bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study
Authors: Pivonello Rosario , Bancos Irina , Feelders Richard A. , Kargi Atil Y. , Kerr Janice M. , Gordon Murray B. , Mariash Cary N. , Terzolo Massimo , Ellison Noel , Moraitis Andreas G. 
Published: July 2021

Introduction/PurposeRelacorilant is a selective glucocorticoid receptor modulator (SGRM) with no progesterone receptor activity. We evaluated the efficacy and safety of relacorilant in patients with endogenous Cushing syndrome (CS).Materials and MethodsA single-arm, open-label, phase 2, dose-finding study with 2 dose groups (NCT02804750, https://clinicaltrials.gov/ct2/show/NCT02804750) was conducted at 19 sites in the U.S. and Europe. Low-dose relacorilant (100-200 mg/d; n = 17) was administered for 12 weeks or high-dose relacorilant (250-400 mg/d; n = 18) for 16 weeks; doses were up-titrated by 50 mg every 4 weeks. Outcome measures included proportion of patients with clinically meaningful changes in hypertension and/or hyperglycemia from baseline to last observed visit. For patients with hypertension, clinical response was defined as a ≥5-mmHg decrease in mean systolic or diastolic blood pressure, measured by a standardized and validated 24-h ABPM. For patients with hyperglycemia, clinical response was defined ad-hoc as ≥0.5% decrease in HbA1c, normalization or ≥50-mg/dL decrease in 2-h plasma glucose value on oral glucose tolerance test, or decrease in daily insulin (≥25%) or sulfonylurea dose (≥50%).Results35 adults with CS and hypertension and/or hyperglycemia (impaired glucose tolerance or type 2 diabetes mellitus) were enrolled, of which 34 (24 women/10 men) received treatment and had postbaseline data. In the low-dose group, 5/12 patients (41.7%) with hypertension and 2/13 patients (15.4%) with hyperglycemia achieved response. In the high-dose group, 7/11 patients (63.6%) with hypertension and 6/12 patients (50%) with hyperglycemia achieved response. Common (≥20%) adverse events included back pain, headache, peripheral edema, nausea, pain at extremities, diarrhea, and dizziness. No drug-induced vaginal bleeding or hypokalemia occurred.ConclusionsThe SGRM relacorilant provided clinical benefit to patients with CS without undesirable antiprogesterone effects or drug-induced hypokalemia.
National Early Warning Score Does Not Accurately Predict Mortality for Patients With Infection Outside the Intensive Care Unit: A Systematic Review and Meta-Analysis
Authors: Zhang Kai , Zhang Xing , Ding Wenyun , Xuan Nanxia , Tian Baoping , Huang Tiancha , Zhang Zhaocai , Cui Wei , Huang Huaqiong , Zhang Gensheng 
Published: July 2021

Background: The prognostic value of the national early warning score (NEWS) in patients with infections remains controversial. We aimed to evaluate the prognostic accuracy of NEWS for prediction of in-hospital mortality in patients with infections outside the intensive care unit (ICU).Methods: We searched PubMed, Embase, and Scopus for related articles from January 2012 to April 2021. Sensitivity, specificity, and likelihood ratios were pooled by using the bivariate random-effects model. Overall prognostic performance was summarized by using the area under the curve (AUC). We performed subgroup analyses to assess the prognostic accuracy of NEWS in selected populations.Results: A total of 21 studies with 107,008 participants were included. The pooled sensitivity and specificity of NEWS were 0.71 and 0.60. The pooled AUC of NEWS was 0.70, which was similar to quick sequential organ failure assessment (qSOFA, AUC: 0.70) and better than systemic inflammatory response syndrome (SIRS, AUC: 0.60). However, the sensitivity (0.55) and AUC (0.63) of NEWS were poor in elder patients. The NEWS of 5 was more sensitive, which was a better threshold for activating urgent assessment and treatment.Conclusions: The NEWS had good diagnostic accuracy for early prediction of mortality in patients with infections outside the ICU, and the sensitivity and specificity were more moderate when compared with qSOFA and SIRS. Insufficient sensitivity and poor performance in the elder population may have limitations as an early warning score for adverse outcomes. NEWS should be used for continuous monitoring rather than a single time point predictive tool.
Circulating Levels of the Short-Chain Fatty Acid Acetate Mediate the Effect of the Gut Microbiome on Visceral Fat
Authors: Nogal Ana , Louca Panayiotis , Zhang Xinyuan , Wells Philippa M. , Steves Claire J. , Spector Tim D. , Falchi Mario , Valdes Ana M. , Menni Cristina 
Published: July 2021

