bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasive Hemodynamic Assessment and Procedural Success of Transcatheter Tricuspid Valve Repair—Important Factors for Right Ventricular Remodeling and Outcome
Authors: Dannenberg Varius , Koschutnik Matthias , Donà Carolina , Nitsche Christian , Mascherbauer Katharina , Heitzinger Gregor , Halavina Kseniya , Kammerlander Andreas A. , Spinka Georg , Winter Max-Paul , Andreas Martin , Mach Markus , Schneider Matthias , Bartunek Anna , Bartko Philipp E. , Hengstenberg Christian , Mascherbauer Julia , Goliasch Georg 
Published: June 2022

IntroductionSevere tricuspid regurgitation (TR) is a common condition promoting right heart failure and is associated with a poor long-term prognosis. Transcatheter tricuspid valve repair (TTVR) emerged as a low-risk alternative to surgical repair techniques. However, patient selection remains controversial, particularly regarding the benefits of TTVR in patients with pulmonary hypertension (PH).AimWe aimed to investigate the impact of preprocedural invasive hemodynamic assessment and procedural success on right ventricular (RV) remodeling and outcome.MethodsAll patients undergoing TTVR with a TR reduction of ≥1 grade without precapillary or combined PH [mean pulmonary artery pressure (mPAP) ≥25 mmHg, mean pulmonary artery Wedge pressure ≤ 15 mmHg, pulmonary vascular resistance ≥3 Wood units] were assigned to the responder group. All patients with a TR reduction of ≥1 grade and precapillary or combined PH were classified as non-responders. Patients with a TR reduction ≥2 grade were directly classified as responders, and patients without TR reduction were directly assigned as non-responders.ResultsA total of 107 patients were enrolled, 75 were classified as responders and 32 as non-responders. We observed evidence of significant RV reverse remodeling in responders with a decrease in RV diameters (−2.9 mm, p = 0.001) at a mean follow-up of 229 days (±219 SD) after TTVR. RV function improved in responders [fractional area change (FAC) + 5.7%, p &lt; 0.001, RV free wall strain +3.9%, p = 0.006], but interestingly further deteriorated in non-responders (FAC −4.5%, p = 0.003, RV free wall strain −3.9%, p = 0.007). Non-responders had more persistent symptoms than responders (NYHA ≥3, 72% vs. 11% at follow-up). Subsequently, non-response was associated with a poor long-term prognosis in terms of death, heart failure (HF) hospitalization, and re-intervention after 2 years (freedom of death, HF hospitalization, and reintervention at 2 years: 16% vs. 78%, log-rank: p &lt; 0.001).ConclusionHemodynamic assessment before TTVR and procedural success are significant factors for patient prognosis. The hemodynamic profiling prior to intervention is an essential component in patient selection for TTVR. The window for edge-to-edge TTVR might be limited, but timely intervention is an important factor for a better outcome and successful right ventricular reverse remodeling.
Abnormal Liver Function Tests Were Related to Short- and Long-Term Prognosis in Critically Ill Patients With Primary Pulmonary Hypertension
Authors: Wang Dayu , Huang Suiqing , Xu Guangtao , Wu Sha , Liu Zhen , Xu Long , Hu Bo , Hou Jian 
Published: June 2022

AimThe aim of this study was to examine the utility of liver function tests (LFTs) in predicting the prognosis of critically ill patients with primary pulmonary hypertension (PPH) with/without liver disease.MethodsWe retrieved the Medical Information Mart for Intensive Care III (MIMIC-III) database to acquire clinical data. From the database, we recruited adult patients that were equal to or older than 18 years with primary pulmonary hypertension (PPH) discharge from intensive care unit (ICU). Then, the relationship between LFTs and duration of hospitalization and ICU stays was examined based on the Spearman correlation. The chi-square assessment was conducted to examine the correlation between LFTs and death rates. Survival curves were plotted with the aid of the Kaplan-Meier technique, and the curves were subsequently compared utilizing the log-rank test. The LFTs were identified as independent predictive variables of death according to the results of multivariable logistic regression. The specificity and sensitivity for mortality were calculated utilizing receiver operating characteristic (ROC) curves and the area under the curve (AUC).ResultsIn total, 198 patients satisfying the inclusion criteria were recruited, among which there were 23 patients with liver disease. Only ALB was correlated with the length of ICU stay in the total PPH group. ALB independently served as a risk variable for hospital mortality and 90-day mortality and was significantly associated with 90-day and 4-year survival rates in both total PPH and PPH without liver disease. AST was correlated with hospital mortality and 90-day survival curves in both total PPH and PPH without liver disease and independently served as a risk factor for hospital and 90-day mortality only in the total PPH group. ALT independently acted as a risk variable for hospital mortality and total bilirubin was correlated with hospital mortality in the total group. The diagnostic performance of the predictive model combining the LFTs was moderately good for the hospital, 90-day, and 4-year mortality. Both Modelı End-Stage ıLiverı Disease (MELD) score and albumin-bilirubin (ALBI) score were independent risk factors for short- and long-term prognosis. And they were also significantly associated with short- and long-term prognosis.ConclusionAmong critically ill patients with PPH and with or without liver illness, aberrant LFT was linked to short- and long-term prognoses.
Sertoli and Germ Cells Within Atrophic Seminiferous Tubules of Men With Non-Obstructive Azoospermia
Authors: Jensen Christian Fuglesang Skjødt , Wang Danyang , Mamsen Linn Salto , Giwercman Aleksander , Jørgensen Niels , Fode Mikkel , Ohl Dana , Dong Lihua , Hildorf Simone Engmann , Pors Susanne Elisabeth , Fedder Jens , Ntemou Elissavet , Andersen Claus Yding , Sønksen Jens 
Published: June 2022

