bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Highly Sensitive Neurofilament Light Chain Assay on an Automated Immunoassay Platform
Authors: Lee Stephen , Plavina Tatiana , Singh Carol M. , Xiong Kuangnan , Qiu Xiaolei , Rudick Richard A. , Calabresi Peter A. , Stevenson Lauren , Graham Danielle , Raitcheva Denitza , Green Christopher , Matias Madeleine , Uzgiris Arejas J. 
Published: July 2022

BackgroundNeurofilament light chain (NfL) is an axonal cytoskeletal protein that is released into the extracellular space following neuronal or axonal injury associated with neurological conditions such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and other diseases. NfL is detectable in the cerebrospinal fluid (CSF) and blood. Numerous studies on MS have demonstrated that NfL is correlated with disease activity, predicts disease progression, and is reduced by treatment with MS disease-modifying drugs, making NfL an attractive candidate to supplement existing clinical and imaging measures in MS. However, for NfL to achieve its potential as a clinically useful biomarker for clinical decision-making or drug development, a standardized, practical, and widely accessible assay is needed. Our objective was to develop a novel NfL assay on an automated, globally available immunoassay platform and validate its performance.MethodsA prototype NfL assay was first developed and evaluated on the ADVIA Centaur® XP immunoassay system from Siemens Healthineers. The lower limit of quantitation (LLoQ), within-lab precision, assay range, cross-reactivity with neurofilament medium and heavy chains, and effect of interfering substances were determined. NfL assay values in serum and CSF were compared with radiological and clinical disease activity measures in patients with MS and ALS, respectively. This assay was further optimized to utilize serum, plasma, and CSF sample types on the Atellica® IM system and transferred to Siemens' CLIA laboratory where it was analytically validated as a laboratory-developed test (LDT).ResultsIn this study, an LLoQ of 1.85 pg/mL, within-lab precision &lt;6%, and an assay range of up to 646 pg/mL were demonstrated with the serum prototype assay. Cross-reactivity of &lt;0.7% with the neurofilament medium and heavy chains was observed. Serum and CSF NfL assay values were associated with radiological and clinical disease activity measures in patients with MS and ALS, respectively. The optimized version of the NfL assay demonstrated specimen equivalence with additional plasma tube types and was analytically validated as an LDT.ConclusionThe analytical performance of the NfL assay fulfilled all acceptance criteria; therefore, we suggest that the assay is acceptable for use in both research and clinical practice settings to determine elevated NfL levels in patients.
Case report: Endovascular treatment of two scalp arteriovenous malformation cases via direct percutaneous catheterization: A case series
Authors: Shi Yuan , Liu Peixi , Liu Yingtao , Quan Kai , Li Peiliang , Li Zongze , Zhu Wei , Tian Yanlong 
Published: July 2022

BackgroundScalp arteriovenous malformations (AVM) are rare vascular malformations reported only in small case series. Scalp AVMs usually present with symptoms, including headache, tinnitus, epilepsy, cerebral ischemia, and necrosis of the scalp, which can cause functional, cosmetic, and psychological problems. There are many difficulties in the treatment of scalp AVM because of its complex characteristics of vascular anatomy, non-uniform structure, and intracranial-extracranial anastomosis.Case descriptionTo illustrate the endovascular treatment of scalp AVM via direct percutaneous puncture while traditional arterial and venous approaches were not available. In this report, access was obtained through a direct puncture of the enlarged frontal vein. Onyx-18 was injected through a microcatheter to occlude draining veins, fistulous connection, and the feeders. An 18-gauge indwelling needle was inserted into draining veins directly. Postembolization angiography demonstrated complete sAVM occlusion immediately and no non-targeted embolization. At a 1-year follow-up, no procedure-related complications and evidence of recurrence were observed.ConclusionThe technique of endovascular embolization via direct percutaneous puncture approach is safe, rapid, and effective for specific sAVM. Treatment options should be made in terms of size, vascular anatomical characteristics of the lesions, patient's preference, cosmetic factors, and available expertise.
The role of vitamin D in the link between physical frailty and cognitive function: A mediation analysis in community-dwelling Chinese older adults
Authors: Xiong Jian , Xue Wen-Xiong 
Published: July 2022

