bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omnibus and robust deconvolution scheme for bulk RNA sequencing data integrating multiple single-cell reference sets and prior biological knowledge
Authors: Chen Chixiang , Leung Yuk Yee , Ionita Matei , Wang Li-San , Li Mingyao 
Published: August 2022

AbstractMotivationCell-type deconvolution of bulk tissue RNA sequencing (RNA-seq) data is an important step toward understanding the variations in cell-type composition among disease conditions. Owing to recent advances in single-cell RNA sequencing (scRNA-seq) and the availability of large amounts of bulk RNA-seq data in disease-relevant tissues, various deconvolution methods have been developed. However, the performance of existing methods heavily relies on the quality of information provided by external data sources, such as the selection of scRNA-seq data as a reference and prior biological information.ResultsWe present the Integrated and Robust Deconvolution (InteRD) algorithm to infer cell-type proportions from target bulk RNA-seq data. Owing to the innovative use of penalized regression with a new evaluation criterion for deconvolution, InteRD has three primary advantages. First, it is able to effectively integrate deconvolution results from multiple scRNA-seq datasets. Second, InteRD calibrates estimates from reference-based deconvolution by taking into account extra biological information as priors. Third, the proposed algorithm is robust to inaccurate external information imposed in the deconvolution system. Extensive numerical evaluations and real-data applications demonstrate that InteRD yields more accurate and robust cell-type proportion estimates that agree well with known biology.Availability and implementationThe proposed InteRD framework is implemented in R and the package is available at https://cran.r-project.org/web/packages/InteRD/index.html.Supplementary informationSupplementary data are available at Bioinformatics online.
Beacon v2 Reference Implementation: a toolkit to enable federated sharing of genomic and phenotypic data
Authors: Rueda Manuel , Ariosa Roberto , Moldes Mauricio , Rambla Jordi 
Published: August 2022

AbstractSummaryBeacon v2 is an API specification established by the Global Alliance for Genomics and Health initiative (GA4GH) that defines a standard for federated discovery of genomic and phenotypic data. Here, we present the Beacon v2 Reference Implementation (B2RI), a set of open-source software tools that allow lighting up a local Beacon instance ‘out-of-the-box’. Along with the software, we have created detailed ‘Read the Docs’ documentation that includes information on deployment and installation.Availability and implementationThe B2RI is released under GNU General Public License v3.0 and Apache License v2.0. Documentation and source code is available at: https://b2ri-documentation.readthedocs.io.Supplementary informationSupplementary data are available at Bioinformatics online.
CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice
Authors: Li Pengyu , Tang Jielin , Yu Zhixin , Jin Cheng , Wang Zhipeng , Li Mengzhen , Zou Dingfeng , Mang Xinyu , Liu Jun , Lu Yan , Miao Shiying , Wang Linfang , Li Kai , Song Wei 
Published: August 2022

AbstractSpermatogenesis is sustained by homeostatic balance between the self-renewal and differentiation of spermatogonial stem cells, which is dependent on the strict regulation of transcription factor and chromatin modulator gene expression. Chromodomain helicase DNA-binding protein 4 is highly expressed in spermatogonial stem cells but roles in mouse spermatogenesis are not fully understood. Here, we report that the germ-cell-specific deletion of chromodomain helicase DNA-binding protein 4 resulted in complete infertility in male mice, with rapid loss of spermatogonial stem cells and excessive germ cell apoptosis. Chromodomain helicase DNA-binding protein 4-knockdown in cultured spermatogonial stem cells also promoted the expression of apoptosis-related genes and thereby activated the tumor necrosis factor signaling pathway. Mechanistically, chromodomain helicase DNA-binding protein 4 occupies the genomic regulatory region of key apoptosis-related genes, including Jun and Nfkb1. Together, our findings reveal the determinant role of chromodomain helicase DNA-binding protein 4 in spermatogonial stem cells survival in vivo, which will offer insight into the pathogenesis of male sterility and potential novel therapeutic targets.
Effectiveness of melatonin adjuvant treatment in cisplatin to prevent depletion of ovarian follicles in mice: systematic review
Authors: Rodrigues Tairini Damiani , Lima Kellen R , Uggioni Maria Laura R , Ferraz Sarah Dagostin , Cardoso Hemmylly Silveira , Colonetti Tamy , da Rosa Maria Inês 
Published: August 2022

