organs but missing the three IRs. Our findings highlight the vital role for IRs in a pharyngeal GRN to control ingestion of high salt.

BackgroundMiscarriage is a major public health concern in low and middle-income countries (LMICs) like Nepal. This study aims to examine the factors associated with miscarriage among pregnant women of reproductive age (15-49 years) in the past 15 years.MethodsThere were a total of weighted sample of 26,376 cross-sectional pregnancy data from Nepal Demographic and Health Surveys (NDHS) 2001, 2006, 2011, and 2016 combined together, which was used in the study. Multilevel logistic regression analysis that adjusted for cluster and survey weights was used to identify factors associated with miscarriage among pregnant women of reproductive age in Nepal.ResultsThe results showed that maternal age, contraception, tobacco smoking, wealth index, respondents' educational status, and, caste/ethnicity were found to be strong factors of miscarriage in Nepal. The likelihood of having a miscarriage among older women (≥40 years) was more than 100% (aOR = 2.12, 95% CI [1.73, 2.59]), among non-users of contraception was 88.9% (aOR = 1.88, 95% CI [1.68, 2.11]) (pConclusionFindings from this study show that miscarriages are associated with maternal age, use of contraception, smoking, wealth index, caste, and ethnicity. Interventions aimed to improve use of contraceptives, avoiding smoking and pregnancy planning on the basis of maternal age, are needed to prevent miscarriage. Also, women from Brahmin ethinicity and those with the highest income index require greater attention when it comes to miscarriage prevention strategies in Nepal.

BackgroundWorksite-based health programs have shown positive impacts on employee health and have led to significant improvements in cardiovascular risk factor profiles. We aimed to determine the effect of cafeteria intervention on cardio-metabolic risk factors diet in a worksite setting (Dhulikhel Hospital) in Nepal.MethodsIn this one-arm pre-post intervention study, we recruited 277 non-pregnant hospital employees aged 18-60 with prediabetes or pre-hypertension. The study was registered in clinicaltrials.gov (NCT03447340; 2018/02/27). All four cafeterias in the hospital premises received cafeteria intervention encouraging healthy foods and discouraging unhealthy foods for six months. We measured blood pressure, fasting glucose level, glycated hemoglobin, cholesterol in the laboratory, and diet intake (in servings per week) using 24-hour recall before and six months after the intervention. The before and after measures were compared using paired-t tests.ResultsAfter six months of cafeteria intervention, the median consumption of whole grains, mono/polyunsaturated fat, fruits, vegetable and nuts servings per week increased by 2.24(pConclusionOverall, we found a decrease in consumption of refined grains and an increase in consumption of whole grains, unsaturated fats, fruits, and nuts observed a modest reduction in blood pressure and LDL cholesterol following a 6-month cafeteria-based worksite intervention incorporating access to healthy foods.

In Nepal, over 1 million individuals have tested positive for SARS-CoV-2. We sought to describe the frequency of nonrecovery from this infection at 6 months and associated symptoms. We conducted a retrospective cohort study of 6142 women who had positive and negative PCR tests for this infection 6 months previously at 3 institutions in Kathmandu. In telephone interviews women provided information on 22 symptoms and their intensities, health status and history, and functional status. Of 3732 women who had tested PCR positive, 630 (16.9%) reported that they were unrecovered. These 630 unrecovered women were distinguished statistically from the 3102 recovered women by more frequent histories of allergies, rheumatoid disease, BCG immunization, Covid vaccination, strep throat and recent URIs, and both weight gain and weight losses of more than 5 kg in the 6 months following testing, and stressful events in the preceding year. Fatigue, pain, difficulty remembering, shortness of breath, heat and cold intolerance and unrefreshing sleep were reported in 41.9% to 10.5% of these 630 unrecovered women. Six months after confirmed SARS-CoV-2 infection 16.9% of Nepali women have long-COVID manifested as an immune, metabolic, and hormonal systems disruptive and dysfunction syndrome.

