bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pangenome graph layout by Path-Guided Stochastic Gradient Descent
Authors: Heumos Simon , Guarracino Andrea , Schmelzle Jan-Niklas M. , Li Jiajie , Zhang Zhiru , Hagmann Jörg , Nahnsen Sven , Prins Pjotr , Garrison Erik 
Published: September 2023

AbstractMotivationThe increasing availability of complete genomes demands for models to study genomic variability within entire populations. Pangenome graphs capture the full genomic similarity and diversity between multiple genomes. In order to understand them, we need to see them. For visualization, we need a human readable graph layout: A graph embedding in low (e.g. two) dimensional depictions. Due to a pangenome graph’s potential excessive size, this is a significant challenge.ResultsIn response, we introduce a novel graph layout algorithm: the Path-Guided Stochastic Gradient Descent (PG-SGD). PG-SGD uses the genomes, represented in the pangenome graph as paths, as an embedded positional system to sample genomic distances between pairs of nodes. This avoids the quadratic cost seen in previous versions of graph drawing by Stochastic Gradient Descent (SGD). We show that our implementation efficiently computes the low dimensional layouts of gigabase-scale pangenome graphs, unveiling their biological features.AvailabilityWe integrated PG-SGD inODGIwhich is released as free software under the MIT open source license. Source code is available athttps://github.com/pangenome/odgi.Contactegarris5@uthsc.edu
Phylociraptor – A unified computational framework for reproducible phylogenomic inference
Authors: Resl Philipp , Hahn Christoph 
Published: September 2023

AbstractMulti-stage phylogenomic analyses require complex computational environments. A unified framework for software- and parameter space exploration, data organisation and -deposition is currently lacking. We present phylociraptor (https://github.com/reslp/phylociraptor), a pipeline facilitating fast, reliable, portable (containerized), and reproducible phylogenomics. We demonstrate phylociraptor’s utility and uncover topological discrepancies associated with software and parameter choices in large-scale datasets (31-101 species, 241-2894 genes) addressing enigmatic questions in fungal and vertebrate evolution.
Apoptosis-coupled senescence causes cancer cell senotherapy
Authors: Youn Byung-Soo 
Published: September 2023

AbstractAlthough new generations of anti-cancer modalities have been accumulated involving immuno-oncology cancers remain prevailing. This implies the current understanding of cancer cell biology is far from satisfactory. Curation of cancers is extremely rare. We hypothesized what could be the easiest Achilles’ Hill of cancer cells such that simple administration can jab cancer cells to be knocked out. Of conspicuous differences between cancer cells and normal cells, for example, metabolism, hypoxia, anaerobic glycolysis, uncontrolled cell proliferation, etc. exist. What could be the easiest and the most reliable anti-cancer modalities? We discovered one was cancer cell senescence (CCS) because cancer cells are the most presenescent (old) cells. We utilized a synthetic polyphenol designated as ONG41008. ONG41008 was able to induce massive senescence of pathologic myofibroblasts (pMFBs) and a vast majority of representative human cancer cells as well as a line of primary NSCLCs. All these cells turned out to be senescence-associated beta-galactosidase (SAbGAL) positive to different degrees, which does not mean real senescence is occurring in these cells. ONG41008 did not harm normal cells and elicited massive senescence in pMFBs without apoptosis. However, ONG41008 caused massive senescence as well as apoptosis in cancer cells. In other words, ONG41008 was capable of sensing intracellular molecular environments between normal cells, cancer cells, and pMFBs. This molecular recognition capability prompted us to explore how ONG4008 behaved on A549 (a human lung adenocarcinoma), PANC1(malignant human ductal adenocarcinoma), and mdr+PC3 (multidrug-resistant human prostate cancer). TP53, p21, and p16 were induced and/or nuclear relocated, suggesting that ONG41008 was recognized by these cells. ONG41008 drove A549 and PANC1 at G2/M phase arrest during 48 hrs, resulting in massive mitotic collapse. All cells died. Moreover, the cisplatin-resistant mdr+PC3 was also eliminated by ONG41008. An array of common components of apoptosis were activated, and especially, induction of Mcl1 was especially notable. These senolytics features were reported to oncogene-induced-senescence (OIS), in which the expression of over two activated oncogenes in the embryonic fibroblasts caused massive senescence and cell death as well. And the signature expression of Mcl1, an anti-apoptotic protein (a long form), was notable but two kinds of short forms are pro-apoptotic proteins. OIS was conductedin vitrocell culture models and whether or not the presence of OIS counterpartin vivoremains to be delineated.Taken together, we discovered a synthetic polyphenol referred to as ONG41008 was both senogenic and senolytic and its senescent impacts may make the cell cycles of the ONG41008-treated cancer cells immensely arrested at the G2/M phase, leading to mitotic slippage and cell death. This interesting observation may be able to create an idealistic anti-cancer modality, specifically killing cancer cells, but normal cells remain unharmed.
Global assessment of effective population sizes: consistent taxonomic differences in meeting the 50/500 rule
Authors: Clarke Shannon H. , Lawrence Elizabeth R. , Matte Jean-Michel , Gallagher Brian K. , Salisbury Sarah J. , Michaelides Sozos N. , Koumrouyan Ramela , Ruzzante Daniel E. , Grant James W.A. , Fraser Dylan J. 
Published: September 2023

