bluuebunny/crossref_metadata_2025_split huggingface dataset:
Findings from the Hispanic Community Health Study/Study of Latinos on the Importance of Sociocultural Environmental Interactors: Polygenic Risk Score-by-Immigration and Dietary Interactions
Authors: McArdle Cristin E. , Bokhari Hassan , Rodell Clinton C. , Buchanan Victoria , Preudhomme Liana K. , Isasi Carmen R. , Graff Mariaelisa , North Kari , Gallo Linda C. , Pirzada Amber , Daviglus Martha L. , Wojcik Genevieve , Cai Jianwen , Perreira Krista , Fernandez-Rhodes Lindsay 
Published: December 2021

Introduction: Hispanic/Latinos experience a disproportionate burden of obesity. Acculturation to US obesogenic diet and practices may lead to an exacerbation of innate genetic susceptibility. We examined the role of gene–environment interactions to better characterize the sociocultural environmental determinants and their genome-scale interactions, which may contribute to missing heritability of obesity. We utilized polygenic risk scores (PRSs) for body mass index (BMI) to perform analyses of PRS-by-acculturation and other environmental interactors among self-identified Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).Methods: PRSs were derived using genome-wide association study (GWAS) weights from a publicly available, large meta-analysis of European ancestry samples. Generalized linear models were run using a set of a priori acculturation-related and environmental factors measured at visit 1 (2008–2011) and visit 2 (2014–2016) in an analytic subsample of 8,109 unrelated individuals with genotypic, phenotypic, and complete case data at both visits. We evaluated continuous measures of BMI and waist-to-hip ratio. All models were weighted for complex sampling design, combined, and sex-stratified.Results: Overall, we observed a consistent increase of BMI with greater PRS across both visits. We found the best-fitting model adjusted for top five principal components of ancestry, sex, age, study site, Hispanic/Latino background genetic ancestry group, sociocultural factors and PRS interactions with age at immigration, years since first arrival to the United States (p &lt; 0.0104), and healthy diet (p &lt; 0.0036) and explained 16% of the variation in BMI. For every 1-SD increase in PRS, there was a corresponding 1.10 kg/m2 increase in BMI (p &lt; 0.001). When these results were stratified by sex, we observed that this 1-SD effect of PRS on BMI was greater for women than men (1.45 vs. 0.79 kg/m2, p &lt; 0.001).Discussion: We observe that age at immigration and the adoption of certain dietary patterns may play a significant role in modifying the effect of genetic risk on obesity. Careful consideration of sociocultural and immigration-related factors should be evaluated. The role of nongenetic factors, including the social environment, should not be overlooked when describing the performance of PRS or for promoting population health in understudied populations in genomics.
SEMA6B Overexpression Predicts Poor Prognosis and Correlates With the Tumor Immunosuppressive Microenvironment in Colorectal Cancer
Authors: Li Tiegang , Yan Zheng , Wang Weiqi , Zhang Rixin , Gan Wenqiang , Lv Silin , Zeng Zifan , Hou Yufang , Yang Min 
Published: December 2021

Background: Semaphorin 6b (SEMA6B) is a member of the semaphorin axon-guidance family and has been demonstrated to both induce and inhibit tumor progression. However, the role of SEMA6B in colorectal cancer (CRC) has remained unclear. This study sought to explore the promising prognostic biomarker for CRC and to understand the expression pattern, clinical significance, immune effects, and biological functions of SEMA6B.Methods: SEMA6B expression in CRC was evaluated via multiple gene and protein expression databases and we identified its prognostic value through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Correlations between SEMA6B expression and components of the tumor immune microenvironment were analyzed by packages implemented in R, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and Tumor-Immune System Interactions database (TISIDB). RNA interference was performed to silence the expression of SEMA6B to explore its biological roles in the colon cancer cell lines HCT116 and LoVo.Results: The messenger RNA (mRNA) level of SEMA6B and the protein expression were higher in CRC tissues than adjacent normal tissues from multiple CRC datasets. High SEMA6B expression was significantly associated with dismal survival. Multivariate Cox regression analysis demonstrated that SEMA6B was an independent prognostic factor for progression-free survival (PFS). The nomogram showed a favorable predictive ability in PFS. Functional enrichment analysis and the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm revealed that the gene cluster associated with the high SEMA6B group were prominently involved in immune responses and inflammatory activities. Notably, SEMA6B expression was positively correlated with infiltrating levels of CD4+ T cells, macrophages, myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), neutrophils, and dendritic cells. Moreover, SEMA6B expression displayed strong correlations with diverse marker sets of immunosuppressive cells in CRC. Integrative analysis revealed that immunosuppressive molecules and immune checkpoints were markedly upregulated in CRC samples with high SEMA6B expression. Furthermore, knockdown of SMEA6B in colon cancer cells significantly inhibited cell proliferation, migration, invasion and reduced the mRNA levels of immunosuppressive molecules.Conclusion: Our findings provide evidence that high SEMA6B expression correlated with adverse prognosis and the tumor immunosuppressive microenvironment in CRC patients. Therefore, SEMA6B may serve as a novel prognostic biomarker for CRC, which offers further insights into developing CRC-targeted immunotherapies.
The Variants at APOA1 and APOA4 Contribute to the Susceptibility of Schizophrenia With Inhibiting mRNA Expression in Peripheral Blood Leukocytes
Authors: Fan Yao , Gao Jun , Li Yinghui , Chen Xuefei , Zhang Ting , You Weiyan , Xue Yong , Shen Chong 
Published: December 2021

