bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFN-γsignaling is required for the efficient replication of murine hepatitis virus (MHV) strain JHM in the brains of infected mice
Authors: Kerr Catherine M. , Proctor-Roser Macie A. , Parthasarathy Srivatsan , O’Connor Joseph J. , Pfannenstiel Jessica J. , Orozco Robin C. , Fehr Anthony R. 
Published: January 2025

ABSTRACTNeurotropic viruses are a major public health concern as they can cause encephalitis and other severe brain diseases. Many of these viruses, including flaviviruses, herpesviruses, rhabdoviruses and alphaviruses enter the brain through the olfactory neuroepithelium (ONE) in the olfactory bulbs (OB). Due to the low percentage of encephalitis that occurs following these infections, it’s thought that the OBs have specialized innate immune responses to eliminate viruses. Murine hepatitis virus strain JHM (JHMV) is a model coronavirus that causes severe encephalitis in mice and can access the brain through olfactory sensory neurons. We’ve shown that a JHMV Mac1-mutant virus, N1347A, has decreased replication and disease in the brains of mice. Here we further show that this virus replicates poorly in the OB. However, it is unknown which innate immune factors restrict N1347A replication in the OB. RNA seq analysis of infected olfactory bulbs showed that IFNγ was upregulated in the OB while IFN-βwas barely detectable at 5 days post-infection. To determine if IFN-γ restricts JHMV N1347A replication, we utilized IFN-γ and IFN-γ receptor (IFN-γR) knockout (KO) mice. Surprisingly we found that JHMV WT and N1347A replicated very poorly in the OB and whole brains of both IFN-γ and IFN-γR KO mice following intranasal infection, though survival and weight loss were unaltered. Furthermore, we determined that microglia were the primary cells producing IFN-γ during the early stages of this infection. We conclude that IFN-γ is required for the efficient replication of JHMV in the brains of infected mice.
A semi-empirical Bayes approach for calibrating weak instrumental bias in sex-specific Mendelian randomization studies
Authors: Huang Yu-Jyun , Kurniansyah Nuzulul , Levey Daniel F. , Gelernter Joel , Huffman Jennifer E. , Cho Kelly , Wilson Peter W.F. , Gottlieb Daniel J. , Rice Kenneth M. , Sofer Tamar 
Published: January 2025

AbstractStrong sex differences exist in sleep phenotypes and also cardiovascular diseases (CVDs). However, sex-specific causal effects of sleep phenotypes on CVD-related outcomes have not been thoroughly examined. Mendelian randomization (MR) analysis is a useful approach for estimating the causal effect of a risk factor on an outcome of interest when interventional studies are not available. We first conducted sex-specific genome-wide association studies (GWASs) for suboptimal-sleep phenotypes (insomnia, obstructive sleep apnea (OSA), short and long sleep durations, and excessive daytime sleepiness) utilizing the Million Veteran Program (MVP) dataset. We then developed a semi-empirical Bayesian framework that (i) calibrates variant-phenotype effect estimates by leveraging information across sex groups, and (ii) applies shrinkage sex-specific effect estimates in MR analysis, to alleviate weak instrumental bias when sex groups are analyzed in isolation. Simulation studies demonstrate that the causal effect estimates derived from our framework are substantially more efficient than those obtained through conventional methods. We estimated the causal effects of sleep phenotypes on CVD-related outcomes using sex-specific GWAS data from the MVP and All of Us. Significant sex differences in causal effects were observed, particularly between OSA and chronic kidney disease, as well as long sleep duration on several CVD-related outcomes. By applying shrinkage estimates for instrumental variable selection, we identified multiple sex-specific significant causal relationships between OSA and CVD-related phenotypes.
Impact of Mydriasis on Image Gradability and Automated Diabetic Retinopathy Screening with a Handheld Camera in Real-World Settings
Authors: Diogenes Iago , Restrepo David , Ribeiro Lucas Zago , Aragaki Andre Kenzo , Malerbi Fernando Korn , Regatieri Caio Saito , Nakayama Luis Filipe 
Published: January 2025

