bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chikungunya’s return amidst 2024 dengue season: Implications for future outbreaks in Bangladesh
Authors: Hasan Anamul , Zamil Md. Fahad , Trina Afrida Tabassum , Hossain Mohammad Sharif , Afreen Sajia , Ahmed Dilruba , Alam Mohammad Shafiul 
Published: December 2024

AbstractChikungunya, an arboviral disease transmitted byAedesmosquitoes, shares clinical similarities with dengue, but is distinguished by prolonged joint pain. Following a major outbreak in Bangladesh in 2017, chikungunya nearly vanished from its territory. The study participants were recruited prospectively following specific inclusion criteria and obtained written informed consent. Out of 1280 febrile individuals screened, 569 met the criteria of fever onset within 2-5 days, accompanied by symptoms such as headache, myalgia, bone and joint pain, rash, nausea, vomiting, or diarrhea. Of these, 474 underwent real-time RT-PCR testing. Among the samples tested, 213 were PCR-positive for at least one arbovirus. Chikungunya cases totaled 55, including 7 coinfections (6 with DENV, and the first documented CHIKV-ZIKV coinfection in Bangladesh). No infections were reported from January to August, with a peak in October and November. Most CHIKV infections (72.7%) had moderate to high viral loads, with common symptoms of joint pain, myalgia, and headaches. The resurgence of Chikungunya in late 2024 underscores the potential for a major outbreak in 2025, necessitating proactive measures to mitigate public health impact and ensure a robust response to this re-emerging threat.
COVID-19 Beliefs, Behaviors, and Perceptions Among Students on a College Campus During the Global Coronavirus Pandemic
Authors: White Avian , Iverson Guy , Wright LaNika , Fallon John T. , Humphrey Charles 
Published: December 2024

AbstractObjectivesElucidating how people think and behave during a disease outbreak may provide valuable insight and help direct programs or surveillance to combat the spread of disease. As universities welcomed students back to their campuses following COVID-19 shutdowns, it became important to know students’ beliefs on COVID-19 and how these beliefs guided behaviors?The objective of this study was to determine how students at East Carolina University felt about COVID-19, which behaviors they exhibited during the pandemic, and whether their feelings and behaviors differed significantly between the Spring and Fall 2021 semesters.MethodsSurveys (N= 408) were distributed to students who were currently enrolled in Environmental Health Science classes during the Spring and Fall semesters of 2021. Questions were developed using a Likert scale and were analyzed to determine significant differences (p < 0.05) between semesters. Statistical analyses were performed using SPSS (SPSS Institute, Chicago, Ill).ResultsResults showed most students felt “somewhat concerned” about the COVID-19 pandemic during both semesters. Significant differences in student concern regarding COVID-19 between Spring and Fall semesters, were not observedp= 0.598. Student behaviors regarding weekly gatherings significant differed between semesters with a reported increase in gatherings of 5+ during the Fall semester,p< 0.001. Interestingly, we found more students indicated during the Spring semester in comparison to the Fall that they believed the vaccine was not safe and they would not take it (p< 0.001).ConclusionOur findings suggest that as the pandemic went on, behavior changes were observed in students between the semesters. This information may be important to officials as cases may fluctuate over time. Knowledge of attitudes and/or behaviors and awareness may help explain these fluctuations, allowing public health professionals to adjust recommendations and focus more intently on populations at risk.
LinAge2: Providing actionable insights and benchmarking with epigenetic clocks
Authors: Fong Sheng , Denisov Kirill A. , Kennedy Brian K. , Gruber Jan 
Published: December 2024

AbstractBiological aging is marked by a decline in resilience at the cellular and systemic levels, driving an exponential increase in mortality risk. Here, we evaluate several clinical and epigenetic clocks for their ability to predict mortality, demonstrating that clocks trained on survival and functional aging outperform those trained on chronological age. We present an enhanced clinical clock that predicts mortality more accurately and provides actionable insights for guiding personalized interventions. These findings highlight the potential of mortality-predicting clocks to inform clinical decision-making and promote strategies for healthy longevity.
CORTADO: Hill Climbing Optimization for Cell-Type Specific Marker Gene Discovery
Authors: Lodi Musaddiq K , Clark Leiliani , Roy Satyaki , Ghosh Preetam 
Published: December 2024