Objective: Abnormal lipid metabolism has a close link to the pathophysiology of schizophrenia (SZ). This study mainly aimed to evaluate the association of variants at apolipoprotein A1 (APOA1) and APOA4 with SZ in a Chinese Han population.Methods: The rs5072 of APOA1 and rs1268354 of APOA4 were examined in a case–control study involving 2,680 patients with SZ from the hospital and 2,223 healthy controls screened by physical examination from the community population. The association was estimated with the odds ratio (OR) and 95% confidence intervals (95% CIs) by logistic regression. The APOA1 and APOA4 messenger RNA (mRNA) in peripheral blood leukocytes were measured by real-time PCR and compared between SZ cases and controls. Serum apoA1 levels were detected by turbidimetric inhibition immunoassay and high-density lipoprotein cholesterol (HDL-C) levels were detected by the homogeneous method.Results: Both of the rs5072 of APOA1 and rs1268354 of APOA4 had statistically significant associations with SZ. After adjustment for age and sex, ORs (95% CIs) of the additive model of rs5072 and rs1268354 were 0.82 (0.75–0.90) and 1.120 (1.03–1.23), and p-values were 3.22 × 10−5 and 0.011, respectively. The association of rs5072 with SZ still presented statistical significance even after Bonferroni correction (p-value×6). SZ patients during the episode presented lower levels of apoA1, HDL-C, mRNA of APOA1 common variants and transcript variant 4, and APOA4 mRNA than controls (p &lt; 0.01) while SZ patients in remission showed a significantly decreased APOA1 transcript variant 3 expression level and increased APOA4 mRNA expression level (p &lt; 0.01). mRNA expression levels of APOA1 transcript variant 4 significantly increased with the variations of rs5072 in SZ during the episode (ptrend = 0.017). After the SZ patients received an average of 27.50 ± 9.90 days of antipsychotic treatment, the median (interquartile) of serum apoA1 in the SZ episode significantly increased from 1.03 (1.00.1.20) g/L to 1.08 (1.00.1.22) g/L with the p-value of 0.044.Conclusion: Our findings suggest that the genetic variations of APOA1 rs5072 and APOA4 rs1268354 contribute to the susceptibility of SZ, and the expression levels of APOA1 and APOA4 mRNA of peripheral blood leukocytes decreased in SZ patients during the episode while APOA4 increased after antipsychotic treatment.
A Comparative Study of Structural and Metabolic Brain Networks in Patients With Mild Cognitive Impairment
Authors: Wei Cuibai , Gong Shuting , Zou Qi , Zhang Wei , Kang Xuechun , Lu Xinliang , Chen Yufei , Yang Yuting , Wang Wei , Jia Longfei , Lyu Jihui , Shan Baoci 
Published: December 2021

