bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metataxonomic analysis demonstrates a shift in duodenal microbiota in South African patients with obstructive jaundice: A pilot study
Authors: Hart Benjamin , Patel Jasmin , Maayer Pieter De , Nweke Ekene Emmanuel , Bizos Damon 
Published: May 2023

ABSTRACTThe human gastrointestinal tract (GIT) is home to an abundance of diverse microorganisms, and the balance of this microbiome plays a vital role in maintaining a healthy GIT. The obstruction of the flow of bile into the duodenum, resulting in obstructive jaundice (OJ), has a major impact on the health of the affected individual. This study sought to identify changes in the duodenal microbiota in South African patients with OJ compared to those without this disorder. Mucosal biopsies were taken from the duodenum of nineteen jaundiced patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and nineteen control participants (non-jaundiced patients) undergoing gastroscopy. DNA extracted from the samples was subjected to 16S rRNA amplicon sequencing using the Ion S5 TM sequencing platform. Diversity metrics and statistical correlation analyses with the clinical data were performed to compare duodenal microbial communities in both groups. Differences in the mean distribution of the microbial communities in the jaundiced and non-jaundiced samples were observed; however, this difference did not reach statistical significance. Of note, there was a statistically significant difference between the mean distributions of bacteria comparing jaundiced patients with cholangitis to those without. On further subset analysis, a significant difference was observed between patients with benign (Cholelithiasis) and malignant disease, namely head of pancreas (HOP) mass (p-values of 0.01). Beta diversity analyses further revealed a significant difference between patients with stone and non-stone related disease when factoring in the Campylobacter-Like Organisms (CLO) test status (p=0.048). This study demonstrated a shift in the microbiota in jaundiced patients, especially considering some underlying conditions of the upper GI tract. Future studies should aim to verify these findings in a larger cohort.
Prevalence and Prognostic Significance of Malnutrition Risk in Patients with Valvular Heart disease: Insight from the China-VHD Study
Authors: Li Ziang , Zhang Bin , li Zhe , Ye Yunqing , Zhang Erli , Zhang Haitong , Zhao Qinghao , Yu Zikai , Wang Weiwei , Guo Shuai , Duan Zhenya , Lv Junxing , Wang Bincheng , Gao Runlin , Xu Haiyan , Wu Yongjian 
Published: May 2023

AbstractBackgroundPrevious studies on the prevalence and prognosis of nutritional status in valvular heart disease (VHD) were primarily limited to aortic valve stenosis. The nutritional status of other types of VHDs remained an underexplored area. This study aimed to evaluate the prevalence of malnutrition risk in different types of VHD and investigate the association between malnutrition risk and adverse clinical events.MethodsA total of 8,908 patients with moderate or severe VHD in the China-VHD Study underwent echocardiography and malnutrition risk assessment using the geriatric nutritional risk index (GNRI). The primary outcome was 2-year all-cause mortality, while the secondary outcome was 2-year major adverse cardiovascular events (MACEs).ResultsAmong 8,908 patients (mean age 61.8±13.4 years; 56% male), approximately half were at risk for malnutrition. Patients with moderate or severe malnutrition risk had significantly higher risks of all-cause death and MACEs in various VHDs compared to those without malnutrition risk (all p<0.02). The strongest association was detected in patients with tricuspid regurgitation (mortality: hazard ratio [HR], 3.18, 95% confidence interval (CI), 1.99-5.10, p<0.001; MACEs: HR, 2.33, 95% CI, 1.58-3.44, p<0.001). Adding GNRI score to the European System for Cardiac Operative Risk Evaluation improved risk stratification and outcome prediction (C-statistic p<0.001; likelihood ratio test p<0.001).ConclusionMalnutrition risk was prevalent in various VHDs and was strongly associated with increased mortality and MACEs. The GNRI score provided incremental prognostic information for clinical outcomes. Future research is needed to evaluate the impact of nutritional interventions on outcomes in these vulnerable patients.What is known- Malnutrition is a prevalent condition among patients with aortic valve stenosis, and it represents a significant modifiable factor associated with adverse clinical outcomes.- Nutritional screening tools is effective in identifying malnutrition in patients with aortic valve stenosis, but its usefulness for other types of valvular heart disease (VHD) is still unclear.What the study adds-Malnutrition risk, as determined by geriatric nutritional risk index (GNRI), was prevalent in patients with all types of VHD.- Compared with patients without malnutritional risk, those with moderate or severe malnutritional risk had a significantly increased risk of all-cause death and major adverse cardiovascular events (MACEs) in various types of VHDs, irrespective of body mass index and cardiac function.- The addition of GNRI to the European System for Cardiac Operative Risk Evaluation (EuroSCORE II) amplified the stratification of patients at risk and improved outcome prediction.
Randomized trial to compare acceptability of Magnesium Sulphate administration for preeclampsia and eclampsia: Springfusor pump versus standard of care
Authors: Ononge Sam , Nakimuli Annettee , Byamugisha Josephat , Adroma Moses , Kiondo Paul , Easterling Thomas , Bracken Hillary 
Published: May 2023

