bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Machine-Learning Approach for Dynamic Prediction of Sepsis-Induced Coagulopathy in Critically Ill Patients With Sepsis
Authors: Zhao Qin-Yu , Liu Le-Ping , Luo Jing-Chao , Luo Yan-Wei , Wang Huan , Zhang Yi-Jie , Gui Rong , Tu Guo-Wei , Luo Zhe 
Published: January 2021

Background: Sepsis-induced coagulopathy (SIC) denotes an increased mortality rate and poorer prognosis in septic patients.Objectives: Our study aimed to develop and validate machine-learning models to dynamically predict the risk of SIC in critically ill patients with sepsis.Methods: Machine-learning models were developed and validated based on two public databases named Medical Information Mart for Intensive Care (MIMIC)-IV and the eICU Collaborative Research Database (eICU-CRD). Dynamic prediction of SIC involved an evaluation of the risk of SIC each day after the diagnosis of sepsis using 15 predictive models. The best model was selected based on its accuracy and area under the receiver operating characteristic curve (AUC), followed by fine-grained hyperparameter adjustment using the Bayesian Optimization Algorithm. A compact model was developed, based on 15 features selected according to their importance and clinical availability. These two models were compared with Logistic Regression and SIC scores in terms of SIC prediction.Results: Of 11,362 patients in MIMIC-IV included in the final cohort, a total of 6,744 (59%) patients developed SIC during sepsis. The model named Categorical Boosting (CatBoost) had the greatest AUC in our study (0.869; 95% CI: 0.850–0.886). Coagulation profile and renal function indicators were the most important features for predicting SIC. A compact model was developed with an AUC of 0.854 (95% CI: 0.832–0.872), while the AUCs of Logistic Regression and SIC scores were 0.746 (95% CI: 0.735–0.755) and 0.709 (95% CI: 0.687–0.733), respectively. A cohort of 35,252 septic patients in eICU-CRD was analyzed. The AUCs of the full and the compact models in the external validation were 0.842 (95% CI: 0.837–0.846) and 0.803 (95% CI: 0.798–0.809), respectively, which were still larger than those of Logistic Regression (0.660; 95% CI: 0.653–0.667) and SIC scores (0.752; 95% CI: 0.747–0.757). Prediction results were illustrated by SHapley Additive exPlanations (SHAP) values, which made our models clinically interpretable.Conclusions: We developed two models which were able to dynamically predict the risk of SIC in septic patients better than conventional Logistic Regression and SIC scores.
Alcohol-Specific Mortality in People With Epilepsy: Cohort Studies in Two Independent Population-Based Datasets
Authors: Gorton Hayley C. , Webb Roger T. , Parisi Rosa , Carr Matthew J. , DelPozo-Banos Marcos , Moriarty Kieran J. , Pickrell W. Owen , John Ann , Ashcroft Darren M. 
Published: January 2021

Objectives: The risk of dying by alcohol-specific causes in people with epilepsy has seldom been reported from population-based studies. We aimed to estimate the relative risk of alcohol-specific mortality in people with epilepsy, and the extent to which problematic alcohol use was previously identified in the patients' medical records.Method: We delineated cohort studies in two population-based datasets, the Clinical Practice Research Datalink (CPRD GOLD) in England (January 01, 2001–December 31, 2014) and the Secure Anonymised Information Linkage (SAIL) Databank in Wales (January 01, 2001–December 31, 2014), linked to hospitalization and mortality records. People with epilepsy were matched to up to 20 persons without epilepsy on gender, age (±2 years) and registered general practice. We identified alcohol-specific death from Office for National Statistics (ONS) records using specified ICD-10 codes. We further identified prescriptions, interventions and hospitalisations related to alcohol use.Results: In the CPRD GOLD, we identified 9,871 individuals in the incident epilepsy cohort and 185,800 in the comparison cohort and, in the SAIL Databank, these numbers were 5,569 and 110,021, respectively. We identified a five-fold increased risk of alcohol-specific mortality in people with epilepsy vs. those without the condition in our pooled estimate across the two datasets (deprivation-adjusted HR 4.85, 95%CI 3.46–6.79).Conclusions: People with epilepsy are at increased risk of dying by an alcohol-specific cause than those without the disorder. It is plausible that serious alcohol misuse could either contribute to the development of epilepsy or it could commence subsequent to epilepsy being diagnosed. Regardless of the direction of the association, it is important that the risk of dying as a consequence of alcohol misuse is accurately quantified in people affected by epilepsy. Systematically-applied, sensitive assessment of alcohol consumption by healthcare professionals, at opportunistic, clinical contacts, with rapid access to quality treatment services, should be mandatory and play a key role in reduction of health harms and mortality.
The Effects of Extracorporeal Shock Wave Therapy on Spastic Muscle of the Wrist Joint in Stroke Survivors: Evidence From Neuromechanical Analysis
Authors: Leng Yan , Lo Wai Leung Ambrose , Hu Chengpeng , Bian Ruihao , Xu Zhiqin , Shan Xiyao , Huang Dongfeng , Li Le 
Published: January 2021

Background: This study combined neuromechanical modeling analysis, muscle tone measurement from mechanical indentation and electrical impedance myography to assess the neural and peripheral contribution to spasticity post stroke at wrist joint. It also investigated the training effects and explored the underlying mechanism of radial extracorporeal shock wave (rESW) on spasticity.Methods: People with first occurrence of stroke were randomly allocated to rESW intervention or control group. The intervention group received one session of rESW therapy, followed by routine therapy which was the same frequency and intensity as the control group. Outcome measures were: (1) NeuroFlexor method measured neural component (NC), elastic component (EC) and viscosity component (VC), and (2) myotonometer measured muscle tone (F) and stiffness (S), (3) electrical impedance myography measured resistance (R), reactance (X) and phase angle (θ); (4) modified Asworth scale; (5) Fugl Meyer Upper limb scale. All outcome measures were recorded at baseline, immediately post rESW and at 1-week follow-up. The differences between the paretic and non-paretic side were assessed by t-test. The effectiveness of rESW treatment were analyzed by repeated-measures one-way analysis of variance (ANOVA) at different time points.Results: Twenty-seven participants completed the study. NC, EC, and VC of the Neuroflexor method, F and S from myotonometer were all significantly higher on the paretic side than those from the non-paretic side. R, X, and θ from electrical impedance were significantly lower on the paretic side than the non-paretic side. Immediately after rESW intervention, VC, F, and S were significantly reduced, and X was significantly increased. The clinical scores showed improvements immediate post rESW and at 1-week follow-up.Conclusions: The observed changes in upper limb muscle properties adds further support to the theory that both the neural and peripheral components play a role in muscle spasticity. ESW intervention may be more effective in addressing the peripheral component of spasticity in terms of muscle mechanical properties changes. The clinical management of post stroke spasticity should take into consideration of both the neural and non-neural factors in order to identify optimal intervention regime.
One-Week Self-Guided Internet Cognitive Behavioral Treatments for Insomnia in Adults With Situational Insomnia During the COVID-19 Outbreak
Authors: Zhang Chenxi , Yang Lulu , Liu Shuai , Xu Yan , Zheng Huirong , Zhang Bin 
Published: January 2021

