bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between long-term PM2.5 exposure and risk for pancreatic cancer: an application of social informatics
Authors: Bhavsar Nrupen A , Jowers Kay , Yang Lexie Z , Guha Sharmistha , Lin Xuan , Peskoe Sarah , McManus Hannah , McElroy Lisa , Bravo Mercedes , Reiter Jerome P , Whitsel Eric , Timmins Christopher
Published: August 2024

There is a profound need to identify modifiable risk factors to screen and prevent pancreatic cancer. Air pollution, including fine particulate matter (PM2.5), is increasingly recognized as a risk factor for cancer. We conducted a case-control study using data from the electronic health record (EHR) of Duke University Health System, 15-year residential history, NASA satellite fine particulate matter (PM2.5), and neighborhood socioeconomic data. Using deterministic and probabilistic linkage algorithms, we linked residential history and EHR data to quantify long-term PM2.5 exposure. Logistic regression models quantified the association between a 1 interquartile range (IQR) increase in PM2.5 concentration and pancreatic cancer risk. The study included 203 cases and 5027 controls (median age of 59 years, 62% female, 26% Black). Individuals with pancreatic cancer had higher average annual exposure (9.4 μg/m3) as compared to an IQR increase in average annual PM2.5, which was associated with greater odds of pancreatic cancer (odds ratio = 1.20; 95% CI, 1.00-1.44). These findings highlight the link between elevated PM2.5 exposure and increased pancreatic cancer risk. They may inform screening strategies for high-risk populations and guide air pollution policies to mitigate exposure.

This article is part of a Special Collection on Environmental Epidemiology.
Causal effects of competing obstetrical interventions: mediators of placental abruption and perinatal mortality
Authors: Ananth Cande V , Loh Wen Wei
Published: August 2024

Placental abruption, the premature placental separation, confers increased perinatal mortality risk with preterm delivery as an important pathway through which the risk appears mediated. Although pregnancies complicated by abruption are often delivered through an obstetrical intervention, many deliver spontaneously. We examined the contributions of clinician-initiated (PTDIND) and spontaneous (PTDSPT) preterm delivery at < 37 weeks as competing causal mediators of the abruption-perinatal mortality association. Using the Consortium for Safe Labor (2002-2008) data (n = 203 990; 1.6% with abruption), we applied a potential outcomes-based mediation analysis to decompose the total effect into direct and mediator-specific indirect effects through PTDIND and PTDSPT. Each mediated effect describes the reduction in the counterfactual mortality risk if that preterm delivery subtype was shifted from its distribution under abruption to without abruption. The total effect risk ratio (RR) of abruption on perinatal mortality was 5.4 (95% CI, 4.6-6.3). The indirect effect RRs for PTDIND and PTDSPT were 1.5 (95% CI, 1.4-1.6) and 1.5 (95% CI, 1.5-1.6), respectively; these corresponded to mediated proportions of 25% each. These findings underscore that PTDIND and PTDSPT each play essential roles in shaping perinatal mortality risks associated with placental abruption.
Evolutionary algorithms simulating molecular evolution: a new field proposal
Authors: Browning Jr. James S L , Tauritz Daniel R , Beckmann John
Published: August 2024

The genetic blueprint for the essential functions of life is encoded in DNA, which is translated into proteins—the engines driving most of our metabolic processes. Recent advancements in genome sequencing have unveiled a vast diversity of protein families, but compared with the massive search space of all possible amino acid sequences, the set of known functional families is minimal. One could say nature has a limited protein ”vocabulary.” A major question for computational biologists, therefore, is whether this vocabulary can be expanded to include useful proteins that went extinct long ago or have never evolved (yet). By merging evolutionary algorithms, machine learning, and bioinformatics, we can develop highly customized ”designer proteins.” We dub the new subfield of computational evolution, which employs evolutionary algorithms with DNA string representations, biologically accurate molecular evolution, and bioinformatics-informed fitness functions, Evolutionary Algorithms Simulating Molecular Evolution.
BioM2: biologically informed multi-stage machine learning for phenotype prediction using omics data
Authors: Zhang Shunjie , Li Pan , Wang Shenghan , Zhu Jijun , Huang Zhongting , Cai Fuqiang , Freidel Sebastian , Ling Fei , Schwarz Emanuel , Chen Junfang
Published: August 2024

Navigating the complex landscape of high-dimensional omics data with machine learning models presents a significant challenge. The integration of biological domain knowledge into these models has shown promise in creating more meaningful stratifications of predictor variables, leading to algorithms that are both more accurate and generalizable. However, the wider availability of machine learning tools capable of incorporating such biological knowledge remains limited. Addressing this gap, we introduce BioM2, a novel R package designed for biologically informed multistage machine learning. BioM2 uniquely leverages biological information to effectively stratify and aggregate high-dimensional biological data in the context of machine learning. Demonstrating its utility with genome-wide DNA methylation and transcriptome-wide gene expression data, BioM2 has shown to enhance predictive performance, surpassing traditional machine learning models that operate without the integration of biological knowledge. A key feature of BioM2 is its ability to rank predictor variables within biological categories, specifically Gene Ontology pathways. This functionality not only aids in the interpretability of the results but also enables a subsequent modular network analysis of these variables, shedding light on the intricate systems-level biology underpinning the predictive outcome. We have proposed a biologically informed multistage machine learning framework termed BioM2 for phenotype prediction based on omics data. BioM2 has been incorporated into the BioM2 CRAN package (https://cran.r-project.org/web/packages/BioM2/index.html).
Situational aesthetics in Ptolemaic culture
Authors: Bing Peter , Höschele Regina
Published: August 2024