AbstractThe advent of single-cell RNA sequencing (scRNA-seq) has greatly enhanced our ability to explore cellular heterogeneity with high resolution. Identifying subpopulations of cells and their associated molecular markers is crucial in understanding their distinct roles in tissues. To address the challenges in marker gene selection, we introduce CORTADO, a computational framework based on hill-climbing optimization for the efficient discovery of cell-type-specific markers. CORTADO optimizes three critical properties: differential expression in the clusters of interest, distinctiveness in gene expression profiles to minimize redundancy, and sparseness to ensure a concise and biologically meaningful marker set. Unlike traditional methods that rely on ranking genes by p-values, CORTADO incorporates both differential expression metrics and penalties for overlapping expression profiles, ensuring that each selected marker uniquely represents its cluster while maintaining biological relevance. Its flexibility supports both constrained and unconstrained marker selection, allowing users to specify the number of markers to identify, making it adaptable to diverse analytical needs and scalable to datasets with varying complexities. To validate its performance, we apply CORTADO to several datasets, including the DLPFC 151507 dataset, the Zeisel mouse brain dataset, and a peripheral blood mononuclear cell dataset. Through enrichment analysis and examination of spatial localization-based expression, we demonstrate the robustness of CORTADO in identifying biologically relevant and non-redundant markers in complex datasets. CORTADO provides an efficient and scalable solution for cell-type marker discovery, offering improved sensitivity and specificity compared to existing methods.
Ganoderma formosanumpolysaccharides enhance antitumor immune responses by downregulating the differentiation of myeloid-derived suppressor cells and tumor-associated macrophages
Authors: Yang Jhe-Yu , Chen Kuei-Liang , Lin Yang-Chia , Chiu Hsien-Chan , Hsieh Hsin-Tien , Chen Chun-Jen 
Published: December 2024

AbstractGanoderma formosanumis a native species ofGanodermaisolated in Taiwan, and our previous studies showed that a polysaccharide fraction, PS-F2, purified from the submerged culture fluid ofG. formosanumATCC 76538 exhibited immunostimulatory and antitumor property. In the current study, we investigated the immunomodulatory and antitumor effects of PS-F2 from a UV-mutatedG. formosanumvariant NTU-1, which produced higher yields of PS-F2 than the original strain. Oral administration of PS-F2 effectively suppressed the growth of colon 26 (CT-26) carcinoma and splenomegaly in tumor-bearing mice without adversely affecting the animals’ health. We found that PS-F2 treatment resulted in augmented cytotoxic T lymphocyte (CTL) while significantly reducing the accumulation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and regulatory T (Treg) cells in the spleen. In the tumor, PS-F2 treatment markedly enhanced CTL and Th1 responses, whereas it reduced the accumulation of tumor-associated macrophages (TAMs). Collectively, our data demonstrate that oral treatment of PS-F2 fromG. formosanumNTU-1 in CT26 tumor-bearing mice activates antitumor immune responses and reduces the accumulation of immunosuppressive cells in the spleen and the tumor, leading to delayed tumor progression.
MAPK15 PROTECTS AGAINST THE DEVELOPMENT OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE
Authors: Inzalaco Giovanni , Gargiulo Sara , Bonente Denise , Gherardini Lisa , Franci Lorenzo , Lorito Nicla , Turco Serena Del , Tatoni Danilo , Tamborrino Tiziana , Bertelli Eugenio , D’Aurizio Romina , Andreassi Maria Grazia , Basta Giuseppina , Gastaldelli Amalia , Morandi Andrea , Barone Virginia , Chiariello Mario 
Published: December 2024

