bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal trends in the prevalence and death of ischemic heart disease in women of childbearing age from 1990 to 2019: a multilevel analysis based on the Global Burden of Disease Study 2019
Authors: Hu Ben , Wang Yan , Chen Dong , Feng Jun , Fan Yinguang , Hou Linlin 
Published: April 2024

BackgroundOur objective is to describe the current prevalence and death of ischemic heart disease (IHD) in women of childbearing age (WCBA) at the global, regional, and national levels and to analyze its temporal trends from 1990 to 2019.MethodsWCBA was defined as women aged 15–49 years. Estimates and 95% Uncertainty Intervals (UI) of IHD prevalence and death numbers for seven age groups were extracted from the 2019 Global Burden of Disease Study. The age-standardized prevalence and death rate (ASPR and ASDR) of IHD in WCBA was estimated using the direct age-standardization method. Joinpoint regression analysis was used to calculate average annual percent change (AAPC) to represent the temporal trends from 1990 to 2019.ResultsBetween 1990 and 2019, the global ASPR of IHD experienced a 3.21% increase, culminating in 367.21 (95% UI, 295.74–430.16) cases per 100,000 individuals. Conversely, the ASDR decreased to 11.11 (95% UI, 10.10–12.30) per 100,000 individuals. In 2019, among the five sociodemographic index (SDI) regions, the highest ASPR was observed in the high-middle SDI region, whereas the highest ASDR was found in the low-middle SDI region. Regionally, the Caribbean reported the highest ASPR (563.11 per 100,000 individuals; 95% UI, 493.13–643.03), and Oceania reported the highest ASDR (20.20 per 100,000 individuals; 95% UI, 13.01–31.03). At the national level, Trinidad and Tobago exhibited the highest ASPR (730.15 per 100,000 individuals; 95% UI, 633.96–840.13), and the Solomon Islands had the highest ASDR (77.77 per 100,000 individuals; 95% UI, 47.80–121.19). Importantly, over the past three decades, the global ASPR has seen a significant increase [AAPC = 0.11%, 95% Confidence Interval (CI): 0.09–0.13; P &lt; 0.001], while the ASDR has demonstrated a significant decreasing trend (AAPC = −0.86%, 95% CI: −1.11 to −0.61; P &lt; 0.001). Air pollution, tobacco use, high systolic blood pressure, elevated body mass index, dietary risks, and high LDL cholesterol have been identified as the leading six risk factors for IHD-related deaths among WCBA in 2019.ConclusionsDespite the significant decline in the global ASDR for IHD among WCBA over the last thirty years, the ASPR continues to escalate. We need to remain vigilant about the increased burden of IHD in WCBA. It calls for aggressive prevention strategies, rigorous control of risk factors, and the enhancement of healthcare coverage to mitigate the disease burden of IHD among WCBA in forthcoming years.
Prognostic value of pulmonary hypertension with a nomogram in acute myocardial infarction patients with reduced left ventricular function
Authors: Liu Qian , Zhao Changying , Dang Peizhu , Li Yongxin , Yan Yang 
Published: April 2024

BackgroundPulmonary hypertension (PH) is a common prognostic factor for acute myocardial infarction (AMI) and its impact may increase when combined with reduced left ventricular function.MethodsThis retrospective cohort study enrolled AMI patients with reduced left ventricular function at the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2022. Basing on the systolic pulmonary artery pressure assessed by echocardiogram, patients were assigned to the PH group and control group. Propensity score matching (PSM) in sex, age and Killip classification was used to match patients between two groups. The primary outcome was defined as 1-year mortality rate, which were obtained from medical records and phone calls.ResultsAfter the PSM, a total of 504 patients were enrolled, with 252 in both groups. No significant difference of the adjusted factors was observed between the two groups. The 1-year mortality rate was significantly higher in the PH group compared with the control group (15.5% vs. 5.3%, P &lt; 0.001). In the cox regression analysis, PH (HR: 2.068, 95% CI: 1.028–4.161, P = 0.042) was identified as an independent risk factor, alongside left ventricular ejection fraction (HR: 0.948; 95% CI: 0.919–0.979; P &lt; 0.001), creatine kinase-MB isoenzymes (HR: 1.002; 95% CI: 1.000–1.003; P = 0.010) and pro-brain natriuretic peptide (HR: 1.000; 95% CI: 1.000–1.000; P = 0.018) for the 1-year mortality in AMI patients with reduced left ventricular function. A nomogram was established using the above factors to predict the 1-year mortality risks in these patients.ConclusionAMI patients with reduced left ventricular function showed higher 1-year mortality rate when concomitant with PH. Four independent risk factors, including PH, were identified and used to establish a nomogram to predict the 1-year mortality risks in these patients.Clinical Trials.gov IDNCT06186713.
Diagnostic value of retinol-binding protein 4 in diabetic nephropathy: a systematic review and meta-analysis
Authors: Cao Xiaodan , Zhong Guanghui , Jin Tinglong , Hu Weijiao , Wang Jin , Shi Bo , Wei Renxiong 
Published: April 2024

ObjectiveDiabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN.MethodsWe searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated.ResultsTwenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71–0.80] and 0.81 (95% CI, 0.76–0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16–5.21), NLR of 0.29 (95% CI, 0.24–0.36) and DOR of 13.76 (95% CI, 9.29–20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82–0.88). No obvious publication bias existed in the Deeks’ funnel plot asymmetry test.ConclusionOur findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN.
Association between a metabolic score for insulin resistance and hypertension: results from National Health and Nutrition Examination Survey 2007–2016 analyses
Authors: Zeng Jing , Zhang Tingting , Yang Yan , Wang Jinjing , Zheng Dan , Hou Yanwei , Tong Ye , Fan Xiaojing , Wang Xuan , Fang Yi 
Published: April 2024

BackgroundThe Metabolic Score for Insulin Resistance (METS-IR) offers a promising and reliable non-insulin-based approach to assess insulin resistance and evaluate cardiometabolic risk. However, evidence for the association between METS-IR and hypertension was still limited.MethodsParticipants from the National Health and Nutrition Examination Survey (NHANES) database from 2007-2016 were selected for weighted multivariable regression analyses, subgroup analyses and restricted cubic spline (RCS) modeling to assess the association between the METS-IR and hypertension, as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP).ResultsThis study enrolled 7,721 adults aged ≥20 years, 2,926 (34.03%) of whom was diagnosed as hypertension. After adjusting for all potential covariates, an increased METS-IR (log2 conversion, denoted as log2METS-IR) was independently associated with a higher prevalence of hypertension (odd ratio [OR] 3.99, 95% confidence interval [CI] 3.19~5.01). The OR for hypertension in subjects with the highest quartile of METS-IR was 3.89-fold (OR 3.89, 95% CI 3.06~4.94) higher than that in those with the lowest quartile of METS-IR. This positive correlation became more significant as METS-IR increased (p for trend &lt; 0.001). Log2METS-IR was significantly correlated with increase in SBP (β 6.75, 95% CI 5.65~7.85) and DBP (β 5.59, 95% CI 4.75~6.43) in a fully adjusted model. Consistent results were obtained in subgroup analyses. Hypertension, SBP and DBP all exhibited a non-linear increase with the rise in METS-IR. The minimal threshold for the beneficial association of METS-IR with hypertension, SBP and DBP were all identified to be 46.88.ConclusionThe findings of this study revealed a significant positive association between METS-IR and hypertension among US adults, suggesting METS-IR as a potential tool for assessing hypertension risk.
The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis
Authors: Zhang Sheng-Xiao , Chen Hao-Ran , Wang Jia , Shao Hong-Fang , Cheng Ting , Pei Ruo-Meng , Su Qin-Yi , Zhang He-Yi , Li Xiao-Feng 
Published: April 2024