BackgroundInfertile men with non-obstructive azoospermia (NOA) have impaired spermatogenesis. Dilated and un-dilated atrophic seminiferous tubules are often present in the testes of these patients, with the highest likelihood of active spermatogenesis in the dilated tubules. Little is known about the un-dilated tubules, which in NOA patients constitute the majority. To advance therapeutic strategies for men with NOA who fail surgical sperm retrieval we aimed to characterize the spermatogonial stem cell microenvironment in atrophic un-dilated tubules.MethodsTestis biopsies approximately 3x3x3 mm3 were obtained from un-dilated areas from 34 patients. They were classified as hypospermatogenesis (HS) (n=5), maturation arrest (MA) (n=14), and Sertoli cell only (SCO) (n= 15). Testis samples from five fertile men were included as controls. Biopsies were used for histological analysis, RT-PCR analysis and immunofluorescence of germ and Sertoli cell markers.ResultsAnti-Müllerian hormone mRNA and protein expression was increased in un-dilated tubules in all three NOA subtypes, compared to the control, showing an immature state of Sertoli cells (p&lt;0.05). The GDNF mRNA expression was significantly increased in MA (P=0.0003). The BMP4 mRNA expression showed a significant increase in HS, MA, and SCO (P=0.02, P=0.0005, P=0.02, respectively). The thickness of the tubule wall was increased 2.2-fold in the SCO-NOA compared to the control (p&lt;0.05). In germ cells, we found the DEAD-box helicase 4 (DDX4) and melanoma-associated antigen A4 (MAGE-A4) mRNA and protein expression reduced in NOA (MAGE-A: 46% decrease in HS, 53% decrease in MA, absent in SCO). In HS-NOA, the number of androgen receptor positive Sertoli cells was reduced 30% with a similar pattern in mRNA expression. The γH2AX expression was increased in SCO as compared to HS and MA. However, none of these differences reached statistical significance probably due to low number of samples.ConclusionsSertoli cells were shown to be immature in un-dilated tubules of three NOA subtypes. The increased DNA damage in Sertoli cells and thicker tubule wall in SCO suggested a different mechanism for the absence of spermatogenesis from SCO to HS and MA. These results expand insight into the differences in un-dilated tubules from the different types of NOA patients.
Clinical Significance of Lifetime Maximum Body Mass Index in Predicting the Development of T2DM: A Prospective Study in Beijing
Authors: Jia Xiaomeng , Wang Anping , Yang Longyan , Cheng Yu , Wang Yajing , Ba Jianming , Dou Jingtao , Mu Yiming , Zhao Dong , Lyu Zhaohui 
Published: June 2022

