bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boosting UPR transcriptional activator XBP1 accelerates acute wound healing
Authors: Wang Jie-Mei , Li Hainan , Xu Liping , Kim Hyunbae , Qiu Yining , Zhang Kezhong 
Published: February 2023

Abstract
Patients’ suffering from large or deep wounds caused by traumatic and/or thermal injuries have significantly lower chances of recapitulating lost skin function through natural healing. We tested whether enhanced unfolded protein response (UPR) by expression of a UPR transcriptional activator, X-box-binding protein 1 (XBP1) can significantly promote wound repair through stimulating growth factor production and promoting angiogenesis. In mouse models of a second-degree thermal wound, a full-thickness traumatic wound, and a full-thickness diabetic wound, the topical gene transfer of the activated form of XBP1 (spliced XBP1, XBP1s) can significantly enhance re-epithelialization and increase angiogenesis, leading to rapid, nearly complete wound closure with intact regenerated epidermis and dermis. Overexpression of XBP1s stimulated the transcription of growth factors in fibroblasts critical to proliferation and remodeling during wound repair, including platelet-derived growth factor BB, basic fibroblast growth factor, and transforming growth factor beta 3. Meanwhile, the overexpression of XBP1s boosted the migration and tube formation of dermal microvascular endothelial cells in vitro. Our functional and mechanistic investigations of XBP1-mediated regulation of wound healing processes provide novel insights into the previously undermined physiological role of the UPR in skin injuries. The finding opens an avenue to developing potential XBP1-based therapeutic strategies in clinical wound care protocols.
Eternally Damned, Yet Socially Conscious? The Volunteerism of Canadian Atheists
Authors: Speed David , Edgell Penny 
Published: February 2023

Abstract
Research suggests that people who are religious may volunteer because religion is innately prosocial (i.e., inclination) or perhaps because religious communities provide volunteering chances (i.e., opportunities). Using data from Statistics Canada (General Social Survey, Cycle 33), we explored the relationship between different religious and nonreligious identities and volunteering behaviors, time commitments to volunteering, and organization types for which respondents volunteered. Results indicated a complex relationship between religious/nonreligious identity, religious attendance, and prayer. We found that (1) atheists were more likely to volunteer than religious individuals who were low on religious attendance; (2) atheists were less likely to volunteer than religious individuals who were high on religious attendance; (3) the difference in volunteering between atheists and religious individuals was driven by the latter’s volunteering in a religious context, not in the broader community. The results suggest that atheists likely have fewer opportunities to volunteer but are similarly inclined to volunteer.
A pragmatic framework for the application of new approach methodologies in one health toxicological risk assessment
Authors: Magurany Kelly A , Chang Xiaoqing , Clewell Rebecca , Coecke Sandra , Haugabrooks Esther , Marty Sue 
Published: February 2023

AbstractGlobally, industries and regulatory authorities are faced with an urgent need to assess the potential adverse effects of chemicals more efficiently by embracing new approach methodologies (NAMs). NAMs include cell and tissue methods (in vitro), structure-based/toxicokinetic models (in silico), methods that assess toxicant interactions with biological macromolecules (in chemico), and alternative models. Increasing knowledge on chemical toxicokinetics (what the body does with chemicals) and toxicodynamics (what the chemicals do with the body) obtained from in silico and in vitro systems continues to provide opportunities for modernizing chemical risk assessments. However, directly leveraging in vitro and in silico data for derivation of human health-based reference values has not received regulatory acceptance due to uncertainties in extrapolating NAM results to human populations, including metabolism, complex biological pathways, multiple exposures, interindividual susceptibility and vulnerable populations. The objective of this article is to provide a standardized pragmatic framework that applies integrated approaches with a focus on quantitative in vitro to in vivo extrapolation (QIVIVE) to extrapolate in vitro cellular exposures to human equivalent doses from which human reference values can be derived. The proposed framework intends to systematically account for the complexities in extrapolation and data interpretation to support sound human health safety decisions in diverse industrial sectors (food systems, cosmetics, industrial chemicals, pharmaceuticals etc.). Case studies of chemical entities, using new and existing data, are presented to demonstrate the utility of the proposed framework while highlighting potential sources of human population bias and uncertainty, and the importance of Good Method and Reporting Practices.
In colon cancer cells fascin1 regulates adherens junction remodeling
Authors: Esmaeilniakooshkghazi Amin , Pham Eric , George Sudeep P. , Ahrorov Afzal , Villagomez Fabian R. , Byington Michael , Mukhopadhyay Srijita , Patnaik Srinivas , Conrad Jacinta C. , Naik Monali , Ravi Saathvika , Tebbutt Niall , Mooi Jennifer , Reehorst Camilla M. , Mariadason John M. , Khurana Seema 
Published: February 2023

