bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional and genetic sex differences for schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus
Authors: Benjamin Kynon JM , Arora Ria , Stolz Joshua M , D’Ignazio Laura , Collado-Torres Leonardo , Hyde Thomas M , Kleinman Joel E , Weinberger Daniel R , Paquola Apuã CM , Erwin Jennifer A 
Published: October 2022

AbstractSchizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. To date, only the prefrontal cortex has been examined in large-scale transcriptome analyses for sex differences in schizophrenia. Here, we examined the BrainSeq Consortium RNA-sequencing and genotypes for the caudate nucleus (n=399), dorsolateral prefrontal cortex (DLPFC; n=377), and hippocampus (n=394) to characterize sex differences in schizophrenia. We identified genomic features (genes, transcripts, exons, and exon-exon junctions) associated with sex, sex-specific expression in schizophrenia, and sex-interacting expression quantitative trait loci (si-eQTL) associated with schizophrenia risk. We found 878 unique genes with sex differences across brain regions, including ANK3, which shows male-biased expression in the caudate nucleus. X-chromosome dosage was significantly decreased in the hippocampus of female and male individuals with schizophrenia. Our sex interaction model revealed 15 novel junctions dysregulated for schizophrenia in a sex-specific manner. Sex-specific schizophrenia analysis identified dozens of expressed, sex-specific features with enrichment in the transcriptional response of cellular stress. Finally, our si-eQTL analysis revealed 974 unique genes, 14 of which are associated with schizophrenia risk. Overall, our results increased the number of annotated sex-biased features, identified sex-specific schizophrenia genes, and provided the first annotation of si-eQTL in the human DLPFC and hippocampus. Altogether, these results point to the importance of sex-informed analysis of sexually dimorphic traits and inform personalized therapeutic strategies in schizophrenia.
Reduction in circulating monocytes correlates with persistent post-COVID pulmonary fibrosis in multi-omic comparison of long-haul COVID and IPF
Authors: Bingham Grace C. , Muehling Lyndsey M. , Li Chaofan , Huang Yong , Abebayehu Daniel , Noth Imre , Sun Jie , Woodfolk Judith A. , Barker Thomas H. , Bonham Catherine 
Published: October 2022

AbstractRationale: Up to 30% of COVID-19 patients experience persistent sequelae, including dyspnea, restrictive physiology, and early radiographic signs of pulmonary fibrosis (PF). The mechanisms that provoke post-COVID progressive PF are poorly understood, and biomarkers to identify at-risk patients are urgently needed. Methods: We evaluated a cohort of 14 symptomatic COVID survivors with impaired respiratory function and imaging worrisome for developing PF, including bilateral reticulation, traction bronchiectasis and/or honeycombing, and compared these to Idiopathic Pulmonary Fibrosis (IPF) patients and age-matched controls without respiratory disease. We performed single-cell RNA-sequencing and multiplex immunostaining on peripheral blood mononuclear cells collected at the COVID-19 patients’ first visit after ICU discharge. Six months later, symptoms, restriction and PF improved in some (Early-Resolving COVID PF), but persisted in others (Late-Resolving COVID PF). Results: Circulating monocytes were significantly reduced in Late-Resolving COVID PF patients compared to Early-Resolving COVID PF and non-diseased controls. Monocyte abundance correlated with pulmonary function tests FVC and DLCO. Differential expression analysis revealed MHC-II class molecules were upregulated on the CD8 T cells of Late-Resolving COVID PF patients but downregulated in monocytes. IPF patients had a similar decrease in monocyte abundance and marked decrease in monocyte HLA-DR protein expression compared to Late-Resolving COVID PF patients. Conclusion: Circulating monocyte abundance may distinguish between patients whose post-COVID PF resolves or persists. Furthermore, fibrotic progression coincided with decreases in HLA-DR expression on monocytes, a phenotype previously associated with dampened antigen stimulation and severe respiratory failure.
A joint transcriptome-wide association study across multiple tissues identifies new candidate susceptibility genes for breast cancer
Authors: Gao Guimin , Fiorica Peter N. , McClellan Julian , Barbeira Alvaro , Li James L. , Olopade Olufunmilayo I. , Im Hae Kyung , Huo Dezheng 
Published: October 2022

