bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiological analysis of the gender-age structure of hospitalized patients with COVID-19 and their mortality in 2020-2021
Authors: Voronin Evgeny M. , Khrapunova Izabella A. , Pechenik Andrey S. , Kravtsova Olga A. , Chen Zhang , Kostinov Mikhail P. , Loktionova Marina N. , Yakovleva Irina V. , Akimkin Vasily G. , Brazhnik Victoria A. 
Published: February 2023

AbstractBackgroundThe pandemic of the new coronavirus infection COVID-19 determines the relevance of conducting a study of the gender-age structure of hospitalized and deceased among the population of Moscow on the example of one of the city clinical hospitals in 2020 – 2021.The aim of the work is to identify the patterns of the epidemic process of COVID-19 in connection with the gender and age characteristics of hospitalized adults and to establish the sex and age groups most susceptible to hospitalization and mortality from COVID-19.Materials and methodsThe analysis of the structure of hospitalized and deceased from COVID-19 in the context of their gender and age composition was carried out. The data of the statistical accounting form F-60u/lech “Journal of infectious diseases” of adults hospitalized in one of the city clinical hospitals of Moscow in 2020 – 2021 were used. Data processing was carried out by a set of standard statistical methods. To identify the true risk groups for hospitalization and mortality, a statistical correction of the sex and age composition of the population of Moscow was used.Results and discussionUsing standard statistical methods in combination with the use of statistical correction of sex and age composition, data on the true risk groups for hospitalization and mortality among the population of Moscow in 2020 – 2021 were obtained.ConclusionThe results obtained in our independent study on the true risk groups for hospitalization and mortality among the population of Moscow complement and introduce new knowledge about the true risk groups for hospitalization and mortality in COVID-19. The patterns identified in this epidemiological analysis are an important component of epidemiological surveillance for making managerial decisions to prevent the spread of SARS-CoV-2 and planning for the provision of inpatient medical care to established gender and age risk groups.
Explainable Machine Learning Predictions of Perceptual Sensitivity for Retinal Prostheses
Authors: Pogoncheff Galen , Hu Zuying , Rokem Ariel , Beyeler Michael 
Published: February 2023

AbstractTo provide appropriate levels of stimulation, retinal prostheses must be calibrated to an individual’s perceptual thresholds (‘system fitting’), despite thresholds varying drastically across subjects, across electrodes within a subject, and over time. Although previous work has identified electrode-retina distance and impedance as key factors affecting thresholds, an accurate predictive model is still lacking. To address these challenges, we 1) fitted machine learning (ML) models to a large longitudinal dataset with the goal of predicting individual electrode thresholds and deactivation as a function of stimulus, electrode, and clinical parameters (‘predictors’) and 2) leveraged explainable artificial intelligence (XAI) to reveal which of these predictors were most important. Our models accounted for up to 77% of the perceptual threshold response variance and enabled predictions of whether an electrode was deactivated in a given trial with F1 and AUC scores of up to 0.740 and 0.913, respectively. Deactivation and threshold models identified novel predictors of perceptual sensitivity, including subject age, time since blindness onset, and electrode-fovea distance. Our results demonstrate that routinely collected clinical measures and a single session of system fitting might be sufficient to inform an XAI-based threshold prediction strategy, which may transform clinical practice in predicting visual outcomes.
Association of Healthy Dietary Patterns and Cardiorespiratory Fitness in the Community
Authors: Mi Michael Y. , Gajjar Priya , Walker Maura E. , Miller Patricia , Xanthakis Vanessa , Murthy Venkatesh L. , Larson Martin G. , Vasan Ramachandran S. , Shah Ravi V. , Lewis Gregory D. , Nayor Matthew 
Published: February 2023