AbstractEffective population size (Ne) is a particularly useful metric for conservation as it affects genetic drift, inbreeding and adaptive potential within populations. Current guidelines recommend a minimumNeof 50 and 500 to avoid short-term inbreeding and to preserve long-term adaptive potential, respectively. However, the extent to which wild populations reach these thresholds globally has not been investigated, nor has the relationship betweenNeand human activities. Through a quantitative review, we generated a dataset with 4145 georeferencedNeestimates from 3576 unique populations, extracted from 712 articles. These data show that certain taxonomic groups are less likely to meet 50/500 thresholds and are disproportionately impacted by human activities; plant, mammal, and amphibian populations had a ≤52% probability of reachingN̂e= 50 and a <5% probability of reachingN̂e= 500. Populations listed as being of conservation concern according to the IUCN Red List had a lowerN̂ethan unlisted populations, and this relationship held true across all taxonomic groups.N̂ewas reduced in areas with a greater Global Human Footprint, especially for amphibians and mammals, however relationships varied between taxa. We also highlight several considerations for future works estimatingN̂e, including the role that gene flow and subpopulation structure plays in the estimation ofN̂ein wild populations, and the need for finer-scale taxonomic analyses. Our findings provide guidance for more specific thresholds based onNeand help prioritize assessment of populations from taxa most at risk of failing to meet conservation thresholds.
Integrative pan-cancer analysis reveals a common architecture of dysregulated transcriptional networks characterized by loss of enhancer methylation
Authors: Ankill Jørgen , Zhao Zhi , Tekpli Xavier , Kure Elin H. , Kristensen Vessela N. , Mathelier Anthony , Fleischer Thomas 
Published: September 2023

AbstractAberrant DNA methylation contributes to gene expression deregulation in cancer. However, these alterations’ precise regulatory role and clinical implications are still not fully understood. In this study, we performed expression-methylation Quantitative Trait Loci (emQTL) analysis to identify deregulated cancer-driving transcriptional networks linked to CpG demethylation pan-cancer. By analyzing 33 cancer types from The Cancer Genome Atlas, we identified and confirmed significant correlations between CpG methylation and gene expression (emQTL) incisandtrans, both across and within cancer types. Bipartite network analysis of the emQTL revealed groups of CpGs and genes related to important biological processes involved in carcinogenesis; specifically, we identified three types of emQTL networks associated with alterations linked to the regulation of proliferation, metabolism, and hormone-signaling. These bipartite communities were characterized by loss of enhancer methylation in transcription factor binding regions (TFBRs) located in enhancers. The underlying CpGs were topologically linked to upregulated genes through chromatin loops. Loss of enhancer methylation and target genes were exemplified in pancreatic cancer. Penalized Cox regression analysis showed a significant prognostic impact of the pan-cancer emQTL. Taken together, our integrative pan-cancer analysis reveals a common architecture of aberrant DNA demethylation that illustrates a convergence of pathological regulatory mechanisms across cancer types.
RGS2 is an innate immune checkpoint for TLR4 and Gαq-mediated IFNγ generation and lung injury
Authors: Joshi Jagdish Chandra , Joshi Bhagwati , Zhang Cuiping , Banerjee Somenath , Vellingiri Vigneshwaran , Raghunathrao Vijay Avin Balaji , Zhang Lianghui , Amin Ruhul , Song Yuanlin , Mehta Dolly 
Published: September 2023

