bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive diversity inEscherichia coliGroup 3 capsules is driven by recombination and plasmid transfer from multiple species
Authors: Hong Yaoqin , Qin Jilong , Forga Xavier Bertran , Totsika Makrina 
Published: April 2023

ABSTRACTBacterial capsules provide protection against environmental challenges and host immunity. Historically,Escherichia coliK serotyping scheme, which relies on the hypervariable capsules, has identified around 80 K forms that fall into four distinct groups. Based on recent work by us and others, we predicted thatE. colicapsular diversity is grossly underestimated. We exploited Group 3 capsule gene clusters, the best genetically defined capsule group inE. coli, to analyse publicly availableE. colisequences for overlooked capsular diversity within the species. We report the discovery of seven novel Group 3 clusters that fall into two distinct subgroups (3A and 3B). The majority of the 3B capsule clusters were found on plasmids, contrary to the defining feature of Group 3 capsule genes localising at theserAlocus on theE. colichromosome. Other new Group 3 capsule clusters were derived from ancestral sequences through recombination events between shared genes found within the serotype variable central region 2. Intriguingly, flanking regions 1 and 3, known to be conserved areas among capsule clusters, showed considerable intra-subgroup variation in clusters from the 3B subgroup, containing genes of shared ancestry with other Enterobacteriaceae species. Variation of Group 3kpsclusters within dominantE. colilineages, including multi-drug-resistant pathogenic lineages, further supports thatE. colicapsules are undergoing rigorous change. Given the pivotal role of capsular polysaccharides in phage predation, our findings raise attention to the need of monitoringkpsevolutionary dynamics in pathogenicE. coliin supporting phage therapy.IMPORTANCECapsular polysaccharides protect pathogenic bacteria against environmental challenges, host immunity, and phage predations. The historicalEscherichia coliK typing scheme, which relies on the hypervariable capsular polysaccharide, has identified around 80 different K forms that fall into four distinct groups. Taking advantage of the supposedly compact and genetically well-defined Group 3 gene clusters, we analysed publishedE. colisequences to identify seven new gene clusters and revealed an unexpected capsular diversity. Genetic analysis revealed that Group 3 gene clusters shared closely related serotype-specific region 2 and were diversified through recombination events and plasmid transfer between multiple Enterobacteriaceae species. Overall, capsular polysaccharides inE. coliare undergoing rigorous change. Given the pivotal role capsules play in phage interactions, this work highlighted the need to monitor the evolutionary dynamics of capsules in pathogenicE. colifor effective phage therapy.
End-to-end deep learning approach to mouse behavior classification from cortex-wide calcium imaging
Authors: Ajioka Takehiro , Nakai Nobuhiro , Yamashita Okito , Takumi Toru 
Published: April 2023

AbstractDeep learning is a powerful tool for neural decoding, broadly applied to systems neuroscience and clinical studies. Interpretable and transparent models which can explain neural decoding for intended behaviors are crucial to identify essential features of deep learning decoders in brain activity. In this study, we examine the performance of deep learning to classify mouse behavioral states from mesoscopic cortex-wide calcium imaging data. Our convolutional neural network (CNN)-based end-to-end decoder combined with recurrent neural network (RNN) classifies the behavioral states with high accuracy and robustness to individual differences on temporal scales of sub-seconds. Using the CNN-RNN decoder, we identify that the forelimb and hindlimb areas in the somatosensory cortex significantly contribute to behavioral classification. Our findings imply that the end-to-end approach has the potential to be an interpretable deep learning method with unbiased visualization of critical brain regions.Author SummaryDeep learning is used in neuroscience, and it has become possible to classify and predict behavior from massive data of neural signals from animals, including humans. However, little is known about how deep learning discriminates the features of neural signals. In this study, we perform behavioral classification from calcium imaging data of the mouse cortex and investigate brain regions important for the classification. By the end-to-end approach, an unbiased method without data pre-processing, we clarify that information on the somatosensory areas in the cortex is important for distinguishing between resting and moving states in mice. This study will contribute to the development of interpretable deep-learning technology.
Typical neural adaptation for familiar images in autistic adolescents
Authors: Westner Britta U. , Bosch Ella , Utzerath Christian , Buitelaar Jan , de Lange Floris P. 
Published: April 2023

