bluuebunny/crossref_metadata_2025_split huggingface dataset:
One-Year Outcomes in Acute Strokes with Hyperglycemia in Low Resource Settings (SHAPE): A Prospective Cohort Study Protocol
Authors: Rajbhandari Bibek , Shakya Yogendra Man , Maharjan Ramesh Kumar , Malla Dipak , Thapa Paras , Regmi Prakash , Shrestha Bikal , Shahi Sumit 
Published: December 2024

ABSTRACTBackgroundStroke is a significant global health issue, serving as a leading cause of death and disability. The burden of this condition is especially severe in low- and middle-income countries, where the majority of stroke-related fatalities occur. Hyperglycemia, a common metabolic disturbance observed in acute stroke patients, is known to worsen clinical outcomes, contributing to higher rates of mortality and morbidity. This study aims to investigate the relationship between hyperglycemia, morbidity and mortality outcomes in patients with acute stroke, assessing how varying glycemic levels influence short-term (1 month), mid-term (3 months), and long-term (1 year) mortality rates.MethodsThe SHAPE study is a prospective cohort study conducted at the Emergency Department of Tribhuvan University Teaching Hospital (TUTH). The study will enroll adults aged over 40 who present with BEFAST-positive symptoms of acute stroke, confirmed through CT/MRI imaging. Participants will be classified into two groups: those exhibiting hyperglycemia (exposed group) and those with normal glycemic levels (unexposed group). Sixty participants will be recruited (30 hyperglycemic and 30 normoglycemic) and followed for one year to assess mortality and functional outcomes using the modified Rankin Scale (mRS). Data collection will involve regular follow-ups through phone calls, clinic visits, and home visits at 1, 3, and 12 months post-stroke. The analysis will include bivariate comparisons for categorical and continuous variables, logistic regression to identify independent predictors of mortality and functional outcomes, and Kaplan-Meier analysis for assessing survival rates.Ethical ConsiderationsThe SHAPE Study was approved by the Ethics Review Committee of the Institute of Medicine (Ref no.. 6-11E2), and written informed consent will be obtained from all participants. Results will be disseminated via a peer-reviewed journal.Trial registration numberClinicalTrials.gov IDNCT06560983
Primary sensory neuron dysfunction underlying mechanical itch hypersensitivity in a Shank3 mouse model of autism
Authors: Huzard Damien , Marias Mélanie , Granat Chloé , Oliva Giulia , Soubeyre Vanessa , Grellier Gawain , Negm Ahmed , Devaux Jérôme , Bourinet Emmanuel , François Amaury 
Published: December 2024

AbstractAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder marked by social deficits, repetitive behaviors, and atypical sensory perception. The link between ASD and skin abnormalities, inducing itchiness, has never been investigated in depth. This study explores mechanical itch sensitivity in the Shank3ΔC/ΔCmouse model. Key observations include heightened scratching in response to skin deformation and hypersensitivity to mechanical itch (i.e. alloknesis) in Shank3ΔC/ΔCmice. In Shank3ΔC/ΔCmice,ex vivoelectrophysiological experiments revealed that C-fiber low-threshold mechanoreceptors (C-LTMRs) were hyporesponsive, and transcriptomic analysis showed a downregulation of TAFA4, a protein secreted by C-LMTRs. Interestingly, pharmacologically inhibiting Aβ-LTMR, important in mechanical itch initiation, abolished the itch hypersensitivity. Also, TAFA4 injections reduced the spontaneous scratching response to skin deformation but failed to restore itch sensitivity. Our data suggest that somatosensory deficits in Shank3ΔC/ΔCmice lead to hypersensitivity to itchiness and indicate that two pathways might regulate mechanical itchiness, dependent on TAFA4.
Proteome Analysis of Soybean Root Apoplast Combined with AlphaFold Prediction RevealMacrophomina phaseolinaInfection Strategies and Potential Targets for Engineering Resistance
Authors: Veeraganti Naveen Prakash Chetan , Sivaramakrishnan Muthusaravanan , Goel Sakshi , Porwal Vasudha , Amrate Pawan Kumar , Shrivastava Manoj Kumar , Chandrasekar Balakumaran 
Published: December 2024