AbstractAdherens junctions (AJs) are a defining feature of all epithelial cells. They regulate epithelial tissue architecture and integrity, and their dysregulation is a key step in tumor metastasis. AJ remodeling is crucial for cancer progression, and it plays a key role in tumor cell survival, growth, and dissemination. Few studies have examined AJ remodeling in cancer cells consequently, it remains poorly understood and unleveraged in the treatment of metastatic carcinomas. Fascin1 is an actin‐bundling protein that is absent from the normal epithelium but its expression in colon cancer is linked to metastasis and increased mortality. Here, we provide the molecular mechanism of AJ remodeling in colon cancer cells and identify for the first time, fascin1's function in AJ remodeling. We show that in colon cancer cells fascin1 remodels junctional actin and actomyosin contractility which makes AJs less stable but more dynamic. By remodeling AJs fascin1 drives mechanoactivation of WNT/β‐catenin signaling and generates “collective plasticity” which influences the behavior of cells during cell migration. The impact of mechanical inputs on WNT/β‐catenin activation in cancer cells remains poorly understood. Our findings highlight the role of AJ remodeling and mechanosensitive WNT/β‐catenin signaling in the growth and dissemination of colorectal carcinomas.
Pathological pseudoprogression to anti-PD-1 inhibitor in metastatic periampullary carcinoma: Case report
Authors: Wang Junhui , Wang Yan , Che Xiaoling 
Published: February 2023

Rationale:
Pseudoprogression has been deemed as a rare clinical phenomenon during the treatment of immune checkpoint inhibitors in patients with advanced cancers, especially in periampullary carcinoma, however, leaving potential molecular mechanism remain unknown.

Patient concerns:
Regular examination after radical pancreaticoduodenectomy because of periampullary carcinoma.

Diagnoses:
Recurrent periampullary carcinoma with metastasis in liver.

Interventions:
Regimens of XELOX (oxaliplatin at a dose of 130 mg/m2, day 1 and oral capecitabine at a dose of 1000 mg/m2 twice a day, day 1–14, every 21 days), and tislelizumab at a dose of 200 mg, day 1, per 21 days, was prescribed as palliative treatment.

Outcomes:
Pseudoprogression and symptom of hair and mustache repigmentation were also observed, which resulted in partial response finally.

Lessons:
Results of the present case suggested that pseudoprogression, along with hair and mustache repigmentation, possibly caused by anti-PD-1 inhibitors, may also happen in patients with periampullary carcinoma, which should be paid attention to. The potential mechanism should be further investigated.
Hepatic failure in a patient with rheumatoid arthritis treated with methotrexate: A case report
Authors: Miyata Masayuki , Ishiwata Sho , Kuroda Masahito , Tasaki Kazuhiro , Migita Kiyoshi , Ohira Hiromasa 
Published: February 2023

Introduction:
Chronic liver damage from methotrexate (MTX) is not uncommon, and fatal outcome is rare. We experienced a case of hepatic failure leading to death. We considered the cause of death through this case and proposed a method to prevent the progression of this liver injury.

Patient concerns:
We report the case of a patient with rheumatoid arthritis treated with MTX for 15 years.

Diagnosis, interventions, and outcomes:
A liver biopsy revealed histological changes similar to those of advanced nonalcoholic steatohepatitis (NASH), most likely induced by MTX. MTX was discontinued after 4 years. Two years after the discontinuation, the patient died of irreversible hepatic failure. Her obesity, complicated by type 2 diabetes mellitus, might have aggravated MTX-induced NASH-like liver injury.