AbstractGenome-wide association studies (GWAS) have identified more than 200 genomic loci for breast cancer risk, but specific causal genes in most of these loci have not been identified. In fact, transcriptome-wide association studies (TWAS) of breast cancer performed using gene expression prediction models trained in breast tissue have yet to clearly identify most target genes. To identify novel candidate genes, we performed a joint TWAS analysis that combined TWAS signals from multiple tissues. We used expression prediction models trained in 47 tissues from the Genotype-Tissue Expression data using a multivariate adaptive shrinkage method along with association summary statistics from the Breast Cancer Association Consortium and UK Biobank data. We identified 380 genes at 129 genomic loci to be significantly associated with breast cancer at the Bonferroni threshold (p < 2.36 × 10−6). Of them, 29 genes were located in 11 novel regions that were at least 1Mb away from published GWAS hits. The rest of TWAS-significant genes were located in 118 known genomic loci from previous GWAS of breast cancer. After conditioning on previous GWAS index variants, we found that 22 genes located in known GWAS loci remained statistically significant. Our study maps potential target genes in more than half of known GWAS loci and discovers multiple new loci, providing new insights into breast cancer genetics.
Early Surgery in Very Preterm Infants is Associated with Brain Abnormalities on Term MRI: A Propensity Score Analysis
Authors: Kojima Katsuaki , Liu Chunyan , Ehrlich Shelley , Kline-Fath Beth M , Jain Shipra , Parikh Nehal A ,   the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Investigators
Published: October 2022

ABSTRACTObjectiveTo investigate the association between exposure to surgery under general anesthesia during the newborn period and brain abnormalities and neurodevelopmental outcomes in very preterm infants. We hypothesized that exposure to surgery under general anesthesia was associated with structural brain abnormalities on MRI at term-equivalent age and neurodevelopmental impairments at two years corrected age.Study designThis prospective observational study includes 392 infants born at or below 32 weeks’ gestational age. Participants completed brain MRI at term-equivalent age and Bayley-III assessment at two years corrected age. We assessed the MRI global brain abnormality score as our primary outcome. Our secondary outcomes were scores on the Bayley-III Cognitive, Language, and Motor subscales. We evaluated the independent effects of surgery on brain MRI abnormalities and neurodevelopmental outcomes using ANOVA analyses after propensity score matching.ResultsAll infants completed brain MRI, and 338 (86%) completed neurodevelopmental testing. Forty-five received surgery under general anesthesia. Exposure to surgery was associated with worse MRI abnormalities. None of the developmental outcomes was associated with surgery after propensity score matching. The global brain abnormality score was associated with the Bayley Cognitive and Motor composite scores.ConclusionsVery preterm infants exposed to surgery under general anesthesia were at higher risk of brain abnormalities on MRI at term but not adverse neurodevelopmental outcomes at two years. Global brain abnormality score on MRI was associated with neurodevelopmental outcomes at two years. Brain MRI measures at term may function as sensitive intermediate measures of neurodevelopmental outcomes for very preterm infants.
Design and validation of an automated radiation therapy treatment planning approach for locally advanced lung cancer
Authors: Pogue Joel A. , Cardenas Carlos E. , Harms Joseph , Soike Michael H. , Kole Adam J. , Schneider Craig S. , Veale Christopher , Popple Richard , Belliveau Jean-Guy , McDonald Andrew M. , Stanley Dennis N. 
Published: October 2022

