bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin resistance in thyroid disorders: association between anti-TPO and HOMA-IR
Authors: Krishnamurthy Hari , Siriwardhane Thushani , Krishna Karthik , Song Qi , Jayaraman Vasanth , Wang Tianhao , Bei Kang , Rajasekaran John J. 
Published: June 2023

ABSTRACTThe association of thyroid disease and diabetes has been classically described. However, the comorbidity of thyroid disparities and insulin resistance is not frequently assessed, especially the sequence of the occurrence of these markers. We performed a retrospective analysis to evaluate the association between thyroid disease and diabetes markers. We further investigated the sequence of occurrence of thyroid and diabetes markers to identify any predictive capabilities of these markers. We evaluated 32787 subjects who were classified based on their serum thyroid hormones and autoantibody levels. Our general prevalence results showed that HOMA-IR was elevated in overt hypothyroid subjects (43.7%) and overt hyperthyroid subjects (42.2%). HbA1C was elevated in subclinical hypothyroid subjects (19.2%), overt hypothyroid subjects (22.3%) and overt hyperthyroid subjects (21.2%). Glucose was significantly elevated in subclinical hypothyroid subjects (24.2%) and overt hyperthyroid subjects (31.0%). Insulin was only significantly elevated in overt hypothyroid subjects (15.1%). Interestingly, we found that 70.3% of subjects who had their HOMA-IR score escalated from negative (HOMA-IR<2.7) to positive (HOMA-IR>2.7) during their multiple visits had anti-TPO 369 (±242) days prior to the onset of this change. Our comprehensive study provided evidence that the presence of anti-TPO may suggest a predictive role in developing insulin resistance later in life.Strengths and limitations of the studyThe strength of our study is the large population size including a larger set of markers from both thyroid disease and diabetes.The limitation in our study is the distorted male and female ratio.
Chronic oxytocin administration stimulates the endogenous oxytocin system: an RCT in autistic children
Authors: Moerkerke Matthijs , Daniels Nicky , Tibermont Laura , Tang Tiffany , Evenepoel Margaux , Van der Donck Stephanie , Debbaut Edward , Prinsen Jellina , Chubar Viktoria , Claes Stephan , Vanaudenaerde Bart , Willems Lynn , Steyaert Jean , Boets Bart , Alaerts Kaat 
Published: June 2023

AbstractBackgroundClinical efficacy of chronic intranasal administration of oxytocin is increasingly explored in autism spectrum disorder (ASD), but to date, little is known regarding its biological effects and in particular how chronic administration regimes impact endogenous oxytocinergic function.MethodsTo fill this gap, this double-blind, randomized, placebo-controlled study explored chronic oxytocin administration effects on endogenous salivary oxytocin levels and oxytocin receptor gene (OXTR) epigenetics (DNA methylation) in 8-to-12-year-old children with ASD (n = 79, 16 females). Biological sampling was performed at baseline (pre-treatment), immediately (24 hours) after the four-week oxytocin administration period (12 IU, twice daily) and at a follow-up session, four weeks after the last nasal spray administration.ResultsCompared to placebo, children receiving the oxytocin nasal spray displayed significantly higher salivary oxytocin levels 24 hours after the last oxytocin nasal spray administration, but no longer at the four-week follow up session. Regarding epigenetics, oxytocin-induced reductions inOXTRmethylation were observed, reflecting a facilitation of oxytocin receptor expression in the oxytocin, compared to the placebo group. Notably, heightened oxytocin levels post-treatment were significantly associated with reducedOXTRDNA methylation and improved feelings of secure attachment.ConclusionFour weeks of chronic oxytocin administration stimulated the endogenous oxytocinergic system in children with ASD, as evidenced by increased salivary oxytocin levels and reducedOXTRDNA methylation (indicating increased receptor expression).
Factors related to the performance of the periodontal specialty in secondary oral health in Brazil
Authors: Simião Vinícius de Moraes , Gonzalez Estéfany Figueiredo , Probst Livia Fernandes , Pinto Rafaela da Silveira , De-Carli Alessandro Diogo 
Published: June 2023

