bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renin–angiotensin system inhibitors reduce cardiovascular mortality in hypertensive patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: insights from the EffecTAVI registry
Authors: Basile Christian , Mancusi Costantino , Franzone Anna , Avvedimento Marisa , Bardi Luca , Angellotti Domenico , Castiello Domenico Simone , Mariani Andrea , Manzo Rachele , De Luca Nicola , Cirillo Plinio , De Simone Giovanni , Esposito Giovanni 
Published: August 2023

ObjectivesArterial hypertension is associated with the triggering of the renin–angiotensin system, leading to left ventricle fibrosis and worse cardiovascular outcomes. In this study, patients with comorbid arterial hypertension and severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) were selected from the EffecTAVI registry to evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on cardiovascular mortality.MethodsWe enrolled 327 patients undergoing TAVI from the EffecTAVI registry. Using Kaplan–Meier event rates and study-stratified multivariable Cox proportional hazards regression models, we evaluated 2-year clinical outcomes according to the ACEI/ARB therapy status at enrollment.ResultsAmong the included patients, 222 (67.9%) were on ACEIs/ARBs at baseline, whereas 105 (32.1%) were not. Treatment with ACEIs/ARBs was significantly associated with a 2-year decrease in the rate of cardiovascular mortality (HR = 0.44, 95% CI: 0.23–0.81, p = 0.009). This association remained stable after both multivariable adjustment and propensity score matching.ConclusionIn a cohort of hypertensive patients with severe AS who were selected from the EffecTAVI registry, ACEI/ARB treatment at baseline was found to be independently associated with a lower risk of 2-year cardiovascular mortality, suggesting a potential benefit of this treatment. More trials are needed to validate this finding and to understand the full benefit of this treatment.
The digitized chronic disease management model: scalable strategies for implementing standardized healthcare and big data analytics in Shanghai
Authors: Sui Mengyun , Cheng Minna , Zhang Sheng , Wang Yuheng , Yan Qinghua , Yang Qinping , Wu Fei , Xue Long , Shi Yan , Fu Chen 
Published: August 2023

BackgroundChronic disease management (CDM) falls under production relations, and digital technology belongs to the realm of productivity. Production relations must adapt to the development of productivity. Simultaneously, the prevalence and burden of chronic diseases are becoming increasingly severe, leveraging digital technology to innovate chronic disease management model is essential.MethodsThe model was built to cover experts in a number of fields, including administrative officials, public health experts, information technology staff, clinical experts, general practitioners, nurses, metrologists. Integration of multiple big data platforms such as General Practitioner Contract Platform, Integrated Community Multimorbidity Management System and Municipal and District-Level Health Information Comprehensive Platform. This study fully analyzes the organizational structure, participants, service objects, facilities and equipment, digital technology, operation process, etc., required for new model in the era of big data.ResultsBased on information technology, we build Integrated Community Multimorbidity Care Model (ICMCM). This model is based on big data, is driven by “technology + mechanism,” and uses digital technology as a tool to achieve the integration of services, technology integration, and data integration, thereby providing patients with comprehensive people-centered services. In order to promote the implementation of the ICMCM, Shanghai has established an integrated chronic disease management information system, clarified the role of each module and institution, and achieved horizontal and vertical integration of data and services. Moreover, we adopt standardized service processes and accurate blood pressure and blood glucose measurement equipment to provide services for patients and upload data in real time. On the basis of Integrated Community Multimorbidity Care Model, a platform and index system have been established, and the platform's multidimensional cross-evaluation and indicators are used for management and visual display.ConclusionsThe Integrated Community Multimorbidity Care Model guides chronic disease management in other countries and regions. We have utilized models to achieve a combination of services and management that provide a grip on chronic disease management.
The relationship between triglyceride-glucose index and albuminuria in United States adults
Authors: Wang Zhaoxiang , Qian Han , Zhong Shao , Gu Tian , Xu Mengjiao , Yang Qichao 
Published: August 2023

