bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of prostate cancer in Algerian population
Authors: Medjani Somia , Chellat-Rezgoune Djalila , Kezai Taher , Chidekh Mohammed , Abadi Noureddine , Satta Dalila 
Published: September 2020

AbstractBackgroundProstate cancer is the most common cancer in the world, and its etiology involves the interaction of genetic and environmental factors. Interindividual differences observed in the metabolism of xenobiotics may be due to polymorphisms of genes encoding the detoxification enzymes. This genetic variability seems to be associated with differences in susceptibility to certain types of cancers, including prostate cancer. Our study has been made in order to investigate a possible genetic predisposition to prostate cancer in an Algerian population, through the analysis of genetic polymorphisms of three enzymes metabolizing xenobiotics namelycytochrome P450 (CYP) 1A1, glutathione S-transferase mu 1(GSTM1) andGST theta 1 (GSTT1).MethodsThe current case–control study included 101 prostate cancer patients and 101 healthy controls. Genotyping ofCYP1A1 T3801Cpolymorphisms andGSTM1/GSTT-nullwas made, respectively, by PCR-RFLP and multiplex PCR.ResultsNo significantly positive associations were found for theCYP1A1 T3801C[p = 0.71, OR = 1.23 (0.56–2.72)] andGSTM1-null[p = 0.26, OR = 1.37 (0.76–2.4)] polymorphisms and prostate cancer susceptibility. However, we detect a highly significant association betweenGSTT1-nullgenotype [p = 0.03, OR = 2.03 (1.06–3.99)],GSTM1/GSTT1-double null genotype [p = 0.027, OR = 2.6; CI (1.07–6.5)] and prostate cancer risk. Furthermore, no statistically significant differences between the studied polymorphisms and tumor parameters (the Gleason score and clinical stages of aggressiveness) at diagnosis of PCa.ConclusionsThe risk of developing prostate cancer in Algeria does not appear to be associated withCYP1A1 T3801Cgenotypes andGSTM1-null, butGSTT1-nullandGSTM1/GSTT1-double null genotypes increased the risk of prostate cancer.
Computationally identifying hot spots in protein-DNA binding interfaces using an ensemble approach
Authors: Pan Yuliang , Zhou Shuigeng , Guan Jihong 
Published: September 2020

AbstractBackgroundProtein-DNA interaction governs a large number of cellular processes, and it can be altered by a small fraction of interface residues, i.e., the so-calledhot spots, which account for most of the interface binding free energy. Accurate prediction of hot spots is critical to understand the principle of protein-DNA interactions. There are already some computational methods that can accurately and efficiently predict a large number of hot residues. However, the insufficiency of experimentally validated hot-spot residues in protein-DNA complexes and the low diversity of the employed features limit the performance of existing methods.ResultsHere, we report a new computational method for effectively predicting hot spots in protein-DNA binding interfaces. This method, calledPreHots(the abbreviation ofPredictingHotspots), adopts an ensemble stacking classifier that integrates different machine learning classifiers to generate a robust model with 19 features selected by a sequential backward feature selection algorithm. To this end, we constructed two new and reliable datasets (one benchmark for model training and one independent dataset for validation), which totally consist of 123 hot spots and 137 non-hot spots from 89 protein-DNA complexes. The data were manually collected from the literature and existing databases with a strict process of redundancy removal. Our method achieves a sensitivity of 0.813 and an AUC score of 0.868 in 10-fold cross-validation on the benchmark dataset, and a sensitivity of 0.818 and an AUC score of 0.820 on the independent test dataset. The results show that our approach outperforms the existing ones.ConclusionsPreHots, which is based on stack ensemble of boosting algorithms, can reliably predict hot spots at the protein-DNA binding interface on a large scale. Compared with the existing methods,PreHotscan achieve better prediction performance. Both the webserver ofPreHotsand the datasets are freely available at:http://dmb.tongji.edu.cn/tools/PreHots/.
Multi-omics profiling reveals microRNA-mediated insulin signaling networks
Authors: Lin Yang-Chi-Dung , Huang Hsi-Yuan , Shrestha Sirjana , Chou Chih-Hung , Chen Yen-Hua , Chen Chi-Ru , Hong Hsiao-Chin , Li Jing , Chang Yi-An , Chiew Men-Yee , Huang Ya-Rong , Tu Siang-Jyun , Sun Ting-Hsuan , Weng Shun-Long , Tseng Ching-Ping , Huang Hsien-Da 
Published: September 2020