AbstractIntroductionIn low-resource settings, magnesium sulphate (MgSO4)for preeclampsia is administered majorly through an injection into the gluteal muscles 4-hourly for 24 hours. The repeated injections are very painful and may lead to infection, abscess formation and reduced compliancy.ObjectiveTo determine the acceptability of Springfusor® pump for the administration of Magnesium Sulphate in preeclampsia and eclampsia.DesignRandomized Open Label Clinical TrialMethodStudy was conducted at Kawempe National Referral Hospital. Eligible women had systolic blood pressure of ≤40mmHg and or diastolic blood pressure >90mmHg, proteinuria ≤+1, and physician’s decision to start on MgSO4. Four-hundred-ninety-six participants were randomized to Springfusor® pump group or control (standard of care) administration of MgSO4. Intervention group had loading dose (4gm of 50% MgSO4intravenously over 20 minutes) and maintenance therapy (1gm of 50% MgSO4intravenously per hour for 24 hours) administered using the Springfusor®. The control group received a loading dose of 4gm of 20% MgSO4IV over 15-20 minutes, followed by 10gm of 50% MgSO4intramuscular (5gm in each buttock) and maintenance dose of 5gm of 50% MgSO4was administered IM every 4 hours for 24 hours. Both arms received the rest of the care for preeclampsia/eclampsia as per the hospital guidelines.Acceptability of method of administration was assessed using a Likert scale (1-5; 1 and 2: acceptable and 3-5: unacceptable). Pain at site of MgSO4administration was assessed using Visual Analogue Scale 1-7, (1 minimal pain and 7 worst pain). Comparisons were assessed with X-square and Students’ t-test.ResultsBaseline characteristics were similar in both arms. Intervention arm was; more acceptable than the standard of care arm, (94.9% vs70.3%; p<0.001), had lower pain score (2.2±1.3 vs. 4.1±1.6; p <0.001) and fewer side effects. Maternal mortality was comparable between groups (0.8% in intervention arm vs 1.2% in the IM arm).TRIAL REGISTRATIONTrial No PACTR201712002887266 (https://pactr.samrc.ac.za/)
The causal association between maternal depression, anxiety and infection in pregnancy and neurodevelopmental disorders among 410,461 children- a population study using quasi-negative control cohorts and sibling analysis
Authors: Hope Holly , Pierce Matthias , Gabr Hend , Radojčić Maja R , Swift Eleanor , Taxiarchi Vicky P , Abel Kathryn M 
Published: May 2023

AbstractBackgroundTo address if the long-standing association between maternal infection, depression/anxiety in pregnancy and offspring neurodevelopmental disorder (NDD) is causal we conducted two negative-control studies.MethodsFour primary care cohorts of UK children (pregnancy, 1 and 2 years prior to pregnancy and siblings) born between 1st January 1990 to 31st December 2017 were constructed.NDD included autism/autism spectrum disorder, attention deficit/hyperactivity disorder, intellectual disability, cerebral palsy, and epilepsy. Maternal exposures included depression/anxiety and/or infection. Maternal (age, smoking status, comorbidities, BMI (Body Mass Index), NDD); child (gender, ethnicity, birth year); and area-level (region and level of deprivation) confounders were captured.The NDD incidence rate among 1) children exposed during or outside of pregnancy and 2) siblings discordant for exposure in pregnancy was compared using Cox-regression models, unadjusted and adjusted for confounders.ResultsThe analysis included 410,461 children of 297,426 mothers and 2,793,018 person-years of follow-up with 8900 NDD cases (incidence rate=3.2 per 1000 person years). After adjustments, depression and anxiety consistently associated with NDD (pregnancy adjusted HR=1.58, 95%CI 1.46-1.72; 1-year adj.HR=1.49, 95%CI 1.39-1.60; 2-year adj.HR=1.62, 95%CI 1.50-1.74); and to a lesser extent, of infection (pregnancy adj. HR=1.16, 95%CI 1.10-1.22; 1-year adj.HR=1.20, 95%CI 1.14-1.27; 2-year adj.HR=1.19 95%CI 1.12-1.25). NDD risk did not differ among siblings discordant for pregnancy exposure to mental illness HR=0.97, 95%CI 0.77-1.21 or infection HR=0.99, 95%CI 0.90-1.08.ConclusionsTriangulation of results from two negative control studies provided no evidence of a specific, and therefore causal, link between in-utero exposure to infection, common mental illness, and later development of NDD.
Aryl Hydrocarbon Receptor Suppresses Eosinophilic Esophagitis Responses through OVOL1 and SPINK7
Authors: Azouz Nurit P. , Klingler Andrea M. , Rochman Mark , Paul Misu , Caldwell Julie M. , Brusilovsky Michael , Dwyer Alexander T. , Chen Xiaoting , Miller Daniel , Lynch Arthur , Forney Carmy , Kottyan Leah C. , Weirauch Matthew T. , Rothenberg Marc E. 
Published: May 2023