Abstract
Introduction: Cisplatin-based chemotherapy is the standard cancer therapy; however, this treatment causes depletion of ovarian follicles in women of reproductive age. Adjuvant treatment with melatonin can protect the ovaries from oxidative stress, reducing the side effects of chemotherapy. The objective was to evaluate the effects of the use of melatonin on the ovarian follicles of mice treated with cisplatin. Methodology: A systematic review was performed. The search strategy used the terms: “cisplatin”, “melatonin,” and “ovarian”. MEDLINE EMBASE, Cochrane Library, and gray literature (Google Scholar) were used as databases. The search was limited to experimental studies, performed on animals, with no language restrictions. Results: The search identified 30 studies and 5 primary studies, published between 2016 and 2021, and met the inclusion criteria, with a total of 115 mice. For the p-FOX3a/FOXO3a pathway, the meta-analysis showed a standard mean difference (SMD) of −4.79 (95% CI −6.16 to −3.42; P &lt; 0.00001, two studies, 38 mice; I2 = 0%). For the p-PTEN pathway, the meta-analysis showed an SMD of −1.65 (95% CI −2.71 to −0.59; P = 0.002, two studies, 38 mice; I2 = 47%). Conclusion: Melatonin variation in efficacy varies according to the dose used in mice previously exposed to cisplatin. However, melatonin was able to alter the p-PTEN and p-FOX3a/FOXO3a pathways.
The long Filamin-A isoform is required for intestinal development and motility: implications for chronic intestinal pseudo-obstruction
Authors: Zada Almira , Zhao Yuying , Halim Danny , Windster Jonathan , van der Linde Herma C , Glodener Jackleen , Overkleeft Sander , de Graaf Bianca M , Verdijk Robert M , Brooks Alice S , Shepherd Iain , Gao Ya , Burns Alan J , Hofstra Robert M W , Alves Maria M 
Published: August 2022

Abstract
Filamin A (FLNA) is a cytoplasmic actin binding protein, recently shown to be expressed as a long and short isoform. Mutations in FLNA are associated with a wide spectrum of disorders, including an X-linked form of chronic intestinal pseudo-obstruction (CIPO). However, the role of FLNA in intestinal development and function is largely unknown. In this study, we show that FLNA is expressed in the muscle layer of the small intestine from early human fetal stages. Expression of FLNA variants associated with CIPO, blocked expression of the long flna isoform and led to an overall reduction of RNA and protein levels. As a consequence, contractility of human intestinal smooth muscle cells was affected. Lastly, our transgenic zebrafish line showed that the flna long isoform is required for intestinal elongation and peristalsis. Histological analysis revealed structural and architectural changes in the intestinal smooth muscle of homozygous fish, likely triggered by the abnormal expression of intestinal smooth muscle markers. No defect in the localization or numbers of enteric neurons was observed. Taken together, our study demonstrates that the long FLNA isoform contributes to intestinal development and function. Since loss of the long FLNA isoform does not seem to affect the enteric nervous system, it likely results in a myopathic form of CIPO, bringing new insights to disease pathogenesis.
Expansion and mechanistic insights into de novo DEAF1 variants in DEAF1-associated neurodevelopmental disorders
Authors: McGee Stacey R , Rajamanickam Shivakumar , Adhikari Sandeep , Falayi Oluwatosin C , Wilson Theresa A , Shayota Brian J , Cooley Coleman Jessica A , Skinner Cindy , Caylor Raymond C , Stevenson Roger E , Quaio Caio Robledo D' Angioli Costa , Wilke Berenice Cunha , Bain Jennifer M , Anyane-Yeboa Kwame , Brown Kaitlyn , Greally John M , Bijlsma Emilia K , Ruivenkamp Claudia A L , Politi Keren , Arbogast Lydia A , Collard Michael W , Huggenvik Jodi I , Elsea Sarah H , Jensik Philip J 
Published: August 2022

