bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Gene Expression and Immune Cell Infiltration in Carotid Intraplaque Hemorrhage Identified Using Integrated Bioinformatics Analysis
Authors: Lv Xiaoshuo , Wang Feng , Sun Mingsheng , Sun Congrui , Fan Xueqiang , Ma Bo , Yang Yuguang , Ye Zhidong , Liu Peng , Wen Jianyan 
Published: May 2022

BackgroundIntraplaque hemorrhage (IPH) is an important feature of unstable plaques and an independent risk factor for cardiovascular events. However, the molecular mechanisms contributing to IPH are incompletely characterized. We aimed to identify novel biomarkers and interventional targets for IPH and to characterize the role of immune cells in IPH pathogenesis.MethodsThe microarray dataset GSE163154 which contain IPH and non-IPH plaque samples was obtained from the Gene Expression Omnibus (GEO). R software was adopted for identifying differentially expressed genes (DEGs) and conducting functional investigation. The hub genes were carried by protein-protein interaction (PPI) network and were validated by the GSE120521 dataset. CIBERSORT deconvolution was used to determine differential immune cell infiltration and the relationship of immune cells and hub genes. We confirmed expression of proteins encoded by the hub genes by immunohistochemistry and western blotting in 8 human carotid endarterectomy samples with IPH and 8 samples without IPH (non-IPH).ResultsWe detected a total of 438 differentially expressed genes (DEGs), of which 248 were upregulated and 190 were downregulated. DEGs were mainly involved in inflammatory related pathways, including neutrophil activation, neutrophil degranulation, neutrophil-mediated immunity, leukocyte chemotaxis, and lysosomes. The hub genes found through the method of degree in the PPI network showed that ITGB2 and ITGAM might play an important role in IPH. Receiver operating characteristic (ROC) results also showed a good performance of these two genes in the test and validation dataset. We found that the proportions of infiltrating immune cells in IPH and non-IPH samples differed, especially in terms of M0 and M2 macrophages. Immunohistochemistry and western blotting analysis showed that expression levels of ITGB2 and ITGAM increased significantly in carotid atherosclerotic plaques with IPH.ConclusionITGB2 and ITGAM are key hub genes of IPH and may play an important role in the biological process of IPH. Our findings advance our understanding of the underlying mechanisms of IPH pathogenesis and provide valuable information and directions for future research into novel targets for IPH diagnosis and immunotherapy.
Association Between Dietary Fiber Intake and Heart Failure Among Adults: National Health and Nutrition Examination Survey 2009–2018
Authors: Zhang Hao , Lin Zhibin , Chen Jun , Gan Daojing , Zhou Haobin , Ma Zhuang , Zeng Xianghui , Xue Yuting , Wang Xiao , Zhan Qiong , Zeng Qingchun , Xu Dingli 
Published: May 2022

ObjectiveTo explore the association between dietary fiber and heart failure (HF).MethodsData were collected from the 2009–2018 National Health and Nutrition Examination Survey. Dietary fiber intake data were obtained from two 24-h dietary recall interviews. Logistic regression and restricted cubic spline models were used to explore the association of dietary intakes of total, cereal, fruit, and vegetable fiber with HF prevalence.ResultsA total of 21869 adults were included in this study. After adjusting for multiple confounding factors, the odds ratios (OR) and 95% confidence intervals (CI) for HF was 0.49 (0.28 to 0.87, P for trend = 0.016) for the highest tertile versus lowest tertile of total fiber intake. Similar results were observed for cereal but not fruit and vegetable fiber intake. Dose-response analysis indicated that dietary intake of total and cereal fiber were inversely associated with HF in a linear manner.ConclusionIntakes of total and cereal fiber were inversely associated with HF in adults.
Impact of Treat-to-Target Therapy on Bone Mineral Density Loss in Patients With Rheumatoid Arthritis: A Prospective Cohort Study
Authors: Huang Hong , Wang Yu , Xie Wenhui , Geng Yan , Gao Dai , Zhang Zhuoli 
Published: May 2022

