bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of multiple pro-inflammatory stimuli in utero on the ileum of extremely premature ovine fetuses
Authors: Heiter Julia , Kemp Matthew W. , Spiller Owen B. , Singer Dominique , Newnham John P. , Kallapur Suhas G. , Jobe Alan H. , Kramer Boris W. 
Published: May 2023

IntroductionChorioamnionitis is common in preterm birth and associated with a higher risk of intestinal inflammation and necrotizing enterocolitis. The intestinal inflammation influences the enteric nervous system development. We hypothesized that inflammation and innervation in the fetal ileum may be modified by chorioamnionitis induced by repeated challenge with lipopolysaccharide and/or preexisting Ureaplasma parvum infection at very low gestational age equivalent to 60% of term.Materials and methodsTime mated ovine fetuses were exposed by intraamniotic injections to chronic Ureaplasma parvum for 24 days and/or lipopolysaccharide for 7 days, 2 days, or 7 &amp; 2 days before delivery at 94 +/-2 days of gestational age (term at approximately 150 days). Intestinal inflammation as well as structural changes of the enteric nervous system were assessed.ResultsLipopolysaccharide exposure increased CD3 and myeloperoxidase-positive cells (p &lt; 0.05). Repetitive exposure to lipopolysaccharide or combined Ureaplasma parvum &amp; lipopolysaccharide exposure increased intestinal inflammation (p &lt; 0.05). The reduction of nuclei of neurons was most significant with repetitive lipopolysaccharide exposures but could be detected in all other intervention groups compared to the control group. Astrocyte-like glial cells increased if exposure to lipopolysaccharide was only 2 days before delivery or chronic exposure to Ureaplasma parvum existed beforehand (p &lt; 0.05).DiscussionAfter exposure to chorioamnionitis induced by Ureaplasma parvum and/or lipopolysaccharide, inflammatory responses as well as structural changes of the enteric nervous system were more pronounced the longer and the more frequent the exposure to pro-inflammatory stimuli before birth. These changes may cause functional effects of clinical importance.
The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice
Authors: Scott Ori , Visuvanathan Shagana , Reddy Emily , Mahamed Deeqa , Gu Bin , Roifman Chaim M. , Cohn Ronald D. , Guidos Cynthia J. , Ivakine Evgueni A. 
Published: May 2023

IntroductionHumans with gain-of-function (GOF) mutations in STAT1 (Signal Transducer and Activator of Transcription 1), a potent immune regulator, experience frequent infections. About one-third, especially those with DNA-binding domain (DBD) mutations such as T385M, also develop autoimmunity, sometimes accompanied by increases in T-helper 1 (Th1) and T-follicular helper (Tfh) CD4 effector T cells, resembling those that differentiate following infection-induced STAT1 signaling. However, environmental and molecular mechanisms contributing to autoimmunity in STAT1 GOF patients are not defined. MethodsWe generated Stat1T385M/+ mutant mice to model the immune impacts of STAT1 DBD GOF under specific-pathogen free (SPF) conditions.ResultsStat1T385M/+ lymphocytes had more total Stat1 at baseline and also higher amounts of IFNg-induced pStat1. Young mutants exhibited expansion of Tfh-like cells, while older mutants developed autoimmunity accompanied by increased Tfh-like cells, B cell activation and germinal center (GC) formation. Mutant females exhibited these immune changes sooner and more robustly than males, identifying significant sex effects of Stat1T385M-induced immune dysregulation. Single cell RNA-Seq (scRNA-Seq) analysis revealed that Stat1T385M activated transcription of GC-associated programs in both B and T cells. However, it had the strongest transcriptional impact on T cells, promoting aberrant CD4 T cell activation and imparting both Tfh-like and Th1-like effector programs. DiscussionCollectively, these data demonstrate that in the absence of overt infection, Stat1T385M disrupted naïve CD4 T cell homeostasis and promoted expansion and differentiation of abnormal Tfh/Th1-like helper and GC-like B cells, eventually leading to sex-biased autoimmunity, suggesting a model for STAT1 GOF-induced immune dysregulation and autoimmune sequelae in humans.
Ultrasound assessment of the respiratory system using diaphragm motion-volume indices
Authors: Boussuges Alain , Chaumet Guillaume , Boussuges Martin , Menard Amelie , Delliaux Stephane , Brégeon Fabienne 
Published: May 2023

