bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resting Cardiac Power Predicts Adverse Outcome in Heart Failure Patients With Preserved Ejection Fraction: A Prospective Study
Authors: Wang Shiqi , Chen Aiqi , Duan Xiaokai 
Published: July 2022

BackgroundWe sought to explore the significance of resting cardiac power/mass in predicting adverse outcome in patients with heart failure with preserved ejection fraction (HFpEF).MethodsThis prospective cohort study included patients with HFpEF and without significant valve disease or right ventricular dysfunction. Cardiac power was normalized to left ventricular (LV) mass and expressed in W/100 g of LV myocardium. Multivariate Cox regression analysis was used to evaluate the association between resting cardiac power/mass and composite endpoint, which included all-cause mortality and heart failure (HF) hospitalization.ResultsA total of 2,089 patients were included in this study. After an average follow-up of 4.4 years, 612 (29.30%) patients had composite endpoint, in which 331 (15.84%) died and 391 (18.72%) experienced HF hospitalization. In multivariate Cox regression analysis, resting power/mass &lt; 0.7 W/m2 was independently associated with composite endpoint, all-cause mortality, cardiovascular mortality and HF hospitalization, with hazard ratios (HR) of 1.309 [95% confidence interval (CI): 1.108–1.546, P = 0.002], 1.697 (95%CI: 1.344–2.143, P &lt; 0.001), 2.513 (95%CI: 1.711–3.689, P &lt; 0.001), and 1.294 (95%CI: 1.052–1.592, P = 0.015), respectively. For composite endpoint, cardiovascular mortality and HF hospitalization, the C statistic increased significantly when incorporating resting cardiac power/mass into a model with established risk factors. For composite endpoint, the continuous net reclassification index after adding resting cardiac power/mass in the original model with N-terminal pro-brain natriuretic peptide was 13.1% (95%CI: 2.9–21.6%, P = 0.007), and the integrated discrimination index was 1.9% (95%CI: 0.8–3.2%, P &lt; 0.001).ConclusionResting cardiac power determined by non-invasive echocardiography is independently associated with the risk of adverse outcomes in HFpEF patients and provides incremental prognostic information.
Saturation Effect of Body Mass Index on Bone Mineral Density in Adolescents of Different Ages: A Population-Based Study
Authors: Ouyang Yujuan , Quan Yingping , Guo Chengyi , Xie Songlin , Liu Changxiong , Huang Xiongjie , Huang Xinfeng , Chen Yanming , Xiao Xiangjun , Ma Nengqian , Xie Ruijie 
Published: July 2022

BackgroundAdolescence is a critical period for bone development, and peak bone mass may be reached in late adolescence. Boosting bone accumulation at this time can help preserve adult bone health and avoid osteoporosis later in life. Body mass index (BMI) has been found to have a favorable impact on bone mineral density (BMD) in previous research. However, excessive obesity is harmful to health and may lead to various systemic diseases. Therefore, finding an appropriate BMI to maintain a balance between obesity and BMD is critical for adolescents.MethodsThe datasets from the National Health and Nutrition Examination Survey (NHANES) 2011–2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between BMI and BMD. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. Subgroup analyses were then conducted based on gender and age.ResultsThis population-based study included a total of 6,143 adolescents aged 8–19 years. In a multivariate linear regression analysis, a good association between BMI and total BMD was shown [0.014 (0.013, 0.014)]. This positive association was maintained in all subgroup analyses grouped by sex and age. Furthermore, the association between BMI and BMD was nonlinear with a saturation point present, as evidenced by smoothed curve fitting. According to the threshold effect study, with an age group of two years, adolescents of different ages had different BMI saturation values with respect to BMD.ConclusionsOur study showed a significant positive and saturated association between BMI and BMD in adolescents aged 8–19 years. Maintaining BMI at saturation values may reduce other adverse effects while achieving optimal BMD.
Case Report: Prenatal Whole-Exome Sequencing Identified a Novel Nonsense Mutation of the KCNH2 Gene in a Fetus With Familial 2q14.2 Duplication
Authors: Zhuang Jianlong , Chen Chunnuan , Wang Yuanbai , Zeng Shuhong , Chen Yu’e , Jiang Yuying , Xie Yingjun , Wang Gaoxiong 
Published: July 2022

