bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract
Authors: Sarno Alice , Leite Avelina , Augusto Carlos , Muller Igor , de Ângelis Luanna , Pimentel Lilian , Queiroz Adriano , Arruda Sergio 
Published: January 2024

IntroductionThe attenuation of BCG has led to the loss of not only immunogenic proteins but also lipid antigens.MethodsThus, we compared the macrophage and T-cell responses to nonpolar lipid extracts harvested from BCG and Mycobacterium tuberculosis (Mtb) to better understand the role of BCG lipids in the already known diminished responses of the vaccine strain.ResultsRelative to Mtb, nonpolar lipid extract from BCG presented a reduced capacity to trigger the expression of the genes encoding TNF, IL-1b, IL-6 and IL-10 in RAW 264.7 macrophages. Immunophenotyping of PBMCs isolated from healthy individuals revealed that lipids from both BCG and Mtb were able to induce an increased frequency of CD4+ and CD8+ T cells, but only the lipid extract from Mtb enhanced the frequency of CD4-CD8-double-negative, γσ+, CD4+HLA-DR+, and γσ+HLA-DR+ T cells relative to the nonstimulated control. Interestingly, only the Mtb lipid extract was able to increase the frequency of CD4+ memory (CD45RO+) T cells, whereas the BCG lipid extract induced a diminished frequency of CD4+ central memory (CD45RO+CCR7-) T cells after 48 h of culture compared to Mtb.DiscussionThese findings show that the nonpolar lipids of the BCG bacilli presented diminished ability to trigger both proinflammatory and memory responses and suggest a potential use of Mtb lipids as adjuvants to increase the BCG vaccine efficacy.
Comprehensive analysis of an endoplasmic reticulum stress-related gene prediction model and immune infiltration in idiopathic pulmonary fibrosis
Authors: Zhu Honglan , Zhou Aiming , Zhang Menglin , Pan Lin , Wu Xiao , Fu Chenkun , Gong Ling , Yang Wenting , Liu Daishun , Cheng Yiju 
Published: January 2024

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease. This study aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in IPF and explore its correlation with immune infiltration.MethodsERS-related differentially expressed genes (ERSRDEGs) were identified by intersecting differentially expressed genes (DEGs) from three Gene Expression Omnibus datasets with ERS-related gene sets. Gene Set Variation Analysis and Gene Ontology were used to explore the potential biological mechanisms underlying ERS. A nomogram was developed using the risk signature derived from the ERSRDEGs to perform risk assessment. The diagnostic value of the risk signature was evaluated using receiver operating characteristics, calibration, and decision curve analyses. The ERS score of patients with IPF was measured using a single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. Subsequently, a prognostic model based on the ERS scores was established. The proportion of immune cell infiltration was assessed using the ssGSEA and CIBERSORT algorithms. Finally, the expression of ERSRDEGs was validated in vivo and in vitro via RT-qPCR.ResultsThis study developed an 8-ERSRDEGs signature. Based on the expression of these genes, we constructed a diagnostic nomogram model in which agouti-related neuropeptide had a significantly greater impact on the model. The area under the curve values for the predictive value of the ERSRDEGs signature were 0.975 and 1.000 for GSE70866 and GSE110147, respectively. We developed a prognostic model based on the ERS scores of patients with IPF. Furthermore, we classified patients with IPF into two subtypes based on their signatures. The RT-qPCR validation results supported the reliability of most of our conclusions.ConclusionWe developed and verified a risk model using eight ERSRDEGs. These eight genes can potentially affect the progression of IPF by regulating ERS and immune responses.
The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study
Authors: Jiang Zong , Cai Xin , Yao Xiaoling , Zhang Shaoqin , Lan Weiya , Jin Zexu , Tang Fang , Ma Wukai , Yao Xueming , Chen Changming , Lan Tianzuo 
Published: January 2024