The Ptolemies fostered a literature of exquisite polish and slender proportions, most strikingly embodied in Callimachus, whose aesthetic principles became synonymous with Alexandrian artistry. At the same time, however, they had a penchant for ostentatious display and gigantism, as evidenced, for example, in Ptolemy Philadelphus’ ‘Grand Procession’. While these two impulses might appear to be at odds, we argue that Ptolemaic patronage embraced a ‘situational aesthetic’, accommodating both the grandiose and the diminutive: these rulers understood that different situations (and their respective audiences) call for different aesthetic approaches.
pyTWMR: transcriptome-wide Mendelian randomization in python
Authors: Oreshkov Sergey , Lepik Kaido , Santoni Federico
Published: August 2024

Motivation

Mendelian randomization (MR) is a widely used approach to estimate causal effect of variation in gene expression on complex traits. Among several MR-based algorithms, transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) enables the uses of multiple SNPs as instruments and multiple gene expression traits as exposures to facilitate causal inference in observational studies.

Results

Here we present a Python-based implementation of TWMR and revTWMR. Our implementation offers GPU computational support for faster computations and robust computation mode resilient to highly correlated gene expressions and genetic variants

Availability and implementation

pyTWMR is available at github.com/soreshkov/pyTWMR.
Foodscapes for salmon and other mobile consumers in river networks
Authors: Rossi Gabriel J , Bellmore J Ryan , Armstrong Jonathan B , Jeffres Carson , Naman Sean M , Carlson Stephanie M , Grantham Theodore E , Kaylor Matthew J , White Seth , Katz Jacob , Power Mary E
Published: August 2024

Mobile consumers track fluctuating resources across heterogeneous landscapes to grow and survive. In river networks, the abundance and accessibility of food and the energetic consequences of foraging vary among habitats and through time, providing a shifting mosaic of growth opportunities for mobile consumers. However, a framework integrating the spatiotemporal dynamics of growth potential within riverscapes has been lacking. We present the concept of foodscapes to depict the dynamic changes in food abundance, food accessibility, and consumer physiology that contribute to spatial and temporal variation of fish growth in rivers. Drawing on case studies of salmonid fishes from Alaska to California, we illustrate how foodscapes can provide a plethora of foraging, growth, and life history opportunities that potentially contribute to population resilience. We identify knowledge gaps in understanding foodscapes and approaches for stewardship that focus on restoring diverse foraging and growth opportunities for fish and other mobile consumers in river networks.
Eco-emotional Responses to Climate Change: A Scoping Review of Social Work Literature
Authors: McCaffery Jillian , Boetto Heather
Published: August 2024

The existential threat of climate change to the future of human and non-human well-being evokes complex emotional responses. The aim of this study was to explore the extent and nature of social work literature relating to eco-emotions. Eco-emotions refer to a diverse array of emotional responses to climate change, for example, anxiety, anger and hope. A scoping review explored scholarly databases to examine literature relating to eco-emotions between 2000 and 2023. Data were extracted from the articles to synthesise key characteristics, and thematic analysis was undertaken to identify themes emerging from the data. The scoping review yielded a total of seven articles with a focus on worry, anxiety, hope and empathy. Themes identified were related to intergenerational relationships, eco-emotional fluidity and multidimensional practice. Drawing on the profession’s established knowledge base, eco-social work provides a framework for engaging with eco-emotions. Furthermore, acknowledging eco-emotions specific to First Nations peoples in the context of colonialism and incorporating Indigenous knowledges to improve planetary health are essential for a decolonised approach to eco-emotional practice. Given social work’s increasing engagement with climate change, this review highlights the need for greater awareness of and engagement with eco-emotions.
Synthesis of terminus-decorated aza[9]helicenes: control of interlayer interaction
Authors: Matsuo Yusuke , Seki Shu , Tanaka Takayuki
Published: August 2024

Azahelicenes are intriguing luminescent materials with a planar chirality. The properties of aza[9]helicene can be perturbed by attaching substituent at the termini. The impact of the terminal decoration has been investigated in view of structural and electronic aspects, leading to the control of interlayer interaction.
SoDCoD: a comprehensive database of Cu/Zn superoxide dismutase conformational diversity caused by ALS-linked gene mutations and other perturbations
Authors: Tabuchi Riko , Momozawa Yurika , Hayashi Yuki , Noma Hisashi , Ichijo Hidenori , Fujisawa Takao
Published: August 2024

A structural alteration in copper/zinc superoxide dismutase (SOD1) is one of the common features caused by amyotrophic lateral sclerosis (ALS)–linked mutations. Although a large number of SOD1 variants have been reported in ALS patients, the detailed structural properties of each variant are not well summarized. We present SoDCoD, a database of superoxide dismutase conformational diversity, collecting our comprehensive biochemical analyses of the structural changes in SOD1 caused by ALS-linked gene mutations and other perturbations. SoDCoD version 1.0 contains information about the properties of 188 types of SOD1 mutants, including structural changes and their binding to Derlin-1, as well as a set of genes contributing to the proteostasis of mutant-like wild-type SOD1. This database provides valuable insights into the diagnosis and treatment of ALS, particularly by targeting conformational alterations in SOD1.

