bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Small-Molecule Inhibitors of SARS-CoV-2 Proteins Using a Computational and Experimental Pipeline
Authors: Lau Edmond Y. , Negrete Oscar A. , Bennett W. F. Drew , Bennion Brian J. , Borucki Monica , Bourguet Feliza , Epstein Aidan , Franco Magdalena , Harmon Brooke , He Stewart , Jones Derek , Kim Hyojin , Kirshner Daniel , Lao Victoria , Lo Jacky , McLoughlin Kevin , Mosesso Richard , Murugesh Deepa K. , Saada Edwin A. , Segelke Brent , Stefan Maxwell A. , Stevenson Garrett A. , Torres Marisa W. , Weilhammer Dina R. , Wong Sergio , Yang Yue , Zemla Adam , Zhang Xiaohua , Zhu Fangqiang , Allen Jonathan E. , Lightstone Felice C. 
Published: July 2021

A rapid response is necessary to contain emergent biological outbreaks before they can become pandemics. The novel coronavirus (SARS-CoV-2) that causes COVID-19 was first reported in December of 2019 in Wuhan, China and reached most corners of the globe in less than two months. In just over a year since the initial infections, COVID-19 infected almost 100 million people worldwide. Although similar to SARS-CoV and MERS-CoV, SARS-CoV-2 has resisted treatments that are effective against other coronaviruses. Crystal structures of two SARS-CoV-2 proteins, spike protein and main protease, have been reported and can serve as targets for studies in neutralizing this threat. We have employed molecular docking, molecular dynamics simulations, and machine learning to identify from a library of 26 million molecules possible candidate compounds that may attenuate or neutralize the effects of this virus. The viability of selected candidate compounds against SARS-CoV-2 was determined experimentally by biolayer interferometry and FRET-based activity protein assays along with virus-based assays. In the pseudovirus assay, imatinib and lapatinib had IC50 values below 10 μM, while candesartan cilexetil had an IC50 value of approximately 67 µM against Mpro in a FRET-based activity assay. Comparatively, candesartan cilexetil had the highest selectivity index of all compounds tested as its half-maximal cytotoxicity concentration 50 (CC50) value was the only one greater than the limit of the assay (&gt;100 μM).
Electroacupuncture and Transcutaneous Electrical Nerve Stimulation Induced Sensations in Bell’s Palsy Patients: A Quantitative Current Intensity Analysis
Authors: Cui Han , Yu Haibo , Huang Xingxian , Wu Lixiong , Zhong Weizheng , Gou Yanhua , Cao Xuemei , Liu Yongfeng , Hong Yuanyuan , Zhang Shaoyun , Zhan Minmin , Li Guanglin , Yang Zhuoxin 
Published: July 2021

BackgroundThe intensity of electrical acupoint stimulation such as electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS) is regulated by the observation of skin shivering or the participant’s comfort response. However, the specific intensity and spatial scope following EA or TENS stimulation are unclear.ObjectiveThis study aimed to test the stimulatory current intensities of lower and upper sensation thresholds in TENS- and EA-based treatment of Bell’s palsy patients. Also, the spatial scope of the stimulation at these current intensities was simulated and measured quantitatively.MethodsA total of 19 Bell’s palsy patients were recruited. Six acupoints on the affected side of the face were stimulated by TENS and EA successively at 30-min intervals. During the stimulation, the current intensity was regulated gradually from 0 to 20 mA, and we simultaneously measured the lower (sensory) and upper (tolerability) sensations. After the treatment by TENS and EA, the modified Chinese version of the Massachusetts General Hospital Acupuncture Sensation Scales (C-MMASS) was applied to survey the de-qi sensations during stimulation. Additionally, we analyzed the correlation between current intensities and C-MMASS and comfort scores. Finite element models were established to depict the spatial distribution of electric field gradients at the lower and upper thresholds.ResultsThe mean sensory and tolerability thresholds of TENS were 3.91–4.37 mA and 12.33–16.35 mA, respectively. The median sensory and tolerability thresholds of EA were 0.2 mA and 2.0–3.2 mA, respectively. We found a significant correlation between total C-MMASS scores and the current intensities at the tolerability threshold of TENS. The finite element model showed that the activated depths of TENS and EA at the lower threshold were 3.8 and 7 mm, respectively, whereas those at the upper threshold were both 13.8 mm. The cross-sectional diameter of the activated area during TENS was 2.5–4 times larger than that during EA.ConclusionThis pilot study provided a method for exploring the current intensity at which the de-qi sensations can be elicited by TENS or EA. The finite element analysis potentially revealed the spatial scope of the electrical stimulation at a specific current intensity.
A Clinical-Radiomic Nomogram Based on Unenhanced Computed Tomography for Predicting the Risk of Aldosterone-Producing Adenoma
Authors: He Keng , Zhang Zhao-Tao , Wang Zhen-Hua , Wang Yu , Wang Yi-Xi , Zhang Hong-Zhou , Dong Yi-Fei , Xiao Xin-Lan 
Published: July 2021