Background: Pathogenic mutations in the KCNH2 gene were associated with long QT syndrome 2 (LQT2), which typically manifest in a prolonged QT interval and may lead to recurrent syncopes, seizure, or sudden death. Limited reports indicated that the KCNH2 mutations would result in LQT2 combined with tetralogy of fallot. Our goal was to present an additional case of LQT2 combined with the tetralogy of fallot in a fetus with a novel KCNH2 mutation.Case presentation: Enrolled in this study was a 23-year-old pregnant woman from Quanzhou Fujian province, China. In her pregnancy, fetal ultrasound anomalies were identified, including tetralogy of fallot, coronary sinus enlargement, and persistent left superior vena cava. No chromosomal abnormality was detected by fetal karyotype analysis. However, 238.1-kb duplication in the 2q14.2 region containing the GLI2 gene was observed in the fetus by chromosomal array analysis, which was inherited from the mother with normal clinical features and interpreted as a variant of uncertain significance (VOUS). Furthermore, whole-exome sequencing (WES) detection identified a novel nonsense c.1907C &gt; G (p.S636*) mutation in the KCNH2 gene in the fetus, and it was classified as a likely pathogenic variant, according to the ACMG guidelines. Parental verification analysis indicated that c.1907C &gt; G (p.S636*) mutation was inherited from the mother.Conclusion: In this study, we believe that 2q14.2 duplication may not be the reason for fetal heart defects; moreover, we described an additional case with KCNH2 gene mutation, which may lead to LQTS and be associated with congenital heart defects. In addition, our study further confirms the application value of the WES technology in prenatal genetic etiology diagnosis of fetuses with structural anomalies and unexplained structural variants.
High Number and Specific Comorbidities Could Impact the Immune Response in COVID-19 Patients
Authors: Liu Dafeng , Yuan Xiaoyan , Gao Fengjiao , Zhao Bennan , Ding Ling , Huan Mingchang , Liu Chao , Jiang Liangshuang 
Published: July 2022

BackgroundCellular immunodeficiency and comorbidities are common in COVID-19 patients.AimThe purpose of this study was to investigate comorbidities impacting on the cellular immunity in COVID-19 patients.MethodsThe research objects included 55 healthy controls and 718 COVID-19 patients who divided into the control group and the COVID-19 group, respectively. Those in the COVID-19 group were divided into subgroups on the basis of the number and types of comorbidities present. Lymphocyte itself and its subsets were compared between the control group and the COVID-19 group, the groups with comorbidities based on the different number and types of comorbidities, and the relationship between the lymphocyte counts and subsets with the number and types of comorbidities was investigated.ResultsCompared with the control group, the lymphocyte counts and T cell subsets were significantly increased in the groups with comorbidities, but both B and NK cell subsets were significantly decreased in the no comorbidity group and in most of the groups with comorbidities (all P&lt;0.05). In the three comorbidities group, the lymphocyte counts and T cell subsets were all significantly decreased, but the CD56+ percentage was obviously increased (all P&lt;0.05). The number of comorbidities was negatively correlated with the lymphocyte counts and the T and NK cell subsets. A negative correlation also existed between cancer and both the lymphocyte counts and the T cell subsets, between chronic hepatitis B and the lymphocyte counts, and between chronic kidney disease and the CD3+ counts. A positive correlation existed between nonalcoholic fatty liver disease (NAFLD) disease and both lymphocyte and CD3+ counts. The risk factors were number of comorbidities for the lymphocyte count, CD3+CD4+ and CD3+CD8+ percentages, NAFLD for the lymphocyte and CD3+ counts, cardiovascular diseases for CD3+CD4+ and CD3+CD8+ percentages, diabetes mellitus for the CD3+CD8+ percentage, and cancer for the CD3+ percentage, respectively.ConclusionsHigh numbers of comorbidities and specific comorbidities could impact the immune response of COVID-19 patients. This study provides a reference for clinicians in the identification of suitable and timely immunotherapy for COVID-19 patients.Clinical Trial Registryhttps://www.chictr.org.cn/enindex.aspx, identifier ChiCTR2000034563.
Increased Interleukin-17 and Glucocorticoid Receptor-β Expression in Interstitial Lung Diseases and Corticosteroid Insensitivity
Authors: Lo Chun-Yu , Wang Chun-Hua , Wang Chih-Wei , Chen Chih-Jung , Huang Hung-Yu , Chung Fu-Tsai , Huang Yu-Chen , Lin Chang-Wei , Lee Chung-Shu , Lin Chun-Yu , Lin Chiung-Hung , Chang Po-Jui , Lin Ting-Yu , Heh Chih-Chen , He Jung-Ru , Chung Kian Fan 
Published: July 2022