BackgroundOsteoporosis is a common comorbidity of rheumatoid arthritis (RA). Although RA disease activity has been demonstrated to be associated with bone loss in previous studies, most of them were cross-sectional studies and not in the context of treat-to-target (T2T) strategies.ObjectivesThis study aimed to evaluate the association of disease activity with bone mineral density (BMD) changes in the context of T2T strategies in a prospective RA cohort.MethodsRA patients were enrolled from a prospective CENTRA cohort of Peking University First Hospital. The follow-ups have been scheduled every 3 to 6 months. BMD was repeated at baseline, 1 year, and then every other year. Demographics, baseline clinical features, laboratory data, and medications at each visit were recorded. Time-adjusted mean disease activity scores were adopted to reflect the overall disease activity during follow-up. The influence of univariable associations between predictors and BMD was investigated using linear regression.ResultsA total of 268 patients were included in our analysis. Their mean age was 50 (12.9) years, and 224 (83.6%) were women. The median (IQR) disease duration was 48.7 (107.6) months. Osteoporosis in the lumbar spine was observed in 23.1% of patients and 9.3% in the femoral neck at enrollment. Older age, higher SDAI score, and lower BMI were associated with osteoporosis at baseline. The proportion of patients who achieved DAS28-ESR, CDAI, and SDAI remission or LDA at the end of the first year was 71.5%, 68.8%, and 67.4%, respectively. Reevaluations of BMD at 1 year were applied to 144 patients. Mean decreases of BMDs were 1.75% at the lumbar spine and 1.40% at the femoral neck at 1 year from baseline, respectively. Patients who achieved remission had less yearly bone loss in the lumbar spine (p = 0.036). Female gender was identified as a risk factor in the multiple linear regression analyses, and lower disease activity and bisphosphonates were protective factors of continuous bone loss.ConclusionDisease activity is associated with bone loss in RA patients in the context of T2T strategies, and those who achieved remission had less yearly bone loss.
Evolution and Biogeography of Freshwater Snails of the Genus Bulinus (Gastropoda) in Afromontane Extreme Environments
Authors: Tumwebaze I. , Clewing C. , Chibwana F. D. , Kipyegon J. K. , Albrecht C. 
Published: May 2022

Mountains are considered island-like systems often characterized by exceptional biodiversity and endemism. There are many highly isolated mountain ranges in Africa that collectively have been called the Afromontane archipelago. Freshwater snails of the genus Bulinus are composed of many veterinary and biomedical important species. These intermediate hosts for schistosomiasis parasites are wide spread and some of the species are considered to be highly adapted to very harsh environmental conditions such as droughts or low temperatures. However, the extent to which the Bulinus have adapted to live in high-altitudes and factors influencing these range shifts are not well investigated. In this study, we analyzed pan-African Bulinus species from various habitats across different altitudinal ranges, focusing on the high mountains or “sky islands” to examine how the contemporary climate and historical geological factors affect species distributions and evolutionary processes. Using a fossil-calibrated multigene phylogeny composed of two mitochondrial genes (cox1, 16S) and two nuclear genes (ITS2 and H3), we tested: 1) how often and when extreme altitudes were colonized, 2) what are the biogeographical affinities and degree of isolation of high-altitude species, 3) which lineages diversified and evolved endemism in the Afromontane environments, and 4) whether the Afromontane regions represent “sky islands”. Bayesian phylogenetic inference employing a fossil-calibrated molecular clock resulted in a strongly supported phylogeny resolving the relationships between the four Bulinus groups. High-altitude colonization exists exclusively within the Bulinus truncatus/tropicus complex. Several independent colonization events occurred in the Pliocene and Pleistocene throughout Africa, mostly from nearby regions of the respective mountain ranges. Most species evolved in low to mid-altitudinal ranges. Endemism is pronounced in the Ethiopian Highlands and those of Kenya and Lesotho. A previously unknown species was found at an extreme altitude (∼4,000 m a.s.l.) on Mt. Elgon/Uganda extending the formerly known altitudinal maximum of the genus by roughly 900 m. The endemic species has already diverged in the Pliocene (∼4 myr) and is currently characterized by low genetic diversity. There is further cryptic diversity in mountain ranges of Lesotho. Our findings are discussed in a biogeographical, conservation and biomedical context.
Investigating the Association Between Seven Sleep Traits and Nonalcoholic Fatty Liver Disease: Observational and Mendelian Randomization Study
Authors: Fan Hong , Liu Zhenqiu , Zhang Xin , Yuan Huangbo , Zhao Xiaolan , Zhao Renjia , Shi Tingting , Wu Sheng , Xu Yiyun , Suo Chen , Chen Xingdong , Zhang Tiejun 
Published: May 2022