SummaryIFNγ, a type II interferon secreted by immune cells, augments tissue responses to injury following pathogenic infections leading to lethal acute lung injury (ALI). Alveolar macrophages (AM) abundantly express Toll-like receptor-4 and represent the primary cell type of the innate immune system in the lungs. A fundamental question remains whether AM generation of IFNg leads to uncontrolled innate response and perpetuated lung injury. LPS induced a sustained increase in IFNg levels and unresolvable inflammatory lung injury in the mice lacking RGS2 but not in RGS2 null chimeric mice receiving WT bone marrow or receiving the RGS2 gene in AM. Thus, indicating RGS2 serves as a gatekeeper of IFNg levels in AM and thereby lung’s innate immune response. RGS2 functioned by forming a complex with TLR4 shielding Gaq from inducing IFNg generation and AM inflammatory signaling. Thus, inhibition of Gaq blocked IFNg generation and subverted AM transcriptome from being inflammatory to reparative type in RGS2 null mice, resolving lung injury.HighlightsRGS2 levels are inversely correlated with IFNγ in ARDS patient’s AM.RGS2 in alveolar macrophages regulate the inflammatory lung injury.During pathogenic insult RGS2 functioned by forming a complex with TLR4 shielding Gαq from inducing IFNγ generation and AM inflammatory signaling.eToc BlurbAuthors demonstrate an essential role of RGS2 in macrophages in airspace to promoting anti-inflammatory function of alveolar macrophages in lung injury. The authors provided new insight into the dynamic control of innate immune response by Gαq and RGS2 axis to prevent ALI.
Neutron Scattering Analysis ofCryptococcus neoformansPolysaccharide Reveals Solution Rigidity and Repeating Fractal-like Structural Patterns
Authors: Wang Ziwei , Teixeira Susana C. M. , Strother Camilla , Bowen Anthony , Casadevall Arturo , Cordero Radamés JB 
Published: September 2023

ABSTRACTCryptococcus neoformansis a fungal pathogen that can cause life-threatening brain infections in immunocompromised individuals. Unlike other fungal pathogens, it possesses a protective polysaccharide capsule that is crucial for its virulence. During infections,Cryptococcuscells release copious amounts of extracellular polysaccharides (exo-PS) that interfere with host immune responses. Both exo-PS and capsular-PS play pivotal roles inCryptococcusinfections and serve as essential targets for disease diagnosis and vaccine development strategies. However, understanding their structure is complicated by their polydispersity, complexity, sensitivity to sample isolation and processing, and scarcity of methods capable of isolating and analyzing them while preserving their native structure. In this study, we employ small-angle neutron scattering (SANS) and ultra-small angle neutron scattering (USANS) for the first time to investigate both fungal cell suspensions and extracellular polysaccharides in solution. Our data suggests that exo- PS in solution exhibits collapsed chain-like behavior and demonstrates mass fractal properties that indicate a relatively condensed pore structure in aqueous environments. This observation is also supported by scanning electron microscopy (SEM). The local structure of the polysaccharide is characterized as a rigid rod, with a length-scale corresponding to 3 to 4 repeating units. This research not only unveils insights into exo-PS and capsular-PS structures but also demonstrates the potential of USANS for studying changes in cell dimensions and the promise of contrast variation in future neutron scattering studies.
Annotated Compendium of 102 Breast Cancer Gene-Expression Datasets
Authors: Nwosu Ifeanyichukwu O. , Tabler Daniel D. , Chipman Greg , Piccolo Stephen R. 
Published: September 2023