BackgroundTreatment responsiveness to corticosteroids is excellent for cryptogenic organizing pneumonia (COP) and sarcoidosis, but suboptimal for idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). We hypothesise that the differential expression of IL-17 contributes to variable corticosteroid sensitivity in different interstitial lung diseases.ObjectiveTo determine the associations among expression of IL-17, glucocorticoid receptor-β and responsiveness to corticosteroid treatment in interstitial lung diseases.MethodsImmunohistochemical (IHC) staining was performed on formalin-fixed paraffin-embedded (FFPE) lung tissues obtained by bronchoscopic, CT-guided or surgical biopsies, and quantified by both cell counting (% positive cells) by individuals and by software IHC Profiler plugin of ImageJ (opacity density score). We studied the effect of IL-17 on corticosteroid sensitivity in human fibroblast MRC5 cell line.ResultsCompared with specimens from patients with COP (n =13) and sarcoidosis (n =13), those from IPF patients (n = 21) had greater GR-β and IL-17 expression and neutrophil infiltration. Radiographic progression after oral corticosteroid treatment was positively correlated with the expression in IL-17 and GR-β/GR-α ratio in all patients (COP, sarcoidosis and IPF) and also within the IPF subgroup only. IL-17 expression level was positively associated with GR-β and GR-β/GR-α ratio. In MRC5 cells, exogenous IL-17 increased the production of collagen I and up-regulated GR-β expression and dexamethasone’s suppressive effect on collagen I production was impaired by IL-17, and silencing IL-17 receptor A gene attenuated the effect of IL-17.ConclusionUp-regulation of GR-β/GR-α ratio by IL-17 could be associated with the relative corticosteroid-insensitivity of IPF.
Depicting Developing Trend and Core Knowledge of Primary Open-Angle Glaucoma: A Bibliometric and Visualized Analysis
Authors: Zhao Liting , Li Jinfei , Feng Lemeng , Zhang Cheng , Zhang Wulong , Wang Chao , He Ye , Wen Dan , Song Weitao 
Published: July 2022

ObjectiveThe prevalence of glaucoma is rising due to an increasing aging population. Because of its insidious and irreversible nature, glaucoma has gradually become the focus of attention. We assessed primary open angle glaucoma, the most common type of glaucoma, to study its present status, global trend, and state of clinical research.MethodsPublications from 2000 to 2021 in Web of Science database were retrieved and analyzed by bibliometrics. VOSviewer and Citespace were used for analysis.ResultsA total of 6,401 publications were included in this review, and we found that the number of publications increased from 139 in 2000 to 563 in 2021. American researchers have published the most papers and had the highest h-index and the most citations, while the Journal of Glaucoma has published the most papers on this topic. Some key researchers, contributing institutions, their partnerships, and scientific masterpieces were identified. The publications we reviewed fall into seven categories: publications on intraocular pressure, normal tension glaucoma, risk factors, the trabecular meshwork, optical coherence tomography, surgery, and mutation. Clear study hotspots were described, which began with epidemiology and transitioned to pathogenesis and diagnosis and then to treatment.ConclusionStudies on primary open angle glaucoma extend well beyond ophthalmology to biochemistry molecular biology, general internal medicine, pharmacology, pharmacy, science technology, and other areas. Interest, research and publications on primary open angle glaucoma are on the rise.
Acute Stroke and Atrial Fibrillation: Risk of Incorrect NOAC Dosage When Estimating Renal Function From Plasma Creatinine Only
Authors: Amoey Danial C. , Thranitz Julia , Münte Thomas F. , Royl Georg 
Published: July 2022