AbstractEosinophilic esophagitis (EoE) is a type 2 allergic disease characterized by esophageal inflammation and epithelial cell dysfunction. Acquired loss of the anti-serine protease of kazal type 7 (SPINK7) in the squamous epithelium of the esophagus has a causal role in EoE pathogenesis. Yet there is a limited understanding of the factors that regulate its expression and responsiveness to inflammatory stimuli. Herein, we identified the transcription factor, ovo like transcriptional repressor 1 (OVOL1) as an esophageal selective gene product that regulates SPINK7 promoter activity. Overexpression ofOVOL1increasedSPINK7expression, whereas, its depletion decreasedSPINK7expression, impaired epithelial barrier and increased production of the pro-atopy cytokine thymic stromal lymphopoietin (TSLP). Mechanistically, ligands of AHR induced nuclear translocation of OVOL1 which in turn promoted epithelial cell differentiation, barrier function andSPINK7expression. Interleukin (IL)-4 and IL-13 abolished AHR ligand-induced OVOL1 nuclear translocation. Stimulation with IL-13 abrogated the nuclear translocation of OVOL1 and promoted enhanced degradation of OVOL1 protein. This effect of IL-13 was dependent on the esophageal specific cysteine protease calpain-14. Translational studies demonstrated loss of OVOL1 protein expression in patients with EoE. In summary, AHR mediates its action via OVOL1-induced SPINK7 transcription, and IL-4 and IL-13 repress this pathway in EoE. As such, activation of the AHR pathway is a potential intervention strategy for reversing EoE.Graphical abstractThe influence of the exposome on regulatory networks in EoE pathogenesis.AHR is activated and influenced by diet nutrients, environmental toxicants, microbiome composition, tryptophan metabolites, and drugs. When AHR is activated, it promotes translocation of OVOL1 to the nucleus, which in turn promotes expression of epithelial genes includingSPINK7. SPINK7 expression promotes epithelial differentiation, barrier function, decreased proteolytic activity, and decreased TSLP production. IL-4 and IL-13 inhibit OVOL1 nuclear translocation and therefore, repressSPINK7expression. IL-13–stimulatedCAPN14expression decreases OVOL1 protein expression andSPINK7transcription.
SQANTI3: curation of long-read transcriptomes for accurate identification of known and novel isoforms
Authors: Pardo-Palacios Francisco J. , Arzalluz-Luque Angeles , Kondratova Liudmyla , Salguero Pedro , Mestre-Tomás Jorge , Amorín Rocío , Estevan-Morió Eva , Liu Tianyuan , Nanni Adalena , McIntyre Lauren , Tseng Elizabeth , Conesa Ana 
Published: May 2023