Objective: In the current global home confinement due to COVID-19, most individuals are facing unprecedented stress which can induce situational insomnia. We explored the efficacy of self-guided online cognitive behavioral treatment for insomnia (CBTI) on situational insomnia during the COVID-19 outbreak.Methods: Participants were recruited from March to April in 2020 in Guangzhou, China. A 1-week Internet CBTI intervention was performed for all individuals with situational insomnia. The Pre-sleep Arousal Scale (PSAS), Insomnia Severity Index (ISI), and Hospital Anxiety and Depression Scale (HADS) were measured before and after the intervention and compared between individuals who completed the intervention and those who did not.Results: One hundred and ninety-four individuals with situational insomnia were included. For PSAS score, significant group effects were found on total score (p = 0.003), somatic score (p = 0.014), and cognitive score (p = 0.009). Time effect was significant on total score (p = 0.004) and cognitive score (p &lt; 0.001). There was a significant group × time effect of the somatic score (p = 0.025). For ISI total score, there were significant time effect (p &lt; 0.001) and group × time effect (p = 0.024). For the HADS score, a significant group effect was found on the anxiety score (p = 0.045). The HADS had significant time effects for anxiety and depressive symptoms (all p &lt; 0.001).Conclusion: Our study suggests good efficacy of CBTI on situational insomnia during COVID-19 for adults in the community, as well as on pre-sleep somatic hyperarousal symptom. The CBTI intervention is not applied to improve pre-sleep cognitive hyperarousal, depression, and anxiety symptoms.
Longitudinal Association of Nut Consumption and the Risk of Cardiovascular Events: A Prospective Cohort Study in the Eastern Mediterranean Region
Authors: Mohammadifard Noushin , Ghaderian Niloufar , Hassannejad Razieh , Sajjadi Firouzeh , Sadeghi Masoumeh , Roohafza Hamidreza , Salas-Salvadó Jordi , Sarrafzadegan Nizal 
Published: January 2021

Background and Aim: There are few pieces of evidence on the association between nut consumption and the risk of cardiovascular disease (CVD) in the Eastern Mediterranean Region. This study investigated the relationship of nut consumption with the risk of CVD and all-cause mortality in the Iranian population.Methods and Results: This population-based prospective cohort study was carried out in 6,504 randomly selected participants aged ≥35 years in central Iran (2001–2013) in the framework of the Isfahan Cohort Study. Dietary data were collected by a validated 48-item food frequency questionnaire. Subjects or their next of kin were interviewed biannually, looking for the possible occurrence of cardiovascular events and all-cause mortality. During the median follow-up of 135 months and 52,704.3 person-years, we found a total of 751 CVD events. In unadjusted model, participants in the highest quartile of nut intake had a lower CVD risk {hazard ratio (HR) [95% confidence interval (CI)]: 0.57(0.47–0.70); P for trend &lt; 0.001}, CVD mortality [HR (95% CI): 0.54 (0.33–0.72); P for trend &lt; 0.001], and all-cause mortality [HR (95% CI): 0.24 (0.14–0.42); P for trend &lt; 0.001]. In the fully adjusted model, the association was diluted, and no significant relationship was found between nut intake and CVD events and all-cause mortality, except for CVD mortality in the highest quartile vs. the lowest one [HR (95% CI): 0.55 (0.30–0.98)].Conclusion: Nut intake had an inverse association with the risk of CVD mortality. It is suggested to perform studies to examine the association of individual types of nuts and different preparation methods on CVD risk and mortality.
Effect of Tumor Size on Long-Term Survival After Resection for Solitary Intrahepatic Cholangiocarcinoma
Authors: Kong Junjie , Cao Yukun , Chai Jiawei , Liu Xihan , Lin Cunhu , Wang Jianping , Liu Jun 
Published: January 2021

BackgroundThe relationship between tumor size and survival in intrahepatic cholangiocarcinoma (ICC) is still controversial. This study aimed to evaluate the prognostic ability of tumor size for solitary ICC after resection and explore optimal cut-off values in different subgroups.MethodsPatients with solitary ICC who underwent liver resection from the Surveillance, Epidemiology, and End Results Program and Shandong Provincial Hospital were retrospectively analyzed. Kaplan-Meier and Cox regression analysis were used to assess the prognostic ability of tumor size. The log-rank test was used to determine the optimal cut-off values, and a minimum P was regarded as the optimal one in different subgroups.ResultsLarge tumor size groups had worse overall survival (OS) than small tumor size groups. Cox regression analysis suggested that tumor size was an independent prognostic factor for OS for solitary ICC after resection. Subgroup analysis showed tumor size was associated with OS for both solitary ICC with and without vascular invasion (VI). Furthermore, the optimal cut-off values for solitary ICC with and without VI were found to be 8 and 3 cm, respectively, which could divide the patients into two groups with significant differences in OS.ConclusionTumor size was an independent prognostic factor for solitary ICC after resection. The existing American Joint Committee on Cancer (AJCC) staging system could be improved if the cut-off value of the T1 stage was changed to 8 cm and if the T2 stage incorporated a tumor size with a cut-off value of 3 cm. Further studies with more cases are needed to validate these findings.
ALT Flare Predicts Hepatocellular Carcinoma Among Antiviral Treated Patients With Chronic Hepatitis B: A Cross-Country Cohort Study
Authors: Du Yanan , Du Bingying , Fang Xiaoyan , Shu Meng , Zhang Yongjing , Chung Hsingwen , Sun Ye , Teng Jiaming , Visalath Phimphone , Qiu Hong , Cai Wei 
Published: January 2021