BackgroundAlthough previous studies have determined limit values of normality for diaphragm excursion and thickening, it would be beneficial to determine the normal diaphragm motion-to-inspired volume ratio that integrates the activity of the diaphragm and the quality of the respiratory system.MethodsTo determine the normal values of selected ultrasound diaphragm motion-volume indices, subjects with normal pulmonary function testing were recruited. Ultrasound examination recorded diaphragm excursion on both sides during quiet breathing and deep inspiration. Diaphragm thickness was also measured. The inspired volumes of the corresponding cycles were systematically recorded using a spirometer. The indices were calculated using the ratio excursion, or percentage of thickening, divided by the corresponding breathing volume. From this corhort, normal values and limit values for normality were determined. These measurements were compared to those performed on the healthy side in patients with hemidiaphragm paralysis because an increase in hemidiaphragm activity has been previously demonstated in such circumstances.ResultsA total of 122 subjects (51 women, 71 men) with normal pulmonary function were included in the study. Statistical analysis revealed that the ratio of excursion, or percentage of thickening, to inspired volume ratio significantly differed between males and females. When the above-mentioned indices using excursion were normalized by body weight, no gender differences were found. The indices differed between normal respiratory function subjects and patients with hemidiaphragm paralysis (27 women, 41 men). On the paralyzed side, the average ratio of the excursion divided by the inspired volume was zero. On the healthy side, the indices using the excursion and the percentage of thickening during quiet breathing or deep inspiration were significantly increased comparedto patients with normal lung function. According to the logistic regression analysis, the most relevant indice appeared to be the ratio of the excursion measured during quiet breathing to the inspired volume.ConclusionThe normal values of the diaphragm motion-volume indices could be useful to estimate the performance of the respiratory system. Proposed indices appear suitable in a context of hyperactivity.
Associations of obesity-related indices with prediabetes regression to normoglycemia among Chinese middle-aged and older adults: a prospective study
Authors: Yang Hongguang , Zhang Minjie , Nie Jiaqi , Zhang Minzhe , Lu Gaolei , Chen Rui , He Qiqiang 
Published: May 2023

BackgroundPrediabetes is associated with increased cardiovascular risk and all-cause mortality, while its regression will decrease the risks. This study investigated the associations of six obesity-related indices (waist-to-height ratio (WHtR), body roundness index (BRI), conicity index (CI), body shape index (ABSI), Chinese visceral adiposity index (CVAI), and triglyceride glucose (TyG) index) with prediabetes regression based on the China Health and Retirement Longitudinal Study (CHARLS), enrolling middle-aged and older adults.MethodsWe included 2,601 participants with prediabetes from CHARLS, who were followed up from 2011–2012 to 2015–2016, with blood samples collected for measuring fasting plasma glucose and hemoglobin A1c. All the obesity-related indices at baseline and their dynamic changes were calculated and categorized into tertiles. Logistic regression analysis was applied to obtain the odds ratio (OR) and 95% confidence intervals (CIs). Attributable fractions (AFs) and 95% CIs of these indices and the dynamic changes were calculated with the AF package in R software, and the cutoff values of initial obesity-related indices were obtained by the receiver operating characteristic (ROC) analysis.ResultsDuring the 4-year follow-up period, 562 (21.61%) participants regressed from prediabetes to normoglycemia. They had lower initial BRI, WHtR, CI, ABSI, CVAI, and TyG than those who did not (P &lt; 0.05). After multivariable adjustment, participants in the first tertile of initial BRI (OR, 1.45, 95%CIs, 1.09–1.93), WHtR (OR, 1.46, 95%CIs, 1.10–1.95), and CVAI (OR, 1.47, 95%CIs, 1.11–1.93) had increased odds of prediabetes regression compared with those in the highest tertile. Participants with decreased TyG (OR, 2.08; 95%CIs, 1.61–2.70) also had increased odds of prediabetes regression compared with those with increased TyG. The cutoff values of initial obesity-related indices were 4.374 for BRI, 0.568 for WHtR, 8.621 for TyG, 1.320 for CI, 0.083 for ABSI, and 106.152 for CVAI, respectively. The AFs were 21.10% for BRI &lt; 4.374, 20.85% for WHtR &lt; 0.568, 17.48% for CVAI &lt; 107.794, and 17.55% for ΔTyG &lt; 0, respectively.ConclusionLow initial BRI, WHtR, and CVAI, as well as TyG reduction, were significantly related to prediabetes regression to normoglycemia, and the AFs were around 20%. Less abdominal fat and insulin resistance reduction would benefit future health outcomes among people with prediabetes.
A nomogram for individually predicting the overall survival in colonic adenocarcinoma patients presenting with perineural invasion: a population study based on SEER database
Authors: Chen Junhong , Zhou Hao , Jin Hengwei , Liu Kai 
Published: May 2023