BackgroundOverweight and obesity are well-known risk factors for type 2 diabetes mellitus (T2DM). The effect of the maximum body mass index (BMImax), which indicates the highest body weight before the diagnosis of T2DM, is not fully understood. This study aimed to explore the predictive value of BMImax in the progression of diabetes.MethodsThis prospective study recruited 2018 subjects with normal glucose tolerance in Beijing, China. The subjects were followed up for eight years, and the association between BMImax and glucose outcomes was evaluated.ResultsNinety-seven of the 2,018 participants developed diabetes by the end of the study. Compared to individuals with normal glucose tolerance, those who developed diabetes were characterized by higher levels of fasting plasma glucose (FPG), 2 h postload glucose (PBG), glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-c), a higher prevalence of a familial history of diabetes and a lower level of high‐density lipoprotein cholesterol (HDL-c). Multivariate regression analysis of sex-stratified groups suggested that FPG, HbA1c, SBP and familial history of diabetes were independent risk factors for diabetes, but that BMImax was a unique indicator for female patients.ConclusionsBMImax might be an independent predictor of T2DM in females, but it does not seem to be associated with the risk of diabetes in males. BMImax could be regarded as an indicator in the prevention and management of diabetes.
Triglyceride-Glucose Index Correlate With Telomere Length in Healthy Adults From the National Health and Nutrition Examination Survey
Authors: Hu Lihua , Zhang Qiaojian , Bai Yi , Hu Guiping , Li Jianping 
Published: June 2022

AimThe present investigation was designed to test the association between leukocyte telomere length (LTL) and two simple markers of insulin resistance, that is, homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride-glucose (TyG) index in U.S. adults without metabolic diseases.MethodsA total of 6489 U.S. adults without diabetes from NHANES 1999–2002 were analyzed. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. HOMA-Index was calculated as fasting plasma glucose (mmol/L) × fasting serum insulin (mU/mL)/22.5. LTL was obtained using the quantitative polymerase chain reaction method. Multivariate linear regression analysis was assessed to evaluate the association of TyG index HOMA-IR with LTL. We further conducted a generalized additive model (GAM) and a fitted smoothing curve with penalized spline method.ResultsIt was found that the mean LTL was 5796.1 bp in the measured healthy adults. Overall, TyG index was significantly associated with LTL, while HOMA-IR was not. Compared with participants in tertile 1 of the TyG index, the β (95% CI) for those in the second (8.27 to 8.77) and third (≥ 8.77) were -4.31 (95% CI: -48.12~39.49) and -95.98 (95% CI: -145.08~-46.89), respectively. Subjects with TyG index ≥ 8.77 had statistically significant shorter LTL (β = -93.33, 95%CI: -134.33~-52.32), compared with TyG index &lt; 8.77. We further explored a dose-response relation between TyG index by a decile approach [≤ 7.81 (reference), 7.81-8.04, 8.04-8.21, 8.21-8.37, 8.37-8.52, 8.52-8.68, 8.68-8.83, 8.83-9.03, 9.03-9.33, and &gt;9.33] and LTL. Five subgroups (TyG index 7.81-8.04, 8.04-8.21, 8.21-8.37, 8.37-8.52, and 8.52-8.68) did not show significant effect on LTL; while there was a significantly shorter LTL for participants with the TyG index &gt; 8.68, supporting a threshold effect of TyG index on LTL.ConclusionsThe results suggested that higher TyG index (&gt; 8.68) was closely related to shorter LTL and the TyG index was better associated with LTL than HOMA-IR.
The Influence of Triclosan on the Thyroid Hormone System in Humans - A Systematic Review
Authors: Homburg Mai , Rasmussen Åse Krogh , Ramhøj Louise , Feldt-Rasmussen Ulla 
Published: June 2022

ObjectivesTriclosan is an antibacterial agent suspected to disrupt the endocrine system. The aim of this study was to investigate the influence of triclosan on the human thyroid system through a systematic literature review of human studies.MethodsEligibility criteria and method of analysis were registered at Prospero (registration number: CRD42019120984) before a systematic search was conducted in Pubmed and Embase in October 2020. Seventeen articles were found eligible for inclusion. Thirteen studies were observational, while four had a triclosan intervention. Participants consisted of pregnant women in eight studies, of men and non-pregnant women in seven studies and of chord samples/newborns/children/adolescents in six studies. The outcomes were peripheral thyroid hormones and thyroid-stimulating hormone (TSH) in blood samples.ResultsSeveral studies found a negative association between triclosan and triiodothyronine and thyroxine, and a positive association with TSH; however, the opposite associations or no associations were also found. In general, the studies had limited measurement timepoints of thyroid outcomes, and the interventional studies used low concentrations of triclosan. Thus, study design limitations influence the quality of the dataset and it is not yet possible to conclude whether triclosan at current human exposure levels adversely affects the thyroid hormone system.ConclusionsFurther larger studies with more continuity and more elaborate outcome measurements of thyroid function are needed to clarify whether triclosan, at current exposure levels, affects the human thyroid hormone system.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42019120984, identifier PROSPERO (CRD42019120984).
Developing Clinical Prediction Models Using Primary Care Electronic Health Record Data: The Impact of Data Preparation Choices on Model Performance
Authors: van Os Hendrikus J. A. , Kanning Jos P. , Wermer Marieke J. H. , Chavannes Niels H. , Numans Mattijs E. , Ruigrok Ynte M. , van Zwet Erik W. , Putter Hein , Steyerberg Ewout W. , Groenwold Rolf H. H. 
Published: June 2022

