bluuebunny/crossref_metadata_2025_split huggingface dataset:
Faecalibacterium prausnitziiinduces an anti-inflammatory response and a metabolic reprogramming in human monocytes
Authors: Danne Camille , Creusot Laura , de Oliveira Formiga Rodrigo , Marquet Florian , Sedda Delphine , Hua Laura , Ruffié Pauline , Pham Hang-Phuong , Salgueiro Iria Alonso , Brot Loic , Michel Marie-Laure , Langella Philippe , Lefevre Jérémie H. , Sokol Harry , Rolhion Nathalie 
Published: October 2024

AbstractBackground and aimsFaecalibacterium prausnitzii, a highly abundant bacterium in the human gut microbiota, has been linked to overall health and is decreased in several pathological conditions, such as Inflammatory Bowel Disease (IBD).F. prausnitziihas shown anti-inflammatory properties in human and mouse models, notably through the induction of IL-10 signaling. Here, we investigated which cell types from human blood and intestinal tissue are responsible for producing IL-10 induced byF. prausnitzii, and providing the first mechanistic insights.MethodsImmune cells isolated from human blood and intestinal lamina propria of patients with IBD and non-inflamed controls, were stimulated with eitherF. prausnitziiEXL01 strain orEscherichia colilipopolysaccharide (LPS) and analysed by Legendplex, ELISA, flow cytometry, RNA-sequencing (RNAseq), and Seahorse technology.ResultsF. prausnitziiEXL01 strain induced the direct and dose-dependent production of IL-10 in CD14+monocytes from the systemic circulation and intestinal tissue of IBD patients and non-inflamed controls, without inducing a pro-inflammatory response as compared to LPS stimulation. RNAseq analysis corroborated these results and revealed thatF. prausnitziiEXL01 strain differentially affects cell energy metabolism compared to LPS. The anti-inflammatory response induced byF. prausnitziiin monocytes was dependent on mitochondrial respiration.ConclusionF. prausnitziiinduces an anti-inflammatory response and rewires energy metabolism in human monocytes, which might explain its beneficial impact on intestinal inflammation and human health in general. These results provide new insight into the mechanisms underlying the anti-inflammatory effects ofF. prausnitziiand are crucial for a better understanding of its potential use in the treatment of IBD.
Genomic and evolutionary evidence for drought adaptation of grass allopolyploid Brachypodium hybridum
Authors: Wang Yuanyuan , Chen Guang , Zeng Fanrong , Deng Fenglin , Yang Zujun , Han Zhigang , Xu Shengchun , Nevo Eviatar , Catalán Pilar , Chen Zhong-Hua 
Published: October 2024

AbstractClimate change increases the frequency and severity of drought worldwide, threatening the environmental resilience of cultivated grasses. However, the genetic diversity in many wild grasses could contribute to the development of climate-adapted varieties. Here, we elucidated the impact of polyploidy on drought response using allotetraploidBrachypodium hybridum(Bh) and its progenitor diploid speciesB. stacei(Bs). Our findings suggest that progenitor species’ genomic legacies resulting from hybridization and whole-genome duplications conferred greater ecological adaptive advantages to Bh over Bs. Genes related to stomatal regulation and immune response from S-subgenomes were under positive selection during speciation, underscoring their evolutionary importance in adapting to environmental stresses. Biased expression in polyploid subgenomes [B. stacei-type (Bhs) andB. distachyon-type (Bhd)] significantly influenced differential gene expression, with the dominant subgenome exhibiting more differential expression.B. hybridumadapted a drought escape strategy characterized by higher photosynthetic capacity and lowerWUEithan Bs, driven by a highly correlated co-expression network involving genes in the circadian rhythm pathway. In summary, our study showed the influence of polyploidy on ecological and environmental adaptation and resilience in modelBrachypodiumgrasses. These insights hold promise for informing the breeding of climate-resilient cereal crops and pasture grasses.
Targeting DNA-PK is a highly conserved poxvirus innate immune evasion mechanism
Authors: Oliveira Marisa , Manna Paul T. , Ribeiro-Rodrigues Damaris , Allport Thomas , Wagner Emma , Brooks Heather , Skinner Michael A. , Giotis Efstathios S. , Chaplin Amanda K. , Guabiraba Rodrigo , Bryant Clare E. , Ferguson Brian J. 
Published: October 2024