BackgroundColonic adenocarcinoma, representing the predominant histological subtype of neoplasms in the colon, is commonly denoted as colon cancer. This study endeavors to develop and validate a nomogram model designed for predicting overall survival (OS) in patients with colon cancer, specifically those presenting with perineural invasion (PNI).MethodsThe Surveillance, Epidemiology, and End Results (SEER) database supplied pertinent data spanning from 2010 to 2015, which facilitated the randomization of patients into distinct training and validation cohorts at a 7:3 ratio. Both univariate and multivariate analyses were employed to construct a prognostic nomogram based on the training cohort. Subsequently, the nomogram’s accuracy and efficacy were rigorously evaluated through the application of a concordance index (C-index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic (ROC) curves.ResultsIn the training cohorts, multivariable analysis identified age, grade, T-stage, N-stage, M-stage, chemotherapy, tumor size, carcinoembryonic antigen (CEA), marital status, and insurance as independent risk factors for OS, all with P-values less than 0.05. Subsequently, a new nomogram was constructed. The C-index of this nomogram was 0.765 (95% CI: 0.755–0.775), outperforming the American Joint Committee on Cancer (AJCC) TNM staging system’s C-index of 0.686 (95% CI: 0.674–0.698). Calibration plots for 3- and 5-year OS demonstrated good consistency, while DCA for 3- and 5-year OS revealed excellent clinical utility in the training cohorts. Comparable outcomes were observed in the validation cohorts. Furthermore, we developed a risk stratification system, which facilitated better differentiation among three risk groups (low, intermediate, and high) in terms of OS for all patients.ConclusionIn this study, we have devised a robust nomogram and risk stratification system to accurately predict OS in colon cancer patients exhibiting PNI. This innovative tool offers valuable guidance for informed clinical decision-making, thereby enhancing patient care and management in oncology practice.
Robotic versus laparoscopic gastrectomy for gastric cancer in patients with obesity: systematic review and meta-analysis
Authors: Yu Xianzhe , Zhu Lingling , Zhang Yan , Feng Qingbo 
Published: May 2023

IntroductionThe number of overweight patients with gastric cancer (GC) is increasing, and no previous study has compared laparoscopic gastrectomy (LG) and robotic gastrectomy (RG) in obese patients with GC. To investigate the perioperative and oncologic outcomes of RG and LG in obese GC patients, we performed a meta-analysis of propensity matched scores and retrospective studies to compare the perioperative parameters, oncologic findings, and short-term postoperative outcomes between the two groups.MethodsThis study was performed according to the PRISMA guidelines. A search was performed on PubMed, Web of Science, EMBASE, and Cochrane Central Register to identify eligible propensity matched scores and retrospective studies conducted and published before December 2022. Data on perioperative and oncological outcomes were included in the meta-analysis.ResultsOverall, we identified 1 propensity score match study and 5 randomized control trials of RG and LG, enrolling a total of 718 patients (197 and 521 patients received RG and LG, respectively). No significant differences were observed between the two groups in terms of complications, bleeding, or lymph node dissection. Of note, RG had a longer procedure time (P = 0.03), earlier oral intake (P = 0.0010), shorter hospital stay (P = 0.0002), and shorter time to defecation (P &lt; 0.00001).ConclusionsThis meta-analysis concluded that patients in the RG group had shorter hospital stays, earlier postoperative feeding, and earlier postoperative ventilation; however, no differences were found in blood loss, number of lymph nodes removed, or overall complications. RG is an effective, safe, and promising treatment for obese patients with GC, compensating for the shortcomings of laparoscopy and allowing for less trauma and faster recovery.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022298967.
Beta-blocker exposure and survival outcomes in patients with advanced pancreatic ductal adenocarcinoma: a retrospective cohort study (BETAPANC)
Authors: Le Bozec Antoine , Brugel Mathias , Djerada Zoubir , Ayad Marya , Perrier Marine , Carlier Claire , Botsen Damien , Nazeyrollas Pierre , Bouché Olivier , Slimano Florian 
Published: May 2023