AbstractObjectiveThe aim of this study was to investigate, at a national level, which individual factors of the work process/infrastructure are associated with the achievement of goals in the periodontics specialty in Brazilian Dental Specialty Centers (CEO).MethodsThis was a quantitative, analytical, cross-sectional study. Secondary data from DATASUS and the external evaluation of the second cycle of the CEO Access and Quality Improvement Program were used. Variable description was carried out in the first stage, and then the bivariate Poisson regression was performed to verify possible associations between the variables and the outcome (achievement of goals in Periodontics in the CEO). In this analysis, the covariates that were associated with the outcome at the p <0.20 significance level were included in the next step of the analysis. Multivariate Poisson regression with a robust estimator was then performed with those that met the above criterion. The variables that showed a p value < 0.05 were considered in the final model.ResultsThe outcome was achieved in more than seven months of the year (mean 7.03 months, SD 4.20). Most CEO monitored the established goals (93.2%), had referral as the only way of access (61.7%), had only municipal coverage (68.4%), carried out planning and periodic evaluation of actions (89.2%). A minority has quotas of procedures by Oral Health teams (OHTs) in Primary Health Care (PHC) (18.8%). The presence of a specialist in periodontics was (on average) 1.16 per CEO and the sum of the workload of dentists working in this specialty was 31.1 hours (SD = 23.9).ConclusionIt was concluded that the individual factors of the work process/infrastructure associated with the achievement of goals in periodontics in Brazilian CEO are: monitoring of established goals, CEO scope and number of professionals working in the specialty.
What contraceptive side effects are women told about during counseling? Evidence from PMA Ethiopia 2019 cross-sectional survey
Authors: Zimmerman Linnea A. , Sarria Isabella , Kassa Munir , Karp Celia , Seme Assefa , Shiferaw Solomon 
Published: June 2023

AbstractBackgroundDespite widespread concerns about contraceptive side effects, few studies explore the specific side effects women are told about during contraceptive counseling. This study explored patterns of counseling on specific side effects by user characteristics in Ethiopia.MethodsData were collected from a nationally representative sample of women between October and December 2019. Analyses were restricted to 2,039 current users of hormonal contraception or the non-hormonal IUD. Descriptive analyses identified the types and number of side effects, across all methods and by the injectable, implant, and pill. Multinomial regression identified factors associated with receipt of counseling on bleeding changes only, non-bleeding changes only, or both, relative to no counseling on side effects, adjusting for method type, source, and socio-economic characteristics.ResultsLess than 10% of users were told of at least one bleeding and non-bleeding side effect. Relative to implant users, injectable and other method users were less likely to be told about bleeding changes only (aRRR: 0.65, 95% CI: 0.46-0.93 and aRRR: 0.31, 95% CI: 0.16-0.61, respectively) and users of other methods were less likely to be told about both a bleeding and non-bleeding change (aRRR: 0.43, 95% CI: 0.19-0.93). Users who received their method from a non-public source were less likely to receive counseling on any kind of side effect and nulliparous women were less likely to be told about both kinds of side effects.ConclusionThere is need to improve counseling in the private sector. Research to understand provider barriers to counseling on side effects is needed.
Multiomic Analysis Identifies a High-Risk Metabolic and TME Depleted Signature that Predicts Early Clinical Failure in DLBCL
Authors: Wenzl Kerstin , Stokes Matt , Novak Joseph P. , Bock Allison M. , Khan Sana , Hopper Melissa A. , Krull Jordan E. , Dropik Abigail R. , Walker Janek S. , Sarangi Vivekananda , Mwangi Raphael , Ortiz Maria , Stong Nicholas , Huang C. Chris , Maurer Matthew J. , Rimsza Lisa , Link Brian K. , Slager Susan L. , Asmann Yan , Mondello Patrizia , Morin Ryan , Ansell Stephen M , Habermann Thomas M. , Feldman Andrew L. , King Rebecca L. , Nowakowski Grzegorz , Cerhan James R. , Gandhi Anita K. , Novak Anne J. 
Published: June 2023

