bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive analysis of SOX17 expression by immunohistochemistry in human epithelial tumors, with an emphasis on gynecologic tumors
Authors: Clark Beth Z , Soong T Rinda , Goel Kanika , Elishaev Esther , Zhao Chengquan , Jones Terri E , Jones Mirka W , Skvarca Lauren B , Motanagh Samaneh A , Carter Gloria J , Fine Jeffrey L , Harinath Lakshmi , Villatoro Tatiana M , Yu Jing , Bhargava Rohit 
Published: July 2024

Abstract

Objectives
The objective of this study was to evaluate SOX17, a transcription factor from the Sry high-mobility group–related box superfamily, as a diagnostic marker to determine site of origin using both whole-tissue sections and tissue microarrays (TMAs).

Methods
SOX17 immunohistochemistry was performed on gynecologic and nongynecologic tissues (N = 1004) using whole-tissue sections and both internally constructed and commercially available TMAs. SOX17 nuclear reactivity was scored as positive or negative on the whole-tissue sections and using the semiquantitative H score method on TMAs.

Results
Using both whole-tissue sections and TMAs, SOX17 was positive in 94% (n = 155) of endometrial tumors and 96% (n = 242) of ovarian tumors. All breast cases (n = 241) and vulvar/cervical squamous cell carcinomas (n = 150) were negative. Among 1004 tumors from 20 sites, the only organs with positive tumors were ovary, uterus, and testis.

Conclusions
SOX17 is a sensitive and specific marker for gynecologic origin in the tissues tested and may be a valuable adjunct to PAX8 and other commonly used markers to confirm endometrial or ovarian origin. SOX17 expression is lower in mucinous tumors, endocervical adenocarcinoma, high-grade neuroendocrine tumors, and undifferentiated/dedifferentiated endometrial carcinoma.
State-of-the-Art-Review: Mechanisms of Action of SGLT2 Inhibitors and Clinical Implications
Authors: Vallon Volker 
Published: July 2024

Abstract

BACKGROUND
Inhibitors of the Na+-coupled glucose transporter SGLT2 (SGLT2i) primarily shift the reabsorption of large amounts of glucose from the kidney’s early proximal tubule to downstream tubular segments expressing SGLT1, and the non-reabsorbed glucose is spilled into the urine together with some osmotic diuresis. How can this protect the kidneys and heart from failing as observed in individuals with and without type 2 diabetes?

GOAL
Mediation analyses identified clinical phenotypes of SGLT2i associated with improved kidney and heart outcome, including a reduction of plasma volume or increase in hematocrit, and lowering of serum urate levels and albuminuria. This review outlines how primary effects of SGLT2i on the early proximal tubule can explain these phenotypes.

RESULTS
The physiology of tubule-glomerular communication provides the basis for acute lowering of GFR and glomerular capillary pressure, which contributes to lowering of albuminuria but also to long term preservation of GFR, at least in part by reducing kidney cortex oxygen demand. Functional co-regulation of SGLT2 with other sodium and metabolite transporters in the early proximal tubule explains why SGLT2i initially excrete more sodium than expected and are uricosuric, thereby reducing plasma volume and serum urate. Inhibition of SGLT2 reduces early proximal tubule gluco-toxicity and by shifting transport downstream may simulate “systemic hypoxia”, and the resulting increase in erythropoiesis, together with the osmotic diuresis, enhances hematocrit and improves blood oxygen delivery. Cardio-renal protection by SGLT2i is also provided by a fasting-like and insulin-sparing metabolic phenotype and, potentially, by off-target effects on the heart and microbiotic formation of uremic toxins.
Impact of a pharmacist-led intervention on prostate cancer illness perception
Authors: Iheanacho Chinonyerem O , Odili Valentine U 
Published: July 2024

Abstract

Purpose
Illness perception (IP) significantly determines illness outcomes. This study determined the impact of a pharmacist educational intervention on IP and the predictors of IP in patients with prostate cancer (PCa).

