bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of non-hospitalized isolation service during COVID-19 pandemic
Authors: Tansawet Amarit , Atiksawedparit Pongsakorn , Piebpien Pongsathorn , Kunakorntham Patratorn , Suthutvoravut Unyaporn , Arnuntasupakul Vanlapa , Numthavaj Pawin , Ingsathit Atiporn , Pattanaprateep Oraluck , Thakkinstian Ammarin 
Published: April 2023

AbstractBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or COVID-19 affected more than 500 million patients worldwide and overwhelmed hospital resources. Rapid increase of new cases forced patient isolation to be conduct outside the hospital where many strategies have been implemented. This study aimed to compare outcomes among non-hospitalized isolation service.MethodsA retrospective cohort study was conducted in asymptomatic and mildly symptomatic adult patients who were allocated to home isolation, community isolation, and hospitel (i.e., hotel isolation) under service of Ramathibodi Hospital and Chakri Naruebodindra Medical Institute. Variables including patients’ characteristics, comorbidities, symptoms, and medication were retrieved for use in inverse-probability-weighted regression adjustment model. Risks and risk differences (RDs) of death, oxygen requirement, and hospitalization were estimated from the model afterward.ResultsA total of 3869 patients were included in the analysis. Mean age was 41.8 ± 16.5 years. Cough was presented in 62.2% of patients, followed by hyposmia (43.7%), runny nose (43.5%), sore throat (42.2%), and fever (38.6%). Among the isolation strategies, hospitel yielded the lowest risks of death (0.3%), oxygen requirement (4.5%), and hospitalization (3.3%). Hospitel had significantly lower oxygen requirements and hospitalization rates compared with home isolation with the RDs (95% CI) of -0.016 (−0.029, -0.002) and -0.025 (−0.038, -0.012), respectively. Death rates did not differ among isolation strategies.ConclusionNon-hospitalized isolation is feasible and could ameliorate hospital demands. Given the lowest risks of death, hospitalization, and oxygen requirement, hospitel might be the best isolation strategy.
SMOOTH protocol: A pilot randomised prospective intra-patient single-blinded observational study for examining the mechanistic basis of ablative fractional carbon dioxide laser therapy in treating hypertrophic scarring
Authors: Chen Yung-Yi , Patel Krupali M. , Imran Rizwana , Hassouna Tarek , Amirize Ezekwe , Abdulsalam Abdulrazak , Bishop Jonathan , Slade Anita , Ventura Maximina , Yarrow Jeremy , Lord Janet M. , Wilson Yvonne , Moiemen Naiem S. 
Published: April 2023

AbstractBackgroundBurn injuries are the fourth most common type of trauma and are associated with substantial morbidity and mortality. The impact of burn injury is clinically significant as burn injuries often give rise to exuberant scarring. Hypertrophic scarring (HTS) is a particular concern as up to 70% of burns patients develop HTS. Laser therapy is used for treating HTS and has shown positive clinical outcomes, although the mechanisms remain unclear limiting approaches to improve its effectiveness. Emerging evidence has shown that fibroblasts and senescent cells are important modifiers of scarring. This study aims to investigate the cellular kinetics in HTS after laser therapy, with a focus on the association of scar reduction with the presence of senescent cells.MethodsWe will conduct a multicentre, intra-patient, single-blinded, randomised controlled longitudinal pilot study with parallel assignments to achieve this objective. 60 participants will be recruited to receive 3 interventional ablative fractional CO2laser treatments over a 12-month period. Each participant will have two scars randomly allocated to receive either laser treatment or standard care. Biopsies will be obtained from laser-treated, scarred- no treatment and non-scarred tissues for immune-histological staining to investigate the longitudinal kinetics of p16INK4A+-senescent cells and fibroblast subpopulations (CD90+/Thy1+and αSMA+). Combined subjective scar assessments including Modified Vancouver Scar Scale, Patient and Observer Scar Assessment Scale and Brisbane Burn Scar Impact Profile; and objective assessment tools including 3D-Vectra-H1 photography, DermaScan®Cortex, Cutometer®and ColoriMeter®DSMIII will be used to evaluate clinical outcomes. These will then be used to investigate the association between senescent cells and scar reduction after laser therapy. This study will also collect blood samples to explore the systemic biomarkers associated with the response to laser therapy.DiscussionThis study will provide an improved understanding of mechanisms potentially mediating scar reduction with laser treatment, which will enable better designs of laser treatment regimens for those living with HTS.Trial registrationClinicalTrials.gov:NCT04736251.
Hybridization and its impact on the ontogenetic allometry of skulls in macaques
Authors: Ito Tsuyoshi , Kimura Ryosuke , Wakamori Hikaru , Tanaka Mikiko , Tezuka Ayumi , Nagano Atsushi J. , Hamada Yuzuru , Kawamoto Yoshi 
Published: April 2023