Conclusion:
Early diagnosis and immediate MTX discontinuation following NASH diagnosis and strict type 2 diabetes mellitus control might have prevented the irreversible progression of liver injury.
The low glutamate diet reduces blood pressure in veterans with Gulf War Illness: A CONSORT randomized clinical trial
Authors: Fiebel Prairie R. , Ramachandra Shalini S. , Holton Kathleen F. 
Published: February 2023

Background:
Gulf War Illness is a multi-symptom condition affecting veterans of the 1990 to 1991 Gulf War, which often presents with comorbid hypertension. The purpose of this study was to analyze the effects of the low glutamate diet, as well as an acute challenge of monosodium glutamate (MSG)/placebo, on resting heart rate, blood oxygenation level, and blood pressure (BP) in this population.

Methods:
These data were measured at 4 time points: baseline, after 1 month on the low glutamate diet, and during each challenge week, where subjects were randomized into a double-blind, placebo-controlled, crossover challenge with MSG/placebo over 3 days each week. Pre-post diet changes were analyzed using paired t tests, change in the percentage of veterans meeting the criteria for hypertension was compared using chi-square or Fisher exact tests, and crossover challenge results were analyzed using general linear modeling in SAS® 9.4.

Results:
There was a significant reduction in systolic BP (sitting and recumbent; both P < .001) and diastolic BP (sitting; P = .02) after 1 month on the diet. The percentage meeting the criteria for hypertension was also significantly reduced (P < .05). Challenge with MSG/placebo did not demonstrate an acute effect of glutamate on blood pressure.

Conclusion:
Overall, these findings suggest that the low glutamate diet may be an effective treatment for lowering blood pressure in veterans with Gulf War Illness. This dietary effect does not appear to be driven by reduced consumption of free glutamate, but rather, by an increase in consumption of non-processed foods.
Efficacy of probiotics on nonalcoholic fatty liver disease: A meta-analysis
Authors: Zhou Xiangyu , Wang Jincheng , Zhou Sufang , Liao Jiajia , Ye Zuoyu , Mao Leiming 
Published: February 2023

Objectives:
The intestinal flora is closely related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). This study intends to systematically evaluate the efficacy and safety of probiotics in the treatment of NAFLD through a meta-analysis of published randomized controlled trials.

Methods:
This study was conducted through a search of published randomized controlled trials using probiotic-related drugs for the treatment of nonalcoholic fatty liver disease (up to April 6, 2022). The JADAD evaluation table was used to evaluate the quality of the literatures included in the search, and the risk of bias was evaluated according to the Cochrane evaluation manual. Finally, RevMan5.4 software was used for meta-analysis.

Results:
A total of 21 randomized clinical trials involving 1037 patients with NAFLD were included in this study. Meta-analysis results showed that after probiotic intervention, liver function, blood lipid level, blood glucose levels and insulin levels were significantly reduced, which had a good effect on improving hepatic steatosis. However, it did not significantly improve BMI, inflammatory factors, or homeostasis model assessment of insulin resistance. Through the subgroup analysis of the course of treatment, it was found that ALT, GGT, TG, and blood sugar improved better in the probiotic treatment course of greater than or equal to 12 weeks.

Conclusion:
This study shows that the use of probiotics therapy has a good regulating effect on liver function, steatosis, blood glucose level, insulin level and blood lipid level in NAFLD patients.
Efficiency of virtual reality for cardiopulmonary resuscitation training of adult laypersons: A systematic review
Authors: Alcázar Artero Petronila Mireia , Pardo Rios Manuel , Greif Robert , Ocampo Cervantes Ana Belén , Gijón-Nogueron Gabriel , Barcala-Furelos Roberto , Aranda-García Silvia , Ramos Petersen Laura 
Published: February 2023

Background:
Virtual reality (VR) is an interesting and promising way to teach cardiopulmonary resuscitation (CPR) to adult laypersons as its high immersive characteristics could improve the level of skills and acquired knowledge in learning basic life support (BLS).