AbstractPurposeRadiation therapy planning for locally-advanced non-small cell lung cancer (NSCLC) is challenging due to the balancing of target coverage and organs-at-risk (OAR) sparing. Using the Varian Ethos Treatment Planning System (TPS), we developed a methodology to automatically generate efficient, high-quality treatment plans for locally-advanced lung cancer patients.Methods and MaterialsFifty patients previously treated with Eclipse-generated plans for inoperable Stage IIIA-IIIC NSCLC were included in this Institutional Review Board (IRB)-approved retrospective study. Fifteen patients were used to iteratively optimize an Ethos TPS planning template, and the remaining thirty-five patients had plans automatically generated without manual intervention using the created template. Ethos and Eclipse plan quality was then assessed using 1) standard dose volume histogram (DVH) metrics, 2) adherence to clinical trial objectives, and 3) radiation oncologist qualitative review.ResultsEthos-generated plans showed improved primary and nodal planning target volume (PTVp and PTVn, respectively) V100% and V95% coverage (p<0.001) and reduced PTVp Dmax values (p=0.023). Furthermore, the Ethos template-generated plans had lower spinal cord Dmax, lungs V5Gy, and heart V25Gy, V30Gy, and V45Gy values (p≤0.021). However, Ethos esophagus metrics (mean, V35Gy, V50Gy, Dmax) and brachial plexus metrics (Dmax) were greater than Eclipse (p≤0.008), but were still clinically acceptable. A large majority (80%) of automatically generated plans had entirely “per protocol” or “variation acceptable” metrics. Three radiation oncologists qualitatively scored the Ethos plans; 78% of plans were scored as clinically acceptable during physician evaluation, with zero plans receiving scores requiring major changes.ConclusionsA standard Ethos template generated lung cancer radiotherapy plans with greater target coverage, increased spinal cord, heart, and lung V5Gy sparing, but increased esophagus and brachial plexus dose, compared to manually generated Eclipse plans. This template elucidates an efficient approach for generating automated, high quality lung radiation therapy treatment plans.
Population-level risk factors related to measles case fatality: a conceptual framework based on expert consultation and literature review
Authors: Sbarra Alyssa N. , Jit Mark , Mosser Jonathan F. , Ferrari Matthew , Cutts Felicity , Papania Mark , Kretsinger Katrina , McCarthy Kevin A. , Thakkar Niket , Gaythorpe Katy A. M. , Gamage Deepa , Krause L. Kendall , Dansereau Emily , Portnoy Allison 
Published: October 2022

AbstractIntroductionA better understanding of population-level factors related to measles case fatality is needed to estimate measles mortality burden and impact of interventions such as vaccination. This study aimed to develop a conceptual framework of mechanisms associated with measles case fatality ratios (CFRs) and assess the scope of evidence available for related indicators in the published literature.MethodsUsing expert consultation, we developed a conceptual framework of mechanisms associated with measles CFR and identified population-level indicators potentially associated with each mechanism. We then conducted a literature review by searching PubMed on October 31, 2021 to determine and classify the scope of evidence for the indicators identified by expert consultation. Studies were included if they contained evidence of an association between an indicator and measles CFR and were excluded if they were from non-human studies or reported non-original data.ResultsExpert consultation identified five mechanisms in a conceptual framework of factors related to measles CFR: health system access and care-seeking behaviors, health system quality, measles control and epidemiology, nutritional status, and risk of secondary infection. Thirty-seven measurable population-level indicators were identified by expert consultation as proxies for the mechanisms. We identified 3772 studies for review and found 49 studies showing at least one significant association with CFR for 15 indicators and only non-significant associations for 5 indicators. Inadequate data were available to evaluate the remaining 17 indicators. A randomized controlled trial provided evidence for a relationship between vitamin A treatment and measles CFR. Average household size, educational attainment, first-dose coverage of measles-containing vaccine, human immunodeficiency virus prevalence, second-dose coverage of measles-containing vaccine, stunting prevalence, surrounding conflict, travel time to major city or settlement, travel time to nearest health care facility, under-five mortality rate, underweight prevalence, vitamin A deficiency prevalence, and wasting prevalence had quantitative observational level evidence. Level of health care available had qualitative evidence of a relationship with measles CFR.ConclusionTo reduce uncertainty in measles CFR estimation, population-level factors representative of underlying mechanisms associated with CFR could be used. Our study used expert consultation and literature review to provide additional insights and a summary of the available evidence of these underlying mechanisms and indicators that could inform future estimations of measles CFR.
COVID treatment and in-hospital length of stay inequalities between race in the US over time
Authors: Althouse Benjamin M. , Baker Charlotte , Smits Peter D , Gratzl Samuel , Lee Ryan H , Cartwright Brianna M Goodwin , Simonov Michael , Wang Michael D , Stucky Nicholas L 
Published: October 2022