Methods
Using a brief IP questionnaire, an interventional study of patients with PCa was conducted in all cancer reference hospitals in one Nigerian state. After a pre-post assessment of patients’ IP, descriptive and inferential statistical analyses were performed. The impact of pharmacists’ intervention on IP was determined by paired-sample statistics and correlation analysis at the 95% CI. Relationships and predictors of IP were determined using Kendall’s tau-b (τb), likelihood ratio, and F tests of equality of means, respectively. P &lt; 0.05 was considered statistically significant.

Results
Pharmacists’ educational intervention significantly improved IP (SEM, 0.13; r = 0.875; P &lt; 0.0001) among the 200 participants. The analyses also showed a significant paired sample difference (2.662; SEM, 0.06; 95%CI, 2.536-2.788; t = 41.69; df = 199; P &lt; 0.0001). All subscales of patients’ IP significantly improved except for illness consequences (P = 0.173) and identity (mean [SD], 4.40 [3.730] in both pre- and postintervention assessments). Pre- and postintervention assessments showed a significant negative relationship of IP with age (τb = –110 [P = 0.040] and τb = –14 [P = 0.021], respectively), Gleason score (τb = –0.125 [P = 0.021] and τb = –0.124 [P=0.012], respectively), and age at diagnosis (τb = –0.103 [P = 0.036] post intervention). IP was significantly dependent on the drug therapy (df = 8; mean square [M] = 6.292; F = 2.825; P = 0.006), alcohol intake (df = 1; M = 9.608; F = 4.082; P = 0.045) and Gleason score (df = 9; M = 6.706; F = 3.068; P = 0.002).

Conclusion
Patients’ IP significantly improved after pharmacists’ educational intervention. Predictors of IP were drug therapies, alcohol use and Gleason score. Findings can be extrapolated in clinical settings to improve treatment outcomes.
DeepIDA-GRU: a deep learning pipeline for integrative discriminant analysis of cross-sectional and longitudinal multiview data with applications to inflammatory bowel disease classification
Authors: Jain Sarthak , Safo Sandra E 
Published: July 2024

Abstract
Biomedical research now commonly integrates diverse data types or views from the same individuals to better understand the pathobiology of complex diseases, but the challenge lies in meaningfully integrating these diverse views. Existing methods often require the same type of data from all views (cross-sectional data only or longitudinal data only) or do not consider any class outcome in the integration method, which presents limitations. To overcome these limitations, we have developed a pipeline that harnesses the power of statistical and deep learning methods to integrate cross-sectional and longitudinal data from multiple sources. In addition, it identifies key variables that contribute to the association between views and the separation between classes, providing deeper biological insights. This pipeline includes variable selection/ranking using linear and nonlinear methods, feature extraction using functional principal component analysis and Euler characteristics, and joint integration and classification using dense feed-forward networks for cross-sectional data and recurrent neural networks for longitudinal data. We applied this pipeline to cross-sectional and longitudinal multiomics data (metagenomics, transcriptomics and metabolomics) from an inflammatory bowel disease (IBD) study and identified microbial pathways, metabolites and genes that discriminate by IBD status, providing information on the etiology of IBD. We conducted simulations to compare the two feature extraction methods.
Biclustering data analysis: a comprehensive survey
Authors: Castanho Eduardo N , Aidos Helena , Madeira Sara C 
Published: July 2024

Abstract
Biclustering, the simultaneous clustering of rows and columns of a data matrix, has proved its effectiveness in bioinformatics due to its capacity to produce local instead of global models, evolving from a key technique used in gene expression data analysis into one of the most used approaches for pattern discovery and identification of biological modules, used in both descriptive and predictive learning tasks. This survey presents a comprehensive overview of biclustering. It proposes an updated taxonomy for its fundamental components (bicluster, biclustering solution, biclustering algorithms, and evaluation measures) and applications. We unify scattered concepts in the literature with new definitions to accommodate the diversity of data types (such as tabular, network, and time series data) and the specificities of biological and biomedical data domains. We further propose a pipeline for biclustering data analysis and discuss practical aspects of incorporating biclustering in real-world applications. We highlight prominent application domains, particularly in bioinformatics, and identify typical biclusters to illustrate the analysis output. Moreover, we discuss important aspects to consider when choosing, applying, and evaluating a biclustering algorithm. We also relate biclustering with other data mining tasks (clustering, pattern mining, classification, triclustering, N-way clustering, and graph mining). Thus, it provides theoretical and practical guidance on biclustering data analysis, demonstrating its potential to uncover actionable insights from complex datasets.
A novel deep machine learning algorithm with dimensionality and size reduction approaches for feature elimination: thyroid cancer diagnoses with randomly missing data
Authors: Tutsoy Onder , Sumbul Hilmi Erdem 
Published: July 2024