Database URL: https://fujisawagroup.github.io/SoDCoDweb/
The biomedical relationship corpus of the BioRED track at the BioCreative VIII challenge and workshop
Authors: Islamaj Rezarta , Wei Chih-Hsuan , Lai Po-Ting , Luo Ling , Coss Cathleen , Gokal Kochar Preeti , Miliaras Nicholas , Rodionov Oleg , Sekiya Keiko , Trinh Dorothy , Whitman Deborah , Lu Zhiyong
Published: August 2024

The automatic recognition of biomedical relationships is an important step in the semantic understanding of the information contained in the unstructured text of the published literature. The BioRED track at BioCreative VIII aimed to foster the development of such methods by providing the participants the BioRED-BC8 corpus, a collection of 1000 PubMed documents manually curated for diseases, gene/proteins, chemicals, cell lines, gene variants, and species, as well as pairwise relationships between them which are disease–gene, chemical–gene, disease–variant, gene–gene, chemical–disease, chemical–chemical, chemical–variant, and variant–variant. Furthermore, relationships are categorized into the following semantic categories: positive correlation, negative correlation, binding, conversion, drug interaction, comparison, cotreatment, and association. Unlike most of the previous publicly available corpora, all relationships are expressed at the document level as opposed to the sentence level, and as such, the entities are normalized to the corresponding concept identifiers of the standardized vocabularies, namely, diseases and chemicals are normalized to MeSH, genes (and proteins) to National Center for Biotechnology Information (NCBI) Gene, species to NCBI Taxonomy, cell lines to Cellosaurus, and gene/protein variants to Single Nucleotide Polymorphism Database. Finally, each annotated relationship is categorized as ‘novel’ depending on whether it is a novel finding or experimental verification in the publication it is expressed in. This distinction helps differentiate novel findings from other relationships in the same text that provides known facts and/or background knowledge. The BioRED-BC8 corpus uses the previous BioRED corpus of 600 PubMed articles as the training dataset and includes a set of newly published 400 articles to serve as the test data for the challenge. All test articles were manually annotated for the BioCreative VIII challenge by expert biocurators at the National Library of Medicine, using the original annotation guidelines, where each article is doubly annotated in a three-round annotation process until full agreement is reached between all curators. This manuscript details the characteristics of the BioRED-BC8 corpus as a critical resource for biomedical named entity recognition and relation extraction. Using this new resource, we have demonstrated advancements in biomedical text-mining algorithm development.

Database URL: https://codalab.lisn.upsaclay.fr/competitions/16381
Changes in Endoscopic Activity and Classification of Lesions With Panenteric Capsule Endoscopy in Patients Treated for Crohn’s Disease—A Prospective Blinded Comparison With Ileocolonoscopy, Fecal Calprotectin, and C-Reactive Protein
Authors: Brodersen Jacob Broder , Kjeldsen Jens , Juel Mie Agerbæk , Knudsen Torben , Rafaelsen Søren Rafael , Jensen Michael Dam
Published: August 2024

Background and Aims

Panenteric capsule endoscopy (PCE) is a minimally invasive modality that may replace ileocolonoscopy (IC) in selected patients with Crohn’s disease (CD). This study aimed to evaluate the dynamics of repeated assessment with PCE in patients receiving medical treatment for ileocolonic CD.

Methods

This prospective, blinded, multicenter study included patients with endoscopically active CD. Patients were scheduled for IC, PCE, fecal calprotectin, and C-reactive protein before and 12 weeks after treatment with corticosteroids or biological therapy. The endoscopic disease activity was assessed with the Simple Endoscopic Score for Crohn’s Disease (SES-CD).

Results

Thirty-one patients entered the study, and PCE visualized 148 (95.5%) and 128 (82.6%) ileocolonic bowel segments before and after medical treatment, respectively. The median SES-CD decreased from 14 (interquartile range [IQR] 8-17) to 5 (IQR 0-14) (p < 0.001) and 14 (IQR 10-17) to 6 (IQR 3-12) (p < 0.001) with IC and PCE, respectively. The repeated measures correlation between PCE and IC was very strong (r = 0.77, p < 0.001), strong compared to fecal calprotectin (r = 0.42, p = 0.003), and moderate compared to C-reactive protein (r = 0.36, p = 0.005). The mean scores for ulcer size, ulcerated surface, and affected surface were comparable between PCE and IC both before and after treatment. PCE had a sensitivity and specificity of 80.6% (95% confidence interval [95% CI] 62.5-92.5) and 93.8% (95% CI 79.2-99.2), respectively, for ulcer healing compared to IC.