AbstractThe sensing of viral nucleic acid by pattern recognition receptors (PRRs) is essential for initiation of a type-I interferon response against infection. Intracellular DNA sensing PRRs are responsible for initiating innate immune responses to poxviruses and other double-stranded DNA viruses. Poxviruses, in turn, encode an armoury of immunomodulators that inhibit this host defence mechanism. DNA-dependent protein kinase (DNA-PK) is an essential component of the cGAS/STING-dependent viral DNA sensing machinery that leads to the initiation of a type-I interferon response during poxvirus infection. Poxviruses counter this host sensing mechanism using the C4/C10 family of proteins that target DNA-PK, interfering with its ability to bind viral DNA. Although the DNA-PK complex, known also for its role in double strand break repair, is conserved across multiple taxa, its function in innate immunity outside mammals is unexplored. Here we analysed the contribution of DNA-PK to poxvirus DNA sensing in chickens, a species that is evolutionarily distant from mammals, but that is also infected by poxviruses. We found that DNA-PK functions as a DNA sensor in chickens, and this process is countered by C4/C10 family members found in fowlpox virus. This host/pathogen interaction is conserved across a broader range of species than other mechanisms of poxvirus antagonism of innate immune sensing, which may reflect the difficulty of the host in evolving escape mechanisms that interfere with a protein that is essential for maintenance of genomic stability.
The TWEAK/Fn14 signaling promotes skeletal muscle wasting during cancer cachexia
Authors: Tomaz da Silva Meiricris , Roy Anirban , Vuong Anh Tuan , Joshi Aniket S. , Josphien Cristeena , Trivedi Meghana V , Hindi Sajedah M , Narkar Vihang , Kumar Ashok 
Published: October 2024

ABSTRACTCachexia is an involuntary loss of body weight mostly due to skeletal muscle wasting. The proinflammatory cytokine TWEAK and its receptor Fn14 constitute a major signaling system that regulates skeletal muscle mass in diverse conditions. However, the role of TWEAK/Fn14 system in the regulation of skeletal muscle mass during cancer-induced cachexia remains poorly understood. In this study, we demonstrate that the levels of Fn14, but not TWEAK, are induced in skeletal muscle of multiple mouse models of cancer cachexia. Targeted deletion of Fn14 inhibits muscle wasting and gene expression of multiple components of the ER stress-induced unfolded protein response (UPR) in the KPC mouse model of pancreatic ductal adenocarcinoma (PDAC) cancer cachexia. The TWEAK/Fn14 signaling activates PERK and IRE1α arm of the UPR and inhibits protein synthesis in cultured primary myotubes. Inhibition of PERK using pharmacological or molecular approaches improves protein synthesis and inhibits atrophy in TWEAK-treated cultured myotubes. Silencing of Fn14 in KPC cells prior to their inoculation in pancreas of mice also attenuates tumor growth without having any significant effect on muscle atrophy. The knockdown of Fn14 inhibits proliferation, migration, and invasion of cultured KPC cells. Finally, our results demonstrate that targeted ablation of Fn14 also attenuates muscle atrophy in the Lewis lung carcinoma model of cancer cachexia. Altogether, our study provides initial evidence that the inhibition of TWEAK/Fn14 signaling can prevent tumor growth and skeletal muscle wasting during cancer-induced cachexia.
Neuropeptide-dependent spike time precision and plasticity in circadian output neurons
Authors: Chong Bryan , Kumar Vipin , Nguyen Dieu Linh , Hopkins Makenzie A. , Ferry Faith S. , Spera Lucia K. , Paul Elizabeth M. , Hutson Anelise N. , Tabuchi Masashi 
Published: October 2024

