bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Australian State-Based Cohort Study of Autoimmune Encephalitis Cases Detailing Clinical Presentation, Investigation Results, and Response to Therapy
Authors: Swayne Andrew , Warren Nicola , Prain Kerri , Gillis David , O'Gorman Cullen , Tsang Benjamin K-T. , Muller Claire , Broadley Simon , Adam Robert J. , McCombe Pamela , Wong Richard C. , Blum Stefan 
Published: February 2021

Introduction: Autoimmune encephalitis is a disorder associated with antibodies directed against central nervous system proteins with variable clinical features. This study aims to add to knowledge of the disease by reporting the details of a cohort of patients with autoimmune encephalitis in Queensland, Australia.Methodology: We surveyed patients with autoimmune encephalitis diagnosed and managed through public hospitals in Queensland, Australia between 2010 and the end of 2019. Cases were identified via case detection through a centralized diagnostic neuroimmunology laboratory (Division of Immunology, HSQ Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia) and a survey of neurologists. Data including demographic details, clinical presentation, investigation results, treatments including immune therapy and outcomes was collected.Results: Sixty cases of antibody positive autoimmune encephalitis were identified. Twenty-eight were of anti-NMDA-receptor encephalitis with other cases associated with antibodies against LGi1, Caspr2, glycine receptor, DPPX, GABAB receptor, IgLON5, GFAP, and SOX1. The number of diagnosed cases, especially of anti-NMDA-receptor encephalitis has markedly increased over the period 2017 to 2019. Clinical presentations were marked by heterogeneous symptom complexes and prolonged hospital admissions. Imaging studies were largely normal or non-specific. There was a response to immune therapy and a low mortality rate. Most cases affected by this disorder were left with ongoing symptoms associated with mild disability.Conclusion: Autoimmune encephalitis in Queensland, Australia is an increasingly common but complex clinical entity marked by heterogeneous presentations, response to immune therapy and outcome results marked by low mortality and incomplete recovery.
The Association Between Metabolic Disturbance and Cognitive Impairments in Early-Stage Schizophrenia
Authors: Peng Xing-Jie , Hei Gang-Rui , Li Ran-Ran , Yang Ye , Liu Chen-Chen , Xiao Jing-Mei , Long Yu-Jun , Shao Ping , Huang Jing , Zhao Jing-Ping , Wu Ren-Rong 
Published: February 2021

Background: Cognitive impairment is one of the core symptoms of schizophrenia, which is considered to be significantly correlated to prognosis. In recent years, many studies have suggested that metabolic disorders could be related to a higher risk of cognitive defects in a general setting. However, there has been limited evidence on the association between metabolism and cognitive function in patients with early-stage schizophrenia.Methods: In this study, we recruited 172 patients with early-stage schizophrenia. Relevant metabolic parameters were examined and cognitive function was evaluated by using the MATRICS Consensus Cognitive Battery (MCCB) to investigate the relationship between metabolic disorder and cognitive impairment.Results: Generally, the prevalence of cognitive impairment among patients in our study was 84.7% (144/170), which was much higher than that in the general population. Compared with the general Chinese setting, the study population presented a higher proportion of metabolic disturbance. Patients who had metabolic disturbance showed no significant differences on cognitive function compared with the other patients. Correlation analysis showed that metabolic status was significantly correlated with cognitive function as assessed by the cognitive domain scores (p &lt; 0.05), while such association was not found in further multiple regression analysis.Conclusions: Therefore, there may be no association between metabolic disorder and cognitive impairment in patients with early-stage schizophrenia.Trial Registration: Clinicaltrials.gov, NCT02880462. Registered August 26, 2016.
Using EEG Alpha States to Understand Learning During Alpha Neurofeedback Training for Chronic Pain
Authors: Patel Kajal , Henshaw James , Sutherland Heather , Taylor Jason R. , Casson Alexander J. , Lopez-Diaz Karen , Brown Christopher A. , Jones Anthony K. P. , Sivan Manoj , Trujillo-Barreto Nelson J. 
Published: February 2021