Conclusions

PCE is responsive in patients treated for CD and may serve as a minimally invasive alternative to IC in selected patients.
Specific Bacterial Co-abundance Groups Are Associated With Inflammatory Status in Patients With Ulcerative Colitis
Authors: Jangi Sushrut , Zhao Naisi , Hsia Katie , Park Young Soo , Michaud Dominique S , Yoon Hyuk
Published: August 2024

Background and Aims

While there is increasing interest in microbiome-directed therapies for patients with ulcerative colitis (UC), the identification of microbial targets remains elusive, underlining the need for novel approaches.

Methods

Utilizing metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn’s & Colitis Foundation, we used a tree-based dichotomous approach to assemble distinct clusters of species-level bacterial co-abundance groups (CAGs). We evaluated the abundance of bacterial CAGs and fungal taxa during remission (n = 166) and activity (n = 46). We examined if the bacterial CAGs identified in our cohorts were conserved in 2 healthy cohorts and a Korean UC cohort.

Results

CAG3 and CAG8, dominated by bacteria from the family Lachnospiraceae, were associated with remission. Low abundance of CAG8 and elevated abundance of Candida genus were predictive of active UC. Constituents from CAG8 were influential hub species of the remission-associated microbial UC network, including Ruminococcus gnavus, Erysipelatoclostridium ramosum, Blautia, and Dorea species. These hub species interactions were preserved in 2 healthy cohorts and were partially recapitulated in a Korean UC cohort. CAG8 abundance correlated with the secondary bile acid production pathway. Bacterial CAGs did not correlate with Candida; however, Bifidobacterium adolescentis and Alistipes putredinis were negatively associated with Candida.

Conclusions

Lachnospiraceae-dominated bacterial CAGs were associated with remission in UC, with key bacterial interactions within the CAG also observed in 2 healthy cohorts and a Korean UC cohort. Bacterial CAG-based analyses may aid in designing candidate consortia for microbiome-based therapeutics.
Epigenetics of violence against women: a systematic review of the literature
Authors: Bailo Paolo , Piccinini Andrea , Barbara Giussy , Caruso Palmina , Bollati Valentina , Gaudi Simona
Published: August 2024

Violence against women is a pervasive global issue with profound impacts on victims’ well-being, extending across cultural boundaries. Besides immediate physical harm, it triggers mental health consequences such as post-traumatic stress disorder (PTSD). Indeed, it is the trauma experienced during a violent event that can lead to epigenetic modifications, ultimately contributing to the onset of PTSD. While research on the epigenetic effects of trauma initially focused on war veterans and disaster survivors, there is a dearth of studies on violence against women. In this article, we performed a systematic review aimed to fill this gap, examining existing studies on the epigenetic impact of violence on women. The review assessed sample sizes, study validity, and gene-specific investigations. Currently, there is insufficient data for a comprehensive meta-analysis, highlighting a nascent stage in understanding this complex issue. Future research is crucial for deeper insights into the epigenetic mechanisms related to violence against women, contributing to improved interventions and support healthcare systems for affected individuals.
Preoperative quality of life predicts complications in thoracic surgery: a retrospective cohort study
Authors: Peters Eagan J , Buduhan Gordon , Tan Lawrence , Srinathan Sadeesh K , Kidane Biniam
Published: August 2024

OBJECTIVES

Patients undergoing thoracic surgery experience high complication rates. It is uncertain whether preoperative health-related quality of life (HRQOL) measurements can predict patients at higher risk for postoperative complications. The objective of this study was to determine the association between preoperative HRQOL and postoperative complications among patients undergoing thoracic surgery.

METHODS

This was a retrospective cohort study of prospectively collected data. Consecutive patients undergoing elective thoracic surgery at a Canadian tertiary care centre between January 2018 and January 2019 were included. Patient HRQOL was measured using the Euroqol-5 Dimension (EQ-5D) survey. Complications were recorded using the Ottawa Thoracic Morbidity and Mortality system. Uni- and multivariable analysis were performed.

RESULTS

Of 515 surgeries performed, 133 (25.8%) patients experienced at least 1 postoperative complication; 345 (67.0%) patients underwent surgery for malignancy. A range of 271 (52.7%) to 310 (60.2%) patients experienced pain/discomfort at each timepoint. On multivariable analysis, lower preoperative EQ-5D visual analogue scale scores were significantly associated with postoperative complications (adjusted odds ratio 0.97, 95% confidence interval 0.95–0.99; P = 0.01). Presence of malignancy was not independently associated with complications (P = 0.68).

CONCLUSIONS

Self-reported preoperative HRQOL can predict incidence of postoperative complications among patients undergoing thoracic surgery. Assessments of preoperative HRQOL may help identify patients at higher risk for developing complications. These findings could be used to direct preoperative risk-mitigation strategies in areas of HRQOL where patients suffer most, such as pain. The full perioperative trajectory of patient HRQOL should be discerned to identify subsets of patients who share common risk factors.
Multimodal Transformers and Their Applications in Drug Target Discovery for Aging and Age-Related Diseases
Authors: Steurer Barbara , Vanhaelen Quentin , Zhavoronkov Alex
Published: August 2024