AbstractThe role of hybridization in morphological diversification is a fundamental topic in evolutionary biology. However, despite the accumulated knowledge on adult hybrid variation, how hybridization affects ontogenetic allometry is less well understood. Here, we investigated the effects of hybridization on postnatal ontogenetic allometry in the skulls of a putative hybrid population of introduced Taiwanese macaques (Macaca cyclopis) and native Japanese macaques (M. fuscata). Genomic analyses indicated that the population consisted of individuals with varying degrees of admixture, formed by male migration from Japanese to Taiwanese macaques. For overall skull shape, ontogenetic trajectories were shifted by hybridization in a nearly additive manner, with moderate transgressive variation observed throughout development. In contrast, for the maxillary sinus (hollow space in the face), hybrids grew as fast as Taiwanese macaques, diverging from Japanese macaques, which showed slow growth. Consequently, adult hybrids showed a mosaic pattern, i.e., the maxillary sinus is as large as that of Taiwanese macaques, while the overall skull shape is intermediate. Our findings suggest that the transgressive variation can be caused by prenatal shape modification and non-additive inheritance on regional growth rates, highlighting the complex genetic and ontogenetic bases underlying hybridization-induced morphological diversification.
THE OLFACTORY RECEPTOR Olfr78 REGULATES DIFFERENTIATION OF ENTEROCHROMAFFIN CELLS IN THE MOUSE COLON
Authors: Dinsart Gilles , Leprovots Morgane , Lefort Anne , Libert Frédérick , Quesnel Yannick , Veithen Alex , Vassart Gilbert , Huysseune Sandra , Parmentier Marc , Garcia Marie-Isabelle 
Published: April 2023

ABSTRACTThe gastrointestinal epithelium constitutes a chemosensory system for microbiota-derived metabolites such as Short Chain Fatty Acids (SCFA). In this study, we investigated spatial distribution of Olfr78, one of the SCFA receptors, in the mouse intestine and studied the transcriptome of colon enteroendocrine cells expressing Olfr78. The receptor is principally detected in the enterochromaffin and L subtypes in the proximal and distal colon, respectively. Using the Olfr78-GFP and VilCre/Olfr78flox transgenic mouse lines, we reveal that loss of epithelial Olfr78 results in impaired enterochromaffin cell differentiation, blocking cells in an undefined secretory lineage state. This is accompanied by dysbiosis, characterized by an increasedFirmicutes/Bacteroidetes ratio, as well as a less efficient antioxidant system in colon crypts. Using organoid cultures, we further show that maintenance of enterochromaffin cells involves activation of the Olfr78 receptor via the SCFA ligand acetate. Altogether, this work provides evidence that Olfr78 contributes to colon homeostasis by regulating enterochromaffin cell differentiation.
A Multi-omic Analysis of the Human Lung Reveals Distinct Cell Specific Aging and Senescence Molecular Programs
Authors: De Man Ruben , McDonough John E , Adams Taylor S , Manning Edward P , Myers Greg , Vos Robin , Ceulemans Laurens , Dupont Lieven , Vanaudenaerde Bart M , Wuyts Wim A , Rosas Ivan O , Hagood James S. , Ambalavanan Namasivayam , Niklason Laura , Hansen Kirk C , Yan Xiting , Kaminski Naftali 
Published: April 2023

