bluuebunny/crossref_metadata_2025_split huggingface dataset:
A global-scale dataset of bat viral detection suggests that pregnancy reduces viral shedding
Authors: Eskew Evan A. , Olival Kevin J. , Mazet Jonna A. K. , Daszak Peter ,   PREDICT Consortium
Published: February 2024

ABSTRACTUnderstanding viral infection dynamics in wildlife hosts can help forecast zoonotic pathogen spillover and human disease risk. Bats are particularly important reservoirs of zoonotic viruses, including some of major public health concern such as Nipah virus, Hendra virus, and SARS-related coronaviruses. Previous work has suggested that metapopulation dynamics, seasonal reproductive patterns, and other bat life history characteristics might explain temporal variation in spillover of bat-associated viruses into people. Here, we analyze viral dynamics in free-ranging bat hosts, leveraging a multi-year, global-scale viral detection dataset that spans eight viral families and 96 bat species from 14 countries. We fit hierarchical Bayesian models that explicitly control for important sources of variation, including geographic region, specimen type, and testing protocols, while estimating the influence of reproductive status on viral detection in female bats. Our models revealed that late pregnancy had a negative effect on viral shedding across multiple data subsets, while lactation had a weaker influence that was inconsistent across data subsets. These results are unusual for mammalian hosts, but given recent findings that bats may have high individual viral loads and population-level prevalence due to dampening of antiviral immunity, we propose that it would be evolutionarily advantageous for pregnancy to either not further reduce immunity or actually increase the immune response, reducing viral load, shedding, and risk of fetal infection. This novel hypothesis would be valuable to test given its potential to help monitor, predict, and manage viral spillover risk from bats.
The Role of Nde1 Phosphorylation in Interkinetic Nuclear Migration and Schizophrenia
Authors: Doobin David J , Helmer Paige , carabalona Aurelie , Bertipaglia Chiara , Vallee Richard B 
Published: February 2024

AbstractNde1 is a cytoplasmic dynein regulatory protein with important roles in vertebrate brain development. One noteworthy function is in the nuclear oscillatory behavior in neural progenitor cells, the control and mechanism of which remain poorly understood. Nde1 contains multiple phosphorylation sites for the cell cycle-dependent protein kinase CDK1, though the function of these sites is not well understood. To test their role in brain development we expressed phosphorylation-state mutant forms of Nde1 in embryonic rat brains usingin uteroelectroporation. We find that Nde1 T215 and T243 phosphomutants block apical interkinetic nuclear migration (INM) and, consequently, mitosis in radial glial progenitor cells. Another Nde1 phosphomutant at T246 also interfered with mitotic entry without affecting INM, suggesting a more direct role for Nde1 T246 in mitotic regulation. We also found that the Nde1 S214F mutation, which is associated with schizophrenia, inhibits CDK5 phosphorylation at an adjacent residue which causes alterations in neuronal lamination. These results together identify important new roles for Nde1 phosphorylation in neocortical development and disease and represent the first evidence for Nde1 phosphorylation roles in INM, neuronal lamination, and schizophrenia.Significance StatementThe results presented in this study show the importance of Nde1 phosphoregulation during successive stages of neocortical development. Nde1 dysregulation may, in turn, have important consequences in human psychiatric disorders, such as schizophrenia, as well. We observed clear and potent effects of specific Nde1 phosphomutants in the control of INM and neural development. Our results provide strong support for new insight into the little-understood mechanism for triggering RGP mitotic entry. In the course of these studies, we obtained clear evidence for a novel post-mitotic role for Nde1 phosphorylation in schizophrenia.
Evaluating Explanations from AI Algorithms for Clinical Decision-Making: A Social Science-based Approach
Authors: Ghanvatkar Suparna , Rajan Vaibhav 
Published: February 2024

AbstractExplainable Artificial Intelligence (XAI) techniques generate explanations for predictions from AI models. These explanations can be evaluated for (i) faithfulness to the prediction, i.e., its correctness about the reasons for prediction, and (ii) usefulness to the user. While there are metrics to evaluate faithfulness, to our knowledge, there are no automated metrics to evaluate the usefulness of explanations in the clinical context. Our objective is to develop a new metric to evaluate usefulness of AI explanations to clinicians. Usefulness evaluation needs to consider both (a) how humans generally process explanations and (b) clinicians’ specific requirements from explanations presented by clinical decision support systems (CDSS). Our new scoring method can evaluate the usefulness of explanations generated by any XAI method that provides importance values for the input features of the prediction model. Our method draws on theories from social science to gauge usefulness, and uses literature-derived biomedical knowledge graphs to quantify support for the explanations from clinical literature. We evaluate our method in a case study on predicting onset of sepsis in intensive care units. Our analysis shows that the scores obtained using our method corroborate with independent evidence from clinical literature and have the required qualities expected from such a metric. Thus, our method can be used to evaluate and select useful explanations from a diverse set of XAI techniques in clinical contexts, making it a fundamental tool for future research in the design of AI-driven CDSS.
Digital Health Technologies for Metabolic Disorders in Older Adults: A Scoping Review Protocol
Authors: Huynh Panitda , Fleisch Elgar , Brändle Michael , Kowatsch Tobias , Jovanova Mia 
Published: February 2024

