bluuebunny/crossref_metadata_2025_split huggingface dataset:
BrcaDx: Precise identification of breast cancer from expression data using a minimal set of features
Authors: Muthamilselvan Sangeetha , Palaniappan Ashok 
Published: March 2023

AbstractBackgroundBreast cancer is the foremost cancer in worldwide incidence, surpassing lung cancer notwithstanding the gender bias. One in four cancer cases among women are attributable to cancers of the breast, which are also the leading cause of death in women. Reliable options for early detection of breast cancer are needed.MethodsUsing public-domain datasets, we screened transcriptomic profiles of breast cancer samples, and identified progression-significant linear and ordinal model genes using stage-informed models. We then applied a sequence of machine learning techniques, namely feature selection, principal components analysis, and k-means clustering, to train a learner to discriminate ‘cancer’ from ‘normal’ based on expression levels of identified biomarkers.ResultsOur computational pipeline yielded an optimal set of nine biomarker features for training the learner, namely NEK2, PKMYT1, MMP11, CPA1, COL10A1, HSD17B13, CA4, MYOC, and LYVE1. Validation of the learned model on an internal testset yielded a performance of 99.5% accuracy. Blind validation on an external dataset yielded a balanced accuracy of 95.5%, demonstrating that the model has effectively reduced the dimensionality of the problem, and learnt the solution. The model was rebuilt using the full dataset, and then deployed as a web app for non-profit purposes at:https://apalania.shinyapps.io/brcadx/. To our knowledge, this is the best-performing freely available tool for the high-confidence diagnosis of breast cancer, and represents a promising aid to medical diagnosis.
Testing the neural noise account: an investigation of visual temporal precision in Tourette syndrome
Authors: Slack Hannah R. , Jackson Georgina M. , Jackson Stephen R. 
Published: March 2023

AbstractTourette syndrome (TS) is a neurological disorder of childhood onset characterised by the occurrence of vocal and motor tics. The pathophysiology of TS has been linked to dysfunction within cortical-striatal-thalamic-cortical (CSTC) brain circuits and alterations in gamma-aminobutyric acid (GABA) signalling within the striatum. Recently, it has been proposed that increased neural noise, leading to decreased signal-to-noise, may be responsible for dysfunctional information processing in TS. Importantly, increased neural noise could impact all stages of the sensorimotor processing, including sensation, action planning, and action execution, and it currently remains to be determined whether this ‘increased neural noise account’ of TS refers to all aspects of information processing, or is specific to particular stages of information processing. We hypothesised that if TS was associated with decreased signal-to-noise when processing visual stimuli, then this might be reflected in a reduction in the precision of their perceptual timing estimates. To examine this, we investigated the precision of perceptual timing in a group of individuals with tic disorder using a visual temporal-order-judgement (TOJ) task.
Association of NOTCH3 with Elastic Fiber Dispersion in the Infrarenal Abdominal Aorta of Cynomolgus Monkeys
Authors: Ito Sohei , Amioka Naofumi , Franklin Michael K. , Wang Pengjun , Liang Ching-Ling , Katsumata Yuriko , Cai Lei , Temel Ryan E. , Daugherty Alan , Lu Hong S. , Sawada Hisashi 
Published: March 2023