AbstractTranscriptomic data from breast-cancer patients are widely available in public repositories. However, before a researcher can perform statistical inferences or make biological interpretations from such data, they must find relevant datasets, download the data, and perform quality checks. In many cases, it is also useful to normalize and standardize the data for consistency and to use updated genome annotations. Additionally, researchers need to parse and interpret metadata: clinical and demographic characteristics of patients. Each of these steps requires computational and/or biomedical expertise, thus imposing a barrier to reuse for many researchers. We have identified and curated 102 publicly available, breast-cancer datasets representing 17,151 patients. We created a reproducible, computational pipeline to download the data, perform quality checks, renormalize the raw gene-expression measurements (when available), assign gene identifiers from multiple databases, and annotate the metadata against the National Cancer Institute Thesaurus, thus making it easier to infer semantic meaning and compare insights across datasets. We have made the curated data and pipeline freely available for other researchers to use. Having these resources in one place promises to accelerate breast-cancer research, enabling researchers to address diverse types of questions, using data from a variety of patient populations and study contexts.
Genome-wide association mapping of bruchid resistance loci in soybean
Authors: Mukuze Clever , Msiska Ulemu M. , Badji Afang , Obua Tonny , Kweyu Sharon V. , Nghituwamhata Selma N. , Rono Evalyne C. , Maphosa Mcebisi , Kasule Faizo , Tukamuhabwa Phinehas 
Published: September 2023

AbstractSoybean is a globally important industrial, food, and cash crop. Despite its importance in present and future economies, its production is severely hampered by bruchids (Callosobruchus chinensis), a destructive storage insect pest, causing considerable yield losses. Therefore, the identification of genomic regions and candidate genes associated with bruchid resistance in soybean is crucial as it helps breeders develop new soybean varieties with improved resistance and quality. In this study, 6 multi-locus methods of the mrMLM model for genome-wide association study were used to dissect the genetic architecture of bruchid resistance using 5 traits: percentage adult bruchid emergence (PBE), percentage weight loss (PWL), growth index (GI), median development period (MDP), and Dobie susceptibility index (DSI) on 100 diverse soybean genotypes, genotyped with 14,469 single-nucleotide polymorphism (SNP) markers. Using the best linear unbiased predictors (BLUPs), 13 quantitative trait nucleotides (QTNs) were identified by the mrMLM model, 3 of which, rs16_14976250, rs1_22916615, and rs16_14975721, were associated with more than 1 bruchid resistance trait. As a result, the identified QTNs linked with resistance traits can be employed in marker-assisted breeding for the accurate and rapid screening of soybean genotypes for resistance to bruchids. Moreover, a gene search on the Phytozome soybean reference genome identified 27 potential candidate genes located within a window of 478.45 kb upstream and downstream of the most reliable QTNs. These candidate genes exhibit molecular and biological functionalities associated with various soybean resistance mechanisms and, therefore, could be incorporated into the farmers’ preferred soybean varieties that are susceptible to bruchids.
Development of the terminal airspaces in the Gray short-tailed opossum (Monodelphis domestica) – 3 D reconstruction by microcomputed tomography
Authors: Ferner Kirsten 
Published: September 2023