ABSTRACTPURPOSE60-70% of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients avoid events within 24 months of diagnosis (EFS24) and the remainder have poor outcomes. Recent genetic and molecular classification of DLBCL has advanced our knowledge of disease biology, yet were not designed to predict early events and guide anticipatory selection of novel therapies. To address this unmet need, we used an integrative multiomic approach to identify a signature at diagnosis that will identify DLBCL at high risk of early clinical failure.PATIENTS AND METHODSTumor biopsies from 444 newly diagnosed DLBCL were analyzed by WES and RNAseq. A combination of weighted gene correlation network analysis and differential gene expression analysis followed by integration with clinical and genomic data was used to identify a multiomic signature associated with high risk of early clinical failure.RESULTSCurrent DLBCL classifiers are unable to discriminate cases who fail EFS24. We identified a high risk RNA signature that had a hazard ratio (HR, 18.46 [95% CI 6.51-52.31]P< .001) in a univariate model, which did not attenuate after adjustment for age, IPI and COO (HR, 20.8 [95% CI, 7.14-61.09]P< .001). Further analysis revealed the signature was associated with metabolic reprogramming and a depleted immune microenvironment. Finally, WES data was integrated into the signature and we found that inclusion ofARID1Amutations resulted in identification of 45% of cases with an early clinical failure which was validated in external DLBCL cohorts.CONCLUSIONThis novel and integrative approach is the first to identify a signature at diagnosis that will identify DLBCL at high risk for early clinical failure and may have significant implications for design of therapeutic options.
Clinical course of COVID-19 patients admitted to the Intensive Care Unit of a tertiary care hospital in Central India
Authors: Modi Asati Alka , Patel Rakesh , Singhal Kritika , Jain Chakresh 
Published: June 2023

AbstractBackgroundCOVID-19 pandemic also known as Corona virus pandemic, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2). In India, the first case of COVID-19 was reported on 30 January 2020 while in Madhya Pradesh on 20 March 2020 and in Rewa on 27 April 2020. Nearly 95 % of people recovered from COVID-19, and nearly three to five percent of cases needed Intensive Care Unit care and most of them needed mechanical ventilation.Materials and MethodsThis was a hospital based cross-sectional study, done among 75 clinical or RT-PCR confirmed cases of COVID-19 infection admitted to the ICU of tertiary care unit.ResultsIn the present study, 63% were male and maximum (35%) belonged to 41-60 years of age. The most common symptom was fever at the time of admission to the hospital. Co-morbidity was reported in 21(28%) of patients. Out of these, majority of patients recorded combination of hypertension and diabetes as the most common comorbidity.ConclusionDelayed medical intervention, advanced age, and the presence of underlying health conditions, such as cardiovascular disease, diabetes, etc., are known risk factors for severe illness and can contribute to worse outcomes and increased mortality in COVID-19 patients.
Aberrant landscapes of maternal meiotic crossovers contribute to aneuploidies in human embryos
Authors: Ariad Daniel , Madjunkova Svetlana , Madjunkov Mitko , Chen Siwei , Abramov Rina , Librach Clifford , McCoy Rajiv C. 
Published: June 2023

AbstractMeiotic recombination is crucial for human genetic diversity and chromosome segregation accuracy. Understanding its variation across individuals and the processes by which it goes awry are long-standing goals in human genetics. Current approaches for inferring recombination landscapes either rely on population genetic patterns of linkage disequilibrium (LD)—capturing a time-averaged view—or direct detection of crossovers in gametes or multi-generation pedigrees, which limits dataset scale and availability. Here, we introduce an approach for inferring sex-specific recombination landscapes using data from preimplantation genetic testing for aneuploidy (PGT-A). This method relies on low-coverage (<0.05×) whole-genome sequencing ofin vitrofertilized (IVF) embryo biopsies. To overcome the data sparsity, our method exploits its inherent relatedness structure, knowledge of haplotypes from external population reference panels, as well as the frequent occurrence of monosomies in embryos, whereby the remaining chromosome is phased by default. Extensive simulations demonstrate our method’s high accuracy, even at coverages as low as 0.02×. Applying this method to PGT-A data from 18,967 embryos, we mapped 70,660 recombination events with∼150 kbp resolution, replicating established sex-specific recombination patterns. We observed a reduced total length of the female genetic map in trisomies compared to disomies, as well as chromosome-specific alterations in crossover distributions. Based on haplotype configurations in pericentromeric regions, our data indicate chromosome-specific propensities for different mechanisms of meiotic error. Our results provide a comprehensive view of the role of aberrant meiotic recombination in the origins of human aneuploidies and offer a versatile tool for mapping crossovers in low-coverage sequencing data from multiple siblings.
emObject: domain specific data abstraction for spatial omics
Authors: Baker Ethan A. G. , Huang Meng-Yao , Lam Amy , Rahim Maha K. , Bieniosek Matthew F. , Wang Bobby , Zhang Nancy R. , Mayer Aaron T. , Trevino Alexandro E. 
Published: June 2023