BackgroundCardioembolic stroke (CS) due to atrial fibrillation (AF) bears a high risk of unfavorable outcome. Treatment with a non-vitamin K antagonist oral anticoagulant (NOAC) reduces this risk. NOAC dosage occurs on a thin line during the acute phase of the stroke unit when the patient is threatened by both recurrent CS and a hemorrhagic stroke. It is often adapted to renal function—usually glomerular filtration rate (GFR)—to prevent both under- and overdosing. This study investigates the hypothetical risk of incorrect NOAC dosage after acute stroke when relying on plasma creatinine alone in comparison to a more exact renal function assessment including urine collection.MethodsIn a cohort study on consecutive 481 patients treated in a stroke unit with acute stroke and AF, the GFR estimated from plasma creatinine (eGFR) was compared to concurrent creatinine clearance measurement (CrCl) from urine collection regarding the hypothetically derived NOAC dosage.ResultsThe risk of incorrect dosage (mean, 95% confidence interval) was 6.9% (4.8–9.5), 26% (23–31), 38% (33–42), and 20% (16–23) for apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. The overall risk for incorrect dosage of any NOAC was 23% (21–25). Thresholds for age and admission eGFR were optimized to achieve an overall risk below 5% by additional CrCl measurements in selected patients (apixaban &lt;36 ml/min and any age, dabigatran &lt;75 ml/min and &gt;70 y, edoxaban &gt;36 ml/min and &gt;58 y, rivaroxaban &lt;76 ml/min and &gt;75 y, any NOAC &lt;81 ml/min and &gt;54 y). The resulting portion of patients requiring an additional CrCl measurement was 10, 60, 80, 55, and 65% for apixaban, dabigatran, edoxaban, rivaroxaban, and any NOAC, respectively.ConclusionsThere is a considerable risk of incorrect NOAC dosage in patients with acute CS treated in a stroke unit that can be lowered by targeted CrCl measurements in selected patients.
Mesonephric-Like Adenocarcinoma of Uterine Corpus: A Clinicopathological and Targeted Genomic Profiling Study in a Single Institution
Authors: Ma Tianshi , Chai Mengyu , Shou Huafeng , Ru Guoqing , Zhao Ming 
Published: July 2022

BackgroundMesonephric-like adenocarcinoma (MLA) is a recently characterized, rare, and aggressive neoplasm that mostly arises in the uterine corpus and ovary. MLA shows characteristic pathological features similar to mesonephric adenocarcinoma of the cervix. The origin of MLA is still controversial and recognition of it remains challenging for pathologists. The aim of this study was to enrich the clinicopathological features of MLA in the uterine corpus and explore its molecular alterations by targeted next-generation sequencing (NGS).MethodsFour cases of MLA were identified among a total of 398 endometrial carcinomas diagnosed in our institution between January 2014 and December 2021. Immunohistochemistry and targeted NGS spanning 437 cancer-relevant genes were performed.ResultsThe most common symptom was abnormal vaginal bleeding, and the average age was 68 years. Histologically, the tumors showed a mixture of varied growth patterns including papillary, glandular, tubular, cribriform, solid, and slit-like architectures, which were lined by columnar to cuboidal cells with overlapping vesicular nuclei and sometimes nuclear grooves. Intraluminal eosinophilic colloid-like secretions were focally evident in three of the four cases. Immunohistochemically, the MLAs were positive for GATA3 (4/4), TTF-1 (3/3), luminal CD10 (3/3), calretinin (2/3), and patchy P16 (3/3) and were negative for ER (0/4) and PR (0/4). The expression of P53 was “wild type” (4/4). By targeted NGS, 3/4 (75%), 2/4 (50%), and 1/4 (25%) cases harbored PIK3CA, KRAS, and PTEN mutations, respectively. None of the tumors had mutations in DNA mismatch repair genes, ARID1A/B, POLE, CTNNB1, SMARCA4, or TP53. At the time of diagnosis, three were presented with FIGO IB stage and one with IIIC stage. Two patients received postoperative chemotherapy and radiotherapy and they were alive without evidence of disease at 8 and 56 months follow-up, respectively. One patient developed pulmonary metastasis 13 months after surgery and chemotherapy, and one was dead of the disease 24 months after the operation without adjuvant therapy.ConclusionsMLA is a rare and aggressive malignancy, representing approximately 1% of all endometrial carcinomas. It exhibits mixed architectures associated with distinctive immunophenotype and recurrent KRAS and PIK3CA mutations, supporting classified as of Müllerian origin with mesonephric differentiation.
Total Barley Maiya Alkaloids Prevent Increased Prolactin Levels Caused by Antipsychotic Drugs and Reduce Dopamine Receptor D2 via Epigenetic Mechanisms
Authors: Cao Yu-Ling , -Zhu Li , Zhang Hong , Meng Jun-Hua , Wu Hua-Jun , Wang Xiong , Wu Jin-Hu , Zou Ji-Li , Fang Mao-Sheng , An Jing , Chen Yong-Gang 
Published: July 2022