ObjectiveTo quantify prediction model performance in relation to data preparation choices when using electronic health records (EHR).Study Design and SettingCox proportional hazards models were developed for predicting the first-ever main adverse cardiovascular events using Dutch primary care EHR data. The reference model was based on a 1-year run-in period, cardiovascular events were defined based on both EHR diagnosis and medication codes, and missing values were multiply imputed. We compared data preparation choices based on (i) length of the run-in period (2- or 3-year run-in); (ii) outcome definition (EHR diagnosis codes or medication codes only); and (iii) methods addressing missing values (mean imputation or complete case analysis) by making variations on the derivation set and testing their impact in a validation set.ResultsWe included 89,491 patients in whom 6,736 first-ever main adverse cardiovascular events occurred during a median follow-up of 8 years. Outcome definition based only on diagnosis codes led to a systematic underestimation of risk (calibration curve intercept: 0.84; 95% CI: 0.83–0.84), while complete case analysis led to overestimation (calibration curve intercept: −0.52; 95% CI: −0.53 to −0.51). Differences in the length of the run-in period showed no relevant impact on calibration and discrimination.ConclusionData preparation choices regarding outcome definition or methods to address missing values can have a substantial impact on the calibration of predictions, hampering reliable clinical decision support. This study further illustrates the urgency of transparent reporting of modeling choices in an EHR data setting.
Keloid Biomarkers and Their Correlation With Immune Infiltration
Authors: Yin Xufeng , Bu Wenbo , Fang Fang , Ren Kehui , Zhou Bingrong 
Published: June 2022

Objective: This work aimed to verify the candidate biomarkers for keloid disorder (KD), and analyze the role of immune cell infiltration (ICI) in the pathology of keloid disorder.Methods: The keloid-related datasets (GSE44270 and GSE145725) were retrieved from the Gene Expression Omnibus (GEO). Then, differential expressed genes (DEGs) were identified by using the “limma” R package. Support vector machine-recursive feature elimination (SVM-RFE) and LASSO logistic regression were utilized for screening candidate biomarkers of KD. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of candidate biomarkers. The candidate biomarkers were further verified through qRT-PCR of keloid lesions and the matched healthy skin tissue collected from eight cases. In addition, ICI in keloid lesions was estimated through single-sample gene-set enrichment analysis (ssGSEA). Finally, the potential drugs to the treatment of KD were predicted in the Connectivity Map Database (CMAP).Results: A total of 406 DEGs were identified between keloid lesion and healthy skin samples. Among them, STC2 (AUC = 0.919), SDC4 (AUC = 0.970), DAAM1 (AUC = 0.966), and NOX4 (AUC = 0.949) were identified as potential biomarkers through the SVM-RFE, LASSO analysis and ROC analysis. The differential expressions of SDC4, DAAM1, and NOX4 were further verified in collected eight samples by qRT-PCR experiment. ICI analysis result showed a positive correlation of DAAM1 expression with monocytes and mast cells, SDC4 with effector memory CD4+ T cells, STC2 with T follicular helper cells, and NOX4 with central memory CD8+ T cells. Finally, a total of 13 candidate small molecule drugs were predicted for keloids treatment in CMAP drug database.Conclusion: We identified four genes that may serve as potential biomarkers for KD development and revealed that ICI might play a critical role in the pathogenesis of KD.
Peritoneal Protein Clearance Is Associated With Cardiovascular Events but Not Mortality in Peritoneal Dialysis Patients
Authors: Niu Wei , Yang Xiaoxiao , Yan Hao , Yu Zanzhe , Li Zhenyuan , Lin Xinghui , Gu Leyi , Ni Zhaohui , Fang Wei 
Published: June 2022

