bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using electronic health record data to determine the safety of aqueous humor liquid biopsies for molecular analyses
Authors: Wolf Julian , Chemudupati Teja , Kumar Aarushi , Franco Joel A. , Montague Artis A. , Lin Charles C. , Lee Wen-Shin , Fisher A. Caroline , Goldberg Jeffrey L. , Mruthyunjaya Prithvi , Chang Robert T. , Mahajan Vinit B. 
Published: November 2023

AbstractPurposeKnowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHR) is cumbersome, but free-text software tools could facilitate efficient searches.DesignRetrospective case series.Participants1418 aqueous humor (AH) liquid biopsies from patients undergoing intraocular surgery.MethodsNatural language unstructured free-text EHR searches were performed using the Stanford Research Repository (STARR) cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed.Main Outcome MeasuresBiopsy associated intraoperative complications and endophthalmitis.Results1418 AH liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50-100μL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was more than seven months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet’s membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis.ConclusionsAnterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of AH samples for molecular analyses. Natural language free-text EHR searches are an efficient approach to reviewing intraoperative procedures.
TREVIXMBD: A Transcriptional Regulation-driven Variational Inference Model to Speculate Gene Expression Mechanism with Integration of Single-cell Multi-omics
Authors: Cao Lan , Zhang Wenhao , Zeng Feng , Wang Ying 
Published: November 2023

ABSTRACTSingle-cell multi-omics technology enables the concurrent measurement of multiple molecular entities, making it critical for unraveling the inherent gene regulation mechanisms driving cell heterogeneity. However, existing multi-omics techniques have limitations in capturing the intricate regulatory interactions among these molecular components. In this study, we introduce TREVIXMBD(Transcriptional REgulation-driven Variational Inference), a novel method that integrates the well-established gene regulation structure with scRNA-seq and scATAC-seq data through an advanced Bayesian framework. TREVIXMBDmodels the generation of gene expression profiles in individual cells by considering the integrated influence of three fundamental biological factors: accessibility of cis-regulatory elements regions, transcription factor (TF) activities and regulatory weights. TF activities and regulatory weights are probabilistically represented as latent variables, which capture the inherent gene regulatory significance. Hence, in contrast to gene expression, TF activities and regulatory weights that depict the cell states from a more intrinsic perspective, can keep consistent across diverse datasets. TREVIXMBDexhibits superior performance when compared to baseline methods in a variety of biological analyses, including cell typing, cell development tracking, and batch effect correction, as validated through comprehensive benchmarking. Moreover, TREVIXMBDcan reveal variations in TF-gene regulation relationships across cells. The pretrained TREVIXMBDmodel can work even when only scRNA-seq is available. Overall, TREVIXMBDintroduces a pioneering biological-mechanism-driven framework for elucidating cell states at a gene regulatory level. The model’s structure is adaptable for the inclusion of additional biological factors, allowing for flexible and more comprehensive gene regulation analysis.
scCross: A Deep Generative Model for Unifying Single-cell Multi-omics with Seamless Integration, Cross-modal Generation, and In-silico Exploration
Authors: Yang Xiuhui , Mann Koren K. , Wu Hao , Ding Jun 
Published: November 2023

AbstractSingle-cell multi-omics illuminate intricate cellular states, yielding transformative insights into cellular dynamics and disease. Yet, while the potential of this technology is vast, the integration of its multifaceted data presents challenges. Some modalities have not reached the robustness or clarity of established scRNA-seq. Coupled with data scarcity for newer modalities and integration intricacies, these challenges limit our ability to maximize single-cell omics benefits. We introduce scCross: a tool adeptly engineered using variational autoencoder, generative adversarial network principles, and the Mutual Nearest Neighbors (MNN) technique for modality alignment. This synergy ensures seamless integration of varied single-cell multi-omics data. Beyond its foundational prowess in multi-omics data integration, scCross excels in single-cell cross-modal data generation, multi-omics data simulation, and profound in-silico cellular perturbations. Armed with these capabilities, scCross is set to transform the field of single-cell research, establishing itself in the nuanced integration, generation, and simulation of complex multi-omics data.
Intellectual disability and neurogenesis defects associated with increased turnover of an O-GlcNAcase variant
Authors: Authier Florence , Attianese Benedetta , Bartual Sergio Galan , Mitchell Conor W. , Ferenbach Andrew T. , Doummar Diane , Charles Perrine , Mignot Cyril , Keren Boris , van Aalten Daan M. F. 
Published: November 2023

