bluuebunny/crossref_metadata_2025_split huggingface dataset:
CARDIOPULMONARY BYPASS-DERIVED PLASMA EXOSOMAL HMGB1 CONTRIBUTES TO ALVEOLAR EPITHELIAL CELL NECROPTOSIS VIA mtDNA/CGAS/STING PATHWAY
Authors: Zhao Yupeng , Zhang Jinyuan , Lu Huihong , Mao Yiliang , Qin Jiawen , Wang Yinglin , Wang Xuebin , Dai Zhiguang , Wang Xiangrui , Yang Zhongwei , Hou Lei 
Published: December 2022

ABSTRACT
Our previous study confirmed that cardiopulmonary bypass (CPB) leads to acute lung injury (ALI) via inducing high-mobility group box 1 (HMGB1) release. Recent research showed that HMGB1 promotes pulmonary injury mainly via exosomes transport. Currently, alveolar epithelial cell (AEC) necroptosis has been demonstrated to be involved in ALI. However, it is unknown whether exosomal inflammatory cytokine HMGB1 promotes ALI by inducing AEC necroptosis, and its underlying mechanisms remain elusive. Here, a prospective cohort study was carried out, in which plasma samples from 21 CPB patients were isolated at four specific time points: pre-CPB, 2, 12, and 24 h after initiation of CPB. Plasma exosomes were extracted via ultra-high-speed centrifugation and cocultured with AEC cell line-A549 cells at increasing concentrations of 50, 100, and 150 μg/mL. Then, HMGB1 antagonist-Box A and mtDNA deficiency ethidium bromide (EtBr) were applied to explore the underlying role of exosomal HMGB1 and cytoplasm mitochondrial DNA in AEC. Western blot analysis showed that plasma exosomal HMGB1 expression gradually increased and peaked at 24 h after CPB. Twenty-four–hour treatment of CPB-derived exosomes at 150 μg/mL for 24 h could induce necroptosis by promoting mitochondrial fission and further elevating cytoplasm mtDNA levels in A549 cells, which was successfully blocked by Box A or EtBr. Most importantly, EtBr significantly inhibited cytoplasm mtDNA downstream guanosine monophosphate (GMP)-AMP synthase (cGAS)/stimulator of interferon gene (STING) signal pathway. Collectively, these data demonstrate that CPB-derived plasma exosomal HMGB1 contributes to AEC necroptosis through the mtDNA/cGAS/STING pathway.
Healthcare Facility Water, Sanitation and Hygiene Service Status and Barriers in Ethiopia: It’s Implication for COVID-19 pandemic and Healthcare Acquired Infection Prevention
Authors: Derso Atimen , Addis Taffere , Mengistie Bezatu , keleb Awoke , Ademas Ayechew 
Published: December 2022

AbstractBackgroundDespite the public health significance of healthcare Water, Sanitation, and Hygiene (WASH) service in reduction of nosocomial infection and improving quality of care is paramount little is known on the status of WASH service in a health care facility at the time of pandemic and the barriers that hinder the service in the health care setting in Ethiopia.ObjectiveThe aim of this study was to assess status of basic water, sanitation, hand hygiene, healthcare waste management, and environmental cleanliness service and its barriers at public health care facilities in the city of Addis Ababa, Ethiopia 2022.MethodsConvergent parallel mixed design was conducted among 86 public health care facilities located in Addis Ababa city. Stratified sampling technique was used to select health care facilities. A semi-structured observational checklist tool was used to measure the availability of services. For the qualitative study, semi-structured interview was conducted among 16 key informants and thematic data analysis was done to identify the barriers.FindingThis study found that no one healthcare facility had basic access to overall WASH services. The independent WASH domain analysis showed that, about 86% healthcare facilities had basic water access, 100% had limited sanitation access, 88.4% had limited hand hygiene service, 69.8% had limited healthcare waste management service, and 97.7% had limited environmental cleaning service. Built environments of WASH infrastructure; Resource availability and allocation; leadership and stakeholder participation; inadequate training and poor behaviour; and legal issues were identified barriers to provision of basic healthcare WASH services.Conclusion and recommendationThe availability of healthcare WASH services in Addis Ababa city remains far from the pace to achieve the sustainable goal target by 2025. The limited access to WASH services makes worsening the prevention and control of COVID-19 pandemics, healthcare acquired infection in the facility. The country need to act now on more financial investment, capacity building, facilitating committed leadership, and participation of stakeholders to ensuring basic WASH services at healthcare setting.
Awake Hippocampal-Cortical Co-reactivation Is Associated with Forgetting
Authors: Tanrıverdi Büşra , Cowan Emily T , Metoki Athanasia , Jobson Katie R. , Murty Vishnu P. , Chein Jason , Olson Ingrid R. 
Published: December 2022

