bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastrointestinal Symptoms and Irritable Bowel Syndrome Are Associated With Female Sex and Smoking in the General Population and With Unemployment in Men
Authors: Nilsson Daniel , Ohlsson Bodil 
Published: September 2021

Background: The influence of daily life exposure on the gastrointestinal tract is not fully understood. This study aimed to examine associations between functional gastrointestinal symptoms and sociodemographic status and lifestyle habits in the general population.Methods: The Malmö Offspring Study (MOS) included 2,648 participants from the general population who had answered a questionnaire about sociodemographic status, lifestyle habits, medical health, and self-reported irritable bowel syndrome (IBS). The visual analog scale for IBS (VAS-IBS) was completed to assess gastrointestinal symptoms the past 2 weeks. Subjects with organic gastrointestinal diseases were excluded. Presence of self-reported IBS and gastrointestinal symptoms the past 2 weeks were used as dependent variables to study the associations with age, sex, body mass index, education, occupation, marital status, smoking, snuff using, alcohol drinking frequency, alcohol amount per drinking occasion, physical activity at work, and physical activity during leisure time, using logistic regression and generalized linear model.Results: Self-reported IBS was associated with gastrointestinal symptoms the past 2 weeks (p &lt; 0.001). There was an association between IBS and female sex (p &lt; 0.001), former smoking (p &lt; 0.001), present smoking (p &lt; 0.001), and an inverse association with drinking 3–4 standard glasses per occasion (p = 0.038). Gastrointestinal symptoms were associated with age 50–59 years (p = 0.009), ≥60 years (p = 0.004), female sex (p &lt; 0.001), studying (p = 0.036), unemployment (p = 0.009), former smoking (p = 0.001), and present smoking (p = 0.012). In men, IBS was associated with middle-age and both IBS and gastrointestinal symptoms were associated with unemployment (p &lt; 0.001 and p = 0.001, respectively). In women, IBS was associated with present smoking (p = 0.022), and gastrointestinal symptoms were associated with former smoking and inversely associated with higher age (p = 0.006) and intermediate physical activity at work (p = 0.008). No associations were found with BMI, education, marital status, or snuff using.Conclusion: Self-reported IBS in the general population shows strongest association with female sex and smoking, whereas gastrointestinal symptoms also are associated with unemployment and inversely associated with higher age. In men, both IBS and gastrointestinal symptoms are associated with unemployment. In women, both IBS and gastrointestinal symptoms are associated with smoking, whereas symptoms are inversely associated with higher age and intermediate physical activity.
Microcatheter-Assisted Trabeculotomy Combined With Deep Sclerectomy and Trabeculectomy in Young to Middle-Aged Adults With Advanced Primary Open-Angle Glaucoma: 1-Year Result
Authors: Zhang Hengli , Yan Xiaowei , Li Fan , Ma Lihua , Geng Yulei , Jiao Kexin , Tang Guangxian 
Published: September 2021

Objective: We aimed to evaluate the safety and clinical efficacy of ab externo microcatheter-assisted trabeculotomy combined with deep sclerectomy and trabeculectomy (MATT-DS-Trab) in the surgical management of advanced primary open-angle glaucoma (POAG).Methods: According to the inclusion criteria, we retrospectively collected and analyzed 37 POAG cases in advanced stage who received MATT-DS-Trab. The intraocular pressure (IOP), best corrected visual acuity (BCVA), use of anti-glaucoma drugs, shape of the filtering bleb, size of the scleral lake, complications, and the surgical success rate were recorded.Results: The mean IOP was 37.50 ± 8.11 mmHg before the operation, while it depleted to 10.08 ± 2.01 and 11.43 ± 2.07 mmHg at 1 week and 12 months after the operation, respectively (both P &lt; 0.001 compared to preoperative IOP). From none to two kinds of anti-glaucoma drugs were used 12 months after surgery on the patients, which were significantly reduced compared with that preoperatively (P &lt; 0.001). An L-type filtering bleb was the main form at all time points after the operation. At 12 months following surgery, an F-type filtering bleb accounted for 5.41% and no E-type filtering bleb was recorded. The length and height of the scleral lake shrunk with time, but there was no statistical significance (P &gt; 0.05). Also, there was no correlation between the size of the scleral pool and the IOP (P &gt; 0.05). At 12 months after the operation, the complete success rates were 94.59, 83.78, and 72.97% according to standards A (≤18 mmHg), B (≤15 mmHg), and C (≤12 mmHg), respectively. Intraoperative complications were mainly anterior chamber hemorrhage, and no complications related to the filtration bleb were observed after the operation.Conclusion: Based on multichannel mechanisms, MATT-DS-Trab is able to effectively reduce IOP in advanced POAG patients, with few serious complications and a high success rate.
Efficacy and Safety of Treatments for Patients With Portal Hypertension and Cirrhosis: A Systematic Review and Bayesian Network Meta-Analysis
Authors: Yao Qigu , Chen Wenyi , Yan Cuilin , Yu Jiong , Jiang Tian'an , Cao Hongcui 
Published: September 2021