AbstractIntroductionMetabolic disorders (type 2 diabetes, insulin resistance, hyperglycemia, obesity, hyperlipidemia, hypertension, nonalcoholic fatty liver disease, and metabolic syndrome) are leading causes of mortality and disability worldwide and disproportionately affect older adults relative to those younger. Digital health technologies (DHTs), such as patient monitoring, digital diagnostics, and digital therapeutics, emerge as promising tools for navigating health in day-to-day life. However, their role in targeting metabolic disorders, particularly among a key demographic of older adults, is not yet fully understood. Thus, this work aims to scope the use of DHTs in managing metabolic health disorders among older adults.Methods and AnalysisWe will conduct a scoping review following the recommended framework by Arksey and O’Malley (1). Our search will focus on three primary concepts: metabolic disorders, DHTs, and older adults. We plan to search five online databases—Cochrane, Embase, PubMed, Scopus, and Web of Science—to identify original research articles published between January 2014 and January 2024. Two reviewers will independently screen articles for inclusion based on predetermined criteria, and a separate reviewer will resolve conflicts. Data will be extracted using a standardized form, and the findings will be synthesized and reported qualitatively and quantitatively.Ethics and disseminationNo ethics approval is required for this protocol and scoping review, as data will be used only from published studies with appropriate ethics approval. Results will be disseminated in a peer-reviewed publication.This protocol has been preregistered on OSF Repository at:https://osf.io/9s8fm.Strengths and limitations of this studyTo our knowledge, this scoping review is the first to scope the landscape of DHTs for targeting metabolic disorders among older adults.We apply the DHT Ecosystem Categorization for a more standardized overview of the peer-reviewed empirical literature across multiple databases and follow rigorous scoping review reporting guidelines.Consistent with the nature of scoping reviews, our study does not include an assessment of the quality of the included studies, only involves studies in English, and does not include non-peer reviewed industry reports, which may also provide relevant information.Since our pre-existing definition of metabolic disorders focuses on various pre-defined major conditions, there exists a possibility that we may not comprehensively capture all possible instances of metabolic disorders among older adults.
Multisectoral prioritization of zoonotic diseases in India: A One Health perspective
Authors: Tiwari Simmi , Roy Indranil , Daptardar Monal , Singh Ruchi , Mishra Anshuman , Kedia Richa , Manocha Harmesh , Diwedi Mayank , Dwivedi Amlesh , Shukla Gaurish , Shewale Ajit , Nale Tushar , Mishra Dipti , Sharma R.P. , Garcia Daniel , Gokhale Runa H. , Desai Meghna , Singh Sujeet 
Published: February 2024

AbstractIntroductionTo tackle the risk of emerging and re-emerging diseases, it is critical for countries with limited resources to prioritize endemic and emerging zoonotic diseases of greatest national concern. One Health is an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals, and ecosystems. In India, as a first step towards a multi-disciplinary, multi-sectoral, One Health approach to preventing and detecting zoonotic disease outbreaks, a national-level multi-stakeholder zoonotic disease prioritization workshop was organized to identify a list of zoonotic diseases of greatest national concern for India.MethodsWe followed the Good Reporting of a Mixed Methods Study (GRAMMS) guidelines to finalize a list of priority zoonotic diseases through a participatory action research approach involving 50 experts in zoonotic diseases. We used a prioritization process based on the U.S. Centers for Disease Control and Prevention’s semi-quantitative One Health Zoonotic Disease Prioritization (OHZDP) Process, with modifications per country need.ResultsWe ranked forty zoonotic diseases based on five criteria: severity of illness in humans, the economic burden of the diseases, pandemic potential, capacity for prevention and control, and potential for introduction or increased transmission in India. The final list of zoonotic diseases ranked in the order of national significance includes the following top ten priority zoonotic diseases: Zoonotic Influenza (Zoonotic Influenza A viruses), Anthrax, Japanese Encephalitis, Leptospirosis, Brucellosis, Dengue, Rabies, Scrub typhus, Plague, and Crimean-Congo hemorrhagic fever. We conducted a sensitivity analysis to assess the impact of each criterion on the prioritized list; this analysis showed minimal changes in ranking for the top ten diseases.ConclusionFor the successful adoption of One Health practices in India, multi-sectoral collaboration is critical at all levels – national, state, and provincial. This collaborative prioritization process conducted at the national level has the potential to catalyse such efforts and enhance zoonotic disease prevention and detection efforts at the state and local levels across India.
On the relationship between concentration buffering and noise reduction in phase separating systems
Authors: Zechner Christoph , Jülicher Frank 
Published: February 2024