AbstractAimsTo evaluate the associations of dietary indices and quantitative CRF measures in a large, community-based sample harnessing metabolomic profiling to interrogate shared biology.MethodsFramingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for CRF quantification (via peak VO2) and completed semi-quantitative FFQs. Dietary quality was assessed by the Alternative Healthy Eating Index (AHEI) and Mediterranean-style Diet Score (MDS), and fasting blood concentrations of 201 metabolites were quantified.ResultsIn 2380 FHS participants (54±9 years, 54% female, BMI 28±5 kg/m2), 1-SD higher AHEI and MDS were associated with 5.1% (1.2 ml/kg/min, p<0.0001) and 4.4% (1.0 ml/kg/min, p<0.0001) greater peak VO2in linear models adjusted for age, sex, total energy intake, cardiovascular risk factors, and physical activity. In participants with metabolite profiling (N=1154), 24 metabolites were concordantly associated with both dietary indices and peak VO2in multivariable-adjusted linear models (FDR<5%). These metabolites included C6 and C7 carnitines, C16:0 ceramide, and dimethylguanidino valeric acid, which were higher with lower CRF and poorer dietary quality and are known markers of insulin resistance and cardiovascular risk. Conversely, C38:7 phosphatidylcholine plasmalogen and C38:7 and C40:7 phosphatidylethanolamine plasmalogens were associated with higher CRF and favorable dietary quality and may link to lower cardiometabolic risk.ConclusionHigher diet quality is associated with greater CRF cross-sectionally in a middle-aged community-dwelling sample, and metabolites highlight potential shared favorable effects on health.
Social deprivation and SARS-CoV-2 testing: a population-based analysis in a highly contrasted Southern France region
Authors: Landier Jordi , Bassez Léa , Bendiane Marc-Karim , Chaud Pascal , Franke Florian , Nauleau Steve , Danjou Fabrice , Malfait Philippe , Rebaudet Stanislas , Gaudart Jean 
Published: February 2023

AbstractBackgroundTesting was the cornerstone of the COVID-19 epidemic response in most countries until vaccination became available for the general population. Social inequalities generally affect access to healthcare and health behaviours, and COVID-19 was rapidly shown to impact deprived population more drastically. In support of the regional health agency in Provence-Alpes-Côte d’Azur (PACA) in South-Eastern France, we analysed the relationship between testing rate and socio-demographic characteristics of the population, to identify gaps in testing coverage and improve targeting of response strategies.MethodsWe conducted an ecological analysis of SARS-CoV-2/COVID-19 testing rate in the PACA region, based on data aggregated at the finest spatial resolution available in France (IRIS) and by periods defined by public health implemented measures and major epidemiological changes. Using general census data, population density, and specific deprivation indices, we used principal component analysis followed by hierarchical clustering to define profiles describing local socio-demographic characteristics. We analysed the association between these profiles and testing rates in a generalized additive multilevel model, adjusting for access to healthcare, presence of a retirement home, and the age profile of the population.ResultsWe identified 6 socio-demographic profiles across the 2,306 analysed IRIS spatial units: privileged, remote, intermediate, downtown, deprived and very deprived (ordered by increasing social deprivation index). Profiles also ranged from rural (remote) to high density urban areas (downtown, very deprived). From July 2020 to December 2021, we analysed SARS-CoV-2/COVID-19 testing rate over 10 periods. Testing rates fluctuated strongly but were highest in privileged and downtown areas, and lowest in very deprived ones. The lowest adjusted testing rate ratios (aTRR) between privileged (reference) and other profiles occurred after implementation of a mandatory healthpass for many leisure activities in July 2021. Periods of contextual testing near Christmas displayed the largest aTRR, especially during the last periods of 2021 after the end of free convenience testing for unvaccinated individuals.ConclusionsWe characterized in-depth local heterogeneity and temporal trends in testing rates and identified areas and circumstances associated with low testing rates, which the regional health agency targeted specifically for the deployment of health mediation activities.
GENIUS: GEnome traNsformatIon and spatial representation of mUltiomicS data
Authors: Sokač Mateo , Kjær Asbjørn , Dyrskjøt Lars , Haibe-Kains Benjamin , Aerts Hugo J.W.L. , Birkbak Nicolai J 
Published: February 2023