Abstract The bacterial enzymes FtsW and FtsI, encoded in the highly conserved dcw gene cluster, are considered to be universally essential for the synthesis of septal peptidoglycan (PG) during cell division. Here, we show that the pathogen Clostridioides difficile lacks a canonical FtsW/FtsI pair, and its dcw-encoded PG synthases have undergone a specialization to fulfill sporulation-specific roles, including synthesizing septal PG during the sporulation-specific mode of cell division. Although these enzymes are directly regulated by canonical divisome components during this process, dcw-encoded PG synthases and their divisome regulators are dispensable for cell division during normal growth. Instead, C. difficile uses a bifunctional class A penicillin-binding protein as the core divisome PG synthase, revealing a previously unreported role for this class of enzymes. Our findings support that the emergence of endosporulation in the Firmicutes phylum facilitated the functional repurposing of cell division factors. Moreover, they indicate that C. difficile, and likely other clostridia, assemble a distinct divisome that therefore may represent a unique target for therapeutic interventions.

Abstract Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis (EBL), which has been reported worldwide. The expression of viral structural proteins: surface glycoprotein (gp51) and three core proteins - p15 (matrix), p24 (capsid), and p12 (nucleocapsid) induce a strong humoral and cellular immune response at first step of infection. CD4+ T-cell activation is generally induced by bovine leukocyte antigen (BoLA) region– positive antigen-presenting cells (APC) after processing of an exogenous viral antigen. Limited data are available on the BLV epitopes from the core proteins recognized by CD4+ T-cells. Thus, immunoinformatic analysis of Gag sequences obtained from 125 BLV isolates from Poland, Canada, Pakistan, Kazakhstan, Moldova and United States was performed to identify the presence of BoLA-DRB3 restricted CD4+ T-cell epitopes. The 379 15-mer overlapping peptides spanning the entire Gag sequence were run in BoLA-DRB3 allele-binding regions using a BoLA-DRB- peptide binding affinity prediction algorithm. The analysis identified 22 CD4+ T-cell peptide epitopes of variable length ranging from 17 to 22 amino acids. The predicted epitopes interacted with 73 different BoLA-DRB3 alleles found in BLV-infected cattle. Importantly, two epitopes were found to be linked with high proviral load in PBMC. A majority of dominant and subdominant epitopes showed high conservation across different viral strains, and therefore could be attractive targets for vaccine development.

Abstract The rapid diversification and high species richness of flowering plants is regarded as ‘Darwin’s second abominable mystery’. Today the global spatiotemporal pattern of plant diversification remains elusive. Using a newly generated genus-level phylogeny and global distribution data for 14,244 flowering plant genera, we describe the diversification dynamics of angiosperms through space and time. Our analyses show that diversification rates increased throughout the early Cretaceous and then slightly decreased or remained mostly stable until the end of the Cretaceous–Paleogene mass extinction event 66 million years ago. After that, diversification rates increased again towards the present. Younger genera with high diversification rates dominate temperate and dryland regions, whereas old genera with low diversification dominate the tropics. This leads to a negative correlation between spatial patterns of diversification and genus diversity. Our findings suggest that global changes since the Cenozoic shaped the patterns of flowering plant diversity and support an emerging consensus that diversification rates are higher outside the tropics.

