bluuebunny/crossref_metadata_2025_split huggingface dataset:
EHR-QC: A streamlined pipeline for automated electronic health records standardisation and preprocessing to predict clinical outcomes
Authors: Ramakrishnaiah Yashpal , Macesic Nenad , Peleg Anton Y. , Tyagi Sonika 
Published: June 2023

ABSTRACTThe adoption of electronic health records (EHRs) has created opportunities to analyze historical data for predicting clinical outcomes and improving patient care. However, non-standardized data representations and anomalies pose major challenges to the use of EHRs in digital health research. To address these challenges, we have developed EHR-QC, a tool comprising two modules: the data standardization module and the preprocessing module. The data standardization module migrates source EHR data to a standard format using advanced concept mapping techniques, surpassing expert curation in benchmarking analysis. The preprocessing module includes several functions designed specifically to handle healthcare data subtleties. We provide automated detection of data anomalies and solutions to handle those anomalies. We believe that the development and adoption of tools like EHR-QC is critical for advancing digital health. Our ultimate goal is to accelerate clinical research by enabling rapid experimentation with data-driven observational research to generate robust, generalisable biomedical knowledge.HighlightsEHR-QC accepts EHR data from a relational database or as a flat file and provide an easy-to-use, customized, and comprehensive solution for data handling activities.It offers a modular standardization pipeline that can convert any EHR data to a standardized data model i.e. OMOP-CDM.It includes an innovative algorithmic solution for clinical concept mapping that surpasses the current expert curation process.We have demonstrated that the imputation performance depends on the nature and missing proportion, hence as part of EHR-QC we included a method that searches for the best imputation method for the given data.It also contains an end-to-end solution to handle other anomalies such as outliers, errors, and other inconsistencies in the EHR data.
Single-cell Spatial Metabolic and Immune Phenotyping of Head and Neck Cancer Tissues Identifies Tissue Signatures of Response and Resistance to Immunotherapy
Authors: Jhaveri Niyati , Cheikh Bassem Ben , Nikulina Nadezhda , Ma Ning , Klymyshyn Dmytro , DeRosa James , Mihani Ritu , Pratapa Aditya , Kassim Yasmin , Bommakanti Sidharth , Shang Olive , He Yan , Zheng Yi , Monkman James , Cooper Caroline , O’Byrne Ken , Anand Bhaskar , Prater Michael , Basu Subham , Hughes Brett G.M. , Kulasinghe Arutha , Braubach Oliver 
Published: June 2023

AbstractHead and neck squamous cell carcinomas (HNSCC) are the seventh most common cancer and represent a global health burden. Immune checkpoint inhibitors (ICIs) have shown promise in treating recurrent/metastatic cases, with durable benefit in ∼30% of patients. Current biomarkers for head and neck tumors are limited in their dynamic ability to capture tumor microenvironment (TME) features, with an increasing need for deeper tissue characterization. Therefore, new biomarkers are needed to accurately stratify patients and predict responses to therapy. Here, we have optimized and applied an ultra-high plex, single-cell spatial protein analysis in HNSCC. Tissues were simultaneously analyzed with a panel of 101 antibodies that targeted biomarkers related to tumor immune, metabolic and stress microenvironments. Our data uncovered a high degree of intra-tumoral heterogeneity intrinsic to head and neck tumors and provided unique insights into the biology of the tumor. In particular, a cellular neighborhood analysis revealed the presence of 6 unique spatial tumor-immune neighborhoods enriched in functionally specialized immune cell subsets across the patient tissue. Additionally, functional phenotyping based on key metabolic and stress markers identified four distinct tumor regions with differential protein signatures. One tumor region was marked by infiltration of CD8+ cytotoxic T cells and overexpression of BAK, a proapoptotic regulator, suggesting strong immune activation and stress. Another adjacent region within the same tumor had high expression of G6PD and MMP9, known drivers of tumor resistance and invasion respectively. This dichotomy of immune activation-induced death and tumor progression in the same sample demonstrates the heterogenous niches and competing microenvironments that underpin clinical responses of therapeutic resistance. Our data integrate single-cell ultra-high plex spatial information with the functional state of the tumor microenvironment to provide insights into a partial response to immune checkpoint inhibitor therapy in HNSCC. We believe that the approach outlined in this study will pave the way towards a new understanding of TME features associated with response and sensitivity to ICI therapies.
A semi-quantitative, rapid, point of care SARS-CoV-2 serologic assay predicts neutralizing antibody levels
Authors: Markmann Alena J. , Bhowmik D. Ryan , Jiang Baowei , Van Hoy Michael , Wang Frank , Hou Yixuan J. , Baric Ralph S. , de Silva Aravinda M. , Bartelt Luther A. 
Published: June 2023