AbstractIt has been proposed that autistic perception may be marked by a reduced influence of temporal context. Under this hypothesis, prior exposure to a stimulus should lead to a weaker or absent alteration of the behavioral and neural response to the stimulus in autism, compared to a typical population. To examine this hypothesis, we recruited two samples of human volunteers: a student sample (N=26), which we used to establish our analysis pipeline, and an adolescent sample (N=36), which consisted of a group of autistic (N=18) and a group of non-autistic (N=18) participants. All participants were presented with visual stimulus streams consisting of novel and familiar image pairs, while they attentively monitored each stream. We recorded task performance and used magnetoencephalography (MEG) to measure neural responses, and to compare the responses to familiar and novel images. We found behavioral facilitation as well as a reduction of event-related field (ERF) amplitude for familiar, compared to novel, images in both samples. Crucially, we found statistical evidence against between-group effects of familiarity on both behavioral and neural responses in the adolescent sample, suggesting that the influence of familiarity is comparable between autistic and non-autistic adolescents. These findings challenge the notion that perception in autism is marked by a reduced influence of prior exposure.
Naïve Huntington’s disease microglia mount a normal response to inflammatory stimuli but display impaired development of innate immune tolerance that can be counteracted by ganglioside GM1
Authors: Steinberg Noam , Galleguillos Danny , Zaidi Asifa , Sipione Simonetta 
Published: April 2023

AbstractChronic activation and dysfunction of microglia have been implicated in the pathogenesis and progression of many neurodegenerative disorders, including Huntington’s Disease (HD). HD is a genetic condition caused by a mutation that affects the folding and function of huntingtin (HTT). Signs of microglia activation have been observed in HD patients even before the onset of symptoms. It is unclear, however, whether pro-inflammatory microglia activation in HD results from cell-autonomous expression of mutant HTT or is the response of microglia to a diseased brain environment, or both. In this study, we used primary microglia isolated from HD knock-in mice (Q140) and wild-type (Q7) mice to investigate their response to inflammatory conditionsin vitroin the absence of confounding effects arising from brain pathology. We show that naïve Q140 microglia do not undergo spontaneous pro-inflammatory activation and respond to inflammatory triggers, including stimulation of TLR4 and TLR2 and exposure to necrotic cells, with similar kinetics of pro-inflammatory gene expression as wild-type microglia. Upon termination of the inflammatory insult, the transcription of pro-inflammatory cytokines is tapered off in Q140 and wild-type microglia with similar kinetics. However, the ability of Q140 microglia to develop tolerance in response to repeated inflammatory stimulations is partially impaired, potentially contributing to the establishment of chronic neuroinflammation in HD. We further show that ganglioside GM1, a glycosphingolipid with anti-inflammatory effects in wild-type microglia, not only decreases the production of pro-inflammatory cytokines and nitric oxide in activated Q140 microglia, but also dramatically dampen microglia response to re-stimulation with LPS in an experimental model of tolerance. These effects are independent from the expression of interleukin 1 receptor associated kinase 3 (Irak-3), a strong modulator of LPS signaling involved in the development of innate immune tolerance and previously shown to be upregulated by immune cell treatment with gangliosides. Altogether, our data suggest that external triggers are required for HD microglia activation, but a cell-autonomous dysfunction that affects the ability of HD microglia to acquire tolerance might contribute to the establishment of neuroinflammation in HD. Administration of GM1 might be beneficial to attenuate chronic microglia activation and neuroinflammation.
Reproductive individuality of clonal fish raised in near-identical environments and its link to early-life behavioral individuality
Authors: Scherer Ulrike , Ehlman Sean M. , Bierbach David , Krause Jens , Wolf Max 
Published: April 2023

ABSTRACTRecent studies have documented among-individual variation that is unexplained by genetic or apparent environmental differences, but it remains an open question whether such seemingly stochastic variation has fitness consequences. We perform a life-history experiment with naturally clonal fish (Poecilia formosa), separated directly after birth into near-identical (i.e., highly standardized) environments, quantifying 2522 offspring from 152 broods over 280 days. We find that (i) individuals differ consistently in the size of offspring and broods produced over consecutive broods, (ii) these differences are observed even when controlling for trade-offs between brood size, offspring size and reproductive onset, indicating individual differences in life-history productivity and (iii) early-life behavioral individuality in activity and feeding patterns, with among-individual differences in feeding being predictive of growth, and consequently offspring size. In this work, we provide experimental evidence that processes unexplained by genetic and apparent environmental differences translate into predictable differences in life-history measures and ultimately fitness.
How Interactions During Viral-Viral Coinfection Can Shape Infection Kinetics
Authors: Pinky Lubna , DeAguero Joseph R , Remien Christopher H , Smith Amber M. 
Published: April 2023

AbstractRespiratory virus infections are a leading cause of disease worldwide with multiple viruses detected in 20-30% of cases and several viruses simultaneously circulating. Some infections with viral copathogens have been shown to result in reduced pathogenicity while other virus pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral-viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV) followed by influenza A virus (IAV) after 3 days. The results suggested that IAV reduced the rate of RSV production while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios not examined experimentally, including different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis showed that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to slower clearance of IAV infected cells by the other viruses. On the contrary, the improved outcome when IAV followed RV could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral-viral coinfections in this way provides new insights about how viral-viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation.
Genetic diversity and demographic history of the leopard seal: a Southern Ocean top predator
Authors: Bender Arona N. , Krause Douglas J. , Goebel Michael E. , Hoffman Joseph I. , Lewallen Eric A. , Carolina A. Bonin 
Published: April 2023