Abstract
Thyroid cancer incidences endure to increase even though a large number of inspection tools have been developed recently. Since there is no standard and certain procedure to follow for the thyroid cancer diagnoses, clinicians require conducting various tests. This scrutiny process yields multi-dimensional big data and lack of a common approach leads to randomly distributed missing (sparse) data, which are both formidable challenges for the machine learning algorithms. This paper aims to develop an accurate and computationally efficient deep learning algorithm to diagnose the thyroid cancer. In this respect, randomly distributed missing data stemmed singularity in learning problems is treated and dimensionality reduction with inner and target similarity approaches are developed to select the most informative input datasets. In addition, size reduction with the hierarchical clustering algorithm is performed to eliminate the considerably similar data samples. Four machine learning algorithms are trained and also tested with the unseen data to validate their generalization and robustness abilities. The results yield 100% training and 83% testing preciseness for the unseen data. Computational time efficiencies of the algorithms are also examined under the equal conditions.
TWCOM: an R package for inference of cell–cell communication on spatially resolved transcriptomics data
Authors: Wu Dongyuan , Datta Susmita 
Published: July 2024

Abstract

Summary
The inference of cell–cell communication is important, as it unveils the intricate cellular behaviors at the molecular level, providing crucial insights essential for understanding complex biological processes and informing targeted interventions in various pathological contexts. Here, we present TWCOM, an R package that implements a Tweedie distribution-based model for accurate cell–cell communication inference. Operating under a generalized additive model framework, TWCOM adeptly handles both single-cell resolution and spot-based spatially resolved transcriptomics data, providing a versatile tool for robust biological sample analysis.

Availability and implementation
The R package TWCOM is available at https://github.com/dongyuanwu/TWCOM. Comprehensive documentation is included with the package.
Increased EHD1 in trophoblasts causes RSM by activating TGFβ signaling
Authors: Wu Xing , Shen Jiayan , Liu Jinjin , Kang Nannan , Zhang Mingshun , Cai Xinyu , Zhen Xin , Yan Guijun , Liu Yang , Sun Haixiang 
Published: July 2024

Abstract

Background
Recurrent spontaneous miscarriage is one of the complications during pregnancy. However, the pathogenesis of recurrent spontaneous miscarriage is far from fully elucidated.

Objective
Since the endocytic pathway is crucial for cellular homeostasis, our study aimed to explore the roles of endocytic recycling, especially EH domain containing 1, a member of the endocytic recycling compartment, in recurrent spontaneous miscarriage.

Study Design
We first investigated the expression of the endocytic pathway member EH domain containing 1 in villi from the normal and recurrent spontaneous miscarriage groups. Then, we performed ribonucleic acid sequencing and experiments in villi, HTR8 cells and BeWo cells to determine the mechanisms by which EH domain containing 1–induced recurrent spontaneous miscarriage. Finally, placenta–specific EH domain containing 1–overexpressing mice were generated to investigate the recurrent spontaneous miscarriage phenotype in vivo.

Results
EH domain containing 1 was expressed in extravillous trophoblasts and syncytiotrophoblast in the villi. Compared with the control group, recurrent spontaneous miscarriage patients expressed higher EH domain containing 1. A high level of EH domain containing 1 decreased proliferation, promoted apoptosis, and reduced the migration and invasion of HTR8 cells by activating the TGFβ receptor 1-SMAD2/3 signaling pathway. The TGFβ receptor 1 antagonist LY3200882 partially reversed the EH domain containing 1 overexpression-induced changes in the cell phenotype. Besides, a high level of EH domain containing 1 also induced abnormal syncytialization, which disturbed maternal–fetal material exchanges. In a mouse model, placenta-specific overexpression of EH domain containing 1 led to the failure of spiral artery remodeling, excessive syncytialization, and miscarriage.