BackgroundPhysical frailty and cognitive aging have important influences on poor clinical outcomes in older adults. Many studies have investigated the association between frailty and cognitive function, but whether vitamin D mediates the association between frailty and cognitive function is unclear. We explored the mediating role of vitamin D on the cross-sectional association between physical frailty and cognitive function using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).MethodsWe analyzed data from 1944 subjects aged 60 years and older from the 2011 CLHLS cohort. Frailty status was identified by the Osteoporotic Fracture Study (SOF) index. The Chinese version of the Mini-Mental State Examination (MMSE) was used to assess cognitive function. Linear regression models were used to examine the association between frailty, vitamin D, and cognition, adjusted for a range of covariates. Mediation analyses tested the indirect effects of vitamin D on physical frailty and cognitive function.ResultPhysical frailty was negatively associated with vitamin D levels and scores on the MMSE, and vitamin D levels were positively associated with scores on the MMSE. Linear regression analysis showed that physical frailty and serum vitamin D concentration were significant predictors of cognitive function. Importantly, mediation analysis showed that serum vitamin D concentration significantly mediated the relationship between physical frailty and cognitive function.ConclusionThe association between physical frailty and cognitive function appears to be mediated by vitamin D. Future studies should explore whether serum vitamin D concentrations may mediate the association between physical frailty and cognitive decline and whether this mediating role is moderated by other factors.
Vitamin D levels and clinical outcomes of SARS-CoV-2 Omicron subvariant BA.2 in children: A longitudinal cohort study
Authors: Peng Denggao , Huang Hua , Liu Zhichao , Gao Yanzhang , Liu Yingxia 
Published: July 2022

ObjectiveTo investigate the picture between vitamin D levels and clinical outcomes of SARS-CoV-2 Omicron subvariant BA.2 in children.MethodsA retrospective, longitudinal cohort study was performed. All included hospitalized cases were divided into the sufficient (sVD) and insufficient vitamin D (iVD) groups according to whether their serum 25-hydroxyvitamin D [25(OH)D] concentration was ≥30 ng/mL. Dynamic changes in clinical parameters were observed for seven time periods within 28 days after admission.ResultsSerum 25(OH)D concentrations were significantly negatively correlated with age in the included cases (r = −0.6; P &lt; 0.001). Compared with the iVD group (n = 80), the sVD group (n = 36) had higher interleukin-6 (18.4 vs. 12.9; P = 0.003) within the first day; higher procalcitonin within the first (0.15 vs. 0.1; P = 0.03), 2–3 (0.14 vs. 0.07; P = 0.03), 4–5 (0.21 vs. 0.07; P = 0.02) days; more lymphocytes within the first (1.6 vs. 1.2; P = 0.02), 2–3 (3.7 vs. 2; P = 0.001), 4–5 (3.9 vs. 2.1; P = 0.01) and 6–7 (4.9 vs. 2.7; P = 0.02) days; notably, higher cycle threshold for N gene (30.6 vs 19.8; P = 0.03) or ORF1ab gene (31.4 vs 20.1; P = 0.03) within 2 to 3 days. Pneumonia lesions were found in eleven and six cases in the iVD and sVD groups, respectively, without significant difference on computed tomography at admission. Six out of eleven and five out of six had a repeat computed tomography after 1–2 weeks. Lesion improvement was more significant in the sVD group (P = 0.04).ConclusionsChildren with vitamin D insufficiency might have poorer clinical outcomes in Omicron subvariant BA.2 infection, especially in older pediatric patients. Further studies are needed to assess effectiveness of supplements in reducing the same.
Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma
Authors: Kui Xue-Yan , Gao Yan , Liu Xu-Sheng , Zeng Jing , Yang Jian-Wei , Zhou Lu-Meng , Liu Xiao-Yu , Zhang Yu , Zhang Yao-Hua , Pei Zhi-Jun 
Published: July 2022