ObjectiveAlpha-neurofeedback (α-NFB) is a novel therapy which trains individuals to volitionally increase their alpha power to improve pain. Learning during NFB is commonly measured using static parameters such as mean alpha power. Considering the biphasic nature of alpha rhythm (high and low alpha), dynamic parameters describing the time spent by individuals in high alpha state and the pattern of transitioning between states might be more useful. Here, we quantify the changes during α-NFB for chronic pain in terms of dynamic changes in alpha states.MethodsFour chronic pain and four healthy participants received five NFB sessions designed to increase frontal alpha power. Changes in pain resilience were measured using visual analogue scale (VAS) during repeated cold-pressor tests (CPT). Changes in alpha state static and dynamic parameters such as fractional occupancy (time in high alpha state), dwell time (length of high alpha state) and transition probability (probability of moving from low to high alpha state) were analyzed using Friedman’s Test and correlated with changes in pain scores using Pearson’s correlation.ResultsThere was no significant change in mean frontal alpha power during NFB. There was a trend of an increase in fractional occupancy, mean dwell duration and transition probability of high alpha state over the five sessions in chronic pain patients only. Significant correlations were observed between change in pain scores and fractional occupancy (r = −0.45, p = 0.03), mean dwell time (r = -0.48, p = 0.04) and transition probability from a low to high state (r = -0.47, p = 0.03) in chronic pain patients but not in healthy participants.ConclusionThere is a differential effect between patients and healthy participants in terms of correlation between change in pain scores and alpha state parameters. Parameters providing a more precise description of the alpha power dynamics than the mean may help understand the therapeutic effect of neurofeedback on chronic pain.
Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost in Glioblastoma: A Phase I Study (ISIDE-BT-2)
Authors: Ferro Marica , Ferro Milena , Macchia Gabriella , Cilla Savino , Buwenge Milly , Re Alessia , Romano Carmela , Boccardi Mariangela , Picardi Vincenzo , Cammelli Silvia , Cucci Eleonora , Mignogna Samantha , Di Lullo Liberato , Valentini Vincenzo , Morganti Alessio Giuseppe , Deodato Francesco 
Published: February 2021

BackgroundGlioblastoma Multiforme (GBM) is the most common primary brain cancer and one of the most lethal tumors. Theoretically, modern radiotherapy (RT) techniques allow dose-escalation due to the reduced irradiation of healthy tissues. This study aimed to define the adjuvant maximum tolerated dose (MTD) using volumetric modulated arc RT with simultaneous integrated boost (VMAT-SIB) plus standard dose temozolomide (TMZ) in GBM.MethodsA Phase I clinical trial was performed in operated GBM patients using VMAT-SIB technique with progressively increased total dose. RT was delivered in 25 fractions (5 weeks) to two planning target volumes (PTVs) defined by adding a 5-mm margin to the clinical target volumes (CTVs). The CTV1 was the tumor bed plus the MRI enhancing residual lesion with 10-mm margin. The CTV2 was the CTV1 plus 20-mm margin. Only PTV1 dose was escalated (planned dose levels: 72.5, 75, 77.5, 80, 82.5, 85 Gy), while PTV2 dose remained unchanged (45 Gy/1.8 Gy). Concurrent and sequential TMZ was prescribed according to the EORTC/NCIC protocol. Dose-limiting toxicities (DLTs) were defined as any G ≥ 3 non-hematological acute toxicity or any G ≥ 4 acute hematological toxicities (RTOG scale) or any G ≥ 2 late toxicities (RTOG-EORTC scale).ResultsThirty-seven patients (M/F: 21/16; median age: 59 years; median follow-up: 12 months) were enrolled and treated as follows: 6 patients (72.5 Gy), 10 patients (75 Gy), 10 patients (77.5 Gy), 9 patients (80 Gy), 2 patients (82.5 Gy), and 0 patients (85 Gy). Eleven patients (29.7%) had G1-2 acute neurological toxicity, while 3 patients (8.1%) showed G ≥ 3 acute neurological toxicities at 77.5 Gy, 80 Gy, and 82.5 Gy levels, respectively. Since two DLTs (G3 neurological: 1 patient and G5 hematological toxicity: 1 patient) were observed at 82.5 Gy level, the trial was closed and the 80 Gy dose-level was defined as the MTD. Two asymptomatic histologically proven radionecrosis were recorded.ConclusionsAccording to the results of this Phase I trial, 80 Gy in 25 fractions accelerated hypofractionated RT is the MTD using VMAT-SIB plus standard dose TMZ in resected GBM.
Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy Can Benefit the Locally Advanced Rectal Cancer Patients With Clinically Positive Lateral Pelvic Lymph Node
Authors: Li Shuai , Zhang Yangzi , Yu Yang , Zhu Xianggao , Geng Jianhao , Teng Huajing , Wang Zhilong , Sun Tingting , Wang Lin , Wang Hongzhi , Li Yongheng , Wu Aiwen , Cai Yong , Wang Weihu 
Published: February 2021

