bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Bilirubin Levels Predict Long-Term Outcomes in Patients With Acute Coronary Syndrome Under Different Glucose Metabolism Status: A 6.5-Year Cohort Study of Three-Vessel Disease
Authors: Liu Yue , Zhang Ce , Jiang Lin , Tian Jian , Zhao Xue-yan , Xu Jing-jing , Liu Ru , Xu Bo , Hui Ru-tai , Gao Run-lin , Yuan Jin-qing , Xu Lian-jun , Song Lei 
Published: August 2021

Background: There is controversy over the relationship between bilirubin and coronary artery disease. This study aimed to evaluate the predictive value of direct bilirubin (DB) in patients with complex acute coronary syndrome (ACS).Methods: From April 2004 to February 2011, 5,322 ACS patients presenting with three-vessel disease were consecutively enrolled. Disease severity and complexity were determined by SYNTAX score (SS) and SS II. The primary endpoint was all-cause death, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE). Stratification of normal glucose regulation, prediabetes, and diabetes was based on a previous diagnosis, hypoglycemic medications, fasting blood glucose, and hemoglobin A1c.Results: Subjects were divided into quartiles according to baseline DB (μmol/L): Q1 (0–1.6), Q2 (1.61–2.20), Q3 (2.21–2.80), and Q4 (&gt;2.80). Multivariable logistic regression analysis showed that DB was an independent predictor of intermediate–high SS. During a median follow-up time of 6.5 years, elevated DB was associated with more all-cause death (p &lt; 0.001) but not MACCE. DB remained to be predictive of all-cause death in the multivariable Cox regression model (Q2 vs. Q1: HR 1.043, 95% CI 0.829–1.312, p = 0.719; Q3 vs. Q1: HR 1.248, 95% CI 1.001–1.155, p = 0.048; Q4 vs. Q1: HR 1.312, 95% CI 1.063–1.620, p = 0.011). When subjects are stratified according to glucose metabolism regulation and treatment strategies, the predictivity of DB was only profound in patients with diabetes or with conservative treatment. Additionally, incorporating DB further improved the discrimination and reclassification abilities of SS II for risk prediction.Conclusion: DB is a potential biomarker for predicting lesion severity and long-term outcomes in ACS patients.
Clinical Characteristics, Prognosis, and Gender Disparities in Young Patients With Acute Myocardial Infarction
Authors: Lv Junxing , Ni Lin , Liu Kexin , Gao Xiaojin , Yang Jingang , Zhang Xuan , Ye Yunqing , Dong Qiuting , Fu Rui , Sun Hui , Yan Xinxin , Zhao Yanyan , Wang Yang , Yang Yuejin , Xu Haiyan 
Published: August 2021

Background: Young people hold a stable or increasing percentage of patients with acute myocardial infarction (AMI) in many countries. However, data on clinical characteristics and outcomes of young AMI patients were insufficient. This study aimed to analyze clinical characteristics, prognosis, and gender disparities in patients aged ≤45 years with AMI.Methods: A total of 24,125 patients from China Acute Myocardial Infarction registry were included in this study. Clinical characteristics, managements, and in-hospital and 2-year outcomes were compared between patients aged ≤45 years and those aged &gt;45 years. Predictors of all-cause death were obtained using multivariate regression models. Gender disparities of AMI were analyzed among young patients.Results: Of 24,125 patients, 2,042 (8.5%, 116 female) were aged ≤45 years. Compared with patients aged &gt;45 years, young patients were more often male, current smokers, and more likely to have medical history of hyperlipidemia. Smoking (72.1%) was the major modifiable risk factor in patients aged ≤45 years. Young patients received more evidence-based medications and had significantly lower risk of both in-hospital and 2-year adverse events than older patients. Education level and left ventricular ejection fraction were independent predictors of 2-year mortality in young patients. Moreover, symptom onset to admission time of young women was significantly longer than that of young men. Young women were less likely to receive percutaneous coronary intervention and suffered higher risk of in-hospital adverse events than young men (adjusted odds ratio for death: 5.767, 95% confidence interval 1.580–21.049, p = 0.0080; adjusted odds ratio for the composite of death, re-infarction, and stroke: 3.981, 95% confidence interval 1.150–13.784, p = 0.0292). Young women who survived at discharge had a higher 2-year cumulative incidence of death (3.8 vs 1.4%, plog−rank = 0.0412).Conclusions: Patients aged ≤45 years constituted a non-negligible proportion of AMI patients, with higher prevalence of smoking and hyperlipidemia but better care and prognosis compared with older patients. There were significant gender disparities of managements and outcomes in young patients. More efforts to improve quality of care in young women are needed.
Diabetes in Patients With Heart Failure With Reduced Ejection Fraction During Hospitalization: A Retrospective Observational Study
Authors: Zhou Yiling , Wang Miye , Wang Si , Li Nan , Zhang Shengzhao , Tang Siqi , Shi Qingyang , Zhao Yuliang , Li Jingwen , Zeng Yuping , Song Huan , Tian Haoming , Li Shuangqing , Li Sheyu 
Published: August 2021