AbstractThe emergence of long-read RNA sequencing (lrRNA-seq) has provided an unprecedented opportunity to analyze transcriptomes at isoform resolution. However, the technology is not free from biases, and transcript models inferred from these data require quality control and curation. In this study, we introduce SQANTI3, a tool specifically designed to perform quality analysis on transcriptomes constructed using lrRNA-seq data. SQANTI3 provides an extensive naming framework to describe transcript model diversity in comparison to the reference transcriptome. Additionally, the tool incorporates a wide range of metrics to characterize various structural properties of transcript models, such as transcription start and end sites, splice junctions, and other structural features. These metrics can be utilized to filter out potential artifacts. Moreover, SQANTI3 includes a Rescue module that prevents the loss of known genes and transcripts exhibiting evidence of expression but displaying low-quality features. Lastly, SQANTI3 incorporates IsoAnnotLite, which enables functional annotation at the isoform level and facilitates functional iso-transcriptomics analyses. We demonstrate the versatility of SQANTI3 in analyzing different data types, isoform reconstruction pipelines, and sequencing platforms, and how it provides novel biological insights into isoform biology. The SQANTI3 software is available athttps://github.com/ConesaLab/SQANTI3.
Increased plasma lipopolysaccharide-binding protein and altered inflammatory mediators in overweight women suggest a state of subclinical endotoxemia
Authors: Metz Christine N. , Xue Xiangying , Chatterjee Prodyot K , Adelson Robert P. , Roth Jesse , Brines Michael , Tracey Kevin J. , Gregersen Peter K. , Pavlov Valentin A. 
Published: May 2023

AbstractChronic low-grade inflammation has been recognized as an underlying event linking obesity to cardiovascular disease (CVD). However, inflammatory alterations in individuals who are overweight remain understudied. To provide insight, we determined the levels of key circulating biomarkers of endotoxemia and inflammation, including lipopolysaccharide-binding protein (LBP), CRP, IL-6, leptin, and adiponectin in adult female subjects (n=40) who were lean or overweight and had high cholesterol and/or high blood pressure - two important conventional risk factors for CVD. Plasma levels of LBP were significantly higher in the overweight group compared with the lean group (P=0.005). The levels of CRP were also significantly higher in overweight subjects (P=0.01), as were IL-6 (P=0.02) and leptin (P=0.002), pro-inflammatory mediators associated with cardiovascular risk. Levels of adiponectin, an adipokine with anti-inflammatory and anti- atherogenic functions, were significantly lower in the overweight group (P=0.002). The leptin/adiponectin ratio, a preferential atherogenic marker was significantly increased in women who are overweight (P=0.02). LBP, CRP, leptin, and adiponectin levels significantly correlated with BMI, but not with age and there was a significant correlation between LBP and IL-6 levels. These results reveal the presence of subclinical endotoxemia and a pro-inflammatory state in overweight women and are of interest for further studies with the goal for improved understanding of cardiovascular health risks in women.
Diversity and distribution of the coral-associated endolithic algaeOstreobiumin the Southwestern Caribbean
Authors: Rodríguez-Bermúdez A.P. , Ramírez-Palma S. , Giraldo-Vaca J.S. , Diaz-Puerto L.M. , Sánchez J.A 
Published: May 2023

AbstractCoral reefs are facing significant environmental challenges. Ocean acidification has the potential to induce the dissolution of coral reefs. The community of micro-bioerosion exhibits a heightened level of concern in the context of ocean acidification. Comprehending the close interplay between bioeroders and corals is of utmost importance in predicting the trajectory of these vulnerable ecosystems. The genusOstreobium, which belongs to the order Bryopsidales (Chlorophyta) and comprises euendolithic chlorophyte algae, has been identified as the primary cause of reef dissolution among microbioeroders. The objective of this study was to comprehend the inherent distribution ofrbcLclades ofOstreobiumin the Southwestern Caribbean corals within a gradient of reef depth. TheOstreobium rbcLvariants were found to be linked with corals belonging to the Agariciidae, Merulinidae, Poritiidae, Siderastreidae, Astroconeiidae, Montastreidae, Mussidae, and Pocilloporidae families. The individuals selected for the current investigation are categorized as members of either the “complex” or “robust” coral groups. Our findings indicate that solely the corals categorized as ‘complex’ exhibit close memberships with the threeOstreobiumsuperclades. In general, the dispersion ofOstreobiumwithin the Southwestern Caribbean region exhibits differentiation among various coral groups and is influenced by geographical and bathymetric factors. TheOstreobium’s diversity is primarily composed of ecological specialists, wherein most clades are linked to particular hosts. Conversely, only a few ecological generalists are associated with multiple hosts, akin to zooxanthellae.Ostreobiumexhibits greater diversity on encrusting corals such as agariciids, which are among the most abundant and widespread coral species in the Caribbean.
Identification and functional validation of an enhancer variant in the 9p21.3 locus associated with glaucoma risk and elevated expression ofp16INK4a
Authors: Zhu Yizhou , Tazearslan Cagdas , Rosenfeld Michael G. , Fiser Andras , Suh Yousin 
Published: May 2023