Background and PurposeThe optimal treatment modality for clinically positive lateral pelvic lymph node (LPLN) from locally advanced rectal cancer (LARC) is unknown. Thus, we aimed to analyze the optimal radiotherapy dose for clinically positive LPLN from LARC.Materials and MethodsWe retrospectively evaluated distal LARC (i.e., within 8 cm from the anal verge) patients with clinically positive LPLN (i.e., ≥7 mm in the short axis). They were divided into two groups based on whether or not they received simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT)–based chemoradiotherapy. The total radiotherapy dose on LPLN were 56-60Gy for SIB-IMRT group and 41.8Gy for non-SIB-IMRT group. The clinical parameters and regrowth rate of LPLN were then compared between the two groups.ResultsA total of 151 patients were evaluated, and 83 and 68 patients were classified to the SIB-IMRT and non-SIB-IMRT group, respectively. The median follow-up period was 22.6 months, and the 2-year LPLN regrowth rate was significantly different between the SIB-IMRT group and the non-SIB-IMRT group (0% vs 10.8%, P=0.024). Further, SIB-IMRT yielded a significantly lower 2-year LPLN regrowth rate in patients whose LPLN measured ≥8 mm in the short axis (0% vs. 15.9%, P=0.019) or ≥10 mm in the long axis (0% vs. 17.6%, P=0.024) compared to patients who were in non-SIB-IMRT group. Meanwhile, there was no significant difference in grade II radiation-related toxicity (30.1% vs. 39.1%, P=0.217) and surgical complications (21.8% vs. 12.2%, P=0.198) between the two groups.ConclusionSIB-IMRT–based neoadjuvant chemoradiotherapy is beneficial for eliminating clinically positive LPLN from LARC without increasing the incidence of radiotherapy-related toxicity and surgical complications, and patients with larger LPLN may gain benefit from this technique.
TIM-3 as a Prognostic Marker and a Potential Immunotherapy Target in Human Malignant Tumors: A Meta-Analysis and Bioinformatics Validation
Authors: Zang Kui , Hui Liangliang , Wang Min , Huang Ying , Zhu Xingxing , Yao Bin 
Published: February 2021

