bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Childhood Neighborhood Quality and the Risk of Cognitive Dysfunction in Chinese Middle-Aged and Elderly Population: The Moderation Effect of Body Mass Index
Authors: Xiong Peng , Liang Xiaohua , Chen Haiyan , Chen Li , Zuo Lei , Jing Chunxia , Hao Guang 
Published: May 2021

Background: Identification of early modifiable factors is crucial to delay or prevent the development of cognitive impairment and reduce the social and economic burden.Objective: This study aimed to examine the longitudinal associations of childhood neighborhood quality (CNQ) with the risk of later-life cognitive dysfunction and the role of body mass index (BMI) in this association.Methods: A total of 8,289 community-dwelling middle-aged and elderly population from wave 2011, wave 2013, and wave 2015 of the China Health and Retirement Longitudinal Study (CHARLS) were included. Cognitive function and CNQ were measured by standardized questionnaires. Multilevel linear regression models were used to estimate the associations of CNQ and cognitive function. The interactions of BMI with CNQ in the progress of cognitive function were also estimated.Results: The participants with higher CNQ had a significantly low risk of cognitive impairment than those with lower CNQ score (β = 0.067, 95% CI: 0.031, 0.103), and the results remained similar (β = 0.039, 95% CI: 0.004, 0.075) after controlling other confounding variables. Furthermore, there was an interaction between BMI with CNQ score (P &lt; 0.001) for the risk of cognitive impairment. In BMI-stratified analysis, we found that the association of CNQ and cognitive function was not statistically significant in overweight or obese population (β = 0.019, 95% CI: −0.032, 0.070), but was statistically significant in people with lower BMI (β = 0.059, 95% CI: 0.010, 0.107).Conclusions: Higher CNQ score is significantly associated with the lower risk of cognitive dysfunction in adulthood. BMI may moderate the associations of CNQ with the risk of cognitive function.
Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease
Authors: Nishijima Haruo , Kimura Tamaki , Mori Fumiaki , Wakabayashi Koichi , Kinoshita Iku , Nakamura Takashi , Kon Tomoya , Suzuki Chieko , Tomiyama Masahiko 
Published: May 2021

BackgroundIt remains unclear why patients with young-onset Parkinson’s disease more often develop levo-dihydroxyphenylalanine (L-dopa)-induced dyskinesia (LID) and have a more severe form than patients with old-onset Parkinson’s disease. Previous studies using animal models have failed to show young-onset Parkinson’s disease enhances LID.ObjectivesTo evaluate the association of age at dopaminergic denervation (onset age) and initiation of L-dopa treatment (treatment age) with LID development in model rats.MethodsWe established rat models of young- and old-lesioned Parkinson’s disease (6-hydroxydopamine lesions at 10 and 88 weeks of age, respectively). Dopaminergic denervation was confirmed by the rotational behavior test using apomorphine. Rats in the young-lesioned group were allocated to either L-dopa treatment at a young or old age, or saline treatment. Rats in the old-lesioned group were allocated to either L-dopa treatment or saline group. We evaluated L-dopa-induced abnormal involuntary movements during the 14-day treatment period. We also examined preprodynorphin mRNA expression in the striatum (a neurochemical hallmark of LID) and the volume of the medial globus pallidus (a pathological hallmark of LID).ResultsLID-like behavior was enhanced in L-dopa-treated young-lesioned rats compared with L-dopa-treated old-lesioned rats. Preprodynorphin mRNA expression was higher in L-dopa-treated young-lesioned rats than in in L-dopa-treated old-lesioned rats. The volume of the medial globus pallidus was greater in L-dopa-treated young-lesioned rats than in L-dopa-treated old-lesioned rats. Treatment age did not affect LID-like behavior or the degree of medial globus pallidus hypertrophy in the young-lesioned model.ConclusionBoth dopaminergic denervation and L-dopa initiation at a young age contributed to the development of LID; however, the former may be a more important factor.
Dual-Phase β-Amyloid PET Captures Neuronal Injury and Amyloidosis in Corticobasal Syndrome
Authors: Schmitt Julia , Palleis Carla , Sauerbeck Julia , Unterrainer Marcus , Harris Stefanie , Prix Catharina , Weidinger Endy , Katzdobler Sabrina , Wagemann Olivia , Danek Adrian , Beyer Leonie , Rauchmann Boris-Stephan , Rominger Axel , Simons Mikael , Bartenstein Peter , Perneczky Robert , Haass Christian , Levin Johannes , Höglinger Günter U. , Brendel Matthias ,   the German Imaging Initiative for Tauopathies (GII4T)
Published: May 2021