BackgroundDiabetes is prevalent worldwide including hospitalized patients with heart failure with reduced ejection fraction (HFrEF). This retrospective study investigated the association of diabetes with in-hospital adverse events in patients with HFrEF.MethodsWe analyzed data from electronic medical records of patients hospitalized with HFrEF in West China Hospital of Sichuan University from January 1, 2011, to September 30, 2018. Propensity score matching balances the baseline characteristics between patients with and without diabetes. Logistic and Poisson regressions investigated the association of diabetes with risks of intubation, cardiogenic shock, acute kidney injury (AKI), intensive care unit (ICU) admission and death during hospitalization, and length of ICU and hospital stay in the matched cases.ResultsAmong 6,022 eligible patients (including 1,998 with diabetes), 1,930 patient pairs with and without diabetes were included by propensity score matching. Patients with diabetes had a significantly increased risk of intubation (odds ratio [OR], 2.69; 95% confidence interval [CI], 2.25–3.22; P&lt;0.001), cardiogenic shock (OR, 2.01; 95% CI, 1.72–2.35; P&lt;0.001), AKI at any stage (OR, 1.67; 95% CI, 1.44–1.94; P&lt;0.001), ICU admission (OR, 1.89; 95% CI, 1.65–2.15; P&lt;0.001), and death (OR, 4.25; 95% CI, 3.06–6.02; P&lt;0.001) during hospitalization. Patients with diabetes had longer ICU (median difference, 1.47 days; 95% CI, 0.96–2.08; P&lt;0.001) and hospital stay (2.20 days; 95% CI, 1.43–2.86; P&lt;0.001) than those without diabetes. There were potential subgroup effects by age and by hypertension, and CKD status on the association of diabetes with risk of AKI at any stage; and subgroup effects by sex and CKD status on the association of diabetes with risk of intubation. The increase in length of hospital stay was larger in patients without hypertension than those with hypertension.ConclusionsAmong patients with HFrEF, those with diabetes have a worse prognosis, including a higher risk of in-hospital intubation, cardiogenic shock, AKI, ICU admission and death during hospitalization, and longer ICU and hospital stay.
Diaphyseal and Metaphyseal Modeling Defects—Clinical Findings and Identification of WRAP53 Deficiency in Craniometadiaphyseal Dysplasia
Authors: Hao Yun , Wang Xiao-Lin , Xiao Jun , Jiao Chun-Lei , Meng Xin-Yao , Guo Jia-Chao , Shao Jing-Fan , Feng Jie-Xiong , He Jin-Peng 
Published: August 2021

