bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic causality and site-specific relationship between sarcopenia and osteoarthritis: a bidirectional Mendelian randomization study
Authors: Jia Xue-Min , Deng Ting-Ting , Su Hang , Shi Hao-Jun , Qin Hao , Yu Gong-Chang , Yin Ying , Liu Fan-Jie , Shi Bin 
Published: January 2024

Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA.Method: We used pooled genetic data from the UK Biobank for ALM(n = 450,243), left-hand grip strength (n = 461,026), right-hand grip strength (n = 461,089) and usual walking pace (n = 459,915). Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA (n = 826,690), hand OA (n = 303,7782), hip OA (n = 353,388) and knee OA (n = 396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted p values (PFDR). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses.Results: We discovered ALM (odds ratio (OR) = 1.103, 95% confidence interval (CI) = 1.052–1.156, PFDR = 2.87E-04), hand grip strength (left, IVW OR = 0.823, 95% CI = 0.712 to 0.952, PFDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, PFDR = 0.020), and usual walking pace (OR = 0.339, 95% CI = 0.204 to 0.564, PFDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (β = −0.258, 95% CI = −0.369 to 0.146, PFDR = 0.6.07E-06), grip strength (left, β = −0.064, 95% CI = −0.104 to 0.024, PFDR = 0.002; right, β = −0.055, 95% CI = −0.095 to 0.014, PFDR = 0.008), and usual walking pace (β = −0.104, 95% CI = −0.147 to 0.061, PFDR = 1.61E-05).Conclusion: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP.
Pharmacogenomics of intravenous immunoglobulin response in Kawasaki disease
Authors: Shrestha Sadeep , Wiener Howard W. , Kajimoto Hidemi , Srinivasasainagendra Vinodh , Ledee Dolena , Chowdhury Sabrina , Cui Jinhong , Chen Jake Y. , Beckley Mikayla A , Padilla Luz A. , Dahdah Nagib , Tiwari Hemant K. , Portman Michael A. 
Published: January 2024

IntroductionKawasaki disease (KD) is a diffuse vasculitis in children. Response to high dose intravenous gamma globulin (IVIG), the primary treatment, varies according to genetic background. We sought to identify genetic loci, which associate with treatment response using whole genome sequencing (WGS).MethodWe performed WGS in 472 KD patients with 305 IVIG responders and 167 non-responders defined by AHA clinical criteria. We conducted logistic regression models to test additive genetic effect in the entire cohort and in four subgroups defined by ancestry information markers (Whites, African Americans, Asians, and Hispanics). We performed functional mapping and annotation using FUMA to examine genetic variants that are potentially involved IVIG non-response. Further, we conducted SNP-set [Sequence] Kernel Association Test (SKAT) for all rare and common variants.ResultsOf the 43,288,336 SNPs (23,660,970 in intergenic regions, 16,764,594 in introns and 556,814 in the exons) identified, the top ten hits associated with IVIG non-response were in FANK1, MAP2K3:KCNJ12, CA10, FRG1DP, CWH43 regions. When analyzed separately in ancestry-based racial subgroups, SNPs in several novel genes were associated. A total of 23 possible causal genes were pinpointed by positional and chromatin mapping. SKAT analysis demonstrated association in the entire MANIA2, EDN1, SFMBT2, and PPP2R5E genes and segments of CSMD2, LINC01317, HIVEPI, HSP90AB1, and TTLL11 genesConclusionsThis WGS study identified multiple predominantly novel understudied genes associated with IVIG response. These data can serve to inform regarding pathogenesis of KD, as well as lay ground work for developing treatment response predictors.
Association between dietary antioxidant levels and chronic obstructive pulmonary disease: a mediation analysis of inflammatory factors
Authors: Liu Ziyi , Li Jiyuan , Chen Tuotuo , Zhao Xue , Chen Qing , Xiao Lihua , Peng Zhenyu , Zhang Hongliang 
Published: January 2024