Objectives:In recent years several18F-labeled amyloid PET (Aβ-PET) tracers have been developed and have obtained clinical approval. There is evidence that Aβ-PET perfusion can provide surrogate information about neuronal injury in neurodegenerative diseases when compared to conventional blood flow and glucose metabolism assessment. However, this paradigm has not yet been tested in neurodegenerative disorders with cortical and subcortical affection. Therefore, we investigated the performance of early acquisition18F-flutemetamol Aβ-PET in comparison to18F-fluorodeoxyglucose (FDG)-PET in corticobasal syndrome (CBS).Methods:Subjects with clinically possible or probable CBS were recruited within the prospective Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer’s Disease (ActiGliA) observational study and all CBS cases with an available FDG-PET prior to Aβ-PET were selected. Aβ-PET was acquired 0–10 min p.i. (early-phase) and 90–110 min p.i. (late-phase) whereas FDG-PET was recorded statically from 30 to 50 min p.i. Semiquantitative regional values and asymmetry indices (AI) were compared between early-phase Aβ-PET and FDG-PET. Visual assessments of hypoperfusion and hypometabolism were compared between both methods. Late-phase Aβ-PET was evaluated visually for assessment of Aβ-positivity.Results:Among 20 evaluated patients with CBS, 5 were Aβ-positive. Early-phase Aβ-PET and FDG-PET SUVr correlated highly in cortical (meanR= 0.86, range 0.77–0.92) and subcortical brain regions (meanR= 0.84, range 0.79–0.90). Strong asymmetry was observed in FDG-PET for the motor cortex (mean |AI| = 2.9%), the parietal cortex (mean |AI| = 2.9%), and the thalamus (mean |AI| = 5.5%), correlating well with AI of early-phase Aβ-PET (meanR= 0.87, range 0.62–0.98). Visual assessments of hypoperfusion and hypometabolism were highly congruent.Conclusion:Early-phase Aβ-PET facilitates assessment of neuronal injury in CBS for cortical and subcortical areas. Known asymmetries in CBS are captured by this method, enabling assessment of Aβ-status and neuronal injury with a single radiation exposure at a single visit.
Posterior Cortical Cognitive Deficits Are Associated With Structural Brain Alterations in Mild Cognitive Impairment in Parkinson’s Disease
Authors: Devignes Quentin , Viard Romain , Betrouni Nacim , Carey Guillaume , Kuchcinski Gregory , Defebvre Luc , Leentjens Albert F. G. , Lopes Renaud , Dujardin Kathy 
Published: May 2021

Context: Cognitive impairments are common in patients with Parkinson’s disease (PD) and are heterogeneous in their presentation. The “dual syndrome hypothesis” suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia.Objective: The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype.Methods: One-hundred and fourteen non-demented PD patients underwent a comprehensive neuropsychological assessment as well as a 3T magnetic resonance imaging scan. Patients were categorized as having no cognitive impairment (n= 41) or as having a frontostriatal (n= 16), posterior cortical (n= 25), or a mixed (n= 32) MCI subtype. Cortical regions were analyzed using a surface-based Cortical thickness (CTh) method. In addition, the volumes, shapes, and textures of the caudate nuclei, hippocampi, and thalami were studied. Tractometric analyses were performed on associative and commissural white matter (WM) tracts.Results: There were no between-group differences in volumetric measurements and cortical thickness. Shape analyses revealed more abundant and more extensive deformations fields in the caudate nuclei, hippocampi, and thalami in patients with posterior cortical deficits compared to patients with no cognitive impairment. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were also observed in the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the striato-parietal tract, and the anterior and posterior commissural tracts. Texture analyses showed a significant difference in the right hippocampus of patients with a mixed MCI subtype.Conclusion: PD-MCI patients with posterior cortical deficits have more abundant and more extensive structural alterations independently of age, disease duration, and severity, which may explain why they have an increased risk of dementia.
Impact of Preinjury Antithrombotic Therapy on 30–Day Mortality in Older Patients Hospitalized With Traumatic Brain Injury (TBI)
Authors: Rønning Pål , Helseth Eirik , Skaansar Ola , Tverdal Cathrine , Andelic Nada , Bhatnagar Rahul , Melberg Mathias , Skaga Nils Oddvar , Aarhus Mads , Halvorsen Sigrun , Helseth Ragnhild 
Published: May 2021