BackgroundImmunotherapy targeting factors related to immune imbalance has been widely employed for RA treatment. This study aimed to evaluate the efficacy and safety of low-dose interleukin (IL)-2 combined with tocilizumab (TCZ), a biologics targeting IL-6, in RA patients.MethodsFifty adults with active RA who met the criteria with complete clinical data were recruited, and divided into three groups: control group (n=15), IL-2 group (n=26), and IL-2+TCZ group (n=9). In addition to basic treatment, participants in the IL-2 group received IL-2 (0.5 MIU/day), while participants in the IL-2+TCZ group received IL-2 (0.5 MIU/day) along with one dose of TCZ (8 mg/kg, maximum dose: 800 mg). All subjects underwent condition assessment, laboratory indicators and safety indicators detection, and records before treatment and one week after treatment.ResultsCompared with the baseline, all three groups showed significant improvement in disease conditions, as evidenced by significantly reduced disease activity indicators. The low-dose IL-2 and combination treatment groups demonstrated a violent proliferation of Tregs, while the absolute number of Th1, Th2, and Th17 cells in the latter group showed a decreasing trend. The decrease in the Th17/Treg ratio was more pronounced in the IL-2+TCZ groups. No significant adverse reactions were observed in any of the patients.ConclusionExogenous low doses of IL-2 combined TCZ were found to be safe and effective in reducing effector T cells and appropriately increasing Treg levels in RA patients with high effector T cell levels. This approach helps regulate immune homeostasis and contributes to the prevention of disease deterioration.Clinical trial registrationhttps://www.chictr.org.cn/showprojEN.html?proj=13909, identifier ChiCTR-INR-16009546.
Enhanced gut microbiome supplementation of essential amino acids in Diploptera punctata fed low-protein plant-based diet
Authors: Ayayee Paul A. , Petersen Nick , Riusch Jennifer , Rauter Claudia , Larsen Thomas 
Published: April 2024

IntroductionBuilding on our previous work, we investigate how dietary shifts affect gut microbial essential amino acid (EAA) provisioning in the lactating cockroach Diploptera punctata.MethodTo that end, we fed cockroaches three distinct diets: a plant-only Gari diet composed of starchy and granulated root tuber Yucca (Manihot esculenta), a dog food diet (DF), and a cellulose-amended dog food (CADF) diet. We anticipated that the high carbohydrate, low protein Gari would highlight increased microbial EAA supplementation to the host.ResultsBy day 28, we observed distinct profiles of 14 bacterial families in the insect gut microbiomes of the three dietary groups. CADF-fed insects predominantly harbored cellulolytic and nitrogen-fixing bacteria families Streptococcaceae and Xanthomonadaceae. In contrast, Gari-fed insects were enriched in anaerobic lignocellulolytic bacteria families Paludibacteraceae and Dysgonomonadaceae, while DF-fed insects had a prevalence of proteolytic anaerobes Williamwhitmaniaceae and sulfate-reducing bacteria Desulfovibrionaceae. Furthermore, we confirmed significantly higher EAA supplementation in Gari-fed insects than in non-Gari-fed insects based on δ13C-EAA offsets between insect and their diets. The δ13C-EAA offsets between DF and CADF were nearly indistinguishable, highlighting the relevance of using the plant-based Gari in this experiment to unequivocally demonstrate this function in this insect. These results were underscored by lower standard metabolic rate (SMR) relative to the DF insect in Gari-fed (intermediate SMR and dietary quality) and CADF (least SMR and dietary quality) insects.DiscussionThe influence of diet on EAA provisioning and SMR responses in insects underscores the need for further exploration into the role of gut microbial functions in modulating metabolic responses
Genetic markers associated with ferroptosis in Alzheimer’s disease
Authors: Sun Yuting , Xiao Yu , Tang Qin , Chen Wei , Lin Lu 
Published: April 2024