Conclusions
Increased expression of EH domain containing 1 impaired the invasion of extravillous trophoblasts mediated by the TGFβ receptor 1-SMAD2/3 signaling pathway and induced abnormal syncytialization of syncytiotrophoblast, which is at least partially responsible for recurrent spontaneous miscarriage.
PathGPS: discover shared genetic architecture using GWAS summary data
Authors: Gao Zijun , Zhao Qingyuan , Hastie Trevor 
Published: July 2024

ABSTRACT
The increasing availability and scale of biobanks and “omic” datasets bring new horizons for understanding biological mechanisms. PathGPS is an exploratory data analysis tool to discover genetic architectures using Genome Wide Association Studies (GWAS) summary data. PathGPS is based on a linear structural equation model where traits are regulated by both genetic and environmental pathways. PathGPS decouples the genetic and environmental components by contrasting the GWAS associations of “signal” genes with those of “noise” genes. From the estimated genetic component, PathGPS then extracts genetic pathways via principal component and factor analysis, leveraging the low-rank and sparse properties. In addition, we provide a bootstrap aggregating (“bagging”) algorithm to improve stability under data perturbation and hyperparameter tuning. When applied to a metabolomics dataset and the UK Biobank, PathGPS confirms several known gene–trait clusters and suggests multiple new hypotheses for future investigations.
Identification of gaps in the delivery of high-quality care of patients with eosinophilic esophagitis
Authors: Njie Cheikh , Richman Courtney , Rebhun Jeffrey , Achalu Sudharshan , Kamal Afrin N , Otaki Fouad , Leiman David A , Kathpalia Priya 
Published: July 2024

Abstract
Quality indicators (QIs) are standardized metrics that can be used to quantify health care delivery and identify important areas for practice improvement. Nine QIs pertaining to the diagnosis and management of eosinophilic esophagitis (EoE) were recently established. We therefore aimed to identify existing gaps in care using these QIs. This is a retrospective, multicenter study utilizing recently established EoE QIs to evaluate practice patterns among adult gastroenterologists in the diagnosis and management of EoE. Three patient cohorts of 30 patients each presenting with dysphagia, food impaction, and new diagnosis of EoE, respectively, were obtained, yielding 120 patients per site to assess for every QI. Summary statistics were reported across two main themes: diagnosis and management. Subsequent analysis of gaps in care was then performed. The domain of diagnosis of EoE (QI 1 and 2) had the most notable gap in care with only 55% of the presenting patients undergoing appropriate evaluation for EoE. The domain of management of EoE had overall higher QI fulfillment—however it also contained significant intra-category variation in care. Notably, while 79% of patients had clinical follow-up within 1 year from remission, only 54% underwent surveillance endoscopy within 2 years of remission. In contrast, 100% of patients with symptomatic strictures independent of histologic response underwent endoscopic dilation (QI 4). Management approaches for EoE are evolving and variation in care delivery exists. We identified significant gaps in both diagnosis of EoE especially amongst patients presenting with index food impaction and long term management of EoE, when retrospectively evaluating care patterns using newly established QIs. This is the first study of its kind to utilize these previously established QIs to objectively identify care gaps that exist in EoE amongst several institutions. These findings also highlight the importance of QIs and standardization of management of complex chronic diseases like EoE to help bridge these gaps and provide a framework to measure adherence to these best practices.
Catheter ablation for atrial fibrillation and impact on clinical outcomes
Authors: Providencia Rui , Ali Hussam , Creta Antonio , Barra Sérgio , Kanagaratnam Prapa , Schilling Richard J , Farkowski Michal , Cappato Riccardo 
Published: July 2024

Abstract

Aims
Catheter ablation is the most effective rhythm-control option in patients with atrial fibrillation (AF) and is currently considered an option mainly for improving symptoms. We aimed to assess the impact of catheter ablation on hard clinical outcomes.