AbstractAge is a major risk factor for lung disease. To understand the mechanisms underlying this association, we characterized the changing cellular, genomic, transcriptional, and epigenetic landscape of lung aging using bulk and single-cell RNAseq (scRNAseq) data. Our analysis revealed age-associated gene networks that reflected hallmarks of aging, including mitochondrial dysfunction, inflammation, and cellular senescence. Cell type deconvolution revealed age-associated changes in the cellular composition of the lung: decreased alveolar epithelial cells and increased fibroblasts and endothelial cells. In the alveolar microenvironment, aging is characterized by decreased AT2B cells and reduced surfactant production, a finding that was validated by scRNAseq and IHC. We showed that a previously reported senescence signature, SenMayo, captures cells expressing canonical senescence markers. SenMayo signature also identified cell-type specific senescence-associated co-expression modules that have distinct molecular functions, including ECM regulation, cell signaling, and damage response pathways. Analysis of somatic mutations showed that burden was highest in lymphocytes and endothelial cells and was associated with high expression of senescence signature. Finally, aging and senescence gene expression modules were associated with differentially methylated regions, with inflammatory markers such asIL1B, IL6R, andTNFbeing significantly regulated with age. Our findings provide new insights into the mechanisms underlying lung aging and may have implications for the development of interventions to prevent or treat age-related lung diseases.
D-Serine agonism of GluN1-GluN3 NMDA receptors regulates the activity of enteric neurons and coordinates gut motility
Authors: Osorio Nancy , Martineau Magalie , Fortea Marina , Rouget Céline , Penalba Virginie , Lee Cindy J. , Boesmans Werend , Rolli-Derkinderen Malvyne , Patel Amit V. , Mondielli Grégoire , Conrod Sandrine , Labat-Gest Vivien , Papin Amandine , Sasabe Jumpei , Sweedler Jonathan V. , Berghe Pieter Vanden , Delmas Patrick , Mothet Jean-Pierre 
Published: April 2023

AbstractThe enteric nervous system (ENS) is a complex network of diverse molecularly defined classes of neurons embedded in the gastrointestinal wall and responsible for controlling the major functions of the gut. As in the central nervous system, the vast array of ENS neurons is interconnected by chemical synapses. Despite several studies reporting the expression of ionotropic glutamate receptors in the ENS, their roles in the gut remain elusive. Here, by using an array of immunohistochemistry, molecular profiling and functional assays, we uncover a new role for D-serine (D-Ser) and non-conventional GluN1-GluN3 N-methyl D-aspartate receptors (NMDARs) in regulating ENS functions. We demonstrate that D-Ser is produced by serine racemase (SR) expressed in enteric neurons. By using bothin situpatch clamp recording and calcium imaging, we show that D-Ser alone acts as an excitatory neurotransmitter in the ENS independently of the conventional GluN1-GluN2 NMDARs. Instead, D-Ser directly gates the non-conventional GluN1-GluN3 NMDARs in enteric neurons from both mouse and guinea-pig. Pharmacological inhibition or potentiation of GluN1-GluN3 NMDARs had opposite effects on mouse colonic motor activities, while genetically driven loss of SR impairs gut transit and fluid content of pellet output. Our results demonstrate the existence of native GluN1-GluN3 NMDARs in enteric neurons and open new perspectives on the exploration of excitatory D-Ser receptors in gut function and diseases.
Leveraging a new data resource to define the response ofC. neoformansto environmental signals
Authors: Kang Yu Sung , Jung Jeffery , Brown Holly , Mateusiak Chase , Doering Tamara L. , Brent Michael R. 
Published: April 2023