BackgroundAcetate is a short-chain fatty acid (SCFA) produced by gut bacteria, which has been implicated in cardio-metabolic health. Here we examine the relationships of circulating acetate levels with gut microbiome composition and diversity and with visceral fat in a large population-based cohort.ResultsMicrobiome alpha-diversity was positively correlated with circulating acetate levels (Shannon, Beta [95%CI] = 0.12 [0.06, 0.18],P= 0.002) after adjustment for covariates. Six serum acetate-associated bacterial genera were also identified, including positive correlations withCoprococcus,Barnesiella,Ruminococcus, andRuminococcaceae NK4A21and negative correlations were observed withLachnoclostridiumandBacteroides.We also identified a correlation between visceral fat and serum acetate levels (Beta [95%CI] = −0.07 [−0.11, −0.04],P= 2.8 × 10–4) and between visceral fat andLachnoclostridium(Beta [95%CI] = 0.076 [0.042, 0.11],P= 1.44 × 10–5). Formal mediation analysis revealed that acetate mediates ∼10% of the total effect ofLachnoclostridiumon visceral fat. The taxonomic diversity showed thatLachnoclostridiumandCoprococcuscomprise at least 18 and 9 species, respectively, including novel bacterial species. By predicting the functional capabilities, we found thatCoprococcusspp. present pathways involved in acetate production and metabolism of vitamins B, whereas we identified pathways related to the biosynthesis of trimethylamine (TMA) and CDP-diacylglycerol inLachnoclostridiumspp.ConclusionsOur data indicates that gut microbiota composition and diversity may influence circulating acetate levels and that acetate might exert benefits on certain cardio-metabolic disease risk by decreasing visceral fat.Coprococcusmay play an important role in host health by its production of vitamins B and SCFAs, whereasLachnoclostridiummight have an opposing effect by influencing negatively the circulating levels of acetate and being involved in the biosynthesis of detrimental lipid compounds.
Utility of Huntington's Disease Assessments by Disease Stage: Floor/Ceiling Effects
Authors: Abreu Daisy , Ware Jennifer , Georgiou-Karistianis Nellie , Leavitt Blair R. , Fitzer-Attas Cheryl J. , Lobo Raquel , Fernandes Ana Raquel , Handley Olivia , Anderson Karen E. , Stout Julie C. , Sampaio Cristina 
Published: July 2021

Introduction: An understanding of the clinimetric properties of clinical assessments, including their constraints, is critical to sound clinical study and trial design. Utilizing data from Enroll-HD—a global, prospective HD observational study and clinical research platform—we examined several well-established HD clinical assessments across all stages of disease for evidence of instrument constraints, specifically floor/ceiling effects, to inform selection of appropriate instruments for use in future studies/trials and identify gaps in instrument utility over the life-course of the disease.Material and Methods: Analyzing publicly available data from 6,614 HD gene-expansion carriers (HDGECs), we grouped participants into deciles based on baseline CAP score, which ranged from 26 to 229. We used descriptive statistics to characterize data distribution for 25 outcome measures (encompassing motor, function, cognition, and psychiatric/behavioral domains) in each CAP decile. A skewness statistic threshold of ±2 was defined a priori to indicate floor/ceiling effects.Results: We found evidence of floor/ceiling effects in the early premanifest stages of disease for most motor and function assessments (e.g., TMS, TFC) and select cognitive tasks (MMSE, Trail Making tests). Other cognitive assessments, and the HADS-SIS scales, performed well ubiquitously, with no evidence of floor/ceiling effects at any disease stage. Floor/ceiling effects were evident at every disease stage for certain assessments, including PBA-s measures. Ceiling effects were apparent for DCL from onset stages onwards, as expected.Discussion: Developing instruments sensitive to subtle differences in performance at the earlier stages of the disease spectrum, particularly in motor and function domains, is warranted.
Force-Control vs. Strength Training: The Effect on Gait Variability in Stroke Survivors
Authors: Patel Prakruti , Casamento-Moran Agostina , Christou Evangelos A. , Lodha Neha 
Published: July 2021