AbstractBiomolecular condensates have been proposed to buffer intracellular concentrations and reduce noise. Recent results demonstrate that concentrations need not be buffered in multicomponent systems, leading to a non-constant saturation concentration (csat) when individual components are varied. Simplified equilibrium considerations suggest that noise reduction might be closely related to concentration buffering and that a fixed saturation concentration is required for noise reduction to be effective. Here we present a theoretical analysis to demonstrate that these suggestions do not apply to mesoscopic fluctuating systems. We show that concentration buffering and noise reduction are distinct concepts, which cannot be used interchangeably. We further demonstrate that concentration buffering – and a constantcsat– are neither necessary nor sufficient for noise reduction to be effective. Clarity about these concepts is important for studying the role of condensates in controlling cellular noise and for the interpretation of concentration relationships in cells.
Decoupled degradation and translation enables noise-modulation by poly(A)-tails
Authors: Grandi Carmen , Emmaneel Martin , Nelissen Frank H. T. , Roosenboom Laura W. M. , Petrova Yoanna , Elzokla Omnia , Hansen Maike M. K. 
Published: February 2024

SUMMARYPoly(A)-tails are crucial for mRNA translation and degradation, but the exact relationship between tail length and mRNA kinetics remains unclear. Here we employ a small library of identical mRNAs that differ only in their poly(A)-tail length to examine their behavior in human embryonic kidney cells. We find that tail length strongly correlates with mRNA degradation rates, but is decoupled from translation. Interestingly, an optimal tail length of ∼100 nucleotides displays the highest translation rate, which is identical to the average endogenous tail length measured by nanopore sequencing. Furthermore, poly(A)-tail length variability––a feature of endogenous mRNAs––impacts translation efficiency but not mRNA degradation rates. Stochastic modelling combined with single-cell tracking reveals that poly(A)-tails provide cells with an independent handle to tune gene expression fluctuations by decoupling mRNA degradation and translation. Together, this work contributes to the basic understanding of gene expression regulation and has potential applications in nucleic acid therapeutics.
Knockout mutations ofNicotiana benthamianadefenses reveal the relative importance of acylsugars, nicotine, and a serine protease inhibitor in a natural setting
Authors: Negin Boaz , Wang Fumin , Fischer Hillary D. , Jander Georg 
Published: February 2024

SummaryPlants produce an immense diversity of defensive specialized metabolites. However, despite extensive functional characterization, the relative importance of different defensive compounds is rarely examined in natural settings. Here, we compare the efficacy of threeNicotiana benthamianadefensive compounds, nicotine, acylsugars, and a serine protease inhibitor, by growing plants with combinations of knockout mutations in a natural setting, quantifying invertebrate interactions, and comparing relative plant performance. Among the three tested compounds, acylsugars had the greatest defensive capacity, affecting aphids, leafhoppers, spiders, and flies. Nicotine mutants displayed increased leafhopper feeding and aphid colonization. Plants lacking both nicotine and acylsugars were more susceptible to flea beetles and thrips. By contrast, knockout of the serine protease inhibitor did not affect insect herbivory in the field. Complementary experiments under controlled laboratory conditions with caterpillars grasshoppers, and aphids confirmed results obtained in a natural setting. We conclude that the three metabolite groups collectively provide broad-spectrum protection toN. benthamiana. However, there is a gradient in their effects on the interacting invertebrates present in the field. Furthermore, we demonstrate that, even if individual metabolites do not have a measurable defensive benefit on their own, they can have an additive effect when combined with other defensive compounds.
Photoreceptor–induced sinapate synthesis contributes to photoprotection in Arabidopsis
Authors: Leonardelli Manuela , Tissot Nicolas , Podolec Roman , Ares-Orpel Florence , Glauser Gaétan , Ulm Roman , Demarsy Emilie 
Published: February 2024