AbstractCircadian rhythms influence various physiological and behavioral processes such as sleep-wake cycles, hormone secretion, and metabolism. InDrosophila, an important set of circadian output neurons are called pars intercerebralis (PI) neurons, which receive input from specific clock neurons called DN1. These DN1 neurons can further be subdivided into functionally and anatomically distinctive anterior (DN1a) and posterior (DN1p) clusters. The neuropeptide diuretic hormones 31 (Dh31) and 44 (Dh44) are the insect neuropeptides known to activate PI neurons to control activity rhythms. However, the neurophysiological basis of how Dh31 and Dh44 affect circadian clock neural coding mechanisms underlying sleep inDrosophilais not well understood. Here, we identify Dh31/Dh44-dependent spike time precision and plasticity in PI neurons. We first find that a mixture of Dh31 and Dh44 enhanced the firing of PI neurons, compared to the application of Dh31 alone and Dh44 alone. We next find that the application of synthesized Dh31 and Dh44 affects membrane potential dynamics of PI neurons in the precise timing of the neuronal firing through their synergistic interaction, possibly mediated by calcium-activated potassium channel conductance. Further, we characterize that Dh31/Dh44 enhances postsynaptic potentials in PI neurons. Together, these results suggest multiplexed neuropeptide-dependent spike time precision and plasticity as circadian clock neural coding mechanisms underlying sleep inDrosophila.
Canary Mating Season Songs Move Between Order and Disorder
Authors: Levin S. , Cohen Y. 
Published: October 2024

AbstractMany complex behaviors involve sequences of basic motor or vocal elements governed by syntactic rules, which facilitate flexible and adaptive actions. Songbirds that crystallize their repertoire of vocal syllables and transitions allow researchers to build probabilistic models of syntax rules, providing insight into underlying neural mechanisms. However, in many complex behaviors, syntax rules change over time, such as during learning or in response to new environmental and social contexts.In this study, we investigated the songs of canaries, a seasonal songbird species. Canaries learn a repertoire of 30-50 syllable types, produce syllables in repeat phrases, and organize these phrases into sequences with long-range syntactic dependencies. Since canaries are known to adapt their repertoire annually, we recorded their songs during the spring mating season and examined the syntactic properties that determine syllable sequencing. Over days and weeks, we observed changes in syllable usage rates, syllable numbers within phrases, phrase positions in songs, and in the long-range dependencies of phrase transitions. Acoustic features of syllables were also found to shift alongside these syntactic changes.Quantifying the variability of these properties revealed that the observed changes were not random. Most birds exhibited a clear trend of moving between order and disorder in their song’s syntactic and acoustic features. Interestingly, this trend varied across individuals; some birds increased their stereotypy and decreased variability across days, while others adopted more disordered and variable song structures.These findings establish canaries as a valuable animal model for studying the neural mechanisms underlying syntax rules in complex motor sequences, their plasticity in social and environmental adaptation, and in implementing individual-specific strategies.
The impact of insertion bias into piRNA clusters on the invasion of transposable elements
Authors: Pritam Shashank , Scarpa Almorò , Kofler Robert , Signor Sarah 
Published: October 2024

AbstractIn our current understanding of transposable element (TE) invasions TEs move freely until they accidentally insert into a piRNA cluster. They are then silenced by the production of piRNA cognate to the TE. Under this model, one would expect that TEs might evolve to avoid piRNA clusters. Yet empirical observations show that some TEs, such as theP-element, insert into piRNA clusters preferentially. We were thus wondering if such a bias could be beneficial for the TE, for example by minimizing harm to the host while still being able to selfishly spread in populations. We decided to model insertion bias to determine if there was ever a situation in which insertion bias was beneficial to the TE. We performed extensive forward simulations of TE invasions with differing insertion biases into piRNA clusters. We found that insertion bias significantly altered the invasion dynamics of TEs, primarily by changing the copy number of the TE in individuals prior to silencing. Insertion into a piRNA cluster reduced the deleterious effects of TEs to the host population, but we found that TEs avoiding piRNA clusters out-compete TEs with a bias towards cluster insertions. Insertion bias was only beneficial to the TE when there was negative selection against TEs and a lack of recombination. Different TEs show different insertion biases into piRNA clusters suggesting they are an attribute of the TE not the host, yet scenarios in which this is beneficial to the TE are quite limited. This opens up an interesting area of future research into the dynamics of insertion bias during TE invasions.Significance StatementThis study challenges the pre-existing understanding of the TE dynamics by investigating the potential adaptive role of insertion bias into piRNA clusters. Using extensive forward simulations, we demonstrate that while insertion bias significantly alters TE invasion dynamics, it is generally not beneficial for the TE’s spread in populations. Our results also show that transposable elements (TEs) that avoid piRNA clusters tend to do better than those that are more likely to preferencially insert into these clusters. This work provides novel insights into the complex dynamics between TEs and host genomes, showing the limited scenarios where the insertion bias could be advantageous to TEs. These results open new area for research into TE invasion dynamics and the evolution of host-TE interactions, further contributing to our understanding of genome evolution and stability.
Development and Multinational Validation of an Ensemble Deep Learning Algorithm for Detecting and Predicting Structural Heart Disease Using Noisy Single-lead Electrocardiograms
Authors: Aminorroaya Arya , Dhingra Lovedeep S , Pedroso Camargos Aline , Vasisht Shankar Sumukh , Coppi Andreas , Khunte Akshay , Foppa Murilo , Brant Luisa CC , Barreto Sandhi M , Ribeiro Antonio Luiz P , Krumholz Harlan M , Oikonomou Evangelos K , Khera Rohan 
Published: October 2024