Purpose:Increased gait variability in stroke survivors indicates poor dynamic balance and poses a heightened risk of falling. Two primary motor impairments linked with impaired gait are declines in movement precision and strength. The purpose of the study is to determine whether force-control training or strength training is more effective in reducing gait variability in chronic stroke survivors.Methods:Twenty-two chronic stroke survivors were randomized to force-control training or strength training. Participants completed four training sessions over 2 weeks with increasing intensity. The force-control group practiced increasing and decreasing ankle forces while tracking a sinusoid. The strength group practiced fast ankle motor contractions at a percentage of their maximal force. Both forms of training involved unilateral, isometric contraction of the paretic, and non-paretic ankles in plantarflexion and dorsiflexion. Before and after the training, we assessed gait variability as stride length and stride time variability, and gait speed. To determine the task-specific effects of training, we measured strength, accuracy, and steadiness of ankle movements.Results:Stride length variability and stride time variability reduced significantly after force-control training, but not after strength training. Both groups showed modest improvements in gait speed. We found task-specific effects with strength training improving plantarflexion and dorsiflexion strength and force control training improving motor accuracy and steadiness.Conclusion:Force-control training is superior to strength training in reducing gait variability in chronic stroke survivors. Improving ankle force control may be a promising approach to rehabilitate gait variability and improve safe mobility post-stroke.
A Deep-Learning Model With the Attention Mechanism Could Rigorously Predict Survivals in Neuroblastoma
Authors: Feng Chenzhao , Xiang Tianyu , Yi Zixuan , Meng Xinyao , Chu Xufeng , Huang Guiyang , Zhao Xiang , Chen Feng , Xiong Bo , Feng Jiexiong 
Published: July 2021

BackgroundNeuroblastoma is one of the most devastating forms of childhood cancer. Despite large amounts of attempts in precise survival prediction in neuroblastoma, the prediction efficacy remains to be improved.MethodsHere, we applied a deep-learning (DL) model with the attention mechanism to predict survivals in neuroblastoma. We utilized 2 groups of features separated from 172 genes, to train 2 deep neural networks and combined them by the attention mechanism.ResultsThis classifier could accurately predict survivals, with areas under the curve of receiver operating characteristic (ROC) curves and time-dependent ROC reaching 0.968 and 0.974 in the training set respectively. The accuracy of the model was further confirmed in a validation cohort. Importantly, the two feature groups were mapped to two groups of patients, which were prognostic in Kaplan-Meier curves. Biological analyses showed that they exhibited diverse molecular backgrounds which could be linked to the prognosis of the patients.ConclusionsIn this study, we applied artificial intelligence methods to improve the accuracy of neuroblastoma survival prediction based on gene expression and provide explanations for better understanding of the molecular mechanisms underlying neuroblastoma.
Prognostic Value of Regression Rate of Plasma EBV DNA After Induction Chemotherapy for Stage II-IVA Nasopharyngeal Carcinoma
Authors: Peng Hao , Chen Bin-bin , Wang Xiao-hui , Mo Yun-Xian , Han Fei 
Published: July 2021

Background/ObjectiveWe aimed to explore the prognostic value of regression rate (RR) of plasma Epstein–Barr virus (EBV) DNA after induction chemotherapy (IC) in patients with stages II–IVA nasopharyngeal carcinoma (NPC).MethodsEligible patients receiving IC followed by concurrent chemoradiotherapy were included. The cut-off value of pre-treatment EBV DNA (pre-IC DNA) and RR were identified by receiver operating curve (ROC). Recursive partitioning analysis (RPA) was applied to create new staging. Harrell’s c-index and time-independent ROC were employed to compare different RPA staging.ResultsIn total, 1,184 patients were included. The cut-off values of pre-IC DNA and RR were 16,200 copies/ml and 95.127% for patients receiving two cycles, and 5,520 copies/ml and 99.994% for those receiving three cycles. Notably, we only focused on patients receiving two cycles of IC. Patients with a RR &gt;95.127% had significantly better 5-year overall survival (OS) than those with a RR ≤95.127% (86.2% vs. 54.3%, P &lt;0.001). Then, RPA1 (pre-IC DNA + TNM staging + RR) and RPA2 (pre-IC DNA + TNM staging + post-IC EBV DNA [post-IC DNA]) staging systems were created. RPA1 staging achieved stronger power in OS prediction than RPA2 staging and TNM staging (c-index: 0.763 [0.714–0.812] vs. 0.735 [0.684–0.786] vs. 0.677 [0.604–0.749]; AUC: 0.736 vs. 0.714 vs. 0.628), indicating that RR had stronger prognostic power than post-IC DNA. Moreover, patients with stages III–IVRPA1 could benefit from high concurrent cumulative platinum dose (≥160 mg/m2).ConclusionRR in conjunction with current TNM staging could better conduct risk stratification, prognosis prediction and help to guide precise concurrent chemotherapy.
Congenital Heart Diseases Impair Female Fertility
Authors: Chien Shao-Ju , Lin Ying-Jui , Lo Mao-Hung , Huang Chien-Fu , Yang Yao-Hsu 
Published: July 2021