ABSTRACTBackgroundThe regional heterogeneity of vascular components and transcriptomes is an important determinant of aortic biology. This notion has been explored in multiple mouse studies. In the present study, we examined the regional heterogeneity of aortas in non-human primates.MethodsAortic samples were harvested from the ascending, descending, suprarenal, and infrarenal regions of young control monkeys and adult monkeys provided with high fructose for 3 years. The regional heterogeneity of aortic structure and transcriptomes was examined by histological and bulk RNA sequencing analyses.ResultsImmunostaining of CD31 and αSMA revealed that endothelial and smooth muscle cells were distributed homogeneously across the aortic regions. In contrast, elastic fibers were less abundant and dispersed in the infrarenal aorta compared to other regions and associated with collagen deposition. Bulk RNA sequencing identified a distinct transcriptome related to the Notch signaling pathway in the infrarenal aorta with significantly increasedNOTCH3mRNA compared to other regions. Immunostaining revealed that NOTCH3 protein was increased in the media of the infrarenal aorta. The abundance of medial NOTCH3 was positively correlated with the dispersion of elastic fibers. Adult cynomolgus monkeys provided with high fructose displayed vascular wall remodeling, such as smooth muscle cell loss and elastic fiber disruption, predominantly in the infrarenal region. The correlation between NOTCH3 and elastic fiber dispersion was enhanced in these monkeys.ConclusionsAortas of young cynomolgus monkeys display regional heterogeneity of their transcriptome and the structure of elastin and collagens. Elastic fibers in the infrarenal aorta are dispersed along with upregulation of medial NOTCH3.HIGHLIGHTS-The present study determined the regional heterogeneity of aortas from cynomolgus monkeys.-Aortas of young cynomolgus monkeys displayed region-specific aortic structure and transcriptomes.-Elastic fibers were dispersed in the infrarenal aorta along with increased NOTCH3 abundance in the media.GRAPHIC ABSTRACT
Optimization of somatic embryogenesis inEuterpe edulisMartius using auxin analogs and atomic force microscopy
Authors: de Mello Tamyris , Taliuli Yanara dos Santos , Silva Tatiane Dulcineia , Zanardo Tadeu Ériton Caliman , Hegedus Clovis Eduardo Nunes , Anjos Breno Benvindo dos , Schmildt Edilson Romais , Ferreira Adésio , Lourenço Maicon Pierre , Pinheiro Patricia Fontes , Aquije Glória Maria de Farias Viégas , Lopes José Carlos , Otoni Wagner Campos , Alexandre Rodrigo Sobreira 
Published: March 2023

AbstractEuterpe edulisMartius is an endangered species of the Atlantic Forest, whose fruits have high antioxidant potential, and propagated exclusively by seeds. The present study assessed the ability of different auxin inducers and picloram analogs to trigger somatic embryogenesis inE. edulis. Immature seeds were harvested, and their zygotic embryos were excised and grown in MS culture medium supplemented with 2,4-D dichlorophenoxyacetic acid (2,4-D) or picloram at 150, 300, 450, 600 µM. The activity of picloram analogs triclopyr and clopyralid was evaluated in semisolid MS medium. At maturation and germination, picloram-derived calli and somatic embryos isolated from triclopyr-grown cultures were first transferred to pre-maturation medium and, after 30 days, to basal MS or MS medium supplemented with either 5 µM abscisic acid or 0.53 µM 1-naphthaleneacetic acid plus 12.3 µM 2-isopentenyladenine. Finally, somatic embryos with root protrusions were transferred to MS medium devoid of sucrose for 30 days and then acclimatized ex vitro. Scanning, transmission, and atomic force microscopy revealed that picloram was superior to 2,4-D but less effective than triclopyr (100 µM) in inducing embryogenesis. Maturation and germination of somatic embryos in E. edulis can be maximized by 5 µM abscisic acid, and selecting calli via atomic force microscopy.HighlightThis work opens novel roads for embryogenic induction, using a new and more efficient inducer than the usual ones, and an innovative evaluation technique based on AFM.
Mutations in S2 subunit of SARS-CoV-2 Omicron spike strongly influence its conformation, fusogenicity and neutralization sensitivity
Authors: Kumar Sahil , Delipan Rathina , Chakraborty Debajyoti , Kanjo Kawkab , Singh Randhir , Singh Nittu , Siddiqui Samreen , Tyagi Akansha , Jha Sujeet , Thakur Krishan G. , Pandey Rajesh , Varadarajan Raghavan , Ringe Rajesh P. 
Published: March 2023