Background: Changes in the metabolic and structural brain networks in mild cognitive impairment (MCI) have been widely researched. However, few studies have compared the differences in the topological properties of the metabolic and structural brain networks in patients with MCI.Methods: We analyzedmagnetic resonance imaging (MRI) and fluoro-deoxyglucose positron emission tomography (FDG-PET) data of 137 patients with MCI and 80 healthy controls (HCs). The HC group data comes from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The permutation test was used to compare the network parameters (characteristic path length, clustering coefficient, local efficiency, and global efficiency) between the two groups. Partial Pearson’s correlation analysis was used to calculate the correlations of the changes in gray matter volume and glucose intake in the key brain regions in MCI with the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-cog) sub-item scores.Results: Significant changes in the brain network parameters (longer characteristic path length, larger clustering coefficient, and lower local efficiency and global efficiency) were greater in the structural network than in the metabolic network (longer characteristic path length) in MCI patients than in HCs. We obtained the key brain regions (left globus pallidus, right calcarine fissure and its surrounding cortex, left lingual gyrus) by scanning the hubs. The volume of gray matter atrophy in the left globus pallidus was significantly positively correlated with comprehension of spoken language (p = 0.024) and word-finding difficulty in spontaneous speech item scores (p = 0.007) in the ADAS-cog. Glucose intake in the three key brain regions was significantly negatively correlated with remembering test instructions items in ADAS-cog (p = 0.020, p = 0.014, and p = 0.008, respectively).Conclusion: Structural brain networks showed more changes than metabolic brain networks in patients with MCI. Some brain regions with significant changes in betweenness centrality in both structural and metabolic networks were associated with MCI.
Early Tranexamic Acid in Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials
Authors: Jiao Xu , Li Mingfei , Li Lulu , Hu Xinyu , Guo Xiaohui , Lu Yun 
Published: December 2021

Objective: Intracranial hemorrhage (ICH) is a common complication of traumatic brain, in which tranexamic acid has been recommended as an additional therapy to prevent a second bleeding. However, the effect of early administration of tranexamic acid for ICH patients remains controversial.Methods: A systematic search was performed in Cochrane Library, Medline, Embase, and Web of Science. Poor outcome refers to significant hemorrhage growth, new intracranial hemorrhage, new focal cerebral ischaemic lesions, the need for neurosurgery, or death. Study heterogeneity and publication bias were estimated.Results: Seven randomized controlled trials involving 3,192 participants were included in our meta-analysis. Tranexamic acid administration in ICH patients was associated with better outcomes of hematoma expansion (odd ratios [OR] 0.79; 95% confidence interval (CI) CI, 0.67–0.93; I2 = 0%; P = 0.006) and growth of hemorrhagic lesions (weighted mean difference [WMD], −1.97 ml; 95% CI, −2.94 to −1.00; I2 = 14%; P &lt; 0.001) than the placebo. No difference was found between the mortality, poor outcome, neurosurgical intervention, new bleeding, and the duration of hospital stay. Moreover, no publication bias was found.Conclusion: Our analysis reveals that the early treatment with tranexamic acid can significantly reduce the incidence of hematoma expansion and the volume of hemorrhagic lesion, but does not exert considerable effects on mortality, poor outcome, neurosurgery, rebleeding, and the duration of stay.
Altered Default Mode Network Is Associated With Cognitive Impairment in CADASIL as Revealed by Multimodal Neuroimaging
Authors: Li Panlong , Huang Qi , Ban Shiyu , Qiao Yuan , Wu Jing , Zhai Yu , Du Xiaoxia , Hua Fengchun , Su Jingjing 
Published: December 2021

Background and Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy caused by mutations in the NOTCH3 gene is a hereditary cerebral small vessel disease, manifesting with stroke, cognitive impairment, and mood disturbances. Functional or structural changes in the default mode network (DMN), which plays important role in cognitive and mental maintenance, have been found in several neurological and mental diseases. However, it remains unclear whether DMN is altered in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).Methods: Multimodal imaging methods, including MRI and positron emission tomography (PET), were applied to evaluate the functional, structural, and metabolic characteristics of DMN in 25 patients with CADASIL and 42 healthy controls.Results: Compared with controls, patients with CADASIL had decreased nodal efficiency and degree centrality of the dorsal medial pre-frontal cortex and hippocampal formation within DMN. Structural MRI and diffusion tensor imaging (DTI) showed decreased gray matter volume and fiber tracks presented in the bilateral hippocampal formation. Meanwhile, PET imaging showed decreased metabolism within the whole DMN in CADASIL. Furthermore, correlation analyses showed that these nodal characteristics, gray matter volume, and metabolic signals of DMN were related to cognitive scores in CADASIL.Conclusions: Our results suggested that altered network characteristics of DMN might play important roles in cognitive deficits of CADASIL.
Combined Application of Sodium Fluorescein and Neuronavigation Techniques in the Resection of Brain Gliomas
Authors: Xue Zhan , Kong Lu , Hao Shuyu , Wang Yu , Jia Guijun , Wu Zhen , Jia Wang , Zhang Junting , Zhang Liwei 
Published: December 2021