IntroductionThe development of chronic obstructive pulmonary disease (COPD) is strongly associated with oxidative stress, but it is unclear whether increasing dietary antioxidant intake reduces the risk of COPD. Therefore, this study assessed the association between antioxidant intake and COPD in US adults aged ≥ 40 years and further examined the correlation using the Composite Dietary Antioxidant Index (CDAI).MethodsThe study included 8,257 US adults aged ≥ 40 years using data from the National Health and Nutrition Examination Survey (NHANES) for three cycles from 2007-2012. Multivariate logistic regression models were used to calculate the correlation between antioxidant intake and CDAI with COPD. Restricted cubic spline was further used to explore the exposure-response relationship. Mediation analysis was used to explore the role of inflammatory factors in the association between CDAI and COPD.ResultsThis study included 8257 participants (4111 women [weighted, 50.7%]; mean [SD] age, 58.8 [11.2] years). In a multivariable-adjusted model of single antioxidant intake, a linear downward association between carotenoid intake and the incidence of COPD (P for trend = 0.052; Pnon- linear = 0.961). In a multivariable adjusted model for CDAI, this association is similarly present (P for trend = 0.018; Pnon-linear = 0.360). Multiple linear regression modeling showed that leukocytes (P = 0.002), alkaline phosphatase (P&lt; 0.001), and c-reactive protein (P&lt; 0.001) were negatively associated with CDAI levels. Meanwhile, mediation analysis revealed that alkaline phosphatase and c-reactive protein partially influenced the association between CDAI and COPD prevalence, with mediation ratios of 6.4% (P&lt; 0.01) and 4.68% (P = 0.04), respectively.ConclusionThe risk of COPD decreased with increased carotenoid intake and CDAI. In addition, CDAI has been found to be strongly associated with inflammatory factors and can reduce the incidence of COPD by mediating inflammatory factors.
Global trends and research status in ankylosing spondylitis clinical trials: a bibliometric analysis of the last 20 years
Authors: Zhang Wenhui , Li Meng , Li Xuhao , Wang Xingxin , Liu Yuanxiang , Yang Jiguo 
Published: January 2024

BackgroundAnkylosing spondylitis (AS) is a rheumatic and autoimmune disease associated with a chronic inflammatory response, mainly characterized by pain, stiffness, or limited mobility of the spine and sacroiliac joints. Severe symptoms can lead to joint deformity, destruction, and even lifelong disability, causing a serious burden on families and society as a whole. A large number of clinical studies have been published on AS over the past 20 years. This study aimed to summarize the current research status and global trends relating to AS clinical trials through a bibliometric analysis.MethodsThe Web of Science Core Collection database was searched for publications related to AS clinical trials published between January 2003 and June 2023. Bibliometric analysis and web visualization were performed using CiteSpace, VOSviewer, and a bibliometric online analysis platform (https://bibliometric.com), which included the number of publications, citations, countries, institutions, journals, authors, references, and keywords.Results1,212 articles published in 201 journals from 65 countries were included in this study. The number of publications related to AS clinical trials is increasing annually. The United States and the Free University of Berlin, the countries and institutions, respectively, that have published the most articles on AS, have made outstanding contributions to this field. The author with the most published papers and co-citations over the period covered by the study was Desiree Van Der Heijde. The journal with the most published and cited articles was Annals of the Rheumatic Diseases. The keywords: “double-blind,” “rheumatoid arthritis,” “efficacy,” “placebo-controlled trial,” “infliximab,” “etanercept,” “psoriatic arthritis” and “therapy” represent the current research hotspots regarding AS.DiscussionThis is the first study to perform a bibliometric analysis and visualization of AS clinical trial publications, providing a reliable research focus and direction for clinicians. Future studies in the field of AS clinical trials should focus on placebo-controlled trials of targeted therapeutic drugs.
Efficacy and safety of anakinra and canakinumab in PSTPIP1-associated inflammatory diseases: a comprehensive scoping review
Authors: Sanz-Cabanillas Juan Luis , Gómez-García Francisco , Gómez-Arias Pedro Jesús , Montilla-López Ana , Gay-Mimbrera Jesús , Ruano Juan , Isla-Tejera Beatriz , Parra-Peralbo Esmeralda 
Published: January 2024