Background and Aim: Aberrant sleep parameters are associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, existing information is inconsistent among studies and involves reverse causation. Therefore, we aimed to investigate the observational associations and causations between sleep traits and NAFLD.Methods: We performed multivariable regression to assess observational associations of seven sleep traits (sleep duration, easiness of getting up in the morning, chronotype, nap during day, snoring, insomnia, and narcolepsy), and NAFLD in the UK Biobank (1,029 NAFLD). The Cox proportional hazards model was applied to derive hazard ratios and 95% confidence intervals (CIs). Furthermore, a bidirectional two-sample Mendelian randomization (MR) approach was used to explore the causal relationships between sleep traits and NAFLD.Results: In the multivariable regression model adjusted for potential confounders, getting up in the morning not at all easy (HR, 1.51; 95% CI, 1.27–1.78) and usually insomnia (HR, 1.46; 95% CI, 1.21–1.75) were associated with the risk of NAFLD. Furthermore, the easiness of getting up in the morning and insomnia showed a dose–response association with NAFLD (Ptrend &lt;0.05). MR analysis found consistent causal effects of NAFLD on easiness of getting up in the morning (OR, 0.995; 95% CI, 0.990–0.999; p = 0.033) and insomnia (OR, 1.006; 95% CI, 1.001–1.011; p = 0.024). These results were robust to weak instrument bias, pleiotropy, and heterogeneity.Conclusions: Findings showed consistent evidence of observational analyses and MR analyses that trouble getting up in the morning and insomnia were associated with an increased risk of NAFLD. Bidirectional MR demonstrated causal effects of NAFLD on sleep traits.
A DNA Damage Repair Gene Signature Associated With Immunotherapy Response and Clinical Prognosis in Clear Cell Renal Cell Carcinoma
Authors: Peng Linjie , Liang Jiaming , Wang Qi , Chen Guodong 
Published: May 2022

Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype in renal cell carcinoma with relatively poor clinical outcomes DNA damage repair genes (DDRGs) as potential biomarkers are rarely reported in predicting immunotherapy response and clinical prognosis for ccRCC.Methods: RNA-seq and clinical data of ccRCC cohort were collected form TCGA database. Univariate Cox regression and LASSO analysis were performed to construct a DDRG risk signature. Functional enrichment analysis was performed to explore latently enriched pathways associated with DDRG signature. Immune cell infiltration level was estimated using gene set enrichment analysis, and immune response of ccRCC was predicted by tumor immune dysfunction and exclusion (TIDE) algorithm. To predict 1-, 3-, and 5-years overall survival (OS), a nomogram was constructed based on independent prognostic factors, whose performance would be evaluated by calibration curve.Results: A total of 47 DNA damage repair related genes (DDRGs) with significant prognostic value were identified in the ccRCC cohort (n = 519). A DDRG risk signature comprising six DRRGs (MSH3, RAD54L, RAD50, EME1, UNG, and NEIL3) were constructed by the LASSO analysis. ccRCC patients were then divided into low- and high-risk groups based on the risk score. Survival analysis revealed that patients in high-risk groups exhibited significantly poorer OS and progression-free survival (PFS), as was confirmed by the testing dataset. Functional enrichment analysis indicated that differentially expressed genes (DEGs) between high- and low-risk groups were mainly associated with immune-related biological processes in ccRCC, among which the immunodeficiency pathway was significantly enriched in the high-risk group. Though the risk signature was significantly correlated with the immune cell infiltration, PD-1 and PD-L1 were less expressed in the DDRG signature, which might indicate the poor response to immunotherapy in the high-risk group. Furthermore, the Cox regression analysis indicated that the DDRG signature can be served as an independent prognostic predictor when compared to clinical characteristics. Based on the independent prognostic predictors, we constructed a nomogram with excellent predictive ability in OS prediction for ccRCC patients.Conclusion: We developed a reliable DDRG risk signature that can independently predict the OS and PFS of ccRCC, which is also promising for predicting immunotherapeutic responses in ccRCC patients.
Stool and Ruminal Microbiome Components Associated With Methane Emission and Feed Efficiency in Nelore Beef Cattle
Authors: Andrade Bruno G. N. , Bressani Flavia A. , Cuadrat Rafael R. C. , Cardoso Tainã F. , Malheiros Jessica M. , de Oliveira Priscila S. N. , Petrini Juliana , Mourão Gerson B. , Coutinho Luiz L. , Reecy James M. , Koltes James E. , Neto Adhemar Z. , R. de Medeiros Sérgio , Berndt Alexandre , Palhares Julio C. P. , Afli Haithem , Regitano Luciana C. A. 
Published: May 2022