AbstractPurposeDiabetic retinopathy (DR) screening in low- and middle-income countries (LMICs) faces challenges due to limited access to specialized care. Portable retinal cameras provide a practical alternative, but image quality, influenced by mydriasis, affects artificial intelligence (AI) model performance. This study examines the role of mydriasis in improving image quality and AI-based DR detection in resource-limited settings.MethodsWe compared the proportion of gradable images between mydriatic and non-mydriatic groups and used logistic regression to identify factors influencing image gradability, including age, gender, race, diabetes duration, and systemic hypertension. A ResNet-200d algorithm was trained on the mBRSET dataset and validated on mydriatic and non-mydriatic images. Performance metrics, such as accuracy, F1 score, and AUC, were evaluated.ResultsThe mydriatic group had a higher proportion of gradable images (82.1% vs. 55.6%,P< 0.001). Factors such as systemic hypertension, older age, male gender, and longer diabetes duration were associated with lower image gradability in non-mydriatic images. Mydriatic images achieved better AI performance, with accuracy (82.91% vs. 79.23%), F1 score (0.83 vs. 0.79), and AUC (0.94 vs. 0.93). Among gradable images, the performance difference was not statistically significant.ConclusionMydriasis improves image gradability and enhances AI model performance in DR screening. However, optimizing AI for non-mydriatic imaging is critical for LMICs where mydriatic agents may be unavailable. Refining AI models for consistent performance across imaging conditions is essential to support the broader implementation of AI-driven DR screening in resource-constrained settings.
Long-read whole-genome sequencing offers novel insights into the biology, stress adaptation, and virulence of neurotropic dematiaceous fungi associated with primary cerebral phaeohyphomycosis
Authors: Samaddar Arghadip , Mendonsa Jenevi Margaret , Nagarathna S , Rudramurthy Shivaprakash M. , Pamidimukkala Umabala , Kindo Anupma Jyoti 
Published: January 2025

ABSTRACTPrimary cerebral phaeohyphomycosis (PCP) is a severe neurological infection caused by neurotropic dematiaceous fungi, affecting both immunocompetent and immunocompromised individuals. Understanding the virulence and adaptation mechanisms of these fungal pathogens is crucial for developing effective treatment strategies. This study employed Oxford Nanopore long-read sequencing to explore the genomes ofCladophialophora bantiana,Fonsecaea monophora, andCladosporium cladosporioides, three key species associated with PCP. KEGG pathway analysis revealed significant enrichments in carbohydrate and amino acid metabolism, highlighting the metabolic versatility of these fungi. The analysis of transposable elements showed varying proportions of repeats, withC. bantianaexhibiting the highest repeat content. Additionally, the presence of diverse families of carbohydrate-active enzymes (CAZymes) emphasized their capacity for metabolizing complex carbohydrates. The analysis also identified enrichments in secondary metabolite (SM) biosynthetic gene clusters and stress adaptation pathways. All three species possess essential genes for thermal stress adaptation, such as HSP60 and HSF1, along with enzymes for detoxifying reactive oxygen species. The examination of pathogenicity-related genes uncovered a range of virulence factors, including lethal and hypervirulence genes, which raise critical concerns for human health. Functional annotations linked many of these genes to CAZymes, SMs, and stress response proteins. Furthermore, multiple efflux transporters and genes associated with antifungal resistance were identified, indicating potential adaptive mechanisms for drug resistance. This study not only advances our understanding of the genomic features of these fungi but also highlights their ecological and clinical significance, providing a foundation for future research into their pathogenicity and resistance mechanisms.
Dissection of the Global Responses of Mandarin Fish Pyloric Caecum to An Acute Ranavirus (MRV) Infection Reveals the Formation of Serositis and Then Ascites
Authors: Zhang Wenfeng , Li Yong , Wu Xiaosi , Sun Qianqian , Fu Yuting , Weng Shaoping , He Jianguo , Dong Chuanfu 
Published: January 2025