AbstractSARS-CoV-2 has remarkable ability to respond to and evolve against the selection pressure by host immunity exemplified by emergence of Omicron lineage. Here, we characterized the functional significance of mutations in Omicron spike. By systematic transfer of mutations in WT spike we assessed neutralization sensitivity, fusogenicity, and TMPRSS2-dependence for entry. The data revealed that the mutations in both S1 and S2 complement to make Omicron highly resistant. Strikingly, the mutations in Omicron S2 modulated the neutralization sensitivity to NTD- and RBD-antibodies, but not to S2 specific neutralizing antibodies, suggesting that the mutations in S2 were primarily acquired to gain resistance to S1-antibodies. Although all six mutations in S2 appeared to act in concert, D796Y showed greatest impact on neutralization sensitivity and rendered WT virus >100-fold resistant to S309, COVA2-17, and 4A8. S2 mutations greatly reduced the antigenicity for NAbs due to reduced exposure of epitopes. In terms of the entry pathway, S1 or S2 mutations only partially altered the entry phenotype of WT and required both sets of mutations for complete switch to endosomal route and loss of syncytia formation. In particular, N856K and L981F in Omicron reduced fusion capacity and explain why subsequent Omicron variants lost them to regain fusogenicity.
Seagrass genomes reveal a hexaploid ancestry facilitating adaptation to the marine environment
Authors: Ma Xiao , Vanneste Steffen , Chang Jiyang , Ambrosino Luca , Barry Kerrie , Bayer Till , Bobrov Alexander A. , Boston LoriBeth , Campbell Justin E , Chen Hengchi , Chiusano Maria Luisa , Dattolo Emanuela , Grimwood Jane , He Guifen , Jenkins Jerry , Khachaturyan Marina , Marín-Guirao Lázaro , Mesterházy Attila , Muhd Danish-Daniel , Pazzaglia Jessica , Plott Chris , Rajasekar Shanmugam , Rombauts Stephane , Ruocco Miriam , Scott Alison , Tan Min Pau , Van de Velde Jozefien , Vanholme Bartel , Webber Jenell , Wong Li Lian , Yan Mi , Sung Yeong Yik , Novikova Polina , Schmutz Jeremy , Reusch Thorsten , Procaccini Gabriele , Olsen Jeanine , Van de Peer Yves 
Published: March 2023

ABSTRACTSeagrasses comprise the only submerged marine angiosperms, a feat of adaptation from three independent freshwater lineages within the Alismatales. These three parallel lineages offer the unique opportunity to study convergent versus lineage-specific adaptation to a fully marine lifestyle. Here, we present chromosome-level genome assemblies from a representative species of each of the seagrass lineages -Posidonia oceanica(Posidoniaceae),Cymodocea nodosa(Cymodoceaceae), andThalassia testudinum(Hydrocharitaceae)-along with an improved assembly forZostera marina(Zosteraceae). We also include a draft genome ofPotamogeton acutifolius, a representative of Potamogetonaceae, the freshwater sister lineage to the Zosteraceae. Genome analysis reveals that all seagrasses share an ancient whole genome triplication (WGT) event, dating to the early evolution of the Alismatales. An additional whole genome duplication (WGD) event was uncovered forC. nodosaandP. acutifolius. Dating of ancient WGDs and more recent bursts of transposable elements correlate well with major geological and recent climatic events, supporting their role as rapid generators of genetic variation. Comparative analysis of selected gene families suggests that the transition from the submerged-freshwater to submerged-marine environment did not require revolutionary changes. Major gene losses related to, e.g., stomata, volatiles, defense, and lignification, are likely a consequence of the submerged lifestyle rather than the cause (‘use it or lose it’). Likewise, genes, often retained from the WGD and WGT, were co-opted for functions requiring the alignment of many small adaptations (‘tweaking’), e.g., osmoregulation, salinity, light capture, carbon acquisition, and temperature. Our ability to manage and conserve seagrass ecosystems depends on our understanding of the fundamental processes underpinning their resilience. These new genomes will accelerate functional studies and are expected to contribute to transformative solutions — as continuing worldwide losses of the ‘savannas of the sea’ are of major concern in times of climate change and loss of biodiversity.
FARL-11 (STRIP1/2) is Required for Sarcomere and Sarcoplasmic Reticulum Organization inC. elegans
Authors: Martin Sterling C.T. , Qadota Hiroshi , Oberhauser Andres F. , Hardin Jeff , Benian Guy M. 
Published: March 2023

