bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of cardiovascular disease after a diagnosis of common psychiatric disorders: a matched cohort study of disease susceptibility and progression trajectory in the UK Biobank
Authors: Han Xin , Zeng Yu , Shang Yannan , Hu Yao , Hou Can , Yang Huazhen , Chen Wenwen , Ying Zhiye , Sun Yajing , Qu Yuanyuan , Wang Junren , Zhang Wei , Fang Fang , Valdimarsdóttir Unnur A. , Song Huan 
Published: September 2021

AbstractBackgroundWhether associations between psychiatric disorders and cardiovascular diseases (CVDs) can be modified by disease susceptibility and the temporal pattern of these associated CVDs remain unknown.MethodsWe conducted a matched cohort study of UK Biobank including 35,227 patients with common psychiatry disorders (anxiety, depression, and stress-related disorders) between 1997 and 2019, together with 176,135 sex- and birth year-individually matched unexposed individuals.ResultsThe mean age at the index date was 51.76 years, and 66.0% of participants were females. During a mean follow-up of 11.94 years, we observed an elevated risk of CVD among patients with studied psychiatry disorders, compared with matched unexposed individuals (hazard ratios [HRs]=1.16, 95% confidence interval [CI]: 1.14-1.19), especially during the first six months of follow-up (HR=1.59 [1.42-1.79]). To assess the modification role of disease susceptibility, we stratified analyses by family history of CVD and by CVD PRS, which obtained similar estimates between subgroups with different susceptibilities to CVD. We conducted trajectory analysis to visualize the temporal pattern of CVDs after common psychiatry disorders, identifying primary hypertension, acute myocardial infarction, and stroke as three main intermediate steps leading to further increased risk of other CVDs.ConclusionsThe association between common psychiatry disorders and subsequent CVD is not modified by predisposition to CVD. Hypertension, acute myocardial infarction, and stroke are three initial CVDs linking psychiatric disorders to other CVD squeals, highlighting a need of timely intervention on these targets to prevent further CVD squeals among all individuals with common psychiatric disorders.
Mutational signature profiling classifies subtypes of clinically different mismatch repair deficient tumors with a differential immunogenic response potential
Authors: Giner-Calabuig Mar , De Leon Seila , Wang Julian , Fehlmann Tara D , Ukaegbu Chinedu , Gibson Joanna , Fernandez Miren Alustiza , Pico Maria-Dolores , Alenda Cristina , Herraiz Maite , Carrillo-Palau Marta , Salces Inmaculada , Reyes Josep , Ortega Silvia P , Obrador Antònia , Cecchini Michael , Syngal Sapna , Stoffel Elena , Ellis Nathan A , Sweasy Joann , Jover Rodrigo , Llor Xavier , Xicola Rosa M 
Published: September 2021

ABSTRACTBackgroundMismatch repair (MMR) deficiency is the hallmark of tumors from Lynch syndrome (LS), sporadicMLH1hypermethylated, and Lynch-like syndrome (LLS), but there is a lack of understanding of the variability in their mutational profiles based on clinical phenotypes. The aim of this study was to perform a molecular characterization to identify novel features that can impact tumor behavior and clinical management.MethodsWe tested 105 MMR-deficient colorectal cancer tumors (25 LS, 35 LLS, and 45 sporadic) for global exome microsatellite instability, cancer mutational signatures, mutational spectrum and neoepitope load.Results78% of tumors showed high contribution of MMR-deficient mutational signatures, high level of global exome microsatellite instability, loss of MLH1/PMS2 protein expression and included sporadic tumors. 22% of tumors showed weaker features of MMR deficiency, 73% lost MSH2/MSH6 expression and included half of LS and LLS tumors. Remarkably, 9% of all tumors lacked global exome microsatellite instability. Lastly, HLA-B07:02 could be triggering the neoantigen presentation in tumors that show the strongest contribution of MMR-deficient tumors.ConclusionsNext-generation sequencing approaches allow for a granular molecular characterization of MMR-deficient tumors, which can be essential to properly diagnose and treat patients with these tumors in the setting of personalized medicine.
M-Phase oscillations in PP1 activity are essential for accurate progression through mammalian oocyte meiosis
Authors: Camlin Nicole J. , Venkatachalam Ilakkiya , Evans Janice P. 
Published: September 2021