ObjectivesAlanine aminotransferase (ALT) level is one of the crucial indexes to evaluate disease status for chronic hepatitis B (CHB) patients. However, whether the ALT level after nucleos(t)ide analog (NA) treatment is associated with hepatocellular carcinoma (HCC) development remains unclear.Materials and MethodsWe evaluated the association between ALT level and HCC occurrence in NA-treated patients and investigated the predictive value of ALT flare for HCC. The associations between ALT level and HCC were analyzed by logistic regression and Cox proportional hazards models.ResultsThere were 21,223 CHB patients at Ruijin Hospital of China and 16,737 CHB patients in the Optum electronic health records (EHR) in the United States (US) treated with NAs between 2010 and 2018. Among them, 8,152 and 4,893 patients who achieved a normal ALT value were included in the study cohorts, respectively. A significant positive dose-dependent correlation between the peak ALT level and HCC was identified in both cohorts. Within the China cohort, ALT flare was significantly associated with increased risks of HCC compared to normal ALT (HR 2.55, 95%CI 1.45–4.50). Stronger increased risks associated with ALT flare were observed in the US cohort (HR 7.62, 95%CI 4.85–11.98).ConclusionsALT flare is a strong predictor for HCC occurrence in the CHB patients treated with NAs. Elevation of ALT, especially ALT flare warrants close monitoring for early HCC detection.
YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia
Authors: Zheng Chao , Luo Jiaqian , Yang Yifan , Dong Rui , Yu Fa-Xing , Zheng Shan 
Published: January 2021

Background and Aim: Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model.Methods: Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status.Results: The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, ANKRD1, which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model.Conclusions: YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.
Commissioning of GPU–Accelerated Monte Carlo Code FRED for Clinical Applications in Proton Therapy
Authors: Gajewski Jan , Garbacz Magdalena , Chang Chih-Wei , Czerska Katarzyna , Durante Marco , Krah Nils , Krzempek Katarzyna , Kopeć Renata , Lin Liyong , Mojżeszek Natalia , Patera Vincenzo , Pawlik-Niedzwiecka Monika , Rinaldi Ilaria , Rydygier Marzena , Pluta Elzbieta , Scifoni Emanuele , Skrzypek Agata , Tommasino Francesco , Schiavi Angelo , Rucinski Antoni 
Published: January 2021

We present commissioning and validation of Fred, a graphical processing unit (GPU)–accelerated Monte Carlo code, for two proton beam therapy facilities of different beam line design: CCB (Krakow, IBA) and EMORY (Atlanta, Varian). We followed clinical acceptance tests required to approve the certified treatment planning system for clinical use. We implemented an automated and efficient procedure to build a parameter library characterizing the clinical proton pencil beam. Beam energy, energy spread, lateral propagation model, and a dosimetric calibration factor were parametrized based on measurements performed during the facility start-up. The Fred beam model was validated against commissioning and supplementary measurements performed with and without range shifter. We obtained 1) submillimeter agreement of Bragg peak shapes in water and lateral beam profiles in air and slab phantoms, 2) <2% dose agreement for spread out Bragg peaks of different ranges, 3) average gamma index (2%/2 mm) passing rate of >95% for >1000 patient verification measurements using a two-dimensional array of ionization chambers, and 4) gamma index passing rate of >99% for three-dimensional dose distributions computed with Fred and measured with an array of ionization chambers behind an anthropomorphic phantom. The results of example treatment planning study on >100 patients demonstrated that Fred simulations in computed tomography enable an accurate prediction of dose distribution in patient and application of Fred as second patient quality assurance tool. Computation of a patient treatment in a CT using 104 protons per pencil beam took on average 2′30 min with a tracking rate of 2.9×105p+/s. Fred was successfully commissioned and validated against the clinical beam model, showing that it could potentially be used in clinical routine. Thanks to high computational performance due to GPU acceleration and an automated beam model implementation method, the application of Fred is now possible for research or quality assurance purposes in most of the proton facilities.
Direct Bullying and Cyberbullying: Experimental Study of Bystanders’ Motivation to Defend Victims and the Role of Anxiety and Identification With the Bully
Authors: Jungert Tomas , Karataş Pinar , Iotti Nathalie Ophelia , Perrin Sean 
Published: January 2021