Given the unprecedented rate of global aging, advancing aging research and drug discovery to support healthy and productive longevity is a pressing socioeconomic need. Holistic models of human and population aging that account for biomedical background, environmental context, and lifestyle choices are fundamental to address these needs, but integration of diverse data sources and large data sets into comprehensive models is challenging using traditional approaches. Recent advances in artificial intelligence and machine learning, and specifically multimodal transformer-based neural networks, have enabled the development of highly capable systems that can generalize across multiple data types. As such, multimodal transformers can generate systemic models of aging that can predict health status and disease risks, identify drivers, or breaks of physiological aging, and aid in target discovery against age-related disease. The unprecedented capacity of transformers to extract and integrate information from large and diverse data modalities, combined with the ever-increasing availability of biological and medical data, has the potential to revolutionize healthcare, promoting healthy longevity and mitigating the societal and economic impacts of global aging.
Racial and Ethnic Variations in Resilience Factors Among Sexual and Gender Minority Midlife and Older Adults
Authors: Nelson Christi L , Oswald Austin G , Jung Hailey H , Fredriksen-Goldsen Karen I
Published: August 2024

Background and Objectives

This study explores resilience factors among sexual and gender minority (SGM) midlife and older adults, identifying historical/environmental, psychological, social, and behavioral predictors, and examining variations across racial/ethnic subgroups. By adopting a resilience-focused perspective, this research contributes to understanding strengths in the SGM community in the context of aging.

Research Design and Methods

Using weighted survey data from Aging with Pride: National Health, Aging, and Sexuality/Gender Study, this research investigates distinct risk and protective factors associated with resilience among SGM midlife and older adults. Subgroup variations were assessed using regression models. Factors moderated by race/ethnicity were integrated into final interaction models.

Results

Hispanic and Black individuals showed significantly higher resilience than non-Hispanic Whites. Lifetime victimization and day-to-day discrimination were negatively associated with resilience. Positive associations were found for higher income, identity affirmation, larger network size, greater social participation, increased physical activity, and sufficient food intake. Interaction models revealed nuanced patterns by subgroups; education negatively impacted resilience among Black individuals, while income positively influenced Hispanic individuals’ resilience. The Other racial/ethnic group demonstrated unique associations between optimal sleep and resilience.

Discussion and Implications

This study shifts from a deficit-based to a resilience-focused approach among SGM midlife and older adults, revealing key strengths within diverse subgroups. Results underscore the significance of recognizing racial/ethnic differences in factors promoting resilience and posing risks for SGM midlife and older adults. Tailoring interventions to address the intersectional needs of SGM aging populations is essential for enhancing their abilities to bounce back from adverse events.
Which Social Variables Predict Diabetes Onset? Robust Findings in Two National Surveys
Authors: Hawkley Louise C , Wroblewski Kristen E , Schumm Philip , Wang Sabrina D , Finch Laura E , McClintock Martha K , Huang Elbert S
Published: August 2024

Background and Objectives

The role of social factors in diabetes onset has been obscured by wide variation in their conceptualization and operationalization. We apply 3 theoretical frameworks to categorize social relationship variables along several dimensions and identify which dimension(s) are robustly associated with incident diabetes in the older adult population.

Research Design and Methods

The National Social Life, Health, and Aging Project (n = 2,365) and the Health and Retirement Study (n =11,824) provided longitudinal data from 57 to 90-year-old respondents over a 4- to 5-year period. Logistic regression models were used to test associations of 15 social variables measured identically in both data sets with diabetes onset measured as respondents’ first report of a physician’s diagnosis.

Results

In both studies, not being married, experiencing strain in a spousal relationship, and feeling lonely were associated with increased risk for diabetes onset at follow-up. Inconsistent or null findings were observed for social support, social activity, network size, number of friends and relatives, living alone, and closeness to network members.

Discussion and Implications

Robust findings in 2 large-scale surveys support the importance of the valence dimension (i.e., positive and negative); specifically, alleviating negative aspects of social life might more effectively reduce risk for diabetes than augmenting positive ones. Findings were not aligned with social variables differing on the subjectivity dimension (i.e., structural, functional, and qualitative aspects of social connections). Future work needs consistent conceptualization and measurement of social factors to correctly identify and categorize risk factors for diabetes onset and other health conditions in older adults.
Rescue of Scn5a mis-splicing does not improve the structural and functional heart defects of a DM1 heart mouse model
Authors: Nitschke Larissa , Hu Rong-Chi , Miller Andrew N , Cooper Thomas A
Published: August 2024

Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant multisystemic disorder for which cardiac features, including conduction delays and arrhythmias, are the second leading cause of disease mortality. DM1 is caused by expanded CTG repeats in the 3′ untranslated region of the DMPK gene. Transcription of the expanded DMPK allele produces mRNAs containing long tracts of CUG repeats, which sequester the Muscleblind-Like family of RNA binding proteins, leading to their loss-of-function and the dysregulation of alternative splicing. A well-characterized mis-regulated splicing event in the DM1 heart is the increased inclusion of SCN5A exon 6A rather than the mutually exclusive exon 6B that normally predominates in adult heart. As previous work showed that forced inclusion of Scn5a exon 6A in mice recapitulates cardiac DM1 phenotypes, we tested whether rescue of Scn5a mis-splicing would improve the cardiac phenotypes in a DM1 heart mouse model. We generated mice lacking Scn5a exon 6A to force the expression of the adult SCN5A isoform including exon 6B and crossed these mice to our previously established CUG960 DM1 heart mouse model. We showed that correction Scn5a mis-splicing does not improve the DM1 heart conduction delays and structural changes induced by CUG repeat RNA expression. Interestingly, we found that in addition to Scn5a mis-splicing, Scn5a expression is reduced in heart tissues of CUG960 mice and DM1-affected individuals. These data indicate that Scn5a mis-splicing is not the sole driver of DM1 heart deficits and suggest a potential role for reduced Scn5a expression in DM1 cardiac disease.
Benefit-Risk Trade-offs and Patient Preferences for Therapy Selection in Ulcerative Colitis: a Multicountry Preference Study
Authors: Gisbert Javier P , Schreiber Stefan , Siegel Corey A , Magro Fernando , Jus Anna , Whichello Chiara , Michaels-Igbokwe Christine , Heidenreich Sebastian , Oortwijn Alessandra , Vermeire Séverine
Published: August 2024