AbstractTightly controlled fluctuations in kinase and phosphatase activity play important roles in regulating M-Phase transitions. Protein Phosphatase 1 (PP1) is one of these phosphatases, with oscillations in PP1 activity driving mitotic M-Phase. Evidence from a variety of experimental systems also points to roles in meiosis. Here we report that PP1 is important for M-Phase transitions through mouse oocyte meiosis. We employed a unique small-molecule approach to inhibit or activate PP1 at distinct phases of mouse oocyte meiosis. These studies show that temporal control of PP1 activity is essential for G2/M transition, metaphase I/anaphase I transition, and the formation of a normal metaphase II oocyte. Our data also reveal that inappropriate activation of PP1 is more deleterious at G2/M transition than at prometaphase I-to-metaphase I, and that an active pool of PP1 during prometaphase is vital for metaphase I/anaphase I transition and metaphase II chromosome alignment. Taken together, these results establish that loss of oscillations in PP1 activity causes a range of severe meiotic defects, pointing to essential roles for PP1 in female fertility, and more broadly, M-Phase regulation.Summary statementAltering the normal cyclical activity of the phosphatase PP1 in oocytes causes a range of severe meiotic defects, pointing to essential roles for PP1 in M-Phase entry, progression, and exit.
Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice
Authors: Doms Shauni , Fokt Hanna , Rühlemann Malte Christoph , Chung Cecilia J. , Künstner Axel , Ibrahim Saleh , Franke Andre , Turner Leslie M. , Baines John F. 
Published: September 2021

AbstractDetermining the forces that shape diversity in host-associated bacterial communities is critical to understanding the evolution and maintenance of metaorganisms. To gain deeper understanding of the role of host genetics in shaping gut microbial traits, we employed a powerful genetic mapping approach using inbred lines derived from the hybrid zone of two incipient house mouse species. Further, we uniquely performed our analysis on microbial traits measured at the gut mucosal interface, which is in more direct contact with host cells and the immune system. A high number of mucosa-associated bacterial taxa have significant heritability estimates; heritabilities are greater for 16S rRNA transcript-compared to gene copy-based traits, and interestingly, are positively correlated with cospeciation rate estimates. Genomewide association mapping identifies 443 loci influencing 123 taxa, with narrow genomic intervals pinpointing promising candidate genes and pathways. Importantly, we identified an enrichment of candidate genes associated with several human diseases, including inflammatory bowel disease, and functional categories including innate immunity and G-protein-coupled receptors. These results highlight key features of the genetic architecture of mammalian host-microbe interactions and how they diverge as new species form.
Molecular insights into the inhibition of glutamate dehydrogenase (GDH) by the dicarboxylic acid metabolites
Authors: Godsora Barsa Kanchan Jyotshna , Prakash Prem , Punekar Narayan S. , Bhaumik Prasenjit 
Published: September 2021