Abstract
De novo deleterious and heritable biallelic mutations in the DNA binding domain (DBD) of the transcription factor deformed epidermal autoregulatory factor 1 (DEAF1) result in a phenotypic spectrum of disorders termed DEAF1-associated neurodevelopmental disorders (DAND). RNA-sequencing using hippocampal RNA from mice with conditional deletion of Deaf1 in the central nervous system indicate that loss of Deaf1 activity results in the altered expression of genes involved in neuronal function, dendritic spine maintenance, development, and activity, with reduced dendritic spines in hippocampal regions. Since DEAF1 is not a dosage-sensitive gene, we assessed the dominant negative activity of previously identified de novo variants and a heritable recessive DEAF1 variant on selected DEAF1-regulated genes in 2 different cell models. While no altered gene expression was observed in cells over-expressing the recessive heritable variant, the gene expression profiles of cells over-expressing de novo variants resulted in similar gene expression changes as observed in CRISPR-Cas9-mediated DEAF1-deleted cells. Altered expression of DEAF1-regulated genes was rescued by exogenous expression of WT-DEAF1 but not by de novo variants in cells lacking endogenous DEAF1. De novo heterozygous variants within the DBD of DEAF1 were identified in 10 individuals with a phenotypic spectrum including autism spectrum disorder, developmental delays, sleep disturbance, high pain tolerance, and mild dysmorphic features. Functional assays demonstrate these variants alter DEAF1 transcriptional activity. Taken together, this study expands the clinical phenotypic spectrum of individuals with DAND, furthers our understanding of potential roles of DEAF1 on neuronal function, and demonstrates dominant negative activity of identified de novo variants.
What establishment expresses
Authors: Ahmed Farrah 
Published: August 2022

Abstract
Religious establishment is said to be wrong partly because of what it expresses. But the typical arguments about what establishment expresses are obscure and ambiguous. This article aims to provide a framework, illustrated by two hypothetical states, to better isolate and understand expressive reasons why establishment might be wrong. The article argues for the disambiguation of expressive claims about establishment, distinguishes between four types of expression, and suggests tests for expression of each type. It illustrates how expressive claims might be contextually assessed using the suggested tests. The article aims to allow lawyers, judges, policymakers, scholars, and members of the public to better understand, assess, and appreciate the moral significance of expressive claims about establishment and, potentially, expressive claims about law and government action more generally.
Using allele scores to identify confounding by reverse causation: studies of alcohol consumption as an exemplar
Authors: Sallis Hannah M , Palmer Tom , Tilling Kate , Davey Smith George , Munafò Marcus R 
Published: August 2022

Abstract

Background
Mendelian randomization (MR) is a form of instrumental variable analysis used to investigate causality using observational data. Another important, although less frequently applied, use of this technique is to investigate confounding due to reverse causality.

Methods
We used a form of reverse MR and data from UK Biobank in a proof-of-principle study to investigate confounding due to reverse causation. Here we focus on the association between alcohol consumption (exposure) and outcomes including educational attainment, and physical and mental health. First, we examined the observational relationship between alcohol consumption and these outcomes. Allele scores were then derived for educational attainment, and physical and mental health, and the association with alcohol consumption (as the outcome) was explored. Sample sizes ranged from 114 941–336 473 in observational analyses and 142 093–336 818 in genetic analyses.

Results
Conventional observational analyses indicated associations between alcohol consumption and a number of outcomes (e.g. neuroticism, body mass index, educational attainment). Analyses using allele scores suggested evidence of reverse causation for several of these relationships (in particular physical health and educational attainment).

Conclusion
Allele scores allow us to investigate reverse causation in observational studies. Our findings suggest that observed associations implying beneficial effects of alcohol consumption may be due to confounding by reverse causation in many cases.
A new genus and species of shrew-like mouse (Rodentia: Muridae) from a new center of endemism in eastern Mindanao, Philippines
Authors: Rowsey Dakota M , Duya Mariano Roy M , Ibañez Jayson C , Jansa Sharon A , Rickart Eric A , Heaney Lawrence R 
Published: August 2022