AbstractSystems consolidation theories posit that consolidation occurs primarily through a coordinated communication between hippocampus and neocortex (McClelland and O’Reilly 1995; Kumaran et al., 2016; Moscovitch and Gilboa, 2022). Recent sleep studies in rodents have shown that hippocampus and visual cortex replay the same information at temporal proximity (“co-replay”) (Ji & Wilson, 2007; Lansink et al., 2009; Wierzynski et al., 2009; Peyrache et al., 2009). We developed a novel TR-based co-reactivation (TRCR) analysis method to study hippocampal-cortical co-replays in humans using functional MRI. Thirty-six young adults completed an image (face or scene)-location paired associate encoding task in the scanner, which were preceded and followed by resting state scans. We identified post-encoding rest TRs (+/− 1) that showed neural reactivation of each image-location trials in both hippocampus (HPC) and category-selective cortex (fusiform face area, FFA). This allowed us to characterize temporally proximal coordinated reactivations (“co-reactivations”) between HPC and FFA. Moreover, we found that increased HPC-FFA co-reactivations were associated with incorrectly recognized trials after a 1-week delay (p= 0.004). Finally, we found that these HPC-FFA co-reactivations were also associated with trials that were initially correctly recognized immediately after encoding but were later forgotten in 1-day (p= 0.043) and 1-week delay period (p= 0.031). We discuss these results from a trace transformation perspective (Winocur and Moscovitch, 2011; Sekeres et al., 2018) and speculate that HPC-FFA co-reactivations may be integrating related events, at the expense of disrupting event-specific details, hence leading to forgetting.
Clinical performance validation of the STANDARD G6PD Test: A multi-country pooled analysis
Authors: Adissu Wondimagegn , Brito Marcelo , Garbin Eduardo , Macedo Marcela , Monteiro Wuelton , Mukherjee Sandip , Myburg Jane , Alam Mohammad Shafiul , Bancone Germana , Bansil Pooja , Pal Sampa , Sharma Abhijit , Zobrist Stephanie , Bryan Andrew , Chu Cindy S , Das Santasabuj , Domingo Gonzalo J , Hann Amanda , Kublin James , Lacerda Marcus VG , Layton Mark , Ley Benedikt , Murphy Sean C , Nosten Francois , Pereira Dhélio , Price Ric N , Talukdar Arunansu , Yilma Daniel , Gerth-Guyette Emily 
Published: December 2022

AbstractIntroductionScreening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency.Methods and FindingsData from similar clinical studies evaluating the performance of the STANDARD™G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement.The sensitivity of the STANDARD™G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%–100%) for G6PD deficient cases with <30% activity and 77% (95% CI 66.8%– 85.4%) for females with intermediate activity between 30%–70%. Specificity was 98.1% (95% CI 97.6%–98.5%) and 92.8% (95% CI 91.6%–93.9%) for G6PD deficient individuals and intermediate females, respectively. The majority (12/20) of G6PD intermediate females with false normal results had activity levels >60% on the reference assay. Negative predictive values for females with G6PD activity >60% was 99.6% (95% CI 99.1%–99.8%) on capillary specimens. Test sensitivity among 396P. vivaxmalaria cases was 100% (69.2%–100.0%) for both deficient and intermediate cases. In the study population, a high proportion of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, the majority cases would receive the correct medication and no true G6PD deficient cases would be treated inappropriately.ConclusionsThe STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.
Artificial light at night advances reproductive phenology and reduces reproductive capacity of a wild plant
Authors: Wang Shuo , Wang Zhihui , Xiao Lu , Zhang Hongxiang , Liu Yanjie 
Published: December 2022