Abstract
Background
MicroRNAs (miRNAs) play a key role in mediating the action of insulin on cell growth and the development of diabetes. However, few studies have been conducted to provide a comprehensive overview of the miRNA-mediated signaling network in response to glucose in pancreatic beta cells. In our study, we established a computational framework integrating multi-omics profiles analyses, including RNA sequencing (RNA-seq) and small RNA sequencing (sRNA-seq) data analysis, inverse expression pattern analysis, public data integration, and miRNA targets prediction to illustrate the miRNA-mediated regulatory network at different glucose concentrations in INS-1 pancreatic beta cells (INS-1), which display important characteristics of the pancreatic beta cells.

Results
We applied our computational framework to the expression profiles of miRNA/mRNA of INS-1, at different glucose concentrations. A total of 1437 differentially expressed genes (DEGs) and 153 differentially expressed miRNAs (DEmiRs) were identified from multi-omics profiles. In particular, 121 DEmiRs putatively regulated a total of 237 DEGs involved in glucose metabolism, fatty acid oxidation, ion channels, exocytosis, homeostasis, and insulin gene regulation. Moreover, Argonaute 2 immunoprecipitation sequencing, qRT-PCR, and luciferase assay identified Crem, Fn1, and Stc1 are direct targets of miR-146b and elucidated that miR-146b acted as a potential regulator and promising target to understand the insulin signaling network.

Conclusions
In this study, the integration of experimentally verified data with system biology framework extracts the miRNA network for exploring potential insulin-associated miRNA and their target genes. The findings offer a potentially significant effect on the understanding of miRNA-mediated insulin signaling network in the development and progression of pancreatic diabetes.
A multiple T cell epitope comprising DNA vaccine boosts the protective efficacy of Bacillus Calmette–Guérin (BCG) against Mycobacterium tuberculosis
Authors: Maurya Sudeep Kumar , Aqdas Mohammad , Das Deepjyoti Kumar , Singh Sanpreet , Nadeem Sajid , Kaur Gurpreet , Agrewala Javed Naim 
Published: September 2020

AbstractBackgroundApproximately 80% - 90% of individuals infected with latentMycobacterium tuberculosis (Mtb)remain protected throughout their life-span. The release of unique, latent-phase antigens are known to have a protective role in the immune response againstMtb. Although the BCG vaccine has been administered for nine decades to provide immunity againstMtb, the number of TB cases continues to rise, thereby raising doubts on BCG vaccine efficacy. The shortcomings of BCG have been associated with inadequate processing and presentation of its antigens, an inability to optimally activate T cells againstMtb, and generation of regulatory T cells. Furthermore, BCG vaccination lacks the ability to eliminate latentMtbinfection. With these facts in mind, we selected six immunodominant CD4 and CD8 T cell epitopes ofMtbexpressed during latent, acute, and chronic stages of infection and engineered a multi-epitope-based DNA vaccine (C6).ResultBALB/c mice vaccinated with the C6 construct along with a BCG vaccine exhibited an expansion of both CD4 and CD8 T cell memory populations and augmented IFN-γ and TNF-α cytokine release. Furthermore, enhancement of dendritic cell and macrophage activation was noted. Consequently, illustrating the elicitation of immunity that helps in the protection againstMtbinfection; which was evident by a significant reduction in theMtbburden in the lungs and spleen of C6 + BCG administered animals.ConclusionOverall, the results suggest that a C6 + BCG vaccination approach may serve as an effective vaccination strategy in future attempts to control TB.
Infection-provoked reversible posterior leukoencephalopathy syndrome in an adult with nephrotic syndrome: a case report
Authors: Li Kuan-Ying , Chien Ching-Fang , Tsai Chin-Ling , Chen Huang-Chi , Wu Meng-Ni , Lai Chiou-Lian , Liou Li-Min 
Published: September 2020

Abstract
Background
Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare and heterogeneous clinico-neuroradiological syndrome characterized by headache, altered mental status, seizures, and visual disturbances. Hypertension and immunosuppression are two of the main factors that predispose an individual to RPLS. However, RPLS can develop when no major risk factors are present. RPLS has been reported in pediatric nephrotic patients, but rarely in adults.