AbstractGlutamate dehydrogenase (GDH) is a salient metabolic enzyme which catalyzes the NAD+ - or NADP+-dependent reversible conversion of α-ketoglutarate (AKG) to L-glutamate; and thereby connects the carbon and nitrogen metabolism cycles in all living organisms. The function of GDH is extensively regulated by both metabolites (citrate, succinate, etc.) and non-metabolites (ATP, NADH, etc.) but sufficient molecular evidences are lacking to rationalize the inhibitory effects by the metabolites. We have expressed and purified NADP+-dependent Aspergillus terreus GDH (AtGDH) in recombinant form. Succinate, malonate, maleate, fumarate and tartrate independently inhibit the activity of AtGDH to different extents. The crystal structures of AtGDH complexed with the dicarboxylic acid metabolites and the coenzyme NADPH have been determined. Although AtGDH structures are not complexed with substrate; surprisingly, they acquire super closed conformation like previously reported for substrate and coenzyme bound catalytically competent Aspergillus niger GDH (AnGDH). These dicarboxylic acid metabolites partially occupy the same binding pocket as substrate; but interact with varying polar interactions and the coenzyme NADPH binds to the Domain-II of AtGDH. The low inhibition potential of tartrate as compared to other dicarboxylic acid metabolites is due to its weaker interactions of carboxylate groups with AtGDH. Our results suggest that the length of carbon skeleton and positioning of the carboxylate groups of inhibitors between two conserved lysine residues at the GDH active site might be the determinants of their inhibitory potency. Molecular details on the dicarboxylic acid metabolites bound AtGDH active site architecture presented here would be applicable to GDHs in general.
Unidirectional Single-File Transport of Full-Length Proteins Through a Nanopore
Authors: Yu Luning , Kang Xinqi , Li Fanjun , Mehrafrooz Behzad , Makhamreh Amr , Fallahi Ali , Foster Joshua C. , Aksimentiev Aleksei , Chen Min , Wanunu Meni 
Published: September 2021

AbstractNanopore sensors could revolutionize single-molecule proteomics by providing a means for identification of known proteins through fingerprinting or by de novo sequencing. However, the complex chemical and physical properties of proteins present multiple challenges to the conventional nanopore sensing method, predominantly, the single-file threading of a protein chain into a nanopore and its transport through it. Herein we describe a general approach for realizing unidirectional transport of full-length proteins through nanopores. We show that the combination of a chemically resistant biological nanopore platform and a high concentration guanidinium chloride buffer enables protein unfolding and unidirectional transport through a pore, propelled by an electroosmotic effect that largely owes to the guanidinium chloride presence. The uniform and slow (~10 µs/amino acid) single-file transport, when combined with supervised machine learning of the electrical current signatures obtained, allows us to use to discern the protein threading orientation and identity. In conjunction with a method for tail-modification of native proteins and higher-resolution nanopores, our approach could offer a path towards direct single-molecule protein fingerprinting without the requirement of a motor enzyme.
Comprehensive analysis of mutational signatures in pediatric cancers
Authors: Thatikonda Venu , Islam S. M. Ashiqul , Jones Barbara C. , Gröbner Susanne N. , Warsow Gregor , Hutter Barbara , Huebschmann Daniel , Fröhling Stefan , Blattner-Johnson Mirjam , Jones David T.W. , Alexandrov Ludmil B. , Pfister Stefan M. , Jäger Natalie 
Published: September 2021

AbstractAnalysis of mutational signatures can reveal the underlying molecular mechanisms of the processes that have imprinted the somatic mutations found in a cancer genome. Here, we present a pan-cancer mutational signatures analysis of single base substitutions (SBS) and small insertion and deletions (ID) in pediatric cancers encompassing 537 whole genome sequenced tumors from 20 molecularly defined cancer subtypes. We identified only a small number of mutational signatures active in pediatric cancers when compared to the previously analyzed adult cancers. Further, we report a significant difference in the proportion of pediatric tumors which show homologous recombination repair defect signature SBS3 compared to prior analyses. Correlating genomic alterations with signature activities, we identified an association of TP53 mutation status with substitution signatures SBS2, SBS8, SBS13 and indel signatures ID2 and ID9, as well as chromothripsis associated with SBS8, SBS40 and ID9. This analysis provides a systematic overview of COSMIC v.3 SBS and ID mutational signatures active across pediatric cancers, which is highly relevant for understanding tumor biology as well as enabling future research in defining biomarkers of treatment response.
The relationships between women’s reproductive factors: a Mendelian randomization analysis
Authors: Prince Claire , Sharp Gemma C , Howe Laura D , Fraser Abigail , Richmond Rebecca C 
Published: September 2021

