bluuebunny/crossref_metadata_2025_split huggingface dataset:
Language Disorder in Progressive Supranuclear Palsy and Corticobasal Syndrome: Neural Correlates and Detection by the MLSE Screening Tool
Authors: Peterson Katie A. , Jones P. Simon , Patel Nikil , Tsvetanov Kamen A. , Ingram Ruth , Cappa Stefano F. , Lambon Ralph Matthew A. , Patterson Karalyn , Garrard Peter , Rowe James B. 
Published: July 2021

Background: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) affect speech and language as well as motor functions. Clinical and neuropathological data indicate a close relationship between these two disorders and the non-fluent variant of primary progressive aphasia (nfvPPA). We use the recently developed Mini Linguistic State Examination tool (MLSE) to study speech and language disorders in patients with PSP, CBS, and nfvPPA, in combination with structural magnetic resonance imaging (MRI).Methods: Fifty-one patients (PSP N = 13, CBS N = 19, nfvPPA N = 19) and 30 age-matched controls completed the MLSE, the short form of the Boston Diagnostic Aphasia Examination (BDAE), and the Addenbrooke’s Cognitive Examination III. Thirty-eight patients and all controls underwent structural MRI at 3 Tesla, with T1 and T2-weighted images processed by surface-based and subcortical segmentation within FreeSurfer 6.0.0 to extract cortical thickness and subcortical volumes. Morphometric differences were compared between groups and correlated with the severity of speech and language impairment.Results: CBS and PSP patients showed impaired MLSE performance, compared to controls, with a similar language profile to nfvPPA, albeit less severe. All patient groups showed reduced cortical thickness in bilateral frontal regions and striatal volume. PSP and nfvPPA patients also showed reduced superior temporal cortical thickness, with additional thalamic and amygdalo-hippocampal volume reductions in nfvPPA. Multivariate analysis of brain-wide cortical thickness and subcortical volumes with MLSE domain scores revealed associations between performance on multiple speech and language domains with atrophy of left-lateralised fronto-temporal cortex, amygdala, hippocampus, putamen, and caudate.Conclusions: The effect of PSP and CBS on speech and language overlaps with nfvPPA. These three disorders cause a common anatomical pattern of atrophy in the left frontotemporal language network and striatum. The MLSE is a short clinical screening tool that can identify the language disorder of PSP and CBS, facilitating clinical management and patient access to future clinical trials.
Safety and Efficacy of Direct Angioplasty in Acute Basilar Artery Occlusion Due to Atherosclerosis
Authors: Ma Gaoting , Sun Xuan , Tong Xu , Jia Baixue , Huo Xiaochuan , Luo Gang , Wang Bo , Deng Yiming , Gao Feng , Song Ligang , Ma Ning , Miao Zhongrong , Mo Dapeng 
Published: July 2021

Background and Purpose: Endovascular treatment (EVT) is one of the promising treatment options in patients with intracranial atherosclerotic disease (ICAD)-related basilar artery occlusion (BAO). In this study, we compared the safety and efficacy of direct angioplasty (DA) with stent-retriever thrombectomy (SRT) with or without rescue treatment in ICAD-related BAO.Methods: We retrospectively evaluated 187 patients who underwent EVT for BAO from January 2012 to July 2018. We identified patients who underwent EVT due to ICAD-related BAO. Patients who accepted SRT with or without rescue treatment were classified into the SRT group. Patients treated with DA with or without stent placement were classified into DA group. Clinical and laboratory findings and outcomes were compared between groups.Results: A total of 108 patients were enrolled, among them 77 underwent SRT and 31 underwent DA; 61 (79.2%) SRT group patients underwent angioplasty with or without stent placement. Compared with patients in the SRT group, those in the DA group experienced a significantly shorter procedure time [60 min (60–120 min) vs. 120 min (60–120 min); p = 0.038] and a lower number of device passes [2 passes (1–2 passes) vs. 3 passes (2–4 passes); p &lt; 0.001]. No significant differences in balloon angioplasty (35.5 vs. 22.1%; p = 0.150), emergent stent placement (64.5 vs. 57.1%; p = 0.481), successful recanalization (93.5 vs. 85.7%; p = 0.340), embolization in distal or new territory (3.2 vs. 9.1%, p = 0.314), and reocclusion (22.6 vs. 9.1%; p = 0.109) among DA and SRT groups were found. Additionally, no differences in symptomatic intracranial hemorrhage incidence [adjusted odds ratio (OR), 0.74; 95% CI, 0.06–9.44; p = 0.815], functional independence (adjusted OR, 1.44; 95% CI, 0.50–4.16; p = 0.497), and mortality rate (adjusted OR, 0.36; 95% CI, 0.06–2.04; p = 0.247) were noted among groups.Conclusions: In certain patients with ICAD-related BAO, DA may shorten procedure time and reduce required device passes compared to SRT. In this study, DA was retrospectively found to be of similar safety and efficacy as SRT.
Association Between Diabetes Medications and the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis
Authors: Qin Xiaocui , Zhang Xia , Li Pinyu , Wang Min , Yan Li , Bao Zeqing , Liu Qili 
Published: July 2021