Background:The impact of extreme changes in weather patterns on the economy and human welfare is one of the biggest challenges our civilization faces. From anthropogenic contributions to climate change, reducing the impact of farming activities is a priority since it is responsible for up to 18% of global greenhouse gas emissions. To this end, we tested whether ruminal and stool microbiome components could be used as biomarkers for methane emission and feed efficiency in bovine by studying 52 Brazilian Nelore bulls belonging to two feed intervention treatment groups, that is, conventional and by-product-based diets.Results:We identified a total of 5,693 amplicon sequence variants (ASVs) in the Nelore bulls’ microbiomes. A Differential abundance analysis with the ANCOM approach identified 30 bacterial and 15 archaeal ASVs as differentially abundant (DA) among treatment groups. An association analysis using Maaslin2 software and a linear mixed model indicated that bacterial ASVs are linked to the host’s residual methane emission (RCH4) and residual feed intake (RFI) phenotype variation, suggesting their potential as targets for interventions or biomarkers.Conclusion:The feed composition induced significant differences in both abundance and richness of ruminal and stool microbial populations in ruminants of the Nelore breed. The industrial by-product-based dietary treatment applied to our experimental groups influenced the microbiome diversity of bacteria and archaea but not of protozoa. ASVs were associated with RCH4emission and RFI in ruminal and stool microbiomes. While ruminal ASVs were expected to influence CH4emission and RFI, the relationship of stool taxa, such asAlistipesand Rikenellaceae (gut group RC9), with these traits was not reported before and might be associated with host health due to their link to anti-inflammatory compounds. Overall, the ASVs associated here have the potential to be used as biomarkers for these complex phenotypes.
Myeloperoxydase and CD15 With Glycophorin C Double Staining in the Evaluation of Skin Wound Vitality in Forensic Practice
Authors: Gauchotte Guillaume , Bochnakian Agathe , Campoli Philippe , Lardenois Emilie , Brix Muriel , Simon Etienne , Colomb Sophie , Martrille Laurent , Peyron Pierre-Antoine 
Published: May 2022

BackgroundThe determination of skin wound vitality based on tissue sections is a challenge for the forensic pathologist. Histology is still the gold standard, despite its low sensitivity. Immunohistochemistry could allow to obtain a higher sensitivity. Upon the candidate markers, CD15 and myeloperoxidase (MPO) may allow to early detect polymorphonuclear neutrophils (PMN). The aim of this study was to evaluate the sensitivity and the specificity of CD15 and MPO, with glycophorin C co-staining, compared to standard histology, in a series of medicolegal autopsies, and in a human model of recent wounds.MethodsTwenty-four deceased individuals with at least one recent open skin wound were included. For each corpse, a post-mortem wound was performed in an uninjured skin area. At autopsy, a skin sample from the margins of each wound and skin controls were collected (n = 72). Additionally, the cutaneous surgical margins of abdominoplasty specimens were sampled as a model of early intravital stab wound injury (scalpel blade), associated with post-devascularization wounds (n = 39). MPO/glycophorin C and CD15/glycophorin C immunohistochemical double staining was performed. The number of MPO and CD15 positive cells per 10 high power fields (HPF) was evaluated, excluding glycophorin C—positive areas.ResultsWith a threshold of at least 4 PMN/10 high power fields, the sensitivity and specificity of the PMN count for the diagnostic of vitality were 16 and 100%, respectively. With MPO/glycophorin C as well as CD15/glycophorin C IHC, the number of positive cells was significantly higher in vital than in non-vital wounds (p &lt; 0.001). With a threshold of at least 4 positive cells/10 HPF, the sensitivity and specificity of CD15 immunohistochemistry were 53 and 100%, respectively; with the same threshold, MPO sensitivity and specificity were 28 and 95%.ConclusionWe showed that combined MPO or CD15/glycophorin C double staining is an interesting and original method to detect early vital reaction. CD15 allowed to obtain a higher, albeit still limited, sensitivity, with a high specificity. Confirmation studies in independent and larger cohorts are still needed to confirm its accuracy in forensic pathology.
Factors Influencing the Outcome of Symptomatic Intracranial Artery Stenosis With Hemodynamic Impairment After Short and Long-Term Stent Placement
Authors: Gong Wentao , Zhang Xianjun , Meng Zhen , Liu Feifei , Li Guangwen , Xiao Juan , Liu Peng , Sun Yujie , Liu Tonghui , Wang Hongxia , Zhang Yong , Wang Naidong 
Published: May 2022

