bluuebunny/crossref_metadata_2025_split huggingface dataset:
A workflow reproducibility scale for automatic validation of biological interpretation results
Authors: Suetake Hirotaka , Fukusato Tsukasa , Igarashi Takeo , Ohta Tazro 
Published: October 2022

BackgroundReproducibility of data analysis workflow is a key issue in the field of bioinformatics. Recent computing technologies, such as virtualization, have made it possible to reproduce workflow execution with ease. However, the reproducibility of results is not well discussed; that is, there is no standard way to verify whether the biological interpretation of reproduced results are the same. Therefore, it still remains a challenge to automatically evaluate the reproducibility of results.ResultsWe propose a new metric, a reproducibility scale of workflow execution results, to evaluate the reproducibility of results. This metric is based on the idea of evaluating the reproducibility of results using biological feature values (e.g., number of reads, mapping rate, and variant frequency) representing their biological interpretation. We also implemented a prototype system that automatically evaluates the reproducibility of results using the proposed metric. To demonstrate our approach, we conducted an experiment using workflows used by researchers in real research projects and the use cases that are frequently encountered in the field of bioinformatics.ConclusionsOur approach enables automatic evaluation of the reproducibility of results using a fine-grained scale. By introducing our approach, it is possible to evolve from a binary view of whether the results are superficially identical or not to a more graduated view. We believe that our approach will contribute to more informed discussion on reproducibility in bioinformatics.
3D model of mouse embryonic pancreas and endocrine compartment using stem cell-derived mesoderm and pancreatic progenitors
Authors: Edri Shlomit , Rosenthal Vardit , Ginsburg Or , Frisch Abigail Newman , Pierreux Christophe E. , Sharon Nadav , Levenberg Shulamit 
Published: October 2022

AbstractThe developing mouse pancreas is surrounded by mesoderm compartments providing signals that induce pancreas formation. Most pancreatic organoid protocols lack this mesoderm niche and only partially capture the pancreatic cell repertoire. This work aimed to generate pancreatic aggregates by differentiating mouse embryonic stem cells (mESCs) into mesoderm progenitors (MPS) and pancreas progenitors (PPs), without using extracellular matrix substitutes. First, mESCs were differentiated into epiblast stem cells (EpiSCs) to enhance the PP differentiation rate. Next, PPs and MPs aggregated together giving rise to various pancreatic cell types, including endocrine, acinar, and ductal cells, and to endothelial cells. Single-cell RNA sequencing analysis revealed a larger endocrine population within the PP+MP aggregates, as compared to PPs alone or PPs in Matrigel aggregates. The PP+MP aggregate gene expression signatures and its endocrine population percentage closely resembled those of the endocrine population found in the mouse embryonic pancreas, which holds promise for studying pancreas development.
Electrophysiological population dynamics reveal context dependencies during decision making in human frontal cortex
Authors: Shih Wan-Yu , Yu Hsiang-Yu , Lee Cheng-Chia , Chou Chien-Chen , Chen Chien , Glimcher Paul W. , Wu Shih-Wei 
Published: October 2022

AbstractDuring economic choice, evidence from monkeys and humans suggest that activity in the orbitofrontal cortex (OFC) encodes the subjective values of options under consideration. Monkey data further suggests that value representations in the OFC are context dependent, representing subjective value in a way influenced by the decision makers’ recent experience. Using stereo electroencephalography (sEEG) in human subjects, we investigated the neural representations of both past and present subjective values in the OFC, insula, cingulate and parietal cortices, amygdala, hippocampus and striatum. Patients with epilepsy (n=20) reported their willingness to pay—a measure of subjective value—for snack food items in a Becker-DeGroot-Marschack (BDM) auction task. We found that the high frequency power (gamma and high-gamma bands) in the OFC positively correlated with the current subjective value but negatively correlated with the subjective value of the good offered on the last trial – a kind of temporal context dependency not yet observed in humans. These representations were observed at both the group level (across electrode contacts and subjects) and at the level of individual contacts. Noticeably, the majority of significant contacts represented either the present or past subjective value, but not both. A dynamic dimensionality-reduction analysis of OFC population trajectories suggested that the past trial begin to influence activity early in the current trial after the current offer was revealed, and that these two properties—current and past subjective values—dominate the electrophysiological signals. Together, these findings indicate that information about the value of the past and present rewards are simultaneously represented in the human OFC, and offer insights into the algorithmic structure of context-dependent computation during human economic choice.
Maternal age, obesity and hyperglycaemia are associated with a delay in preimplantation development in a mouse model of type 2 diabetes
Authors: Lilao-Garzón Joaquín , Brito-Casillas Yeray , Quesada-Canales Oscar , Wägner Ana M , Muñoz-Descalzo Silvia 
Published: October 2022

