bluuebunny/crossref_metadata_2025_split huggingface dataset:
DAB2IP Plays Important Clinical Significance and Correlates With Immune Infiltration in Renal Cell Carcinoma
Authors: Cao Haoyuan , Zhang Jiandong , Wang Wei 
Published: June 2020

Background: Disabled homolog 2-interacting protein is a new member of the Ras GTPase superfamily involved in the regulation of cell proliferation, apoptosis, and metastasis. However, the expression of disabled homolog 2-interacting protein in renal cell carcinoma, its correlation with cancer prognosis, and tumor infiltrating lymphocytes remains unclear. Methods: The expression of disabled homolog 2-interacting protein was analyzed by UALCAN database, GEPIA database and the evaluation of disabled homolog 2-interacting protein effects on clinical prognosis. Prognostic factor analysis was used to identify the correlations between disabled homolog 2-interacting protein and cancer immune infiltration via the TIMER database. In addition, COXPRESdb database was used to analyze the enrichment of disabled homolog 2-interacting protein co-expression genes. Results: Compared to the normal tissues, the messenger RNA expression levels of DAB2IP are higher in 8 while lower in 15 types of tumor tissues. Furthermore, disabled homolog 2-interacting protein has high expression in kidney chromophobe and low expression in both kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. The messenger RNA expression levels of disabled homolog 2-interacting protein decrease gradually due to the increasing tumor staging which positively correlates with disease-free survival and overall survival in both kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. The expression levels of disabled homolog 2-interacting protein also positively correlate with the tumor purity of kidney chromophobe, kidney renal clear cell carcinoma, and kidney renal papillary cell carcinoma samples. Besides, the expression of disabled homolog 2-interacting protein in renal cell carcinoma has negative correlation with the immune infiltration, and the immune infiltration of B cells and CD8+ T cells affects the prognosis of kidney renal papillary cell carcinoma. Enrichment analysis of disabled homolog 2-interacting protein co-expressed genes suggested that its biological role was mainly in regulating GTPase activity. Conclusions: These findings suggest that disabled homolog 2-interacting protein functions as a tumor suppressor in the progression of renal cell carcinoma, and the expression of disabled homolog 2-interacting protein is related to the immune infiltrating cells and affects the survival of renal cell carcinoma. Disabled homolog 2-interacting protein can be a novel clinical biomarker for patients with renal cell carcinoma, which also provides new insights for the future treatments of renal cell carcinoma.
Combined high-intensity interval training and green tea supplementation enhance metabolic and antioxidant status in response to acute exercise in overweight women
Authors: Ghasemi Elham , Afzalpour Mohammad Esmaeil , Nayebifar Shila 
Published: June 2020

AbstractThirty sedentary overweight women were randomly assigned to three groups (n = 10), including HIIT + green tea, HIIT + placebo and green tea. The training program included 3 sessions/week HIIT while the supplement consuming groups took 3 * 500 mg of green tea tablets/day for 10 weeks. Results indicated that 10 weeks of HIIT and green tea meaningfully pronounced baseline serum levels of SIRT1 (P ≤ 0.0001), PGC-1α (P ≤ 0.0001) and CAT (P ≤ 0.0001). In addition, significant increase was observed in three indicators in HIIT + green tea group in comparison with two other research groups. Further, the responses of SIRT1 (P ≤ 0.01) and CAT (P ≤ 0.002) increased significantly to second acute exercise in all three groups. The combination of HIIT and green tea consumption may induce increasing SIRT1 and CAT in response to acute exercise and can improve antioxidant system, body composition and VO2 max results rather than green tea and training alone, in young sedentary overweight women.
Mental health and smoking cessation—a population survey in England
Authors: Brose Leonie S. , Brown Jamie , McNeill Ann 
Published: June 2020