IntroductionAssociation of peritoneal protein clearance (Pcl) with outcomes in patients with peritoneal dialysis (PD) is uncertain. Thus, we aimed to investigate its impact on cardiovascular events and all-cause mortality in patients with PD and factors associated with Pcl.MethodsPrevalent patients with PD from January 2014 to April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters and Angiopoietin-2-Tie2 system cytokines. Mass transfer area coefficient of creatinine (MTACcr) and Pcl were calculated. Patients were dichotomized into two groups by the median Pcl level (68.5 ml/day) and were followed up prospectively until the end of the study (1 October 2018).ResultsA total of 318 patients with PD [51.2% men, mean age 56.7 ± 14.3 y, median PD duration 31.5 (12.1–57.2) months] were enrolled. Among them, 25.7% were comorbid with diabetes and 28.6% had a history of cardiovascular disease (CVD). After being followed up for up to 43.9 (24.2–50.3) months, 63 had developed cardiovascular events, and 81 patients were died. Among them, the high Pcl group had occurred 39 cardiovascular events and 51 deaths, and the low Pcl group had 24 cardiovascular events and 30 deaths. Kaplan-Meier analysis showed that both the occurrence of cardiovascular events and all-cause mortality were increased in patients with high Pcl. However, after adjusting for important confounders and serum Angiopoietin-2 (Angpt-2) level, Pcl was still an independent risk factor for cardiovascular events [hazard ratio (HR) = 1.006 (1.000–1.012), p = 0.038] but not mortality. On multivariate regression analysis, serum albumin, MTACcr, and body mass index (BMI) were found to be independently associated with Pcl.ConclusionHigh Pcl is an independent risk factor for cardiovascular events but not all-cause mortality. The prediction of cardiovascular events by Pcl was independent of serum Angpt-2.
Uric Acid Enhances Neurogenesis in a Parkinsonian Model by Remodeling Mitochondria
Authors: Lee Ji Eun , Shin Yu Jin , Kim Yi Seul , Kim Ha Na , Kim Dong Yeol , Chung Seok Jong , Yoo Han Soo , Shin Jin Young , Lee Phil Hyu 
Published: June 2022

BackgroundAdult neurogenesis is the process of generating new neurons to enter neural circuits and differentiate into functional neurons. However, it is significantly reduced in Parkinson’s disease (PD). Uric acid (UA), a natural antioxidant, has neuroprotective properties in patients with PD. This study aimed to investigate whether UA would enhance neurogenesis in PD.MethodsWe evaluated whether elevating serum UA levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mouse model would restore neurogenesis in the subventricular zone (SVZ). For a cellular model, we primary cultured neural precursor cells (NPCs) from post-natal day 1 rat and evaluated whether UA treatment promoted cell proliferation against 1-methyl-4-phenylpyridinium (MPP+).ResultsUric acid enhanced neurogenesis in both in vivo and in vitro parkinsonian model. UA-elevating therapy significantly increased the number of bromodeoxyuridine (BrdU)-positive cells in the SVZ of PD animals as compared to PD mice with normal UA levels. In a cellular model, UA treatment increased the expression of Ki-67. In the process of modulating neurogenesis, UA elevation up-regulated the expression of mitochondrial fusion markers.ConclusionIn MPTP-induced parkinsonian model, UA probably enhanced neurogenesis via regulating mitochondrial dynamics, promoting fusion machinery, and inhibiting fission process.
Changes in Periodic Limb Movements of Sleep After the Use of Continuous Positive Airway Pressure Therapy: A Meta-Analysis
Authors: Lin Tzu-Chao , Zeng Bing-Yan , Wu Meng-Ni , Chen Tien-Yu , Chen Yen-Wen , Yeh Pin-Yang , Tseng Ping-Tao , Hsu Chung-Yao 
Published: June 2022

BackgroundBoth obstructive sleep apnea (OSA) and periodic limb movements of sleep (PLMS) are common in the sleep laboratory. The severity of OSA can be improved by using continuous positive airway pressure (CPAP). However, increasing evidence has shown an elevated periodic limb movement index (PLMI) in patients with OSA who use CPAP, although the pathophysiology is still unknown. This meta-analysis aimed to investigate changes in PLMS after using CPAP and the potential pathophysiology of these changes.MethodsClinical trials in adult humans investigating the comorbidity between PLMS and CPAP were identified and analyzed using random-effects model meta-analysis.ResultsThis meta-analysis included 14 studies comprising 2,938 patients with OSA. The PLMI was significantly increased after using CPAP with a difference in means of 1.894 (95% confidence interval = 0.651–3.138, p = 0.003). Subgroup analysis showed that CPAP was only significantly associated with an increase in PLMI in the patients without PLMS at baseline (p = 0.045) and in those with a baseline body-mass index &lt;30 kg/m2 (p = 0.045). The use of CPAP, apnea-hypopnea index, and arousal index were positively correlated with changes in PLMI.ConclusionThese characteristics may serve as qualitative predictive indicators of changes in PLMI after CPAP usage. Further analysis of the quantitative relationships between PLMI and the predictive indicators may be warranted.Trial RegistrationPROSPERO (registration number: CRD42021252635).