AbstractRecent advances in high-parameter spatial biology have yielded a rapidly growing new class of biological data, allowing researchers to more comprehensively characterize cellular state and morphology in native tissue context. However, spatial biology lacks a cohesive data abstraction on which to build novel computational tools and algorithms, making it difficult to fully leverage these emergent data. Here, we present emObject, a domain-specific data abstraction for spatial biology data and experiments. We demonstrate the simplicity, flexibility, and extensibility of emObject for a range of spatial omics data types, including the analysis of Visium, MIBI, and CODEX data, as well as for integrated spatial multiomic experiments. The development of emObject is an essential step towards building a unified data science ecosystem for spatial biology and accelerating the pace of scientific discovery.
Restoration of metabolic functional metrics from label-free, two-photon cervical tissue images using multiscale deep-learning-based denoising algorithms
Authors: Vora Nilay , Polleys Christopher M. , Sakellariou Filippos , Georgalis Georgios , Thieu Hong-Thao , Genega Elizabeth M. , Jahanseir Narges , Patra Abani , Miller Eric , Georgakoudi Irene 
Published: June 2023

AbstractLabel-free, two-photon imaging captures morphological and functional metabolic tissue changes and enables enhanced understanding of numerous diseases. However, this modality suffers from low signal arising from limitations imposed by the maximum permissible dose of illumination and the need for rapid image acquisition to avoid motion artifacts. Recently, deep learning methods have been developed to facilitate the extraction of quantitative information from such images. Here, we employ deep neural architectures in the synthesis of a multiscale denoising algorithm optimized for restoring metrics of metabolic activity from low-SNR, two-photon images. Two-photon excited fluorescence (TPEF) images of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavoproteins (FAD) from freshly excised human cervical tissues are used. We assess the impact of the specific denoising model, loss function, data transformation, and training dataset on established metrics of image restoration when comparing denoised single frame images with corresponding six frame averages, considered as the ground truth. We further assess the restoration accuracy of six metrics of metabolic function from the denoised images relative to ground truth images. Using a novel algorithm based on deep denoising in the wavelet transform domain, we demonstrate optimal recovery of metabolic function metrics. Our results highlight the promise of denoising algorithms to recover diagnostically useful information from low SNR label-free two-photon images and their potential importance in the clinical translation of such imaging.
Sexual Dimorphism of Skeletal Muscle in a Mouse Model of Breast Cancer: A Functional and Molecular Analysis
Authors: Rentz Lauren E. , Whetsell Marcella , Clayton Stuart A. , Mizener Alan D. , Holásková Ida , Chapa Matthew G. , Hoblitzell E. Hannah , Eubank Timothy D. , Pistilli Emidio E. 
Published: June 2023