IntroductionThis scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by abnormal IL-1 pathway activation due to genetic mutations.MethodsOur methodology adhered to a pre-published protocol and involved a thorough search of MEDLINE and EMBASE databases up to February 2022, following the Joanna Briggs Institute Reviewer’s Manual and the PRISMA Extension for Scoping Reviews. The review included studies reporting on IL-1 pathway inhibitor use in PAID patients.ResultsFrom an initial pool of 5,225 articles, 36 studies involving 43 patients were selected. The studies predominantly used observational designs and exhibited diversity in patient demographics, treatment approaches, and outcomes. Anakinra and canakinumab demonstrated promise in treating sterile pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) and PSTPIP1-associated myeloid-related-proteinemia inflammatory (PAMI) syndromes, with scant data on other syndromes. Notably, there was a paucity of information on the adverse effects of these treatments, necessitating cautious interpretation of their safety profile.ConclusionCurrent evidence on IL-1 pathway inhibitors for PAID is primarily from observational studies and remains limited. Rigorous research with larger patient cohorts is imperative for more definitive conclusions. Collaborative efforts among specialized research centers and international health initiatives are key to advancing this field.
Prevention of exacerbation in patients with moderate-to-very severe COPD with the intent to modulate respiratory microbiome: a pilot prospective, multi-center, randomized controlled trial
Authors: Hua Jian-lan , Yang Zi-feng , Cheng Qi-jian , Han Yao-pin , Li Zheng-tu , Dai Ran-ran , He Bin-feng , Wu Yi-xing , Zhang Jing 
Published: January 2024

IntroductionConsidering the role of bacteria in the onset of acute exacerbation of COPD (AECOPD), we hypothesized that the use of influenza-Streptococcus pneumoniae vaccination, oral probiotics or inhaled amikacin could prevent AECOPD.MethodsIn this pilot prospective, muti-central, randomized trial, moderate-to-very severe COPD subjects with a history of moderate-to-severe exacerbations in the previous year were enrolled and assigned in a ratio of 1:1:1:1 into 4 groups. All participants were managed based on the conventional treatment recommended by GOLD 2019 report for 3 months, with three groups receiving additional treatment of inhaled amikacin (0.4 g twice daily, 5–7 days monthly for 3 months), oral probiotic Lactobacillus rhamnosus GG (1 tablet daily for 3 months), or influenza-S. pneumoniae vaccination. The primary endpoint was time to the next onset of moderate-to-severe AECOPD from enrollment. Secondary endpoints included CAT score, mMRC score, adverse events, and survival in 12 months.ResultsAmong all 112 analyzed subjects (101 males, 96 smokers or ex-smokers, mean ± SD age 67.19 ± 7.39 years, FEV1 41.06 ± 16.09% predicted), those who were given dual vaccination (239.7 vs. 198.2 days, p = 0.044, 95%CI [0.85, 82.13]) and oral probiotics (248.8 vs. 198.2 days, p = 0.017, 95%CI [7.49, 93.59]) had significantly delayed onset of next moderate-to-severe AECOPD than those received conventional treatment only. For subjects with high symptom burden, the exacerbations were significantly delayed in inhaled amikacin group as compared to the conventional treatment group (237.3 vs. 179.1 days, p = 0.009, 95%CI [12.40,104.04]). The three interventions seemed to be safe and well tolerated for patient with stable COPD.ConclusionThe influenza-S. pneumoniae vaccine and long-term oral probiotic LGG can significantly delay the next moderate-to-severe AECOPD. Periodically amikacin inhalation seems to work in symptomatic patients. The findings in the current study warrants validation in future studies with microbiome investigation.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT03449459.
Younger age is associated with cardiovascular pathological phenotype of severe COVID-19 at autopsy
Authors: Giugni Fernando R. , Duarte-Neto Amaro N. , da Silva Luiz Fernando F. , Monteiro Renata A. A. , Mauad Thais , Saldiva Paulo H. N. , Dolhnikoff Marisa 
Published: January 2024

IntroductionCOVID-19 affects patients of all ages. There are few autopsy studies focusing on the younger population. We assessed an autopsy cohort aiming to understand how age influences pathological outcomes in fatal COVID-19.MethodsThis study included autopsied patients, aged 6 months to 83 years, with confirmed COVID-19 in 2020–2021. We collected tissue samples from deceased patients using a minimally invasive autopsy protocol and assessed pathological data following a systematic approach.ResultsEighty-six patients were included, with a median age of 55 years (IQR 32.3–66.0). We showed that age was significantly lower in patients with acute heart ischemia (p = 0.004), myocarditis (p = 0.03) and lung angiomatosis (p &lt; 0.001), and significantly higher in patients with exudative diffuse alveolar damage (p = 0.02), proliferative diffuse alveolar damage (p &lt; 0.001), lung squamous metaplasia (p = 0.003) and lung viral atypia (p = 0.03), compared to patients without those findings. We stratified patients by their age and showed that cardiovascular findings were more prevalent in children and young adults. We performed principal component analysis and cluster of pathological variables, and showed that cardiovascular variables clustered and covariated together, and separated from pulmonary variables.ConclusionWe showed that age modulates pathological outcomes in fatal COVID-19. Younger age is associated with cardiovascular abnormalities and older age with pulmonary findings.
First record of Aspergillus nomiae as a broad-spectrum entomopathogenic fungus that provides resistance against phytopathogens and insect pests by colonization of plants
Authors: Zhang Zhengkun , Tian Yifan , Sui Li , Lu Yang , Cheng Ke , Zhao Yu , Li Qiyun , Shi Wangpeng 
Published: January 2024