ABSTRACTThe application of next-generation sequencing (NGS) has transformed cancer research. As costs have decreased, NGS has increasingly been applied to generate multiple layers of molecular data from the same samples, covering genomics, transcriptomics, and methylomics. Integrating these types of multi-omics data in a combined analysis is now becoming a common issue with no obvious solution, often handled on an ad-hoc basis, with multi-omics data arriving in a tabular format and analyzed using computationally intensive statistical methods. These methods particularly ignore the spatial orientation of the genome and often apply stringent p-value corrections that likely result in the loss of true positive associations. Here, we present GENIUS (GEnome traNsformatIon and spatial representation of mUltiomicS data), a framework for integrating multi-omics data using deep learning models developed for advanced image analysis. The GENIUS framework is able to transform multi-omics data into images with genes displayed as spatially connected pixels and successfully extract relevant information with respect to the desired output. Here, we demonstrate the utility of GENIUS by applying the framework to multi-omics datasets from the Cancer Genome Atlas. Our results are focused on predicting the development of metastatic cancer from primary tumors, and demonstrate how through model inference, we are able to extract the genes which are driving the model prediction and likely associated with metastatic disease progression. We anticipate our framework to be a starting point and strong proof of concept for multi-omics data transformation and analysis without the need for statistical correction.
Prioritizing Complex Disease Genes from Heterogeneous Public Databases
Authors: Gong Eric , Chen Jake Y. 
Published: February 2023

AbstractBackgroundComplex human diseases are defined not only by sophisticated patterns of genetic variants/mutations upstream but also by many interplaying genes, RNAs, and proteins downstream. Analyzing multiple genomic and functional genomic data types to determine a short list of genes or molecules of interest is a common task called “gene prioritization” in biology. There are many statistical, biological, and bioinformatic methods developed to perform gene prioritization tasks. However, little research has been conducted to examine the relationships among the technique used, merged/separate use of each data modality, the gene list’s network/pathway context, and various gene ranking/expansions.MethodsWe introduce a new analytical framework called “Gene Ranking and Iterative Prioritization based on Pathways” (GRIPP) to prioritize genes derived from different modalities. Multiple data sources, such as CBioPortal, PAGER, and COSMIC were used to compile the initial gene list. We used the PAGER software to expand the gene list based on biological pathways and the BEERE software to construct protein-protein interaction networks that include the gene list to rank order genes. We produced a final gene list for each data modality iteratively from an initial draft gene list, using glioblastoma multiform (GBM) as a case study.ConclusionWe demonstrated that GBM gene lists obtained from three modalities (differential gene expressions, gene mutations, and copy number alterations) and several data sources could be iteratively expanded and ranked using GRIPP. While integrating various modalities of data can be useful to generate an integrated ranked gene list related to any specific disease, the integration may also decrease the overall significance of ranked genes derived from specific data modalities. Therefore, we recommend carefully sorting and integrating gene lists according to each modality, such as gene mutations, epigenetic controls, or differential expressions, to procure modality-specific biological insights into the prioritized genes.
Single cell transcriptomics identifies adipose tissue CD271+ progenitors for enhanced angiogenesis in limb ischemia
Authors: Inoue Oto , Goten Chiaki , Hashimuko Daiki , Yamaguchi Kosei , Takeda Yusuke , Nomura Ayano , Ootsuji Hiroshi , Takashima Shinichiro , Iino Kenji , Takemura Hirofumi , Halurkar Manasi , Lim Hee-Woong , Hwa Vivian , Sanchez-Gurmaches Joan , Usui Soichiro , Takamura Masayuki 
Published: February 2023

SUMMARYTherapeutic angiogenesis using mesenchymal stem/stromal cell grafts have shown modest and controversial effects in preventing amputation for patients with critical limb ischemia. Through single-cell transcriptomic analysis of human tissues, we identified CD271+progenitors specifically from subcutaneous adipose tissue (AT) as having the most prominent pro-angiogenic gene profile distinct from other stem cell populations. AT-CD271+progenitors demonstrated robustin vivoangiogenic capacity, over conventional adipose stromal cell grafts, characterized by long-term engraftment, augmented tissue regeneration, and significant recovery of blood flow in a xenograft model of limb ischemia. Mechanistically, the angiogenic capacity of CD271+progenitors is dependent on functional CD271 and mTOR signaling. Notably, the number and angiogenic capacity of CD271+progenitors was strikingly reduced in insulin resistant donors. Our study highlights the identification of AT-CD271+progenitors within vivosuperior efficacy for limb ischemia. Furthermore, we showcase comprehensive single-cell transcriptomics strategies for identification of suitable grafts for cell therapy.HIGHLIGHTSAdipose tissue stromal cells have a distinct angiogenic gene profile among human cell sources.CD271+progenitors in adipose tissue have a prominent angiogenic gene profile.CD271+progenitors show superior therapeutic capacities for limb ischemia.CD271+progenitors are reduced and functionally impaired in insulin resistant donors.GRAPHICAL ABSTRACT
Nicotinic acetylcholine receptor signaling maintains epithelial barrier integrity
Authors: Katheder Nadja S. , Browder Kristen C. , Chang Diana , De Mazière Ann , Kujala Pekka , van Dijk Suzanne , Klumperman Judith , Lai Zijuan , Sangaraju Dewakar , Jasper Heinrich 
Published: February 2023