BackgroundSolute carrier family 17 member 9 (SLC17A9) encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. SLC17A9 is involved in the occurrence and development of various cancers, but its biological role in liver hepatocellular carcinoma (LIHC) is unclear.MethodsThe expression level of SLC17A9 was assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumor tissues and adjacent normal liver tissues. The receiver operating characteristic (ROC) and R software package performed diagnosis and prognosis. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment and co-expression of SLC17A9, gene–gene interaction (GGI), and protein–protein interaction (PPI) networks were performed using R, GeneMANIA, and STRING. Western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence, colony formation, wound scratch assay, ATP production assays, and high connotation were applied to determine the effect of SLC17A9 knockdown on HEPG2 (hepatocellular liver carcinoma) cells. TIMER, GEPIA, and TCGA analyzed the relationship between SLC17A9 expression and immune cells, m6A modification, and ferroptosis.ResultsSLC17A9 expression in LIHC tissues was higher than in normal liver tissues (p &lt; 0.001), and SLC17A9 was related to sex, DSS (disease-specific survival), and PFI (progression-free interval) (p = 0.015, 0.006, and 0.023). SLC17A9 expression has diagnostic (AUC: 0.812; CI: 0.770–0.854) and prognostic potential (p = 0.015) in LIHC. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) functional enrichment analysis showed that SLC17A9 was closely related to neuronal cell body, presynapse, axonogenesis, PI3K/Akt signaling pathway. GGI showed that SLC17A9 was closely related to MYO5A. PPI showed that SLC17A9 was closely related to SLC18A3. SLC17A9 silencing inhibited HepG2 cells proliferation, migration, colony formation, and reduced their ATP level. SLC17A9 expression level was related to immune cells: B cells (r = 0.094, P = 8.06E-02), CD4+ T cells (r = 0.184, P = 5.95E-04), and macrophages (r = 0.137, P = 1.15E-02); m6A modification: HNRNPC (r = 0.220, p &lt; 0.001), METTL3 (r = 0.180, p &lt; 0.001), and WTAP (r = 0.130, p = 0.009); and ferroptosis: HSPA5 (r = 0.240, p &lt; 0.001), SLC7A11 (r = 0.180, p &lt; 0.001), and FANCD2 (r = 0.280, p &lt; 0.001).ConclusionOur data show that SLC17A9 may influence LIHC progression. SLC17A9 expression correlates with tumor immune infiltration, m6A modification, and ferroptosis in LIHC and may have diagnostic and prognostic value in LIHC.
Baseline serum uric acid level is associated with progression-free survival, disease control rate, and safety in postoperative patients with colorectal cancer treated by FOLFOX, FOLFIRI, or XELOX
Authors: Zhang Xi , Chen Qing-hong , Yang Ying , Lin Jing-xin , Li Yan-chun , Zhong Tian-yu , Chen Jie , Wu Si-qi , Chen Xiao-hu , Zhou Rui-si , Lin Jia-man , Wang Dong-qing , He Qiu-xing , You Yan-ting , Zhou Xing-hong , Zuo Qiang , Liu Yan-yan , Cheng Jing-ru , Wu Yi-fen , Zhao Xiao-shan 
Published: July 2022

BackgroundHigh serum uric acid (SUA) levels increase the risk of overall cancer morbidity and mortality, particularly for digestive malignancies. Nevertheless, the correlation between SUA level and clinical outcomes of the postoperative patients with colorectal cancer (CRC) treated by chemotherapy is unclear. This study aimed at exploring the relationship between baseline SUA level and progression-free survival (PFS), disease control rate (DCR), and safety in postoperative CRC patients receiving chemotherapy.Patients and MethodsWe conducted a retrospective study to evaluate the relationship between baseline SUA level and PFS, DCR, and incidence of serious adverse events of 736 postoperative CRC patients treated with FOLFOX, FOLFIRI or XELOX at our center.ResultsData from our center suggested that high baseline SUA level is linked to poor PFS in non-metastatic CRC patients using FOLFOX (HR=2.59, 95%CI: 1.29-11.31, p=0.018) and in male patients using FOLFIRI (HR=3.77, 95%CI: 1.57-39.49, p=0.012). In patients treated by FOLFIRI, a high SUA is also linked to a low DCR (p=0.035). In patients using FOLFOX, high baseline SUA level is also linked to a high incidence of neutropenia (p=0.0037). For patients using XELOX, there is no significant correlation between SUA level and PFS, effectiveness, or safety.ConclusionsThese findings imply that a high SUA level is a promising biomarker associated with poor PFS, DCR and safety of postoperative CRC patients when treated with FOLFOX or FOLFIRI.
Effect of Pyroptosis-Related Genes on the Prognosis of Breast Cancer
Authors: Zhou Ying , Zheng Jianfeng , Bai Mengru , Gao Yuzhen , Lin Nengming 
Published: July 2022

