bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacteroides fragilis outer membrane vesicles preferentially activate innate immune receptors compared to their parent bacteria
Authors: Gilmore William J. , Johnston Ella L. , Bitto Natalie J. , Zavan Lauren , O'Brien-Simpson Neil , Hill Andrew F. , Kaparakis-Liaskos Maria 
Published: September 2022

The release of bacterial membrane vesicles (BMVs) has become recognized as a key mechanism used by both pathogenic and commensal bacteria to activate innate immune responses in the host and mediate immunity. Outer membrane vesicles (OMVs) produced by Gram-negative bacteria can harbor various immunogenic cargo that includes proteins, nucleic acids and peptidoglycan, and the composition of OMVs strongly influences their ability to activate host innate immune receptors. Although various Gram-negative pathogens can produce OMVs that are enriched in immunogenic cargo compared to their parent bacteria, the ability of OMVs produced by commensal organisms to be enriched with immunostimulatory contents is only recently becoming known. In this study, we investigated the cargo associated with OMVs produced by the intestinal commensal Bacteroides fragilis and determined their ability to activate host innate immune receptors. Analysis of B. fragilis OMVs revealed that they packaged various biological cargo including proteins, DNA, RNA, lipopolysaccharides (LPS) and peptidoglycan, and that this cargo could be enriched in OMVs compared to their parent bacteria. We visualized the entry of B. fragilis OMVs into intestinal epithelial cells, in addition to the ability of B. fragilis OMVs to transport bacterial RNA and peptidoglycan cargo into Caco-2 epithelial cells. Using HEK-Blue reporter cell lines, we identified that B. fragilis OMVs could activate host Toll-like receptors (TLR)-2, TLR4, TLR7 and nucleotide-binding oligomerization domain-containing protein 1 (NOD1), whereas B. fragilis bacteria could only induce the activation of TLR2. Overall, our data demonstrates that B. fragilis OMVs activate a broader range of host innate immune receptors compared to their parent bacteria due to their enrichment of biological cargo and their ability to transport this cargo directly into host epithelial cells. These findings indicate that the secretion of OMVs by B. fragilis may facilitate immune crosstalk with host epithelial cells at the gastrointestinal surface and suggests that OMVs produced by commensal bacteria may preferentially activate host innate immune receptors at the mucosal gastrointestinal tract.
Disease predisposition of human leukocyte antigen class II genes influences the gut microbiota composition in patients with primary biliary cholangitis
Authors: Huang Chun-Yang , Zhang Hai-Ping , Han Wei-Jia , Zhao Dan-Tong , Liao Hui-Yu , Ma Yin-Xue , Xu Bin , Li Li-Juan , Han Ying , Liu Xiu-Hong , Wang Qi , Lou Jin-Li , Zhang Xiao-Dan , Zhao Juan , Li Wen-Juan , Liu Yan-Min , Yan Hui-Ping 
Published: September 2022

BackgroundThe human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown.MethodsA cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from 43 of the 151 fully HLA-typed patients to analyze their microbiota compositions via 16S RNA gene sequencing.ResultsOf the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA DRB1*08:03 than did the controls (21.2% vs. 9.0%, P=0.0001). HLA-DRB1*03:01, DRB1*07:01, DRB1*14:05, and DRB1*14:54 frequencies were also increased but did not reach significance after Bonferroni’s correction. Conversely, the DQB1*03:01 frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%, P=0.0010). The patients’ gut microbiota were analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA DRB1 high-risk alleles) than in FHRAC-negative patients (P&lt;0.05). Of the top 10 microbial genera, Lachnospiraceae_incertae_sedis was higher in the FHRAC-positive patients than in the FHRAC-negative patients (P&lt;0.05). linear discriminant analysis (LDA) effect-size (LEfSe) analysis showed different microbes at different levels in the FHRAC-negative patients but not in the FHRAC-positive patients. DQB1*03:01-positive patients contained mostly Lactobacillaceae at the family level. A comparison of the FHRAC-positive patients with and without liver cirrhosis showed that the abundances of Veillonella were significantly higher in patients with cirrhosis and FHRAC than in those without cirrhosis and are FHRAC-negative.ConclusionThe HLA class II genes may influence the gut microbiota compositions in patients with PBC. Differential gut microbiota were expressed at different taxonomic levels. Some bacterial abundances may be increased in FHRAC-positive patients with PBC and cirrhosis.
Identification of immune-related endoplasmic reticulum stress genes in sepsis using bioinformatics and machine learning
Authors: Gong Ting , Liu Yongbin , Tian Zhiyuan , Zhang Min , Gao Hejun , Peng Zhiyong , Yin Shuang , Cheung Chi Wai , Liu Youtan 
Published: September 2022