Methods:
This systematic review assesses current literature about BLS training with VR and its possible effect on CPR-quality parameters, self-efficacy, perceived learning, and learners’ satisfaction and short and long-term patients’ outcome. We screened the Cochrane Library, PubMed, CINAHL, MEDLINE Ovid, Web of Science, and Scopus databases and included only clinical trials and quasi-experimental studies published from inception to October 1, 2021, which analyzed adult laypersons’ BLS training with the use of VR. Primary outcomes were CPR parameters (chest compression rate and depth, Automated External Defibrillator use). Secondary outcomes were self-efficacy, perceived learning and learners satisfaction, and patients’ outcomes (survival and good neurologic status). The risk of bias of included study was assessed using the Cochrane Handbook for Systematic Reviews of Interventions tool to evaluate randomized control trials and the transparent reporting of evaluations with nonrandomized designs checklist for nonrandomized studies.

Results:
After full article screening, 6 studies were included in the systematic review (731 participants) published between 2017 and 2021. Because of the heterogeneity of the studies, we focused on describing the studies rather than meta-analysis. The assessment of the quality of evidence revealed overall a very low quality. Training with VR significantly improved the rate and depth of chest compressions in 4 out of 6 articles. VR was described as an efficient teaching method, exerting a positive effect on self-efficacy, perception of confidence, and competence in 2 articles.

Conclusion:
VR in BLS training improves manual skills and self-efficacy of adult laypersons and may be a good teaching method in a blended learning CPR training strategy. VR may add another way to divide complex parts of resuscitation training into easier individual skills. However, the conclusion of this review suggests that VR may improve the quality of the chest compressions as compared to instructor-led face-to-face BLS training.
Oral Care Associated With Less Microaspiration in Ventilated Cardiac Patients
Authors: Patel Nishant , Lin Philip , Stack Michael , Conrad Janet M. , Fakioglu Harun , Abomoelak Bassam , Horvath Karoly , Mehta Devendra I. 
Published: February 2023

Background and Objective:
Aspiration is common in mechanically ventilated patients and may predispose patients to aspiration pneumonia, chemical pneumonitis, and chronic lung damage. Pepsin A is a specific marker of gastric fluid aspiration and is often detected in ventilated pediatric patients. We investigated the effect of oral care and throat suctioning in the detection of pepsin A in tracheal aspirates (TAs) up to 4 hours after these procedures.

Methods:
Twelve pediatric patients between age 2 weeks to 14 years who underwent intubation for cardiac surgery were enrolled in this study. Six of the 12 patients were consented before their surgery with initial specimen collected at the time of intubation and last one shortly before extubation (intubation duration < 24 hours). The remaining 6 patients were consented after cardiac surgery. All specimens were collected per routine care per respiratory therapy protocol and shortly before extubation (intubation duration > 24 hours). Tracheal fluid aspirates were collected every 4 to 12 hours in the ventilated patients. Enzymatic assay for gastric pepsin A and protein determination were performed. The time of oral care and throat suctioning within 4 hours prior was recorded prospectively.

Results:
A total of 342 TA specimens were obtained from the 12 intubated pediatric patients during their course of hospitalization; 287 (83.9%) showed detectable total pepsin (pepsin A and C) enzyme activity (> 6 ng/mL) and 176 (51.5%) samples had detectable pepsin A enzyme levels (>6 ng/mL of pepsin A). Only 29 samples of 76 samples (38.2%) had evidence of microaspiration after receiving oral care, while 147 of 266 (55.3%) samples were pepsin A positive when no oral care was provided. Odds ratio is 0.50 (Cl 0.30–0.84), and the number needed to treat is 5.8 (Confidence interval 3.4–22.3). Testing air filters for pepsin was not beneficial.