ObjectiveOsteoarthritis (OA) is the most prevalent joint disease globally, serving as a primary cause of pain and disability. However, the pathological processes underlying OA remain incompletely understood. Several studies have noted an association between cytokines and OA, yet the causal link between them remains ambiguous. This study aims to identify cytokines potentially causally related to OA using Mendelian randomization (MR) analysis, informing early clinical diagnosis and treatment decisions.MethodsWe conducted a genome-wide association study (GWAS) on 12 OA traits involving 177,517 cases and 649,173 controls from 9 international cohorts. For discovery MR analysis, we used 103 cytokines from two European populations as instrumental variables (IVs). Concurrently, another European population OA GWAS database (36,185 cases and 135,185 controls) was used to replicate MR analysis, employing the inverse variance weighted (IVW) method as the primary analytic approach. Additional methods tested included MR Egger, Weighted median, and Weighted mode. We merged the MR findings through meta-analysis. Heterogeneity testing, level pleiotropy testing (MR Egger intercept test and MRPRESSO), and sensitivity analysis via Leave One Out (LOO) were conducted to verify result robustness. Lastly, reverse MR analysis was performed.ResultsThe meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; P&lt;0.010). We also observed associations between MCP4 (OR=0.930, 95% CI: 0.890-0.970; P&lt;0.010) and CCL25 (OR=0.930, 95% CI: 0.890-0.970; P&lt;0.010) with reduced OA risk. The sensitivity analysis results corroborate the robustness of these findings.ConclusionOur MR analysis indicates a potential causal relationship between CX3CL1, MCP4, CCL25, and OA risk changes. Further research is warranted to explore the influence of cytokines on OA development.
Retrospective cohort study to evaluate the continuous use of anticholesterolemics and diuretics in patients with COVID-19
Authors: Oliveira Fabrício Marcus Silva , Caetano Mônica Maria Magalhães , Godoy Ana Raquel Viana de , Oliveira Larissa Lilian de , Melo Mambrini Juliana Vaz de , Rezende Marina Santos , Fantini Marina Pinheiro Rocha , Oliveira Mendes Tiago Antônio De , Medeiros Nayara Ingrid , Guimarães Henrique Cerqueira , Fiuza Jacqueline Araújo , Gaze Soraya Torres 
Published: January 2024

PurposeThe purpose of this study is to evaluate the interference of the continuous use of drug classes in the expression of biomarkers during the first week of hospitalization and in the prognosis of patients with COVID-19.MethodsThe patients diagnosed with COVID-19 and confirmed with SARS-CoV-2 by RT-qPCR assay underwent the collection of fasting whole blood samples for further analysis. Other data also extracted for this study included age, sex, clinical symptoms, related comorbidities, smoking status, and classes of continuous use. Routine serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, N-terminal fragment of B-type natriuretic peptide, and cardiac troponin, were measured.ResultsIn this cross-sectional study, a total of 176 patients with COVID-19 hospitalizations were included. Among them, 155 patients were discharged (88.5%), and 21 patients died (12%). Among the drug classes evaluated, we verified that the continuous use of diuretic 4.800 (1.853–11.67) (p = 0.0007) and antihypercholesterolemic 3.188 (1.215–7.997) (p = 0.0171) drug classes presented a significant relative risk of death as an outcome when compared to the group of patients who were discharged. We evaluated biomarkers in patients who used continuous antihypercholesterolemic and diuretic drug classes in the first week of hospitalization. We observed significant positive correlations between the levels of CRP with cardiac troponin (r = 0.714), IL-6 (r = 0.600), and IL-10 (r = 0.900) in patients who used continuous anticholesterolemic and diuretic drug classes and were deceased. In these patients, we also evaluated the possible correlations between the biomarkers AST, NT-ProBNP, cardiac troponin, IL-6, IL-8, and IL-10. We observed a significantly negative correlations in AST levels with NT-ProBNP (r = −0.500), cardiac troponin (r = −1.00), IL-6 (r = −1.00), and IL-10 (r = −1.00) and a positive correlation with IL-8 (r = 0.500). We also observed significant negative correlation in the levels of NT-ProBNP with IL-10 (r = −0.800) and a positive correlation with cardiac troponin (r = 0.800). IL-6 levels exhibited positive correlations with cardiac troponin (r = 0.800) and IL-10 (r = 0.700).ConclusionIn this study, we observed that hospitalized COVID-19 patients who continued using anticholesterolemic and diuretic medications showed a higher number of correlations between biomarkers, indicating a poorer clinical prognosis. These correlations suggest an imbalanced immune response to injuries caused by SARS-CoV-2.
Progressive pulmonary fibrosis in myositis-specific antibody-positive interstitial pneumonia: a retrospective cohort study
Authors: Wang Huijuan , Wang Yuanying , Sun Di , Yu Shiwen , Du Xuqin , Ye Qiao 
Published: January 2024