Background and Aims:Viral hepatitis are one of the main causes of liver cirrhosis. The treatment of portal hypertension caused by liver cirrhosis is difficult and diverse, and the therapeutic effect is unknown. Bayesian network meta-analysis was performed to compare the efficacy and safety of treatments for patients with portal hypertension and cirrhosis, including a transjugular intrahepatic portosystemic shunt (TIPS), endoscopic therapy, surgical therapy and medications.Methods:Eligible articles were searched for in PubMed, Embase, Cochrane Library and Web of Science databases from their inception until June 2020. Using the “gemtc-0.8.4” package in R v.3.6.3 software and the Just Another Gibbs Sampler v.4.2.0 program, network meta-analysis was performed using a random effects model within a Bayesian framework. The odds ratios for all-cause rebleeding, bleeding-related mortality, overall survival (OS), treatment failure and hepatic encephalopathy were determined within the Bayesian framework.Results:Forty randomized controlled trials were identified, including 4,006 adult patients and nine treatment strategies. Our results showed that distal splenorenal shunt and TIPS provided the best control of hemorrhage. Endoscopic variceal ligation with medication resulted in the highest OS rate. Medication alone resulted in poor OS and treatment failure.Conclusions:We performed a systematic comparison of diverse treatments for cirrhotic patients with portal hypertension. Our meta-analysis indicated that a TIPS and distal splenorenal shunt resulted in lower rates of rebleeding than did other therapies. Furthermore, drugs are more suitable for combination therapy than monotherapy.
Rat Hepatitis E Virus: Presence in Humans in South-Western France?
Authors: Parraud Delphine , Lhomme Sébastien , Péron Jean Marie , Da Silva Isabelle , Tavitian Suzanne , Kamar Nassim , Izopet Jacques , Abravanel Florence 
Published: September 2021

Background: Hepatitis E Virus (HEV) is one of the most common causes of hepatitis worldwide, and South-Western France is a high HEV seroprevalence area. While most cases of HEV infection are associated with the species Orthohepevirus-A, several studies have reported a few cases of HEV infections due to Orthohepevirus-C (HEV-C) that usually infects rats. Most of these human cases have occurred in immunocompromised patients. We have screened for the presence of HEV-C in our region.Methods and Results: We tested 224 sera, mostly from immunocompromised patients, for HEV-C RNA using an in-house real time RT-PCR. Liver function tests gave elevated results in 63% of patients: mean ALT was 159 IU/L (normal &lt; 40 IU/L). Anti-HEV IgG (49%) and anti-HEV IgM (9.4%) were frequently present but none of the samples tested positive for HEV-C RNA.Conclusion: HEV-C does not circulate in the human population of South-Western France, despite the high seroprevalence of anti-HEV IgG.
Optimal Positive End Expiratory Pressure Levels in Ventilated Patients Without Acute Respiratory Distress Syndrome: A Bayesian Network Meta-Analysis and Systematic Review of Randomized Controlled Trials
Authors: Zhou Jing , Lin Zhimin , Deng Xiumei , Liu Baiyun , Zhang Yu , Zheng Yongxin , Zheng Haichong , Wang Yingzhi , Lai Yan , Huang Weixiang , Liu Xiaoqing , He Weiqun , Xu Yuanda , Li Yimin , Huang Yongbo , Sang Ling 
Published: September 2021