BackgroundSepsis-induced apoptosis of immune cells leads to widespread depletion of key immune effector cells. Endoplasmic reticulum (ER) stress has been implicated in the apoptotic pathway, although little is known regarding its role in sepsis-related immune cell apoptosis. The aim of this study was to develop an ER stress-related prognostic and diagnostic signature for sepsis through bioinformatics and machine learning algorithms on the basis of the differentially expressed genes (DEGs) between healthy controls and sepsis patients.MethodsThe transcriptomic datasets that include gene expression profiles of sepsis patients and healthy controls were downloaded from the GEO database. The immune-related endoplasmic reticulum stress hub genes associated with sepsis patients were identified using the new comprehensive machine learning algorithm and bioinformatics analysis which includes functional enrichment analyses, consensus clustering, weighted gene coexpression network analysis (WGCNA), and protein-protein interaction (PPI) network construction. Next, the diagnostic model was established by logistic regression and the molecular subtypes of sepsis were obtained based on the significant DEGs. Finally, the potential diagnostic markers of sepsis were screened among the significant DEGs, and validated in multiple datasets.ResultsSignificant differences in the type and abundance of infiltrating immune cell populations were observed between the healthy control and sepsis patients. The immune-related ER stress genes achieved strong stability and high accuracy in predicting sepsis patients. 10 genes were screened as potential diagnostic markers for sepsis among the significant DEGs, and were further validated in multiple datasets. In addition, higher expression levels of SCAMP5 mRNA and protein were observed in PBMCs isolated from sepsis patients than healthy donors (n = 5).ConclusionsWe established a stable and accurate signature to evaluate the diagnosis of sepsis based on the machine learning algorithms and bioinformatics. SCAMP5 was preliminarily identified as a diagnostic marker of sepsis that may affect its progression by regulating ER stress.
Effects of sodium humate and probiotics on growth performance enzyme activity and microbial environment of Litopenaeus vannamei in high-density zero‐water exchange systems
Authors: Liao Wuquan , Lin Zexu , Liao Minze , Xue Yuan , Zhou Jianing , Wang Yue , Hou Danqing , Sun Chengbo 
Published: September 2022

The study investigates the outcomes of adding sodium humate and sodium humate with probiotics (Lysinibacillus,Bacillus subtilis) to culture water on the growth performance, enzyme activity, and microbial environment of shrimp. The sodium humate and probiotics concentrations were 3 mg/L and 105CFU/mL in the culture water.Litopenaeus vannamei(0.31 ± 0.03 g) at a density of 300 shrimps/m3were cultured in nine buckets for a 43-days culture experiment. The results showed that the survival rate (SR) ofL. vannameiin sodium humate group and sodium humate with probiotics group were (88.44%) and (86.07%), with the sodium humate group outcome being significantly better than the control group. The shrimps’ final body weight and specific growth rate (SGR) in the two experimental groups were significantly higher than the control group. The feed conversion rate (FCR) was significantly lower than the control group. The ammonia nitrogen concentration in sodium humate with probiotics group was significantly lower than the control group on the 15th day. The activities of intestinal amylase, lipase, trypsin and hepatopancreas superoxide dismutase (SOD), phenol oxidase (PO), and catalase (CAT) in sodium humate group were significantly higher than the control group. Notably, SOD, PO, and lipase activities in sodium humate with probiotics group were significantly higher than the control group. Illumina MiSeq high-throughput sequencing showed that the Chao and Ace indices of the culture water microflora in experimental groups were higher than the control group, and the sodium humate group was significantly higher than the control group. At the phylum level, Proteobacteria, Bacteroidetes, and Actinobacteria were the dominant bacterial communities in the intestine and culture water ofL. vannamei, Proteobacteria was the most abundant phyla. At the genus level, the relative abundance ofPseudohongiellaof water microflora in the control group was significantly lower than the experimental groups.Ruggiella(15.22-19.56%) was the most abundant genera of intestinal microflora. These results infer that the addition of sodium humate enhances the growth performance, digestive enzymes, and some immune enzyme activities, improving the richness of the water microbial community ofL. vannamei.
Non-conventional interventions to prevent gonorrhea or syphilis among men who have sex with men: A scoping review
Authors: Tran Julien , Fairley Christopher K. , Bowesman Henry , Aung Ei T. , Ong Jason J. , Chow Eric P. F. 
Published: September 2022