AbstractThe ongoing COVID-19 pandemic has caused millions of deaths and the continued emergence of new variants suggests continued circulation in the human population. In the current time of vaccine availability and new therapeutic development, including antibody-based therapies, many questions about long-term immunity and protection remain uncertain. Identification of protective antibodies in individuals is often done using highly specialized and challenging assays such as functional neutralizing assays, which are not available in the clinical setting. Therefore, there is a great need for the development of rapid, clinically available assays that correlate with neutralizing antibody assays to identify individuals who may benefit from additional vaccination or specific COVID-19 therapies. In this report, we apply a novel semi-quantitative method to an established lateral flow assay (sqLFA) and analyze its ability to detect the presence functional neutralizing antibodies from the serum of COVID-19 recovered individuals. We found that the sqLFA has a strong positive correlation with neutralizing antibody levels. At lower assay cutoffs, the sqLFA is a highly sensitive assay to identify the presence of a range of neutralizing antibody levels. At higher cutoffs, it can detect higher levels of neutralizing antibody with high specificity. This sqLFA can be used both as a screening tool to identify individuals with any level of neutralizing antibody to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or as a more specific tool to identify those with high neutralizing antibody levels who may not benefit from antibody-based therapies or further vaccination.
A framework for identifying fertility gene targets for mammalian pest control
Authors: Clark Anna C , Alexander Alana , Edison Rey , Esvelt Kevin , Kamau Sebastian , Dutoit Ludovic , Champer Jackson , Champer Samuel E , Messer Philipp W , Gemmell Neil J 
Published: June 2023

ABSTRACTFertility-targeted gene drives have been proposed as an ethical genetic approach for managing wild populations of vertebrate pests for public health and conservation benefit.This manuscript introduces a framework to identify and evaluate target gene suitability based on biological gene function, gene expression, and results from mouse knockout models.This framework identified 16 genes essential for male fertility and 12 genes important for female fertility that may be feasible targets for mammalian gene drives and other non-drive genetic pest control technology. Further, a comparative genomics analysis demonstrates the conservation of the identified genes across several globally significant invasive mammals.In addition to providing important considerations for identifying candidate genes, our framework and the genes identified in this study may have utility in developing additional pest control tools such as wildlife contraceptives.
Deleterious functional consequences of perfluoroalkyl substances accumulation into the myelin sheath
Authors: Butruille L. , Jubin P. , Martin E. , Aigrot MS. , Lhomme M. , Fini JB. , Demeneix B. , Stankoff B. , Lubetzki C. , Zalc B. , Remaud S. 
Published: June 2023