ObjectivesIdiopathic inflammatory myopathy (IIM) frequently coexists with interstitial pneumonia (IP) and is commonly the initial or sole manifestation accompanied by positive myositis-specific autoantibodies (MSAs), even in the absence of meeting diagnostic criteria. This study aims to evaluate the proportion of progressive pulmonary fibrosis (PPF) and identify potential predictors influencing the progression of pulmonary fibrosis in patients with MSA-IP.MethodsThis descriptive study employed a retrospective cohort design, enrolling patients diagnosed with interstitial pneumonia and positive MSAs at Beijing Chao-Yang Hospital in a sequential manner. Clinical data were systematically collected from the patients’ medical records during regular follow-up visits conducted every 3 to 6 months. Cox regression analysis was utilized to identify independent predictors of PPF in patients with positive MSAs and interstitial pneumonia.ResultsA total of 307 patients were included in the study, with 30.6% of them developing PPF during a median follow-up period of 22 months. Kaplan–Meier survival curves demonstrated a significantly lower survival in the PPF patients compared to the non-PPF patients (median 11.6 months vs. 31 months, p = 0.000). An acute/subacute onset of interstitial pneumonia (HR 3.231, 95%CI 1.936–5.392, p = 0.000), lower diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 6.435, 95%CI 4.072–10.017, p = 0.001), and the presence of diffuse alveolar damage (DAD) on high-resolution computed tomography (HRCT) (HR 8.679, 95%CI 1.974–38.157, p = 0.004) emerged as independent predictors of PPF. Notably, the implementation of triple therapy comprising glucocorticoids, immunosuppressants, and antifibrotic drugs was associated with a reduced risk of developing PPF (HR 0.322, 95%CI 0.115–0.899, p = 0.031).ConclusionApproximately 30.6% of patients with MSA-IP may develop PPF within the follow-up period. Patients presenting with an acute/subacute onset of interstitial pneumonia, lower predicted DLCO SB% and evidence of DAD on HRCT are more susceptible to developing PPF. Conversely, the administration of triple therapy appears to serve as a protective factor against the development of PPF in patients with MSA-IP.
Systemic inflammation among adults with diagnosed and undiagnosed cardiometabolic conditions: a potential missed opportunity for cardiovascular disease prevention
Authors: Mainous Arch G. , Sharma Pooja , Jo Ara 
Published: January 2024

ContextSystemic inflammation is associated with cardiovascular morbidity and mortality. Since inflammation is not screened in the population, the prevalence, particularly among individuals with undiagnosed cardiometabolic disease, is unclear.ObjectiveTo assess the prevalence of elevated inflammation using high sensitivity C-reactive protein (hs-CRP) (&gt;0.30 mg/dL) in adults with no cardiometabolic disease, undiagnosed disease and diagnosed disease.MethodsWe conducted a cross-sectional analysis of the 2015–2020 National Health and Nutrition Examination Survey which allows for population estimates of the US population. Adults &gt; = 20 years old were included. HsCRP levels &gt;0.30 mg/dL represented inflammation. Individuals were classified into disease defined as having one or more of the following: diagnosed disease--diabetes, hypertension, hyperlipidemia, or obesity by diagnosis; undiagnosed disease (self-report of no doctor diagnosis but positive biomarker); no disease.Results12,946 unweighted individuals representing 315,354,183 adults in the US population were assessed. The proportion of adults with systemic inflammation is 34.63%. The proportion of individuals aged 20 years and older with no disease, undiagnosed disease and diagnosed disease and inflammation was 15.1, 29.1 and 41.8%, respectively. When stratifying by race/ethnicity among individuals with elevated inflammation Non-Hispanic Black people have the highest prevalence (50.35%) in individuals with diagnosed disease followed by Hispanics (46.13%) and Non-Hispanic White people (40.15%) (p &lt; 0.01). In logistic regressions adjusted for sociodemographic variables, individuals with undiagnosed cardiometabolic disease have an increased risk of elevated inflammation as measured by CRP (OR 2.38; 95%CI = 1.90–2.99).ConclusionIn conclusion, a substantial proportion of the adult population, particularly minority and low socioeconomic populations, have elevated inflammation. Systemic inflammation may be a potential focus for disease prevention and disease progression in primary care.
Surgical therapy and outcome of descending necrotizing mediastinitis in Chinese: a single-center series
Authors: Zhao Zhewei , Ma Dongjie , Xu Yuan , Guo Chao , Li Shanqing , Wang Jian , Wang Mu , Qin Yingzhi , Liu Hongsheng 
Published: January 2024