Background: Diaphyseal and metaphyseal modeling defects lead to severe changes in bone mass and shape, which are common features in osteoporosis that linked to non-vertebral fractures. Original mechanism of diaphyseal and metaphyseal modeling defects has proved elusive. Studying rare syndromes can elucidate mechanisms of common disorders and identify potential therapeutic targets.Methods: We evaluated a family pedigree with craniometadiaphyseal dysplasia (CRMDD, OMIM 269300), a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and absent of normal metaphyseal flaring and diaphyseal constriction. Systemic radiographic examination and serum hormone test were made for this rare disease. One patient and her two normal parents were examined by means of whole-exome sequencing (WES) to identify the candidate pathogenic gene and rule out mucopolysaccharidosis and Prader–Willi Syndrome by means of Sanger sequencing.Results: There are several conspicuous radiographic characteristics: (1) bullet-shaped phalanges, (2) long and narrow pelvic inlet, absent of supra-acetabular constriction, (3) round rod-shaped long tubular bones, (4) prominent aiploic mastoid, (5) bending-shaped limb, genua varus and genu varum, and (6) congenital dislocation of elbow. Here, we did not find any wormian bones, and there are several typical clinical characteristics: (1) macrocephaly and wide jaw, (2) Avatar elf-shaped ears, pointed and protruding ears, (3) hypertrophy of limbs, (4) flat feet and giant hand phenomenon, (5) nail dystrophy, (6) limb deformity, (7) high-arched palate, (8) superficial hemangiomas, (9) tall stature, and intellectual disability. In this patient, we found biallelic frameshift deletion mutations in WRAP53, and those two mutations were transmitted from her parents respectively.Conclusions: We describe her clinical and radiological findings and presented a new subtype without wormian bones and with a tall stature. Our study showed that craniometadiaphyseal dysplasia was caused by a deficiency of WRAP53 with autosomal recessive inheritance.
Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats
Authors: Poles Marietta Z. , Nászai Anna , Gulácsi Levente , Czakó Bálint L. , Gál Krisztián G. , Glenz Romy J. , Dookhun Dishana , Rutai Attila , Tallósy Szabolcs P. , Szabó Andrea , Lőrinczi Bálint , Szatmári István , Fülöp Ferenc , Vécsei László , Boros Mihály , Juhász László , Kaszaki József 
Published: August 2021

Background and AimsThe systemic host response in sepsis is frequently accompanied by central nervous system (CNS) dysfunction. Evidence suggests that excessive formation of neutrophil extracellular traps (NETs) can increase the permeability of the blood–brain barrier (BBB) and that the evolving mitochondrial damage may contribute to the pathogenesis of sepsis-associated encephalopathy. Kynurenic acid (KYNA), a metabolite of tryptophan catabolism, exerts pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenous KYNA or its synthetic analogues SZR-72 and SZR-104 affect BBB permeability secondary to NET formation and influence cerebral mitochondrial disturbances in a clinically relevant rodent model of intraabdominal sepsis.MethodsSprague–Dawley rats were subjected to fecal peritonitis (0.6 g kg-1 ip) or a sham operation. Septic animals were treated with saline or KYNA, SZR-72 or SZR-104 (160 µmol kg-1 each ip) 16h and 22h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic parameters to calculate rat organ failure assessment (ROFA) scores. NET components (citrullinated histone H3 (CitH3); myeloperoxidase (MPO)) and the NET inducer IL-1β, as well as IL-6 and a brain injury marker (S100B) were detected from plasma samples. After 24h, leukocyte infiltration (tissue MPO) and mitochondrial complex I- and II-linked (CI–CII) oxidative phosphorylation (OXPHOS) were evaluated. In a separate series, Evans Blue extravasation and the edema index were used to assess BBB permeability in the same regions.ResultsSepsis was characterized by significantly elevated ROFA scores, while the increased BBB permeability and plasma S100B levels demonstrated brain damage. Plasma levels of CitH3, MPO and IL-1β were elevated in sepsis but were ameliorated by KYNA and its synthetic analogues. The sepsis-induced deterioration in tissue CI–CII-linked OXPHOS and BBB parameters as well as the increase in tissue MPO content were positively affected by KYNA/KYNA analogues.ConclusionThis study is the first to report that KYNA and KYNA analogues are potential neuroprotective agents in experimental sepsis. The proposed mechanistic steps involve reduced peripheral NET formation, lowered BBB permeability changes and alleviation of mitochondrial dysfunction in the CNS.
Evolution of Globus Pallidus Targeting for Parkinson's and Dystonia Deep Brain Stimulation: A 15-Year Experience
Authors: Holanda Vanessa M. , Eisinger Robert Stephen , Almeida Leonardo , Tsuboi Takashi , Wang Huimin , Okun Michael S. , Deeb Wissam , Patterson Addie , Wagle Shukla Aparna , Lobo Lopes Janine , Foote Kelly Douglas 
Published: August 2021