ObjectiveFerroptosis is implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and vascular dementia, implying that it may have a regulatory effect on the progression of these diseases. However, the specific role of ferroptosis-related genes (FRGs) in Alzheimer’s disease (AD) is not yet fully understood. The aim of the study was to detect ferroptosis related genes with regulatory functions in the disease and explore potential mechanisms in AD.MethodsHub FRGs were obtained through multiple algorithms based on the GSE5281 dataset. The screening process was implemented by R packages including limma, WGCNA, glm and SVM-RFE. Gene Ontology classification and pathway enrichment analysis were performed based on FRGs. Biological processes involved with hub FRGs were investigated through GSVA and GSEA methods. Immune infiltration analysis was performed by the R package CIBERSORT. Receiver operating characteristic curve (ROC) was utilized to validate the accuracy of hub FRGs. The CeRNA network attempted to find non-coding RNA transcripts which may play a role in disease progression.ResultsDDIT4, MUC1, KLHL24, CD44, and RB1 were identified as hub FRGs. As later revealed by enrichment analysis, the hub FRGs had important effects on AD through involvement in diverse AD pathogenesis-related pathways such as autophagy and glutathione metabolism. The immune microenvironment in AD shows increased numbers of resting NK cells, macrophages, and mast cells, with decreased levels of CD8 T cells when compared to healthy samples. Regulatory T cells were positively correlated with MUC1, KLHL24, and DDIT4 expression, while RB1 showed negative correlations with eosinophils and CD8 T cells, suggesting potential roles in modulating the immune environment in AD.ConclusionOur research has identified five hub FRGs in AD. We concluded that ferroptosis may be involved in the disease.
Detection of elevated levels of PINK1 in plasma from patients with idiopathic Parkinson’s disease
Authors: Hong Xianchai , Zheng Yi , Hou Jialong , Jiang Tao , Lu Yao , Wang Wenwen , Zhou Shuoting , Ye Qianqian , Xie Chenglong , Li Jia 
Published: April 2024

BackgroundsNumerous lines of evidence support the intricate interplay between Parkinson’s disease (PD) and the PINK1-dependent mitophagy process. This study aimed to evaluate differences in plasma PINK1 levels among idiopathic PD, PD syndromes (PDs), and healthy controls.MethodsA total of 354 participants were included, consisting of 197 PD patients, 50 PDs patients, and 107 healthy controls were divided into two cohorts, namely the modeling cohort (cohort 1) and the validated cohort (cohort 2). An enzyme-linked immunosorbent assay (ELISA)-based analysis was performed on PINK1 and α-synuclein oligomer (Asy-no). The utilization of the area under the curve (AUC) within the receiver-operating characteristic (ROC) curves served as a robust and comprehensive approach to evaluate and quantify the predictive efficacy of plasma biomarkers alone, as well as combined models, in distinguishing PD patients from controls.ResultsPINK1 and Asy-no were elevated in the plasma of PD and PDs patients compared to healthy controls. The AUCs of PINK1 (0.771) and Asy-no (0.787) were supposed to be potentially eligible plasma biomarkers differentiating PD from controls but could not differentiate PD from PDs. Notably, the PINK + Asy-no + Clinical RBD model showed the highest performance in the modeling cohort and was comparable with the PINK1 + Clinical RBD in the validation cohort. Moreover, there is no significant correlation between PINK1 and UPDRS, MMSE, HAMD, HAMA, RBDQ-HK, and ADL scores.ConclusionThese findings suggest that elevated PINK1 in plasma holds the potential to serve as a non-invasive tool for distinguishing PD patients from controls. Moreover, the outcomes of our investigation lend support to the plausibility of implementing a feasible blood test in future clinical translation.
Modeling sporadic juvenile ALS in iPSC-derived motor neurons explores the pathogenesis of FUSR503fs mutation
Authors: Chen Li , Chen Guojie , Zhang Mengting , Zhang Xiaojie 
Published: April 2024

IntroductionFused in sarcoma (FUS) mutations represent the most common genetic etiology of juvenile amyotrophic lateral sclerosis (JALS), for which effective treatments are lacking. In a prior report, we identified a novel FUS mutation, c.1509dupA: p. R503fs (FUSR503fs), in a sporadic JALS patient.MethodsThe physicochemical properties and structure of FUSR503fs protein were analyzed by software: Multi-electrode array (MEA) assay, calcium activity imaging assay and transcriptome analysis were used to explore the pathophysiological mechanism of iPSC derived motor neurons.ResultsStructural analysis and predictions regarding physical and chemical properties of this mutation suggest that the reduction of phosphorylation and glycosylation sites, along with alterations in the amino acid sequence, may contribute to abnormal FUS accumulation within the cytoplasm and nucleus of induced pluripotent stem cell– derived motor neurons (MNs). Multi-electrode array and calcium activity imaging indicate diminished spontaneous electrical and calcium activity signals in MNs harboring the FUSR503fs mutation. Transcriptomic analysis reveals upregulation of genes associated with viral infection and downregulation of genes involved in neural function maintenance, such as the ATP6V1C2 gene. Treatment with ropinirole marginally mitigates the electrophysiological decline in FUSR503fs MNs, suggesting the utility of this cell model for mechanistic exploration and drug screening.DiscussioniPSCs-derived motor neurons from JALS patients are promising tools for drug screening. The pathological changes in motor neurons of FUSR503fs may occur earlier than in other known mutation types that have been reported.
RFWD3 modulates response to platinum chemotherapy and promotes cancer associated phenotypes in high grade serous ovarian cancer
Authors: Taylor Sarah J. , Hollis Robert L. , Gourley Charlie , Herrington C. Simon , Langdon Simon P. , Arends Mark J. 
Published: April 2024