AbstractExposure to persistent organic pollutants during the perinatal period is of particular concern because of the potential increased risk of neurological disorders in adulthood. Here we questioned whether exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) could alter myelin formation and regeneration. First, we show that PFOS, and to a lesser extent PFOA, accumulated into the myelin sheath of postnatal day 21 (p21) mice, whose mothers were exposed to either PFOA or PFOS (20mg/L)viadrinking water during late gestation and lactation, suggesting that accumulation of PFOS into the myelin could interfere with myelin formation and function. In fact, PFOS, but not PFOA, disrupted the generation of oligodendrocytes, the myelin-forming cells of the central nervous system, derived from neural stem cells localised in the subventricular zone of p21 exposed animals. Then, cerebellar slices were transiently demyelinated using lysophosphatidylcholine and remyelination was quantified in the presence of either PFOA or PFOS. Only PFOS impaired remyelination, a deleterious effect rescued by adding thyroid hormone (TH). Similarly to our observation in the mouse, we also showed that PFOS altered remyelination inXenopus laevisusing the Tg(Mbp:GFP-ntr) model of conditional demyelination and measuring, then, the number of oligodendrocytes. The functional consequences of PFOS-impaired remyelination were shown by its effects using a battery of behavioural tests. In sum, our data demonstrate that perinatal PFOS exposure disrupts oligodendrogenesis and myelin function through modulation of TH action. PFOS exposure may exacerbate genetic and environmental susceptibilities underlying myelin disorders, the most frequent being multiple sclerosis.HighlightsOur investigation points the deleterious effects of PFOS incorporation into the myelin sheathPFOS interfere dramatically with the generation of remyelinating and functional repair of demyelinating lesionsOur study points to a potential link between these persistent pollutants and the recent increase in prevalence of multiple sclerosis
An ethogram method for the analysis of human distress in the aftermath of public conflicts
Authors: Pallante Virginia , Ejbye-Ernst Peter , Lindegaard Marie Rosenkrantz 
Published: June 2023

ABSTRACTResearch on nonhuman animals has widely documented the behavioural expression of distress in a conflict context. In humans, however, this remains largely unknown due to the lack of direct access to real-life conflict events. Here, we took the aftermath of 129 video recorded street fights and applied the ethological method to explore the behavioural cues of people previously involved in a fight. Drawing on observations on nonhuman behaviour and inductively identified behaviours, we developed and inter-coder reliability tested an ethogram for the behavioural repertoire of distress. We further quantitively analysed the behaviours with a correlation matrix and PCA, that revealed that the behaviours we observed were not displayed in combination with each other, showing a variability in how people express distress. Since both human and nonhuman primates react to conflict situations with similar expressions of distress, we suggest a comparative approach to understand the evolutionary roots of human behaviour.
Albumin-binding recombinant human IL-18BP ameliorates macrophage activation syndrome and atopic dermatitis via direct IL-18 inactivation
Authors: Jang Young-Saeng , Lee Kyungsun , Park Mihyun , Park Jin Joo , Choi Ga Min , Kim Chohee , Dehkohneh Shima Barati , Chi Susan , Han Jaekyu , Song Moo Young , Han Yong-Hyun , Cha Sang-Hoon , Kang Seung Goo 
Published: June 2023

AbstractGiven the clinical success of cytokine blockade in managing diverse inflammatory human conditions, this approach could be exploited for numerous refractory or uncontrolled inflammatory conditions by identifying novel targets for functional blockade. IL-18, a pro-inflammatory cytokine, is relatively underestimated as a therapeutic target, despite accumulated evidence indicating the unique roles of IL-18 in acute and chronic inflammatory conditions, such as macrophage activation syndrome. Herein, we designed a new form of IL-18 blockade, i.e., APB-R3, a long-acting recombinant human IL-18BP linked to human albumin-binding Fab fragment, SL335, for extending half-life. We then explored the pharmacokinetics and pharmacodynamics of APB-R3. In addition to an extended serum half-life, APB-R3 alleviates liver inflammation and splenomegaly in a model of the macrophage activation syndrome induced in IL-18BP knockout mice. Moreover, APB-R3 substantially controlled skin inflammation in a model of atopic dermatitis. Thus, we report APB-R3 as a new potent IL-18 blocking agent that could be applied to treat IL-18-mediated inflammatory diseases.
Assessment ofBlighia sapidaon Cholinergic and Antioxidant Enzymes; Possible Use of the Plant Stem-Bark Extract as a Biological Pest Controlling Agent
Authors: Adekola M.B. , Oriyomi O.V. 
Published: June 2023