ABSTRACTPlants must balance light capture for photosynthesis with protection from potentially harmful ultraviolet radiation (UV). Photoprotection is mediated by concerted action of photoreceptors, but the underlying molecular mechanisms are not fully understood. In this study, we provide evidence that UV RESISTANCE LOCUS 8 (UVR8) UV-B-, phytochrome red-, and cryptochrome blue-light photoreceptors converge on the induction ofFERULIC ACID 5-HYDROXYLASE 1(FAH1) that encodes a key enzyme in the phenylpropanoid biosynthesis pathway, leading to the accumulation of UV-absorbing sinapate esters.FAH1induction depends on the bZIP transcription factors ELONGATED HYPOCOTYL 5 (HY5) and HY5-HOMOLOG (HYH) that function downstream of all three photoreceptors. Noticeably, mutants with hyperactive UVR8 signalling rescuefah1UV sensitivity. Targeted metabolite profiling suggests that this phenotypic rescue is due to the accumulation of UV-absorbing metabolites derived from precursors of sinapate synthesis, namely coumaroyl-glucose and feruloyl-glucose. Our genetic dissection of the phenylpropanoid pathway combined with metabolomic and physiological analyses show that both sinapate esters and flavonoids contribute to photoprotection with sinapates playing a major role for UV screening. Our findings indicate that photoreceptor-mediated regulation ofFAH1and subsequent accumulation of sinapate “sunscreen” compounds is a key protective mechanism to mitigate damage, preserving photosynthetic performance, and ensuring plant survival under UV.
Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screening and single-cell sequencing
Authors: Castellanos-Rueda Rocío , Wang Kai-Ling K. , Forster Juliette L. , Driessen Alice , Frank Jessica A. , Martínez María Rodríguez , Reddy Sai T. 
Published: February 2024

ABSTRACTChimeric antigen receptor (CAR) T cells represent a promising approach for cancer treatment, yet challenges remain such as limited efficacy due to a lack of T cell persistence. Given its critical role in promoting and modulating T cell responses, it is crucial to understand how alterations in the CAR signaling architecture influence T cell function. Here, we designed a combinatorial CAR signaling domain library and performed repeated antigen stimulation assays, pooled screening and single-cell sequencing to investigate T-cell responses triggered by different CAR architectures. Parallel comparisons of CAR variants, at early, middle and late timepoints during chronic antigen stimulation systematically assessed the impact of modifying signaling domains on T cell activation and persistence. Our data reveal the predominant influence of membrane-proximal domains in driving T cell phenotype. Additionally, we highlight the critical role of CD40 costimulation in promoting potent and persistent T cell responses, followed by CTLA4, which induces a long-term cytotoxic phenotype. This work deepens the understanding of CAR T cell biology and may be used to guide the future engineering of CAR T cell therapies.
Long-term Culturing ofPseudomonas aeruginosain Static, Minimal Nutrient Medium Results in Increased Pyocyanin Production, Reduced Biofilm Production, and Loss of Motility
Authors: Cecil Rhiannon , Ornelas Elana , Phan Anh , Yoder-Himes Deborah 
Published: February 2024

AbstractPseudomonas aeruginosais a multidrug-resistant opportunistic human pathogen that can survive in many natural and anthropogenic environments. It is a leading cause of morbidity in individuals with cystic fibrosis and is one of the most prevalent pathogens associated with nosocomial infections in the United States. It has been shown that this organism can survive and persist in low nutrient environments such as sink drains and inside the respiratory system of human hosts. How adaptation to these types of environments influences phenotypic traits of this organism has not been well studied. Here we implemented an experimental evolution system designed to imitate these environmental niches and identified phenotypic changes that occurred as a result of adaptation to such environments in six strains ofP. aeruginosawith varying life history and colony phenotypes. We observed that adaptation to low nutrient environments resulted in decreased generation time, reduced cell size, reduced biofilm formation, increased pyocyanin production, and decreased motility. Our work is significant as it allows us to predict how this organism will evolve in hospital and domestic environments and can help us improve treatment options for patients.
Credit card repayments in a Latin American country: a psychological perspective
Authors: Delgado Fuentealba Carlos Leandro , Muñoz Mendoza Jorge Andrés , Veloso Ramos Carmen Lissette , Cornejo-Saavedra Edinson Edgardo , Sepúlveda Yelpo Sandra María , Fuentes-Solís Rodrigo 
Published: February 2024

PurposeThis paper aims to analyze decisions about payment rates on credit card statements by using background factors and perceptions that indirectly influence beliefs, according to the theory of planned behavior.Design/methodology/approachSince legal and institutional frameworks and household financial surveys are heterogeneous among countries, household data on the Chilean economy is used as the starting point in this matter.FindingsThe probability that an individual chooses to pay amounts less than the total billing of their credit cards rises with essential variables related to perceived behavioral control. Being the head of the household, being younger, perceiving a high or excessive financial burden of debt and facing unfavorable and unexpected situations that divert the budget, among others, are relevant to repayment decisions.Originality/valueThe novelty of this article is that its psychological approach differs from the traditional focus of economic rationality regarding credit cards. The results are relevant for policymakers and financial regulators due to implications for household behavioral finance and means of payment.