PurposeTriglyceride-glucose (TyG) index is a simple and reliable indicator of metabolic dysfunction. We aimed to investigate a possible relationship between TyG index and albuminuria in the United States adult population.MethodsThis cross-sectional study was conducted among adults with complete TyG index and urinary albumin/urinary creatinine (UACR) from 2011-2018 National Health and Nutrition Examination Survey (NHANES). The independent relationship between TyG index and albuminuria (UACR&gt;30mg/g) was evaluated. TyG index was compared with insulin resistance represented by homeostatic model assessment of insulin resistance (HOMA-IR), and metabolic syndrome. Subgroup analysis was also performed.ResultsA total of 9872 participants were included in this study, and the average TyG index was 8.53 ± 0.01. The proportion of albuminuria gradually increased with the increase of TyG index quartile interval. Elevated TyG index was independently associated with albuminuria, and this association persisted after additional adjustments for HOMA-IR or dichotomous metabolic syndrome. The area under the ROC curve (AUC) of TyG index was larger than that of log (HOMA-IR). Subgroup analysis suggested that the relationship between TyG index and albuminuria is of greater concern in age&lt;60, overweight/obese, diabetic, and metabolic syndrome patients.ConclusionThe TyG index may be a potential epidemiological tool to quantify the role of metabolic dysfunction, rather than just insulin resistance, in albuminuria in the United States adult population. Further large-scale prospective studies are needed to confirm our findings.
Ets1 and IL17RA cooperate to regulate autoimmune responses and skin immunity to Staphylococcus aureus
Authors: Battaglia Michael , Sunshine Alex C. , Luo Wei , Jin Richard , Stith Alifa , Lindemann Matt , Miller Lloyd S. , Sinha Satrajit , Wohlfert Elizabeth , Garrett-Sinha Lee Ann 
Published: August 2023

IntroductionEts1 is a lymphoid-enriched transcription factor that regulates B- and Tcell functions in development and disease. Mice that lack Ets1 (Ets1 KO) develop spontaneous autoimmune disease with high levels of autoantibodies. Naïve CD4 + T cells isolated from Ets1 KO mice differentiate more readily to Th17 cells that secrete IL-17, a cytokine implicated in autoimmune disease pathogenesis. To determine if increased IL-17 production contributes to the development of autoimmunity in Ets1 KO mice, we crossed Ets1 KO mice to mice lacking the IL-17 receptor A subunit (IL17RA KO) to generate double knockout (DKO) mice.MethodsIn this study, the status of the immune system of DKO and control mice was assessed utilizing ELISA, ELISpot, immunofluorescent microscopy, and flow cytometric analysis of the spleen, lymph node, skin. The transcriptome of ventral neck skin was analyzed through RNA sequencing. S. aureus clearance kinetics in in exogenously infected mice was conducted using bioluminescent S. aureus and tracked using an IVIS imaging experimental scheme.ResultsWe found that the absence of IL17RA signaling did not prevent or ameliorate the autoimmune phenotype of Ets1 KO mice but rather that DKO animals exhibited worse symptoms with striking increases in activated B cells and secreted autoantibodies. This was correlated with a prominent increase in the numbers of T follicular helper (Tfh) cells. In addition to the autoimmune phenotype, DKO mice also showed signs of immunodeficiency and developed spontaneous skin lesions colonized by Staphylococcus xylosus. When DKO mice were experimentally infected with Staphylococcus aureus, they were unable to clear the bacteria, suggesting a general immunodeficiency to staphylococcal species. γδ T cells are important for the control of skin staphylococcal infections. We found that mice lacking Ets1 have a complete deficiency of the γδ T-cell subset dendritic epidermal T cells (DETCs), which are involved in skin woundhealing responses, but normal numbers of other skin γδ T cells. To determine if loss of DETC combined with impaired IL-17 signaling might promote susceptibility to staph infection, we depleted DETC from IL17RA KO mice and found that the combined loss of DETC and impaired IL-17 signaling leads to an impaired clearance of the infection.ConclusionsOur studies suggest that loss of IL-17 signaling can result in enhanced autoimmunity in Ets1 deficient autoimmune-prone mice. In addition, defects in wound healing, such as that caused by loss of DETC, can cooperate with impaired IL-17 responses to lead to increased susceptibility to skin staph infections.
A prospective observational cohort study of the efficacy of tofacitinib plus iguratimod on rheumatoid arthritis with usual interstitial pneumonia
Authors: Wang Shuhua , Li Yao , Tang Yanchun , Xie Weilin , Zhang Yue , Liu Qingyan 
Published: August 2023