AbstractLeopard seals (Hydrurga leptonyx) are top predators that can exert substantial top-down control of their Antarctic prey species. However, population trends and genetic diversity of leopard seals remain understudied, limiting our understanding of their ecological role. We investigated the genetic diversity, effective population size and demographic history of leopard seals to provide fundamental data that contextualizes their predatory influence on Antarctic ecosystems. Ninety leopard seals were sampled in the northern Antarctic Peninsula, during the austral summers of 2008–2019 and a 405bp region of the mitochondrial control region was sequenced for each individual. We uncovered moderate levels of nucleotide (π = 0.013) and haplotype (Hd = 0.96) diversity, and the effective population size was estimated at around 24,000 individuals (NE= 24,376; range 16,876 – 33,126). Consistent with findings from other ice-breeding pinnipeds, Bayesian skyline analysis also revealed evidence for population expansion during the last glacial maximum, suggesting that historical population growth may have been boosted by an increase in the abundance of sea ice. Although leopard seals can be found in warmer, sub-Antarctic locations, the species’ core habitat is centered around the Antarctic, making it inherently vulnerable to the loss of sea ice habitat due to climate change. Therefore, detailed assessments of past and present leopard seal population trends are needed to inform policies for Antarctic ecosystems.
Decoding the Cure-all Effects of Ginseng
Authors: Loo Shining , Kam Antony , Dutta Bamaprasad , Zhang Xiaohong , Feng Nan , Sze Siu Kwan , Liu Chuan-Fa , Wang Xiaoliang , Tam James P. 
Published: April 2023

AbstractGinseng has been known as a “cure-all” traditional medicine to treat various illnesses and as an adaptogen to relieve stress. However, the known active compounds of ginseng are small-molecule metabolites. Here we report ginsentides, which are disulfide-dense, super-stable and cell-penetrating peptides with 31–33 amino acids, as active compounds and adaptogens that restore homeostasis in response to stress. Using mass spectrometry-based target identification and functional studies, we show that ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via the PI3K/Akt signaling pathway. Ginsentides were also found to alleviate α1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of the aorta, decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40, inhibit P2Y12 receptors, reduce platelet aggregation, and thrombus formation in the lung. Orally administered ginsentides were effective in anti-stress behavior using animal models of tail suspension and forced swimming tests. Together, these results suggest that ginsentides interact with multiple systems to restore homeostasis by reversing stress-induced physiological changes and provide new insights into the panacea medicinal effects of ginseng.
CARE: a novel wearable-derived feature linking circadian amplitude to human cognitive functions
Authors: Cui Shuya , Lin Qingmin , Gui Yuanyuan , Zhang Yunting , Lu Hui , Zhao Hongyu , Wang Xiaolei , Li Xinyue , Jiang Fan 
Published: April 2023

AbstractCircadian rhythms play a critical role in regulating physiological and behavioral processes, with amplitude being a key parameter for their characterization. However, accurately quantifying circadian amplitude in natural settings remains a challenge, as traditional melatonin methods require lab settings and are often costly and time-consuming. Wearable devices are a promising alternative as they can collect consecutive 24-h data for multiple days. The most commonly used measure of circadian amplitude from wearable device data, relative amplitude, is subject to the masking effect of behaviors and fails to leverage the rich information in high-dimensional data, as it only uses the sum of activity counts in time windows of pre-specified lengths. Therefore, in this study, we firstly proposed a pipeline to derive a novel feature to characterize circadian amplitude, namedcircadianactivityrhythmenergy (CARE), which can well address the above-mentioned challenges by decomposing raw accelerometer time series data, and then we validated the new feature CARE by assessing its correlation with melatonin amplitude (Pearson’sr= 0.46,P =0.007) in a dataset of 33 healthy participants. Secondly, we investigated its association with cognitive functions in two datasets: an adolescent dataset (Chinese SCHEDULE-A, n = 1,703) and an adult dataset (the UK Biobank dataset, n = 92,202), and we found that the CARE was significantly associated with the Global Executive Composite (β= 28.02,P= 0.016) in adolescents, and reasoning ability (OR = 0.01,P <0.001), short-term memory (OR = 3.42,P <0.001), and prospective memory (OR = 11.47,P <0.001) in adults. And finally, we explored the causal relationship using Mendelian randomization analysis in the adult dataset. We identified one genetic locus with 126 SNPs associated with CARE using genome-wide association study (GWAS), of which 109 variants were used as instrumental variables to conduct causal analysis. The results suggested that CARE had a significant causal effect on reasoning ability (β= -59.91,P< 0.0001), short-term memory (β= 7.94,P< 0.0001), and prospective memory (β= 16.85,P< 0.0001). The findings suggested that CARE is an effective wearable-based metric of circadian amplitude with a strong genetic basis and clinical significance, and its adoption can facilitate future circadian studies and potential interventions to improve circadian rhythms and cognitive functions.
Self-help digital psychosocial intervention for older adults with subthreshold depressive symptoms in primary care in Brazil (PRODIGITAL): Protocol for an individually randomised controlled trial
Authors: Didone Thiago Vinicius Nadaleto , Nakamura Carina Akemi , Seward Nadine , Moretti Felipe Azevedo , Souza dos Santos Monica , Mendes de Sá Martins Mariana , Pereira Luara Aragoni , da Silva Bitencourt Evelyn , Oliveira da Costa Marcelo , Queiroz de Souza Caio Hudson , Macias de Oliveira Gabriel , Machado Marcelo , Murdoch Jamie , Van de Ven Pepijn , Hollingworth William , Peters Tim J. , Araya Ricardo , Scazufca Marcia 
Published: April 2023