Abstract
The Philippine archipelago hosts an exceptional diversity of murid rodents that have diversified following several independent colonization events. Here, we report the discovery of a new species of rodent from Mt. Kampalili on eastern Mindanao Island. Molecular and craniodental analyses reveal this species as a member of a Philippine “New Endemic” clade consisting of Tarsomys, Limnomys, and Rattus everetti (tribe Rattini). This new species of “shrew-mouse” is easily distinguished from its relatives in both craniodental and external characteristics including a long, narrow snout; small eyes and ears; short, dark, dense fur dorsally and ventrally; stout body with a tapering, visibly haired tail shorter than head and body length; stout forepaws; bulbous and nearly smooth braincase; narrow, tapering rostrum; short incisive foramina; slender mandible; and narrow, slightly opisthodont incisors. This new genus and species of murid rodent illustrates that murids of the tribe Rattini have exhibited greater species and morphological diversification within the Philippines than previously known and provides evidence that Mt. Kampalili represents a previously unrecognized center of mammalian endemism on Mindanao Island that is deserving of conservation action.
Heterozygous BRCA1 and BRCA2 and Mismatch Repair Gene Pathogenic Variants in Children and Adolescents With Cancer
Authors: Kratz Christian P , Smirnov Dmitrii , Autry Robert , Jäger Natalie , Waszak Sebastian M , Großhennig Anika , Berutti Riccardo , Wendorff Mareike , Hainaut Pierre , Pfister Stefan M , Prokisch Holger , Ripperger Tim , Malkin David 
Published: August 2022

Abstract

Background
Genetic predisposition is has been identified as a cause of cancer, yet little is known about the role of adult cancer predisposition syndromes in childhood cancer. We examined the extent to which heterozygous pathogenic germline variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, MSH2, MSH6, MLH1, and PMS2 contribute to cancer risk in children and adolescents.

Methods
We conducted a meta-analysis of 11 studies that incorporated comprehensive germline testing for children and adolescents with cancer. ClinVar pathogenic or likely pathogenic variants (PVs) in genes of interest were compared with 2 control groups. Results were validated in a cohort of mainly European patients and controls. We employed the Proxy External Controls Association Test to account for different pipelines.

Results
Among 3975 children and adolescents with cancer, statistically significant associations with cancer risk were observed for PVs in BRCA1 and 2 (26 PVs vs 63 PVs among 27 501 controls, odds ratio = 2.78, 95% confidence interval = 1.69 to 4.45; P &lt; .001) and mismatch repair genes (19 PVs vs 14 PVs among 27 501 controls, odds ratio = 7.33, 95% confidence interval = 3.64 to 14.82; P &lt;.001). Associations were seen in brain and other solid tumors but not in hematologic neoplasms. We confirmed similar findings in 1664 pediatric cancer patients primarily of European descent.

Conclusion
These data suggest that heterozygous PVs in BRCA1 and 2 and mismatch repair genes contribute with reduced penetrance to cancer risk in children and adolescents. No changes to predictive genetic testing and surveillance recommendations are required.
The Changing Face of Cancer Surgery During Multiple Waves of COVID-19
Authors: Fu Rui , Kamalraj Pabiththa , Li Qing , Hallet Julie , Gomez David , Sutradhar Rinku , Eskander Antoine 
Published: August 2022

Abstract
COVID-19 has had a detrimental effect on the provision of cancer surgery, but its impact beyond the first 6 months of the pandemic remains unclear. We used data on 799 220 cancer surgeries performed in Ontario, Canada, during 2018-2021 and segmented regression to address this knowledge gap. With the arrival of the first COVID-19 wave (March 2020), mean cancer surgical volume decreased by 57%. Surgical volume then rose by 2.5% weekly and reached prepandemic levels in 8 months. The surgical backlog after the first wave was 47 639 cases. At the beginning of the second COVID-19 wave (January 2021), mean cancer surgical volume dropped by 22%. Afterward, surgical volume did not actively recover (2-sided P = .25), resulting in a cumulative backlog of 66 376 cases as of August 2021. These data urge the strengthening of the surgical system to quickly clear the backlog in anticipation of a tsunami of newly diagnosed cancer patients in need of surgery.
Semi-analytic forecasts for JWST – VI. Simulated light-cones and galaxy clustering predictions
Authors: Yung L Y Aaron , Somerville Rachel S , Ferguson Henry C , Finkelstein Steven L , Gardner Jonathan P , Davé Romeel , Bagley Micaela B , Popping Gergö , Behroozi Peter 
Published: August 2022