Case presentation
A 42-year-old Asian woman with nephrotic syndrome presented with seizures, headaches, and nausea. Her blood pressure was controlled, and no immunosuppressants had been prescribed. All symptoms and tests indicated RPLS following infection with pneumonia, which was successfully treated by immediate administration antibiotic and anti-epileptic medications. Seizures did not recur during a 2-year follow-up period.

Conclusions
When patients with nephrotic syndrome have an infection, RPLS symptoms should be investigated thoroughly. With early diagnosis and appropriate treatment of RPLS, morbidity and mortality can be prevented.
Relationship between the invasion of lymphocytes and cytokines in the tumor microenvironment and the interval after single brachytherapy hypofractionated radiotherapy and conventional fractionation radiotherapy in non-small cell lung Cancer
Authors: Li Lin , Yue Hong Cheng , Han Yun Wei , Liu Wei , Xiong Liang Geng , Zhang Jian Wen 
Published: September 2020

Abstract
Background
The effect of brachytherapy on lymphocytes and cytokines in the tumor microenvironment is unclear. This study aimed to analyze the relationship between the invasion of lymphocytes and cytokines in the tumor microenvironment and the interval after single brachytherapy hypofractionated radiotherapy (SBHFRT) and conventional fractionation radiotherapy (CFRT) in non-small cell lung cancer (NSCLC).

Methods
Lewis tumor-bearing mice were randomly divided into control, CFRT, and SBHFRT groups. On days 7 and 14 after radiation, the expression levels of CD86+, CD4+, CD8+, and Foxp3+ cells, and levels of Ki-67+ protein were detected by immunohistochemistry, and the tumor necrosis rate was calculated. Following this, the levels of interleukin-10 (IL-10), IL-12, and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay. The apoptosis rate was evaluated via flow cytometry. The tumor volume and tumor growth inhibition rate (TGIR) were calculated on day 14. Tumor metabolism was assessed via 18F-FDG micropositron emission tomography/computer tomography.

Results
The tumor volume reduced by 22.0% and TGIR increased by 92.2% (p < 0.05) in the SBHFRT group. Further, on days 7 and 14 after radiation, tumor metabolism, Ki-67+ and Foxp3+ expression levels, and IL-10 levels were lower, and tumor necrosis and apoptosis rates; CD86+, CD4+, and CD8+ expression levels; and IL-12 and IFN-γ levels were higher in the SBHFRT group than in the CFRT group, particularly on day 7.

Conclusion
SBHFRT could lead to more accumulation of dendritic cells, anti-tumor lymphocytes, and cytokines, and further reduce the aggregation of immunosuppressive lymphocytes and cytokines in the tumor microenvironment compared with CFRT, and the difference was the most obvious on day 7 after radiation. The clinical significance of the findings remains to be further verified.
Effect of the electrode array-retina gap distance on visual function in patients with the Argus II retinal prosthesis
Authors: Naidu Abhishek , Ghani Nimra , Yazdanie Mohammad Saad , Chaudhary Khurram 
Published: September 2020

Abstract
Background
Post-implantation visual outcomes in patients with the Argus II Retinal Prosthesis is dependent on a multitude of factors including the positioning of the electrode array on the retina. The purpose of this study is to determine whether the average electrode array-retina gap distance correlates with objective visual function outcomes and sensitivity detection thresholds in patients implanted with the Argus II Retinal Prosthesis.