Abstract Sand traps in irrigation networks are typically used in mitigating canal sedimentation. In irrigation networks located in basins of high sediment yield due to the presence of volcanoes, it is essential to assess the vulnerability of sand traps. Using sediment yield at irrigation scheme inlets, sand trap vulnerability can be evaluated. This study aims to understand the vulnerability of irrigation sand traps throughout the Progo–Opak–Serang (POS) Volcanic River Basin, Indonesia, via mapping the sediment yield distributions in the basin. We employed the Revised Universal Soil Loss Equation to estimate soil loss, where the results show that the average soil loss in the POS River Basin is 179.69 tons/ha/year that falls under the category of moderate erosion potential, while the average sediment yield for the whole basin is 51.04 tons/ha/year. Parts of the basin with high yields of more than 180 tons/ha/year were mostly found along the volcanic mountains such as Sindoro, Sumbing, Merapi, Merbabu, and Telomoyo, and the Menoreh Hills. The model demonstrated relatively high performance with R2, NSE, RMSE, and MAE of 0.89, 0.82, 0.14, and 0.11, respectively. Within the POS Basin, Badran, Kalibawang, and Blawong are the three most vulnerable irrigation sand traps, with sediment yield values of 252.83, 178.92, and 63.49 tons/ha/year, respectively; they are all located in sub-watershed outlets. The vulnerability assessment conducted in this study can be used for the decision support system to prioritize irrigation sand traps towards a more effective irrigation system development.

The Hindu Kush Himalaya (HKH) is one of the most flood-prone regions in the world, yet heavy cloud cover and limited in situ observations have hampered efforts to monitor the impact of heavy rainfall, flooding, and inundation during severe weather events. This paper introduces HydroSAR, a Sentinel-1 SAR-based hazard monitoring service which was co-developed with in-region partners to provide year-round, low-latency weather hazard information across the HKH. This paper describes the end user-focused concept and overall design of the HydroSAR service. It introduces the main processing algorithms behind HydroSAR’s broad product portfolio, which includes qualitative visual layers as well as quantitative products measuring the surface water extent and water depth. We summarize the cloud-based implementation of the developed service, which provides the capability to scale automatically with the event size. A performance assessment of our quantitative algorithms is described, demonstrating the capabilities to map the flood extent and water depth with an accuracy of >90% and

Abstract Nepal is an endemic country for dengue infection with rolling of every 3 year’s clear cyclic outbreaks with exponential growth since 2019 outbreak and the virus gearing towards the non-foci temperate hill regions. However, the information regarding circulating serotype and genotype is not frequent. This research discusses on the clinical features, diagnosis, epidemiology, circulating serotype and genotype among 61 dengue suspected cases from different hospitals of Nepal during the window period 2017–2018 between the two outbreaks of 2016 and 2019. E-gene sequences from PCR positive samples were subjected to phylogenetic analysis under time to most recent common ancestor tree using Markov Chain Monte Carlo (MCMC) and BEAST v2.5.1. Both evolution and genotypes were determined based on the phylogenetic tree. Serotyping by Real-time PCR and Nested PCR showed the co-circulation of all the 3 serotypes of dengue in the year 2017 and only DENV-2 in 2018. Genotype V for DENV-1 and Cosmopolitan Genotype IVa for DENV-2 were detected. The detected Genotype V of DENV-1 in Terai was found close to Indian genotype while Cosmopolitan IVa of DENV-2 found spreading to geographically safe hilly region (now gripped to 9 districts) was close to South-East Asia. The genetic drift of DENV-2 is probably due to climate change and rapid viral evolution which could be a representative model for high altitude shift of the infection. Further, the increased primary infection indicates dengue venturing to new populations. Platelets count together with Aspartate transaminase and Aalanine transaminase could serve as important clinical markers to support clinical diagnosis. The study will support future dengue virology and epidemiology in Nepal.