Methods and results
We performed a systematic review of randomized controlled trials (RCTs) comparing catheter ablation vs. optimized medical treatment. We searched MEDLINE, EMBASE, and CENTRAL on 8 January 2024, for trials published ≤10 years. We pooled data through risk ratio (RR) and mean differences (MDs), with 95% confidence interval (CI), and calculated the number needed to treat (NNT). Sub-group and sensitivity analyses were performed for the presence/absence of heart failure (HF), paroxysmal/persistent AF, early ablation, higher/lower quality, and published ≤5 vs. &gt;5 years. Twenty-two RCTs were identified, including 6400 patients followed for 6–52 months. All primary endpoints were significantly reduced by catheter ablation vs. medical management: all-cause hospitalization (RR = 0.57, 95% CI 0.39–0.85, P = 0.006), AF relapse (RR = 0.48, 95% CI 0.39–0.58, P &lt; 0.00001), and all-cause mortality (RR = 0.69, 95% CI 0.56–0.86, P = 0.0007, NNT = 44.7, driven by trials with HF patients). A benefit was also demonstrated for all secondary endpoints: cardiovascular mortality (RR = 0.55, 95% CI 0.34–0.87), cardiovascular (RR = 0.83, 95% CI 0.71–0.96), and HF hospitalizations (RR = 0.71, 95% CI 0.56–0.89), AF burden (MD = 20.6%, 95% CI 5.6–35.5), left ventricular ejection fraction (LVEF) recovery (MD = 5.7%, 95% CI 3.5–7.9), and quality of life (MLHFQ, AFEQT, and SF-36 scales).

Conclusion
Catheter ablation significantly reduced hospitalizations, AF burden, and relapse, and improved quality of life. An impact on hard clinical outcomes, with an important mortality reduction and improvement in LVEF, was seen for patients with AF and HF.
‘JOY to great Caesar’: popular songs on Farinel’s Ground in late 17th-century England
Authors: Schönlau Stephan 
Published: July 2024

Abstract
This article represents a follow-up to a previous article on ‘Farinel’s Ground’, published in the May 2021 issue of this journal. There, I had focused on the numerous instrumental versions of this extremely popular ground bass, not least because the late 17th- and early 18th-century folia—as it was known more widely across Europe—seems to have been primarily an instrumental genre. Nevertheless, the popularity of this ground in the 1680s—and of some of the divisions associated with it—gave rise to a number of vocal versions or ballads, some of which may have been at least comparable in popularity to the instrumental versions printed in The Genteel Companion (1683) and The Division-Violin (1684). Sharing the same melody and bass (whether notated or implied), these ballads were written and published during some of the most turbulent years in British history (1682–1702). While the origins of the first of these, Thomas D’Urfey’s The King’s Health or ‘JOY to great Caesar’, can be traced to the violin and recorder divisions on Farinel’s Ground published at more or less the same time as D’Urfey’s song, the song itself seems to have spawned a number of offshoots, including later instrumental versions referring to its textual incipit. Resulting from a study of the music, text and context of songs on ‘Farinel’s Ground, this article also discusses issues applicable to English broadside ballads of the 17th century more generally, such as changes in the political environment and the at times almost decorative function of musical notation on broadsides.
Riboflavin overproduction on lignocellulose hydrolysate by the engineered yeast Candida famata
Authors: Dzanaeva Ljubov S , Wojdyła Dominik , Fedorovych Dariya V , Ruchala Justyna , Dmytruk Kostyantyn V , Sibirny Andriy A 
Published: July 2024

Abstract
Lignocellulose (dry plant biomass) is an abundant cheap inedible residue of agriculture and wood industry with great potential as a feedstock for biotechnological processes. Lignocellulosic substrates can serve as valuable resources in fermentation processes, allowing the production of a wide array of chemicals, fuels, and food additives. The main obstacle for cost-effective conversion of lignocellulosic hydrolysates to target products is poor metabolism of the major pentoses, xylose and L-arabinose, which are the second and third most abundant sugars of lignocellulose after glucose. We study the oversynthesis of riboflavin in the flavinogenic yeast Candida famata and found that all major lignocellulosic sugars, including xylose and L-arabinose, support robust growth and riboflavin synthesis in the available strains of C. famata. To further increase riboflavin production from xylose and lignocellulose hydrolysate, genes XYL1 and XYL2 coding for xylose reductase and xylitol dehydrogenase were overexpressed. The resulting strains exhibited increased riboflavin production in both shake flasks and bioreactors using diluted hydrolysate, reaching 1.5 g L−1.