ABSTRACTThe harmful effects of synthetic pesticides include neurological, behavioural dysfunctions, hormonal imbalances, and water pollution. Hydro-alcohol extract of the stem bark ofB. sapidawas studied for pesticidal effects on Glutathione S-transferases (GST) and acetylcholinesterase (AChE) using a rat model. Various concentrations of the extract were administered to six different groups, of three male and three female groups of rats (50 mg/kg, 100 mg/kg and 150 mg/kg bwt. respectively), two synthetic 10% (w/v) groups and a control group. Blood plasma, liver, and brain were obtained at the end of 28 days sub-acute test, from the Wistar rats for biochemical assay.The results showed that there was a significant decrease (P < 0.05) in acetylcholinesterase (AChE) activities in the brain of female rats while that of males was not significant (P > 0.05) compared to control. Also in GST, a significant increase (P < 0.05) in all the doses in liver but only at 100 mg/kg and 150 mg/kg in plasma of female rats, was observed compared to control while in male rats, a significant increase in both liver and plasma at 100 mg/kg and 150 mg/kg but not significant at 50 mg/kg was observed. The non-significant difference was observed in alkaline phosphatase (ALP) aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total protein (TP) activities in both sexes at 50 mg/kg compared to control.It was concluded that hydro-alcohol extract ofB. sapidasignificantly reduced the levels of AChE and GST activities at higher and lower doses respectively. This property of the plant could be exploited in the formulation of agents useful in pest control.
Remodelling of the endothelial cell transcriptional program via paracrine and DNA-binding activities of MPO
Authors: Zheng Ruiyuan , Moynahan Kyle , Georgomanolis Theodoros , Pavlenko Egor , Geissen Simon , Mizi Athanasia , Grimm Simon , Nemade Harshal , Rehimi Rizwan , Bastigkeit Jil , Lackmann Jan-Wilm , Adam Matti , Rada-Iglesias Alvaro , Nuernberg Peter , Klinke Anna , Poepsel Simon , Baldus Stephan , Papantonis Argyris , Kargapolova Yulia 
Published: June 2023

ABSTRACTMyeloperoxidase (MPO) is an enzyme that functions in host defence by catalysing the formation of reactive oxygen intermediates. Synthesized majorly by myeloid progenitor cell types and neutrophils, MPO is released into the vascular lumen during inflammation, where it may adhere and subsequently enter endothelial cells coating vascular walls. Here, we show that MPO actually enters the nucleus of these endothelial cells and binds chromatin independently of its enzymatic activity to cause changes in chromatin structure. At its binding sites, MPO drives chromatin decondensation, while enhancing condensation at flanking regions. We further show that MPO binds loci relevant for the activation of the endothelial-to- mesenchymal transition (EndMT) and the migratory potential of ECs. Finally, MPO interacts with the RNA- binding factor ILF3 affecting its relative abundance between cytoplasm and nucleus. This leads to ILF3:MPO- driven transcriptional and post-transcriptional regulation. Accordingly, MPO-knockout mice show reduced EC numbers at scars formed after myocardial infarction, indicating reduced neovascularization. In summary, we describe a non-enzymatic role for MPO in coordinating EndMT and controlling the fate of endothelial cells through direct chromatin binding and association with such co-factors as ILF3.
17α-estradiol Alleviates High-Fat Diet-Induced Inflammatory and Metabolic Dysfunction in Skeletal Muscle of Male and Female Mice
Authors: Bubak Matthew P. , Mann Shivani N. , Borowik Agnieszka K. , Pranay Atul , Batushansky Albert , Mondal Samim Ali , Diodge Stephen M. , Davidyan Arik , Szczygiel Marcelina M. , Peelor Fredrick R. , Rigsby Sandra , Broomfield Matle , Lacy Charles I. , Rice Heather C. , Stout Michael B. , Miller Benjamin F. 
Published: June 2023