AbstractAims/hypothesisDelayed maternal age, obesity and diabetes are associated with reduced fertility. We investigated how age and obesity/metabolic syndrome impact fertility and hypothesized that its decrease is due to defects in preimplantation embryo development.MethodsThree groups of female C57Bl6 mice (12 weeks, 9 months and 1 year old) were fed either a high fat diet for 8 weeks, to induce obesity and the metabolic syndrome, or a control chow diet. Body weight and composition, glucose tolerance and insulin resistance were assessed. Fecundity was evaluated by mating and pregnancy rates, as well as number of embryos. Embryo quality was assessed morphologically, and cell fate composition was analysed in preimplantation embryos by state-of-the-art single cell quantitative confocal image analysis.ResultsThe high fat diet was associated with increased adiposity, glucose intolerance and insulin resistance, especially in the older mice. Fecundity was affected by age, more than by the diet. Both age and high fat diet were associated with reduced cell fate allocation, indicating a delay in preimplantation embryo development, and with increased expression of GATA3, an inhibitor of placentation.Conclusion/InterpretationThese results support that age and the metabolic syndrome reduce fertility through mechanisms which are present at conception very early in pregnancy.What is already known about this subject?Lifestyle changes in modern societies have led to an increase in obesity and type 2 diabetes, and women tend to become pregnant later than ever. These factors have a negative influence on female fecundity.In mice, diet induced obesity is associated with poor quality oocytes that affect overall embryonic development.What is the key question?Do age and high fat diet influence cell fate differentiation during preimplantation embryo development?What are the new findings?Body composition and glucose metabolism are altered due to high fat diet even when weight is not affected in young animals.Although there are no differences in mating and fertilization rates, embryo quality is lower with high fat diet.Cells not fully committed to a cell fate (epiblast or primitive endoderm) are increased in embryos from mature dams or fed a high fat diet, indicating a delay in preimplantation embryo development.How might this impact on clinical practice in the foreseeable future?Our findings show a delay in early embryo development associated to obesity and maternal age. This delay could be responsible for the low fertility observed in women with type 2 diabetes and obesity.
Quantitative dose-response analysis untangles host bottlenecks to enteric infection
Authors: Campbell Ian W. , Hullahalli Karthik , Turner Jerrold R. , Waldor Matthew K. 
Published: October 2022

AbstractHost bottlenecks prevent many infections before the onset of disease by eliminating invading pathogens. Monitoring the diversity of a barcoded population of the diarrhea causing bacteriumCitrobacter rodentiumduring colonization of its natural host, mice, allowed us to determine the number of cells that found the infection by establishing a replicative niche. The size of the pathogen’s founding population scaled with dose and was controlled by a severe yet slow-acting bottleneck. Reducing stomach acid or changing host genotype modestly relaxed the bottleneck without breaking the fractional relationship between dose and founders. In contrast, disrupting the microbiota caused the founding population to no longer scale with the size of the inoculum and allowed the pathogen to infect at almost any dose, indicating that the microbiota creates the dominant bottleneck. Further, in the absence of competition with the microbiota, the diversity of the pathogen population slowly contracted as the population was overtaken by bacteria that lost the critical virulence island, the locus of enterocyte effacement (LEE). Collectively, our findings reveal that the mechanisms of protection by colonization bottlenecks are reflected in and can be generally defined by the impact of dose on the pathogen’s founding population.
Single Cell Transcriptomics Reveals the Hidden Microbiomes of Human Tissues
Authors: Mahmoudabadi Gita , Crasta Sheela ,   Tabula Sapiens Consortium, Quake Stephen R. 
Published: October 2022