Background

To help navigate the complex treatment landscape of ulcerative colitis (UC), we quantified the benefit-risk trade-offs that patients were willing to make when choosing treatment.

Methods

Patients completed an online discrete choice experiment. Eligible patients had a UC diagnosis for ≥6 months, were aged ≥18 years, and resided in France, Germany, Italy, Spain, or the UK. Patients chose between 2 hypothetical treatments set up to ensure trade-offs were made. Clinical trial data, literature review, and patient interviews identified treatment attributes. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. A patient-centric benefit-risk assessment of 200 mg of filgotinib was conducted as an example to show how measured trade-offs can be used.

Results

Overall, 631 patients participated; patients had a mean age of 42.2 years and were predominantly male (75.3%). Achieving and maintaining clinical remission was the most important factor for patients (RAI 32.4%); to achieve this, patients were willing to accept slightly higher risks of blood clots, serious infections, and malignancies compared with lower risk treatment profiles. Patients also valued the convenience of oral treatments, avoiding steroids, and the ability to attend school/work. The patient-centric benefit-risk assessment suggested patients are significantly more likely to prefer Janus kinase 1 preferential inhibitor filgotinib over placebo.

Conclusions

Achieving clinical remission was the highest treatment priority for patients. To attain this, patients were willing to accept some slightly higher risk treatment profiles. Patient choices in the benefit-risk assessment suggested patients were significantly more likely to prefer filgotinib over placebo.
Life-course influences of poverty on violence and homicide: 30-year Brazilian birth cohort study
Authors: Murray Joseph , Degli Esposti Michelle , Loret de Mola Christian , Martins Rafaela , Smith Andrew D A C , Moffitt Terrie E , Heron Jon , Miranda Vanessa Iribarrem , Lima Natalia , Horta Bernardo L
Published: August 2024

Background

Homicide is the leading cause of death among young people in Latin America, one of the world’s most violent regions. Poverty is widely considered a key cause of violence, but theories suggest different effects of poverty, depending on when it is experienced in the life-course. Longitudinal studies of violence are scarce in Latin America, and very few prospective data are available worldwide to test different life-course influences on homicide.

Methods

In a prospective birth cohort study following 5914 children born in southern Brazil, we examined the role of poverty at birth, in early childhood, and in early adulthood on violence and homicide perpetration, in criminal records up to age 30 years. A novel Structured Life Course Modelling Approach was used to test competing life-course hypotheses about ‘sensitive periods’, ‘accumulation of risk’, and ‘downward mobility’ regarding the influence of poverty on violence and homicide.

Results

Cumulative poverty and poverty in early adulthood were the most important influences on violence and homicide perpetration. This supports the hypothesis that early adulthood is a sensitive period for the influence of poverty on lethal and non-lethal violence. Results were replicable using different definitions of poverty and an alternative outcome of self-reported fights.

Conclusion

Cumulative poverty from childhood to adulthood was an important driver of violence and homicide in this population. However, poverty experienced in early adulthood was especially influential, suggesting the importance of proximal mechanisms for violence in this context, such as unemployment, organized crime, drug trafficking, and ineffective policing and justice systems.
The “Clinching Effect” and Affective Polarization: Exposure to Incivility via Social Media in the Presence of Online News
Authors: Brundidge Jennifer , Garrett R Kelly
Published: August 2024

The contemporary media environment is often characterized as awash in uncivil and divisive messages. Central to this characterization, are social media, where partisans may engage in uncivil exchanges with outgroup members. The Internet has also become a key source of partisan news content, which is often filled with vitriol and “outrage” toward “the other side.” Using panel survey data from a large and diverse general-population sample of the US, the current study considers the influence of exposure to incivility on social media and online news use on a particularly emotional form of division, affective polarization. Fixed effects regression analyses find no main effects, but significant interaction effects between exposure to incivility via social media and online news use (pro-attitudinal, counter-attitudinal, and nonpartisan online news use) on affective polarization. Exposure to incivility via social media as a form of personal contact, appears to supplement the effect of partisan online news (and vice versa), whether pro-attitudinal or counter-attitudinal, intensifying affective polarization. However, when combined with exposure to incivility on social media, nonpartisan news appears to have an attenuating effect on affective polarization.
MicroRNA miR-27a-5p Reduces Intestinal Inflammation Induced by Clostridioides difficile Flagella by Regulating the Nuclear Factor–κB Signaling Pathway
Authors: Kobeissy Philippe Hussein , Denève-Larrazet Cécile , Marvaud Jean-Christophe , Kansau Imad
Published: August 2024

Background

Clostridioides difficile is a major cause of nosocomial postantibiotic infections, often resulting in severe inflammation and watery diarrhea. Previous studies have highlighted the role of C. difficile flagellin FliC in activating Toll-like receptor 5 and triggering nuclear factor–κB (NF-κB) cell signaling, leading to the release of proinflammatory cytokines. However, the microRNA (miRNA)–mediated regulatory mechanisms underlying the FliC-induced inflammatory response remain unclear.