Background: Diabetes mellitus (DM) increases the risk of Parkinson's disease (PD). However, whether DM medications play a part on that increased PD risk is unclear. We designed this meta-analysis to assess the influence of different oral DM medications on the PD risk in patients with DM.Methods: We searched PubMed, Embase, and CENTRAL databases for relevant studies up until January 2021. We pooled adjusted outcomes to assess the PD risk in patients using different DM medications including sulfonylurea, metformin, glitazones (GTZ), dipeptidyl peptidase-4 inhibitors (DPP4i), and glucagon-like peptide-1 agonists (GLP1a).Results: We included 10 studies in our analysis. Our results indicate a lack of significant association between the PD risk and the use of sulfonylureas (three studies; HR, 1.26; 95% CI, 0.95 to 1.66; I2, 70%; p = 0.11), DPP4i (three studies; HR, 0.69; 95% CI, 0.35 to 1.38; I2, 88%; p = 0.30), metformin (five studies; HR, 1.23; 95% CI, 0.98 to 1.78; I2, 84%; p = 0.13), and GTZ (six studies; HR, 0.88; 95% CI, 0.66 to 1.16; I2, 92%; p = 0.35). After exclusion of a single study in the GTZ analysis, our results indicate a significantly reduced PD risk with GTZ use (HR, 0.78; 95% CI, 0.65 to 0.93; I2, 59%; p = 0.06). Similarly, after the exclusion of a single study, our results indicate a significantly increased PD risk with the use of metformin (HR, 1.50; 95% CI, 1.11 to 2.02; I2, 80%; p = 0.008). We also found a significantly reduced PD risk with the use of GLP1a (two studies; HR, 0.41; 95% CI, 0.19 to 0.87; I2, 0%; p = 0.02).Conclusion: The role of different DM medications on the PD risk remains unclear, and the quality of studies is low. While our analysis suggests a lack of association between the use of metformin, GTZ, DPP4i, and sulfonylureas and the PD risk, metformin (to a higher degree) and GTZ may still increase the risk. Limited data suggest a protective effect of GLP1a on the PD risk.
Outcomes of a Multicenter Safety and Efficacy Study of the SuitX Phoenix Powered Exoskeleton for Ambulation by Patients With Spinal Cord Injury
Authors: Koljonen Paul Aarne , Virk Anna Sternin , Jeong Yoon , McKinley Michael , Latorre Juan , Caballero Amaya , Hu Yong , Wong Yat Wa , Cheung Kenneth , Kazerooni Homayoon 
Published: July 2021