ObjectivesThis study aims to assess the efficacy of tofacitinib (TOF) plus iguratimod (IGU) in rheumatoid arthritis (RA) with usual interstitial pneumonia (UIP) (RA-UIP).MethodsThis was a prospective observational cohort, single-center study. Data from 78 RA-UIP patients treated with TOF plus IGU, IGU plus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and csDMARDs were analyzed. Clinically relevant responses in RA activity assessment, pulmonary function tests (PFTs), and high-resolution computed tomography (HRCT) assessment at baseline and follow-up were compared between groups to evaluate the efficacy of TOF plus IGU.ResultsA total of 78 patients were followed up for at least 6 months after treatment. There were significant changes in sedimentation rate (ESR), C reactive protein (CRP), and disease activity score (DAS) 28-CRP during the follow-up within each treatment group, but there was no statistically significant difference between the two groups. After 6 months of TOF plus IGU treatment, forced vital capacity (FVC)% (84.7 ± 14.7 vs. 90.7 ± 15.4) and HRCT fibrosis score (7.3 ± 3.4 vs. 7.0 ± 5.6) showed a significant improvement compared to the csDMARDs group (P = 0.031, P = 0.015). The TOF plus IGU-treated patients had a significantly higher regression and lower deterioration than the csDMARDs-treated patients (P = 0.026, P = 0.026) and had a significantly higher response (regression + stability), with overall response rates of 66.7% (16/24) vs. 35.7% (10/28) (P = 0.027), respectively.ConclusionOur results indicate that TOF plus IGU can simultaneously relieve RA and RA-UIP and be better than the csDMARDs with a higher response rate in RA-UIP, which may be a potential choice for “dual treat-to-target”.
Microbiome dysbiosis occurred in hypertrophic scars is dominated by S. aureus colonization
Authors: Yu Jiarong , Mao Zhigang , Zhou Zengding , Yuan Bo , Wang Xiqiao 
Published: August 2023

BackgroundThe mechanisms of hypertrophic scar formation and its tissue inflammation remain unknown.MethodsWe collected 33 hypertrophic scar (HS) and 36 normal skin (NS) tissues, and detected the tissue inflammation and bacteria using HE staining, Gram staining, and transmission electronic microscopy (TEM), in situ hybridization and immunohistochemistry for MCP-1, TNF-α, IL-6 and IL-8. In addition, the samples were assayed by 16S rRNA sequencing to investigate the microbiota diversity in HS, and the correlation between the microbiota and the indices of Vancouver Scar Scale(VSS)score.ResultsHE staining showed that a dramatically increased number of inflammatory cells accumulated in HS compared with NS, and an enhanced number of bacteria colonies was found in HS by Gram staining, even individual bacteria could be clearly observed by TEM. In situ hybridization demonstrated that the bacteria and inflammation cells co-localized in the HS tissues, and immunohistochemistry indicated the expression of MCP-1, TNF-α, IL-6, and IL-8 were significantly upregulated in HS than that in NS. In addition, there was a significantly different microbiota composition between HS and NS. At the phylum level, Firmicutes was significantly higher in HS than NS. At the genus level, S. aureus was the dominant species, which was significantly higher in HS than NS, and was strongly correlated with VSS indices.ConclusionMicrobiome dysbiosis, dominated by S. aureus, occurred in HS formation, which is correlated with chronic inflammation and scar formation, targeting the microbiome dysbiosis is perhaps a supplementary way for future scar management.
Post-COVID symptoms are associated with endotypes reflecting poor inflammatory and hemostatic modulation
Authors: An Andy Yi , Baghela Arjun , Zhang Peter G. Y. , Blimkie Travis M. , Gauthier Jeff , Kaufmann Daniel Elias , Acton Erica , Lee Amy H. Y. , Levesque Roger C. , Hancock Robert E. W. 
Published: August 2023