Objectives: To explore the effectiveness and safety of the combined application of sodium fluorescein and neuronavigation techniques in the resection of brain gliomas in different locations and patients of different ages.Methods: Fifty clinical cases of brain gliomas treated at the Department of Neurosurgery of Beijing Tiantan Hospital were collected from March 2014 to March 2019. These cases were divided into a supratentorial group (24 cases) and a brainstem group (26 cases) based on location and an adult group (28 cases) and a pediatric group (22 cases) based on age. Fluorescein-guided surgery was performed: the adult group received 5 mg/kg sodium fluorescein before opening the dura, while the pediatric group received 2.5 mg/kg during resection. Tumor visualization was evaluated by the enhancement of yellow fluorescein and considered “satisfactory” if the illumination demarcated the tumor boundary. Additionally, the consistency between fluorescein and neuronavigation was analyzed. The Karnofsky performance score (KPS) of all patients was recorded and assessed at admission, discharge, and the 6-month follow-up.Results: In the 28 adult cases, 4 were unsatisfactory, while in the 22 pediatric cases, 2 were unsatisfactory; in 7 cases, there was an inconsistency between yellow fluorescein enhancement and neuronavigation, 6 were in the supratentorial group, and 1 was in the brainstem group. Statistical analysis showed no significant differences in the satisfactory rate between the adult and pediatric groups (P = 0.575), whereas there were significant differences inconsistency between the supratentorial group and brainstem group (P = 0.031). The mean KPS at admission was between 70 and 100, which was not significantly different from that at discharge (P = 0.839), but the KPS at the 6-month follow-up was significantly higher than that at admission (P = 0.041).Conclusions: The consistency between sodium fluorescein and the neuronavigation system was higher in the brainstem group than in the supratentorial group; a half dose of sodium fluorescein (2.5 mg/kg) was sufficient for pediatric patients. The combined utilization of sodium fluorescein and neuronavigation techniques may confer glioma patients the opportunity to obtain better clinical outcomes after surgery.
Postural Asymmetries and Assistive Devices Used by Adults With Cerebral Palsy in Lying, Sitting, and Standing
Authors: Rodby-Bousquet Elisabet , Agustsson Atli 
Published: December 2021

Purpose: To describe the use of assistive devices and postural asymmetries in lying, sitting and standing positions in adults with cerebral palsy, and to analyze postural asymmetries and any associations with their ability to maintain or change position and time in these positions.Methods: A cross-sectional study based on data from the Swedish Cerebral Palsy follow-up program of 1,547 adults aged 16–76 years, at Gross Motor Function Classification System (GMFCS) levels I (n = 330), II (n = 323), III (n = 235), IV (n = 298), and V (n = 361). Assistive devices such as wheelchairs, seating systems, adjustable beds, standing equipment and time in each position were reported. The Posture and Postural Ability Scale was used to identify asymmetries and rate the ability to maintain or change position. Binary logistic regression models were used to estimate odds ratios (OR) for postural asymmetries in supine, sitting and standing.Results: Assistive devices were used by 63% in sitting (range 5–100% GMFCS levels I–V), 42% in lying (4–92% levels I-V), and 32% in standing (2–70% levels II–V). Wheelchairs were used as seating systems by 57%. Most adults had postural asymmetries in supine (75%; range 35–100% levels I–V), sitting (81%; 50–99% levels I–V) and standing (88%; 65–100% levels I–V). Men were more likely than women to have postural asymmetries, and the likelihood of postural asymmetries increased with age, GMFCS levels and inability to change position. Inability to maintain position increased the probability of postural asymmetries in all positions from OR 2.6 in standing to OR 8.2 in lying and OR 13.1 in sitting.Conclusions: Almost twice as many adults used assistive devices in sitting than in lying or standing. Two thirds of the adults who used standing devices used it for &lt;1 h per day, indicating that they might spend the remaining 23 out of 24 h per day either sitting or lying. Asymmetric postures were frequent across all ages and were highly associated with inability to change or maintain position.
Trauma Communications Center Coordinated Severity-Based Stroke Triage: Protocol of a Hybrid Type 1 Effectiveness-Implementation Study
Authors: Gropen Toby I. , Ivankova Nataliya V. , Beasley Mark , Hess Erik P. , Mittman Brian , Gazi Melissa , Minor Michael , Crawford William , Floyd Alice B. , Varner Gary L. , Lyerly Michael J. , Shoemaker Camella C. , Owens Jackie , Wilson Kent , Gray Jamie , Kamal Shaila 
Published: December 2021