AbstractBackgroundTo reduce inequalities between individuals with and without mental health problems, a better understanding is required of triggers and success of quit attempts among the third of smokers with mental health problems. The aim was to assess whether there are differences by mental health status in (i) triggers for quit attempts, (ii) use of evidence-based support (iii) and quit success.MethodsMonthly cross-sectional household surveys of representative samples of the adult population in England. In 2016/2017, 40,831 adults were surveyed; 1956 who had attempted to stop smoking cigarettes in the past year were included. Logistic regressions assessed associations between mental health (ever diagnosis, past-year treatment, past-month distress), triggers, support used and quit success, adjusting for sociodemographic and smoking characteristics.ResultsConcern about future health, current health problems and expense of smoking were the most common triggers overall. For respondents with an ever diagnosis, past-year treatment or serious past-month distress, quit attempts were more frequently triggered by current health problems. Non-evidence-based support and e-cigarettes were used most often, and this did not differ by mental health status. Respondents with an ever diagnosis and moderate or serious distress were less likely to have used non-prescription nicotine replacement therapy (NRT). Respondents with past-year treatment or serious distress were more likely to have used prescription medication/behavioural support. Quit success did not differ by mental health status. Compared with non-evidence-based support, non-prescription NRT conferred no benefit. There was some evidence that prescription medication/behavioural support was beneficial (depending on outcome and adjustment, ORs ranged from 1.46, 95% CI 0.92–2.31, to 1.69, 1.01–2.86). E-cigarettes were associated with higher success rates after adjustment for different indicators of mental health (ORs ranged from 2.21, 1.64–2.98, to 2.25, 1.59–3.18).ConclusionsSmokers with mental health problems were more likely to have attempted to quit because of health problems and were more likely to have used gold standard support (medication and behavioural support) than other smokers. E-cigarettes were strongly associated with increased success and were used similarly by those with and without mental health problems, indicating that improved uptake of e-cigarettes for smoking cessation among smokers with mental health problems could help address inequalities.
COVID-19: a retrospective cohort study with focus on the over-80s and hospital-onset disease
Authors: Brill Simon E. , Jarvis Hannah C. , Ozcan Ezgi , Burns Thomas L. P. , Warraich Rabia A. , Amani Lisa J. , Jaffer Amina , Paget Stephanie , Sivaramakrishnan Anand , Creer Dean D. 
Published: June 2020

Abstract
Background
Data from the UK COVID-19 outbreak are emerging, and there are ongoing concerns about a disproportionate effect on ethnic minorities. There is very limited information on COVID-19 in the over-80s, and the rates of hospital-onset infections are unknown.

Methods
This was a retrospective cohort study from electronic case records of the first 450 patients admitted to our hospital with PCR-confirmed COVID-19, 77% of the total inpatient caseload to date. Demographic, clinical and biochemical data were extracted. The primary endpoint was death during the index hospital admission. The characteristics of all patients, those over 80 years of age and those with hospital-onset COVID-19 were examined.

Results
The median (IQR) age was 72 (56, 83), with 150 (33%) over 80 years old and 60% male. Presenting clinical and biochemical features were consistent with those reported elsewhere. The ethnic breakdown of patients admitted was similar to that of our underlying local population. Inpatient mortality was high at 38%.
Patients over 80 presented earlier in their disease course and were significantly less likely to present with the typical features of cough, breathlessness and fever. Cardiac co-morbidity and markers of cardiac dysfunction were more common, but not those of bacterial infection. Mortality was significantly higher in this group (60% vs 28%, p < 0.001). Thirty-one (7%) patients acquired COVID-19 having continuously been in hospital for a median of 20 (14, 36) days. The peak of hospital-onset infections occurred at the same time as the overall peak of admitted infections. Despite being older and more frail than those with community-onset infection, their outcomes were no worse.

Conclusions
Inpatient mortality was high, especially among the over-80s, who are more likely to present atypically. The ethnic composition of our caseload was similar to the underlying population. While a significant number of patients acquired COVID-19 while already in hospital, their outcomes were no worse.
Lower or higher HDL-C levels are associated with cardiovascular events in the general population in rural China
Authors: Yu Shasha , Guo Xiaofan , Li Guang Xiao , Yang Hongmei , Zheng Liqiang , Sun Yingxian 
Published: June 2020

Abstract
Background
The present study aims to estimate whether high-density lipoprotein cholesterol (HDL-C) is correlated with cardiovascular events (CVEs) and cardiovascular mortality (CVM) in a large sample of the general population in rural areas of China.

Methods
Adult participants (n = 10,266, age = 53.79 ± 10.49 years; 46.5% men) were enrolled from the Northeast China Rural Cardiovascular Health Study (NCRCHS). Laboratory testing, blood pressure, weight, height, and questionnaires about socioeconomic status were collected.

Results
In all, 585 nonfatal or fatal CVEs and 212 cardiovascular deaths were documented during a 4.66-year follow-up. Compared to the reference groups (HDL-C between 1.5 and 1.99 mmol/L), either lower or higher levels of HDL-C were correlated with an increased incidence of CVEs but not CVM [hazard ratio (HR) the lowest = 1.369, 95% confidence interval, 1.007–1.861; HR the highest = 1.044, 0.509–2.231]. Elevated CVM was seen in the lowest HDL-C category (1.840; 1.121–3.021).