Background: The dopamine D2 receptor (DRD2) plays an important role in the increased prolactin (PRL) levels associated with the pathogenesis of antipsychotic drugs (ADs). Elevated prolactin levels can affect people’s quality of life. Maiya alkaloids has been used to treat diseases associated with high PRL levels. Maiya, is a processed product of the mature fruits of Hordeum vulgare L. (a gramineous plant) after sprouting and drying and also a common Chinese herbal drug used in the clinic, is traditionally used to treat abnormal lactation, and is currently used clinically for the treatment of abnormal PRL levels.Aims: Epigenetic mechanisms can be related to DRD2 expression. We investigated the role of DRD2 methylation in the induction of PRL expression by ADs and the mechanism underlying the effects of total barley maiya alkaloids (TBMA) on this induction.Methods: The methylation rate of DRD2 in 46 people with schizophrenia who took risperidone was detected by MassARRAY sequencing. Humans were long term users of Ris. Seventy Sprague Dawley female rats were divided into seven groups. A rat model of risperidone-induced PRL was established, and the potential protective effects of TBMA and its components [e.g., hordenine (Hor)] on these increased PRL levels were investigated. The PRL concentration was detected by Enzyme-linked immunosorbent assay. PRL, DRD2, and DNA methyltransferase (DNMT1, DNMT3α, and DNMT3β) protein and mRNA expression were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The positive rate of methylation in the DRD2 promoter region of rats was detected by MassARRAY sequencing.Results: Clinical studies showed that the positive rate of DRD2 methylation associated with increased PRL levels induced by ADs was significantly higher than in the normal prolactinemia (NPRL) group. In vivo and vitro, TBMA and Hor inhibited this induction of PRL expression and increased DRD2 expression by inhibiting the expression of the DNMTs.Conclusions: TBMA and hordenine increased DRD2 expression by inhibiting DNMT-dependent DRD2 methylation.
Pharmacokinetics and Main Metabolites of Anwulignan in Mice
Authors: Chen Cong , Feng Yanbo , Li Han , Lin Hao , Jing Shu , Li He , Wang Chunmei , Chen Jianguang , Sun Jinghui 
Published: July 2022

Anwulignan is a representative component of Chinese traditional medicine Schisandra sphenanthera, with strong pharmacological activities. However, there are few reports on its pharmacokinetics and metabolites in the body. In this study, a metabolomic method based on UHPLC-Q-Orbitrap-MS was used to study the pharmacokinetics of anwulignan in the blood, organs, urine, and feces samples of mice after the intragastric administration of anwulignan (10 mg/kg). The pharmacokinetic parameters were calculated, and the distribution characteristics and main metabolites of anwulignan in the body of mice were analyzed. The results showed that the retention time of anwulignan in the body of mice was longer (t1/2 = 7.1 h), and anwulignan was widely distributed in the body (Vz/F = 32.81 L/kg), especially in the liver. The order of anwulignan concentration in the tissues of mice from high to low was the liver &gt; heart &gt; brain &gt; kidney &gt; lung &gt; spleen. Anwulignan was mainly excreted through the digestive tract in the form of its prototype and metabolites, indicating that it might experience an enterohepatic circulation. A total of seven metabolites were identified, and the demethylation, hydroxylation, dehydroxylation, and demethoxylation were considered to be the main metabolic ways of anwulignan in the body of mice.
High Security Settings in Flanders: An Analysis of Discharged and Long-Term Forensic Psychiatric Patients
Authors: Jeandarme Inge , Goktas Gokhan , Boucké Jan , Dekkers Ingrid , De Boel Laurent , Verbeke Geert 
Published: July 2022

BackgroundTwo Forensic Psychiatric Centres (FPC) were implemented the last decade in Flanders in Ghent (2014) and Antwerp (2017). FPCs are forensic institutions for forensic psychiatric patients with a high recidivism risk and a high security need. The objective of FPCs is to create a care process with sufficient flow (from high to lower forms of security), and transitions (from specialized forensic care to regular psychiatric care).AimsTo examine the characteristics of the high security population in FPCs, treatment length, number of discharges, and discharge locations and to determine the profile of long-term patients within an FPC.MethodsA retrospective file study of an admission cohort of 654 patients admitted to FPC Ghent or FPC Antwerp was conducted. Sociodemographic, clinical, judicial and risk characteristics were analyzed. Bivariate analyses were used to test the difference between two groups: the group that was discharged to a lower security level vs. the group of long-term patients.ResultsMost patients had psychosis and personality disorders, while comorbidity was also high. Judicial histories were extensive, with many sexual index offenses. During a 6-year follow-up period, the number of referrals back to prison was low. Nearly a third of the population was discharged to a setting with a lower security level. Long-term patients typically presented with more personality disorders, higher psychopathy traits and higher risk scores and were more frequently subjected to coercive measures during treatment.ConclusionsThe Flemish FPC population is characterized by a high proportion of sex offenders as well as a high proportion of personality-disordered patients. It is this last group, and the group with elevated psychopathy traits, who remain for longer than expected and is difficult to resocialize. This study further highlights the need for clear criteria to assess the conditions of these long-term patients in Flanders.