ABSTRACTBackground and AimsAI-enhanced 12-lead ECG can detect a range of structural heart diseases (SHDs) but has a limited role in community-based screening. We developed and externally validated a noise-resilient single-lead AI-ECG algorithm that can detect SHD and predict the risk of their development using wearable/portable devices.MethodsUsing 266,740 ECGs from 99,205 patients with paired echocardiographic data at Yale New Haven Hospital, we developed ADAPT-HEART, a noise-resilient, deep-learning algorithm, to detect SHD using lead I ECG. SHD was defined as a composite of LVEF<40%, moderate or severe left-sided valvular disease, and severe LVH. ADAPT-HEART was validated in four community hospitals in the US, and the population-based cohort of ELSA-Brasil. We assessed the model’s performance as a predictive biomarker among those without baseline SHD across hospital-based sites and the UK Biobank.ResultsThe development population had a median age of 66 [IQR, 54-77] years and included 49,947 (50.3%) women, with 18,896 (19.0%) having any SHD. ADAPT-HEART had an AUROC of 0.879 (95% CI, 0.870-0.888) with good calibration for detecting SHD in the test set, and consistent performance in hospital-based external sites (AUROC: 0.852-0.891) and ELSA-Brasil (AUROC: 0.859). Among those without baseline SHD, high vs. low ADAPT-HEART probability conferred a 2.8- to 5.7-fold increase in the risk of future SHD across data sources (all P<0.05).ConclusionsWe propose a novel model that detects and predicts a range of SHDs from noisy single-lead ECGs obtainable on portable/wearable devices, providing a scalable strategy for community-based screening and risk stratification for SHD.
Endovascular Thrombectomy for Acute Stroke with Large Ischemic Core: A Meta-analysis of Randomized Clinical Trials
Authors: Lin Chun-Hsien , Lee Meng , Ovbiagele Bruce , Liebeskind David S , Sanz-Cuesta Borja , Saver Jeffrey L 
Published: October 2024

ABSTRACTBackgroundEndovascular thrombectomy (EVT) is standard treatment for an acute ischemic stroke due to large-vessel occlusions (AIS-LVO) with a small ischemic core, but the effect of EVT on AIS-LVO with a large ischemic core remains unclear. The objective was to assess the benefit and safety of EVT for AIS-LVO with large ischemic cores.Methods and FindingPubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1 2000 to September 25 2025. Randomized clinical trials (RCTs) of patients with AIS-LVO and large ischemic cores that compared EVT plus medical care vs. medical care alone were evaluated. Risk ratio (RR) with 95% CI was used to measure outcomes of EVT vs. medical care alone. Primary outcome was functional independence, defined as modified Rankin Scale (mRS) of 0 to 2 at 90 days; and lead secondary outcome was reduced disability, defined as ordinal shift of mRS. Safety outcomes were requiring constant care or death (mRS 5 to 6), death, and early symptomatic intracranial hemorrhage (sICH). We included 6 RCTs comprising 1870 patients (women 826 [44.2%]) with AIS-LVO. Pooled results showed that at 90 days, EVT vs. medical care alone was associated with greater functional independence (RR 2.53, 95% CI, 1.95-3.29; number needed to treat [NNT], 9) and reduced disability (common odds ratio 1.63, 95% CI 1.38-1.93; NNT, 4). EVT vs. medical care alone was associated with a lower risk of requring constant care or death (RR 0.74, 95% CI 0.66 to 0.84; NNT, 7). The rates of death and early sICH were not significantly different between the EVT and medical care alone groups.ConclusionsEVT combined with medical care compared with medical care alone may be associated with improved functional outcomes and reduced severe disability or death at 90 days for acute stroke with large ischemic cores.PROSPERO registration numberCRD42024514605
Toxic Metals Impact Gut Microbiota and Metabolic Risk in Five African-Origin Populations
Authors: Jorgensen Julianne A. , Choo-Kang Candice , Wang Luyu , Issa Lina , Gilbert Jack A. , Ecklu-Mensah Gertrude , Luke Amy , Bedu-Addo Kweku , Forrester Terrence , Bovet Pascal , Lambert Estelle V. , Rae Dale , Argos Maria , Kelly Tanika N. , Sargis Robert M. , Dugas Lara R. , Dai Yang , Layden Brian T. 
Published: October 2024