Background: To find the optimal positive end expiratory pressure (PEEP) in mechanical ventilated patients without Acute Respiratory Distress Syndrome (ARDS), we conducted a Bayesian network meta-analysis and systematic review of randomized controlled trials (RCTs) comparing different level of PEEP based on a novel classification of PEEP level: ZEEP group (PEEP = 0 cm H2O); lower PEEP group (PEEP = 1–6 cm H2O); intermediate PEEP group (PEEP = 7–10 cm H2O); higher PEEP group (PEEP &gt; 10 cm H2O).Result: Twenty eight eligible studies with 2,712 patients were included. There were no significant differences in the duration of mechanical ventilation between higher and intermediate PEEP (MD: 0.020, 95% CI: −0.14, 0.28), higher and lower PEEP (MD: −0.010, 95% CI: −0.23, 0.22), higher PEEP and ZEEP (MD: 0.010, 95% CI: −0.40, 0.22), intermediate and lower PEEP (MD: −0.040, 95% CI: −0.18, 0.040), intermediate PEEP and ZEEP (MD: −0.010, 95% CI: −0.42, 0.10), lower PEEP and ZEEP (MD: 0.020, 95% CI: −0.32, 0.13), respectively. Higher PEEP was associated with significantly higher PaO2/FiO2 ratio(PFR) when compared to ZEEP (MD: 73.24, 95% CI: 11.03, 130.7), and higher incidence of pneumothorax when compared to intermediate PEEP, lower PEEP and ZEEP (OR: 2.91e + 12, 95% CI: 40.3, 1.76e + 39; OR: 1.85e + 12, 95% CI: 29.2, 1.18e + 39; and OR: 1.44e + 12, 95% CI: 16.9, 8.70e + 38, respectively). There was no association between PEEP levels and other secondary outcomes.Conclusion: We identified higher PEEP was associated with significantly higher PFR and higher incidence of pneumothorax. Nonetheless, in terms of other outcomes, no significant differences were detected among four levels of PEEP.Systematic Review Registration: The study had registered on an international prospective register of systematic reviews, PROSPERO, on 09 April 2021, identifier: [CRD42021241745].
Resveratrol Improves Growth Performance, Intestinal Morphology, and Microbiota Composition and Metabolism in Mice
Authors: Zhuang Yu , Huang Huijun , Liu Shuang , Liu Feng , Tu Qiang , Yin Yulong , He Shanping 
Published: September 2021

BackgroundResveratrol (RSV) plays a vital role in alleviating various stresses and improving intestinal health. The current study was conducted to explore whether RSV alleviates weaning stress through improving gut health in a weaning mouse model. Forty 21-day-old weaned mice were randomly assigned to a control group without RSV treatment and three treatment groups with 10, 20, and 50 mg/kg RSV for 28 days.ResultsThe results showed that RSV at a dose of 20 mg/kg improved total body weight, intestinal morphology (villus length and the ratio of villus length to crypt depth), and the levels of intestinal barrier proteins (claudin-1 and occludin), but had little effect on the food intake, crypt depth, and serum free amino acids of mice. Compared with the control group, mice supplemented with RSV had decreased mRNA expression of genes related to inflammatory cytokines (IL-6 and IL-1β), but increased mRNA expression of genes related to host defense peptides (Defa3, Defa5, Defa20, and Lyz) and short-chain fatty acids (SCFAs) production (propionic acid, isobutyric acid, butyric acid, and isovaleric acid). In addition, 16S rRNA sequencing results showed that RSV supplementation increased the richness indices of intestinal microbiota (Chao, ACE) and shaped the composition of intestinal microbiota (e.g., increased β-diversity of intestinal microbiota community). Meanwhile, RSV supplementation increased genes of Butyricicoccus, Ruminococcus_1, and Roseburia, which are producers of SCFAs. Furthermore, RSV supplementation significantly influenced the metabolism of intestinal microbiota, namely, amino acids metabolism, lipid metabolism, and defense mechanisms.ConclusionRSV can improve growth performance and intestinal morphology in weaning mice, possibly through improving gut immune response and microbiota function.
Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1
Authors: Gao Xiaopan , Yu Xia , Zhu Kaixiang , Qin Bo , Wang Wei , Han Pu , Aleksandra Wojdyla Justyna , Wang Meitian , Cui Sheng 
Published: September 2021

Mycobacterium tuberculosis (Mtb) caused an estimated 10 million cases of tuberculosis and 1.2 million deaths in 2019 globally. The increasing emergence of multidrug-resistant and extensively drug-resistant Mtb is becoming a public health threat worldwide and makes the identification of anti-Mtb drug targets urgent. Elongation factor G (EF-G) is involved in tRNA translocation on ribosomes during protein translation. Therefore, EF-G is a major focus of structural analysis and a valuable drug target of antibiotics. However, the crystal structure of Mtb EF-G1 is not yet available, and this has limited the design of inhibitors. Here, we report the crystal structure of Mtb EF-G1 in complex with GDP. The unique crystal form of the Mtb EF-G1-GDP complex provides an excellent platform for fragment-based screening using a crystallographic approach. Our findings provide a structure-based explanation for GDP recognition, and facilitate the identification of EF-G1 inhibitors with potential interest in the context of drug discovery.
A Plant Stress-Responsive Bioreporter Coupled With Transcriptomic Analysis Allows Rapid Screening for Biocontrols of Necrotrophic Fungal Pathogens
Authors: Belt Katharina , Foley Rhonda C. , O’Sullivan Cathryn A. , Roper Margaret M. , Singh Karam B. , Thatcher Louise F. 
Published: September 2021