ABSTRACTIntroductionDemonstrated health inequalities persist in the United States. SARS-CoV-2 (COVID) has been no exception, with access to treatment and hospitalization differing across race or ethnic group. Here we aim to assess differences in treatment with remdesivir and hospital length of stay across four waves of the pandemic.MethodsUsing a subset of the Truveta data we examine odds ratios (OR) of in-hospital remdesivir treatment and risk ratios (RR) of in-hospital length of stay between Black or African American (Black) to white patients. We adjusted for confounding factors such as age, sex, and comorbidity status.ResultsThere were statically significant lower rates of remdesivir treatment and longer in-hospital lengths of stay comparing Black patients to white patients early in the pandemic (OR for treatment: 0.88, 95% confidence interval [CI]: 0.80, 0.96; RR for length of stay: 1.17, CI: 1.06, 1.21). Rates became close to parity between groups as the pandemic progressed.ConclusionsWhile inpatient remdesivir treatment rates increased and length of stay decreased over the beginning course of the pandemic, there are still inequalities in patient care.
Overexpression of Cancer- and Neurotransmitter-Associated Genes in the Nucleus Accumbens of Smokers
Authors: Stein Richard , Mamdani Firoza , Bunney Blynn , Cartagena Preston , Vawter Marquis P. , Schatzberg Alan F. , Barchas Jack , Lee Francis S. , Myers Richard , Watson Stanley J. , Akil Huda , Bunney William E. , Sequeira Adolfo 
Published: October 2022

AbstractThe effects of smoking in the human brain were explored at the molecular level in thenucleus accumbens(NAcc), a key brain region involved in tobacco addiction. Gene expression data from post-mortem NAcc were analyzed according to smoking habits: Never smokers, Former smokers and Current smokers at the time of death. The effect of smoking was determined using an ANCOVA model, controlling for potential confounders (psychiatric diagnosis, gender, age, post-mortem interval, and brain pH) followed by pair-wise post-hoc comparisons. Q-values (false discovery rate adjusted p-values) < 0.05 were used in combination with a fold change of > ±1.3 to identify the most relevant genes. The greatest number of differentially expressed genes (DEGs) were found in subjects with a recent history of smoking (Current smokers) compared to either Former or Never smokers. Only two genes were differentially expressed between Former and Never smokers, suggesting that the effects of smoking on gene expression in the brain may be transient. Ingenuity Pathway Analysis (IPA) of DEGs identified a significant over-representation of neurotransmitter system genes (glutamate, GABA) in Current smokers. IPA also revealed many genes associated with cancer in Current smokers compared to Former and Never smokers despite no known cancer in any subjects. Genes associated with neoplasms, glioblastoma, gliomas and tumor regulations are among the top 10 transcripts.Our findings show that active smokers have a significant increase in cancer-related genes and alterations in glutamate and GABA neurotransmitter systems in the NAcc. To our knowledge this is the first study to identify cancer-related genes in the NAcc in Current smokers who have no evidence of cancer.
Horizontal transferred T-DNA and haplotype-based phylogenetic analysis uncovers the origin of sweetpotato
Authors: Yan Mengxiao , Li Ming , Wang Yunze , Wang Xinyi , Moeinzadeh M-Hossein , Quispe-Huamanquispe Dora G. , Fan Weijuan , Wang Yuqin , Nie Haozhen , Wang Zhangying , Heider Bettina , Jarret Robert , Kreuze Jan F. , Gheysen Godelieve , Wang Hongxia , Bock Ralph , Vingron Martin , Yang Jun 
Published: October 2022