AbstractAccumulation of lipids in the liver characterizes metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disease worldwide. As liver injury progresses to metabolic dysfunction-associated steatohepatitis (MASH), MASLD can predispose individuals to cirrhosis and hepatocellular carcinoma. Here, we characterized the first knockout mouse model for mitogen-activated protein kinase 15 (MAPK15) and revealed its critical role in controlling lipid homeostasis in the liver. Indeed,Mapk15-/-mice exhibited a MASLD-like phenotype, and hepatocellular models allowed us to demonstrate that dysregulated accumulation of lipids was due to increased expression and membrane localization of the CD36 fatty acid translocase. Consistently,Mapk15-/-mice exhibited elevated hepatic levels of CD36 and feeding them with a western-type diet significantly accelerated their progression to a MASH-like phenotype. Ultimately, transcriptomic analysis of human cohorts revealed increased liver expression ofMAPK15in MASLD patients, compared to unaffected individuals, ultimately supporting a protective role for MAPK15 against this disease. Overall, our data highlight a critical role for MAPK15 in liver physiopathology, by contributing to maintain physiological intracellular levels of lipids in this tissue.
Framework for assessing the risk to a field from fraudulent research
Authors: Ni Chaoqun , Hutchins B. Ian 
Published: December 2024

AbstractConcerns over research integrity are rising, with increasing attention to potential threats from untrustworthy authors. We established a framework to gauge the potential negative influence of researchers potentially engaged in misconduct. The field of Alzheimer’s Disease (AD) research has been a focal point of these worries. This study aims to assess the risk posed by questionable studies or individuals potentially engaging in fraudulent science in research by examining citation relationships among papers, taking AD research as an illustrative example. Analysis of citation network structure can elucidate the potential propagation of misinformation arising at the author level. Our analysis revealed that there aren’t any single authors or papers whose citation connections jeopardize a major portion of the field’s literature. This indicates a low probability of single entities undermining the majority of works in this area. However, our findings suggest that attention to research integrity of the most influential scientists is warranted. Some scientists can reach a sizable minority of the literature through citations to their work. Emphasizing oversight of the integrity of these authors is crucial, given their influence on the field. Our study introduces an analytical framework adaptable across various fields and disciplines to evaluate potential risks from fraudulence.
MATING FREQUENCY MEDIATES PERSONALITY EXPRESSION IN FACULTATIVELY POLYANDROUS MITES
Authors: Schausberger Peter , Usugi Shogo , Wang Chenhao , Hinomoto Norihide 
Published: December 2024

AbstractAnimal personalities are characterized by within-individual consistency linked to among-individual variability. Personality expression may change during ontogeny and is often dependent on major life history transitions and events such as mating and the onset of reproduction. While the influence of female personalities on sexual selection and mating has long been known, the influence of the females’ mates on female personality expression after mating is poorly understood. Here we hypothesized that in facultatively polyandrous animals multiple mating increases the females’ assets, also called the residual reproductive value (RRV), due to direct and/or indirect benefits. Based on the predictions of the asset protection principle, higher RRV should promote behaviors that reduce the risk of fitness loss and hence mediate behavioral repeatability displayed in groups. We tested our hypothesis in the group-living, plant-inhabiting predatory mitePhytoseiulus persimilis. To this end, predatory mite females were presented with either a single mate or two mates in sequence and their post-mating repeatability in activity and sociability was evaluated in groups that were composed of females of the same and mixed mating types (monandrous and polyandrous). Mating frequency had little effects on activity patterns but pronounced effects on sociability traits. Polyandrous females were on average more sociable as well as more repeatable in sociability than monandrous females. These behavioral shifts reflect greater risk aversion and strategies to mitigate inter-individual conflicts within groups to enhance asset protection. Our study suggests that the mating frequency can critically influence female personality expression after mating in facultatively polyandrous animals and highlights the importance of considering mate-related variables in animal personality research.
Crossover model of Lep-Rec reveals higher heritability of recombination
Authors: Rastas Pasi , Kivioja Teemu 
Published: December 2024