ABSTRACTExposure to toxic metals impacts obesity and type 2 diabetes (T2DM) risk. Yet, the underlying mechanisms remain largely unknown. Gut microbiota has been strongly associated with progression of cardiometabolic risk. To determine whether high metal exposures and gut dysbiosis interact to promote metabolic dysregulation and cardiometabolic risk, we assessed relationships between these factors. We analyzed cross-sectional associations between arsenic, lead, mercury, cadmium, and cardiometabolic health markers in 178 randomly selected African-origin adults (52% female, 51% obese, mean age=43.0±6.4 years) from Ghana, South Africa, Seychelles, Jamaica, and USA. Metal levels were dichotomized to high or low at the median level of each metal. We analyzed associations between gut microbiome taxa, metal levels, clinical measures (BMI, fasting blood glucose, and blood pressure) and diagnoses (hypertension, obesity, and diabetes status). High vs. low lead and arsenic exposures had a significant effect on beta diversity (p <0.05). 71 taxa were associated with high lead levels: 30 with elevated BMI, 22 with T2DM, and 23 with elevated fasting blood glucose (p<0.05). 115 taxa were associated with high arsenic levels: 32 with elevated BMI, 33 with T2DM, and 26 with elevated blood glucose (p<0.05). Of the taxa associated with high lead and arsenic exposure and either elevated BMI or fasting blood glucose, porphyrin metabolism was the most enriched metabolic pathway. These data collectively provide the first findings in a human study that the gut microbiome may drive the association between lead and arsenic exposure and obesity and T2DM risk.
Understanding Public Attitudes Towards Human Papillomavirus Vaccination in Japan: Insights from Social Media Stance Analysis Using Large Language Models
Authors: Liu Junyu , Niu Qian , Nagai-Tanima Momoko , Aoyama Tomoki 
Published: October 2024

AbstractBackgroundDespite the reinstatement of proactive human papillomavirus (HPV) vaccine recommendations in 2022, Japan continues to face persistently low HPV vaccination rates, posing significant public health challenges. Misinformation, complacency, and accessibility issues have been identified as key factors undermining vaccine uptake.ObjectiveThis study aims to understand how factors such as misinformation, public health events, and attitudes toward other vaccines, like COVID-19, influence HPV vaccine hesitancy, by analyzing the evolution of public attitudes towards HPV vaccination in Japan by examining social media content.MethodsWe collected tweets related to HPV vaccine from 2011 to 2021. Traditional natural language processing (NLP) methods and large language models (LLMs) was utilized to perform stance analysis on collected data. The analysis included stance identification, time series analysis, topic modeling, and logic analysis. We framed our findings within the context of the WHO’s 3Cs model—Confidence, Complacency, and Convenience.ResultsPublic confidence in the HPV vaccine fluctuated in response to government policies and media events, with misinformation playing a critical role in eroding trust. Complacency increased following the suspension of recommendations in 2013 but decreased as advocacy resumed in 2020. Accessibility (Convenience) was also found to be a key determinant of vaccination uptake. HPV vaccines are often used as supportive evidence towards other vaccines, such as COVID-19.ConclusionsOur findings underscore the importance of targeted public health interventions to restore and maintain vaccine confidence in Japan. While vaccine confidence has shown a slow increase, sustained efforts are necessary to secure long-term improvements. Confidence in one vaccine may positively influence perceptions of other vaccines. Addressing misinformation, reducing complacency, and enhancing vaccine accessibility are key strategies to improve uptake. Increased confidence in HPV vaccines appeared to have a positive influence on confidence in other vaccines, such as COVID-19. This study also demonstrates the utility of LLMs in offering a deeper understanding of public health attitudes. To effectively combat vaccine hesitancy and improve coverage, interventions must prioritize consistent communication, localized strategies, and an integrated approach to vaccine narratives.