AbstractDisruption of epithelial barriers is a common disease manifestation in chronic degenerative diseases of the airways, lung and intestine. Extensive human genetic studies have identified risk loci in such diseases, including in chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases (IBD). The genes associated with these loci have not fully been determined, and functional characterization of such genes requires extensive studies in model organisms. Here, we report the results of a screen inDrosophila melanogasterthat allowed for rapid identification, validation and prioritization of COPD risk genes that were selected based on risk loci identified in human genome-wide association studies (GWAS) studies. Using intestinal barrier dysfunction in flies as a readout, our results validate the impact of candidate gene perturbations on epithelial barrier function in 56% of the cases, resulting in a prioritized target gene list. We further report the functional characterization in flies of one family of these genes, encoding for nicotinic acetylcholine receptor subunits (nAchR). We find that nAchR signaling in enterocytes of the fly gut promotes epithelial barrier function and epithelial homeostasis by regulating the production of the peritrophic matrix. Our findings identify COPD associated genes critical for epithelial barrier maintenance, and provide insight into the role of epithelial nAchR signaling for homeostasis.
Severe neurometabolic phenotype innpc1-/-zebrafish with a C-terminal mutation
Authors: Quelle-Regaldie Ana , Gandoy-Fieiras Nerea , Rodríguez-Villamayor Paula , Maceiras Sandra , Losada Ana Paula , Folgueira Mónica , Cabezas-Sáinz Pablo , Barreiro-Iglesias Antón , Villar-López María , Quiroga Berdeal María Isabel , Sánchez Laura , Sobrido María-Jesús 
Published: February 2023

ABSTRACTNiemann Pick disease type C (NPC) is an autosomal recessive neurodegenerative lysosomal disorder characterized by an accumulation of lipids in different organs. Clinical manifestations can start at any age and include hepatosplenomegaly, intellectual impairment, and cerebellar ataxia.NPC1is the most common causal gene, with over 460 different mutations with heterogeneous pathological consequences. We generated a zebrafish NPC1 model by CRISPR/Cas9 carrying a homozygous mutation in exon 22, which encodes the end of the cysteine-rich luminal loop of the protein. This is the first zebrafish model with a mutation in this gene region, which is frequently involved in the human disease. We observed a high lethality innpc1mutants, with all larvae dying before reaching the adult stage.Npc1mutant larvae were smaller than wild type (wt) and their motor function was impaired. We observed vacuolar aggregations positive to cholesterol and sphingomyelin staining in the liver, intestine, renal tubules and cerebral gray matter of mutant larvae. RNAseq comparison betweennpc1mutants and controls showed 249 differentially expressed genes, including genes with functions in neurodevelopment, lipid exchange and metabolism, muscle contraction, cytoskeleton, angiogenesis, and hematopoiesis. Lipidomic analysis revealed significant reduction of cholesteryl esters and increase of sphingomyelin in the mutants. Compared to previously available zebrafish models, our model seems to recapitulate better the early onset forms of the NPC disease. Thus, this new model of NPC will allow future research in the cellular and molecular causes/consequences of the disease and on the search for new treatments.
DRomics, a workflow to exploit dose-response omics data in ecotoxicology
Authors: Delignette-Muller Marie Laure , Siberchicot Aurélie , Larras Floriane , Billoir Elise 
Published: February 2023