Background: The objective of this research was to evaluate the fertility of Taiwanese women with diagnoses of congenital heart diseases (CHDs). The study also investigated how different forms of CHDs may have variously influenced fertility.Methods: We directed this nationwide, population-based and retrospective matched-cohort research by using data from the Taiwan National Health Insurance Research Database. The CHD group (n = 6602) included women with congenital structural heart diseases, aged 16–45 years in 2000. The non-CHD group (n = 6602) was matched according to urbanization and income. The outcomes, involving live birth, abortion, and fertility rates, were followed until the end of 2013. Poisson regression was used to evaluate the incidence rate ratios (IRRs).Results: The CHDs had an inferior rate of live births (IRR 0.74 [95% CI 0.71–0.78]) than the non-CHD group. There was also a lower fertility rate in the CHD group (IRR 0.81 [95% CI 0.78–0.84]) than the non-CHD group. Abortion rates between the two groups were similar.Conclusion: Congenital structural heart disease compromises female fertility, even among patients with simple forms of CHDs. It is suggested that pregnant patients with CHDs are early appeared to and advised personally with multidisciplinary care to improve their outcomes.
Mechanism of Anti-Inflammatory and Antibacterial Effects of QingXiaoWuWei Decoction Based on Network Pharmacology, Molecular Docking and In Vitro Experiments
Authors: Zhang Qian , Li Xue , Li Jun , Hu Yuxia , Liu Jing , Wang Fang , Zhang Wei , Chang Fuhou 
Published: July 2021

Background and Aim: QingXiaoWuWei Decoction (QXWWD) is a traditional Chinese medicine that is commonly used in clinical settings to treat inflammatory and bacterial diseases. However, there is still a lot to learn about its molecular mechanism. A network pharmacology approach was applied to investigate the pharmacological mechanisms of QXWWD in inflammation treatment.Methods: The basic mechanisms involved in the anti-inflammatory and antibacterial potentials of QXWWD were identified using network pharmacology and molecular docking. The principal components of QXWWD were identified by the HPLC-Q-Exactive-MS method. The antibacterial bioactivity of QXWWD was further investigated using the Kirby-Bauer disc diffusion method and the determination of the minimum inhibitory concentration. The anti-inflammatory activity of QXWWD was evaluated using mice ear swelling test, RAW264.7 cell culture, and pro-inflammatory cytokines measurement. Skin irritation and HE staining were employed to evaluate the safety of QXWWD topical use and to depict the drug’s potential therapeutic function. The hub genes and signaling pathways associated with inflammatory and bacterial diseases were validated by western blot in addition to biochemical and pathological markers.Results: Our findings revealed that the ethanolic extract of QXWWD had a strong inhibitory effect against Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae. Meanwhile, QXWWD was potentially effective in suppressing ear swelling, elevated white blood cell counts, and the TNF-α, IL-1, and IL-6 levels. According to skin irritation, QXWWD was found to be safe when tested for topical application. The results of HE staining showed that the possible therapeutic role of QXWWD was related to the change in skin microstructure. Also, the network pharmacology, molecular docking as well as Q-Exactive-MS and HPLC analysis suggested that the synergistic effect of quercetin, luteolin and other ingredients could serve as main contributor of QXWWD for its anti-inflammatory and antibacterial activities. Moreover, the JUN, MAPK1, RELA, NFKBIA, MYC, and AKT1 were the potential identified key targets, and MAPK/PI3K/Akt was among the possibly involved signaling pathways in the anti-inflammatory and antibacterial activities of QXWWD.Conclusions: From a therapeutic standpoint, QXWWD may be a promising antibacterial and anti-inflammatory agent for the treatment of bacterial, acute, and chronic dermatitis.
Magnitude and Predictors of Health Care Workers Depression During the COVID-19 Pandemic: Health Facility-Based Study in Eastern Ethiopia
Authors: Yadeta Tesfaye Assebe , Dessie Yadeta , Balis Bikila 
Published: July 2021