School bullying among young adolescents is a globally pervasive problem, but is less common when bystanders are motivated to defend victims. Thus, the focus of this experimental study is on motivation to defend victims of bullying.Methods: A total of 388 students (Mage = 12.22 years, 49.7% girls) from two Turkish public schools (5th–8th grade) participated in a vignette experiment. Students were randomized to one of two vignettes (direct vs. cyberbullying). Self-report measures of motivation to defend, trait anxiety, depression, and identification with the victim or bully were used.Results: Participants reported more autonomous motivation in the cyberbullying condition, while those who witnessed direct bullying reported higher anxiety and depression.Results also revealed that this type of condition was associated with anxiety and depression, while anxiety was associated with autonomous motivation to defend. Finally, participants in the direct bullying condition were more likely to identify with the bully.Conclusion: Findings advance our understanding of when and why adolescents are motivated to help victims of bullying because they give a richer picture of what they assess when deciding whether or not they should intervene.
Serum Levels of FGF21, β-Klotho, and BDNF in Stable Coronary Artery Disease Patients With Depressive Symptoms: A Cross-Sectional Single-Center Study
Authors: Wu Yeshun , Chen Zijun , Duan Jiahao , Huang Kai , Zhu Bin , Yang Ling , Zheng Lu 
Published: January 2021

Background:The incidence of depressive symptoms (DS) in patients with stable coronary artery disease (SCAD) is significantly higher than those in healthy population, and that DS are independent risk factors for cardiovascular events. Previous studies have reported that fibroblast growth factor 21 (FGF21), β-klotho, mature brain-derived neurotrophic factor (mBDNF), and BDNF precursor (proBDNF) play important roles in the pathogenesis and treatment of coronary heart disease and depression. With this in mind, the present study aimed to clarify the relationship between FGF21, β-klotho, mBDNF, and proBDNF and SCAD with comorbid depression, in addition to also exploring the underlying mechanisms of these disease processes.Methods:A total of 116 patients with SCAD and 45 healthy controls were recruited. Patients with SCAD were further divided into two subgroups based on the Zung Self-Rating Depression Scale (SDS), which were characterized as those with no DS (NDS) and those with DS. Baseline data were collected, and serum levels of FGF21, β-klotho, mBDNF, and proBDNF were determined.Results:In SCAD patients, Gensini scores—denoting the degree of coronary arteriostenosis—were significantly greater in the DS group than in the NDS group. There was also a positive correlation between the Gensini scores and the SDS scores. Patients in the SCAD group demonstrated a lower serum FGF21. Serum β-klotho, mBDNF, and mBDNF/proBDNF were also significantly lower in the DS group than in the NDS group. Furthermore, β-klotho and mBDNF were negatively correlated with the SDS scores. Additionally, SCAD patients were divided into lower- and higher-level groups using hierarchical cluster analysis, with the results highlighting that patients in the lower mBDNF group had a higher incidence of DS.Conclusions:The depression score was positively correlated with the severity of coronary artery stenosis, and serum FGF21, β-klotho, mBDNF, and proBDNF were closely related to the development of DS in patients with SCAD. These observations suggest FGF21, β-klotho, mBDNF, and proBDNF as potential diagnostic and/or therapeutic targets for SCAD with co-morbid depression.