AbstractMacrophomina phaseolina(Tassi) Goid. is a hemibiotrophic pathogen that causes charcoal rot (CR) disease in various legumes, including soybean. To date, no reliable resistance gene sources have been identified in soybean or other legumes to combatM. phaseolina. Therefore, the identification of mechanistic targets is crucial for improving resistance against the pathogen. The apoplast is a critical region where intense molecular cross-talk occurs between plants and pathogens, and the outcome of their interactions is determined in this compartment. Here, we employed label-free quantitative (LFQ) proteomics to investigate the dynamics of soybean root apoplast duringM. phaseolinainfection. We have detected several secreted proteins ofM. phaseolinaand differential regulation of soybean-secreted proteins in root apoplast during infections. Glycome analysis and callose deposition assays have revealed changes in soybean root cell wall compositions and potential polysaccharide targets ofM. phaseolina. AlphaFold 2 (AF2) analysis was instrumental in revealing several interesting sequence-unrelated structurally similar (SUSS) effectors and effectors with novel structural folds secreted byM. phaseolina. Structured-guided engineering of protease-inhibitor complexes is emerging as an important strategy to engineer resistance in plants against pathogens. AlphaFold Multimer (AFM) analysis of candidate-secreted proteins from soybean andM. phaseolinahas predicted cysteine and serine protease-inhibitor complexes with high confidence. We have validated these interactions using molecular dynamics (MD) and competitive activity-based protein profiling (ABPP) approaches. Therefore, our work provides insights into Soybean-M. phaseolinainteractions in the root apoplast and unveil potential candidates for engineering resistance.
Catestatin improves heart metabolic flexibility by promoting mitochondrial structure and function
Authors: Chirasani Venkat R. , Kal Satadeepa , Biswas Nilima , Mahata Sumana , Tang Kechun , Pasqua Teresa , Avolio Ennio , Jati Suborno , Bandyopadhyay Gautam , Head Brian P. , Patel Hemal H. , van den Bogaart Geert , Sahoo Debashis , Senapati Sanjib , Mahata Sushil K. 
Published: December 2024

AbstractHypertension, a major cause of cardiomyopathy, is one of the most critical risk factors for heart failure and mortality worldwide. Loss of metabolic flexibility of cardiomyocytes is one of the major causes of heart failure. Although Catestatin (CST) treatment is known to be both hypotensive and cardioprotective, its effect on cardiac metabolism is unknown. In this study, we undertook a transcriptomic approach to identify differentially expressed genes that were filtered using Boolean implication relationships to develop a model of gene regulation in saline or CST-supplemented CST knockout (CST-KO) mice. The analysis revealed a set of gene signatures (fibroblast, cardiomyocyte, and macrophage) rescued after CST supplemented CST-KO mice compared to wild-type. Furthermore, we independently validated these gene signature models using publicly available patient datasets. Since the gene signature includes genes related to glucose, fatty acid metabolism, and mitochondrial function, we assessed the glucose and fatty acid uptake after CST treatment. We found that CST treatment can restore the cardiac metabolic inflexibility in CST-KO heart due to the metabolic shift of glucose utilization to fatty acid as energy source. Binding studies after immunoprecipitation and mass spectrometry revealed CST binding with ATP synthase, supported by molecular simulation and computational modeling that predicted CST binding to α/β subunit of ATP synthase. Colocalization of CST with mitochondria and increased mitochondrial membrane potential and ATP production upon CST treatment in neonatal cardiomyocytes further exhibit CST as a key regulator of cardiac metabolism and mitochondrial function.
Protists as mediators of complex microbial and viral associations
Authors: Schulz Frederik , Yan Ying , Weiner Agnes K.M. , Ahsan Ragib , Katz Laura A. , Woyke Tanja 
Published: December 2024