AbstractIntellectual Disability (ID) is characterised by substantial limitations in cognitive function and adaptive behaviour, affecting 1-3% of the population. Protein O-GlcNAcylation is a posttranslational modification of nucleocytoplasmic proteins regulated by two opposing enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recently, missense mutations inOGThave been shown to segregate with ID, associated with compensatory reduction of OGA expression, although it is unclear whether this is mechanistically linked to the disease. Here, we report a patient with a K885Nde novomissense mutation in the C-terminal pseudo histone acetyltransferase domain of OGA, associated with ID, infantile spasms and autism. While the K885N mutation does not affect protein stability or activityin vitro, this residue sits in the canonical GCN5 acetyltransferase family acceptor binding cleft. Strikingly, mouse embryonic stem cells edited to harbour the K885N mutation show increased OGA turnover and defects in neurogenesis. Taken together, these data suggest a link between missense mutations in OGA and ID.
A distinct T cell receptor signature associates with cardiac outcome in myocardial infarction patients
Authors: Le Gouge Kenz , Ashour DiyaaElDin , Heinrichs Margarete , Stys Paul , Barennes Pierre , Stangl Verena , Rech Lavinia , Hoefler Gerald , Kashofer Karl , Gassenmaier Tobias , Boivin-Jahns Valerie , Jahns Roland , Hofmann Ulrich , Schmitt Dominik , Frey Anna , Störk Stefan , Frantz Stefan , Rainer Peter P. , Ramos Gustavo Campos , Mariotti-Ferrandiz Encarnita 
Published: November 2023

AbstractMyocardial infarction (MI) is associated with an inflammatory process mainly attributed to innate immune components. Very recently, the role of T-cells in both inflammation and healing has been suggested through various human and mouse studies. Previous studies showed that CD4+ and CD8+ T cells affect post-MI repair but did not investigate how to leverage T cell biology to predict post-MI outcomes in patients. For instance, the antigenic trigger of T-cells is still unknown in human. Indeed, others and we identified T-cell specific for myosin infiltrating the myocardium in mouse models of MI, recent studies identified expanded clones in human myocardium, altogether suggesting a tissue-specific T-cell activation. However, it is still unclear how acute post-MI immune responses shape long-term cardiac functional outcomes in individual patients. In this study, we analyzed the role of T-cell in predicting post-MI repair by analyzing the T-cell receptor (TCR) repertoire. Indeed, the TCR repertoire is now considered as a marker of the clinical status of individuals. Previous studies in infectious but also autoimmune contexts showed the potential of the TCR repertoire to predict the disease. Therefore, assessing the dynamic changes in global TCR repertoires may provide valuable information about the antigen-specific immune responses underlying post-MI healing. In our study, we carefully selected patients that suffered from MI on a prospective cohort. The TCR repertoire has been analyzed by next generation sequencing at the index hospitalization with the aim to identify features predict of their healing outcome assessed at 12 months post-MI. While no major variations have been found in diversity of TCR gene usage, we identified unique TCR signatures predicting one-year cardiac functional outcomes. Our result enables early immune-based risk stratification of MI patients and calls for larger studies to develop novel predictive biomarkers and possibly new therapeutics.
Diverging the anthracycline class of anti-cancer drugs for superior survival of acute myeloid leukemia patients
Authors: Qiao Xiaohang , van der Zanden Sabina Y. , Li Xiaoyang , Tan Minkang , Zhang Yunxiang , Song Ji-Ying , van Gelder Merle A. , Hamoen Feija L. , Janssen Lennert , Zuur Charlotte L. , Pang Baoxu , van Tellingen Olaf , Li Junmin , Neefjes Jacques 
Published: November 2023