BackgroundAs a novel immune checkpoint molecular, T-cell immunoglobulin mucin 3 (TIM-3) is emerging as a therapeutic target for cancer immunotherapy. However, the predictive role of TIM-3 in cancer remains largely undetermined. This study was designed to investigate the role of TIM-3 in cancer.MethodsPublications were searched using multiple databases. The hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. To further confirm the prognostic effect of TIM-3, The Cancer Genome Atlas (TCGA) data were applied. Functional analysis of TIM-3 was also investigated.Results28 studies with 7284 patients with malignant tumors were identified. Based on multivariate Cox regression analysis, TIM-3 was an independent prognostic indicator for poor overall survival (OS) (HR= 1.54, 95% CI = 1.19-1.98, P = 0.001). However, TIM-3 was not correlated with cancer-specific survival and disease-free survival (DFS). Particularly, TIM-3 showed a worse prognosis in non-small cell lung carcinoma and gastric cancer; but it showed a favorable prognosis in breast cancer. Functional analysis showed that TIM-3 was closely correlated with immune responses such as T-cell activation and natural killer cell-mediated cytotoxicity. Moreover, TIM-3 expression was found to be related to worse OS in 9491 TCGA patients (HR = 1.2, P &lt; 0.001), but was not associated with DFS.ConclusionsTIM-3 was an independent prognostic factor. Meanwhile, TIM-3 played a crucial role in tumor immune responses. This supports TIM-3 as a promising target for cancer immunotherapy.
Survival After Combining Stereotactic Body Radiation Therapy and Tyrosine Kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma
Authors: Liu Yang , Zhang Zhiling , Han Hui , Guo Shengjie , Liu Zhuowei , Liu Mengzhong , Zhou Fangjian , Dong Pei , He Liru 
Published: February 2021

BackgroundStereotactic body radiation therapy (SBRT) and tyrosine kinase inhibitors (TKIs) are effective treatments for metastatic renal cell carcinoma, but data on combining these two modalities are scarce. We aimed to investigate the survival outcomes of SBRT plus TKIs.MethodsData of patients treated with TKIs from December 2007 to June 2019 were collected. Patients received SBRT plus TKIs (TKI + SBRT group) or TKIs alone (TKI alone group). Local control (LC), time to change of systemic therapy (TTS), and overall survival (OS) were assessed.ResultsA total of 190 patients were included, and 85 patients received TKI + SBRT. The 2-year LC rate was 92.8%. The median OS in the TKI + SBRT group was significantly longer than that of the TKI alone group (63.2 vs 29.8 months; P &lt; 0.001). In multivariate analysis, IMDC intermediate (HR 1.96; 95% CI 1.10–3.48; P = 0.022) and poor risk (HR 2.43; 95% CI 1.25–4.75; P = 0.009), oligometastasis (HR 0.41; 95% CI 0.26–0.65; P &lt; 0.001), and the addition of SBRT (HR 0.48; 95% CI 0.31–0.75; P = 0.001) were prognostic factors for OS. Patients with oligometastasis (P = 0.009) and those with IMDC favorable (P = 0.044) or intermediate (P = 0.002) risk had significantly longer OS with TKI + SBRT. The median TTS were 21.5, 6.4, and 9.0 months in patients receiving SBRT before first-line TKI failure, SBRT after first-line TKI failure, and first-line TKI alone (P &lt; 0.001). Five patients (5.9%) experienced SBRT-related grade 3 toxicities.ConclusionsCombining SBRT with TKIs is tolerable and associated with longer OS in selected patients, such as those with oligometastasis and favorable or intermediate risk.
A Novel Creatinine-Based Equation to Estimate Glomerular Filtration Rate in Chinese Population With Chronic Kidney Disease: Implications for DOACs Dosing in Atrial Fibrillation Patients
Authors: Zhou Ling-Yun , Yin Wen-Jun , Zhao Jun , Zhang Bi-Kui , Hu Can , Liu Kun , Wang Jiang-Lin , Zhou Ge , Chen Lin-Hua , Zuo Shan-Ru , Xie Yue-Liang , Zuo Xiao-Cong 
Published: February 2021