Streptomyces are soil-borne Actinobacteria known to produce a wide range of enzymes, phytohormones, and metabolites including antifungal compounds, making these microbes fitting for use as biocontrol agents in agriculture. In this study, a plant reporter gene construct comprising the biotic stress-responsive glutathione S-transferase promoter GSTF7 linked to a luciferase output (GSTF7:luc) was used to screen a collection of Actinobacteria candidates for manipulation of plant biotic stress responses and their potential as biocontrol agents. We identified a Streptomyces isolate (KB001) as a strong candidate and demonstrated successful protection against two necrotrophic fungal pathogens, Sclerotinia sclerotiorum and Rhizoctonia solani, but not against a bacterial pathogen (Pseudomonas syringe). Treatment of Arabidopsis plants with either KB001 microbial culture or its secreted compounds induced a range of stress and defense response-related genes like pathogenesis-related (PR) and hormone signaling pathways. Global transcriptomic analysis showed that both treatments shared highly induced expression of reactive oxygen species and auxin signaling pathways at 6 and 24 h posttreatment, while some other responses were treatment specific. This study demonstrates that GSTF7 is a suitable marker for the rapid and preliminary screening of beneficial bacteria and selection of candidates with potential for application as biocontrols in agriculture, including the Streptomyces KB001 that was characterized here, and could provide protection against necrotrophic fungal pathogens.
Comprehensive Analysis of HDAC Family Identifies HDAC1 as a Prognostic and Immune Infiltration Indicator and HDAC1-Related Signature for Prognosis in Glioma
Authors: Fan Yuxiang , Peng Xinyu , Wang Yubo , Li Baoqin , Zhao Gang 
Published: September 2021

Background: The histone deacetylase (HDAC) family limited accessibility to chromatin containing tumor suppressor genes by removing acetyl groups, which was deemed a path for tumorigenesis. Considering glioma remained one of the most common brain cancers with a dichotomy prognosis and limited therapy responses, HDAC inhibitors were an area of intensive research. However, the expression profiles and prognostic value of the HDACs required more elucidation.Methods: Multiple biomedical databases were incorporated, including ONCOMINE, GEPIA, TCGA, CGGA, GEO, TIMER, cBioPortal, and Metascape, to study expression profiles, prognostic value, immune infiltration, mutation status, and enrichment of HDACs in glioma. STRING and GeneMANIA databases were used to identify HDAC1-related molecules. LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating characteristic (ROC) analyses were performed for HDAC1-related signature construction and validation.Results:HDAC1 was significantly overexpressed in glioma, while HDAC11 was downregulated in glioblastoma. Except for HDAC 6/9/10, the HDAC family expression was significantly associated with glioma grade. Most of the HDAC family also correlated with glioma genetic mutations. Higher HDAC1 expression level predicted more dismal overall survival (OS) (p &lt; 0.0001) and disease-free survival (DFS) (p &lt; 0.0001), but a higher level of HDAC11 held more favorable OS (p = 2.1e−14) and DFS (p = 4.8e−08). HDAC4 displayed the highest mutation ratio, at 2.6% of the family. The prognostic value of HDAC1 was validated with ROC achieving 0.70, 0.77, 0.75, and 0.80 as separability for 1-, 3-, 5-, and 10-years OS predictions in glioma, respectively. Moreover, HDAC1 expression positively correlated with neutrophil (r = 0.60, p = 2.88e-47) and CD4+ T cell infiltration (r = 0.52, p = 3.96e-35) in lower-grade glioma. The final HDAC1-related signature comprised of FKBP3, HDAC1 (Hazard Ratio:1.49, 95%Confidence Interval:1.20–1.86), PHF21A, RUNX1T1, and RBL1, and was verified by survival analysis (p &lt; 0.0001) and ROC with 0.80, 0.84, 0.83, and 0.88 as separability for 1-, 3-, 5-, and 10-years OS predictions, respectively. The signature was enriched in chromatin binding.Conclusion: HDAC family was of clinical significance for glioma. Most of the HDAC family significantly correlated with the glioma grade, IDH1 mutation, and 1p/19q codeletion. HDAC1 was both a prognostic and immune infiltration indicator and a central component of the HDAC1-related signature for precise prognosis prediction in glioma.
Amyloid-Beta Influences Memory via Functional Connectivity During Memory Retrieval in Alzheimer's Disease
Authors: Li Binyin , Zhang Miao , Jang Ikbeom , Ye Guanyu , Zhou Liche , He Guiying , Lin Xiaozhu , Meng Hongping , Huang Xinyun , Hai Wangxi , Chen Shengdi , Li Biao , Liu Jun 
Published: September 2021