Objective: The aim of this study is to evaluate the evolution of GPi DBS targeting.Methods: This retrospective, single-center study included patients implanted with GPi DBS leads for dystonia or PD during the years 2004 to 2018 at the University of Florida Fixel Institute for Neurological Diseases. Each patient underwent a high-resolution targeting study on the day prior to the surgery, which was fused with a high resolution CT scan that was acquired on the day of the procedure. Intraoperative target location was selected using a digitized 3D Schaltenbrand-Bailey atlas. All patients underwent a high-resolution head CT scan without contrast approximately one month after lead implantation and accurate measurement of neuroanatomical lead position was acquired after fusion of pre-operative and post-operative image studies.Results: We analyzed 253 PD patients with 352 leads and 80 dystonia patients with 141 leads. During 15 years of follow-up, lead locations in the PD group migrated more laterally (β = 0.09, p &lt; 0.0001), posteriorly [slope (β) = 0.04, p &lt; 0.05], and dorsally (β = 0.07, p &lt; 0.001), whereas leads in the dystonia group did not significantly change position aside from a trend in the dorsal direction (β = 0.06, p = 0.053).Conclusion: The evolving target likely results from multiple factors including improvements in targeting techniques and clinical feedback intraoperatively and post-operatively. Our demonstrates the potential importance of a systematic post-operative DBS lead measurement protocol to ensure quality control and to inform and optimize DBS programming.
Patient Outcomes in Disorders of Consciousness Following Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Individual Patient Data
Authors: O'Neal Christen M. , Schroeder Lindsey N. , Wells Allison A. , Chen Sixia , Stephens Tressie M. , Glenn Chad A. , Conner Andrew K. 
Published: August 2021

Background: There are few treatments with limited efficacy for patients with disorders of consciousness (DoC), such as minimally conscious and persistent vegetative state (MCS and PVS).Objective: In this meta-analysis of individual patient data (IPD), we examine studies utilizing transcranial magnetic stimulation (TMS) as a treatment in DoC to determine patient and protocol-specific factors associated with improved outcomes.Methods: We conducted a systematic review of PubMed, Ovid Medline, and Clinicaltrials.gov through April 2020 using the following terms: “minimally conscious state,” or “persistent vegetative state,” or “unresponsive wakefulness syndrome,” or “disorders of consciousness” and “transcranial magnetic stimulation.” Studies utilizing TMS as an intervention and reporting individual pre- and post-TMS Coma Recovery Scale-Revised (CRS-R) scores and subscores were included. Studies utilizing diagnostic TMS were excluded. We performed a meta-analysis at two time points to generate a pooled estimate for absolute change in CRS-R Index, and performed a second meta-analysis to determine the treatment effect of TMS using data from sham-controlled crossover studies. A linear regression model was also created using significant predictors of absolute CRS-R index change.Results: The search yielded 118 papers, of which 10 papers with 90 patients were included. Patients demonstrated a mean pooled absolute change in CRS-R Index of 2.74 (95% CI, 0.62–4.85) after one session of TMS and 5.88 (95% CI, 3.68–8.07) at last post-TMS CRS-R assessment. The standardized mean difference between real rTMS and sham was 2.82 (95% CI, −1.50 to 7.14), favoring rTMS. The linear regression model showed that patients had significantly greater CRS-R index changes if they were in MCS, had an etiology of stroke or intracranial hemorrhage, received 10 or more sessions of TMS, or if TMS was initiated within 3 months from injury.Conclusions: TMS may improve outcomes in MCS and PVS. Further evaluation with randomized, clinical trials is necessary to determine its efficacy in this patient population.
A 20-Year Research Trend Analysis of the Influence of Anesthesia on Tumor Prognosis Using Bibliometric Methods
Authors: Luo Jiamei , Shi Yumiao , Wang Xiaoqiang , Zhang Ruirui , Chen Sifan , Yu Weifeng , Su Diansan , Tian Jie 
Published: August 2021

BackgroundBibliometric analysis is used to gain a systematic understanding of developments in the field of the influence of anesthesia on tumor prognosis and changes in research hot spots over the past 20 years.MethodsRelevant publications from the Web of Science Core Collection (WoSCC) were downloaded on May 5, 2021. Acquired data were then analyzed using the Online Analysis Platform of Literature Metrology (http://biblimetric.com) and the CiteSpace software was used to analyze and predict trends and hot spots in this field.Results1,521 publications on the influence of anesthesia on tumor prognosis were identified and 1494 qualifying records were included in the final analysis. The leading country in this field was the United States of America (USA). The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and Pennsylvania State University (State College, PA, USA) featured the highest number of publications among all institutions. Co-citation cluster labels revealed characteristics of ten main clusters: total intravenous anesthesia, opioid growth factor receptor, gastric cancer cell, opioid receptor, murine model, natural killer cell activity, health-related quality, glioma cell, opioid switching and mu-type opioid receptor. Keyword burst detection indicated that randomized controlled trials (RCTs), volatile anesthetics, and ropivacaine were the newly emerging research hot spots.ConclusionsThis study compiled 1494 publications covering anesthesia and tumor prognosis research and showed that the direction of these studies is likely in transition from opioids and their receptors to other anesthetics, and from retrospective studies to prospective randomized controlled trials. It provides guidance for further research and clinical applications on choosing anesthetic methods and drugs.
Current Understanding of Hearing Loss in Sporadic Vestibular Schwannomas: A Systematic Review
Authors: Gan Jinlu , Zhang Yanling , Wu Jingnan , Lei Deqiang , Zhang Fangcheng , Zhao Hongyang , Wang Lei 
Published: August 2021