Background:Depression of health care workers was related to work absences, resignations, and poor work performance, affecting the quality of patient care and the health care system. The Coronavirus disease pandemic has had an effect on the mental health of health care workers. Health care workers are facing challenges that can be stressful, overwhelming, and cause strong emotions, may put them at higher risk to develop depression. There is limited evidence that assesses health care workers' depression and its associated factors in the study area during the Coronavirus disease pandemic. Therefore this study aimed to assess depression and associated factors among health care workers in eastern Ethiopia.Method:The cross-sectional study design was conducted from October 26th to November 15, 2020. A total of 265 health care workers from 10 health facilities participated. Patient Health Questionnaire was used for the collection of depressive symptoms. The data were analyzed by using STATA version 14 software. To assess the association between depression and the predictors Adjusted Odds Ratio along with a 95% confidence interval was estimated by using logistic regression analysis. A statistical significance was declared atp-value ≤ 0.05.Results:Of the total 265 study participant, 176 (66.4%) and 95% CI: 60.4%, 71.8% of them reported depressive symptoms. Of 176 reported symptoms of depression 27.9, 24.1, 9.4, 3.7, and 1.1% were had minimal, mild, moderate, moderate-severe, and severe depressive symptoms respectively. The multivariable logistic regression analysis revealed the odds of depression were 2.34 times higher among female participants compared to male participants (AOR: 2.34, 95%CI: 1.09-5.02). In addition, the odds of depression for participants who perceived susceptibility to COVID-19 was 4.05 times higher among their counterpart (AOR: 4.05, 95%CI: 1.12-14.53).Conclusions:Health care workers who experienced depression in the study was high. Health care workers' mental health needs to be protected during the COVID-19 pandemic. Female health care workers and health care workers perceived susceptibility of COVID-19 need attention.
Parent/Carer-Reported Experience of Shared Decision Making at Child and Adolescent Mental Health Services: A Multilevel Modelling Approach
Authors: Liverpool Shaun , Hayes Daniel , Edbrooke-Childs Julian 
Published: July 2021

Background and Objective: Shared decision making (SDM) has been associated with positive outcomes at child and adolescent mental health services (CAMHS). However, implementing SDM is sometimes challenging. Understanding the factors associated with parent/carer experience of SDM could provide empirical evidence to support targeted efforts to promote SDM. This study aimed to explore the frequency of parent/carer-reported experience of SDM and examine possible associations between SDM and clinician's perceptions of the (a) children's and young people's psychosocial difficulties, (b) additional complex problems, and (c) impact of the psychosocial difficulties.Methods: Secondary analysis was conducted on administrative data collected from CAMHS between 2011 and 2015. The sample was composed of 3,175 cases across 58 sites in England. Frequencies were recorded and associations were explored between clinician-reported measures and parent/carer-reported experiences of SDM using a two-level mixed-effect logistic regression analytic approach.Results: Almost 70% of parents/carers reported experiencing higher levels of SDM. Individual-level variables in model one revealed statistically significant (p &lt;0.05) associations suggesting Asian parents/carers (OR = 1.95, 95% CI [1.4, 2.73]) and parents/carers having children with learning difficulties (OR = 1.45, 95% CI [1.06, 1.97]) were more likely to report higher levels of SDM. However, having two parents/carers involved in the child's care and treatment decisions (OR = 0.3, 95% CI [0.21, 0.44]) and being a parent/carer of a child or young person experiencing conduct problems (OR = 0.78, 95% CI [0.63, 0.98]) were associated with lower levels of SDM. When adjusting for service level data (model two) the presence of conduct problems was the only variable found to be significant and predicted lower levels of SDM (OR = 0.29, 95% CI [0.52, 0.58]).Conclusion: Multilevel modelling of CAMHS administrative data may help identify potential influencing factors to SDM. The current findings may inform useful models to better predict and support SDM.