Introduction: Preclinical studies have demonstrated the possible role of beta-adrenergic receptors in pancreatic ductal adenocarcinoma (PDAC) tumor invasion and migration. The current study aimed to explore the possible association between survival outcomes and beta-blocker (BB) exposure in patients with advanced PDAC.Methods: This retrospective single-center study included 182 patients with advanced PDAC. Clinical [age, sex, BMI, cardiovascular condition, presence (SBB) or absence (NSBB) of beta-1 selectivity of BB, exposure duration, and multimorbidity], oncological (stage and anticancer treatment regimen), and biological (renal and liver function) data were collected. The endpoints were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for survival outcomes associated with BB exposure were estimated using Cox regression model and propensity score (PS) methods.Results: Forty-one patients (22.5%) were exposed to BB. A total of 104 patients progressed (57.1%) to PDAC and 139 (76.4%) patients died at the end of follow-up (median, 320 days; IQR, 438.75 days). When compared to the non-exposed group, there was no increase in survival outcomes associated with BB use (OS: HR = 1.38, 95% CI = 0.80–2.39, p = 0.25; PFS: adjusted HR = 0.95, 95% CI = 0.48–1.88, p = 0.88). Similar results were obtained using the PS method. Compared to no BB usage, SBB use was associated with a significant decrease in OS (HR = 1.80, 95% CI = 1.16–2.80, p &lt; 10−2).Conclusion: BB exposure was not associated with improved PDAC survival outcomes. Beta-1-selectivity was not independently associated with any differences.
Differential responses from the left postcentral gyrus, right middle frontal gyrus, and precuneus to meal ingestion in patients with functional dyspepsia
Authors: Chen Yiping , Yu Risheng , DeSouza Joseph F. X. , Shen Yuze , Zhang Hanyun , Zhu Chunpeng , Huang Peiyu , Wang Caihua 
Published: May 2023

BackgroundFunctional dyspepsia (FD) is most often a meal-induced syndrome. Studies using resting-state functional magnetic resonance imaging (rs-fMRI) reported abnormal connectivity in areas related to pain processing in FD. However, only a few studies have attempted to determine how meal ingestion affects the brain's working patterns. Through rs-fMRI, this study observed how meal ingestion affected brain regions related to visceral hypersensitivity and emotional response networks in FD patients.MethodsA total of 30 FD patients and 32 healthy controls (HC) were enrolled and underwent clinical investigations. Rs-fMRI was performed twice after a 4-h fast and 50 min after a meal. The mean functional connectivity strength (FCS) values were extracted from brain regions with significant differences to show the trend of changes related to meal ingestion after FCS analyses.ResultsDepression, anxiety, sleep disturbances, and weight loss were more common in FD patients (P ≤ 0.001). Compared with HCs (corrected cluster P-value &lt; 0.05), FD patients had significantly higher FCS in the right middle frontal gyrus before meals and higher meal-induced FCS in the left postcentral gyrus. HCs had greater meal-induced activation in the right precuneus and anterior cingulate cortex. FD patients had a decreasing trend in the right inferior frontal gyrus compared to the increasing trend in HCs. We only found anxiety to be negatively correlated with FCS in the right inferior frontal gyrus in FD (r = −0.459, p = 0.048, uncorrected).ConclusionsIn this study, we discovered that FD patients have different perceptual and emotional responses to food intake in defined brain areas, providing promising impetus for understanding pathogenic brain mechanisms in FD.
Impact of social determinants of health on individuals living with generalized myasthenia gravis and implications for patient support programs
Authors: Hughes Tom , Anderson Ashley E. L. , Habib Ali A. , Perez Kathy , Bergin Cathleen , Suchotliff Sharon , Zvosec Cecilia , McDaniel Dajzsa , Sato Mai , Whangbo Albert , Phillips Glenn 
Published: May 2023