ObjectivesWe assessed nonconventional interventions that did not traditionally focus on increasing condom use and/or testing among men who have sex with men (MSM) and the evidence for these interventions.MethodsGuided by the Participants, Concept and Context (PCC) framework, we searched five online databases from inception to 9 August 2021 for original research on interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis in MSM. Two researchers screened titles and abstracts to assess eligibility, reviewed articles' full text and resolved discrepancies through discussion. We charted relevant study information, and the included studies were critically appraised.ResultsOf 373 articles retrieved, 13 studies were included. These studies were conducted in Australia (n = 3), Belgium (n = 2), China (n = 3), the Netherlands (n = 1) and the US (n = 4). Two randomized controlled trials (RCTs) of doxycycline as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) reduced any STI incidence (gonorrhea, syphilis, or chlamydia), but only doxycycline PEP significantly reduced syphilis incidence. Six studies of interventions that facilitated self-collection, self-examination, and self-testing, found varied evidence for gonorrhea and/or syphilis prevention. Four RCTs and one single-arm trial examined the efficacy of mouthwash, but the evidence remains inconclusive on whether mouthwash use can prevent transmission between men.ConclusionWe found evidence for doxycycline PEP in reducing syphilis incidence, evidence on the use of mouthwash to prevent gonorrhea transmission between men remains inconclusive. More evidence is needed for interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis.
Appropriate empirical antifungal therapy is associated with a reduced mortality rate in intensive care unit patients with invasive fungal infection: A real-world retrospective study based on the MIMIC-IV database
Authors: Zhang Man-ka , Rao Zhi-guo , Ma Tao , Tang Ming , Xu Tian-qi , He Xiao-xu , Li Zhou-ping , Liu Yin , Xu Qing-jie , Yang Ke-yu , Gong Yi-fan , Xue Jing , Wu Mei-qing , Xue Xiao-yan 
Published: September 2022

ObjectiveThe study aimed to determine the prevalence and pathogens of invasive fungal infection (IFI) among intensive care unit (ICU) patients. The next goal was to investigate the association between empirical antifungal treatment and mortality in ICU patients.MethodsUsing microbiological events, we identified all ICU patients with IFI and then retrieved electronic clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The data were statistically analyzed using t-tests, chi-square tests, log-rank tests, and Cox regression.ResultsThe most commonly reported fungi were Candida (72.64%) and Aspergillus (19.08%). The most frequently prescribed antifungal medication was fluconazole (37.57%), followed by micafungin (26.47%). In the survival study of ICU patients and patients with sepsis, survivors were more likely to receive empirical antifungal treatment. In contrast, non-empirical antifungal therapy was significantly associated with poor survival in patients with positive blood cultures. We found that the current predictive score makes an accurate prediction of patients with fungal infections challenging.ConclusionsOur study demonstrated that empirical antifungal treatment is associated with decreased mortality in ICU patients. To avoid treatment delays, novel diagnostic techniques should be implemented in the clinic. Until such tests are available, appropriate empirical antifungal therapy could be administered based on a model that predicts the optimal time to initiate antifungal therapy. Additional studies should be conducted to establish more accurate predictive models in the future.
Chinese SLE Treatment and Research Group Registry (CSTAR) XIV: the subjective well-being of patients with systemic lupus erythematosus
Authors: Shi Yue , Bi Dandan , Wang Yanhong , Li Ruofan , Wu Lijun , Zhao Cheng , Wu Zhenbiao , Duan Xinwang , Xu Jian , Zhan Feng , Yang Min , Liu Shengyun , Li Qin , Zhang Shuo , Liu Lingshan , Zhao Jiuliang , Tian Xinping , Li Xinying , Wang Qian , Zeng Xiaofeng ,   CSTAR Co-authors
Published: September 2022