BackgroundsPyroptosis, a newly pattern of specific programmed cell death, has been reported to participate in several cancers. However, the value of pyroptosis in breast cancer (BRCA) is still not clear.MethodsHerein, we analyzed the data of BRCA from both The Cancer Genome Atlas (TCGA) and GSEA MSigDB database. Based on the obtained pyroptosis-related genes (PRGs), we searched the interactions by STRING. After that, we performed clustering analysis by ConsensusClusterPlus. The PRGs with significant prognostic value were then screened through univariate cox regression and further evaluate by constructing a risk model by least absolute shrinkage and selection operator (LASSO) Cox regression. The immune and sensitivity to drugs were also predicted by comprehensive algorithms. Finally, real-time quantitative PCR (qPCR) was performed on two of the screened signature PRGs.ResultsA total of 49 PRGs were obtained from public database and 35 of them were significantly differentially expressed genes (DEGs). Cluster analysis was then performed to explore the relationship between DEGs with overall survival. After that, 6 optimal PRGs (GSDMC, IL-18, CHMP3, TP63, GZMB and CHMP6) were screened out to construct a prognostic signature, which divide BRCA patients into two risk groups. Risk scores were then confirmed to be independent prognostic factors in BRCA. Functional enrichment analyses showed that the signature were obviously associated with tumor-related and immune-associated pathways. 79 microenvironmental cells and 11 immune checkpoint genes were found disparate in two groups. Besides, tumor immune dysfunction and exclusion (TIDE) scores revealed that patients with higher risk scores are more sensitive to immune checkpoint blockade treatment. Patients in the low-risk group were more sensitive to Cytarabine, Docetaxel, Gefitinib, Paclitaxel, and Vinblastine. Inversely, patients in the high-risk group were more sensitive to Lapatinib. Finally, we found that, CHMP3 were down-regulated in both BRCA tissues and cell lines, while IL-18 were up-regulated.ConclusionPRGs play important roles in BRCA. Our study fills the gaps of 6 selected PRGs in BRCA, which were worthy for the further study as predict potential biomarkers and therapeutic targets.
Isochlorogenic Acid C Alleviates High-Fat Diet-Induced Hyperlipemia by Promoting Cholesterol Reverse Transport
Authors: Zheng Liuyi , Lin Guangyao , Li Ruyue , Gan Haining , Huang Xuejun , Yao Nan , Cai Dake , Zhao Ziming , Hu Zixuan , Li Minyi , Xu Huazhen , Li Leyi , Peng Sha , Zhao Xinxin , Lai Yijing , Chen Yuxing , Huang Dane 
Published: July 2022

Background: Promoting cholesterol reverse transport (RCT) has been proven to be a promising hyperlipidemia therapy since it is more effective for the treatment of atherosclerosis (AS) caused by hyperlipidemia. Liver X receptor (LXR) agonists can accelerate RCT, but most of them trigger undesirable liver steatosis due to the activation of liver LXRα.Aim: We aim to figure out whether isochlorogenic acid C (ICAC) facilitates RCT without causing hepatic steatosis.Methods:In vitro study, we established foam macrophages and macrophages with loaded NBD-cholesterol models to investigate the competence of RCT promoting ICAC. RT-qPCR and Western blot were used to verify ICAC’s regulation of RCT and NF-κB inflammatory pathways. In this in vivo study, male 6-week-old C57BL/6 mice were fed a high-fat diet (HFD) to investigate ICAC’s anti-hyperlipidemic effect and its functions in regulating RCT. The anti-hyperlipidemic effect of ICAC was evaluated by blood and liver lipid levels, liver hematoxylin, oil red o staining, and liver coefficient. Finally, mRNA levels of genes involved in RCT and inflammation pathways in the liver and intestine were detected by RT-qPCR.Results: ICAC prevented macrophages from foaming by up-regulating the LXRα mediated RCT pathway and down-regulating expression of the cholesterol absorption genes LDLR and CD36, as well as suppressing iNOS, COX2, and IL-1β inflammatory factors. In HFD-fed mice, ICAC significantly lowered the lipid level both in the serum and the liver. Mechanistic studies showed that ICAC strengthened the RCT pathway in the liver and intestine but didn’t affect liver LXRα. Furthermore, ICAC impeded both adipogenesis and the inflammatory response in the liver.Conclusion: ICAC accelerated RCT without affecting liver LXRα, thus resulting in a lipid-lowering effect without increasing liver adipogenesis. Our results indicated that ICAC could be a new RCT promoter for hyperlipidemia treatment without causing liver steatosis.
Hiccups induced by aripiprazole combined with sertraline in an adolescent with olfactory reference disorder: A case report
Authors: Li Zhe , Xiong Zhenzhen , Jiang Xingmei , Li Zhixiong , Yuan Yiwen , Li Xiao 
Published: July 2022