Methods

miRNA expression levels were analyzed in Caco-2 intestinal epithelial cells following FliC stimulation and infection with the epidemic C. difficile R20291 strain or its unflagellated mutant by reverse transcription–quantitative polymerase chain reaction. Chemical inhibitors were used to block NF-κB signaling, and their impact on miR-27a-5p expression was assessed. Knockdown and overexpression experiments with miRNA inhibitor and mimic respectively were conducted to elucidate the functional role of miR-27a-5p in FliC-induced inflammatory responses. Additionally, a mouse model of C. difficile infection was treated with miR-27a-5p to evaluate its therapeutic potential in vivo.

Results

miR-27a-5p showed significant FliC-dependent overexpression in Caco-2 cells. Inhibition of NF-κB signaling suppressed miR-27a-5p overexpression. Knockdown of miR-27a-5p increased NF-κB activation and cytokine production (tumor necrosis factor α and interleukin 8), while its overexpression had the opposite effect. Moreover, miR-27a-5p was overexpressed in the ceca of C. difficile–infected mice, correlating with intestinal interleukin 8 levels. Treatment of infected mice with the miR-27a-5p mimic reduced disease severity and intestinal inflammation.

Conclusions

miR-27a-5p plays a crucial role in regulating C. difficile–induced inflammation, suggesting its potential as a therapeutic target for controlling severe infection. These findings offer valuable insights into potential therapeutic strategies for managing C. difficile infection and associated inflammatory complications.
In vitro activity of delafloxacin against clinical levofloxacin-resistant Helicobacter pylori isolates
Authors: Luzarraga Victor , Cremniter Julie , Plouzeau Chloé , Michaud Anthony , Broutin Lauranne , Burucoa Christophe , Pichon Maxime
Published: August 2024

Background

Increasing antibiotic resistance in Helicobacter pylori necessitates research on new active molecules. In 2017, delafloxacin, a new fluoroquinolone with chemical properties of activity under acidic conditions, was approved for treatment of community-acquired bacterial pneumonia and acute bacterial skin and soft-tissue infections. Mutations in gyrA are responsible for fluoroquinolone resistance, but certain clinical isolates of H. pylori appear to display a dual phenotype: resistance to levofloxacin associated with very low delafloxacin MICs.

Objectives

To estimate epidemiological cut-off (ECOFF) values and to identify mutations in the gyrA gene, specific to FQ resistance, without increasing the MICs of delafloxacin.

Methods

Clinical strains (n = 231) were collected in the bacteriology laboratory of Poitiers University Hospital over a 2 year period to determine the ECOFF of delafloxacin. Retrospectively, 101 clinical strains with an levofloxacin-resistant phenotype (MIC > 1 mg/L) were selected from 2018 to 2022 for delafloxacin MIC determination and QRDR (gyrA) sequencing.

Results

The estimated ECOFF of delafloxacin was ≤0.125 mg/L. No H. pylori isolate showed a levofloxacin-sensitive phenotype with a delafloxacin MIC of >0.125 mg/L. Among the levofloxacin-resistant H. pylori isolates, 53.5% had delafloxacin MICs of ≤0.125 mg/L. The N87I mutation was associated with dual levofloxacin/delafloxacin resistance (P < 0.001) in contrast to the N87K and D91N mutations (P > 0.05). Mutations D91G and D91Y were not associated with a delafloxacin resistance phenotype (P > 0.05).

Conclusions

Delafloxacin seems to be a therapeutic alternative for levofloxacin-resistant strains with greater in vitro activity. However, further clinical/biological investigations are required to determine its efficacy in H. pylori eradication.
Gestating sows with a restricted feed allowance require a longer adaptation period before collecting feces compared with lactating sows in total tract digestibility assessments using index method
Authors: Choi Hyunjun , Jo Hyunwoong , Kim Sung Woo , Kim Beob Gyun
Published: August 2024