AbstractWith the rapid increase in artificial light at night (ALAN) during the last century, a growing proportion of the world’s ecosystems have been exposed to ALAN. While the effects of low-intensity ALAN on morphology and phenology are well known in laboratory and greenhouse studies, little is known about these effects of ALAN on wild plants. Moreover, how these morphological and phenological responses affect the fitness of wild plants is unclear.Using the annual herbaceous plant,Elsholtzia densa, as a model species, we performed a field manipulation experiment and tested the responses of plant morphology, reproductive phenology, and reproductive capacity to ALAN.We found that ALAN significantly increased the specific leaf area but decreased the number of secondary branches. It also advanced the onset of budding, blooming, fruiting, and seed maturity from 3.4 to 6.2 d. In addition, ALAN significantly increased the length of the top inflorescences of the species but decreased the percentage of the individuals with undeveloped top inflorescences. Consequently, ALAN reduced the number of fruity inflorescences.Our results demonstrated that low-intensity ALAN, even with a relatively short period of exposure (i.e., one growing season), could cause passive responses in morphological traits of the wild plant, resulting in a decline in its reproductive capacity. In addition, the advanced reproductive phenology (e.g., flowering and blooming) induced by ALAN may cause plant-pollinator mismatches and threaten species coexistence at the community level.
Modeling and Predicting Cancer Clonal Evolution with Reinforcement Learning
Authors: Ivanovic Stefan , El-Kebir Mohammed 
Published: December 2022

AbstractCancer results from an evolutionary process that typically yields multiple clones with varying sets of mutations within the same tumor. Accurately modeling this process is key to understanding and predicting cancer evolution. Here, we introduce CloMu (Clone ToMutation), a flexible and low-parameter tree-generative model of cancer evolution. CloMu uses a two-layer neural network trained via reinforcement learning to determine the probability of new mutations based on the existing mutations on a clone. CloMu supports several prediction tasks, including the determination of evolutionary trajectories, tree selection, causality and interchangeability between mutations, and mutation fitness. Importantly, previous methods support only some of these tasks, and many suffer from overfitting on datasets with a large number of mutations. Using simulations, we demonstrate that CloMu either matches or outperforms current methods on a wide variety of prediction tasks. In particular, for simulated data with interchangeable mutations, current methods are unable to uncover causal relationships as effectively as CloMu. On breast cancer and leukemia cohorts, we show that CloMu determines similarities and causal relationships between mutations as well as the fitness of mutations. We validate CloMu’s inferred mutation fitness values for the leukemia cohort by comparing them to clonal proportion data not used during training, showing high concordance. In summary, CloMu’s low-parameter model facilitates a wide range of prediction tasks regarding cancer evolution on increasingly available cohort-level datasets.
Drivers of the negative diversity-invasibility relationship: nutrient availablity, allelopathy, soil biota and soil legacy effects
Authors: Oduor Ayub M. O. , van Kleunen Mark , Liu Yanjie 
Published: December 2022

ABSTRACTElton’s diversity-invasibility hypothesis predicts that high-diversity native communities should be less easily invaded than low-diversity communities. Although various mechanisms have been proposed to explain it, it remains unclear which of those mechanisms is more important and whether they operate simultaneously. Using one pool of native plant species and one pool of invasive alien plant species that naturally co-occur in China, we here tested in four separate experiments whether nutrient availability, allelopathy, soil microbiota and soil-legacy effects can all mediate the diversity-invasibility relationship. While soil-nutrient availability, allelopathy, soil biota and soil-legacy effects separately influenced biomass production of alien plant species and native plant communities, our results suggest that only soil biota and allelopathy influenced diversity-invasibility relationship in our study system. Importantly, by excluding the potential effects of allelopathy and soil biota in the nutrient-competition experiment, nutrient competition alone is not necessarily related to the negative diversity-invasibility relationship.
Causal network inference based on cross-validation predictability
Authors: Zhang Yuelei , Li Qingcui , Chang Xiao , Chen Luonan , Liu Xiaoping 
Published: December 2022