IntroductionAspergillus nomiae is known as a pathogenic fungus that infects humans and plants but has never been reported as an entomophagous fungus (EPF) that can provide other functions as an endotype.MethodsA strain of EPF was isolated and identified from diseased larvae of Spodoptera litura in a soybean field and designated AnS1Gzl-1. Pathogenicity of the strain toward various insect pests was evaluated, especially the ability to colonize plants and induce resistance against phytopathogens and insect pests.ResultsThe isolated EPF strain AnS1Gzl-1 was identified as A. nomiae; it showed strong pathogenicity toward five insect pests belonging to Lepidoptera and Hemiptera. Furthermore, the strain inhibited the growth of Sclerotinia sclerotiorum in vitro, a causal agent of soil-borne plant disease. It colonized plants as an endophyte via root irrigation with a high colonization rate of 90%, thereby inducing plant resistance against phytopathogen infection, and disrupting the feeding selectivity of S. litura larvae.DiscussionThis is the first record of a natural infection of A. nomiae on insects. A. nomiae has the potential to be used as a dual biocontrol EPF because of its ability to not only kill a broad spectrum of insect pests directly but also induce resistance against phytopathogens via plant colonization.
Dietary β-hydroxybutyric acid improves the growth performance of young ruminants based on rumen microbiota and volatile fatty acid biosynthesis
Authors: Chai Jianmin , Liu Zeyue , Wu Jun , Kang Yuan , Abdelsattar Mahmoud M. , Zhao Wei , Wang Shiqin , Yang Shuli , Deng Feilong , Li Ying , Zhuang Yimin , Zhang Naifeng 
Published: January 2024

IntroductionThe ketone body β-hydroxybutyric acid (BHB) plays critical roles in cellular proliferation and metabolic fuel utilization; however, its effects on the rumen microbiota remain unknown.MethodsHere, three doses of BHB (low, medium, and high) were supplemented to early-weaned goat kids.ResultsCompared with controls, the beneficial effects of BHB on growth and rumen development were observed in goats at 90 days of age (d). The low dose of dietary BHB increased the concentration of rumen acetate, propionate, and butyrate on d90. The sequencing results of the rumen microbiota revealed marked shifts in rumen microbial community structure after early-weaned goat kids consumed BHB for 2 months. The signature bacterial ASVs for each treatment were identified and were the main drivers contributing to microbial interactions in the rumen. The bacteria associated with rumen weight were also correlated with body weight. Some classified bacterial signatures, includingPrevotella, Olsenella umbonate, andRoseburia faecis, were related to rumen volatile fatty acids and host development.ConclusionOverall, dietary BHB altered rumen microbiota and environments in young goats, which contributed to rumen development and growth.
Evaluation of microbiological epidemiology and clinical characteristics of maternal bloodstream infection: a 10 years retrospective study
Authors: Guo Junfei , Wu Yongbing , Li Huan , Deng Wenyu , Lai Weiming , Gu Chunming , Luo Mingyong 
Published: January 2024