AbstractBackgroundWomen’s reproductive factors include their age at menarche and menopause, the age at which they start and stop having children, and the number of children they have. Studies that have linked these factors with disease risk have largely investigated individual reproductive factors and have not considered the genetic correlation and total interplay that may occur between them. This study aimed to investigate the nature of the relationships between eight female reproductive factors.MethodsWe used data from the UK Biobank and genetic consortia with data available for the following reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age at first sex and lifetime number of sexual partners. Linkage disequilibrium score regression (LDSC) was performed to investigate the genetic correlation between reproductive factors. We then applied Mendelian randomization (MR) methods to estimate the causal relationships between these factors. Sensitivity analyses were used to investigate directionality of the effects, test for evidence of pleiotropy and account for sample overlap.ResultsLDSC indicated that most reproductive factors are genetically correlated (rg range: |0.06 – 0.94|), though there was little evidence for genetic correlations between lifetime number of sexual partners and age at last birth, number of births and ever being parous (rg < 0.01). MR revealed potential causal relationships between many reproductive factors, including later age at menarche (1 SD increase) leading to a later age at first sexual intercourse (Beta (B)=0.09 SD, 95% confidence intervals (CI)=0.06,0.11), age at first birth (B=0.07 SD, CI=0.04,0.10), age at last birth (B=0.06 SD, CI=0.04,0.09) and age at menopause (B=0.06 SD, CI=0.03,0.10). Later age at first birth was found to lead to a later age at menopause (B=0.21 SD, CI=0.13,0.29), age at last birth (B=0.72 SD, CI=0.67,0.77) and a lower number of births (B=-0.38 SD, CI=-0.44,-0.32).ConclusionThis study presents evidence that women’s reproductive factors are genetically correlated and causally related. Future studies examining the health sequelae of reproductive factors should consider a woman’s entire reproductive history, including the causal interplay between reproductive factors.
World Science against COVID-19: Gender and Geographical Distribution of Research
Authors: González-Álvarez Julio 
Published: September 2021

AbstractIn just a year and a half, an enormous volume of scientific research has been generated throughout the world to study a virus/disease that turned into a pandemic. All the articles on COVID-19 or SARS-CoV-2 included in the SCI-EXPANDED database (Web of Science), signed by more than a third of a million of authorships, were analyzed. Gender could be identified in 92% of the authorships. Women represent 40% of all authors, a similar proportion as first authors, but just 30% as last/senior authors. The pattern of collaboration shows an interesting finding: when a woman signs as a first or last/senior author, the article byline approximates gender parityAccording to the corresponding address, the USA shares 22.8% of all world articles, followed by China (14.4%), Italy (7.8%), the UK (5.8%), India (4.2%), Spain (3.8%), Germany (3.6%), France (2.9%), Turkey (2.5%), and Canada (2.4%).Despite their short lives, the papers received an average of 11 citations. The high impact of papers from China is striking (25.1 citations; the UK, 12.4 citations; the USA, 11.3 citations), presumably because the disease emerged in China, and the first publications (very cited) came from there.
Metabolic snapshot of plasma samples reveals new pathways implicated in SARS-CoV-2 pathogenesis
Authors: Albóniga Oihane E. , Jimйnez Daniel , Sбnchez-Conde Matilde , Vizcarra Pilar , Ron Raquel , Herrera Sabina , Martнnez-Sanz Javier , Moreno Elena , Moreno Santiago , Barbas Coral , Serrano-Villar Sergio 
Published: September 2021