AbstractMicrobial eukaryotes (aka protists) are known for their important roles in nutrient cycling across different ecosystems. However, the composition and function of protist-associated microbiomes remains largely elusive. Here, we employ cultivation-independent single-cell isolation and genome-resolved metagenomics to provide detailed insights into underexplored microbiomes and viromes of over 100 currently uncultivable ciliates and amoebae isolated from diverse environments. Our findings reveal unique microbiome compositions and hint at an intricate network of complex interactions and associations with bacterial symbionts and viruses. We observed stark differences between ciliates and amoebae in terms of microbiome and virome compositions, highlighting the specificity of protist-microbe interactions. Over 115 of the recovered microbial genomes were affiliated with known endosymbionts of eukaryotes, including diverse members of the Holosporales, Rickettsiales, Legionellales, Chlamydiae, Dependentiae, and more than 250 were affiliated with possible host-associated bacteria of the phylum Patescibacteria. We also identified more than 80 giant viruses belonging to diverse viral lineages, of which some were actively expressing genes in single cell transcriptomes, suggesting a possible association with the sampled protists. We also revealed a wide range of other viruses that were predicted to infect eukaryotes or host-associated bacteria. Our results provide further evidence that protists serve as mediators of complex microbial and viral associations, playing a critical role in ecological networks. The frequent co-occurrence of giant viruses and diverse microbial symbionts in our samples suggests multipartite associations, particularly among amoebae. Our study provides a preliminary assessment of the microbial diversity associated with lesser-known protist lineages and paves the way for a deeper understanding of protist ecology and their roles in environmental and human health.
Errors-in-variables and validation problems in reaction norm predictions for wild populations
Authors: Ergon Rolf 
Published: December 2024

ABSTRACTStudies of phenotypic responses in wild populations are often based on reaction norm models where the environmental drivers in many cases are related to climate change. Such input signals will never be exactly known, and there will always be measurement errors also in the recorded responses. In parameter estimation these errors give rise to errors-in-variables problems, especially in form of overfitting caused by errors in the input measurements. A second important feature of such phenotypic response problems is that the environmental inputs must be given appropriate but largely unknown reference values. A third problem is that it is difficult to find good validation methods for predicted responses. Essential aspects of these problems are here studied by use of a reaction norm model in its simplest univariate form, characterized by a mean intercept value and a mean plasticity slope value, and the overall conclusion is that validated disentanglement of plasticity and genetic adaptation based on realistically short data for wild populations is a difficult task. In a proposed validation method, the available input-output data is split into one part for modeling and one part for validation, and the feasibility of this approach is studied in simulations with use of a prediction error method, which is essentially a maximum likelihood method. It is also argued that validation of a chosen or estimated reference environment in practice is impossible when the data comes from the (unintended) anthropogenic global warming experiment, where no independent experimental data exists. When the evolution is slow because of small genetic variances, overlapping generations and long lifetimes, or because of near optimal adaptive plasticity, the best quantitative genetics option may be to assume a constant plasticity slope value, equal to the initial value. It turns out to be easy to estimate this value, but that should be done without setting other unknown parameter values to zero. This option is appealing also because it removes the dependence of a guessed or estimated reference environment.
Direct RNA Oxford Nanopore sequencing distinguishes between modifications in tRNA at the U34position
Authors: Kusmirek W. , Strozynska N. , Martin-Arroyo Cerpa P. , Dziergowska A , Leszczynska G. , Nowak R. , Adamczyk M. 
Published: December 2024

ABSTRACTThe measurement of tRNA modifications with single transcript resolution has been feasible for only a few modifications due to the lack of available methods. This limitation does not allow to advance basic research studies on the dynamic nature of tRNA modification and its cellular function in time and space, neither to develop modern diagnostic tools for several already known tRNA-dependent human diseases. Nanopore is a well-established sequencing method that has proven to be efficient for the study of RNA. The analysis of tRNA modifications by Nanopore is still under development. We have investigated the efficacy of nanopore technology to discriminate between complex modifications of uridine 34 in tRNA, which affect the base-calling properties of neighbouring bases and are therefore difficult to accurately predict. We have developed new methods to chemically and enzymatically synthesise single modified tRNA molecules with modifications at the anticodon loop. Nanopore technology captures the features produced by uridine with and without a thiol group when present on synthetic tRNA molecules. Thus, Oxford Nanopore Technology (ONT) has great potential for developing strategies to accurately identify the modification status of the tRNA anticodon loop (ACL), which encompasses the most complex modifications on uridine-containing RNA motifs.Abstract Figure
MicroRNA profiling identifies novel regulators of stem cell function in the adultDrosophilaintestine
Authors: Sreejith Perinthottathil , Yon Joshuah , Lapenta Kalina , Biteau Benoit 
Published: December 2024