1.AbstractBreast cancer incidence in men is statistically rare; however, given the lack of screening in males, more advanced stages at initial diagnosis results in lower 5-year survival rates for men with breast cancer compared to women. A sexual dimorphism, with respect to the effect of tumor growth on cachexia incidence and severity, has also been reported across cancer types. The purpose of this study was to examine the sexual dimorphism of breast cancer as it pertains to skeletal muscle function and molecular composition. Using female and male transgenic PyMT mice, we tested the hypothesis that isometric contractile properties and molecular composition of skeletal muscle would be differentially affected by breast tumors. PyMT tumor-bearing mice of each sex, corresponding to maximal tumor burden, were compared to their respective controls. RNA-sequencing of skeletal muscle revealed different pathway alterations that were exclusive to each sex. Further, differentially expressed genes and pathways were substantially more abundant in female tumor mice, with only minimal dysregulation in male tumor mice, each compared to their respective controls. These differences in the transcriptome were mirrored in isometric contractile properties, with greater tumor-induced dysfunction in females than male mice, as well as muscle wasting. Collectively, these data support the concept of sexually dimorphic responses to cancer in skeletal muscle and suggest these responses may be associated with the clinical differences in breast cancer between the sexes. The identified sex-dependent pathways within muscle of male and female mice provide a framework to evaluate therapeutic strategies targeting tumor-associated skeletal muscle alterations.Statement of significanceThe PyMT mouse model of breast cancer, which recapitulates clinical characteristics, exhibits differences in molecular and functional responses of skeletal muscle that are sex-dependent.
Combination fedratinib and venetoclax has activity against human B-ALL with high FLT3 expression
Authors: Rinella Sean P , Bell Haley C , Hess Nicholas J , Hoang Nguyet-Minh , Nguyen Thao Trang , Turicek David P , Shi Lei , Rui Lixin , LaBelle James L , Capitini Christian M 
Published: June 2023

AbstractTreatment of relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) remains a challenge, particularly in patients who do not respond to traditional chemotherapy or immunotherapy. The objective of this study was to assess the efficacy of fedratinib, a semi selective JAK2 inhibitor and venetoclax, a selective BCL-2 inhibitor, on human B-ALL using both single-agent and combinatorial treatments. The combination treatment of fedratinib and venetoclax improved killing of the human B-ALL cell lines RS4;11 and SUPB-15 in vitro over single-agent treatments. This combinatorial effect was not detected in the human B-ALL cell line NALM-6, which was less responsive to fedratinib due to the absence of Flt3 expression. The combination treatment induces a unique gene expression profile relative to single-agent treatment and with an enrichment in apoptotic pathways. Finally, the combination treatment was superior to single agent treatment in an in vivo xenograft model of human B-ALL, with a two-week treatment regimen significantly improving overall survival while inducing CD19 expression. Overall, our data demonstrates the efficacy of a combinatorial treatment strategy of fedratinib and venetoclax against human B-ALL expressing high levels of Flt3.Statement of ImplicationThe combination treatment of fedratinib and venetoclax has activity against human B-ALL with high FLT3 expression and has the potential to be a salvage therapy for patients with relapsed/refractory B-ALL.
Hidden protein-altering variants influence diverse human phenotypes
Authors: Hujoel Margaux L.A. , Handsaker Robert E. , Sherman Maxwell A. , Kamitaki Nolan , Barton Alison R. , Mukamel Ronen E. , Terao Chikashi , McCarroll Steven A. , Loh Po-Ru 
Published: June 2023

AbstractStructural variants (SVs) comprise the largest genetic variants, altering from 50 base pairs to megabases of DNA. However, SVs have not been effectively ascertained in most genetic association studies, leaving a key gap in our understanding of human complex trait genetics. We ascertained protein-altering SVs from UK Biobank whole-exome sequencing data (n=468,570) using haplotype-informed methods capable of detecting sub-exonic SVs and variation within segmental duplications. Incorporating SVs into analyses of rare variants predicted to cause gene loss-of-function (pLoF) identified 100 associations of pLoF variants with 41 quantitative traits. A low-frequency partial deletion ofRGL3exon 6 appeared to confer one of the strongest protective effects of gene LoF on hypertension risk (OR = 0.86 [0.82–0.90]). Protein-coding variation in rapidly-evolving gene families within segmental duplications—previously invisible to most analysis methods—appeared to generate some of the human genome’s largest contributions to variation in type 2 diabetes risk, chronotype, and blood cell traits. These results illustrate the potential for new genetic insights from genomic variation that has escaped large-scale analysis to date.