AbstractMandarin fish ranavirus (MRV), a variant of largemouth bass virus (LMBV), is a distinct member of the genusRanaviruswithin the familyIridoviridae. Acute MRV infection predominantly affects the pyloric caecum, a critical visceral organ in mandarin fish, and is hypothesized to drive the characteristic external clinical sign of severe ascites. In this study, we reveal that acute MRV infection initially targets the serosal layer of the pyloric caecum of mandarin fish, leading to rapid progression into fibrinous serositis characterized by serosal hypertrophy, fibrosis, hyperemia, edema, and tissue adhesions. Using single-cell RNA sequencing, we dissect the cellular composition of epithelial, immune, and stromal populations, identifying significant enrichment of macrophages and granulocytes, alongside T and natural killer cells, as key mediators of acute cytokine and inflammatory responses. Then, robust experimental evidence demonstrates that MRV attacks specific immune cell subsets of T and B cells and stromal cells of fibroblasts, myofibroblasts, endothelial cells, and pericytes, resulting in upregulation of genes and pathways associated with extracellular matrix (ECM) formation, collagen biosynthesis, and vascular remodeling in the hyperplastic serosal zone. Additionally, both host-derived type V collagens and MRV-encoded collagens are implicated in ECM formation in the hypertrophic serosa. Collectively, this study provides a comprehensive single-cell resolution analysis of the pyloric caecum’s response to acute MRV infection and highlights virus- driven serositis as the underlying cause of severe ascites in mandarin fish.ImportanceThe pyloric caecum is a vital digestive and immune organ in many bony fish species, including the mandarin fish, a carnivorous species with an exceptionally developed pyloric caecum comprising 207–326 caeca per individual. While MRV/LMBV infects various fish species, severe ascites is uniquely observed in infected mandarin fish. This study demonstrates that acute MRV infection induces fibrinous serositis in the pyloric caecum, characterized by hyperemia, edema, and hyperplasia, ultimately resulting in ascites and mortality. Leveraging single-cell RNA sequencing, we provide a detailed landscape of the cell types affected or involved in the inflammatory response, revealing their roles in the pathogenesis of serositis. These findings advance our understanding of MRV-induced pathology and its species-specific manifestations.
Trans-generational maintenance of mitochondrial DNA integrity in oocytes during early folliculogenesis
Authors: Xie Qin , Wu Haibo , Qiu Jiaxin , Liu Junbo , Lyu Qifeng , Long Hui , Li Wenzhi , Zhang Shuo , Jiang Xueyi , Zhou Yuxiao , Gao Yining , Hsueh Aaron J. W. , Kuang Yanping , Suo Lun 
Published: January 2025

AbstractMutations in mitochondrial DNA (mtDNA) can lead to mitochondrial and cellular dysfunction. However, recent studies suggest that there is purifying selection against mutant mtDNAs during transgenerational transmission. We investigated the mtDNA dynamics during ovarian follicle development. Using base-editing, we generated mice harboring a 3177 G>A mutation corresponding to the human Leber hereditary optic neuropathy (LHON)-related mtDNA mutation and confirmed the transgenerational reduction of mutant mtDNA. Using a mouse follicle culture system in which pathogenic mtDNA mutations were introducedin vitrofollowed by mtDNA sequencing and digital PCR, we found this germline heteroplasmy shift during early folliculogenesis was induced by the decrease of mutant mtDNA together with compensatory replication of wild-type mtDNA. In contrast, synonymous mtDNA mutations did not impact the mtDNA dynamics. These findings show that mice can eliminate certain pathogenic mtDNA mutations in the germline during early folliculogenesis, maintaining mitochondrial integrity across generations.
A Geometric Optical Analysis of Human Retinal Cells and the Hypothesis of Monocular Stereoscopic Vision
Authors: Ding Yong , Ding Dalu , Ding Dawei , Jiang Rongzhi 
Published: January 2025