Conclusions
Lower or higher HDL-C was associated with a higher incidence of CVEs but not CVM in the general population of rural China. Perhaps if an appropriate level of HDL-C is maintained, CVEs can be effectively prevented.
Wnt-driven LARGE2 mediates laminin-adhesive O-glycosylation in human colonic epithelial cells and colorectal cancer
Authors: Dietinger Vanessa , García de Durango Cira R. , Wiechmann Svenja , Boos Sophie L. , Michl Marlies , Neumann Jens , Hermeking Heiko , Kuster Bernhard , Jung Peter 
Published: June 2020

Abstract
Background
Wnt signaling drives epithelial self-renewal and disease progression in human colonic epithelium and colorectal cancer (CRC). Characterization of Wnt effector pathways is key for our understanding of these processes and for developing therapeutic strategies that aim to preserve tissue homeostasis. O-glycosylated cell surface proteins, such as α-dystroglycan (α-DG), mediate cellular adhesion to extracellular matrix components. We revealed a Wnt/LARGE2/α-DG signaling pathway which triggers this mode of colonic epithelial cell-to-matrix interaction in health and disease.

Methods
Next generation sequencing upon shRNA-mediated silencing of adenomatous polyposis coli (APC), and quantitative chromatin immunoprecipitation (qChIP) combined with CRISPR/Cas9-mediated transcription factor binding site targeting characterized LARGE2 as a Wnt target gene. Quantitative mass spectrometry analysis on size-fractionated, glycoprotein-enriched samples revealed functional O-glycosylation of α-DG by LARGE2 in CRC. The biology of Wnt/LARGE2/α-DG signaling was assessed by affinity-based glycoprotein enrichment, laminin overlay, CRC-to-endothelial cell adhesion, and transwell migration assays. Experiments on primary tissue, human colonic (tumor) organoids, and bioinformatic analysis of CRC cohort data confirmed the biological relevance of our findings.

Results
Next generation sequencing identified the LARGE2 O-glycosyltransferase encoding gene as differentially expressed upon Wnt activation in CRC. Silencing of APC, conditional expression of oncogenic β-catenin and endogenous β-catenin-sequestration affected LARGE2 expression. The first intron of LARGE2 contained a CTTTGATC motif essential for Wnt-driven LARGE2 expression, showed occupation by the Wnt transcription factor TCF7L2, and Wnt activation triggered LARGE2-dependent α-DG O-glycosylation and laminin-adhesion in CRC cells. Colonic crypts and organoids expressed LARGE2 mainly in stem cell-enriched subpopulations. In human adenoma organoids, activity of the LARGE2/α-DG axis was Wnt-dose dependent. LARGE2 expression was elevated in CRC and correlated with the Wnt-driven molecular subtype and intestinal stem cell features. O-glycosylated α-DG represented a Wnt/LARGE2-dependent feature in CRC cell lines and patient-derived tumor organoids. Modulation of LARGE2/α-DG signaling affected CRC cell migration through laminin-coated membranes and adhesion to endothelial cells.

Conclusions
We conclude that the LARGE2 O-glycosyltransferase-encoding gene represents a direct target of canonical Wnt signaling and mediates functional O-glycosylation of α-dystroglycan (α-DG) in human colonic stem/progenitor cells and Wnt-driven CRC. Our work implies that aberrant Wnt activation augments CRC cell-matrix adhesion by increasing LARGE/α-DG-mediated laminin-adhesiveness.

Graphical abstract
Simulation of human gait with body weight support: benchmarking models and unloading strategies
Authors: Apte Salil , Plooij Michiel , Vallery Heike 
Published: June 2020

Abstract
Background
Gait training with partial body weight support (BWS) has become an established rehabilitation technique. Besides passive unloading mechanisms such as springs or counterweights, also active systems that allow rendering constant or modulated vertical forces have been proposed. However, only pilot studies have been conducted to compare different unloading or modulation strategies, and conducting experimental studies is costly and time-consuming. Simulation models that predict the influence of unloading force on human walking may help select the most promising candidates for further evaluation. However, the reliability of simulation results depends on the chosen gait model. The purpose of this paper is two-fold: First, using human experimental data, we evaluate the accuracy of some of the most prevalent walking models in replicating human walking under the influence of Constant-Force BWS: The Simplest Walking model (SW), the Spring-Loaded Inverted Pendulum model (SLIP) and the Muscle-Reflex (MR) gait model. Second, three realizations of BWS, based on Constant-Force (CF), Counterweight (CW) and Tuned-Spring (TS) approaches, are compared to each other in terms of their influence on gait parameters.