AbstractSkeletal muscle has a central role in maintaining metabolic homeostasis. 17α-estradiol (17α-E2), a naturally-occurring non-feminizing diastereomer of 17β-estradiol that demonstrates efficacy for improving metabolic outcomes in male, but not female, mice. Despite several lines of evidence showing that 17α-E2 treatment improves metabolic parameters in middle-aged obese and old male mice through effects in brain, liver, and white adipose tissue little is known about how 17α-E2 alters skeletal muscle metabolism, and what role this may play in mitigating metabolic declines. Therefore, this study aimed to determine if 17α-E2 treatment improves metabolic outcomes in skeletal muscle from obese male and female mice following chronic high fat diet (HFD) administration. We hypothesized that male, but not female, mice, would benefit from 17α-E2 treatment during HFD. To test this hypothesis, we used a multi-omics approach to determine changes in lipotoxic lipid intermediates, metabolites, and proteins related to metabolic homeostasis. In male mice, we show that 17α-E2 alleviates HFD-induced metabolic detriments of skeletal muscle by reducing the accumulation of diacylglycerol (DAGs) and ceramides, inflammatory cytokine levels, and reduced the abundance of most of the proteins related to lipolysis and beta-oxidation. In contrast to males, 17α-E2 treatment in female mice had little effect on the DAGs and ceramides content, muscle inflammatory cytokine levels, or changes to the relative abundance of proteins involved in beta-oxidation. These data support to the growing evidence that 17α-E2 treatment could be beneficial for overall metabolic health in male mammals.
A generic reference defined by consensus peaks for scATAC-seq data analysis
Authors: Meng Qiuchen , Wu Xinze , Chen Wenchang , Zhao Yubo , Li Chen , Wei Zheng , Li Jiaqi , Xi Xi , Chen Sijie , Zhang Catherine , Chen Shengquan , Li Jiaqi , Wang Xiaowo , Jiang Rui , Wei Lei , Zhang Xuegong 
Published: June 2023

AbstractThe rapid advancement of transposase-accessible chromatin using sequencing (ATAC-seq) technology, particularly with the emergence of single-cell ATAC-seq (scATAC-seq), has accelerated the studies of gene regulation. However, the absence of a generic feature reference for ATAC-seq data limits single-cell analyses and hinders the development of comprehensive cell atlases. To address this, we constructed a generic chromatin accessibility reference by aggregating peaks from 624 high-quality bulk ATAC-seq datasets, defining more than 1 million consensus peaks (cPeaks). Leveraging a deep neural network model, we expanded cPeaks to include previously unobserved regions, enhancing their coverage across diverse tissues and cell types. cPeaks exhibit consistent shapes across tissue types, sequencing technologies, and peak-calling methods, indicating that they represent inherent genomic features. Compared to existing feature defining methods and references, cPeaks show superior performance in scATAC-seq analyses, improving cell annotation and rare cell type identification. Additionally, cPeaks provide insights into chromatin dynamics during cellular differentiation and tumor progression. cPeaks can serve as a robust reference for chromatin accessibility studies to promote cross-dataset consistency and accelerate biological discoveries.
Microstructural dynamics of motor learning and sleep-dependent consolidation: a diffusion imaging study
Authors: Stee Whitney , Legouhy Antoine , Guerreri Michele , Villemonteix Thomas , Zhang Hui , Peigneux Philippe 
Published: June 2023

SummaryDiffusion-weighted magnetic resonance imaging (DWI) allows the observation of (micro)structural brain remodelling in cortical and subcortical regions after time-limited motor learning. Post-learning sleep consolidation should lead to long-term microstructural brain changes, but concrete evidence remains limited. Here, we used both conventional diffusion tensor imaging (DTI) and Neurite Orientation Dispersion & Density Imaging (NODDI), that estimates dendritic and axonal complexity in white and grey matter, to investigate the microstructural brain mechanisms underlying time- and sleep-dependent motor memory consolidation. Sixty-one young healthy adults underwent 2 DWI sessions, with sequential motor training in between, on day 1 followed by the experimental night of total sleep deprivation or regular sleep. After 3 recovery nights at home, they underwent 2 further DWI sessions separated by a motor retraining session. Sequential motor learning resulted in immediate modifications in structural parameters in occipitoparietal and temporal regions, as well as in subcortical regions of interest. Similar changes were observed following relearning but at a smaller magnitude. Regarding delayed consolidation effects, learning-related changes only partially persisted 3 days after initial learning, and no post-learning sleep effect was detected. Our results show rapid motor learning-related remodelling, reflecting temporary processes in learning-related neuronal brain plasticity. Post-learning sleep-related cellular changes remain to be evidenced, possibly using more sophisticated brain imaging measures and spanning more extended timescales to allow the expression of structural changes.