AbstractDespite of the scientific and human efforts to understand COVID-19, there are questions still unanswered. Variations in the metabolic reaction to SARS-CoV-2 infection could explain the striking differences in the susceptibility to infection and the risk of severe disease. Here, we used untargeted metabolomics to examine novel metabolic pathways related to SARS-CoV-2 susceptibility and COVID-19 clinical severity using capillary electrophoresis coupled to a time-of-flight mass spectrometer (CE-TOF-MS) in plasma samples. We included 27 patients with confirmed COVID-19 early after symptom onset who were prospectively followed and 29 healthcare workers heavily exposed to SARS-CoV-2 but with low susceptibility to infection (‘nonsusceptible’). We found that the metabolite profile was predictive of the study group. We identified a total of 55 metabolites as biomarkers of SARS-CoV-2 susceptibility or COVID-19 clinical severity. We report the discovery of new plasma biomarkers for COVID-19 that provide mechanistic explanations for the clinical consequences of SARS-CoV-2, including mitochondrial and liver dysfunction as a consequence of hypoxemia (citrulline, citrate, and BAIBA), energy production and amino acid catabolism (L-glycine, L-alanine, L-serine, L-proline, L-aspartic acid and L-histidine), endothelial dysfunction and thrombosis (citrulline, L-ADMA, 2-AB, and Neu5Ac), and we found interconnections between these pathways. In summary, in this first report of the metabolomic profile of individuals with severe COVID-19 and SARS-CoV-2 susceptibility by CE-MS, we define several metabolic pathways implicated in SARS-CoV-2 susceptibility and COVID-19 clinical progression that could be developed as biomarkers of COVID-19.
The usefulness of IFRS-compliant reports: perceptions of Sri Lankan investors and lenders
Authors: Bandara Saman , Falta Michael 
Published: September 2021

PurposeThis paper aims to examine differential perceptions of lenders and investors on (1) the use, perceived usefulness, importance and adequacy of annual reports, (2) the importance of qualitative characteristics (QCs) and (3) the perceived impact of International Financial Reporting Standards (IFRS) on financial reporting quality (FRQ) in Sri Lanka.Design/methodology/approachA questionnaire survey study of practising professionals consisting of Sri Lankan investors (N = 214) and lenders (N = 235).FindingsIn relation to (1), lenders and investors rank three out of ten information sources ahead of the remaining seven: both include annual reports and personal knowledge. However, the highest average response for lenders is direct communication with clients, and for investors, it is stock market publications. Within annual reports, both decision-makers identify financial statements as the most useful part. Concerning (2), they both identified understandability as the most important QC followed by timeliness. Relevance ranked last, surprisingly. In relation to (3), both groups perceived that the new IFRS reporting environment improved the FRQ compared to the previous Sri Lanka Accounting Standards regime.Practical implicationsRanking understandability as the most important QC in terms of decision usefulness contradicts IASB's categorisation. The authors provide empirical data on the perceived degree of success of adopting IFRS in a developing economy.Originality/valueThe authors design a decision-oriented (lending vs investing) and context-specific (IASB's financial reporting framework) questionnaire to examine the perceptions of key capital providers separately on the issues mentioned above in “Purpose” within a developing economy. The survey fits into two aspects of the decision-useful theory: useful to make what decisions and useful to whom.
“I Drew Myself Right There”: third grade girls restorying for visual justice
Authors: Wiseman Angela M. , Turner Jennifer D. , Cappello Marva 
Published: September 2021

PurposeThis paper aims to present three girls’ visual annotations and digital responses that restory a scene in the picturebook I’m New Here. The authors focus on how children use multimodal tools to reflect their critical knowledge of the world by illuminating how this group of girls responded to and incorporated broader social issues.Design/methodology/approachThis study takes place in a third-grade classroom. Using qualitative methods that build on critical multimodal literacy, the authors documented and analyzed children’s visual and digital interpretations. Data were generated from classroom sessions that incorporated interactive readalouds, as well as students’ annotated visual images, sketches, video and digital responses. The collaborative analytic process involved multiple passes to interpret visual, textual and multimodal elements.FindingsThe analyses revealed how Aliyah, Tiana and Carissa used multimodal tools to engage in the process of restorying. Through their multimodal composition, they designed images that illuminated their solidarity with the young female character wearing the hijab; their desire to disrupt xenophobic bullying; and their hope for a respectful and inclusive climate in their own classroom.Originality/valueIn this paper, the authors examine how three girls in a third-grade classroom restory using critical multimodal literacy methods. These girls’ multimodal responses reflected how they disrupted dominant storylines of exclusionary practices. Their authentic acts of visual advocacy give us hope for the future.