IntroductionSocial determinants of health (SDOH) are important contributors to health outcomes, and better understanding their impact on individuals diagnosed with rare, chronic diseases with high burden and unmet need is critical. Characterizing SDOH burden can help improve the design of patient support programs (PSPs), using targeted approaches to remove barriers to access.MethodsThis study used a mixed-methods strategy employing a quantitative survey, which was designed based on qualitative interviews, to understand the unmet needs and awareness/utilization of PSPs among individuals living with generalized myasthenia gravis (gMG) and experiencing SDOH barriers. The survey was completed by 38 individuals living with gMG, of which the majority were non-White/Caucasian, unemployed, low income, and enrolled in public insurance. Common SDOH challenges, awareness/utilization of available PSPs, and unmet needs were identified.ResultsFinancial and mental health concerns were the most common among individuals living with gMG and experiencing SDOH barriers throughout diagnosis, accessing treatment, initiating treatment, and continuing treatment. Awareness and utilization of existing support services were low, especially when accessing treatment. Educational, financial, and personalized support with high “human touch” were commonly perceived as the most valuable resources.ImplicationsTo better serve the needs of individuals with gMG experiencing SDOH barriers, PSPs should use a targeted approach to offer services tailored to harder-to-reach populations. Further, providers, advocacy groups, manufacturers, and public organizations in the gMG ecosystem should strengthen collaborations with PSPs to enable individuals living with gMG to access the services they need to improve their health outcomes.
Virtual reality and collaborative learning: a systematic literature review
Authors: van der Meer Nesse , van der Werf Vivian , Brinkman Willem-Paul , Specht Marcus 
Published: May 2023

Background: While research on Virtual Reality’s potential for education continues to advance, research on its support for Collaborative Learning is small in scope. With remote collaboration and distance learning becoming increasingly relevant for education (especially since the COVID-19 pandemic), an understanding of Virtual Reality’s potential for Collaborative Learning is of importance. To establish how this immersive technology can support and enhance collaboration between learners, this systematic literature review analyses scientific research on Virtual Reality for Collaborative Learning with the intention to identify 1) skills and competences trained, 2) domains and disciplines addressed, 3) systems used and 4) empirical knowledge established.Method: Two scientific databases—Scopus and Web of Science—were used for this review. Following the PRISMA method, a total of 139 articles were analyzed. Reliability of this selection process was assessed using five additional coders. A taxonomy was used to classify these articles. Another coder was used to assess the reliability of the primary coder before this taxonomy was applied to the selected articlesResults: Based on the literature reviewed, skills and competences developed are divided into five categories. Educational fields and domains seem interested in Virtual Reality for Collaborative Learning because of a need for innovation, communities and remote socialization and collaboration between learners. Systems primarily use monitor-based Virtual Reality and mouse-and-keyboard controls. A general optimism is visible regarding the use of Virtual Reality to support and enhance Collaborative LearningConclusion: Five distinct affordances of Virtual Reality for Collaborative Learning are identified: it 1) is an efficient tool to engage and motivate learners, 2) supports distance learning and remote collaboration, 3) provides multi- and interdisciplinary spaces for both learning and collaborating, 4) helps develop social skills and 5) suits Collaborative Learning-related paradigms and approaches. Overall, the reviewed literature suggests Virtual Reality to be an effective tool for the support and enhancement of Collaborative Learning, though further research is necessary to establish pedagogies.