PurposeTo develop and validate a clinical-radiomic nomogram for the preoperative prediction of the aldosterone-producing adenoma (APA) risk in patients with unilateral adrenal adenoma.Patients and MethodsNinety consecutive primary aldosteronism (PA) patients with unilateral adrenal adenoma who underwent adrenal venous sampling (AVS) were randomly separated into training (n = 62) and validation cohorts (n = 28) (7:3 ratio) by a computer algorithm. Data were collected from October 2017 to June 2020. The prediction model was developed in the training cohort. Radiomic features were extracted from unenhanced computed tomography (CT) images of unilateral adrenal adenoma. The least absolute shrinkage and selection operator (LASSO) regression model was used to reduce data dimensions, select features, and establish a radiomic signature. Multivariable logistic regression analysis was used for the predictive model development, the radiomic signature and clinical risk factors integration, and the model was displayed as a clinical-radiomic nomogram. The nomogram performance was evaluated by its calibration, discrimination, and clinical practicability. Internal validation was performed.ResultsSix potential predictors were selected from 358 texture features by using the LASSO regression model. These features were included in the Radscore. The predictors included in the individualized prediction nomogram were the Radscore, age, sex, serum potassium level, and aldosterone-to-renin ratio (ARR). The model showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.900 [95% confidence interval (CI), 0.807 to 0.993], and good calibration. The nomogram still showed good discrimination [AUC, 0.912 (95% CI, 0.761 to 1.000)] and good calibration in the validation cohort. Decision curve analysis presented that the nomogram was useful in clinical practice.ConclusionsA clinical-radiomic nomogram was constructed by integrating a radiomic signature and clinical factors. The nomogram facilitated accurate prediction of the probability of APA in patients with unilateral adrenal nodules and could be helpful for clinical decision making.
Body Composition Variables as Radiographic Biomarkers of Clinical Outcomes in Metastatic Renal Cell Carcinoma Patients Receiving Immune Checkpoint Inhibitors
Authors: Martini Dylan J. , Olsen T. Anders , Goyal Subir , Liu Yuan , Evans Sean T. , Magod Benjamin , Brown Jacqueline T. , Yantorni Lauren , Russler Greta Anne , Caulfield Sarah , Goldman Jamie M. , Nazha Bassel , Kissick Haydn T. , Harris Wayne B. , Kucuk Omer , Carthon Bradley C. , Master Viraj A. , Bilen Mehmet Asim 
Published: July 2021