AbstractThe efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxification of anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are now a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S.. To address this, we examined different clinically relevant anthracycline drugs with respect to a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. We show that different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical trials as it potently kills cancer cells, does not induce therapy-related malignancies or cardiotoxicity, and can be safely administered even after a maximum cumulative dose of either ida- or doxorubicin has been reached. Retrospective analysis of aclarubicin used in second-line treatment of relapsed/refractory AML patients showed similar survival effects to its use in first line, leading to an almost 25% increase in 5-year overall survival. Considering individual anthracyclines as different drugs provides new treatment options that strongly improve survival of cancer patients while limiting the toxic side-effects.Abstract Figure
Improving SARS-CoV-2 variants monitoring in the absence of genomic surveillance capabilities: a serological study in Bolivian blood donors in October 2021 and June 2022
Authors: Inchauste Lucia , Nurtop Elif , Bautista Machicado Lissete , Leigue Roth Yanine , Lenz Gonzales Shirley , Herrera Maria Luisa , Mina Villafan Katty , Mamani Mamani Pedro , Ramos Espinoza Marcelo , Pavel Suarez Juan Carlos , Garcia Copa Juan Cansio , Leigue Zabala Yitzhak , Arancibia Cardozo Etzel , Gallian Pierre , de Lamballerie Xavier , Priet Stéphane 
Published: November 2023

AbstractUnlike genomic data, serological data have not been previously leveraged to evaluate the SARS-CoV-2 variants circulation. In Bolivia, sustained genomic surveillance capacities were lacking especially at the beginning of the pandemic. In 2021 and 2022 we estimated the prevalence of anti-SARS-CoV-2 antibodies in Bolivian blood donors and explored the feasibility of using virus serum neutralization data for variants thought to have circulated to map their circulation across all departments over a year-long follow-up period. Anti-S1 and anti-NCP SARS-CoV-2 IgGs were studied, along with virus neutralization tests for ancestral-D614G, Gamma, Delta, and Omicron BA.1 lineages of SARS-CoV-2. Between 2021 and 2022, the overall prevalence of anti-S1 and anti-NCP antibodies increased reaching values over 90%, demonstrating that a large proportion of the Bolivian population was no longer naïve to the virus. Viral neutralization data, analyzed through multiple approaches, revealed the spread of the Gamma variant up to 2021, particularly impacting northern departments. In 2022, Gamma continued to circulate in southernmost departments of the country and the emergence of Omicron BA.1 was detected. These trends align with publicly available genomic data from neighboring countries. Our serological analyses successfully identified both new antigenic groups, such as Omicron BA.1, and individual variants related to previously circulating groups, such as Delta. The study contributes insights into overall population immunity to SARS-CoV-2 and variant-specific immunity levels across different regions of Bolivia. It also emphasizes the potency of seroprevalence studies in informing public health decisions and underscore their value in capturing the initial phases of emerging epidemics when variant diversity is limited, facilitating timely genomic surveillance setup.
The association between parental, obstetric, socioeconomic, and lifestyle factors and the development of childhood obesity: A Danish Cohort Study
Authors: Christiansen Elizabeth la Cour , Thagaard Ida Näslund , Hedley Paula L. , Lautrup Hansen Majbrit Johanne , Frithioff-Bøjsøe Christine , Larsen Torben , Holm Jens-Christian , Christiansen Michael , Krebs Lone 
Published: November 2023