The objective of the present experiment was to determine the minimum adaptation period for total tract digestibility experiments in gestating and lactating sows using the indigestible index method. Five gestating and 5 lactating sows at parities 3 to 5 were used. An indigestible index of 0.5% chromic oxide was supplemented to a diet based on corn and soybean meal. The daily feed allowance for gestating sows was 2 kg and 2 equal meals were provided to the sows. Lactating sows were fed 6 kg of feed per day in 3 equal meals. After feeding a diet without supplemental chromic oxide for 5 d, index-supplemented diets were provided to the gestating and lactating sows. Feces were collected at 24-h intervals for 9 and 7 d from gestating and lactating sows, respectively. Fecal Cr concentrations increased linearly (P < 0.001) and quadratically (P < 0.001) with collection time in both gestating and lactating sows. Minimum adaptation periods were estimated by one-slope broken-line model. The break point of Cr concentrations in feces was day 7.2 (SE = 0.3) in the gestating sows and day 4.2 (SE = 0.2) in the lactating sows, respectively. Apparent total tract digestibility of dry matter, organic matter, and energy on day 4 was less (P < 0.001) than that on days 8 to 9 in gestating sows fed the experimental diet with a 2-kg feed allowance. In lactating sows fed the experimental diets with a 6-kg feed allowance, the apparent total tract digestibility of dry matter, organic matter, and energy on day 3 was less (P < 0.05) than that on days 5 to 7. In conclusion, at least 8 d of adaptation period are required for gestating sows to determine total tract digestibility using Cr as the indigestible index method whereas 5 d of adaptation period are required for lactating sows. An insufficient adaptation period results in lower digestibility values.
Deaf role-models for Deaf children in hearing families: a scoping review
Authors: Joy Angela , Ledger Susan , Duncan Jill
Published: August 2024

The use of Deaf role-models (DRMs) with Deaf children born into hearing families is a practice aimed at improving outcomes for Deaf children, yet there is little peer-reviewed research available to influence future direction of such. This scoping review directs attention to available research on DRMs as a socio-linguistic and cultural viewpoint for balancing a predominantly audiological approach for early intervention for Deaf children. Systematic database searches initially yielded 132 records, of which seven articles were included in this scoping review. Findings are presented as five themes: ‘Deaf Gain’ and associated cultural capital, effective communication, developmental influences, family (or caregiver) attitudes to Deafness, and administration of DRM programs. Few formalized DRM programs were identified within the literature. The review concludes with recommendations for further exploration of the DRM experiences of Deaf people and their families within Australia.
Pollinator response to livestock grazing: implications for rangeland conservation in sagebrush ecosystems
Authors: Goosey Hayes B , Blanchette Gabrielle E , Naugle David E
Published: August 2024

World food supplies rely on pollination, making this plant–animal relationship a highly valued ecosystem service. Bees pollinate flowering plants in rangelands that constitute up to half of global terrestrial vegetation. Livestock grazing is the most widespread rangeland use and can affect insect pollinators through herbivory. We examined management effects on bee abundance and other insect pollinators on grazed and idle sagebrush rangelands in central Montana, USA. From 2016 to 2018, we sampled pollinators on lands enrolled in rest-rotation grazing, unenrolled grazing lands, and geographically separate idle lands without grazing for over a decade. Bare ground covered twice as much area (15% vs. 7) with half the litter (12% vs. 24) on grazed than idle regardless of enrollment. Bee pollinators were 2–3 times more prevalent in grazed than idle in 2016–2017. In 2018, bees were similar among grazed and idled during an unseasonably wet and cool summer that depressed pollinator catches; captures of secondary pollinators was similar among treatments 2 of 3 study years. Ground-nesting bees (94.6% of total bee abundance) were driven by periodic grazing that maintained bare ground and kept litter accumulations in check. In contrast, idle provided fewer nesting opportunities for bees that were mostly solitary, ground-nesting genera requiring unvegetated spaces for reproduction. Managed lands supported higher bee abundance that evolved with bison grazing on the eastern edge of the sagebrush ecosystem. Our findings suggest that periodic disturbance may enhance pollinator habitat, and that rangelands may benefit from periodic grazing by livestock.
Schistosomiasis in migrants: bridging the gap in Italy’s treatment guidelines and access
Authors: Comelli Agnese , Angheben Andrea , Albonico Marco , Calleri Guido , Zammarchi Lorenzo , Napoli Christian , Marrone Rosalia
Published: August 2024

Schistosomiasis is a widespread disease that can cause serious health issues if not diagnosed and treated promptly. Fortunately, there is an effective and safe treatment available: praziquantel (PZQ). In countries with a high influx of migrants from schistosomiasis-endemic regions, it is crucial to ensure the availability of PZQ. This discussion will address the barriers and the need for PZQ in Italy.
The emerging role of cysteine-rich peptides in pollen–pistil interactions
Authors: Xue Jiao , Du Qian , Yang Fangfang , Chen Li-Yu
Published: August 2024

Unlike early land plants, flowering plants have evolved a pollen tube that transports a pair of non-motile sperm cells to the female gametophyte. This process, known as siphonogamy, was first observed in gymnosperms and later became prevalent in angiosperms. However, the precise molecular mechanisms underlying the male–female interactions remain enigmatic. From the landing of the pollen grain on the stigma to gamete fusion, the male part needs to pass various tests: how does the stigma distinguish between compatible and incompatible pollen? what mechanisms guide the pollen tube towards the ovule? what factors trigger pollen tube rupture? how is polyspermy prevented? and how does the sperm cell ultimately reach the egg? Successful male–female communication is essential for surmounting these challenges, with cysteine-rich peptides (CRPs) playing a pivotal role in this dialogue. In this review, we summarize the characteristics of four distinct classes of CRPs, systematically review recent progress in the role of CRPs in four crucial stages of pollination and fertilization, consider potential applications of this knowledge in crop breeding, and conclude by suggesting avenues for future research.