Rational selection of active biomolecules in the synthesis of nanoparticles for reducing the precursor and functionalizing the nanoparticles (NPs) can offer remarkable comeback of biocompatibility and biological applicability. This work aimed at the synthesis of a cost-effective, ecofriendly, and a facile approach of silver nanoparticles (AgNPs) using methanolic leaf extract of Artemisia vulgaris. The phytochemical constituents present in the methanolic extract were characterized by qualitative chemical tests and spectroscopic measurements and employed for the reduction of silver nitrate into silver nanoparticles. Formation of AgNPs was monitored by UV-visible spectroscopic measurement. Fourier transform infrared (FTIR) spectroscopy reflected the presence of characteristic functional groups associated with the phytochemical constituents involved in the formation of nanoparticles. The crystalline phase and morphology of the NPs were assessed form X-ray diffraction (XRD) spectra and field emission scanning electron microscopy (FESEM), respectively. XRD pattern revealed the crystalline nature of nanoparticles with grain size of ∼ 28 nm based on the Debye Scherer formula. Study of antimicrobial activity of AgNPs against Gram-positive bacteria Bacillus subtili, Gram-negative bacteria Escherichia coli, and fungus Candida albicans exhibited good potential to control the bacterial and fungal growth.

Background: Medical students are subjected to various stressors throughout their training, which has a considerable impact on their physical and mental health. Some students have positive ways of coping, while others take to maladaptive coping measures. This study aims to assess severity, sources of stress, and coping strategies among medical students of a non-Western low-income country from South Asia. Methods: A self-administered questionnaire-based cross-sectional study was carried out. Demographic variables were collected and stress level was assessed using PSS 14 (Perceived Stress Scale 14). The sources of stress were assessed using MSSQ (Medical Student Stressor Questionnaire) and coping strategies were evaluated using the Brief-Coping Orientation to Problems Experienced 28. Results: The response rate was 95%. The mean PSS score was 27.85. Overall, 55% of students were stressed (male 52%, female 60%), the difference among gender was not significant. Basic science students perceived higher levels of stress than clinical clerkship students. Academic related stressors caused higher stress, whereas other variables caused moderate stress. The major stressors were examinations, inadequate time to study, poor marks, extensive amount of learning content, and the need to performing well in the exam. The five most common coping strategies used were active coping, acceptance, planning, self-distraction, and instrumental support. The least common coping mechanism was substance use. All MSSQ domains positively correlated with the total PSS score. Students with higher PSS scores were likely to use behavioral disengagement, venting, and self-blame as the primary coping strategies. Conclusions: Stress level among the medical students is high and mainly in relation to academia. Inadequate guidance from teachers contributed significantly. Stressed students were likely to use maladaptive coping strategies. Strategies to enhance teacher-student communication and adaptive coping measures should be implemented. Further studies should be done to evaluate the effects of stress on the academic outcomes of students.

IntroductionIntimate partner violence (IPV) is a major public health issue in Nepal. IPV has social and economic impacts on women, family, and the wider society. In this study, we aimed to determine factors associated with IPV among currently partnered women aged 15-49.MethodsWe conducted a secondary data analysis of the Nepal Demographic and Health Survey (NDHS) 2022. The study examines the lifetime prevalence of IPV. IPV was measured in three domains: experience of physical violence, emotional violence, and sexual violence. Weighted univariate and multivariable logistic regression analysis were applied to determine factors associated with IPV. The results of logistic regression were presented as crude odds ratio (COR) and adjusted odds ratio (AOR) and their 95% confidence interval (CI).ResultsOf 3853 women, 27.2% had experienced any form of IPV. The lifetime prevalence of physical violence, emotional violence, and sexual violence were 23.2%, 12.8%, and 7.1%, respectively. Higher odds of physical violence were reported among women aged 35-49 years (AOR: 2.13, 95% CI: 1.58-2.87), women without formal education (AOR: 1.51, 95% CI: 1.10-2.06), and women who justified wife-beating (AOR: 1.23, 95% CI: 1.00-1.52). Women from poor households (AOR: 1.61, 95% CI: 1.12-2.35) and women with uneducated partners (AOR: 1.66, 95% CI: 1.08-2.58) were at higher risk of experiencing sexual violence. Women with unemployed husbands reported a higher risk of physical violence (AOR: 2.72, 95% CI: 1.45-5.06) and emotional violence (AOR: 1.61, 95% CI: 1.12-2.35).ConclusionAlmost one in three currently partnered women experienced some form of IPV in their lifetime. Various sociodemographic, partner-related, and women's empowerment-related factors were associated with experiencing IPV. Acknowledging and addressing these factors is essential to mitigating the high rates of IPV among reproductive aged women.