ABSTRACTBackgroundChildhood obesity is a multifactorial disease with complex etiology. Obstetrical factors are seldom taken into considerations.ObjectivesTo investigate the association between parental, obstetric and lifestyle characteristics, and childhood overweight and obesity.MethodsThis retrospective cohort study evaluated associations between birthweight, pre-pregnancy BMI, birth mode, paternal BMI, family history of obesity, parental status, and maternal socioeconomic status and the outcome variable childhood overweight and obesity using logistic regression. Data regarding parental and childhood characteristics were collected through self-administered questionnaires, and obstetric information was retrieved from the Danish Medical Birth Registry.ResultsThe incidence of childhood overweight and obesity was 11.3 % at a median (IQR) age of 6.51 years (IQR = 2.84). In obese mothers and children who were macrosomic at birth (birthweight ≥4,500 g), the incidence was 21.6% and 23.4%, respectively.Risk factors for childhood overweight and obesity were macrosomia, (aOR 2.34, 95% CI 1.24-2.19), maternal- and (aOR 2.48, 95% CI 1.78-3.45) paternal overweight and obesity (aOR 2.17, 95% CI 1.44-3.34) and birthweight z-score (aOR 1.13, 95% CI 1.03-1.23). Combining maternal obesity and a macrosomic child gave the highest risk (aOR 7.49, 95% CI 2.05-24.86) Other predictors were divorced-(aOR 2.04, 95% CI 1.13-3.57) and living as a single parents (aOR 3.80, 95% CI 1.31-10.16).ConclusionsMacrosomia combined with maternal obesity was the strongest risk factor for childhood overweight and obesity. Other individual risk factors are parental obesity and socioeconomic factors. This supports the role of lifestyle modification, education-based policies and interventions to prevent high birth weight in counteracting childhood obesity.
Genetic analysis of 104 pregnancy phenotypes in 39,194 Chinese women
Authors: Xiao Han , Li Linxuan , Yang Meng , Zeng Jingyu , Zhou Jieqiong , Tao Ye , Zhou Yan , Cai Mingzhi , Liu Jiuying , Huang Yushan , Zhong Yuanyuan , Liu Panhong , Cao Zhongqiang , Mei Hong , Cai Xiaonan , Hu Liqin , Zhou Rui , Xu Xun , Yang Huanming , Wang Jian , Zhu Huanhuan , Zhou Aifen , Jin Xin 
Published: November 2023

AbstractMaternity is a special period in a woman’s life that involves substantial physiological, psychological, and hormonal changes. These changes may cause alterations in many clinical measurements during pregnancy, which can be used to monitor and diagnose maternal disorders and adverse postnatal outcomes. Exploring the genetic background of these phenotypes is key to elucidating the pathogenesis of pregnancy disorders. In this study, we conducted a large-scale molecular biology analysis of 104 pregnancy phenotypes based on genotype data from 39,194 Chinses women. Genome- wide association analysis identified a total of 407 trait-locus associations, of which 75.18% were previously reported. Among the 101 novel associations for 37 phenotypes, some were potentially pregnancy-specific and worth further experimental investigation. For example,ESR1with fasting glucose, hemoglobin, hematocrit, and several leukocytoses;ZSCAN31with blood urea nitrogen. We further performed pathway- based analysis and uncovered at least one significant pathway for 24 traits, in addition to previously known functional pathways, novel findings included birthweight with “Reactome signaling by NODAL”, twin pregnancy with “Reactome mitotic G1-G1/S phases”. The partitioning heritability analysis recapitulated known trait-relevant tissue/cell types, and also discovered interesting results including twin pregnancy with “embryoid bodies” cell-type enrichment, the delivery type cesarean section with “fallopian tube”, and birth weight with “ovary and embryonic stem cells”. In terms of both sample size and the variety of phenotypes, our work is one of the largest genetic studies of pregnancy phenotypes across all populations. We believe that this study will provide a valuable resource for exploring the genetic background of pregnancy phenotypes and also for further research on pregnancy-related diseases and adverse neonatal outcomes.
Unveiling the Impact of Arsenic Toxicity on Immune Cells in Atherosclerotic Plaques: Insights from Single-Cell Multi-Omics Profiling
Authors: Makhani Kiran , Yang Xiuhui , Dierick France , Subramaniam Nivetha , Gagnon Natascha , Ebrahimian Talin , Wu Hao , Ding Jun , Mann Koren K. 
Published: November 2023