Objective: To examine the safety and efficacy of ambulation utilizing a semi-passive and lightweight powered exoskeleton by spinal cord injury (SCI) patients.Methods: This is a multi-center, open-label, prospective cohort study across three facilities. A cohort of 40 individuals with SCI from T4-L5 was recruited into a 20-session training and assessment protocol, utilizing the SuitX Phoenix. All patients were tested using a 10-m-walk test (10 MWT), 6-min-walk test (6 MWT), and Timed up &amp; Go test (TUG). Patient satisfaction, pain, exertion, changes in affect, as well as overall comfort and confidence were reported using a satisfaction survey, Rated Perceived Exertion (RPE) scale, and Positive and Negative Affect Schedule (PANAS). Safety outcomes, adverse events, and device malfunctions were reported.Results: Forty participants completed the study. There were no serious adverse events. All participants reported moderate to high levels of comfort and confidence using the device. All patients were able to achieve FIM of &gt;4 on transitional movements and walking. The neurological level of injury had a statistically significant association with walking speed, WISCI-II, and FIM. Participants with an incomplete spinal cord injury had a higher FIM, faster speed, and higher WISCI-II in all outcome measures.Conclusion: This is the first study to examine the safety and efficacy of SuitX Phoenix for ambulation by SCI patients. We have shown that Phoenix is efficacious in allowing adults with SCI T4 to L5 perform walking and transitional movements. This study also reports the safety-profile of the device, user satisfaction, and psychological trends during training.
Development and External Validation of a Nomogram for Predicting Cancer-Specific Survival of Non-Small Cell Lung Cancer Patients With Ipsilateral Pleural Dissemination
Authors: Wang Zhenfan , Li Hao , Liu Taorui , Sun Zewen , Yang Fan , Jiang Guanchao 
Published: July 2021

BackgroundNon-small-cell lung cancer (NSCLC) patients with ipsilateral pleural dissemination are defined as M1a in the eighth of American Joint Committee on Cancer (AJCC) TNM staging. We aimed to build a nomogram to predict lung cancer specific survival (LCSS) of NSCLC patients with ipsilateral pleural dissemination and to compare the impact of primary tumor resection (PTR) on LCSS among patients with different features.MethodsA total of 3,918 NSCLC patients with ipsilateral pleural dissemination were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We selected and integrated significant prognostic factors based on competing risk regression to build a nomogram. The model was subjected to internal validation within SEER cohort and external validation with the cohort of 97 patients from Peking University People’s Hospital.ResultsAge (P &lt; 0.001), gender (P = 0.037), T stage (P = 0.002), N stage (P &lt; 0.001), metastasis pattern (P = 0.005), chemotherapy (P &lt; 0.001), and PTR (P &lt; 0.001) were independent prognostic factors. The calibration curves presented a good consistency and the Harrell’s C-index of nomogram were 0.682 (95%CI: 0.673–0.691), 0.687 (95%CI: 0.670–0.704) and 0.667 (95%CI: 0.584–0.750) in training, internal, and external validation cohort, respectively. Interaction tests suggested a greater LCSS difference caused by PTR in patients without chemotherapy (P &lt; 0.001).ConclusionsWe developed a nomogram based on competing risk regression to reliably predict prognosis of NSCLC patients with ipsilateral pleural dissemination and validated this nomogram in an external Chinese cohort. This novel nomogram might be a practical tool for clinicians to anticipate the 1-, 3- and 5-year LCSS for NSCLC patients with pleural dissemination. Subgroup analysis indicated that patients without chemotherapy could get more benefit from PTR. In order to assess the role of PTR in the management of M1a patients more accurately, further prospective study would be urgently required.
Validation of Potential Protein Markers Predicting Chemoradioresistance in Early Cervical Cancer by Immunohistochemistry
Authors: Jeong Soo Young , Chung Joon-Yong , Byeon Sun-Ju , Kim Chul Jung , Lee Yoo-Young , Kim Tae-Joong , Lee Jeong-Won , Kim Byoung-Gie , Chae Ye Lin , Oh So Young , Choi Chel Hun 
Published: July 2021