BackgroundImmune checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). Biomarkers for mRCC patients treated with ICI are limited, and body composition is underutilized in mRCC. We investigated the association between body composition and clinical outcomes in ICI-treated mRCC patients.MethodsWe performed a retrospective analysis of 79 ICI-treated mRCC patients at Winship Cancer Institute from 2015-2020. Baseline CT images were collected at mid-L3 and segmented using SliceOMatic v5.0 (TomoVision). Density of skeletal muscle (SM), subcutaneous fat, inter-muscular fat, and visceral fat were measured and converted to indices by dividing by height(m)2 (SMI, SFI, IFI, and VFI, respectively). Total fat index (TFI) was defined as the sum of SFI, IFI, and VFI. Patients were characterized as high versus low for each variable at gender-specific optimal cuts using overall survival (OS) as the primary outcome. A prognostic risk score was created based on the beta coefficient from the multivariable Cox model after best subset variable selection. Body composition risk score was calculated as IFI + 2*SM mean + SFI and patients were classified as poor (0-1), intermediate (2), or favorable risk (3-4). Kaplan-Meier method and Log-rank test were used to estimate OS and PFS and compare the risk groups. Concordance statistics (C-statistics) were used to measure the discriminatory magnitude of the model.ResultsMost patients were male (73%) and most received ICI as first (35%) or second-line (51%) therapy. The body composition poor-risk patients had significantly shorter OS (HR: 6.37, p&lt;0.001), PFS (HR: 4.19, p&lt;0.001), and lower chance of CB (OR: 0.23, p=0.044) compared to favorable risk patients in multivariable analysis. Patients with low TFI had significantly shorter OS (HR: 2.72, p=0.002), PFS (HR: 1.91, p=0.025), and lower chance of CB (OR: 0.25, p=0.008) compared to high TFI patients in multivariable analysis. The C-statistics were higher for body composition risk groups and TFI (all C-statistics ≥ 0.598) compared to IMDC and BMI.ConclusionsRisk stratification using the body composition variables IFI, SM mean, SFI, and TFI may be prognostic and predictive of clinical outcomes in mRCC patients treated with ICI. Larger, prospective studies are warranted to validate this hypothesis-generating data.
Effects of Pain-Reporting Education Program on Children's Pain Reports—Results From a Randomized Controlled Post-operative Pediatric Pain Trial
Authors: Zontag Dafna , Honigman Liat , Kuperman Pora , Treister Roi 
Published: July 2021

Objective: Accurate assessment of patients' pain is an essential part of adequate analgesic treatment. Although reporting pain is a complex task, limited-to-no instructions are provided to pediatric patients regarding this process. Our goal in this randomized parallel-group clinical trial (Clinicaltrial.gov study protocol number NCT04306679) was to evaluate if a training program designed to improve children's ability to understand and use pain scales in a post-surgical setting would affect their pain scores.Methods: Eligible children (aged 8–17), hospitalized for elective surgery and their parents were randomized into two groups. Pre-surgery the intervention group underwent a multi-media program aimed to teach and train how to report pain. The control group received standard pre-surgical instructions. Post-surgery, the children reported their pain on 4 pain scales. The primary outcome was the concordance between children's pain intensity scores reported on four pain scales, both in terms of within-child standard deviation and absolute difference.Results: Ninety-six children met inclusion criteria and completed the study. The trained subjects' pain reports had significantly (p = 0.002) lower within-subject standard deviation (0.41 ± 0.31) than the control group (0.67 ± 0.46). In line, regarding absolute difference, the concordance of children's pain reports was twice better in the trained group (mean difference of 0.43 ± 0.40) than in the control group (0.88 ± 0.70) (p &lt; 0.001).Discussion: Our results suggests that children's ability to report pain is a skill that can be improved. Future studies should test the potential clinical impacts of educational interventions aimed to improve pain assessment in children and adults.
T-Cell Exhaustion Status Under High and Low Levels of Hypoxia-Inducible Factor 1α Expression in Glioma
Authors: Liu Shuai , Liu Xing , Zhang Chuanbao , Shan Wei , Qiu Xiaoguang 
Published: July 2021

Background: Hypoxia-inducible factor 1α (HIF1A), the principal regulator of hypoxia, is involved in the suppression of antitumor immunity. We aimed to describe the T-cell exhaustion status of gliomas under different levels of HIF1A expression.Methods: In this study, 692 patients, whose data were collected from the Chinese Glioma Genome Atlas (CGGA) database, and 669 patients, whose data were collected from The Cancer Genome Atlas database, were enrolled. We further screened the data of a cohort of paired primary and recurrent patients from the CGGA dataset (n = 50). The abundance of immune cells was calculated using the transcriptome data. The association between HIF1A and T-cell exhaustion-related genes and immune cells was investigated.Results: According to the median value of HIF1A expression, gliomas were classified into low-HIF1A-expression and high-HIF1A-expression groups. The expression levels of PDL1 (CD274), FOXO1, and PRDM1 in the high-HIF1A-expression group were significantly higher in both glioblastoma (GBM) and lower-grade glioma. The abundance of exhausted T cells and B cells was significantly higher in the high-HIF1A-expression group, while that of macrophage, monocyte, and natural killer cell was significantly higher in the low-HIF1A-expression group in both GBM and lower-grade glioma. After tumor recurrence, the expression of HIF1A significantly increased, and the correlation between HIF1A expression levels and exhausted T cells and induced regulatory T cells became stronger.Conclusion: In diffuse gliomas, the levels of T-cell exhaustion-associated genes and the abundance of immune cells were elevated under high HIF1A expression. Reversing hypoxia may improve the efficacy of immunotherapy.
Aggression Dimensions Among Athletes Practising Martial Arts and Combat Sports
Authors: Kostorz Karolina , Sas-Nowosielski Krzysztof 
Published: July 2021