AbstractThe hexaploid sweetpotato is one of the most important root crops worldwide. However, its genetic origins are controversial. In this study, we identified two progenitors of sweetpotato by horizontal gene transferred IbT-DNA and haplotype-based phylogenetic analysis. The diploid progenitor is the diploid form of I. aequatoriensis, contributed the B1 subgenome, IbT-DNA2 and lineage 2 type of chloroplast genome to sweetpotato. The tetraploid progenitor of sweetpotato is I. batatas 4x, donating the B2 subgenome, IbT-DNA1 and lineage 1 type of chloroplast genome. Sweetpotato derived from the reciprocal cross between the diploid and tetraploid progenitors and a subsequent whole genome duplication. We also detected biased gene exchanges between subgenomes. The B1 to B2 subgenome conversions were almost 3-fold higher than the B2 to B1 subgenome conversions. This study sheds lights on the evolution of sweetpotato and paves a way for the improvement of sweetpotato.
Comparison of personality structures between methodologies: personality ratings and behavioural observations in Japanese macaques (Macaca fuscata)
Authors: Katayama Kosho , Nakamichi Masayuki , Yamada Kazunori 
Published: October 2022

AbstractIn this study, we aimed to clarify the structure of personality of Japanese macaques (Macaca fuscata) using two methods, personality ratings and behavioural observation, which are frequently used in primate personality studies. Principal component analysis of personality ratings sampled in two waves that were assessed with questionnaires (Stevenson-Hinde and Zunz questionnaire in Wave 1 and Hominoid Personality Questionnaire in Wave 2) revealed four components for each wave: Dominance, Aggressiveness, Dependency, and Component4 and Dominance, Aggressiveness, Sociability, and Activity. By calculating the correlation coefficients for principal component loadings of personality ratings, we compared the personality structure of other primates from previous studies with that of Japanese macaques. Based on these results, we propose that the factors common to macaques and capuchin monkeys fall into the following four categories of Dominance, which correlates with dominance rank; Excitability, which expresses aggression and neuroticism; Sociability, which indicates how actively they try to interact with others; and Activity, which expresses exploratory behaviour and openness. Analysis of data from behavioural observation extracted four components: Kin-biased-approaching, Grooming-diversity, Activity, and Aggressiveness. Principal component scores were calculated from each rating and behavioural observation data, and correlation coefficients were used to examine whether the same personality traits were found in both these methods. In this analysis, the raters did not collect behavioural data to ensure that data from both these methods did not overlap. No identical personality traits were found between the two methods. This result may indicate that there was no specific personality structure in Japanese macaques and that each method assessed different aspects of behavioural patterns pertaining to animal behaviour. It is difficult to assume from this study the cross-situational consistency conventionally assumed by personality psychology, and the results suggest that individuals vary in the way their behaviour changes in response to their environment, that is, coherence.
Notch signaling pathway in tooth shape variations
Authors: Mitsiadis Thimios A. , Pagella Pierfrancesco , Rodrigues Helder Gomes , Tsouknidas Alexander , Ramenzoni Liza L. , Radtke Freddy , Mehl Albert , Viriot Laurent 
Published: October 2022

AbstractEvolutionary changes in vertebrates are linked to genetic alterations that often affect tooth-crown shape, which is a criterion of speciation events. The Notch pathway is highly conserved between species and controls morphogenetic processes in most developing organs, including teeth. Epithelial loss of the Notch-ligand Jagged1 in developing mouse molars affects the location, size and interconnections of their cusps that lead to minor tooth-crown shape modifications convergent to those observed along Muridae evolution. These alterations are due to the modulation of numerous genes, where Notch signaling is a hub for essential morphogenetic networks. A three-dimensional metamorphosis approach allowed tooth morphology prediction in individuals carrying Jagged1 mutations. These results shed new light on Notch/Jagged1-mediated signaling as one of the crucial components for dental variations in evolution.Significance statementDental microevolution changes in vertebrates are regulated by the Notch signaling pathway.