BackgroundIn a previous study, a proteomic panel consisting of BCL-2, HER2, CD133, CAIX, and ERCC1 significantly predicted survival in patients with locally advanced cervical cancer. However, the prognostic significance of these proteins has not been assessed in early cervical cancer. The present study investigated the clinical significance and chemoradioresistance prediction power of these proteins in patients with early-stage cervical cancer.Materials and MethodsBCL-2, HER2, CD133, CAIX, and ERCC1 expression was determined by the immunohistochemical staining of 336 cervical cancer tissue microarrays. The associations of these proteins with clinicopathologic characteristics and disease progression were assessed.ResultsThere was a trend of low CAIX expression (p=0.082) and high ERCC1 expression (p=0.059) in patients with a favorable response to adjuvant radiation. High HER2 expression was significantly associated with shorter disease-free survival (DFS) in the total group (5-year DFS of 80.1% vs. 92.2%, p=0.004). A prognostic significance remained in multivariate analysis (Hazard ratio, HR=2.10, p=0.029). In the adjuvant radiation group, low CAIX and high ERCC1 expression indicated significantly unfavorable DFS (75.0% vs. 89.0%, p=0.026 and 76.8% vs. 88.6%, p=0.022, respectively). Low CAIX expression remained an independent prognostic marker in multivariate analysis (HR=0.45, p=0.037). The combined molecular-clinical model using random survival forest method predicted DFS with improved power compared with that of the clinical variable model (C-index 0.77 vs. 0.71, p=0.006).ConclusionHER2, CAIX, and ERCC1 expression can be predictive protein markers for clinical outcomes in early cervical cancer patients treated primarily with radical surgery with or without adjuvant radiation.
Differential Expression Profile of lncRNA in Glioma Cells and the Effect of lncRNA NKX3-1 on Glioma Cells Through Fem1b/SPDEF Pathway
Authors: Cai Yang , Wang Ming , Cui Yan , Tan Zhigang , Jiang Yugang 
Published: July 2021

ObjectiveTo investigate the differential expression of lncRNA in glioma cells, as well as the effect of lncRNA NKX3-1 on glioma cells.MethodsGlioma-related data were first downloaded from the TCGA database and analyzed using bioinformatics, after which the lncRNA NKX3-1 was chosen for further experiments. The expression of the lncRNA NKX3-1 in glioma tumor samples was detected using qRT-PCR. The subcellular localization of lncRNA NKX3-1 was determined using fluorescence in situ hybridization (FISH). CCK-8, flow cytometry, cell scratch, and transwell assays were used to detect cell proliferation, apoptosis, and invasion. The downstream pathway of lncRNA NKX3-1 was investigated using luciferase assays and detected using western blot, transwell, and cell scratch assays.ResultsThe differential expression profile of lncRNA in glioma was obtained. NKX3-1 lncRNA was found to be significantly increased in glioma tumor tissues. LncRNA NKX3-1 was found in the nucleus. Proliferation, invasion, and migration of glioma cells were significantly increased (P &lt;0.05) in the lncRNA NKX3-1 overexpression group, while apoptosis ability was significantly decreased (P &lt;0.05). Tumor volume and weight were significantly increased in the lncRNA NKX3-1 overexpression group in nude mice (P &lt;0.05). LncRNA NKX3-1 significantly increased the luciferase activity of Fem1b 3’-UTR-WT reporter genes (P &lt;0.05) as well as the levels of SPDEF protein (P &lt;0.05). The protein level of FEM1B was significantly reduced. Cell invasion and migration were significantly increased (P &lt;0.05) in the lncRNA NKX3-1 overexpression group plus SPDEF group.ConclusionWe investigated the differential expression profile of lncRNAs in glioma and discovered that the lncRNA NKX3-1 plays an important role in cancer promotion via the Fem1b/SPDEF pathway.
Targeting Glycogen Synthase Kinase 3 Beta Regulates CD47 Expression After Myocardial Infarction in Rats via the NF-κB Signaling Pathway
Authors: Xu Li-Na , Wang Shu-Hui , Su Xue-Ling , Komal Sumra , Fan Hong-Kun , Xia Li , Zhang Li-Rong , Han Sheng-Na 
Published: July 2021