Methods
Five patients with implantation of the Argus II Retinal Prosthesis were enrolled in this single-institution retrospective study. Patient demographics were collected from medical records. Visual function data (Square Localization [SL] and Direction of Motion [DOM]) and Optical Coherence Tomography (Cirrus HD-OCT) images were extracted retrospectively from the Argus II Retinal Prosthesis Post-Approval study. Visual function tests were performed with the device OFF and ON at each study visit. Electrode array-retina gap distances were measured at each of the array’s 60 electrodes using the Cirrus HD-OCT software in both the nasotemporal and superoinferior planes. Data was obtained at baseline, and post-operative month 1, month 3, month 6, and year 1. Sensitivity detection thresholds were obtained at the initial programming visit and each reprogramming session.

Results
Three patients performed significantly better in SL visual function testing with the device ON. Patients that worsened in visual function testing with the device ON in both SL and DOM testing had a statistically significant decrease in performance. The electrode array-retina gap distance was found to effect performance in SL testing in a patient-dependent manner. No effect was found between the electrode-array gap distance and DOM testing or sensitivity detection threshold.

Conclusion
Our results demonstrate that the electrode array-retina gap distance may affect visual function outcomes in SL testing in certain patients with the Argus II Retinal Prosthesis, and the direction and magnitude of this effect is likely patient-dependent. Furthermore, complete apposition between the electrode array and retina may not always be necessary to achieve optimal visual outcomes.
Testing an individualized digital decision assist system for the diagnosis and management of mental and behavior disorders in children and adolescents
Authors: Clausen Carolyn E. , Leventhal Bennett L. , Nytrø Øystein , Koposov Roman , Westbye Odd Sverre , Røst Thomas Brox , Bakken Victoria , Koochakpour Kaban , Thorvik Ketil , Skokauskas Norbert 
Published: September 2020

Abstract
Background
Nearly half of all mental health disorders develop prior to the age of 15. Early assessments, diagnosis, and treatment are critical to shortening single episodes of care, reducing possible comorbidity and long-term disability. In Norway, approximately 20% of all children and adolescents are experiencing mental health problems. To address this, health officials in Norway have called for the integration of innovative approaches. A clinical decision support system (CDSS) is an innovative, computer-based program that provides health professionals with clinical decision support as they care for patients. CDSS use standardized clinical guidelines and big data to provide guidance and recommendations to clinicians in real-time. IDDEAS (Individualised Digital DEcision Assist System) is a CDSS for diagnosis and treatment of child and adolescent mental health disorders. The aim of IDDEAS is to enhance quality, competency, and efficiency in child and adolescent mental health services (CAMHS).

Methods/design
IDDEAS is a mixed-methods innovation and research project, which consists of four stages: 1) Assessment of Needs and Preparation of IDDEAS; 2) The Development of IDDEAS CDSS Model; 3) The Evaluation of the IDDEAS CDSS; and, 4) Implementation & Dissemination. Both qualitative and quantitative methods will be used for the evaluation of IDDEAS CDSS model. Child and adolescent psychologists and psychiatrists (n = 30) will evaluate the IDDEAS` usability, acceptability and relevance for diagnosis and treatment of attention-deficit/hyperactivity disorder.

Discussion
The IDDEAS CDSS model is the first guidelines and data-driven CDSS to improve efficiency of diagnosis and treatment of child and adolescent mental health disorders in Norway. Ultimately, IDDEAS will help to improve patient health outcomes and prevent long-term adverse outcomes by providing each patient with evidence-based, customized clinical care.

Trial registration
ISRCTN, ISRCTN12094788. Ongoing study, registered prospectively 8 April 2020 10.1186/ISRCTN12094788
Qualitative analysis of clinicians’ perspectives on the use of a computerized decision aid in the treatment of psychotic disorders
Authors: Roebroek Lukas O. , Bruins Jojanneke , Delespaul Philippe , Boonstra Albert , Castelein Stynke 
Published: September 2020

Abstract
Background
Clinical decision aids are used in various medical fields to support patients and clinicians when making healthcare decisions. Few attempts have been made to implement such tools in psychiatry. We developed Treatment E-Assist (TREAT); a routine outcome monitoring based computerized clinical decision aid, which generates personalized treatment recommendations in the care of people with psychotic disorders. The aim of this study is to investigate how TREAT is used and evaluated by clinicians and how this tool can be improved.