IntroductionPersistent symptoms after COVID-19 infection (“long COVID”) negatively affects almost half of COVID-19 survivors. Despite its prevalence, its pathophysiology is poorly understood, with multiple host systems likely affected. Here, we followed patients from hospital to discharge and used a systems-biology approach to identify mechanisms of long COVID.MethodsRNA-seq was performed on whole blood collected early in hospital and 4-12 weeks after discharge from 24 adult COVID-19 patients (10 reported post-COVID symptoms after discharge). Differential gene expression analysis, pathway enrichment, and machine learning methods were used to identify underlying mechanisms for post-COVID symptom development.ResultsCompared to patients with post-COVID symptoms, patients without post-COVID symptoms had larger temporal gene expression changes associated with downregulation of inflammatory and coagulation genes over time. Patients could also be separated into three patient endotypes with differing mechanistic trajectories, which was validated in another published patient cohort. The “Resolved” endotype (lowest rate of post-COVID symptoms) had robust inflammatory and hemostatic responses in hospital that resolved after discharge. Conversely, the inflammatory/hemostatic responses of “Suppressive” and “Unresolved” endotypes (higher rates of patients with post-COVID symptoms) were persistently dampened and activated, respectively. These endotypes were accurately defined by specific blood gene expression signatures (6-7 genes) for potential clinical stratification.DiscussionThis study allowed analysis of long COVID whole blood transcriptomics trajectories while accounting for the issue of patient heterogeneity. Two of the three identified and externally validated endotypes (“Unresolved” and “Suppressive”) were associated with higher rates of post-COVID symptoms and either persistently activated or suppressed inflammation and coagulation processes. Gene biomarkers in blood could potentially be used clinically to stratify patients into different endotypes, paving the way for personalized long COVID treatment.
B vitamins supplementation induced shifts in phytoplankton dynamics and copepod populations in a subtropical coastal area
Authors: Wang Lin , Zhao Hancheng , Sanganyado Edmond , Liang Bo , Chen Xiaohan , Ma Qun , Lin Jianqing , Liu Wenhua 
Published: August 2023

IntroductionB vitamins play a crucial role in shaping phytoplankton and zooplankton communities in marine ecosystems, yet their impact on community dynamics remains poorly understood.MethodsWe carried out in situ incubation experiments of B vitamins supplementation to explore the response pattern of phytoplankton and zooplankton community compositions.ResultsThe results showed that vitamins B1, B2, B6 and B12 promoted the growth of phytoplankton, and the total Chl α in 87.5% of the supplemented B vitamin treatments showed a significant positive response (p &lt; 0.05). Supplementation with these B vitamins significantly altered the community composition of phytoplankton, and 75% of the B vitamin-supplemented treatments showed an increase in the relative abundance of Minutocellus, Thalassiosirales, Odontella, Prymnesiales and Ditylum, considered mainly to be the result of B vitamin auxotrophy. In contrast, a significant decrease in Copepoda, including Calanoida and Cyclopoida, was observed in 87.5% of treatments. The observed shifts in community composition were attributed to the auxotrophy of certain diatoms and Prymnesiales for B vitamins. These shifts subsequently led to negative correlations (Spearman Rho &lt; -0.8) between the abundance of these phytoplankton species and Copepoda populations.DiscussionThese findings advance our understanding of the complex interactions between micronutrient availability and plankton community dynamics.
Management of acute COPD exacerbations in the internal medicine departments in Israel–a national survey
Authors: Bar-Shai Amir , Freund Ophir , Ovdat Tal , Segel Michael J. , Klempfner Robert , Elis Avishay 
Published: August 2023

BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Acute exacerbations of COPD (AECOPD) drastically affect the clinical course of the disease. We aimed to evaluate the treatment of AECOPD in the internal medicine departments in Israel, nationwide.MethodsThe COPD Israeli survey (COPDIS) is the first national survey of patients admitted with AECOPD to internal medicine departments between 2017 and 2019. The survey includes prospective (n = 344) and retrospective (n = 1,166) data from 13 medical centers. We analyzed the pre-hospital, in-hospital, and pre-discharge care. Hospital evaluation, outcomes and discharge recommendations were assessed as well.ResultsThe mean (±SD) age was 74 (±8) years, and 54% were males. 74% had comorbidities, and 88% had a diagnosis of COPD in their history. 70% of the patients received systemic steroids and antibiotics during their hospitalization, yet upon discharge, a lower rate of antibiotics prescription (10%) was found. Treatment with most long-acting bronchodilators dramatically dropped during admission, compared with their pre-hospital use. Overall, a long-acting bronchodilator (LABD) was used by 47% before admission, 28% in-hospital, and was prescribed to 54% at discharge. The discharge plan included a referral to pulmonary rehabilitation in only 11% and a smoking cessation recommendation in 43% of active smokers. The in-hospital mortality was 3% and the 1-year mortality rate was 25%. In multivariate analysis, performing a chest X-ray (adjusted OR 0.64, 95% CI 0.46–0.90) and prescribing LABD at discharge (AOR 0.73, 95% CI 0.57–0.95) were independent predictors for lower 1-year mortality.ConclusionOur results demonstrate AECOPD characteristics in Israel, and highlight several important gaps in AECOPD healthcare, which must be addressed to improve patient care.
Association of the gut microbiota with clinical variables in obese and lean Emirati subjects
Authors: Ahmad Manal Ali , Karavetian Mirey , Moubareck Carole Ayoub , Wazz Gabi , Mahdy Tarek , Venema Koen 
Published: August 2023

BackgroundGrowing evidence supports the role of gut microbiota in obesity, yet exact associations remain largely unknown. Specifically, very little is known about this association in the Emirati population.MethodsWe explored differences in gut microbiota composition, particularly the Firmicutes/Bacteroidetes (F/B) ratio, between 43 obese and 31 lean adult Emirate counterparts, and its association with obesity markers, by using V3-V4 regions of 16 S ribosomal RNA gene sequencing data. Furthermore, we collected anthropometric and biochemical data.ResultsThe two major phyla in obese and lean groups were Firmicutes and Bacteroidetes. We observed a significantly lower alpha diversity (Shannon index) in obese subjects and a significant difference in beta diversity and phylum and genus levels between the two groups. The obese group had higher abundances of Verrucomicrobia and Saccharibacteira and lower abundances of Lentisphaerae. Acidaminococcus and Lachnospira were more abundant in obese subjects and positively correlated with adiposity markers. No correlations were found between the gut microbiota and biochemical variables, such as fasting blood sugar, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.ConclusionWe reveal significant differences in the gut microbiota between obese and lean adult Emiratis and an association between certain microbial genera of the gut microbiota and obesity. A better understanding of the interactions between gut microbes, diet, lifestyle, and health is warranted.
Causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomization study
Authors: Li Hanjing , Li Candong 
Published: August 2023

BackgroundStudies showed that development of gut microbial dysbiosis has a close association with type 2 diabetes (T2D). It is not yet clear if there is a causal relationship between gut microbiota and T2D.MethodsThe data collected from the published genome-wide association studies (GWASs) on gut microbiota and T2D were analyzed. Two-sample Mendelian randomization (MR) analyses were performed to identify causal relationship between bacterial taxa and T2D. Significant bacterial taxa were further analyzed. To confirm the findings’ robustness, we performed sensitivity, heterogeneity, and pleiotropy analyses. A reverse MR analysis was also performed to check for potential reverse causation.ResultsBy combining the findings of all the MR steps, we identified six causal bacterial taxa, namely, Lachnoclostridium, Oscillospira, Roseburia, Ruminococcaceae UCG003, Ruminococcaceae UCG010 and Streptococcus. The risk of T2D might be positively associated with a high relative abundance of Lachnoclostridium, Roseburia and Streptococcus but negatively associated with Oscillospira, Ruminococcaceae UCG003 and Ruminococcaceae UCG010. The results of MR analyses revealed that there were causal relationships between the six different genera and T2D. And the reverse MR analysis did not reveal any evidence of a reverse causality.ConclusionThis study implied that Lachnoclostridium, Roseburia and Streptococcus might have anti-protective effect on T2D, whereas Oscillospira, Ruminococcaceae UCG003 and Ruminococcaceae UCG010 genera might have protective effect on T2D. Our study revealed that there was a causal relationship between specific gut microbiota genera and T2D.