AbstractThe human microbiome has been studied extensively across those sites in the body that are readily accessible to sampling. Internal organs and tissues, however, have remained largely unexplored and, in the absence of infectious disease, are widely assumed to be free of microorganisms. Using single-cell transcriptomic data from the Tabula Sapiens spanning 11 human organ donors, 19 tissue types, 400,000+ annotated cells, 100+ cell types, and ∼70 billion sequences, we created an atlas of the human tissue microbiome with cell type resolution across three domains of life which we refer to as the Tabula Sapiens Microbiome. Together with data from 8 additional donors derived from a different set of experimental techniques for validation, we identified sequences from numerous bacterial, viral and fungal species in human tissues. We mapped the likely microbial flow routes in the body from external-facing microbiomes and natural environments to internal tissues and tumors, demonstrating the existence of several unexpected routes. In the case of tumor microbiomes, we find a considerable number of bacterial genera found in tumors are detectable across tumor-free tissues, suggesting that tumor microbiomes are in part sourced from adjacent normal tissues, even those from distant sites. Finally, by increasing the resolution of sampling from tissues to cell types, we quantified the microbial load and diversity across different human cell types to reveal a network of host cell type and microbe associations. For example, we identified traces of both latent and active Epstein Barr Virus infections in various cell types such as splenic plasma cells. Broad exploration of the human tissue microbiomes may provide insights which ultimately are of clinical importance.
Post-pubertal developmental trajectories of laryngeal shape and size in humans
Authors: Riede Tobias , Stein Amy , Baab Karen L. , Hoxworth Joseph M. 
Published: October 2022

AbstractLaryngeal morphotypes have been hypothesized related to both phonation and to laryngeal pathologies. Morphotypes have not been validated or demonstrated quantitatively and sources of shape and size variation are incompletely understood but could be critical for the explanation of behavioral changes (e.g., changes of physical properties of a voice) and for therapeutic approaches to the larynx. Therefore results are likely to have implications for surgeons and speech language pathologists. A stratified human sample was interrogated for phenotypic variation of the vocal organ. First, computed tomography image stacks were used to generate three-dimensional reconstructions of the thyroid cartilage. Then cartilage shapes were quantified using multivariate statistical analysis of high dimensional shape data from margins and surfaces of the thyroid cartilage. The effects of sex, age, body mass index (BMI) and body height on size and shape differences were analyzed. We found that sex, age, BMI and the age-sex interaction showed significant effects on the mixed sex sample. Among males, only age showed a strong effect. The thyroid cartilage increased in overall size, and the angulation between left and right lamina decreased in older males. Age, BMI and the age-height interaction were statistically significant factors within females. The angulation between left and right lamina increased in older females and was smaller in females with greater BMI. A cluster analysis confirmed the strong age effect on larynx shape in males and a complex interaction between the age, BMI and height variables in the female sample. The investigation demonstrated that age and BMI, two risk factors in a range of clinical conditions, are associated with shape and size variation of the human larynx. The effects influence shape differently in female and male larynges. The male-female shape dichotomy is partly size-dependent but predominantly size-independent.
Background prostate tissue is quantitatively abnormal on MRI in patients with clinically significant prostate cancer
Authors: Conlin Christopher C , Karunamuni Roshan , Hussain Troy S , Zhong Allison Y , Kallis Karoline , Do Deondre D , Lui Asona J , Mani Garnier , Ollison Courtney , Domingo Mariluz Rojo , Shabaik Ahmed , Kane Christopher J , Bagrodia Aditya , McKay Rana R , Kuperman Joshua M , Rakow-Penner Rebecca , Hahn Michael E , Dale Anders M , Seibert Tyler M 
Published: October 2022