BackgroundSystemic lupus erythematosus (SLE) can significantly influence patients’ quality of life and subjective well-being (SWB), but the relationships between clinical characteristics, SWB, and related psychological factors have been little studied.ObjectiveTo measure SWB in patients with SLE and examine how major clinical determinants, emotional variables, and related positive factors affect SWB.MethodsOverall, 1,110 patients with SLE from the Chinese SLE Treatment and Research Group (CSTAR) and 198 age and gender-matched individuals from the general population without self-reported SLE were invited to complete questionnaires of SWB evaluated by the satisfaction with life scale (SWLS), emotional variables assessed by the patient health questionnaire-9 (PHQ-9), and general anxiety disorder-7 (GAD-7) and related positive factors assessed by the self-esteem scale (SES), general self-efficacy scale (GESE), and Connor-Davidson resilience scale (CD-RISC). The multivariate linear regression was used to examine the relationship between clinical manifestations and SWB.ResultsLife satisfaction was significantly lower (p &lt; 0.001) in patients with SLE than in the general population. Active skin involvement (OR = 0.923, 95% CI = 0.868–0.981, p &lt; 0.05) was negatively associated with life satisfaction scores, and age at enrollment (OR = 1.160, 95% CI = 1.092–1.230, p &lt; 0.001) were positively associated with life satisfaction scores in the multivariate regression model. The cumulative organ damage was significantly associated with depression (OR = 1.085, 95% CI = 1.022–1.153, p &lt; 0.01) and the loss of self-esteem (OR = 1.067, 95% CI = 1.004–1.133, p &lt; 0.05).ConclusionSWB provides useful insight into the impact of SLE on psychological health and opportunities to improve quality of life and clinical care.
Extended effects of a wearable sensory prosthesis on gait, balance function and falls after 26 weeks of use in persons with peripheral neuropathy and high fall risk—The walk2Wellness trial
Authors: Oddsson Lars I. E. , Bisson Teresa , Cohen Helen S. , Iloputaife Ikechukwu , Jacobs Laura , Kung Doris , Lipsitz Lewis A. , Manor Brad , McCracken Patricia , Rumsey Yvonne , Wrisley Diane M. , Koehler-McNicholas Sara R. 
Published: September 2022

BackgroundWe recently reported that individuals with impaired plantar sensation and high fall risk due to sensory peripheral neuropathy (PN) improved gait and balance function following 10 weeks of use of Walkasins®, a wearable lower limb sensory prosthesis that provides directional specific mechanical tactile stimuli related to plantar pressure measurements during standing and walking (RxFunction Inc., Eden Prairie, MN, United States). Here, we report 26-week outcomes and compare pre- and in-study fall rates. We expected improvements in outcomes and reduced fall rates reported after 10 weeks of use to be sustained.Materials and methodsParticipants had clinically diagnosed PN with impaired plantar sensation, high fall risk (Functional Gait Assessment, FGA score &lt; 23) and ability to sense tactile stimuli above the ankle at the location of the device. Additional outcomes included 10 m Gait Speed, Timed Up and Go (TUG), Four-Stage Balance Test, and self-reported outcomes, including Activities-Specific Balance Confidence scale and Vestibular Disorders Activities of Daily Living Scale. Participants tracked falls using a calendar.ResultsWe assessed falls and self-reported outcomes from 44 individuals after 26 weeks of device use; 30 of them conducted in-person testing of clinical outcomes. Overall, improvements in clinical outcomes seen at 10 weeks of use remained sustained at 26 weeks with statistically significant increases compared to baseline seen in FGA scores (from 15.0 to 19.2), self-selected gait speed (from 0.89 to 0.97 m/s), and 4-Stage Balance Test (from 25.6 to 28.4 s), indicating a decrease in fall risk. Non-significant improvements were observed in TUG and fast gait speed. Overall, 39 falls were reported; 31 of them did not require medical treatment and four caused severe injury. Participants who reported falls over 6 months prior to the study had a 43% decrease in fall rate during the study as compared to self-report 6-month pre-study (11.8 vs. 6.7 falls/1000 patient days, respectively, p &lt; 0.004), similar to the 46% decrease reported after 10 weeks of use.ConclusionA wearable sensory prosthesis can improve outcomes of gait and balance function and substantially decreases incidence of falls during long-term use. The sustained long-term benefits in clinical outcomes reported here lessen the likelihood that improvements are placebo effects.Clinical trial registrationClinicalTrials.gov, identifier #NCT03538756.
Dexmedetomidine exerts an anti-inflammatory effect via α2 adrenoceptors to alleviate cognitive dysfunction in 5xFAD mice
Authors: Luo Su-mei , Li Long-yan , Guo Li-zhe , Wang Lu , Wang Yan-feng , Chen Na , Wang E. 
Published: September 2022