Objective: Elderly patients are frequently in need of antithrombotic therapy for reducing thrombotic events. The association between antithrombotic drugs and survival after traumatic brain injury (TBI) is, nevertheless, unclear.Methods: This retrospective study included patients ≥65 years admitted to a Norwegian Level 1 trauma center with TBI identified on cerebral computed tomography (cerebral-CT) during 2014–2019. Preinjury use of antiplatelets and anticoagulants was compared to the prescription rate in the general Norwegian population. The primary outcome was 30-day mortality. Uni- and multivariate logistic regression analyses estimated the association between the use of antithrombotic drugs and mortality.Results: The study includes 832 consecutive TBI patients ≥65 years. The median age was 76 years, 58% were males, 51% had moderate or severe TBI, and 39% had multiple traumas. Preinjury use of antithrombotics was registered in 471/832 (55.6%) patients; antiplatelet therapy alone in 268, anticoagulant therapy alone in 172, and combined antiplatelet and anticoagulant therapy in 31. Antiplatelet use did not differ between the study cohort and the general Norwegian population ≥65 years (31 vs. 31%, p = 0.87). Anticoagulant therapy was used more commonly in the study cohort than in the general Norwegian population (24 vs. 19%, p = 0.04). Combined use of antiplatelet and anticoagulant therapy was significantly associated with 30-day mortality, while preinjury antiplatelet or anticoagulation treatment alone was not. No difference in 30-day mortality between patients using VKA, DOACs, or LMWH was encountered.Conclusions: In this cohort, neither antiplatelet nor anticoagulant therapy alone was associated with increased 30-day mortality. Anticoagulant use was more prevalent among TBI patients than the general population, suggesting that anticoagulation might contribute to the initiation of intracranial bleeding after blunt head trauma. Combined antiplatelet and anticoagulant therapy posed increased risk of 30-day mortality.
Occupational Injuries and Use of Benzodiazepines: A Systematic Review and Metanalysis
Authors: Garbarino Sergio , Lanteri Paola , Bragazzi Nicola Luigi , Gualerzi Giovanni , Riccò Matteo 
Published: May 2021

Background: Benzodiazepines have been widely used in clinical practice for over four decades and continue to be one of the most consumed and highly prescribed class of drugs available in the treatment of anxiety, depression, and insomnia. The literature indicates that Benzodiazepine users at a significantly increased risk of Motor Vehicle accidents compared to non-users but the impact on injuries at workplace is not well-defined. We aimed to investigate whether use of benzodiazepine is associated with increased risk of occupational injuries (OI).Methods: PubMed, Embase, and Scopus databases were searched. A meta-analysis was performed to calculate odds ratio (OR) and 95% confidence interval (CI) among case controls, cross-sectional studies, either questionnaire or laboratory exams based.Results: A total of 13 studies met inclusion criteria, involving 324,168 OI from seven different countries, with an estimated occurrence of benzodiazepine positivity of 2.71% (95% CI 1.45–4.98). A total of 14 estimates were retrieved. Of them, 10 were based on laboratory analyses, three on institutional databases, while one study was based on questionnaires. Regarding the occupational groups, three estimates focused on commercial drivers (0.73%, 95% CI 0.12–4.30), that exhibited a reduced risk ratio for benzodiazepine positivity compared to other occupational groups (RR 0.109, 95% CI 0.063–0.187). Eventually, no increased risk for benzodiazepine positivity was identified, either from case control studies (OR 1.520, 95% CI 0.801–2.885, I2 76%), or cross sectional studies, when only laboratory based estimates were taken in account (OR 0.590, 95% CI 0.253–1.377, I2 63%).Conclusions: Even though benzodiazepines have the potential to increase injury rates among casual and chronic users, available evidence are insufficient to sustain this hypothesis, particularly when focusing on laboratory-based studies (i.e., studies the characterized the benzodiazepine immediately before the event).
Predictive Role of the Apparent Diffusion Coefficient and MRI Morphologic Features on IDH Status in Patients With Diffuse Glioma: A Retrospective Cross-Sectional Study
Authors: Zhang Jun , Peng Hong , Wang Yu-Lin , Xiao Hua-Feng , Cui Yuan-Yuan , Bian Xiang-Bing , Zhang De-Kang , Ma Lin 
Published: May 2021