BackgroundDescending Necrotizing Mediastinitis (DNM) is an acute and often fatal infection that affects the neck and mediastinum. DNM treatment consists of broad-spectrum antibiotics, early diagnosis, and surgical debridement with multidisciplinary cooperation. However, owing to the rarity and complexity of this disease, the mortality rate is high. This retrospective study analyzed a single-center experience of managing DNM in Chinese patients over the last 10 years.MethodsA single-center, retrospective, observational, and descriptive study was conducted on 31 patients with DNM at Peking Union Medical College Hospital from 2012 to 2022. Case report forms were used to collect data which were then analyzed with a focus on surgical management and outcomes.ResultsThis study examined the outcomes of 31 patients diagnosed with DNM at our hospital. The most common comorbidities on admission were hypertension (48%) and diabetes mellitus (42%). The degree of diffusion of DNM according to Endo’s classification was classified as follows: type I in 7 patients (22.6%), type IIA in 5 (16.1%), and type IIB in 19 patients (61.3%). Among these patients, 13 (41.9%) were found to have a single microbial infection, while 16 (51.6%) were found to have polymicrobial infections. In all cases, neck drainage was performed via cervicotomy, with multiple drains (64.5%) and vacuum sealing drainage (VSD) (35.5%). Mediastinal drainage was performed via a cervical mediastinotomy (51.6%), video-assisted thoracic surgery (VATS) (41.9%), or thoracotomy (6.5%). The 30-day mortality rate was 25.8% and 24.0 days of the average length of hospital stay.ConclusionEarly accurate diagnosis and timely intervention have been shown to be correlated with a positive prognosis. Cervicothoracic CT (computed tomography) is essential for the diagnosis, staging, and evaluation of the optimal surgical treatment. Cervicotomy and video-assisted thoracoscopic surgery with percutaneous drainage is effective, even in advanced cases. Additionally, the application of VSD in cervical incision did not improve prognosis but may shorten the length of ICU (intensive care unit) and hospital stays.
Christensenella minuta, a new candidate next-generation probiotic: current evidence and future trajectories
Authors: Ignatyeva Olga , Tolyneva Darya , Kovalyov Aleksandr , Matkava Lorena , Terekhov Mikhail , Kashtanova Daria , Zagainova Anzhelika , Ivanov Mikhail , Yudin Vladimir , Makarov Valentin , Keskinov Anton , Kraevoy Sergey , Yudin Sergey 
Published: January 2024