Purpose: The main aim of the research was to analyse aggression dimensions among athletes practising martial arts and combat sports.Material and Methods: There were 219 respondents. The Buss and Perry Aggression Questionnaire (BPAQ) in the Polish adaptation by Siekierka was applied.Results: Martial arts apprentices turned out to present a statistically significantly lower level of hostility (p &lt; 0.001) and of the general aggression index (p = 0.04) than combat sports athletes. It turned out that lower level of aggression was noted in female participants (physical aggression (p &lt; 0.001), verbal aggression (p = 0.004), hostility (p &lt; 0.001), and the general aggression index (p &lt; 0.001). Analysis revealed that the training experience and the training rank did not differentiated the level of the respondents' particular aggression dimensions.Conclusions: It would be advisable to perform parallel analyses in other areas of Poland and take into account the respondents' education and place of residence.
Measuring the Quality of Life in Forensic Psychiatric Hospitals
Authors: Büsselmann Michael , Titze Larissa , Lutz Maximilian , Dudeck Manuela , Streb Judith 
Published: July 2021

Background: In Germany, a large proportion of mentally ill offenders spends many years in a forensic psychiatric hospital. To ensure that the highly restrictive living conditions in these closed institutions meet patient needs, research must assess and analyze patient quality of life. For this purpose, we adapted the Measuring the Quality of Prison Life questionnaire to measure the quality of life in forensic psychiatric hospitals from the patient perspective. This study aimed to assess the reliability (internal consistency) and construct validity of the adapted questionnaire.Methods: To evaluate the questionnaire, a one-time survey was carried out at 13 forensic psychiatric hospitals in Germany. Item characteristics and internal consistency of the scale and subscales were calculated and the factor structure was tested using confirmatory factor analysis. To test of responsiveness we compared the mean quality of life between the 13 hospitals and further investigated whether the patients' evaluation of quality of life is depending on age and duration of accommodation.Results: The analysis of the psychometric properties revealed very good item characteristics and very good to excellent internal reliability. Construct validity was demonstrated. Patient's quality of life was significantly associated with age and duration of accommodation.Discussion: The adapted Measuring the Quality of Prison Life questionnaire is a reliable and valid instrument for measuring quality of life in forensic psychiatric hospitals and can be used in the future to compare hospitals and identify the strengths and weaknesses of each.
Associations Between Child Maltreatment and Depressive Symptoms Among Chinese College Students: An Analysis of Sex Differences
Authors: Chen Xiaoliang , Zhang Sheng , Huang Guoliang , Xu Yan , Li Qian , Shi Jingman , Li Wenyan , Wang Wanxin , Guo Lan , Lu Ciyong 
Published: July 2021

Background: Depressive symptoms and child maltreatment are both global public health problems among young adults. This study aimed to investigate the associations between five types of child maltreatment and depressive symptoms among Chinese college students, with a focus on potential sex differences.Methods: A cross-sectional study of a nationally representative sample of Chinese college students was conducted from March to June 2019 with a multistage, stratified cluster, random sampling method. In total, 30,179 college students from 60 colleges of 10 Chinese province-level regions completed standard questionnaires, including a history of child maltreatment and current depressive symptoms.Results: The prevalence of depressive symptoms among college students in China was 7.3%. After adjusting for control variables, physical abuse (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.17–1.23), emotional abuse (aOR = 1.21, 95% CI = 1.19–1.23), sexual abuse (aOR = 1.19, 95% CI = 1.16–1.22), physical neglect (aOR = 1.14, 95% CI = 1.12–1.16) and emotional neglect (aOR = 1.08, 95% CI = 1.07–1.09) were all positively associated with depressive symptoms. Notably, a cumulative effect of child maltreatment on depressive symptoms among Chinese college students was observed. Moreover, sex differences in the associations of emotional abuse, emotional neglect, and the number of maltreatment types with depressive symptoms were statistically significant (P &lt; 0.05). Further stratification analyses showed that female students who experienced emotional abuse and emotional neglect had a higher risk of depressive symptoms than male students, and the cumulative effect of maltreatment types was stronger for females than males.Conclusion: Five types of child maltreatment and their co-occurrence were associated with an increased risk of depressive symptoms among college students. Furthermore, the effects of emotional abuse, emotional neglect and the number of maltreatment types on depressive symptoms were stronger for females than for males. These findings can promote understanding of the effects of child maltreatment on depressive symptoms, and prevention and intervention strategies for depressive symptoms should consider the type of child maltreatment and sex differences.
From Wish to Reality: Soteria in Regular Care—Proof of Effectiveness of the Implementation of Soteria Elements in Acute Psychiatry
Authors: Wolf Theresa , Fabel Philine , Kraschewski Adrian , Jockers-Scherübl Maria C. 
Published: July 2021