AbstractProtein phosphatase 2A (PP2A) functions in a variety of cellular contexts. PP2A can assemble into four different complexes based on the inclusion of different regulatory or targeting subunits. The B’’’ regulatory subunit “striatin” forms the STRIPAK complex consisting of striatin, a catalytic subunit (PP2AC), striatin interacting protein 1 (STRIP1), and MOB family member 4 (MOB4). In yeast andC. elegans,STRIP1 is required for formation of the endoplasmic reticulum (ER). Since the sarcoplasmic reticulum (SR) is the highly organized muscle-specific version of ER, we sought to determine the function of the STRIPAK complex in muscle usingC. elegans. CASH-1 (striatin) and FARL-11 (STRIP1/2) form a complexin vivo, and each protein is localized to SR. Missense mutations and single amino acid losses infarl-11andcash-1each result in similar sarcomere disorganization. A missense mutation infarl-11shows no detectable FARL-11 protein by immunoblot, disruption of SR organization around M-lines, and altered levels of the SR Ca+2release channel UNC-68.SummaryProtein phosphatase 2A forms a STRIPAK complex when it includes the targeting B’’’ subunit “striatin” and STRIP1. STRIP1 is required for formation of ER. We show that in muscle STRIP1 is required for organization of SR and sarcomeres.
Massively parallel characterization of transcriptional regulatory elements in three diverse human cell types
Authors: Agarwal Vikram , Inoue Fumitaka , Schubach Max , Martin Beth K. , Dash Pyaree Mohan , Zhang Zicong , Sohota Ajuni , Noble William Stafford , Yardimci Galip Gürkan , Kircher Martin , Shendure Jay , Ahituv Nadav 
Published: March 2023

ABSTRACTThe human genome contains millions of candidatecis-regulatory elements (CREs) with cell-type-specific activities that shape both health and myriad disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these CREs. Here, we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of over 680,000 sequences, representing a nearly comprehensive set of all annotated CREs among three cell types (HepG2, K562, and WTC11), finding 41.7% to be functional. By testing sequences in both orientations, we find promoters to have significant strand orientation effects. We also observe that their 200 nucleotide cores function as non-cell-type-specific ‘on switches’ providing similar expression levels to their associated gene. In contrast, enhancers have weaker orientation effects, but increased tissue-specific characteristics. Utilizing our lentiMPRA data, we develop sequence-based models to predict CRE function with high accuracy and delineate regulatory motifs. Testing an additional lentiMPRA library encompassing 60,000 CREs in all three cell types, we further identified factors that determine cell-type specificity. Collectively, our work provides an exhaustive catalog of functional CREs in three widely used cell lines, and showcases how large-scale functional measurements can be used to dissect regulatory grammar.
Split-Transformer Impute (STI): A Transformer Framework for Genotype Imputation
Authors: Mowlaei Mohammad Erfan , Li Chong , Jamialahmadi Oveis , Dias Raquel , Chen Junjie , Jamialahmadi Benyamin , Rebbeck Timothy Richard , Carnevale Vincenzo , Kumar Sudhir , Shi Xinghua 
Published: March 2023

AbstractMotivationDespite recent advances in sequencing technologies, genome-scale datasets continue to have missing bases and genomic segments. Such incomplete datasets can undermine downstream analyses, such as disease risk prediction and association studies. Consequently, the imputation of missing information is a common pre-processing step for which many methodologies have been developed. However, the imputation of genotypes of certain genomic regions and variants, including large structural variants, remains a challenging problem.ResultsHere, we present a transformer-based deep learning framework, called a split-transformer impute (STI) model, for accurate genome-scale genotype imputation. Empowered by the attention-based transformer model, STI can be trained for any collection of genomes automatically using self-supervision. STI handles multi-allelic genotypes naturally, unlike other models that need special treatments. STI models automatically learned genome-wide patterns of linkage disequilibrium (LD), evidenced by much higher imputation accuracy in high LD regions. Also, STI models trained through sporadic masking for self-supervision performed well in imputing systematically missing information. Our imputation results on the human 1000 Genomes Project show that STI can achieve high imputation accuracy, comparable to the state-of-the-art genotype imputation methods, with the additional capability to impute multi-allelic structural variants and other types of genetic variants. Moreover, STI showed excellent performance without needing any special presuppositions about the patterns in the underlying data when applied to a collection of yeast genomes, pointing to easy adaptability and application of STI to impute missing genotypes in any species.
Biological representation disentanglement of single-cell data
Authors: Piran Zoe , Cohen Niv , Hoshen Yedid , Nitzan Mor 
Published: March 2023