Objective: Amnesia in Alzheimer's disease (AD) appears early and could be caused by encoding deficiency, consolidation dysfunction, and/or impairment in the retrieval of stored memory information. The relationship between AD pathology biomarker β-amyloid and memory dysfunction is unclear.Method: The memory task functional MRI and amyloid PET were simultaneously performed to investigate the relationship between memory performance, memory phase-related functional connectivity, and cortical β-amyloid deposition. We clustered functional networks during memory maintenance and compared network connectivity between groups in each memory phase. Mediation analysis was performed to investigate the mediator between β-amyloid and related cognitive performance.Results: Alzheimer's disease was primarily characterized by decreased functional connectivity in a data-driven network composed of an a priori default mode network, limbic network, and frontoparietal network during the memory maintenance (0.205 vs. 0.236, p = 0.04) and retrieval phase (0.159 vs. 0.183, p = 0.017). Within the network, AD had more regions with reduced connectivity during the retrieval than the maintenance and encoding phases (chi-square p = 0.01 and &lt; 0.001). Furthermore, the global cortical β-amyloid negatively correlated with network connectivity during the memory retrieval phase (R = – 0.247, p = 0.032), with this relationship mediating the effect of cortical β-amyloid on memory performance (average causal mediation effect = – 0.05, p = 0.035).Conclusion: We demonstrated that AD had decreased connectivity in specific networks during the memory retrieval phase. Impaired functional connectivity during memory retrieval mediated the adverse effect of β-amyloid on memory. These findings help to elucidate the involvement of cortical β-amyloid (Aβ) in the memory performance in the early stages of AD.
The Dimethyl Fumarate Experience: A Handy Drug With Broad Clinical Utility
Authors: Lorefice Lorena , Casaglia Elisa , Fronza Marzia , Frau Jessica , Fenu Giuseppe , Pilotto Silvy , Coghe Giancarlo , Barracciu Maria A. , Cocco Eleonora 
Published: September 2021

Objectives: The aim of this study was to characterize multiple sclerosis (MS) patients exposed to dimethyl fumarate (DMF) and to evaluate the predictors of therapeutic response. In addition, the study offers a picture of how DMF use has changed over the past few years in naive or switcher patients.Methods: In this observational monocentric study, we examined the prescription flow of DMF in MS patients categorized as naive or switchers (for safety/tolerability, ineffectiveness, and de-escalation strategy) from 2015 to 2019. Clinical and magnetic resonance imaging data of DMF-treated patients were analyzed, and NEDA-3 status at 24 months was evaluated by the three assessment components (absence of clinical relapses, no Expanded Disability Status Scale progression, no radiological activity). Determinants of therapeutic response were also evaluated using regression analysis.Results: The sample included 595 MS patients exposed to DMF categorized as naive (158; 26.5%) and switchers for reasons of safety/tolerability (198; 33.3%), inefficacy (175; 29.4%), and de-escalation strategy (64; 10.8%). A 15% increase in DMF use in naive and horizontal shift groups was observed in the last 3 years of observation, whereas there was a drop, with prescription passed from ~20% to &lt;5%, as an exit strategy from second-line therapies. NEDA-3 status was calculated for 340 patients after 24 months of DMF treatment and achieved in 188 (55.3%) of these. Analyzing the predictors of DMF response, we observed that lower annualized relapse rate (ARR) in 2 years pretreatment [hazard ratio (HR) = 0.49, p = 0.001] and being naive patients (HR = 1.38, p = 0.035) were associated with achievement of NEDA-3. Analogously, ARR in 2 years pretreatment affected the NEDA-3 achievement at 24 months in patients of the de-escalation group (HR = 0.07, p = 0.041), also indicating an effect related to the DMF initiation within 3 months (HR = 1.24, p = 0.029).Conclusion: Our findings confirm DMF as a handy drug with broad clinical utility, with greater benefits for naive patients and horizontal switchers. Additionally, an increase in the flow of DMF prescriptions in these two groups of patients was also observed in our cohort.