BackgroundDespite declining smoking prevalence globally, South Asia faces a rising burden. In Nepal, existing tobacco control laws haven't curbed use, with 28.9% of young adults engaging in tobacco use. This study investigates tobacco use and associated factors among medical, dental, and nursing students at a Nepalese tertiary care center.ObjectiveWe aimed to assess tobacco use prevalence and identify factors associated with it among future healthcare professionals, considering their distinct roles in tobacco control. Medical students can contribute through clinical counseling and public health advocacy, dental students through oral health education, and nursing students through patient education and community outreach.MethodsA cross-sectional study involving 427 medical, dental, and nursing students was conducted. Data was collected using online questionnaires distributed via email and social media. Descriptive statistics and Chi-square tests were used for analysis.ResultsThe study found that 45% of participants were aged 22-25, with females comprising the majority (53.2%). Nearly half (49.2%) belonged to the medical faculty, and 24.4% were in their first year. Furthermore, among those who smoke, 53% reported smoking less than 5 cigarettes daily. The analysis revealed significant associations between smoking with age (p = 0.01), year of study (p = 0.001), parental smoking history (p = 0.001), and having friends who smoke (p = 0.001).ConclusionOur findings highlight the moderate prevalence of cigarette smoking among medical students, with family and friends emerging as major influences. Stress relief was a common reason, particularly among young females and first-year students. These results emphasize the urgent need for comprehensive tobacco control programs within medical institutions to equip future healthcare professionals to effectively address smoking issues.

IntroductionThe outbreak of a global pandemic like COVID-19 has highlighted significant distress around mental health. The burden of mental health issues like anxiety and depression requires evidence-based intervention, especially in low-income settings like Nepal. The study aims to determine the prevalence of anxiety and depression and the factors associated with it among hypertensive patients.Materials and methodsThe quantitative cross-sectional study design was used for this study. The study was conducted among 374 samples from selected wards of Kathmandu Metropolitan using a convenience sampling technique. Face-to-face interviews were conducted using a structured interview schedule. A Chi-square test was used to identify the statistical significance between dependent and independent variables. Binary logistic regression analysis was performed to determine the factors associated with anxiety and depression.ResultsThe prevalence of anxiety and depression among hypertensive patients during the COVID-19 pandemic was 27.8% and 24.3% respectively. According to the results of bivariate logistic regression analysis, smoking/tobacco consumption, staying in quarantine, positive COVID-19 test result, history of COVID-19 positive in the family, History of death due to COVID-19 in the family, visiting a hospital during the COVID-19 pandemic appeared as influencing factors of both anxiety and depression.ConclusionOur findings suggest that COVID-19 has a substantial effect on the mental health of hypertensive patients. This study highlights the need to develop early intervention and coping strategies among this population to minimize the negative impact of COVID-19 on their mental health and well-being.

IntroductionUnderstanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia.MethodsWe performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures.ResultsData from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, pConclusionIn men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