The aim of this study was to investigate the effects of the GSK-3β/NF-κB pathway on integrin-associated protein (CD47) expression after myocardial infarction (MI) in rats. An MI Sprague Dawley rat model was established by ligating the left anterior descending coronary artery. The rats were divided into three groups: Sham, MI, and SB + MI (SB216763) groups. Immunohistochemistry was used to observe the changes in cardiac morphology. A significant reduction in the sizes of fibrotic scars was observed in the SB + MI group compared to that in the MI group. SB216763 decreased the mRNA and protein expression of CD47 and NF-κB during MI. Primary rat cardiomyocytes (RCMs) and the H9c2 cell line were used to establish in vitro hypoxia models. Quantitative real-time PCR and western blotting analyses were conducted to detect mRNA and protein expression levels of CD47 and NF-κB and apoptosis-related proteins, respectively. Apoptosis of hypoxic cells was assessed using flow cytometry. SB216763 reduced the protein expression of CD47 and NF-κB in RCMs and H9c2 cells under hypoxic conditions for 12 h, and alleviated hypoxia-induced apoptosis. SN50 (an NF-κB inhibitor) also decreased CD47 protein expression in RCMs and H9c2 cells under hypoxic conditions for 12 h and protected cells from apoptosis. GSK-3β upregulates CD47 expression in cardiac tissues after MI by activating NF-κB, which in turn leads to myocardial cell damage and apoptosis.
Relationship Between Mean Vancomycin Trough Concentration and Mortality in Critically Ill Patients: A Multicenter Retrospective Study
Authors: Hou Yanli , Ren Jiajia , Li Jiamei , Jin Xuting , Gao Ya , Li Ruohan , Zhang Jingjing , Wang Xiaochuang , Li Xinyu , Wang Gang 
Published: July 2021

Background: It remains unclear whether the mean vancomycin trough concentration (VTC) derived from the entire course of therapy is of potential benefit for critically ill patients. This study was conducted to explore the association between mean serum VTC and mortality in intensive care units (ICUs).Methods: 3,603 adult patients with two or more VTC records after receiving vancomycin treatment in the eICU Collaborative Research Database were included in this multicenter retrospective cohort study. Mean VTC was estimated using all measured VTCs and investigated as a continuous and categorical variable. Patients were categorised into four groups according to mean VTC: &lt;10, 10–15, 15–20, and &gt;20 mg/L. Multivariable logistic regression and subgroup analyses were performed to investigate the relationship of mean VTC with mortality.Results: After adjusting for a series of covariates, logistic regression analyses indicated that mean VTC, as a continuous variable, was positively correlated with ICU (odds ratio, 1.038, 95% confidence interval, [1.014–1.063]) and hospital (1.025 [1.005–1.046]) mortalities. As a categorical variable, mean VTC of 10–15 mg/L was not associated with reduced ICU (1.705 [0.975–2.981]) and hospital (1.235 [0.829–1.841]) mortalities. Mean VTC of 15–20 mg/L was not correlated with a lower risk of hospital mortality (1.370 [0.924–2.029]). Moreover, mean VTCs of 15–20 and &gt;20 mg/L were significantly associated with higher ICU mortality (1.924 [1.111–3.332]; 2.428 [1.385–4.258]), and mean VTC of &gt;20 mg/L with higher hospital mortality (1.585 [1.053–2.387]) than mean VTC of &lt;10 mg/L. Similar results were observed in patients with different Acute Physiology and Chronic Health Evaluation IV score, creatinine clearance, age, and body mass index subgroups.Conclusion: Mean VTC was not associated with reduced ICU/hospital related mortality. Our results suggested that VTC monitoring might not guarantee vancomycin efficacy for ICU patients.
Comparison of the Safety and Efficacy of Interferon Alpha-2a and Cyclosporine-A When Combined With Glucocorticoid in the Treatment of Refractory Behçet’s Uveitis: A Randomized Controlled Prospective Study
Authors: Qian Yujing , Qu Yi , Gao Fei , Pei Minghang , Liang Anyi , Xiao Junyan , Zhao Chan , Zhang Meifen 
Published: July 2021