AbstractDue to its internal state or external environment, a cell’s gene expression profile contains multiple signatures, simultaneously encoding information about its characteristics. Disentangling these factors of variations from single-cell data is needed to recover multiple layers of biological information and extract insight into the individual and collective behavior of cellular populations. While several recent methods were suggested for biological disentanglement, each has its limitations; they are either task-specific, cannot capture inherent nonlinear or interaction effects, cannot integrate layers of experimental data, or do not provide a general reconstruction procedure. We presentbiolord, a deep generative framework for disentangling known and unknown attributes in single-cell data. Biolord exposes the distinct effects of different biological processes or tissue structure on cellular gene expression. Based on that, biolord allows generating experimentally-inaccessible cell states by virtually shifting cells across time, space, and biological states. Specifically, we showcase accurate predictions of cellular responses to drug perturbations and generalization to predict responses to unseen drugs. Further, biolord disentangles spatial, temporal, and infection-related attributes and their associated gene expression signatures in a single-cell atlas ofPlasmodiuminfection progression in the mouse liver. Biolord can handle partially labeled attributes by predicting a classification for missing labels, and hence can be used to computationally extend an infected hepatocyte population identified at a late stage of the infection to earlier stages. Biolord applies to diverse biological settings, is implemented using the scvi-tools library, and is released as open-source software athttps://github.com/nitzanlab/biolord.
Evaluating Effects of Resting-State Electroencephalography Data Pre-Processing on a Machine Learning Task for Parkinson’s Disease
Authors: Vlieger Robin , Daskalaki Elena , Apthorp Deborah , Lueck Christian J. , Suominen Hanna 
Published: March 2023

AbstractResting-state electroencephalography (RSEEG) is a method under consideration as a potential biomarker that could support early and accurate diagnosis of Parkinson’s disease (PD). RSEEG data is often contaminated by signals arising from other electrophysiological sources and the environment, necessitating pre-processing of the data prior to applying machine learning methods for classification. Importantly, using differing degrees of pre-processing will lead to different classification results. This study aimed to examine this by evaluating the difference in experimental results when using re-referenced data, data that had undergone filtering and artefact rejection, and data without muscle artefact. The results demonstrated that, using a Random Forest Classifier for feature selection and a Support Vector Machine for disease classification, different levels of pre-processing led to markedly different classification results. In particular, the presence of muscle artefact was associated with inflated classification accuracy, emphasising the importance of its removal as part of pre-processing.
Association of magnesium depletion score with cardiovascular disease and its association with longitudinal mortality in cardiovascular disease patients
Authors: Ye Liu , Zhang Cheng , Duan Qin , Shao Yue , Zhou Jianzhong 
Published: March 2023

AbstractBackgroundDietary magnesium and serum magnesium play an important part in cardiovascular disease (CVD). However, the correlation between magnesium depletion score (MDS) and the development and CVD prognosis remains unclear. This analysis examines the cross-sectional relationship between MDS and CVD, and the longitudinal correlation between MDS and all-cause and cardiovascular mortality in CVD individuals.MethodsIn all, 42,711 individuals were selected from the National Health and Nutrition Examination Survey, including 5,015 subjects with CVD. The correlation between MDS and total and individual CVD was examined using the survey-weighted multiple logistic regression analysis. Among 5,011 CVD patients, 2,285 and 927 participants were recorded with all-cause and cardiovascular deaths, respectively. We applied survey-weighted Cox proportional hazards regression analyses to investigate the impact of MDS on the mortality of CVD individuals.ResultsCVD group had higher MDS levels than the non-CVD groups. After controlling all confounding factors, individuals with MDS scored 1-2, and ≥3 had higher odds of total CVD and specific CVD than those with MDS scored 0. The relationship between MDS and total CVD was stable and significant in all subgroups. The fully adjusted Cox regression model presented that the risk of all-cause and cardiovascular deaths increased 2.41 and 2.00 times in participants with MDS≥3 compared to those with MDS scored 0.ConclusionsMDS is a vital risk factor for CVD’s prevalence and all-cause and cardiovascular deaths.What is new?MDS is a significant positive correlation with CVD’s prevalence in US adults.High MDS markedly elevated the risk of all-cause and cardiovascular deaths among participants with CVD.What are the clinical implications?MDS can be used to evaluate the prevention and prognosis of cardiovascular diseases.