AbstractBackgroundT2-weighted MRI is standard for detecting clinically significant prostate cancer (csPCa) by identifying visible lesions that stand out from the background prostate.PurposeTo determine whether patients with csPCa have abnormalT2-weighted signal in non-lesion, background prostate tissue (BP).MethodsThis retrospective study included two patient cohorts who underwent 3T MRI examination for suspected csPCa. Median (urine-normalized)T2-weighted signal was computed for BP and compared between patients with and without csPCa. csPCa discrimination performance ofT2-weighted BP signal was evaluated using area under receiver operating characteristic curves (AUC).T2andS0(a proxy for proton density) were computed and compared between patients with and without csPCa.T2was also recomputed using larger buffers around csPCa lesions. csPCa discrimination performance was compared between two predictors: Restriction Spectrum Imaging (RSI)C1and RSIC1normalized by global prostate medianT2-weighted signal.ResultsCohort 1: 46 patients (age: 64±10 years). Cohort 2: 151 patients (65±8 years). Urine-normalizedT2-weighted signal was systematically lower in BP of subjects with csPCa (p≤0.034) and indicated the presence of cancer (cohort 1: AUC=0.80; cohort 2: AUC=0.68). BPT2was significantly lower in csPCa patients (p≤0.011), whileS0was not (p≥0.30). BPT2measurements were stable to within 5% with buffers from 0 to 30 mm around visible lesions. csPCa discrimination improved with incorporation of BPT2-weighted signal (cohort 1: AUC=0.72 for RSIC1alone, versus 0.81 with BPT2-weighted signal; cohort 2: AUC=0.63 versus 0.76).ConclusionLowerT2-weighted signal in BP suggests the presence of csPCa.
Potential protective link between type I diabetes and Parkinson’s disease risk and progression
Authors: Senkevich Konstantin , Alipour Paria , Chernyavskaya Ekaterina , Yu Eric , Noyce Alastair J , Gan-Or Ziv 
Published: October 2022

AbstractBackgroundEpidemiological studies suggested an association between Parkinson’s disease (PD) and type 2 diabetes, but less is known about type 1 diabetes (T1D) and PD.ObjectivesTo explore the association between T1D and PD.MethodsWe used Mendelian randomization, linkage disequilibrium score regression and transcriptome wide association analysis (TWAS) to examine the association between PD and T1D.ResultsMendelian randomization showed a potentially protective role of T1D for PD risk (inverse-variance weighted (IVW); OR (95% CI) 0.97 (0.94-0.99); p=0.039), as well as motor (IVW; 0.94 (0.88-0.99); p=0.044) and cognitive progression (IVW; 1.50 (1.08-2.09); p=0.015). We further found negative genetic correlation between T1D and PD (rg=-0.17, p=0.016), and identified nine genes in cross-tissue TWAS that were associated with both traits.ConclusionsOur results suggest a potential genetic link between T1D and PD risk and progression. Larger comprehensive epidemiological and genetic studies are required to validate our findings.
Utility of human judgment ensembles during times of pandemic uncertainty: A case study during the COVID-19 Omicron BA.1 wave in the USA
Authors: Venkatramanan Srinivasan , Cambeiro Juan , Liptay Tom , Lewis Bryan , Orr Mark , Dempsey Gaia , Telionis Alex , Crow Justin , Barrett Chris , Marathe Madhav 
Published: October 2022

AbstractResponding to a rapidly evolving pandemic like COVID-19 is challenging, and involves anticipating novel variants, vaccine uptake, and behavioral adaptations. Human judgment systems can complement computational models by providing valuable real-time forecasts. We report findings from a study conducted on Metaculus, a community forecasting platform, in partnership with the Virginia Department of Health, involving six rounds of forecasting during the Omicron BA.1 wave in the United States from November 2021 to March 2022. We received 8355 probabilistic predictions from 129 unique users across 60 questions pertaining to cases, hospitalizations, vaccine uptake, and peak/trough activity. We observed that the case forecasts performed on par with national multi-model ensembles and the vaccine uptake forecasts were more robust and accurate compared to baseline models. We also identified qualitative shifts in Omicron BA.1 wave prognosis during the surge phase, demonstrating rapid adaptation of such systems. Finally, we found that community estimates of variant characteristics such as growth rate and timing of dominance were in line with the scientific consensus. The observed accuracy, timeliness, and scope of such systems demonstrates the value of incorporating them into pandemic policymaking workflows.
Coverage and factor associated to the uptake of Intermittent preventive treatment for malaria during pregnancy (IPTp) in Cameroun in 2018: an analysis from the 2018 Cameroon Demographic Health Survey data
Authors: Ken Dominique Guimsop , Talla Ange Faustine Kenmogne , Kodji Haoua , Ateudjieu Jerome 
Published: October 2022