Methods
We conducted simulations in Matlab/Simulink to model the behaviour of each gait model under all three BWS conditions. Nine simulations were undertaken in total and gait parameter response was analysed in each case. Root mean square error (mrmse) w.r.t human data was used to compare the accuracy of gait models. The metrics of interest were spatiotemporal parameters and the vertical ground reaction forces. To scrutinize the BWS strategies, loss of dynamic similarity was calculated in terms of root mean square difference in gait dynamics (Δgd) with respect to the reference gait under zero unloading. The gait dynamics were characterized by a dimensionless number Modela-w.

Results
SLIP model showed the lowest mrmse for 6 out of 8 gait parameters and for 1 other, the mrmse value were comparable to the MR model; SW model had the highest mrmse. Out of three BWS strategies, Tuned-Spring strategies led to the lowest Δgd values.

Conclusions
The results of this work demonstrate the usefulness of gait models for BWS simulation and suggest the SLIP model to be more suitable for BWS simulations than the Simplest Walker and the Muscle-reflex models. Further, the Tuned-Spring approach appears to cause less distortions to the gait pattern than the more established Counterweight and Constant-Force approaches and merits experimental verification.
Bioactive fluorenes. Part III: 2,7-dichloro-9H-fluorene-based thiazolidinone and azetidinone analogues as anticancer and antimicrobial against multidrug resistant strains agents
Authors: Hussein Essam M. , Alsantali Reem I. , Morad Moataz , Obaid Rami J. , Altass Hatem M. , Sayqal Ali , Abourehab Mohamed A. S. , Elkhawaga Amal A. , Aboraia Ahmed S. M. , Ahmed Saleh A. 
Published: June 2020

Abstract
Background
Thiazoles, thiazolidinones and azetidinones are highly ranked amongst natural and synthetic heterocyclic derivatives due to their great pharmaceutical potential.

Results
New thiazolidinone and azetidinone class of bioactive agents based on 4-(2,7-dichloro-9H-fluoren-4-yl)thiazole moiety have been successfully synthesized. 4-(2,7-dichloro-9H-fluoren-4-yl)thiazol-2-amine was synthesized and allowed to react with various aryl/heteroaryl aldehydes to afford the corresponding Schiff base intermediates. The target thiazolidinone and azetidinone analogues have derived from Schiff bases by their reactions with thioglycolic acid and chloroacetyl chloride, respectively. The newly synthesized compounds were then evaluated for their antimicrobial activity against some multidrug resistant strains and examined for cytotoxic activity against normal lung fibroblast (WI-38), human lung carcinoma (A549), and human breast carcinoma (MDA-MB-231) cell lines to develop a novel class of fluorene-based bioactive agents. The mode of action and the binding interaction of the synthesized compound with the active sites of dihydrofolate reductase enzyme were well identified by fluorescence-activated cell sorting (FACS) analysis and molecular docking study.

Conclusion
Some of the synthesized compounds showed remarkable activity against A-549 and MDA-MB-231 when compared to Taxol, which was used as a reference drug. 2,7-dichloro-9H-fluorene-based azetidinones are more efficient as antimicrobial and anticancer agents compared to dichloro-9H-fluorene-based thiazolidinones derivatives.
Clinical characteristics and prognostic value of the KRAS G12C mutation in Chinese non-small cell lung cancer patients
Authors: Liu Si-Yang , Sun Hao , Zhou Jia-Ying , Jie Guang-Ling , Xie Zhi , Shao Yang , Zhang Xian , Ye Jun-Yi , Chen Chun-Xiang , Zhang Xu-Chao , Zhou Qing , Yang Jin-Ji , Wu Yi-Long 
Published: June 2020

Abstract
Background
The KRAS mutation is the second most common genetic variant in Chinese non-small cell lung cancer (NSCLC) patients. At the 2019th World Conference of Lung Cancer, the KRAS G12C-specific inhibitor AMG510 showed promising results in the phase I clinical trial. However, the frequency, clinical characteristics, and prognostic significance of the KRAS G12C mutation in Chinese NSCLC patients are rarely reported.

Methods
Next-generation sequencing was used to confirm the KRAS mutation status in 40,804 NSCLC patients from multiple centers (mCohort). Survival data were collected retrospectively from 1456 patients at one of the centers, the Guangdong Lung Cancer Institute (iCohort).