Background: Over/under-estimating renal function may increase inappropriate dosing strategy associated adverse outcomes; however, previously reported equations to estimate renal function have limited accuracy in chronic kidney disease (CKD) patients. Consequently, we intended to develop a novel equation to precisely estimate renal function and subsequently guide clinical treatment for CKD patients.Methods: A novel approach, Xiangya-s equation, to estimate renal function for CKD patients was derived by linear regression analysis and validated in 1885 patients with measured glomerular filtration rate (mGFR) &lt; 60 ml/min/1.73 m2 by renal dynamic imaging at three representative hospitals in China, with the performance evaluated by accuracy, bias and precision. In the meanwhile, 2,165 atrial fibrillation (AF) patients who initiated direct oral anticoagulants (DOACs) between December 2015 and December 2018 were identified and renal function was assessed by estimated creatinine clearance (eCrCl). Events per 100 patient-years was calculated. Cox proportional hazards regression was applied to compare the incidence of outcomes of each group.Results: Xiangya-s equation demonstrated higher accuracy, lower bias and improved precision when compared with 12 creatinine-based and 2 CysC-based reported equations to estimate GFR in multi-ethnic Chinese CKD patients. When we applied Xiangya-s equation to patients with AF and CKD prescribed DOACs, wide variability was discovered in eCrCl calculated by the Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Xiangya equation which we had developed for generally patients and Xiangya-s equations, which persisted after grouping by different renal function stages. Equation choice affected drug-dosing adjustments, with the formulas agreeing for only 1.19%, 5.52%, 33.22%, 26.32%, and 36.61% of potentially impacted patients for eCrCl cutoffs of &lt;15, &lt;30, 15–49, 30–49, ≥50 ml/min, respectively. Relative to CG equation, accordance in DOACs dosage was 81.08%, 88.54%, 62.25%, and 47.68% for MDRD, CKD-EPI, Xiangya and Xiangya-s equations for patients with CrCl &lt; 50 ml/min (eCrCl cutoffs of &lt;30, 30–49, ≥50 ml/min), respectively. Reclassification of renal function stages by Xiangya-s equation was significantly associated with stroke or systemic embolism, non-major clinically relevant bleeding and any bleeding events.Conclusion: Xiangya-s equation provides more accurate GFR estimates in Chinese CKD patients who need consecutive monitoring of renal function, which may assist clinicians in choosing appropriate drug dosages.
Characterization of the CDAA Diet-Induced Non-alcoholic Steatohepatitis Model: Sex-Specific Differences in Inflammation, Fibrosis, and Cholesterol Metabolism in Middle-Aged Mice
Authors: Kucsera Dániel , Tóth Viktória E. , Gergő Dorottya , Vörös Imre , Onódi Zsófia , Görbe Anikó , Ferdinandy Péter , Varga Zoltán V. 
Published: February 2021

BackgroundThe prevalence of non-alcoholic steatohepatitis (NASH) rapidly increases with associated metabolic disorders such as dyslipidemia; therefore, NASH is now considered an independent risk factor of cardiovascular diseases. NASH displays sex-linked epidemiological, phenotypical, and molecular differences; however, little is known about the background of these sex-specific differences on the molecular level.ObjectivesWe aimed to assess sex-specific differences in the expression of inflammatory and fibrotic genes, as well as in cholesterol metabolism, focusing on the expression of Pcsk9 in several tissues in a mouse model of NASH that shows the typical features of the human condition.Methods and ResultsWe fed 10-months-old male and female C57Bl/6J mice with a NASH-inducing CDAA or corresponding control diet for 8 weeks. We found that, compared to the control male mice baseline, hepatic Pcsk9 expression as well as serum PCSK9 level was significantly higher in females, and both circulating PCSK9 level and the hepatic Pcsk9 gene were markedly decreased in female mice during NASH development. Histological analysis revealed that male and female mice develop a similar degree of steatosis; however, fibrosis was more pronounced in males upon CDAA diet feeding. Strikingly, female mice have higher hepatic expression of the pro-inflammatory cytokines (Il1b, Ifng), and increased IL-1β cleavage by the NLRP3 inflammasome, and a decrease in Clec4f+ resident Kupffer cell population in comparison to males in the CDAA-fed groups.ConclusionThis is the first demonstration that there are critical sex-specific differences during NASH development in middle-aged mice regarding inflammation, fibrosis, and cholesterol metabolism and that changes in PCSK9 and IL-1β are likely important contributors to sex-specific changes during the transition to NASH.
Depression Following COVID-19 Lockdown in Severely, Moderately, and Mildly Impacted Areas in China
Authors: Han Xuerui , Chen Shuquan , Bi Kaiwen , Yang Zeyun , Sun Pei 
Published: February 2021