AbstractWe propose a geometric optical model that describes real-image formation via monocular vision in three dimensions. We only assume that the ganglion cell nuclei, bipolar cell nuclei, and photoreceptor cell nuclei in the human retina can be treated as microlenses and actively participate in imaging. In particular, we suggest that monocular vision operates via an array of high-magnification micro-real-image telescopes oriented in various azimuthal directions. The main elements of each telescope are the following. The first is the cornea and crystalline lens, which serve as objective lenses with tunable focal lengths. The second is a paired array of ganglion cell nuclei and bipolar cell nuclei, which act as a conjugate mirror. The third is an individual photoreceptor cell nuclei (cone or rod nuclei), which function as a micro-eyepiece. The fourth is the outer segment of each photoreceptor cell, which serves as a micro-object-distance sensor.We also hypothesize that six combinations of conjugate mirrors and micro-eyepiece arrays work within the human eye. Each combination is responsible for perceiving different ranges of object distances. We further hypothesize that the process by which one human eye perceives object distances involves two stages: from near to finite distances, and from finite distances to infinite distances. In different stages, the distance between different optical elements is tuned so that the object distance can be computed a specific formula when the photocurrent at the retina photoreceptor’s outer segment layer vanishes.Lastly, we conduct computational simulations. We find that there are two possible processes. By tuning the distances between the elements of our optical model, the eye can perceive object distances as close as 25 cm to dozens of meters in one process and dozens of meters to kilometers in the other process, depending on the sensitivity of the eye to small changes in focal plane spacing.
Plant nutritional and metabolic responses to drought and elevated CO2revealed by machine learning-enabled non-targeted metabolomics
Authors: Chang Hsin-Fang , Caso-McHugh Theresa , Des Marais David L. 
Published: January 2025

AbstractProjected atmospheric CO2rise, coupled with intensification of drought in many regions, impacts the physiology of C3plants beyond photosynthesis and carbon metabolism. The interaction between CO2and drought affects the concentrations of many nutrients in crops, often resulting in excessive agrochemical use and less nutritious food production. To address these challenges, we investigated nutrient dynamics inBrachypodium distachyon, a model crop plant, under ambient and elevated CO2, factorially combined with well-watered or drought treatments. Integrative analyses of plant physiology, transcriptomics, and machine learning-enabled non-targeted metabolomics revealed that plant elemental composition and metabolomic responses to elevated CO2strongly depend on water availability and differ between shoots and roots. Elevated CO2and drought significantly impaired nitrogen status, with root nitrate uptake being more negatively affected than ammonium uptake. However, elevated CO2increased iron partitioning in shoots under drought, potentially driven by enhanced carbon availability facilitating chelator synthesis for iron translocation. The high accumulation of sphingolipids in roots under combined stresses suggests a protective role against ionome imbalances. These findings highlight how climate stressors interact to shape plant nutrient dynamics, providing insights that can guide agricultural practices and breeding strategies to optimize nutrient management and foster sustainable agriculture under changing climate.
Molecular Landscape of the Mouse Adrenal Gland and Adjacent Adipose by Spatial Transcriptomics
Authors: Blatkiewicz Małgorzata , Hryhorowicz Szymon , Szyszka Marta , Suszyńska-Zajczyk Joanna , Pławski Andrzej , Plewiński Adam , Porzionato Andrea , Malendowicz Ludwik K. , Rucinski Marcin 
Published: January 2025

AbstractThe adrenal glands play a vital role in maintaining homeostasis and managing stress through the production and secretion of steroid hormones. Despite extensive research, the molecular mechanisms underlying adrenal zonation and cellular differentiation remain poorly understood. By employing spatial transcriptomics, this study has mapped the adult CD1 IGS mouse adrenal gland, thereby identifying unique genetic markers of zonal differentiation and dynamic cellular interactions. Five cellular clusters, corresponding to the cortex and medulla compartments, were identified, along with two adipose tissue clusters (brown and white). These findings confirm the centripetal differentiation model, highlighting the gradual transition of cell populations from the capsule through cortical zones. Through ligand-receptor interaction analysis, a complex regulatory network governing inter- and intra-zone communication was identified, thereby emphasising the adrenal gland’s central role in integrating endocrine and neuroendocrine signals, particularly in response to stress. This comprehensive spatial transcriptomic map of the adult mouse adrenal gland provides original insights into adrenal biology and constitutes a valuable resource for future research.
Inter-community participatory social network analysis: re-envisioning humanitarian accountability with climate-related displaced communities in Bangladesh
Authors: Ji Hyeonggeun 
Published: January 2025