BackgroundAs the field of probiotic research continues to expand, new beneficial strains are being discovered. The Christensenellaceae family and its newly described member, Christensenella minuta, have been shown to offer great health benefits. We aimed to extensively review the existing literature on these microorganisms to highlight the advantages of their use as probiotics and address some of the most challenging aspects of their commercial production and potential solutions.MethodsWe applied a simple search algorithm using the key words “Christensenellaceae” and “Christensenella minuta” to find all articles reporting the biotherapeutic effects of these microorganisms. Only articles reporting evidence-based results were reviewed.ResultsThe review showed that Christensenella minuta has demonstrated numerous beneficial properties and a wider range of uses than previously thought. Moreover, it has been shown to be oxygen-tolerant, which is an immense advantage in the manufacturing and production of Christensenella minuta-based biotherapeutics. The results suggest that Christensenellaceae and Christensenella munita specifically can play a crucial role in maintaining a healthy gut microbiome. Furthermore, Christensenellaceae have been associated with weight management. Preliminary studies suggest that this probiotic strain could have a positive impact on metabolic disorders like diabetes and obesity, as well as inflammatory bowel disease.ConclusionChristensenellaceae and Christensenella munita specifically offer immense health benefits and could be used in the management and therapy of a wide range of health conditions. In addition to the impressive biotherapeutic effect, Christensenella munita is oxygen-tolerant, which facilitates commercial production and storage.
Increase in invasive group A streptococcal infections in Milan, Italy: a genomic and clinical characterization
Authors: Mangioni Davide , Fox Valeria , Saltini Paola , Lombardi Andrea , Bussini Linda , Carella Francesco , Cariani Lisa , Comelli Agnese , Matinato Caterina , Muscatello Antonio , Teri Antonio , Terranova Leonardo , Cento Valeria , Carloni Sara , Bartoletti Michele , Alteri Claudia , Bandera Alessandra 
Published: January 2024

BackgroundGroup A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally.MethodsGAS strains collected in 09/2022–03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed. Clinical/epidemiological data were combined with whole-genome sequencing to: (i) define resistome/virulome, (ii) identify putative transmission chains, (iii) explore associations between emm-types and clinical severity.ResultsTwenty-eight isolates were available, 19/28 (67.9%) from adults and 9/28 (32.1%) from pediatric population. The criteria for iGAS were met by 19/28 cases (67.9%), of which 11/19 (39.3%) met the further criteria for severe-iGAS. Pediatric cases were mainly non-invasive infections (8/9, 88.9%), adult cases were iGAS and severe-iGAS in 18/19 (94.7%) and 10/19 (52.6%), respectively. Thirteen emm-types were detected, the most prevalent being emm1 and emm12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of emm1.0 and emm12.0 strains revealed pairwise SNP distance always &gt;10, inconsistent with unique transmission chains. Emm12.0-type, found to almost exclusively carry virulence factors speH and speI, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%, p = 0.007 and 66.7 vs. 0.0%, p &lt; 0.001, respectively), while emm1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%, p = 0.045).ConclusionsThis study showed that multiple emm-types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific emm-types could be associated with disease severity or invasiveness. Overall, these results support the integration of classical epidemiological studies with genomic investigation to appropriately manage severe infections and improve surveillance.
Shrub expansion raises both aboveground and underground multifunctionality on a subtropical plateau grassland: coupling multitrophic community assembly to multifunctionality and functional trade-off
Authors: Ding Leilei , Chen Hong , Wang Mengya , Wang Puchang 
Published: January 2024

IntroductionShrubs have expanded into grasslands globally. However, the relative importance of aboveground and underground diversity and the relative importance of underground community assembly and diversity in shaping multifunctionality and functional trade-offs over shrub expansion remains unknown.MethodsIn this study, aboveground and underground multitrophic communities (abundant and rare archaea, bacteria, fungi, nematodes, and protists) and 208 aboveground and underground ecosystem properties or indicators were measured at three stages (Grass, Mosaic, Shrub) of shrub expansion on the Guizhou subtropical plateau grassland to study multifunctionality and functional trade-offs.ResultsThe results showed that shrub expansion significantly enhanced aboveground, underground, and entire ecosystem multifunctionality. The functional trade-off intensities of the aboveground, underground, and entire ecosystems showed significant V-shaped changes with shrub expansion. Shrub expansion improved plant species richness and changed the assembly process and species richness of soil abundant and rare subcommunities. Plant species diversity had a greater impact on multifunctionality than soil microbial diversity by more than 16%. The effect of plant species diversity on functional trade-offs was only one-fifth of the effect of soil microbial diversity. The soil microbial species richness did not affect multifunctionality, however, the assembly process of soil microbial communities did. Rather than the assembly process of soil microbial communities, the soil microbial species richness affected functional trade-offs.DiscussionOur study is the first to couple multitrophic community assemblies to multifunctionality and functional trade-offs. Our results would boost the understanding of the role of aboveground and underground diversity in multifunctionality and functional trade-offs.