ABSTRACTOmics technologies has opened new possibilities to assess environmental risks and to understand the mode(s) of action of pollutants. Coupled to dose-response experimental designs, they allow a non-targeted assessment of organism responses at the molecular level along an exposure gradient. However, describing the dose-response relationships on such high-throughput data is no easy task. In a first part, we review the software available for this purpose, and their main features. We set out arguments on some statistical and modeling choices we have made while developing the R package DRomics and its positioning compared to others tools. The DRomics main analysis workflow is made available through a web interface, namely a shiny app named DRomics-shiny. Next, we present the new functionalities recently implemented. DRomics has been augmented especially to be able to handle varied omics data considering the nature of the measured signal (e.g. counts of reads in RNAseq) and the way data were collected (e.g. batch effect, situation with no experimental replicates). Another important upgrade is the development of tools to ease the biological interpretation of results. Various functions are proposed to visualize, summarize and compare the responses, for different biological groups (defined from biological annotation), optionally at different experimental levels (e.g. measurements at several omics level or in different experimental conditions). A new shiny app named DRomicsInterpreter-shiny is dedicated to the biological interpretation of results. The institutional web pagehttps://lbbe.univ-lyon1.fr/fr/dromicsgathers links to all resources related to DRomics, including the two shiny applications.
Plastid fatty acid export (FAX) proteins inArabidopsis thaliana- the role of FAX1 and FAX3 in growth and development
Authors: Bugaeva Wassilina , Könnel Anne , Peter Janick , Mees Julia , Hankofer Valentin , Schick Cordula , Schmidt Alexander , Banguela-Castillo Alexander , Philippar Katrin 
Published: February 2023

AbstractIn plant cells, fatty acid (FA) synthesis occurs in the plastid stroma and thus requires subsequent FA export for lipid assembly in the endoplasmic reticulum. In this context, the membrane-intrinsic protein FAX1 has been described to mediate FA-export across the plastid inner envelope (IE). InArabidopsis,FAX1 function is crucial for pollen cell wall formation, male fertility, cellular lipid homeostasis and plant biomass. Based on conserved structural features and sequence motifs, we here define the plant FAX-protein family localized in plastids. Besides their membrane-intrinsic domain, the plastid-targeted FAX1-FAX3 contain distinct N-terminal stretches. Among them, the apolipoprotein-like α-helical bundle of FAX2 is the most prominent. Further, we could unequivocally localize FAX2 and FAX3 proteins together with FAX1 to the IE membrane of chloroplasts and develop a topology model for FAX1, FAX2, and FAX3. In yeast, all plastid FAX proteins – i.e. FAX1, FAX2, FAX3, FAX4 – can complement for FA-transport function. For FAX1 we show a new function in pollen tube growth as well as together with FAX3 in seed/embryo development and in rosette leaf growth. Since in comparison tofax1single knockout mutants,fax1/fax3double knockouts are seedling lethal and not able to develop mature rosette leaves, we conclude that FAX1 and FAX3 function together in vegetative leaf growth.HighlightWe define distinct structural features of plant FAX proteins in plastids and demonstrate that FAX1 and FAX3 have complementary functions in vegetative leaf growth.
The critical role ofDmnt1during spermatogenesis is not predictable, but knockdown does cause pervasive differential transcription
Authors: Cunningham Christopher B. , Shelby Emily A. , McKinney Elizabeth C. , Schmitz Robert J. , Moore Allen J. , Moore Patricia J. 
Published: February 2023

AbstractCytosine methylation and its machinery influence the gene expression of many eukaryotes; however, insects are an exception to this general tenet despite many lineages retaining methyltransferases and methylated genomes. Here, we tested thea priorihypothesis that perturbed genetic pathways will be associated with meiosis using transcriptomics because previous our work usingOncopeltus fasciatusshows that gametogenesis is interrupted at meiosis following knockdown ofDNA methyltransferase 1(Dnmt1). Testes, which are almost exclusively contain gametes at varying stages of development, were sampled at 7-days and 14-days following knockdown ofDmnt1using RNAi. Using microscopy, we found actively dividing spermatocysts were reduced at both sampling points. However, we found limited support of perturbation for our predicted cell cycle and meiotic pathways and only at 14-days. We found that Gene Ontology terms had no preferential enrichment for meiosis-associated genes. Following oura prioritests, we used the full dataset to uncover further candidate pathways influenced byDnmt1knockdown. Very few genes were differentially expressed at 7-days, but nearly half were at 14-days. We did not find strong candidate pathways for howDnmt1knockdown was achieving its effect through Gene Ontology term overrepresentation analysis. Given the evidence from microscopy, we proposeDnmt1knockdown results in condensed nuclei after mitosis-meiosis transition and then cellular arrest. This explanation posits that differential gene expression is a product of comparing healthy to arrested cells and is not a targeted response.