ABSTRACT
In anticipation of the new era of high-redshift exploration marked by the commissioning of the James Webb Space Telescope (JWST), we present two sets of galaxy catalogues that are designed to aid the planning and interpretation of observing programs. We provide a set of 40 wide-field light-cones with footprints spanning approximately ∼1000 arcmin2 containing galaxies up to z = 10, and a new set of eight ultradeep light-cones with 132 arcmin2 footprints, containing galaxies up to z ∼ 12 down to the magnitudes expected to be reached in the deepest JWST surveys. These mock light-cones are extracted from dissipationless N-body simulations and populated with galaxies using the well-established, computationally efficient Santa Cruz semi-analytic model for galaxy formation. We provide a wide range of predicted physical properties, and simulated photometry from Near-Infrared Camera (NIRCam) and many other instruments. We explore the predicted counts and luminosity functions and angular two-point correlation functions for galaxies in these simulated light-cones. We also explore the predicted field-to-field variance using multiple light-cone realizations. We find that these light-cones reproduce the available measurements of observed clustering from 0.2 ≲ z ≲ 7.5 very well. We provide predictions for galaxy clustering at high redshift that may be obtained from future JWST observations. All of the light-cones presented here are made available through a web-based interactive data release portal.
Markov state models elucidate the stability of DNA influenced by the chiral 5S-Tg base
Authors: Wang Shu-dong , Zhang Ru-bo , Eriksson Leif A 
Published: August 2022

AbstractThe static and dynamic structures of DNA duplexes affected by 5S-Tg (Tg, Thymine glycol) epimers were studied using MD simulations and Markov State Models (MSMs) analysis. The results show that the 5S,6S-Tg base caused little perturbation to the helix, and the base-flipping barrier was determined to be 4.4 kcal mol−1 through the use of enhanced sampling meta-eABF calculations, comparable to 5.4 kcal mol−1 of the corresponding thymine flipping. Two conformations with the different hydrogen bond structures between 5S,6R-Tg and A19 were identified in several independent MD trajectories. The 5S,6R-Tg:O6HO6•••N1:A19 hydrogen bond is present in the high-energy conformation displaying a clear helical distortion, and near barrier-free Tg base flipping. The low-energy conformation always maintains Watson–Crick base pairing between 5S,6R-Tg and A19, and 5S-Tg base flipping is accompanied by a small barrier of ca. 2.0 KBT (T = 298 K). The same conformations are observed in the MSMs analysis. Moreover, the transition path and metastable structures of the damaged base flipping are for the first time verified through MSMs analysis. The data clearly show that the epimers have completely different influence on the stability of the DNA duplex, thus implying different enzymatic mechanisms for DNA repair.
Evaluating data integrity in ribosome footprinting datasets through modelled polysome profiles
Authors: Hedayioglu Fabio , Mead Emma J , O'Connor Patrick B F , Skiotys Matas , Sansom Owen J , Mallucci Giovanna R , Willis Anne E , Baranov Pavel V , Smales C Mark , von der Haar Tobias 
Published: August 2022

Abstract
The assessment of transcriptome-wide ribosome binding to mRNAs is useful for studying the dynamic regulation of protein synthesis. Two methods frequently applied in eukaryotic cells that operate at different levels of resolution are polysome profiling, which reveals the distribution of ribosome loads across the transcriptome, and ribosome footprinting (also termed ribosome profiling or Ribo-Seq), which when combined with appropriate data on mRNA expression can reveal ribosome densities on individual transcripts. In this study we develop methods for relating the information content of these two methods to one another, by reconstructing theoretical polysome profiles from ribosome footprinting data. Our results validate both approaches as experimental tools. Although we show that both methods can yield highly consistent data, some published ribosome footprinting datasets give rise to reconstructed polysome profiles with non-physiological features. We trace these aberrant features to inconsistencies in RNA and Ribo-Seq data when compared to datasets yielding physiological polysome profiles, thereby demonstrating that modelled polysomes are useful for assessing global dataset properties such as its quality in a simple, visual approach. Aside from using polysome profile reconstructions on published datasets, we propose that this also provides a useful tool for validating new ribosome footprinting datasets in early stages of analyses.