Background: Inflammation promotes the progression of Alzheimer’s disease (AD). In this study, we explored the effect of dexmedetomidine on inflammation and cognitive function in a mouse model of AD.Methods: 5xFAD mice were intragastrically administered saline, dexmedetomidine, or dexmedetomidine and yohimbine for 14 days. The effects of dexmedetomidine on the acquisition and retention of memory in the Morris water-maze test and Y maze were evaluated. The deposition of amyloid beta protein (Abeta) and cytokine levels in the hippocampus were assessed. The expression of Bace1 protein and NFκB-p65 protein was assessed by Western blotting.Results: Compared with WT mice, 5xFAD mice exhibited cognitive impairment in the Morris water maze test and Y maze test. Cognitive decline was alleviated by dexmedetomidine and this was reversed by the α2 adrenoceptor antagonist yohimbine. Compared with saline treatment, dexmedetomidine led to a reduction in the Abeta deposition area (p &lt; 0.05) and in the mean gray value (p &lt; 0.01) in the hippocampus of 5xFAD mice. Compared with saline treatment, dexmedetomidine inhibited the activation of astrocytes and microglia in the hippocampal DG of 5xFAD mice and reduced the area of GFAP (p &lt; 0.01) and IBA1 (p &lt; 0.01). The level of IL-1β in the hippocampus decreased significantly after dexmedetomidine treatment compared with saline treatment in 5xFAD mice (p &lt; 0.01). Yohimbine neutralized the effects of dexmedetomidine. Dexmedetomidine inhibited the expression of BACE1 and NF-κB p65 (p &lt; 0.01), and these changes were reversed by yohimbine treatment.Conclusion: Dexmedetomidine alleviates cognitive decline, inhibits neuroinflammation, and prevents the deposition of Abeta in 5xFAD mice. The effect is mediated by the α2 adrenoceptor-mediated anti-inflammatory pathway. Dexmedetomidine may be effective for the treatment of AD and a better choice for the sedation of AD.
Metabolic syndrome predictors of brain gray matter volume in an age-stratified community sample of 776 Mexican- American adults: Results from the genetics of brain structure image archive
Authors: Kotkowski Eithan , Price Larry R. , DeFronzo Ralph A. , Franklin Crystal G. , Salazar Maximino , Garrett Amy S. , Woolsey Mary , Blangero John , Duggirala Ravindranath , Glahn David C. , Fox Peter T. 
Published: September 2022

IntroductionThis project aimed to investigate the association between biometric components of metabolic syndrome (MetS) with gray matter volume (GMV) obtained with magnetic resonance imaging (MRI) from a large cohort of community-based adults (n = 776) subdivided by age and sex and employing brain regions of interest defined previously as the “Neural Signature of MetS” (NS-MetS).MethodsLipid profiles, biometrics, and regional brain GMV were obtained from the Genetics of Brain Structure (GOBS) image archive. Participants underwent T1-weighted MR imaging. MetS components (waist circumference, fasting plasma glucose, triglycerides, HDL cholesterol, and blood pressure) were defined using the National Cholesterol Education Program Adult Treatment Panel III. Subjects were grouped by age: early adult (18–25 years), young adult (26–45 years), and middle-aged adult (46–65 years). Linear regression modeling was used to investigate associations between MetS components and GMV in five brain regions comprising the NS-MetS: cerebellum, brainstem, orbitofrontal cortex, right insular/limbic cluster and caudate.ResultsIn both men and women of each age group, waist circumference was the single component most strongly correlated with decreased GMV across all NS-MetS regions. The brain region most strongly correlated to all MetS components was the posterior cerebellum.ConclusionThe posterior cerebellum emerged as the region most significantly associated with MetS individual components, as the only region to show decreased GMV in young adults, and the region with the greatest variance between men and women. We propose that future studies investigating neurological effects of MetS and its comorbidities—namely diabetes and obesity—should consider the NS-MetS and the differential effects of age and sex.