PurposeHumanitarian accountability is practiced with the normative aim of challenging systematic inequalities and power imbalance in humanitarian governance. This study interrogates the actual practices of humanitarian accountability from the perspectives of climate-related displaced communities in Bangladesh.Design/methodology/approachInter-community participatory social network analysis (PSNA) was adopted during the fieldwork to centralise the perspectives of climate-related displaced people in knowledge construction. The on-site revision of the research design manifested methodological reflexivity, fostering epistemological plurality.FindingsThe universal practice of downward accountability shows limited sensitivity to local power asymmetries in rural Bangladeshi society. This apolitical approach is often co-opted by humanitarian agencies, further marginalising displaced people in governing process. In contrast, the nuanced concept of an accountable humanitarian network represents a socially embedded practice driven by local actors and institutions, emphasising respect for the rights and agency of displaced people.Originality/valueThe findings were co-constructed by the author, research assistant and participants, contributing to methodological reflexivity in disaster studies and advancing humanitarian accountability practice.
Building the next generation of researchers: an “EPIC” student mentoring process
Authors: Yzaguirre Melissa , Miller Debra , Padilla Flores Daisy , Holtrop Kendal 
Published: January 2025

PurposeThe purpose of this paper is to describe an intervention-based research mentoring opportunity for higher education students in health- and mental health-related disciplines.Design/methodology/approachThis paper includes a retrospective case study to demonstrate the application of a unique research mentoring method with a voluntary interdisciplinary team of undergraduate and graduate students on a project funded by the National Institutes of Health in the United States of America. The research mentoring experience is described through a pedagogical approach based directly on the focal intervention under study (e.g. GenerationPMTO).FindingsWe present the process of an intervention-based model of research mentoring as a unique opportunity to build student research skills and provide exposure to evidence-based interventions applicable to general health populations. Findings demonstrate the research team’s success in forming a collaborative research mentoring environment, performing key research tasks effectively and making reliable fidelity ratings.Practical implicationsThis paper provides novel insight into an isomorphic process using intervention-based research mentoring as a pedagogy to enhance students’ research skills and application.Originality/valueUnderstanding effective research mentoring approaches can influence the trajectory for future generations of mental health researchers and scholars who may not otherwise be exposed to research in their clinical training programs or courses of study. This paper provides insight and recommendations for how mentors can engage higher education students intentionally in research opportunities using intervention-based research mentoring.
The interplay of green capabilities, organizational culture and green marketing strategy to explain green competitive advantage
Authors: Alhemimah Arej , Ali Murad , Badghish Saeed , Latan Hengky , Lopes de Sousa Jabbour Ana Beatriz 
Published: January 2025

PurposeThis study examines the dynamic capability and resource-based view theories in the context of the tourism and hospitality industry, examining how the green dynamic capabilities of firms interact with green marketing strategies to influence their level of green competitive advantage under the boundary condition of the green organizational culture of Saudi Arabia’s tourism and hospitality sector.Design/methodology/approachUsing multi-sourced and three-wave time-lagged data from 136 managers and their subordinates within the Saudi Arabian tourism industry to test the hypotheses.FindingsThe results reveal that all hypotheses were accepted, affirming the direct, mediating, moderating and moderated mediating associations among green dynamic capabilities, green marketing strategies, green organizational culture and green competitive advantage.Originality/valueThis study offers valuable insights for practitioners and policymakers seeking to enhance the sustainability performance and competitive advantage of firms in the ever-evolving tourism sector.