AbstractIdentifying causal relations or causal networks among molecules/genes, rather than just their correlations, is of great importance but challenging in biology and medical field, which is essential for unravelling molecular mechanisms of disease progression and developing effective therapies for disease treatment. However, there is still a lack of high-quality causal inference algorithms for any observed data in contrast to time series data. In this study, we developed a new causal concept for any observed data and its causal inference algorithm built on cross-validated predictability (CVP) can quantify the causal effects among molecules/genes in the whole system. The causality was extensively validated by combining a large variety of statistical simulation experiments and available benchmark data (simulated data and various real data). Combining the predicted causal network and the real benchmark network, the CVP algorithm demonstrates high accuracy and strong robustness in comparison with the mainstream algorithms. In particular, the CVP algorithm is robust in identifying reliable driver genes and network biomarkers from the perspective of network biology, with the prediction results outperforming the mainstream conventional methods for predicting driver genes. CRISPR-Cas9 knockdown experiments in the liver cancer have validated that the functional driver genes identified by the CVP algorithm effectively inhibit the growth and colony formation of liver cancer cells. By knockdown experiments, we demonstrated the accuracy and significance of the causality predicted by CVP and identified the novel regulatory targets of functional driver genes SNRNP200 and RALGAPB in the liver cancer. These inferred causal networks explain regulatory patterns in different biological contexts in a clear sense and provide biological insights into molecular mechanisms of disease progression from a causality perspective.
Transcriptomic landscape and potential therapeutic targets for human testicular aging revealed by single-cell RNA sequencing
Authors: Xia Kai , He Siyuan , Luo Peng , Dong Lin , Gao Feng , Chen Xuren , Ye Yunlin , Gao Yong , Ma Yuanchen , Zhang Yadong , Yang Qiyun , Han Dayu , Feng Xin , Wan Zi , Cai Hongcai , Ke Qiong , Wang Tao , Li Weiqiang , Tu Xiang’an , Sun Xiangzhou , Deng Chunhua , Xiang Andy Peng 
Published: December 2022

AbstractBackground:Testicular aging is known to cause male age-related fertility decline and hypogonadism, but the underlying molecular mechanisms remain unclear.Methods:We survey the single-cell transcriptomic landscape of testes from young and old men and examine age-related changes in germline and somatic niche cells.Results:In-depth evaluation of the gene expression dynamics of germline cells reveals that disturbance of base-excision repair pathway is a major feature of aging spermatogonial stem cells (SSCs), suggesting that defective DNA repair of SSCs may serve as a potential driver for increased de novo germline mutations with age. Further analysis of aging-associated transcriptional changes shows that stress-related changes and apoptotic signaling pathway accumulate in aged somatic cells. We identify age-related impairment of redox homeostasis in aged Leydig cells and find that pharmacological treatment with antioxidants alleviate this cellular dysfunction of Leydig cells and promote testosterone production. Lastly, our results reveal that decreased pleiotrophin (PTN) signaling is a contributing factor for testicular aging.Conclusions:These findings provide a comprehensive understanding of the cell-type-specific mechanisms underlying human testicular aging at a single-cell resolution, and suggest potential therapeutic targets that may be leveraged to address age-related male fertility decline and hypogonadism.Funding:This work was supported by the National Key Research and Development Program of China (2018YFA0107200, 2018YFA0801404), the National Natural Science Foundation of China (32130046, 82171564, 82101669, 81871110, 81971759), the Key Research and Development Program of Guangdong Province (2019B020234001), the Natural Science Foundation of Guangdong Province, China (2022A1515010371), the Major Project of Medical Science and Technology Development Research Center of National Health Planning Commission, China (HDSL202001000), the Open Project of NHC Key Laboratory of Male Reproduction and Genetics (Family Planning Research Institute of Guangdong Province) (KF202001), the Guangdong Province Regional Joint Fund-Youth Fund Project (2021A1515110921), the China Postdoctoral Science Foundation (2021M703736).
Absence of the bile acid enzyme CYP8B1 increases brain chenodeoxycholic acid and reduces neuronal excitotoxicity in mice
Authors: Monteiro-Cardoso Vera F. , Yeo Xin Yi , Bae Han-Gyu , Mayan David Castano , Wehbe Mariam , Lee Sejin , Krishna-K Kumar , Baek Seung Hyun , Palomera Leon F. , Shanmugam Sangeetha , Sem Kai Ping , Parsons Matthew P. , Hayden Michael R. , Liehn Elisa A. , Sajikumar Sreedharan , Davanger Svend , Jo Dong-Gyu , Jung Sangyong , Singaraja Roshni R. 
Published: December 2022