ABSTRACTCryptococcus neoformansis an opportunistic fungal pathogen with a polysaccharide capsule that becomes greatly enlarged in the mammalian host and duringin vitrogrowth under host-like conditions. To understand how individual environmental signals affect capsule size and gene expression, we grew cells in all combinations of five signals implicated in capsule size and systematically measured cell and capsule sizes. We also sampled these cultures over time and performed RNA-Seq in quadruplicate, yielding 881 RNA-Seq samples. Analysis of the resulting data sets showed that capsule induction in tissue culture medium, typically used to represent host-like conditions, requires the presence of either CO2or exogenous cyclic AMP (cAMP). Surprisingly, adding either of these pushes overall gene expression in the opposite direction from tissue culture media alone, even though both are required for capsule development. Another unexpected finding was that rich medium blocks capsule growth completely. Statistical analysis further revealed many genes whose expression is associated with capsule thickness; deletion of one of these significantly reduced capsule size. Beyond illuminating capsule induction, our massive, uniformly collected dataset will be a significant resource for the research community.IMPORTANCECryptococcus neoformansis an opportunistic yeast that kills ∼150,000 people each year. This major impact on human health makes it imperative to understand the basic biology ofC. neoformansand the factors that mediate its virulence. One key virulence factor is a polysaccharide capsule that expands greatly during infection. To help define capsule synthesis and fungal biology, we provided cells with many different combinations of host-like signals and sampled the cultures over time for transcriptional analysis. The resulting time resolved data set is by far the largest gene expression resource ever produced forC. neoformans(881 RNA-seq samples), further enriched by accompanying capsule images and measurements. It revealed surprising findings, including that rich medium suppresses capsule size regardless of other signals. This landmark data resource will be enormously valuable to the research community as it continues to define the relationships between environmental signals and cryptococcal gene expression, biology, and virulence.
Auditory hemispheric asymmetry as a specialization for actions and objects
Authors: Robert Paul , Zatorre Robert , Gupta Akanksha , Sein Julien , Anton Jean-Luc , Belin Pascal , Thoret Etienne , Morillon Benjamin 
Published: April 2023

AbstractWhat is the function of auditory hemispheric asymmetry? We propose that the identification of sound sources relies on two complementary and perceptually relevant acoustic invariants — actions and objects — that are processed asymmetrically and sufficient to model and categorize any sound. We observed that environmental sounds are an independent combination of purely temporal and spectral acoustic modulations. Behaviorally, discrimination of actions relied on temporal modulations, while discrimination of objects relied on spectral modulations. Functional magnetic resonance imaging data showed that actions and objects are respectively decoded in the left and right hemispheres, in bilateral superior temporal and left inferior frontal regions. This asymmetry reffects a generic differential processing — through differential neural sensitivity to temporal and spectral modulations present in all environmental sounds — that supports the efficient categorization of actions and objects. These results provide an ecologically valid framework of the functional role of auditory brain asymmetry.
Investigation of the usefulness of liver-specific deconvolution method toward legacy data utilization
Authors: Azuma Iori , Mizuno Tadahaya , Morita Katsuhisa , Suzuki Yutaka , Kusuhara Hiroyuki 
Published: April 2023

AbstractBackgroundImmune responses in the liver are related to the development and progression of liver failure, and precise prediction of their behavior is important. Deconvolution is a methodology for estimating the immune cell proportions from the transcriptome, and it is mainly applied to blood-derived samples and tumor tissues. However, the influence of tissue-specific modeling on the estimation results has rarely been investigated. In this study, we constructed a system to evaluate the performance of the deconvolution method on liver transcriptome data.ResultsWe prepared seven mouse liver injury models using small-molecule compounds with known hepatotoxicity and established a dataset with corresponding liver bulk RNA-Seq and immune cell proportions, covering various immune responses. RNA-Seq expression for nine leukocyte subsets and four liver-associated cell types were obtained from the Gene Expression Omnibus (GEO) to provide a reference covering liver component cells. Here, we found that the combination of reference cell sets affects the estimation results of reference-based deconvolution methods. We established a liver tissue-specific deconvolution by optimizing the reference cell set for each cell to be estimated. We applied this model to independent datasets and showed that liver-specific modeling focusing on reference cell sets is highly extrapolatable.ConclusionsWe provide an approach of liver-specific modeling when applying reference-based deconvolution to bulk RNA-Seq data and show its importance. It is expected to enable sophisticated estimation from rich tissue data accumulated in public databases and to obtain information on aggregated immune cell trafficking.
Assessing drug safety by identifying the axis of arrhythmia in cardiomyocyte electrophysiology
Authors: Heitmann Stewart , Vandenberg Jamie I , Hill Adam P 
Published: April 2023