AbstractMalaria in pregnancy is a major public health issue, contributing to significantly increasing mother and children mortality and morbidity. Intermittent preventive treatment of malaria using Sulfadoxine-Pyrimethamine (IPTp-SP) is one of the key interventions recommended by WHO and in Cameroon to reduce the morbidity of Malaria in Pregnancy. The present study aims to assess the distribution and determinants of poor uptake of IPTp-SP (< 3 doses) among pregnant women in Cameroon.We conducted a secondary analysis of data extracted from the Cameroun Demographic Health Survey conducted in 2018. Data were collected using a questionnaire administered in face to face to mothers with at least one child under 5, selected using a 2-stage stratified sampling process. Frequencies of mothers exposed to less than 3 doses of IPTp-SP were estimated with a 95% CI. A case-control design was used to assess the association between key suspected determinants and being exposed to less than 3 doses of IPTp-SP. This was measured by estimating crude and adjusted Odd-Ratios (ORs).A total of 13527 childbearing age women were interviewed, of which 5528 (40.9%) met our selection criteria. Among those, 845 (15.3%) had not attended any Antenatal care (ANC) visit, 1109 (20%) had attended 1 to 3 visits, 3379 (61.1%) had attended 4 to 7 visits and only 195 (3.5%) had attended at least 8 visits. In all, 3398 (61.5%, CI: 60.2-62.8) had received less than 3 doses of IPTp-SP. Maternal age below 26 years (aOR=1.17, CI: 1.01-1.35), residence in an area of lower malaria endemicity (aOR=1.26, CI: 1.00-1.58), residence in the Sahelian regions (aOR=5.81, CI: 2.46-13.69), and having attended less than 4 ANC visits (aOR=1.30, CI: 1.08-1.57) were predictors of poor uptake of IPTp-SP. Conversely, residence in major cities (aOR=0.65, CI: 0.50-0.84), having attended a first ANC visit at 3 months or less of pregnancy (aOR=0.66, CI: 0.57-0.78) and having been followed on ANC by a medical doctor (aOR=0.22, CI: 0.13-0.35), were preventing factors for poor uptake of IPTp3+. Highest level of education (aOR= 1.10, CI: 0.90-1.32) was not found associated with the uptake of IPTp-SP.Therefore, only a third of pregnant women in Cameroon take an optimal dose of IPTp-SP. This proportion vary widely with the place of residence, being significantly low in the Sahelian regions. Interventions to address identified determinants of low coverage of IPTp-SP like maternal age below 26 years, ANC characteristics or being resident of area with lower malaria endemicity ought to be tested.
Spatiotemporal Correlation between Obesity Prevalence and the Percentage of Households using Air-conditioners in the United States
Authors: Li Evan , Wang Alexander , Xu Carter , Twum Felix , Zhang Jian 
Published: October 2022

PurposeThe axiom that obesity epidemic was driven by steady increases in energy intake has been challenged by empirical evidence, including the failure to make meaningful progress either treating or preventing obesity. Adopting new paradigm were urgently needed. We aimed to collect ecological evidences to support an alternative hypotheses that increased usage of air-conditioners (AC) may contribute to obesity epidemic in the U.S.MethodU.S. national survey data were retrieved from public domains, including the % of homes with AC units (AC ownership), dietary energy intake, and obesity prevalence. Correlation efficient were estimated, and Joint point regressions were ran to describe time segments and estimate annual percentage change (APC).ResultsNationally, Obesity prevalence significantly associated with the increasing trend of AC ownership (partialr=0.046, andp< 0.05) not dietary energy intake (r < 0.0001, andp= 0.58). When stratified by region, the rank of obesity prevalence across regions was consistent with that of AC ownership throughout the study period; the South led the increasing trends for both AC ownership and obesity prevalence. The climbing national trend of obesity slowed down around 2002 (before 2002 APC=4.38, and APC=2.22 after) following the saturation of AC penetration in the South (before 1994, APC=1.04,p< 0.05, and APC=0.05 after 1994,p> 0.05.ConclusionsSpatiotemporal correlations support the hypothesis that penetration of AC may contribute to the obesity epidemic. Further investigation may lead to novel therapies and a new avenue to explore the strategies addressing twin clusters of pandemics, obesity, and climate change.