Results
In the mCohort, 3998 patients (9.8%) were confirmed to harbor a KRAS mutation, of whom 1179 (29.5%) had the G12C subtype. In the iCohort, 130 NSCLC patients (8.9%) had a KRAS mutation and 42 (32.3%) had the G12C subtype. The G12C subgroup included more male patients (85.2% vs 67.4%, P < 0.0001) and more smokers (76.2% vs 53.4%, P = 0.02) than did the non-G12C subgroup. Both the KRAS mutation group and KRAS G12C mutation subgroup were associated with a shorter median overall survival (OS) than wildtype tumors (15.1 vs 26.7 months, hazard ratio [HR]KRAS = 1.50, P = 0.002; 18.3 vs 26.7 months, HRG12C = 1.66, P = 0.007). In Cox regression analysis, smoking (HR = 1.39, P = 0.05) and stage IV disease (HR = 2.72, P < 0.001) remained as independent predictors of shorter OS. Both the KRAS mutation (HR = 1.30, P = 0.07) and KRAS G12C mutation (HR = 1.47, P = 0.07) reached borderline significance.

Conclusions
In the largest sample used thus for, our study found that approximately 10% of Chinese NSCLC patients had KRAS mutations. Of these, nearly 30% harbored the KRAS G12C mutation subtype, which was most common in male smokers. The KRAS G12C mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which could potentially be improved by G12C-specific inhibitors in the future.
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Low rate of high-level athletes maintained a return to pre-injury sports two years after arthroscopic treatment for femoroacetabular impingement syndrome
Authors: Abrahamson Josefin , Lindman Ida , Sansone Mikael , Öhlin Axel , Jonasson Pall , Karlsson Jón , Baranto Adad 
Published: June 2020

Abstract
Purpose
The aim was to investigate the rate of athletes still active at their pre-injury sports level two years after arthroscopic treatment for femoroacetabular impingement syndrome (FAIS), and examine this between different sports and gender, and its correlation to patient-reported outcome measures (PROMs).

Method
High-level athletes planned for arthroscopic treatment for FAIS were included prospectively in a Swedish hip arthroscopy registry between 2011 and 2017, and 717 met the inclusion criteria. Self-reported sporting activity was recorded preoperatively. The subjects answered PROMs, including the HSAS, iHOT-12 and HAGOS pre- and postoperatively.

Results
A total of 551 athletes (median age 26, interquartile range 20–34 years; 23% women) had completed follow-up PROMs, at mean 23.4 ± 7.2 months postoperatively. In total, 135 (24.5%) were active at their pre-injury level of sports at follow-up (RTSpre). Athletes ≤30 years at time of surgery (n = 366; median age 22 years) had higher rate of RTSpre (31.4%) compared with athletes > 30 years (n = 185; median age 40 years) (10.8%; p < 0.001). All athletes had improvements in iHOT-12 and HAGOS, two years postoperatively (p < 0.001), while RTSpre athletes reported significantly better PROMs, pre- and postoperatively, and had greater improvements two years postoperatively, compared with athletes not active at pre-injury level.

Conclusion
Only 25% of all high-level athletes and 31% of athletes ≤30 years were still active at their pre-injury sports level two years after arthroscopic treatment for FAIS. Athletes still active had significantly and clinically greater improvement regarding hip symptoms, function and quality of life, as compared with athletes not active at pre-injury level, two years postoperatively.
Active fault-diagnosis method using adaptive allocator and fault-tolerant adaptive control system design
Authors: Kawaguchi Natsuki , Araki Nozomu , Sato Takao , Kuroda Masaharu , Asami Toshihiko 
Published: June 2020

AbstractA new approach to the active fault diagnosis (AFD) for input redundant plants is presented in this paper. A test signal which helps the diagnosis is injected to the plant in addition to nominal control input in the AFD typically. One feature of the proposed AFD is adaptive allocation of the test signal. The adaptive allocator which distributes the test signal and injects it to the redundant actuators is introduced in this paper. A fault-diagnosis (FD) system that estimates fault location and its magnitude from adaptive parameter of the adaptive allocator is constructed with a simple neural network (NN) model. Furthermore, a A fault-tolerant adaptive control system which includes the adaptive test signal allocator is designed based on the model reference adaptive control (MRAC) technique. The adaptive laws of the adaptive allocator and controller are derived by using a suitable Lyapunov function. By performing experiments using a two-input redundant plant, we show the effectiveness and applicability of the proposed AFD and MRAC system.