Background: Polycystic ovary syndrome’s (PCOS) main feature is hyperandrogenism, which is linked to a higher risk of metabolic disorders. Gene expression analyses in adipose tissue and skeletal muscle reveal dysregulated metabolic pathways in women with PCOS, but these differences do not necessarily lead to changes in protein levels and biological function. Methods: To advance our understanding of the molecular alterations in PCOS, we performed global proteomic and phosphorylation site analysis using tandem mass spectrometry, and analyzed gene expression and methylation. Adipose tissue and skeletal muscle were collected at baseline from 10 women with and without PCOS, and in women with PCOS after 5 weeks of treatment with electrical stimulation. Results: Perilipin-1, a protein that typically coats the surface of lipid droplets in adipocytes, was increased whereas proteins involved in muscle contraction and type I muscle fiber function were downregulated in PCOS muscle. Proteins in the thick and thin filaments had many altered phosphorylation sites, indicating differences in protein activity and function. A mouse model was used to corroborate that androgen exposure leads to a shift in muscle fiber type in controls but not in skeletal muscle-specific androgen receptor knockout mice. The upregulated proteins in muscle post treatment were enriched in pathways involved in extracellular matrix organization and wound healing, which may reflect a protective adaptation to repeated contractions and tissue damage due to needling. A similar, albeit less pronounced, upregulation in extracellular matrix organization pathways was also seen in adipose tissue. Conclusions: Our results suggest that hyperandrogenic women with PCOS have higher levels of extra-myocellular lipids and fewer oxidative insulin-sensitive type I muscle fibers. These could be key factors leading to insulin resistance in PCOS muscle while electric stimulation-induced tissue remodeling may be protective. Funding: Swedish Research Council (2020-02485, 2022-00550, 2020-01463), Novo Nordisk Foundation (NNF22OC0072904), and IngaBritt and Arne Lundberg Foundation. Clinical trial number NTC01457209.

Ethnomedicinally, more than 2000 plants were found to be used in Nepal. Among them, the red colored rhizome of Angiopteris helferiana and the bark of Saurauia fasciculata have been used widely to treat muscle fatigue, bone pain, fever, postpartum hemorrhage, and thirst by healers in Kaski and Tanahun districts, Nepal. However, scientific evidence towards their traditional uses is lacking till December, 2023. Therefore, we report the phytochemicals, total phenolic content (TPC), total flavonoid content (TFC), total carbohydrate content (TCC), antioxidant and antibacterial activities of A. helferiana and S. fasciculata extracts. Phytochemical analysis indicated that A. helferiana and S. fasciculata extracts were potential sources of chemicals such as phenols, flavonoids, tannins, terpenoids, saponins, and carbohydrates. The TPC, TFC, and TCC of extracts were determined by using an ultraviolet visible spectrophotometer. Among the extracts tested, A. helferiana extracts showed the highest phenolic and carbohydrate contents of 208.33 ± 12.96 mg of gallic acid equivalent/g and 564.16 ± 2.92 mg of D-glucose equivalent/g of dry extract, respectively. Similarly, S. fasciculata revealed the highest flavonoid content of 30.35 ± 0.1 mg quercetin equivalent/g of dry extract. The extract of A. helferiana and S. fasciculata exhibited potent antioxidant activity by scavenging 2,2-diphenyl-1-picrylhydrazyl radicals with an IC50 of 25.9 µg/ml and 31.07 µg/ml, respectively. The antibacterial activity of the A. helferiana and S. fasciculata extract against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was determined using an agar-well diffusion protocol that revealed the potential antibacterial activity of A. helferiana against E. coli. The present study will help validate the traditional uses of A. helferiana rhizomes and S. fasciculata barks as a healing medicine and inspire the researcher towards further research, development, and formulation.

The growth of digital platforms has led to the proliferation of Online Communities, providing individuals with opportunities to seek help and share knowledge. A key challenge of help-related platforms that address technical questions (i.e., utilitarian, rather than opinion or supportive) is to ensure the contributions address seekers' specific information needs. Despite growing academic interest in such platforms, research has mainly focused on factors that influence the quantity of contributions, ignoring whether these contributions effectively helped the seekers. To fill this research gap, this study draws upon theories of self-determination and motivation crowding to examine contributing behaviors that result in successful helping. By analyzing a rich dataset collected from an online Q&A platform, we find that gains in a help provider's past rewards positively influence the success of contribution. Further, while previous studies suggest that external rewards result in a high quantity of contribution, our findings show that an inflated frequency of contribution leads to a crowding-out effect. Specifically, the contribution frequency has a curvilinear relationship with the success of the contribution. Taken together, these findings demonstrate there is a need to revisit the gamification mechanism on help-related platforms to ensure the success of knowledge contribution. This is crucial for the sustainability of these platforms as low-quality answers can lead users to mistrust and eventually leave the platform.