Many classes of drugs can induce fatal cardiac arrhythmias by disrupting the electrophysiology of cardiomyocytes. Safety guidelines thus require all new drugs to be assessed for pro-arrhythmic risk prior to conducting human trials. The standard safety protocols primarily focus on drug blockade of the delayed-rectifier potassium current (IKr). Yet the risk is better assessed using four key ion currents (IKr, ICaL, INaL, IKs). We simulated 100,000 phenotypically diverse cardiomyocytes to identify the underlying relationship between the blockade of those currents and the emergence of ectopic beats in the action potential. We call that relationship the axis of arrhythmia. It serves as a yardstick for quantifying the arrhythmogenic risk of any drug from its profile of multi-channel block alone. We tested it on 109 drugs and found that it predicted the clinical risk labels with an accuracy of 88.1% to 90.8%. Pharmacologists can use our method to assess the safety of novel drugs without resorting to animal testing or unwieldy computer simulations.Significance StatementMany classes of drugs interfere with the electrical signaling of the heart, leading to arrhythmias and cardiac arrest. Newly developed drugs must therefore undergo mandatory safety testing in animals prior to human trials. Computational models of cardiac electrophysiology offer an ethical alternative, but the current methods are difficult to apply beyond specialist computing laboratories. This study uses such models to identify the underlying relationship between drugs and cardiac arrhythmias. Those findings are then translated into a compact metric that can be applied using simple pen and paper calculations. The new metric allows pharmacology laboratories to assess the safety of novel drugs without using animals or unwieldy computer simulations.
Does ipsilateral remapping following hand loss impact motor control of the intact hand?
Authors: Tucciarelli Raffaele , Ejaz Naveed , Wesselink Daan B. , Kolli Vijay , Hodgetts Carl J. , Diedrichsen Jörn , Makin Tamar 
Published: April 2023

AbstractWhat happens once a cortical territory becomes functionally redundant? We addressed brain and behavioural adaptations for the intact hand in individuals with a missing hand. Previous studies reported increased ipsilateral activity in the somatosensory territory of the missing hand (i.e., remapping) in acquired amputees, but not in individuals with a congenitally missing hand (one-handers). It is unclear whether remapping in amputees involves recruiting more neural resources to support the intact hand, and whether such activity is increased in tasks that demand greater motor control. We investigated sensorimotor learning and neural representation of the intact hand in one-handers and amputees using a multi-finger configuration task, as well as univariate and multivariate fMRI. We found that ipsilateral activity increased with motor demand - but only in the amputees group. However, these changes did not reflect behavioural differences. The representation of the finger configurations, as revealed by multivariate analysis, was stronger in amputees and closer to the typical representation found in controls’ contralateral hand territory, compared to one-handers. This collaborative contra-ipsilateral activity may reflect the intact hand’s efference copy. One-handers struggled to learn difficult finger configurations, but this did not translate to differences in univariate or multivariate activity relative to controls. Together with a supplementary structural white matter analysis, our results suggest that enhanced activity in the missing hand territory may not reflect intact hand function. Instead, we suggest that plasticity is more restricted than generally assumed and may depend on the availability of homologous pathways acquired early in life.Significant StatementWe studied whether brain resources in the missing-hand territory support demanding intact hand motor control in people who were born with one hand or lost a hand later in life. We found that amputees had increased activity in the brain area used for the missing hand, but no improvement in the performance of their intact hand. This collaborative contra-ipsilateral activity may reflect the intact hand’s efference copy. One-handers showed slight deficits while learning to perform complex motor movements, but no brain activity differences in the missing hand territory, compared to controls. Our results suggest that brain plasticity is limited and may depend on early life experiences.