BackgroundDNA damage repair is frequently dysregulated in high grade serous ovarian cancer (HGSOC), which can lead to changes in chemosensitivity and other phenotypic differences in tumours. RFWD3, a key component of multiple DNA repair and maintenance pathways, was investigated to characterise its impact in HGSOC.MethodsRFWD3 expression and association with clinical features was assessed using in silico analysis in the TCGA HGSOC dataset, and in a further cohort of HGSOC tumours stained for RFWD3 using immunohistochemistry. RFWD3 expression was modulated in cell lines using siRNA and CRISPR/cas9 gene editing, and cells were characterised using cytotoxicity and proliferation assays, flow cytometry, and live cell microscopy.ResultsExpression of RFWD3 RNA and protein varied in HGSOCs. In cell lines, reduction of RFWD3 expression led to increased sensitivity to interstrand crosslinking (ICL) inducing agents mitomycin C and carboplatin. RFWD3 also demonstrated further functionality outside its role in DNA damage repair, with RFWD3 deficient cells displaying cell cycle dysregulation, reduced cellular proliferation and reduced migration. In tumours, low RFWD3 expression was associated with increased tumour mutational burden, and complete response to platinum chemotherapy.ConclusionRFWD3 expression varies in HGSOCs, which can lead to functional effects at both the cellular and tumour levels.
Incidence and seasonality of Kawasaki disease in children in the Philippines, and its association with ambient air temperature
Authors: Celis-Seposo Aden Kay , Madaniyazi Lina , Seposo Xerxes , Hashizume Masahiro , Yoshida Lay Myint , Toizumi Michiko 
Published: April 2024

BackgroundDespite an unknown cause, Kawasaki disease (KD) is currently the primary leading cause of acquired heart disease in developed countries in children and has been increasing in recent years. Research efforts have explored environmental factors related to KD, but they are still unclear especially in the tropics. We aimed to describe the incidence of KD in children, assess its seasonality, and determine its association with ambient air temperature in the National Capital Region (NCR), Philippines from January 2009 to December 2019.MethodsMonthly number of KD cases from the Philippine Pediatric Society (PPS) disease registry was collected to determine the incidence of KD. A generalized linear model (GLM) with quasi-Poisson regression was utilized to assess the seasonality of KD and determine its association with ambient air temperature after adjusting for the relevant confounders.ResultsThe majority of KD cases (68.52%) occurred in children less than five years old, with incidence rates ranging from 14.98 to 23.20 cases per 100,000 population, and a male-to-female ratio of 1.43:1. Seasonal variation followed a unimodal shape with a rate ratio of 1.13 from the average, peaking in March and reaching the lowest in September. After adjusting for seasonality and long-term trend, every one-degree Celsius increase in the monthly mean temperature significantly increased the risk of developing KD by 8.28% (95% CI: 2.12%, 14.80%). Season-specific analysis revealed a positive association during the dry season (RR: 1.06, 95% CI: 1.01, 1.11), whereas no evidence of association was found during the wet season (RR: 1.10, 95% CI: 0.95, 1.27).ConclusionWe have presented the incidence of KD in the Philippines which is relatively varied from its neighboring countries. The unimodal seasonality of KD and its linear association with temperature, independent of season and secular trend, especially during dry season, may provide insights into its etiology and may support enhanced KD detection efforts in the country.