AbstractGlaucoma is a leading cause of irreversible blindness, with advanced age being the single most significant risk factor. However, the mechanisms underlying the relationship between aging and glaucoma remain unclear. Genome-wide association studies (GWAS) have successfully identified genetic variants strongly associated with increased glaucoma risk. Understanding how these variants function in pathogenesis is crucial for translating genetic associations into molecular mechanisms and, ultimately, clinical applications. The chromosome 9p21.3 locus is among the most replicated glaucoma risk loci discovered by GWAS. Nonetheless, the absence of protein-coding genes in the locus makes interpreting the disease association challenging, leaving the causal variant and molecular mechanism elusive. In this study, we report the identification of a functional glaucoma risk variant, rs6475604. By employing computational and experimental methods, we demonstrated that rs6475604 resides in a repressive regulatory element. Risk allele of rs6475604 disrupts the binding of YY1, a transcription factor known to repress the expression of a neighboring gene in 9p21.3, p16INK4A, which plays a crucial role in cellular senescence and aging. These findings suggest that the glaucoma disease variant contributes to accelerated senescence, providing a molecular link between glaucoma risk and an essential cellular mechanism for human aging.
Considerable genetic diversity and structure despite endemism and limited ecological specialization in the Hayden’s ringlet,Coenonympha haydenii
Authors: Springer Amy , Gompert Zachariah 
Published: May 2023

AbstractUnderstanding the processes that underlie the development of population genetic structure is central to the study of evolution. Patterns of genetic structure, in turn, can reveal signatures of local adaptation, barriers to gene flow, or even the genesis of speciation. However, it is unclear whether the processes that dominate the development of genetic structure differ in populations with a severely restricted range relative to widespread species. For example, in narrowly endemic species, is population structure likely to be adaptive in nature (e.g., via niche specialization), or rather the result of genetic drift (e.g., isolation by distance)? In this study, we investigated patterns of genetic diversity and structure in the narrow endemic Hayden’s ringlet butterfly. Specifically, we asked to what degree genetic structure in the Hayden’s ringlet can be explained by isolation by distance, barriers to gene flow, and host association. We employed a genotyping-by-sequencing (GBS) approach coupled with host preference assays, Bayesian modeling, and population genomic analyses to answer these questions. Our results suggest that despite their restricted range, levels of genetic diversity in the Hayden’s ringlet are comparable to those seen in non-endemic butterfly species. Hayden’s ringlets showed a strong preference for feeding on grasses vs. sedges, but neither host preference nor potential host availability at sampling sites correlated with genetic structure. We conclude that geography, in the form of barriers to migration and simple isolation by distance, were the major drivers of differentiation in this endemic species.
Race, Sex and Age Disparities in the Performance of ECG Deep Learning Models Predicting Heart Failure
Authors: Kaur Dhamanpreet , Hughes John W. , Rogers Albert J. , Kang Guson , Narayan Sanjiv M. , Ashley Euan A. , Perez Marco V. 
Published: May 2023

ABSTRACTBackgroundDeep learning models may combat widening racial disparities in heart failure outcomes through early identification of individuals at high risk. However, demographic biases in the performance of these models have not been well studied.MethodsThis retrospective analysis used 12-lead ECGs taken between 2008 - 2018 from 290,252 patients referred for standard clinical indications to Stanford Hospital. The primary model was a convolutional neural network model trained to predict incident heart failure within 5 years. Biases were evaluated on the testing set (160,312 ECGs) using area under the receiver operating curve (AUC), stratified across the protected attributes of race, ethnicity, age, and sex.Results50,956 incident cases of heart failure were observed within 5 years of ECG collection. The performance of the primary model declined with age. There were no significant differences observed between racial groups overall. However, the primary model performed significantly worse in Black patients aged 0 - 40 compared to all other racial groups in this age group, with differences most pronounced among young Black women. Disparities in model performance did not improve with integration of race, ethnicity, gender, and/or age into model architecture, by training separate models for each racial group, nor by providing the model with a dataset of equal racial representation. Using probability thresholds individualized for race, age, and gender offered substantial improvements in F1-scores.ConclusionThe biases found in this study warrant caution against perpetuating disparities through the development of machine learning tools for the prognosis and management of heart failure. Customizing the application of these models by using probability thresholds individualized by race/ethnicity, age, and sex may offer an avenue to mitigate existing algorithmic disparities.