PurposeTo evaluate isocitrate dehydrogenase (IDH) status in clinically diagnosed grade II~IV glioma patients using the 2016 World Health Organization (WHO) classification based on MRI parameters.Materials and MethodsOne hundred and seventy-six patients with confirmed WHO grade II~IV glioma were retrospectively investigated as the study set, including lower-grade glioma (WHO grade II, n = 64; WHO grade III, n = 38) and glioblastoma (WHO grade IV, n = 74). The minimum apparent diffusion coefficient (ADCmin) in the tumor and the contralateral normal-appearing white matter (ADCn) and the rADC (ADCmin to ADCn ratio) were defined and calculated. Intraclass correlation coefficient (ICC) analysis was carried out to evaluate interobserver and intraobserver agreement for the ADC measurements. Interobserver agreement for the morphologic categories was evaluated by Cohen’s kappa analysis. The nonparametric Kruskal-Wallis test was used to determine whether the ADC measurements and glioma subtypes were related. By univariable analysis, if the differences in a variable were significant (P&lt;0.05) or an image feature had high consistency (ICC &gt;0.8; κ &gt;0.6), then it was chosen as a predictor variable. The performance of the area under the receiver operating characteristic curve (AUC) was evaluated using several machine learning models, including logistic regression, support vector machine, Naive Bayes and Ensemble. Five evaluation indicators were adopted to compare the models. The optimal model was developed as the final model to predict IDH status in 40 patients with glioma as the subsequent test set. DeLong analysis was used to compare significant differences in the AUCs.ResultsIn the study set, six measured variables (rADC, age, enhancement, calcification, hemorrhage, and cystic change) were selected for the machine learning model. Logistic regression had better performance than other models. Two predictive models, model 1 (including all predictor variables) and model 2 (excluding calcification), correctly classified IDH status with an AUC of 0.897 and 0.890, respectively. The test set performed equally well in prediction, indicating the effectiveness of the trained classifier. The subgroup analysis revealed that the model predicted IDH status of LGG and GBM with accuracy of 84.3% (AUC = 0.873) and 85.1% (AUC = 0.862) in the study set, and with the accuracy of 70.0% (AUC = 0.762) and 70.0% (AUC = 0.833) in the test set, respectively.ConclusionThrough the use of machine-learning algorithms, the accurate prediction of IDH-mutant versus IDH-wildtype was achieved for adult diffuse gliomas via noninvasive MR imaging characteristics, including ADC values and tumor morphologic features, which are considered widely available in most clinical workstations.
Detection of Disease-Causing SNVs/Indels and CNVs in Single Test Based on Whole Exome Sequencing: A Retrospective Case Study in Epileptic Encephalopathies
Authors: Sun Dan , Liu Yan , Cai Wei , Ma Jiehui , Ni Kun , Chen Ming , Wang Cheng , Liu Yongchu , Zhu Yuanyuan , Liu Zhisheng , Zhu Feng 
Published: May 2021

Background: Epileptic encephalopathies (EEs) are a pediatric entity with highly phenotypic and genetic heterogeneity. Both single nucleotide variants (SNVs)/Indels and copy number variations (CNVs) could be the causes. Whole exome sequencing (WES) is widely applied to detect SNVs/Indels, but the bioinformatics approach for detecting CNVs is still limited and weak. In the current study, the possibility of profiling both disease-causing SNVs/Indels and CNVs in a single test based on WES in EEs was evaluated.Methods: The infants diagnosed with EEs were enrolled from a single pediatric epilepsy center between January 2018 and February 2020. Demographic and clinical data were collected. In WES data, the pathogenic SNVs were identified through an in-house pipeline, and pathogenic CNVs were identified by CNVkit. The diagnostic rate was evaluated, and the molecular findings were characterized.Results: A total of 73 infants were included; 36 (49.32%) of them were males. The median age was 7 months. Thirty-two (43.84%) infants had been diagnosed with epilepsy syndrome. The most common type of syndrome was West syndrome (22/73, 30.1%), followed by Dravet syndrome (20/77, 27.4%). Fifty-four (73.97%) had intellectual development delay. The genetic cause of EEs, pathogenic or likely pathogenic variants, were successfully discovered in 46.6% (34/73) of the infants, and 29 (39.7%) infants carried SNVs/Indels, while 5 (6.8%) carried CNVs. The majority of the disease-causing variants were inherited in de novo pattern (25, 71.4%). In addition to showing that the variants in the ion channel encoding genes accounted for the main etiology, we discovered and confirmed two new disease-causing genes, CACNA1E and WDR26. Five discovered CNVs were deletions of 2q24.3, 1p36, 15q11-q13, 16p11.2, and 17p13.3, and all were confirmed by array comparative genomic hybridization.Conclusion: The application of both SNVs/Indels and CNVs detection in a single test based on WES yielded a high diagnosis rate in EEs. WES may serve as a first-tier test with cost-effective benefit in EEs.
Efficacy of Increased Salt and Water Intake on Pediatric Vasovagal Syncope: A Meta-Analysis Based on Global Published Data
Authors: Wang Yaru , Wang Yuanyuan , Li Xueying , Du Junbao , Zhang Hao , Jin Hongfang , Liao Ying 
Published: May 2021