ObjectiveAlthough the incidence of bloodstream infection (BSI) during pregnancy is relatively low, it can lead to unfavorable outcomes. The aim of our study was to analyze the clinical and microbiological characteristics of maternal bacteremia and to assess maternal and fetal outcomes.MethodsOur study was a retrospective study conducted in a tertiary women and children’s hospital in Guangzhou, China, from 2013 to 2022. Data were extracted from medical records and the laboratory information system. The participants were divided into groups, and the difference between the groups was analyzed.ResultsThe incidence of maternal BSI during the 10 years study period was 10.2 cases/10,000 maternities, with a peak found from 2014 to 2016. Escherichia coli (48%) was the predominant causative pathogen, followed by Streptococcus agalactiae (13%). Gestational diabetes mellitus (GDM) (15%) was the most common underlying condition among maternal BSI episodes. Urinary tract (13%) and genital tract (28%) were the predominant source of BSI. About 14% of neonates were infected, and BSI was the most common type of infection. E. coli was the predominant pathogen in mother-neonate pairs with concurrent BSI. Premature rupture of membranes (PROM, OR:4.68) and preterm birth (OR:3.98) were the risk factors predicting neonatal infection. More than 85% of the E. coli were resistant to ampicillin (AMP) and 50% of the E. coli were extended-spectrum β-lactamase (ESBL)-producing bacteria.ConclusionMaternal BSI is a rare event, but continuous monitoring on the aspects of pathogen composition, antimicrobial resistance characteristics, and risk factors for adverse outcomes remains necessary to further reduce poor outcomes and mitigate bacterial resistance.
Membrane properties modulation by SanA: implications for xenobiotic resistance in Salmonella Typhimurium
Authors: Aleksandrowicz Adrianna , Kolenda Rafał , Baraniewicz Karolina , Thurston Teresa L. M. , Suchański Jarosław , Grzymajlo Krzysztof 
Published: January 2024

IntroductionMultidrug resistance in bacteria is a pressing concern, particularly among clinical isolates. Gram-negative bacteria like Salmonella employ various strategies, such as altering membrane properties, to resist treatment. Their two-membrane structure affects susceptibility to antibiotics, whereas specific proteins and the peptidoglycan layer maintain envelope integrity. Disruptions can compromise stability and resistance profile toward xenobiotics. In this study, we investigated the unexplored protein SanA’s role in modifying bacterial membranes, impacting antibiotic resistance, and intracellular replication within host cells.MethodsWe generated a sanA deletion mutant and complemented it in trans to assess its biological function. High-throughput phenotypic profiling with Biolog Phenotype microarrays was conducted using 240 xenobiotics. Membrane properties and permeability were analyzed via cytochrome c binding, hexadecane adhesion, nile red, and ethidium bromide uptake assays, respectively. For intracellular replication analysis, primary bone marrow macrophages served as a host cells model.ResultsOur findings demonstrated that the absence of sanA increased membrane permeability, hydrophilicity, and positive charge, resulting in enhanced resistance to certain antibiotics that target peptidoglycan synthesis. Furthermore, the sanA deletion mutant demonstrated enhanced replication rates within primary macrophages, highlighting its ability to evade the bactericidal effects of the immune system. Taking together, we provide valuable insights into a poorly known SanA protein, highlighting the complex interplay among bacterial genetics, membrane physiology, and antibiotic resistance, underscoring its significance in understanding Salmonella pathogenicity.
One year of treatment with elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis homozygous for the F508del mutation causes a significant increase in liver biochemical indexes
Authors: Castaldo Alice , Gelzo Monica , Iacotucci Paola , Longobardi Annalisa , Taccetti Giovanni , Terlizzi Vito , Carnovale Vincenzo 
Published: January 2024

Introduction: Modulators of cystic fibrosis transmembrane conductance regulator mutated protein significantly improved the outcome of patients with cystic fibrosis (CF). We describe 63 patients who were independently followed up in two CF regional centers (i.e., Campania and Tuscany regions).Methods: All patients were homozygous for the F508del mutation and were treated with lumacaftor/ivacaftor (LI) for 3 years, followed by 1 year of treatment with elexacaftor/tezacaftor/ivacaftor (ETI). We studied the biochemical parameters of liver damage and cholesterol metabolism.Results: Beyond the improvement of BMI and lung function with LI treatment and even more with ETI, we found that the 3 years of LI treatment significantly improved liver function parameters (total and conjugated bilirubin, ALT, AP, and GGT), while the subsequent ETI treatment caused a significant increase of such parameters.Discussion: We confirm that treatment with LI does not correct hypocholesterolemia, whereas treatment with ETI significantly increases serum cholesterol. Such an increase is likely due to enhanced de novo biosynthesis, as indicated by the significant increase in serum lathosterol, and it is likely that the subsequent liver cholesterol accumulation may contribute to triggering inflammation and worsening liver biochemical indexes. The increase in serum bilirubin and ALT that we observed in approximately 94% and 84% of patients treated with ETI, respectively, suggests further investigation of the impact of ETI therapy on liver function indexes.