Methods
Clinicians working with TREAT during a clinical trial were asked to participate in semi-structured interviews. The Unified Theory of Acceptance and Use of Technology (UTAUT) was used as a sensitizing theory to structure a part of the interview questions. The transcripts were analyzed using inductive thematic analysis to uncover the main themes.

Results
Thirteen clinicians (mean age: 49) of which eight psychiatrists and five nurse practitioners, participated in this study. Eight clinicians experienced TREAT as beneficial, whereas five experienced no additional benefits. Thematic analysis revealed five themes surrounding usage and evaluation of TREAT, views on TREAT’s graphic representation of routine outcome monitoring results, guideline based treatment recommendations, contextual factors, effects on patients and effects on shared decision-making. Performance and effort expectancy were perceived as high by clinicians. The facilitating conditions were optimal and perceived social influence was low.

Conclusion
This article presents a qualitative evaluation by clinicians of a computerized clinical decision aid in psychosis care. TREAT was viewed by most clinicians as beneficial during their consultations. The graphic representation of routine outcome monitoring results was well-appreciated and provided input to discuss treatment planning with patients. The treatment recommendations did not change most treatment decisions but supported clinical reasoning. However, some clinicians were unconvinced about TREAT’s benefits. The delivery, applicability and the availability of resources require improvement to increase TREAT’s efficacy. Not all patients responded well to TREAT but the observed facilitation of shared decision-making is promising. All four predictors of the Unified Theory of Acceptance and Use of Technology were positively evaluated by the majority of clinicians.
Increased frequency of intentional weight loss associated with reduced mortality: a prospective cohort analysis
Authors: Willis Erik A. , Huang Wen-Yi , Saint-Maurice Pedro F. , Leitzmann Michael F. , Salerno Elizabeth A. , Matthews Charles E. , Berndt Sonja I. 
Published: September 2020

Abstract
Background
Due to the high prevalence of obesity and the difficulty in maintaining weight loss, repeated bouts of weight loss are a common occurrence. However, there are inconsistencies in epidemiological studies regarding repetitive weight fluctuations being associated with increased risk of mortality. Therefore, the purpose of this prospective cohort analysis was to determine the long-term association of the frequency of weight loss attempts on mortality.

Methods
This prospective cohort study used data collected from adult AARP members living in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, or Pennsylvania) or 2 metropolitan areas (Atlanta, Georgia, or Detroit, Michigan) and participating in the National Institutes of Health–AARP Diet and Health Study between 2004 and 2006. Self-reported data were analyzed for 161,738 middle-aged adults. During an average 7 years of follow-up, 21,194 deaths were recorded. Hazard ratios of all-cause, cardiovascular, and cancer mortality were estimated adjusting for demographic, lifestyle, and behavioral risk factors.

Results
Increased frequency of weight loss attempts of at least five pounds was associated with lower mortality (ptrend < 0.010). Multivariate hazard ratios (95% confidence intervals) for all-cause death among individuals who successfully attempted weight loss compared with those who did not make any attempts were 0.94 (0.90–0.98) for 1–2 attempts, 0.96 (0.91–1.01) for 3–4 attempts, 0.91 (0.85–0.96) for 5–6 attempts, 0.91 (0.85–0.98) for 7–8 attempts, 0.87 (0.80–0.95) for 9–10 attempts, and 0.88 (0.82–0.94) for 11+ attempts. Similar results were noted for men and women, participants with healthy weight and overweight/obesity, and even among those who gained weight over time. Protective associations were also observed for deaths due to cardiovascular disease and cancer.

Conclusions
Increased frequency of intentionally losing at least five pounds in mid-life was associated with a lower risk of future death. Repeated attempts with moderate amounts of weight loss may provide benefit in terms of longevity.

Trial registration number
ClinicalTrials.gov number, NCT00340015