AbstractPrecise control of stem cell activity is critical to maintain homeostasis and regenerative capacity of adult tissues and limit proliferative syndromes. Hence, stem cell-specific complex regulatory networks exist to exquisitely maintain gene expression and adapt it to tissue demand, controlling self-renewal, fate commitment and differentiation of developing and adults cell lineages. One of the essential and conserved regulatory components that fine-tune gene expression are microRNAs, which post-transcriptionally regulate stability and translation of messengers. microRNAs have been identified as critical stem cell regulators across stem cell populations and organisms. Here, we report the profiling of microRNAs expressed in stem cells and their immediate daughter cells in theDrosophilaadult intestine. Our analysis identifies over 60 miRs that can be reliably detected in these sorted progenitor cells; a few of these have been reported to control fly intestinal stem cells, but most have yet to be investigated in the adult intestinal lineage. To validate the relevance of our unbiased analysis, we chose to characterize the phenotypes associated with genetic manipulations of two of these microRNAs, miR-31a and miR-34, which are conserved in other organisms, but whose function has not been investigated in the Drosophila midgut. We found that miR-31a acts as anti-proliferation factor and is important for the re-entry of ISC into quiescence after tissue damage. Additionally, we demonstrate that miR-34 is essential for ISC proliferation, but its over-expression also prevents proliferation, highlighting the complexity of miR-mediated control of stem cell function. Altogether, our work establishes a new critical resource to investigate the detailed mechanisms that control stem cell proliferation and intestinal differentiation under homeostatic conditions, in response to tissue damage, or during epithelial transformation and aging.
Plasmodium falciparumexpresses fewervargenes at lower levels during asymptomatic dry season infections than clinical malaria cases
Authors: Ceesay Sukai , Kampmann Martin , Votborg-Novél Lasse , Hansson Helle Smedegaard , Jensen Rasmus Weisel , Carrasquilla Manuela , Cisse Hamidou , Turner Louise , Dabbas Usama , Ntalla Christina , Bandermann Silke , Doumbo Safiatou , Doumtabe Didier , Ongoiba Aissata , Kayentao Kassoum , Traore Boubacar , Crompton Peter D , Lavstsen Thomas , Portugal Silvia 
Published: December 2024

AbstractIn seasonal transmission areas, clinical malaria occurs during the wet season when mosquitoes are present, while in the dry season, malaria transmission is interrupted and clinical cases are rare. In Mali,Plasmodium falciparumcan persist in low parasitaemic asymptomatic individuals through the six-month dry season and shows reduced cytoadhesion of infected erythrocytes, evidenced by the circulation of further developed parasite stages compared to clinical malaria cases. How prolonged circulation of infected erythrocytes is achieved remains unknown. Here, we exploredvargene expression in subclinical infections and clinical malaria cases of Malian children, collected during the dry and wet seasons. We sequenced expressedvarDBLα-tags, used bioinformatic tools to predict their domain composition, binding phenotype and upstream sequence type; and determined their relationship to seasonality and clinical presentation. We found that parasites of asymptomatic infections expressed fewervargenes, with a larger proportion ofvartranscripts attributed to one or a fewvars. In contrast, clinical cases exhibited expression of manyvargenes at lower proportions. We found that parasites of asymptomatic carriers expressed a mixture of CD36- and EPCR-binding PfEMP1, which changed over time. We confirmed thatvarsencoding CD36-binding PfEMP1 dominated in non-severe malaria cases, and found no significant difference in expressedvartypes between dry and wet seasons. Asymptomatic carriers were older, had higher titers of anti-P. falciparumantibodies, and broader reactivity to PfEMP1, suggesting that host immunity was the main determinant limitingvartranscript variation in asymptomatic carriers. However, by RNAseq and qRT-PCR we also observed significantly higher totalvartranscript levels in malaria cases compared to asymptomatic carriers, suggesting that in addition to the parasite’s switching and the host’s immune selection of expressedvargenes, parasites able to sustain long-term infections may be poised for reduced PfEMP1 expression.
Shedding light on dark sectors with high-energy muons at the NA64 experiment at the CERN SPS
Authors: Andreev Yu. M. , Banerjee D. , Oberhauser B. Banto , Bernhard J. , Bisio P. , Charitonidis N. , Crivelli P. , Depero E. , Dermenev A. V. , Donskov S. V. , Dusaev R. R. , Enik T. , Frolov V. N. , Gardikiotis A. , Gertsenberger S. V. , Girod S. , Gninenko S. N. , Hösgen M. , Joosten R. , Kachanov V. A. , Kambar Y. , Karneyeu A. E. , Kasianova E. A. , Kekelidze G. , Ketzer B. , Kirpichnikov D. V. , Kirsanov M. M. , Kolosov V. N. , Kramarenko V. A. , Kravchuk L. V. , Krasnikov N. V. , Kuleshov S. V. , Lyubovitskij V. E. , Lysan V. , Matveev V. A. , Fredes R. Mena , Yanssen R. G. Mena , Bueno L. Molina , Mongillo M. , Peshekhonov D. V. , Polyakov V. A. , Radics B. , Salamatin K. M. , Samoylenko V. D. , Shchukin D. A. , Soto O. , Sieber H. , Tikhomirov V. O. , Tlisova I. V. , Toropin A. N. , Tuzi M. , Veit B. M. , Volkov P. V. , Volkov V. Yu. , Voronchikhin I. V. , Zamora-Saá J. , Zhevlakov A. S. ,   NA64 Collaboration
Published: December 2024