Objective: This study was designed to assess the efficacy of increased salt and water intake in the treatment of pediatric vasovagal syncope (VVS) based on a meta-analysis of global data.Methods: Following the established inclusion criteria, seven databases, Cochrane Library, EMBASE, PubMed, Web of Science, VIP, Wanfang, and China National Knowledge Infrastructure (CNKI), were searched using specific terms. The Cochrane Bias risk assessment tool was used as a quality assessment tool of the included studies, and publication bias was assessed by funnel plots. Review Manager 5.4 software was used to analyze the efficacy of the included studies, taking the negative changing rate of the head-up tilt test (HUTT) and recurrence rate of syncope or presyncope as therapeutic efficacy evaluations.Results: In total, 5 randomized controlled trials (RCTs) were finally obtained, using the negative changing rate of the HUTT as an efficacy evaluation, while in 4 of the studies, the recurrence rate of syncope or presyncope was also evaluated. A total of 233 children with VVS were included in the salt and water intervention group. The cases in the control group were treated with non-medicinal conventional therapy. The results revealed that the negative changing rate of the HUTT in the intervention group (144/233, 61.8%) was higher than that in the control group (48/179, 26.8%), and the difference was significant (P &lt; 0.00001). The recurrence rate of syncope or presyncope in the intervention group (85/195, 43.6%) was lower than that in the control group (86/144, 59.7%), and the difference was significant (P = 0.002).Conclusion: The current findings suggest that increased salt and water intake may increase the negative changing rates of the HUTT and reduce syncope or presyncope recurrence rates in pediatric patients with VVS.
Recommendations for the Implementation of Hospital Based HTA in Poland: Lessons Learned From International Experience
Authors: Gałązka-Sobotka Małgorzata , Kowalska-Bobko Iwona , Lach Krzysztof , Mela Aneta , Furman Maciej , Lipska Iga 
Published: May 2021

Introduction: The main challenge of modern hospitals is purchasing medical technologies. Hospital-based health technology assessments (HB-HTAs) are used in healthcare facilities around the world to support management boards in providing relevant technologies for patients.Aim: This study was undertaken to update the existing body of knowledge on the characteristics of HB-HTA systems/models in the selected European countries. Insights gained from this study were used to provide an optimal approach for implementing HB-HTA in Poland.Materials and methods: Firstly, we carried out a systematic review in PubMed and embase. Secondly, we searched for gray literature via the AdHopHTA online handbook and the design book of the AdHopHTA project, as well as literature describing healthcare systems provided by the WHO. Then, we conducted in-depth interviews with HB-HTA experts from four countries. Finally, we selected ten countries from Europe and prepared frameworks for data collection and analyses.Results: The selected countries (Switzerland, Spain, France, Italy, Denmark, Finland, Sweden, the Netherlands, and Austria) are examples of decentralized or deconcentrated healthcare systems. In terms of HB-HTA, differences in organisational models (independent group, stand-alone, integrated-essential, integrated-specialised), type of financing (internally vs. externally), collaboration with an HTA National Agency and other stakeholders (e.g., Patients’ Associations) were identified. HB-HTA engages multi-skilled staff with various academic backgrounds and operates mainly on a voluntary basis.Conclusion: Strengths and weaknesses associated with various organisational models must be carefully considered in the context of support for decentralized or centralized models of implementation while embarking on HTA activities in Polish hospitals.