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has led to overwhelming levels of distress as it spread rapidly from Wuhan, Hubei province to other regions in China. To contain the transmission of COVID-19, China has executed strict lockdown and quarantine policies, particularly in provinces with the highest severity (i.e., Hubei). Although the challenges faced by individuals across provinces may share some similarities, it remains unknown as to whether and how the severity of COVID-19 is related to elevation in depression.Methods: The present study compared depression among individuals who lived in mildly, moderately, and severely impacted provinces in China following the lockdown (N = 1,200) to norm data obtained from a representative sample within the same provinces in 2016 (N = 950), and examined demographic correlates of depression in 2020.Results: Residents in 2020, particularly those living in more heavily impacted provinces, reported increased levels of depression than the 2016 sample. Subsequent analyses of sub-dimensions of depression replicated the findings for depressed mood but not for positive affect, as the latter only declined among residents in the most severely impacted area. Increased depressed mood was associated with female, younger age, fewer years of education, and being furloughed from work, whereas reduced positive affect was associated with younger age and fewer years of education only.Conclusions: This study underscored the impact of COVID-19 on depression and suggested individual characteristics that may warrant attention.
A Multicomponent Intervention Program With Overweight and Obese Adolescents Improves Body Composition and Cardiorespiratory Fitness, but Not Insulin Biomarkers
Authors: Schneiders Letícia de Borba , Brand Caroline , Borfe Leticia , Gaya Anelise Reis , Brazo-Sayavera Javier , Renner Jane Dagmar Pollo , Reuter Cézane Priscila 
Published: February 2021

Objective: To verify the effect of a multicomponent intervention with overweight/obese adolescents on physical fitness, body composition, and insulin biomarkers.Methods: A quasi-experimental study with 37 adolescents, aged 10 to 17 years, of both sexes, overweight and obese, allocated in two groups (Intervention—IG Group, n = 17; Control—GC Group, n = 20). The IGs were submitted to a multicomponent intervention for 6 months (three weekly sessions) consisting of physical exercises (sports, functional circuit, recreational, and water activities) and nutritional and psychological guidance. Participants were assessed before and after intervention on body composition [body mass index (BMI), body fat, waist circumference, and waist-to-hip ratio (WHR)], physical fitness [cardiorespiratory fitness (CRF) and abdominal strength], and biomarkers of insulin (glucose, insulin, evaluation of the homeostasis model of insulin, and resistin resistance). The prevalence of responders in both groups was obtained according to the theoretical model applied in previous studies similar to this one to determine the cutoff points for response to intervention. Poisson regression was used to verify the difference in the prevalence ratio (PR) of the interviewees between the groups.Results: The responders' prevalence between groups CG and IG showed significant differences for body fat (CG = 30.0%; IG = 70.6%; PR = 1.396; p &lt; 0.001), WHR (CG = 30.0%; IG = 76.5%; PR = 1.730; p &lt; 0.001), and CRF (CG = 15.0%; IG = 52.5%; PR = 1.580; p &lt; 0.001).Conclusions: A 6-month multicomponent intervention program improved certain body composition parameters and the CRF of overweight and obese adolescents but did not improve insulin biomarkers.Clinical Trial Registration: Clinical Trials under Protocol ID: 54985316.0.0000.5343.