Background:Hiccup can cause significant distress to patients and affect medication compliance. Individuals with olfactory reference disorder (ORD) who might develop persistent hiccups when treated with a combination of antidepressant and antipsychotic, leading to significant distress and impairment.Case summaryWe report a rare case of an adolescent with ORD who was treated with aripiprazole combined with sertraline and who began to hiccup persistently after 6 days on this treatment. He stopped hiccupping after the aripiprazole had been suspended for 12 h. After discharge, the patient continued on sertraline alone and reported no hiccupping at 1-month follow-up.ConclusionClinicians should consider that the combination of aripiprazole and sertraline can induce hiccups during the acute administration period in adolescents with ORD.
Cost-effectiveness of community diabetes screening: Application of Akaike information criterion in rural communities of Nigeria
Authors: Anyasodor Anayochukwu Edward , Nwose Ezekiel Uba , Bwititi Phillip Taderera , Richards Ross Stuart 
Published: July 2022

BackgroundThe prevalence of diabetes mellitus (DM) is increasing globally, and this requires several approaches to screening. There are reports of alternative indices for prediction of DM, besides fasting blood glucose (FBG) level. This study, investigated the ability of combination of biochemical and anthropometric parameters and orodental disease indicators (ODIs) to generate models for DM prediction, using Akaike information criterion (AIC) to substantiate health economics of diabetes screening.MethodsFour hundred and thirty-three subjects were enrolled in the study in Ndokwa communities, Delta State, Nigeria, and their glycaemic status was determined, using the CardioChek analyser® and previous data from the Prediabetes and Cardiovascular Complications Study were also used. The cost of screening for diabetes (NGN 300 = $0.72) in a not-for-profit organization/hospital was used as basis to calculate the health economics of number of individuals with DM in 1,000 participants. Data on the subjects' anthropometric, biochemical and ODI parameters were used to generate different models, using R statistical software (version 4.0.0). The different models were evaluated for their AIC values. Lowest AIC was considered as best model. Microsoft Excel software (version 2020) was used in preliminary analysis.ResultThe cost of identifying &lt;2 new subjects with hyperglycemia, in 1,000 people was ≥NGN 300,000 ($ 716). A total of 4,125 models were generated. AIC modeling indicates FBG test as the best model (AIC = 4), and the least being combination of random blood sugar + waist circumference + hip circumference (AIC ≈ 34). Models containing ODI parameters had AIC values &gt;34, hence considered as not recommendable.ConclusionThe cost of general screening for diabetes in rural communities may appear high and burdensome in terms of health economics. However, the use of prediction models involving AIC is of value in terms of cost-benefit and cost-effectiveness to the healthcare consumers, which favors health economics.
A neurobehavioral therapy approach to the rehabilitation and support of persons with brain injury: Practice-based evidence from a UK charitable rehabilitation provider
Authors: Coetzer Rudi , Ramos Sara da Silva 
Published: July 2022

BackgroundThe treatment and rehabilitation for people with acquired brain injury is continually evolving, with increasing recognition of the importance of approaches that adopt a multi-disciplinary biopsychosocial perspective focused on improving adjustment, social participation, and wellbeing. However, there is significant variability as to how such approaches are delivered, across the various stages of recovery, rehabilitation settings, and within different healthcare systems.ObjectiveThis paper had three aims. The first was to describe the neurobehavioral therapy (NBT) approach to brain injury rehabilitation adopted in our charitable organization. The second aim was to report how the NBT approach evolved in response to changes in referral patterns, and patient needs within a broader, longer-term clinical pathway. The third aim was to assess the effectiveness of the NBT approach by analyzing outcome data.MethodsRetrospective analyses of standardized outcome data were completed to investigate the effectiveness of our approach. Case vignettes are provided to illustrate the key components of the approach.ResultsOutcome data suggested that the approach is effective in delivering positive outcomes for patients. Furthermore, the data show differences in presentation between three clinical streams (restoration, compensation, and scaffolding) within the NBT approach.ConclusionsThis paper describes the adaption of the ‘traditional' neurobehavioral approach to brain injury rehabilitation into a model of delivery that can benefit a more diverse range of people living with the heterogenous and long-term consequences of brain injury.