AbstractMillions worldwide are exposed to elevated levels of arsenic. This significantly increases their risk of developing atherosclerosis, a pathology primarily driven by immune cells. While the impact of arsenic on immune cell populations in atherosclerotic plaques has been broadly characterized, cellular heterogeneity is a substantial barrier to in-depth examinations of the cellular dynamics for varying immune cell populations. Here, we present one of the first single-cell multi-omics profiling of atherosclerotic plaques in apolipoprotein E knockout (apoE-/-) mice to understand the transcriptomic and epigenetic changes in various immune cells induced by arsenic. Our data reveal that arsenic alters the transcriptional profile of macrophages in a subtype-specific manner with implicated shifts in cell-cell interaction and cell fate predictions. Additionally, our data suggest that arsenic-mediated changes in chromosome accessibility are more profound than their effects on the transcriptome, hence revealing markers of arsenic exposure and potential targets of interventions.TeaserArsenic changes gene expression and epigenome primarily of macrophages in atherosclerotic plaque, suggesting intervention targets.
Population genomic history of the endangered Anatolian and Cyprian mouflons in relation to worldwide wild, feral and domestic sheep lineages
Authors: Atağ Gözde , Kaptan Damla , Yüncü Eren , Vural Kıvılcım Başak , Mereu Paolo , Pirastru Monica , Barbato Mario , Leoni Giovanni Giuseppe , Güler Merve N. , Er Tuğçe , Eker Elifnaz , Yazıcı Tunca Deniz , Kılıç Muhammed Sıddık , Altınışık N. Ezgi , Çelik Ecem Ayşe , Miranda Pedro Morell , Dehasque Marianne , Floridia Viviana , Götherström Anders , Bilgin C. Can , Togan İnci , Günther Torsten , Özer Füsun , Hadjisterkotis Eleftherios , Somel Mehmet 
Published: November 2023

AbstractOnce widespread in their homelands, Anatolian mouflon (Ovis gmelini anatolica) and Cyprian mouflon (Ovis gmelini ophion) were driven to near extinction during the 20th century and are currently listed as endangered populations by the IUCN. While the exact origins of these lineages remain unclear, they have been suggested to be close relatives of domestic sheep or remnants of proto-domestic sheep groups. Here, we study whole genome sequences of n=5 Anatolian mouflons and n=10 Cyprian mouflons in terms of population history and diversity, relative to eight other extant sheep lineages. We find reciprocal genetic affinity between Anatolian and Cyprian mouflons and domestic sheep, higher than all other studied wild sheep genomes, including the Iranian mouflon (Ovis gmelini). Despite similar recent population dynamics, Anatolian and Cyprian mouflons exhibit disparate diversity levels, which can potentially be attributed to founder effects, island isolation, introgression from domestic lineages, or different bottleneck dynamics. The lower relative mutation load found in Cyprian compared to Anatolian mouflons suggests the purging of recessive deleterious variants in the former. This agrees with estimates of a long-term small effective population size in the Cyprian mouflon. Both subspecies harbor considerable numbers of runs of homozygosity (ROH) blocks <2 Mb, which reflects the effect of small population size. Expanding our analyses to worldwide wild and feralOvisgenomes, we observe varying viability metrics among different lineages, and a limited consistency between viability metrics and conservation status. Factors such as recent inbreeding, introgression, and unique population dynamics may contribute to the observed disparities.