Background:Mechanical thrombectomy (MT) can improve the outcomes of patients with large vessel occlusion (LVO), but a minority of patients with LVO are treated and there are disparities in timely access to MT. In part, this is because in most regions, including Alabama, the emergency medical service (EMS) transports all patients with suspected stroke, regardless of severity, to the nearest stroke center. Consequently, patients with LVO may experience delayed arrival at stroke centers with MT capability and worse outcomes. Alabama's trauma communications center (TCC) coordinates EMS transport of trauma patients by trauma severity and regional hospital capability. Our aims are to develop a severity-based stroke triage (SBST) care model based on Alabama's trauma system, compare the effectiveness of this care pathway to current stroke triage in Alabama for improving broad, equitable, and timely access to MT, and explore stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability.Methods:This is a hybrid type 1 effectiveness-implementation study with a multi-phase mixed methods sequential design and an embedded observational stepped wedge cluster trial. We will extend TCC guided stroke severity assessment to all EMS regions in Alabama; conduct stakeholder interviews and focus groups to aid in development of region and hospital specific prehospital and inter-facility stroke triage plans for patients with suspected LVO; implement a phased rollout of TCC Coordinated SBST across Alabama's six EMS regions; and conduct stakeholder surveys and interviews to assess context-specific perceptions of the intervention. The primary outcome is the change in proportion of prehospital stroke system patients with suspected LVO who are treated with MT before and after implementation of TCC Coordinated SBST. Secondary outcomes include change in broad public health impact before and after implementation and stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability using a mixed methods approach. With 1200 to 1300 total observations over 36 months, we have 80% power to detect a 15% improvement in the primary endpoint.Discussion:This project, if successful, can demonstrate how the trauma system infrastructure can serve as the basis for a more integrated and effective system of emergency stroke care.
Plasma Uric Acid Helps Predict Cognitive Impairment in Patients With Amyotrophic Lateral Sclerosis
Authors: Tang Jiahui , Yang Yuan , Gong Zhenxiang , Li Zehui , Huang Lifang , Ding Fengfei , Liu Mao , Zhang Min 
Published: December 2021

Objective: Uric acid as an antioxidant plays an important role in neurodegenerative disease. Our objective is to investigate the relationship between plasma uric acid and cognitive impairment in patients with amyotrophic lateral sclerosis (ALS).Methods: In this cross-sectional study, 124 ALS patients were screened by the Edinburgh Cognitive and Behavioral Screen (ECAS) and classified according to the revised Strong's criteria. Additionally, based on total ECAS cut-off score patients were categorized into those with cognitive impairment (ALS-cie) and those without cognitive impairment (ALS-ncie), and clinical data and uric acid level were compared between the two groups. Parameters with significant differences were further included in a multivariate linear regression analysis with ECAS score as a dependent variable. Hold-out validation was performed to evaluate the fitness of regression model.Results: Up to 60% of ALS patients showed cognitive or/and behavioral impairment. The ALS-cie group had lower education level (p &lt; 0.001), older age at symptom onset (p = 0.001), older age at testing (p = 0.001), and lower plasma uric acid (p = 0.01). Multivariate analysis showed increased uric acid (β = 0.214, p = 0.01), lower age at testing (β = −0.378, p &lt; 0.001), and higher education level (β = 0.424, p &lt; 0.001) could predict higher ECAS score (F = 19.104, R2 = 0.381, p &lt; 0.0001). Validation analysis showed that predicted ECAS score was significantly correlated with raw ECAS score in both the training set (rs = 0.621, p &lt; 0.001) and the testing set (rs = 0.666, p &lt; 0.001).Conclusions: Cognitive impairment was a common feature in our Chinese ALS patients. Plasma uric acid might help evaluate the risk of cognitive impairment in ALS patients when combined with education level and age at testing.