AbstractSubthreshold depression is a substantial risk factor for the development of major depression. It is associated with poorer health, functional disabilities, and reduced quality of life in older adults. There is a paucity of cost-effective psychosocial interventions for this population in primary care worldwide, particularly in low- and middle-income countries. We present a protocol for evaluating the effectiveness and cost-effectiveness of the Viva Vida programme, a 6-week self-help digital psychosocial intervention for treating older adults with subthreshold depressive symptoms in primary care with a two-arm, individually randomised controlled trial with a 1:1 allocation ratio with integrated economic and process evaluations. We will include 450 individuals 60 years and older with subthreshold depressive symptoms (score between five and below 10 on the 9-item Patient Health Questionnaire (PHQ-9)), registered with one of the 46 primary care clinics in Guarulhos, Brazil. The Viva Vida programme will be delivered via automated audio and visual WhatsApp messages, with psychoeducation and behavioural activation content. It involves 48 messages, delivered twice daily, four days a week. Participants in the control arm will receive a single message with general information about depression. The primary outcome is the depressive symptoms at the three-month follow-up as measured by PHQ-9, which will be compared between study arms. The cost-effectiveness of the intervention will be assessed at five months. A detailed process evaluation will explore context and implementation outcomes. The Viva Vida programme is an innovative digital psychosocial intervention delivered via WhatsApp messaging without the participation of health professionals. The evaluation of the Viva Vida programme will contribute to the development of simple and cost-effective models of remote self-help interventions for reducing depressive symptoms among older adults with subthreshold depression in primary care. The protocol is registered with Registro Brasileiro de Ensaios Clinicos (ReBEC) (RBR-6c7ghfd).
Anticoagulation and associated complications in Veno-Arterial Extracorporeal Membrane Oxygenation in Adult Patients: A Protocol for a Systematic Review and Meta-Analysis
Authors: Vlok Ruan , Buscher Hergen , Delaney Anthony , Garside Tessa , Myburgh John , Nair Priya 
Published: April 2023

AbstractBackgroundVeno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a rapidly expanding therapy with a relatively limited evidence base. Due to both quantitative and qualitative acquired coagulopathies in VA-ECMO, bleeding remains a major complication and with potentially catastrophic outcomes. Simultaneously, coagulation activation occurs via blood contact with the extracorporeal circuit, which risks not only vital organ emboli, but also the circuit viability. This carries the risk of equally catastrophic complications. As such, VA-ECMO patients are routinely anticoagulated. A large variation in practice exists surrounding anticoagulation in VA-ECMO. Despite an increasing uptake in the therapy, the evidence base is limited and current guidelines surrounding anticoagulation practice are based on expert opinion. We will perform a study level systematic review and meta-analysis of VA-ECMO patients comparing anticoagulation strategies, including the agent of anticoagulation, the method of monitoring and the targeted degree of anticoagulation to assess the association between described anticoagulation strategies and bleeding and thrombotic complications.MethodsWe will perform a study level meta-analysis of randomised controlled trials (RCTs) and cohort studies that report on bleeding and thrombotic complications in VA-ECMO. Our primary objective is to describe the incidence of bleeding and thrombotic complications associated with individual anticoagulation strategies. In order to be included, a study must report the anticoagulant drug used, the method of monitoring used, or the anticoagulation target used, and at least one outcome of interest. Four databases will be systematically reviewed by two authors. Two authors will extract and assess for risk of bias using the Cochrane Risk of Bias tool for RCTs and the ROBINS-I tool for observational studies. Data will be analysed via incidence rates of bleeding and thrombotic complications, with a subgroup analysis of each anticoagulation strategy where able. The study will be reported in line with PRISMA guidelines.