ObjectiveStent placement is a feasible approach worldwidely for patients with symptomatic intracranial artery stenosis (sICAS) and hemodynamic impairment (HI) who are at high risk of recurrent stroke after medical treatment. Exploration of factors associated with poor outcomes after stent placement could help develop better individualized therapeutic strategies.MethodsThis study conducted a post-hoc analysis of a prospective, multicenter registry study of stent use for sICAS with HI in China. Patient and clinical demographics, and stenotic lesion images were analyzed using univariate and multivariate Cox regression to the time until any endpoints or the end of the follow-up period. The short-term endpoint included any transient ischemic attack (TIA), stroke, or death within 1 month after stent placement. The long-term endpoints included the short-term endpoints and any TIA or stroke in the region of the affected artery that occurred more than 1 month after stent placement.ResultsTwo hundred and ninety two patients were included, with 13 short-term and 39 long-term endpoints. Multivariate Cox regression analysis revealed that lesions at the arterial origin or bifurcation (Hazard Ratio (HR) = 7.52; 95% CI, 1.89–29.82; p = 0.004) were significantly associated with higher short-term risk. Baseline renal insufficiency reduced the risk (HR = 0.08; 95% CI: 0.01–0.68; p = 0.021). Factors significantly associated with higher long-term risk included irregular or ulcerated plaques at the lesion (HR = 2.15; 95% CI: 1.07–4.33; p = 0.031). Subgroup analyses indicated that higher risk occurred in the older age group (age&gt;59 years, HR = 3.73, 95% CI: 1.27–10.97, p = 0.017), and not in the younger group (age≤59 years, HR = 1.12, 95% CI: 0.42–3.03, p = 0.822).ConclusionIrregular or ulcerated plaques in older patients and lesions at the arterial opening or bifurcation were more likely to result in adverse endpoints for stent placement during long or short -term follow-up. Investigation of these factors might facilitate the development of individualized therapeutic strategies for this population.Clinical Trial Registrationhttp://www.clinicaltrials.gov, identifier: NCT01968122.
Unusual Histopathological Findings in Mechanically Removed Stroke Thrombi – A Multicenter Experience
Authors: Aspegren Oskar , Staessens Senna , Vandelanotte Sarah , Desender Linda , Cordonnier Charlotte , Puy Laurent , Bricout Nicolas , De Meyer Simon F. , Andersson Tommy , Arnberg Fabian 
Published: May 2022

BackgroundSeveral studies have investigated the histopathology of mechanically retrieved thrombi from stroke patients. Thrombi with unusual components constitute about 1–2% of all stroke thrombi in clinical practice. Knowledge about these rare components is limited.ObjectivesTo characterize the histopathology of unusual stroke thrombi from a real-world setting with relation to clinical presentation, patient characteristics and procedural aspects of mechanical thrombectomy.MethodsOne-thousand and eight thrombi retrieved from stroke patients with mechanical thrombectomy at three different hospitals were retrospectively reviewed for unusual histological components. Fifteen thrombi were included in the study for further histopathological analysis. Clinical data and data on procedural aspects were collected.ResultsWe identified six cases with large amounts of extracellular DNA, of which three were calcified. All six cases except one received anticoagulant therapy. We describe two types of calcifications that differ with respect to general calcification morphology, von Kossa staining pattern, macrophage immunophenotype and presence of multinucleated giant cells. Cholesterol-rich (n = 3), adipocyte-like pattern-rich (n = 2), collagen-rich (n = 2) and myxomatous (n = 1) thrombi were also identified and are discussed with regard to pathogenesis and clinical and intervention characteristics. Finally, a thrombus with parts of a vascular wall is described. Suggestions for future studies are made and clinical and technical aspects of the management for these rare but important patients are discussed.ConclusionIn our retrospective multicenter study, we characterized stroke thrombi histopathologically and found subgroups of thrombi defined by presence of rarely seen components. These defined subgroups showed relation to underlying cardiovascular disease, patient characteristics, and mechanical thrombectomy technique. Knowledge about these components may increase our understanding of stroke pathophysiology and influence interventional procedures.