Conclusion:
Oral care is a highly effective measure to prevent microaspiration of gastric fluid in ventilated pediatric patients. The number needed to treat (5.8) suggests this is a very effective prevention strategy. Our study suggests that pepsin A is a useful and sensitive biomarker that allows identification of gastric aspiration.
Methods for Mediation Analysis with High-Dimensional DNA Methylation Data: Possible Choices and Comparison
Authors: Clark-Boucher Dylan , Zhou Xiang , Du Jiacong , Liu Yongmei , Needham Belinda L , Smith Jennifer A , Mukherjee Bhramar 
Published: February 2023

AbstractEpigenetic researchers often evaluate DNA methylation as a mediator between social/environmental exposures and disease, but modern statistical methods for jointly evaluating many mediators have not been widely adopted. We compare seven methods for high-dimensional mediation analysis with continuous outcomes through both diverse simulations and analysis of DNAm data from a large national cohort in the United States, while providing an R package for their implementation. Among the considered choices, the best-performing methods for detecting active mediators in simulations are the Bayesian sparse linear mixed model by Song et al. (2020) and high-dimensional mediation analysis by Gao et al. (2019); while the superior methods for estimating the global mediation effect are high-dimensional linear mediation analysis by Zhou et al. (2021) and principal component mediation analysis by Huang and Pan (2016). We provide guidelines for epigenetic researchers on choosing the best method in practice and offer suggestions for future methodological development.
Psychometric Properties of the NIH Toolbox Cognition and Emotion Batteries Among Children and Adolescents with Congenital Heart Defects
Authors: Wallace Julia , Ceschin Rafael , Lee Vince K. , Beluk Nancy H. , Burns Cheryl , Beers Sue , Lo Cecilia , Panigrahy Ashok , Badaly Daryaneh 
Published: February 2023

AbstractObjectiveThe NIH Toolbox offers brief, computerized measures of cognitive and psychosocial functioning. However, its psychometric properties were established among typically developing children and adolescents. The current study provides the first comprehensive assessment of its psychometric properties among young patients with congenital heart defects (CHD).Study DesignWe prospectively recruited 58 patients with CHD and 80 healthy controls between the ages of 6 and 17. Participants completed the NIH Toolbox Cognition and Emotion Batteries, a battery of clinician-administered neuropsychological tests, and ratings of their quality of life. Their parents also completed ratings of their functioning.ResultsOn the Cognition Battery, we found expectable group differences and developmentally expected gains across ages. For the most part, composites and subtests were significantly correlated with neuropsychological measures of similar constructs. Higher scores were generally associated with ratings of better day-to-day functioning among children with CHD. On the Emotion Battery, we found no significant group differences, echoing prior research. For the most part, scales showed acceptable internal consistency among both groups. There was adequate construct coherence for most of questionnaires among healthy control but not participants with CHD. Correlations with a comparison tool were largely within expectable directions.ConclusionThe NIH Toolbox may provide a valid and useful assessment of cognitive functioning among children and adolescents with CHD. While it may offer reliable and valid scales of psychosocial functioning, further research is needed to understand the meaningfulness of the scales for participants with CHD.
Aneurysmal Growth in Type-B Aortic Dissection: Assessing the Impact of Patient-Specific Inlet Conditions on Key Haemodynamic Indices
Authors: Stokes C. , Ahmed D. , Lind N. , Haupt F. , Becker D. , Hamilton J. , Muthurangu V. , Tengg-Kobligk H. von , Papadakis G. , Balabani S. , Díaz-Zuccarini V. 
Published: February 2023

AbstractType-B Aortic Dissection is a cardiovascular disease in which a tear develops in the intimal layer of the descending aorta, allowing pressurized blood to delaminate the layers of the vessel wall. In medically managed patients, long-term aneurysmal dilatation of the false lumen (FL) is considered virtually inevitable and is associated with poorer disease outcomes. While the pathophysiological mechanisms driving FL dilatation are not yet understood, hemodynamic factors are believed to play a key role. Computational Fluid Dynamics (CFD) and 4D-Flow MRI (4DMR) analyses have revealed correlations between flow helicity, oscillatory wall shear stress, and aneurysmal dilatation of the FL. In this study, we compare CFD simulations using a patient-specific, three-dimensional, three-component inlet velocity profile (3D IVP) extracted from 4DMR data against simulations with flow rate-matched uniform and axial velocity profiles that remain widely used in the absence of 4DMR. We also evaluate the influence of measurement errors in 4DMR data by scaling the 3D IVP to the degree of imaging error detected in prior studies. We observe that oscillatory shear and helicity are highly sensitive to inlet velocity distribution and flow volume throughout the FL and conclude that the choice of IVP may greatly affect the future clinical value of simulations.