ObjectiveHearing loss is the most common initial symptom in patients with sporadic vestibular schwannomas (SVS). Hearing preservation is an important goal of both conservative and surgical therapy. However, the mechanism of SVS-associated hearing loss remains unclear. Thus, we performed this systematic review to summarize the current understanding of hearing loss in the SVS and distill a testable hypothesis to further illuminate its underlying mechanism.MethodsA systematic review querying four databases (PubMed, Medline, Embase, and Web of Science) was performed to identify studies evaluating hearing loss in patients with SVS and exploring the potential mechanisms of hearing impairment.ResultsA total of 50 articles were eligible and included in this review. After analysis, the retrieved studies could be categorized into four types: (1) 29 studies explore the relationship between hearing loss and the growth pattern of the tumor (e.g., tumor size/volume, growth rate, tumor location, etc.); (2) ten studies investigate the potential role of cochlear dysfunction in hearing deterioration, including structural abnormality, protein elevation in perilymph, and cochlear malfunctioning; (3) two studies looked into SVS-induced impairment of auditory pathway and cortex; (4) in the rest nine studies, researchers explored the molecular mechanism underlying hearing loss in SVS, which involves molecular and genetic alterations, inflammatory response, growth factors, and other tumor-associated secretions.ConclusionsMultiple factors may contribute to the hearing impairment in SVS, including the growth pattern of tumor, cochlear dysfunction, impairment of auditory pathway and cortex, genetic and molecular changes. However, our current understanding is still limited, and future studies are needed to explore this multifactorial hypothesis and dig deeper into its underlying mechanism.
Multi-Omics Analysis of the Expression and Prognosis for FKBP Gene Family in Renal Cancer
Authors: Sun Zeqiang , Qin Xin , Fang Juanjuan , Tang Yueqing , Fan Yidong 
Published: August 2021

BackgroundThe FK506-binding protein (FKBP) is a family of intracellular receptors that can bind specifically to the immunosuppressant FK506 and rapamycin. Although FKBPs play crucial roles in biological processes and carcinogenesis, their prognostic value and molecular mechanism in clear cell renal cell carcinoma (ccRCC) remain unclear.MethodsUsing pan-cancer data from The Cancer Genome Atlas (TCGA) and public databases, we analyzed the expression and correlation of FKBPs in 33 tumor types. Survival and Cox regression analyses were employed to explore the prognostic value of FKBPs. The relationship with tumor microenvironment and stemness indices was taken into account to evaluate the function of FKBPs. We constructed a risk score model to predict the prognosis of patients with ccRCC. The receiver operating characteristic (ROC) curve was performed to further test the prognostic ability of our model. Nomogram, joint effects analysis, and clinical relevance were performed to assist the clinician. Gene set enrichment analysis (GSEA) and cell line experiments were performed to investigate the function and molecular mechanisms of FKBPs in patients with ccRCC. Paired clinical specimens and multi-omics analysis were used to further validate and explore the factors affecting gene expression in ccRCC patients.ResultsThe expression levels of FKBP10 and FKBP11 were higher in ccRCC tissues than in normal tissues. The alteration in expression may be because of the degree of DNA methylation. Increased expression levels of FKBP10 and FKBP11 were associated with worse overall survival (OS). More importantly, GSEA revealed that FKBP10 is mainly involved in cell metabolism and autophagy, whereas FKBP11 is mainly associated with immune-related biological processes and autophagy. Cell Counting Kit 8 (CCK-8) and Transwell assays revealed that knockdown of FKBP10 and FKBP11 inhibits proliferation, migration, and invasion of the ccRCC cell line.ConclusionFKBP10 and FKBP11 play important roles in ccRCC phenotypes and are potential prognostic markers as well as new therapeutic targets for patients with ccRCC.