A search for dark sectors is performed using the unique M2 beam line at the CERN Super Proton Synchrotron. New particles (X) could be produced in the bremsstrahlung-like reaction of high-energy 160 GeV positively charged muons impinging on an active target, μN→μNX, followed by their decays, X→invisible. The experimental signature would be a scattered single muon from the target, with about less than half of its initial energy and no activity in the subdetectors located downstream from the interaction point. The full sample of the 2022 run is analyzed through the missing-energy/momentum channel, with total statistics of (1.98±0.02)×1010 muons on target. We demonstrate that various muonphilic scenarios involving different types of mediators, such as scalar or vector particles, can be probed simultaneously with such a technique. For the vector case, besides a Lμ−Lτ Z′ vector boson, we also consider an invisibly decaying dark photon (A′→invisible). This search is complementary to NA64 running with electrons and positrons, thus opening the possibility to expand the exploration of the thermal light dark matter parameter space by combining the results obtained with the three beams.

Published by the American Physical Society
2024
Higgs boson production at
μ+μ+
colliders
Authors: Hamada Yu , Kitano Ryuichiro , Matsudo Ryutaro , Okawa Shohei , Takai Ryoto , Takaura Hiromasa , Treuer Lukas 
Published: December 2024

We study Higgs boson production at μ+μ+ colliders at high energy. Since both initial-state particles are positively charged, there is no W boson fusion at the leading order, as it requires a W+W− pair. However, we find that the cross section of the higher-order, γ-and Z-mediated W boson fusion process is large at high center-of-mass energies s, growing as (logs)3. This is in contrast to the logs behavior of the leading-order W boson fusion. Thus, even though it is a higher-order process, the rate of Higgs boson production for 10 TeV energies at μ+μ+ colliders with polarized beams can be as high as about half of the one at μ+μ− colliders, assuming the same integrated luminosity. To calculate the cross section of this process accurately, we carefully treat the collinear emission of the photon in the intermediate state. The thereby obtained large cross section furthermore shows the significance of Higgs production with an extra W boson in the final state also at μ+μ− and e+e− colliders.

Published by the American Physical Society
2024
Cross-national benchmarking and acceptance of pandemic mitigation policies: human value approach
Authors: Mandal Purnendu , Bagchi Kallol , Udo Godwin 
Published: December 2024

PurposeThis study analyzes the reasons for satisfaction or dissatisfaction among people with public health mitigation policies, particularly with focus on human values. Recent studies reveal that the citizenry of various nations reacted to government policy measures differently when asked if they are satisfied with government handling of COVID-19. Human values such as openness-to-change and conservation might influence the acceptance of pandemic mitigation measures.Design/methodology/approachA structural equation model (SEM) is proposed, which incorporates mitigation strategies and human value variables. National health survey data of the COVID-19 pandemic in Great Britain and Italy is used to test several hypotheses.FindingsThe model analysis suggests that prioritizing public health, monitoring and tracking people, border closures and restricting people’s movement played important roles in the satisfaction of government handling of the COVID-19 pandemic. Individuals with a high conservation value are more likely to have a higher probability of dissatisfaction with the government’s handling of COVID-19 pandemic. During a pandemic, the citizens are more willing to trade a good economy for public health. They are also more willing to sacrifice privacy in the government’s efforts to track the spread.Originality/valueThis is a unique study which combines human value variables and mitigation policies in determining acceptance of government policies among citizenry during national health crisis. A SEM modeling framework is presented to analyze empirically several hypotheses.