IntroductionNasopharyngeal carcinoma (NPC) shows geographic and ethnic variation with specific etiopathogenesis. This study characterized the distribution of NPC patients stratified by ethnicity, geography, and histology in a tertiary-level cancer center in Nepal.MethodsA descriptive retrospective study was designed to analyze NPC cases from different regions among patients visiting the hospital from 2016 to 2021. Demographic and clinical information was obtained from medical records. Ethical approval was granted by the Nepal Health Research Council (NHRC). Data analyses and visualization were carried out with R software.ResultsDuring the six-year period, a total of 65 individuals were diagnosed with NPC, comprising 42 males and 23 females. Patient median age was 43 years (range 11-85 years). A bimodal age distribution of cases was observed with peaks in patients aged 30-39 years and 50-59 years. Of the NPC patients studied, 29 were from Koshi Province, with 7 cases from Ilam district and 6 cases from Morang district. There were 18 patients in Bagmati Province, and Kathmandu district had the highest number of cases within this region, with 8 patients. The highest proportion of cases were observed among patients of Janajati ethnicity (60%), including Rai, Limbu, and Sherpa people. Histologically, undifferentiated non-keratinizing NPC was the most commonly observed subtype, accounting for 43.1% of cases, followed by 20% differentiated non-keratinizing NPC and 4.6% keratinizing NPC across the entire sample population. The majority of patients (75.3%) were diagnosed at an advanced stage (stage III or IV) with none diagnosed at stage I.ConclusionsIn our study, most cases of NPC occurred in patients from provinces in eastern Nepal (Koshi province), and of the Janajati ethnic community. The most common histological subtype was undifferentiated non-keratinizing carcinoma. Further epidemiological studies could address differences in prevalence and the challenge of late presentation of NPC patients in Nepal.

Human experiences with nature are important for our culture, economy, and health. Anthropogenically-driven climate change is causing widespread shifts in biodiversity and resident urban wildlife are no exception. We modelled over 2,000 animal species to predict how climate change will impact terrestrial wildlife within 60 Canadian and American cities. We found evidence of an impending great urban shift where thousands of species will disappear across the selected cities, being replaced by new species, or not replaced at all. Effects were largely species-specific, with the most negatively impacted taxa being amphibians, canines, and loons. These predicted shifts were consistent across scenarios of greenhouse gas emissions, but our results show that the severity of change will be defined by our action or inaction to mitigate climate change. An impending massive shift in urban wildlife will impact the cultural experiences of human residents, the delivery of ecosystem services, and our relationship with nature.

Neutrophils are primed for neutrophil extracellular trap (NET) formation during diabetes, and excessive NET formation from primed neutrophils compromises wound healing in patients with diabetes. Here, we demonstrate that trained immunity mediates diabetes-induced NET priming in neutrophils. Under diabetic conditions, neutrophils exhibit robust metabolic reprogramming comprising enhanced glycolysis via the pentose phosphate pathway and fatty acid oxidation, which result in the accumulation of acetyl-coenzyme A. Adenosine 5′-triphosphate-citrate lyase-mediated accumulation of acetyl-coenzyme A and histone acetyltransferases further induce the acetylation of lysine residues on histone 3 (AcH3K9, AcH3K14, and AcH3K27) and histone 4 (AcH4K8). The pharmacological inhibition of adenosine 5′-triphosphate-citrate lyase and histone acetyltransferases completely inhibited high-glucose-induced NET priming. The trained immunity of neutrophils was further confirmed in neutrophils isolated from patients with diabetes. Our findings suggest that trained immunity mediates functional changes in neutrophils in diabetic environments, and targeting neutrophil-trained immunity may be a potential therapeutic target for controlling inflammatory complications of diabetes.