Purpose: To evaluate and compare the efficacy and safety of interferon alpha-2a (IFN-α2a) and cyclosporine-A (CsA) in patients with refractory Behçet’s uveitis (BU).Methods: In this 12-month randomized, controlled, prospective trial, 26 participants (44 eyes) completed the study. Patients were randomly allocated to the IFN-α2a or CsA groups. All patients in both groups received a standardized prednisone burst and tapering schedule as per protocol. The primary outcome measures were response rate, complete remission rate, and tolerance rate. The secondary outcome measures included time to achieve complete remission, the logarithm of the minimum angle of resolution (logMAR) of best-corrected visual acuity (BCVA), and Behçet’s disease ocular attack score 24 (BOS24). T-tests and non-parametric tests were used to compare quantitative variables, and chi-square tests were performed to compare qualitative variables.Results: The response and complete remission rates were 85.7% (12/14 patients) and 50.0% (7/14 patients) in the IFN-α2a group, compared with 66.7% (8/12 patients) and 25.0% (3/12 patients) in the CsA group, respectively (p &gt; 0.05). Complete remission was achieved at 3.3 and 7.0 months after initiation of IFN-α2a and CsA (p = 0.023). LogMAR BCVA significantly improved 1 month after IFN-α2a initiation (23 eyes) (p = 0.002), and this beneficial effect remained statistically significant during the entire follow-up period (p &lt; 0.05); however, this improvement was not observed in the CsA group (21 eyes). At the endpoint, LogMAR BCVA in the IFN-α2a group was significantly better (0.22 vs. 0.31, p = 0.031) with a higher improvement rate (60.9 vs. 47.6%, p &gt; 0.05). Moreover, compared to the CsA group, more eyes in the IFN-α2a group had a lower BOS24 score (87.0 vs. 57.1%, p = 0.042). None of the patients had any side effects that influenced the medication adherence.Conclusion: Compared to CsA plus corticosteroid, IFN-α2a plus corticosteroid appears to induce a better treatment response, a significantly greater improvement in visual acuity, and more stable remission of intraocular inflammation in a 12-month study period.
Downregulation of Interleukin-13 Receptor α2 Inhibits Angiogenic Formation Mediated by Chitinase 3-Like 1 in Late Atherosclerotic Lesions of apoE−/− Mice
Authors: Xue Qi , Chen Lei , Yu Jianwu , Sun Kewang , Ye Lifang , Zheng Jianlei 
Published: July 2021

Aim: Chitinase 3-like 1 (CHI3L1) has the potential to prompt proliferation and angiogenic formation. Interleukin-13 receptor α2 (IL-13Rα2) was regarded as a receptor of CHI3L1; however, it is unknown whether CHI3L1 adjusts the neovascularization in late atherosclerotic lesions of apoE−/− mice via IL-13Rα2.Methods: Silicone collars were placed around one of the common carotid arteries of apoE−/− mice fed with a high-fat diet. The mice were further injected with Ad.CHI3L1 alone or Ad.CHI3L1 + Ad.IL-13Rα2 shRNA through the caudal vein. The plaque areas in the whole aorta and aortic root were evaluated by Oil Red O staining and H&amp;E staining. The contents of CD31, CD42b, and collagen in carotid plaques were investigated by immunohistochemistry and Masson trichrome staining. The role of CHI3L1 in migration and tube formation of human umbilical vein endothelial cells (HUVECs) was determined by transwell and Matrigel tests. The effect of CHI3L1 on the expression of AKT and extracellular signal-regulated kinase (ERK) was evaluated with the Western blot.Results: The plaque loads in the aorta were significantly more extensive in apoE−/− mice injected with Ad.CHI3L1 than those with Ad.CHI3L1 + Ad.IL-13Rα2 shRNA. CHI3L1 significantly increased the contents of CD31 and CD42b and decreased the element of collagen in late-stage atherosclerotic lesions of the carotid arteries. The effects of CHI3L1 on migration, tube formation, and upregulation of phospho-AKT and phospho-ERK of HUVECs were prohibited by inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) as well as IL-13Rα2 shRNA.Conclusion: To some extent, CHI3L1 promotes migration and tube formation of HUVECs and neovascularization in atherosclerotic plaques possibly mediated by IL-13Rα2 through AKT and ERK signal pathways.