AbstractMeiotic recombination, a process that reshuffles DNA between parental chromosomes, is almost universal in multicellular organisms. Recombination accelerates the response to selection by breaking the linkage and creating new allelic combinations that can affect the fitness of the progeny. This motivates us to characterise recombination rate variation and to take it into account in evolutionary models and studies.Linkage mapping utilises recombination to obtain recombination distances for genetic markers. With (whole) genome sequencing data, very dense linkage maps can be produced, locating crossovers precisely in the genome. This enables direct and accurate calculation of recombination distances, correction of possible errors in the genome and maps, and studying the relation between recombination and physical base-pair distances. This is now a relevant problem, as high-quality genomes are emerging for many species, and available dense linkage map data would supplement these genomes.Here we present a novel software Lep-Rec to compute the local re-combination rate, i.e. the percentage of crossovers per individual per megabase (cM/Mb) along the genome. Moreover, it can also estimate the underlying, only partly observed, tetrad crossover distribution for each chromosome, while modelling crossover and chromatid interference. Together with Lep-MAP3 and Lep-Anchor, Lep-Rec forms a complete toolbox for studying recombination and crossovers: Lep-MAP3 can robustly construct linkage maps for large number of markers and individuals, while Lep-Anchor can anchor, validate and correct genome assemblies using linkage maps, and together these software provide consistent and complete physical and linkage maps for further analysis with Lep-Rec. Lep-Rec is available fromhttp://sourceforge.net/projects/lep-anchor.Finally, we demonstrate the performance of Lep-Rec using real and simulated data: It outperforms and simplifies currently available tools and its estimated crossover distribution can improve association analysis and heritability estimates of recombination.
Neural differences in conflict monitoring and stimulus expectancy processes in experienced meditators are likely driven by enhanced attention
Authors: Hill Aron T. , Chung Sung Wook , Emonson Melanie , Corcoran Andrew W. , Fitzgibbon Bernadette M. , Fitzgerald Paul B. , Bailey Neil W. 
Published: December 2024

AbstractObjectivesMindfulness meditation has been linked to enhanced attention and executive function, likely resulting from practice-related effects on neural activity patterns. In this study, we used an event-related potential (ERP) paradigm to examine brain responses related to conflict monitoring and attention in experienced mindfulness meditators to better understand key factors driving meditation-related effects.MethodsWe measured electroencephalography-derived N2 and P3 ERPs reflecting conflict monitoring and attention processes from 35 meditators and 29 non-meditators across both an easy and a hard Go/Nogo task (50% Nogo and 25% Nogo stimuli, respectively).ResultsMeditators displayed distinct neural activity patterns compared to non-meditators, with enhanced N2 responses in fronto-midline electrodes following hard Nogo trials (pFDR= 0.011,np2= 0.111). The fronto-midline N2 ERP was also larger following Nogo trials than Go trials, in the harder task condition, and was related to correct responses. Meditators also exhibited a more frontally distributed P3 ERP in the easy task compared to the hard task, while non-meditators showed a more frontally distributed P3 ERP in the hard task (pFDR= 0.015,np2= 0.079).ConclusionsMindfulness meditation was associated with distinct topographical patterns of neural activity in the attention task, without corresponding increases in global neural activity amplitudes. These meditation-related effects appear to be driven by attention-specific mechanisms, despite the examined neural activity being associated with conflict monitoring and stimulus expectancy. Our findings suggest that the cognitive benefits of meditation may only emerge in tasks that actively engage targeted cognitive processes, such as sustained attention.
A photoswitchable positive allosteric modulator to control the activation of the metabotropic glutamate receptor 5 by light
Authors: Dumazer Anaëlle , Borras-Tuduri Roser , Truong Iona , Cong Xiaojing , Malhaire Fanny , Rovira Xavier , Gomez-Santacana Xavier , Givalois Laurent , Lebon Guillaume , Llebaria Amadeu , Goudet Cyril 
Published: December 2024