Objective:This article examines the influence of the implementation of Soteria elements on coercive measures in an acute psychiatric ward after reconstruction in 2017, thereby comparing the year 2016 to the year 2019. The special feature is that this is the only acute psychiatric ward in Hennigsdorf Hospital, connected now both spatially and therapeutically to an open ward and focusing on the treatment of patients suffering from schizophrenia and schizophrenia spectrum disorders.Methods:The following parameters were examined: aggressive assaults, use of coercion (mechanical restraints), duration of treatment in open or locked ward, type of discharge, coercive medication, and dosage of applied antipsychotics. For this purpose, the data of all legally accommodated patients in the year 2016 (before the reconstruction) and 2019 (after the reconstruction) were statistically analyzed in a pre–post mirror quasi-experimental design.Results:In 2019, the criteria of the Soteria Fidelity Scale for a ward with Soteria elements were reached. In comparison to 2016 with a comparable care situation and a comparable patient clientele, there was now a significant decrease in aggressive behavior toward staff and fellow patients, a significantly reduced number of fixations, a significantly reduced overall duration of inpatient stay, and a significant increase in treatment time in the open area of our acute ward.Conclusion:The establishment of Soteria elements in the acute psychiatric ward leads to a verifiable less violent environment of care for severely ill patients and to a drastic reduction in coercive measures.
interRAI Subjective Quality of Life Scale for Mental Health and Addiction Settings: A Self-Reported Measure Developed From a Multi-National Study
Authors: Luo Hao , Hirdes Alice , Heikkilä Jyrki , De Cuyper Kathleen , Van Audenhove Chantal , Saari Margaret , Hirdes John P. 
Published: July 2021

Background: Measuring Quality of Life (QoL) in mental health using self-reported items is important for evaluating the quality of service and understanding the person's experience of the care received.Objective: The aim of this research was to develop and validate a self-reported QoL instrument for inpatient and community mental health settings.Methods: Data were collected from diverse research sites in Canada, Belgium, Russia, Finland, Brazil, and Hong Kong, using the 37-item interRAI Quality of Life Survey for Mental Health and Addictions. The survey was administrated to 2,218 participants from inpatient and community mental health settings, assisted living, and the general community. We randomly divided the sample into a training and a test sample (70 and 30%, respectively). We conducted principal component analysis (PCA) and exploratory factor analysis (EFA) using the training sample to identify potential factor structure. Confirmatory factor analysis (CFA) models were then fitted to finalize and externally validate the measurement model using training and test data, respectively.Results: PCA, EFA, and CFA of the training sample collectively suggested a 23-item scale measuring four latent constructs: well-being and hope (8 items), relationship (7 items), support (5 items), and activity (3 items). This model was supported by the CFA of the test sample. The goodness-of-fit statistics root mean square error, comparative fit index and Tucker-Lewis index were 0.03, 1.00, and 0.99, respectively. Estimated Cronbach's alpha based on the test data was 0.92. Raw Cronbach's alpha values for the subscales were 0.86 for well-being and hope, 0.86 for relationship, 0.69 for support, and 0.72 for activity.Conclusions: The interRAI SQoL-MHA scale is a valid instrument to measure QoL in mental health settings. The instrument will support the evaluation of the quality of care and can also be used for future research to produce SQoL-MHA values on a quality adjusted-life-year scale, facilitating the evaluation of various mental health interventions.