AbstractMarsupials are born with structurally immature lungs when compared to eutherian mammals. The Gray short-tailed opossum (Monodelphis domestica) is born at the late canalicular stage of lung development. Despite the high degree of immaturity, the lung is functioning as respiratory organ, however supported by the skin for gas exchange during the first postnatal days. Consequently, the majority of lung development takes place in ventilated functioning state during the postnatal period.X-ray computed tomography (µCT) was used to three-dimensionally reconstruct the terminal airspaces in order to reveal the timeline of lung morphogenesis. In addition, lung and air space volume as well as surface area were determined to assess the functional relevance of the structural changes in the developing lung. The development of the terminal air spaces was examined in 35 animals from embryonic day 13, during the postnatal period (neonate to 57 days) and in adults. At birth, the lung ofM. domesticaconsists of few large terminal air spaces, which are poorly subdivided and open directly from short lobar bronchioles. During the first postnatal week the number of smaller terminal air spaces increases and numerous septal ridges indicate a process of subdivision, attaining the saccular stage by 7 days. The 3 D reconstructions of the terminal air spaces demonstrated massive increases in air sac number and architectural complexity during the postnatal period. Between 28 and 35 days alveolarization started. Respiratory bronchioles, alveolar ducts and a typical acinus developed. With alveolarization the volume of the air spaces and the surface area for gas exchange increased markedly. The structural transformation from large terminal sacs to the final alveolar lung in the Gray short-tailed opossum follows similar patterns as described in other marsupial and placental mammals. The processes involved in sacculation and alveolarization during lung development seem to be highly conservative within mammalian evolution.
Evaluating and Improving Health Equity and Fairness of Polygenic Scores
Authors: Zhang Tianyu , Klei Lambertus , Liu Peng , Chouldechova Alexandra , Roeder Kathryn , G’Sell Max , Devlin Bernie 
Published: September 2023

AbstractPolygenic scores (PGS) are quantitative metrics for predicting phenotypic values, such as human height or disease status. Some PGS methods require only summary statistics of a relevant genome-wide association study (GWAS) for their score. One such method is Lassosum, which inherits the model selection advantages of Lasso to select a meaningful subset of the GWAS single nucleotide polymorphisms as predictors from their association statistics. However, even efficient scores like Lassosum, when derived from European-based GWAS, are poor predictors of phenotype for subjects of non-European ancestry; that is, they have limited portability to other ancestries. To increase the portability of Lassosum, when GWAS information and estimates of linkage disequilibrium are available for both ancestries, we propose Joint-Lassosum. In the simulation settings we explore, Joint-Lassosum provides more accurate PGS compared with other methods, especially when measured in terms of fairness. Like all PGS methods, Joint-Lassosum requires selection of predictors, which are determined by data-driven tuning parameters. We describe a new approach to selecting tuning parameters and note its relevance for model selection for any PGS. We also draw connections to the literature on algorithmic fairness and discuss how Joint-Lassosum can help mitigate fairness-related harms that might result from the use of PGS scores in clinical settings. While no PGS method is likely to be universally portable, due to the diversity of human populations and unequal information content of GWAS for different ancestries, Joint-Lassosum is an effective approach for enhancing portability and reducing predictive bias.
Antifungal efficacy of natural antiseptic products againstCandida auris
Authors: Wu Wing-Gi , Luk Kristine Shik , Hung Mei-Fan , Tsang Wing-Yi , Lee Kin-Ping , Lam Bosco Hoi-Shiu , Cheng Ka-Lam , Cheung Wing-Sze , Tang Hau-Ling , To Wing-Kin 
Published: September 2023

ABSTRACTCandida aurisis an emerging fungal pathogen responsible for healthcare associated infections and outbreaks with high mortality around the world. It readily colonizes the skin, nares, respiratory and urinary tract of hospitalized patients, and such colonization may lead to invasiveCandidainfection in susceptible patients. However, there is no recommended decolonization protocol forC. aurisby international health authorities. The aim of this study is to evaluate the susceptibility ofC. auristo commonly used synthetic and natural antiseptic products using an in vitro, broth microdilution assay. Synthetic antiseptics including chlorhexidine, povidone-iodine, and nystatin were shown to be fungicidal againstC. auris. Among the natural antiseptics tested, tea tree oil and manuka oil were both fungicidal againstC. aurisat concentrations less than or equal to 1.25% (v/v). Manuka honey inhibitedC. aurisat 25% (v/v) concentrations. Among the commercial products tested, manuka body wash and mouthwash were fungicidal againstC. aurisat concentrations less than or equal to 0.39% (w/v) and 6.25% (v/v) of products as supplied for use, respectively, while tea tree body wash and MedihoneyTMwound gel demonstrated fungistatic properties. In conclusion, this study demonstrated good in vitro antifungal efficacy of tea tree oil, manuka oil, manuka honey, and commercially available antiseptic products containing these active ingredients. Future studies are warranted to evaluate the effectiveness of these antiseptic products in clinical settings.