1.AbstractThe metabotropic glutamate receptor 5 (mGlu5) is widely expressed in the brain, where it plays an important role in synaptic plasticity, learning and memory, making it a therapeutic target of interest in various neurological disorders. In this study, we developed a photoswitchable positive allosteric modulator (PAM) of the mGlu5, as a novel tool for this clinically relevant drug target. To that aim, we used an azologisation strategy of the mGlu5PAM agonist VU0424465 leading to the molecule azoglurax. We observed a reversible photoisomerization of azoglurax in solution with optimal wavelengths of 365 nm and 435 nm fortranstocisandcistotransisomerization, respectively. In cell-based assays, azoglurax potentiates the agonist-induced activity of mGlu5with a sub-micromolar potency in the dark. This potency is reduced under UV illumination. Similar to its parent molecule, azoglurax acts as an allosteric agonist of mGlu5, activating the receptor in absence of glutamate, as demonstrated on a glutamate-insensitive mutant receptor. Docking and site-directed mutagenesis experiments also suggest that azoglurax and VU0424465 bind the same pocket. In addition, molecular dynamics oncis-azoglurax-bound mGlu5suggests that it azoglurax cis isomer does not bind stably in the receptor, in contrast to thetrans-isomer, explaining the difference of activity between the two isomers. In conclusion, azoglurax is the first mGlu5photoswitchable PAM agonist reported to date, retaining the properties and the binding mode of its parent in the dark, while the insertion of an azobenzene confers light-regulated activity.Graphical abstract
Scaling up drug combination surface prediction
Authors: Huusari Riikka , Wang Tianduanyi , Szedmak Sandor , Dias Diogo , Aittokallio Tero , Rousu Juho 
Published: December 2024

AbstractDrug combinations are required to treat advanced cancers and other complex diseases. Compared to monotherapy, combination treatments can enhance efficacy and reduce toxicity by lowering the doses of single drugs – and there especially synergistic combinations are of interest. Since drug combination screening experiments are costly and time consuming, reliable machine learning models are needed for prioritizing potential combinations for further studies. Most of the current machine learning models are based on scalar-valued approaches, which predict individual response values or synergy scores for drug combinations. We take a functional output prediction approach, in which full, continuous dose-response combination surfaces are predicted for each drug combination on the cell lines. We investigate the predictive power of the recently proposed comboKR method, which is based on a powerful input-output kernel regression technique and functional modelling of the response surface. In this work, we develop a scaled-up formulation of the comboKR, that also implements improved modeling choices: 1) we incorporate new modeling choices for the output drug combination response surfaces to the comboKR framework, and 2) propose a projected gradient descent method to solve the challenging pre-image problem that traditionally is solved with simple candidate set approaches. We provide thorough experimental analysis of comboKR 2.0 with three real-word datasets within various challenging experimental settings, including cases where drugs or cell lines have not been encountered in the training data. Our comparison with synergy score prediction methods further highlights the relevance of dose-response prediction approaches, instead of relying on simple scoring methods.
WNT signaling coordinately controls mouse limb bud outgrowth and establishment of the digit-interdigit pattern
Authors: Malkmus Jonas , Morabito Angela , Lopez-Delisle Lucille , Avino Esteban Laura , Mayran Alexandre , Zuniga Aimee , Sharpe James , Zeller Rolf , Sheth Rushikesh 
Published: December 2024

AbstractSelf-organization, such as the emergence of a pattern from a homogenous state, is a fascinating property of biological systems. Early limb bud outgrowth and patterning in mice are controlled by a robust and self-regulatory signaling system, and initiation of the periodic digit-interdigit pattern appears under control of a self-regulatory Turing system. Previous studies established the requirement of WNT and BMP signaling for both early limb bud and digit-interdigit morphogenesis, but the molecular changes underlying the transition from early limb bud signaling to the digit-interdigit patterning system remained unknown. Here, we use small molecule inhibitors to rapidly but transiently block WNT signaling to identify the early transcriptional targets that are altered during disruption and recovery of limb bud and digit development. Together, this study highlights the overarching role of WNT signaling in controlling early limb bud outgrowth and patterning, and establishment of the periodic digit-interdigit pattern. Finally, the transient WNT signaling disruption approach reveals the plasticity and robustness of these self-organizing limb bud and digit patterning systems.Summary StatementIt was unknown how the signaling system controlling early limb bud development transitions to the periodic digit-interdigit patterning system. We show that WNT signaling controls this transition as an integral part of both signalling systems.