AbstractBackgroundBile acids (BAs), which act in the liver-brain axis, are liver-derived signaling molecules found in the brain. However, how they modulate neurological function remains largely unknown.MethodsTo assess the role of BAs in the brain, we generated mice with absent 12α-hydroxylase (Cyp8b1), a BA synthesis enzyme, and determined if brain BA levels were altered in these mice, and if and how this may modulate neuronal function.ResultsThe absence of CYP8B1 increased brain levels of the primary BA chenodeoxycholic acid (CDCA), and decreased ischemic stroke infarct area. Furthermore, CDCA administration reduced ischemic stroke lesion area inwild-typemice. Excitotoxicity due to elevated extra-cellular glutamate contributes to neuronal death in ischemic stroke. Neurons fromCyp8b1-/-mice showed reduced susceptibility to glutamate-induced toxicity, and exogenous CDCA reduced glutamate-induced toxicity in neurons fromwild-typemice. These data suggest that CDCA-mediated decreases in excitotoxic neuronal death contributes to the reduced stroke lesion area inCyp8b1-/-mice. Aberrant N-methyl-D-aspartate receptor (NMDAR) over-activation contributes to excitotoxicity. CDCA decreased NMDAR-mediated excitatory post-synaptic currents (EPSCs) inwild-typebrain slices, by reducing over-activation of the NMDAR subunit GluN2B. In line with this, synaptic NMDAR activity was also decreased inCyp8b1-/-brain slices. Expression level and synaptic distribution of GluN2B were unaltered inCyp8b1-/-mice, suggesting that CDCA may directly antagonize GluN2B-containing NMDARs.ConclusionsOur data suggests that CDCA acts in the liver-brain axis and decreases the aberrant over-activation of neuronal GluN2B-containing NMDARs, contributing to neuroprotection.
Severe Acute Respiratory Syndrome Coronavirus 2 detection in induced sputum of asthmatic patients using saliva sampling device
Authors: Moermans Catherine , Gerday Sara , Bricmont Noémie , Bonhiver Romane , Schleich Florence , Guiot Julien , Njock Makon Sébasien , Henket Monique , Guissard Françoise , Paulus Virginie , Di Valentin Emmanuel , Minner Frédéric , Gillet Laurent , Bureau Fabrice , Louis Renaud 
Published: December 2022

AbstractSince the beginning of the severe acute respiratory syndrome coronavirus 2 pandemic, the potential contamination of the induced sputum obtained from asthmatic patients in routine is a question of concern. The goal of this study was to assess this contamination using a saliva sample collection device. One hundred seventy-five sputum samples of asthmatic patients without fever were tested. We did not identify any positive PCR on sputum samples from asthmatic patients reporting chronic/episodic respiratory symptoms similar to what is seen in case of COVID-19. This technique was useful to evaluate the contamination of sputum samples generated during the pandemic.
Proteome-wide structure-based accessibility analysis of ligandable and detectable cysteines in chemoproteomic datasets
Authors: White Matthew E. H. , Gil Jesús , Tate Edward W. 
Published: December 2022

AbstractCovalent drug discovery, in particular targeting reactive cysteines, has undergone a resurgence over the past two decades, demonstrated by recent clinical successes of covalent inhibitors for high-priority cancer targets. Reactive cysteine profiling, first pioneered by the Cravatt lab, has emerged in parallel as a powerful approach for proteome-wide on- and off-target profiling. Thus far however, structural analysis of liganded cysteines has been restricted to experimentally determined protein structures. We combined AlphaFold-predicted amino acid side chain accessibilities for >95% of the human proteome with a meta-analysis of thirteen public cysteine profiling datasets, totalling 40,070 unique cysteine residues, revealing accessibility biases in sampled cysteines primarily dictated by warhead chemistry. Analysis of >3.5 million cysteine-fragment interactions further suggests that exposed cysteine residues are preferentially targeted by elaborated fragments and drug-like compounds. We finally propose a framework for benchmarking coverage of ligandable cysteines in future cysteine profiling approaches, considering both selectivity for high-priority residues and quantitative depth. All analysis and produced resources (freely available atwww.github.com/TateLab) are readily extendable to reactive amino acids beyond cysteine, and related questions in chemical biology.