bluuebunny/crossref_metadata_2025_split huggingface dataset:
An immunogenic cell death-related regulators classification patterns and immune microenvironment infiltration characterization in intracranial aneurysm based on machine learning
Authors: Turhon Mirzat , Maimaiti Aierpati , Gheyret Dilmurat , Axier Aximujiang , Rexiati Nizamidingjiang , Kadeer Kaheerman , Su Riqing , Wang Zengliang , Chen Xiaohong , Cheng Xiaojiang , Zhang Yisen , Aisha Maimaitili 
Published: September 2022

BackgroundImmunogenic Cell Death (ICD) is a novel way to regulate cell death and can sufficiently activate adaptive immune responses. Its role in immunity is still emerging. However, the involvement of ICD in Intracranial Aneurysms (IA) remains unclear. This study aimed to identify biomarkers associated with ICDs and determine the relationship between them and the immune microenvironment during the onset and progression of IAMethodsThe IA gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in IA were identified and the effects of the ICD on immune microenvironment signatures were studied. Techniques like Lasso, Bayes, DT, FDA, GBM, NNET, RG, SVM, LR, and multivariate analysis were used to identify the ICD gene signatures in IA. A consensus clustering algorithm was used for conducting the unsupervised cluster analysis of the ICD patterns in IA. Furthermore, enrichment analysis was carried out for investigating the various immune responses and other functional pathways. Along with functional annotation, the weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network and module construction, identification of the hub gene, and co-expression analysis were also carried out.ResultsThe above techniques were used for establishing the ICD gene signatures of HMGB1, HMGN1, IL33, BCL2, HSPA4, PANX1, TLR9, CLEC7A, and NLRP3 that could easily distinguish IA from normal samples. The unsupervised cluster analysis helped in identifying three ICD gene patterns in different datasets. Gene enrichment analysis revealed that the IA samples showed many differences in pathways such as the cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, chemokine signaling pathway, NOD-like receptor signaling pathway, viral protein interaction with the cytokines and cytokine receptors, and a few other signaling pathways compared to normal samples. In addition, the three ICD modification modes showed obvious differences in their immune microenvironment and the biological function pathways. Eight ICD-regulators were identified and showed meaningful associations with IA, suggesting they could severe as potential prognostic biomarkers.ConclusionsA new gene signature for IA based on ICD features was created. This signature shows that the ICD pattern and the immune microenvironment are closely related to IA and provide a basis for optimizing risk monitoring, clinical decision-making, and developing novel treatment strategies for patients with IA.
PD-1 inhibition plus platinum-based chemotherapy (PBC) or PBC alone in the first-line treatment of locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma
Authors: Zhang Xuanye , Zhou Yixin , Chen Hualin , Chen Chen , Lin Zuan , He Li-na , Du Wei , Chen Tao , Hong Shaodong , Fu Sha 
Published: September 2022

BackgroundPulmonary lymphoepithelioma-like carcinoma (PLELC) is a distinctive subtype of non-small cell lung carcinoma that was not well presented in clinical studies. The management of advanced PLELC remains an important, unmet need due to the paucity of high-grade evidence. Herein, we carried out a multicenter, retrospective study to assess the effectiveness and tolerability of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone for patients with advanced PLELC in the first-line setting.Patients and MethodsThis retrospective study enrolled patients with advanced PLELC receiving first-line treatment with PD-1 inhibition plus chemotherapy (IO-Chemo group) or chemotherapy alone (Chemo group) in three medical centers in China. The survival outcomes, efficacy, and safety profile were investigated. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), and adverse events (AEs).ResultsA total of 133 patients were enrolled. PFS was significantly longer in the IO-Chemo group (median 12.8 months [95% CI 5.2-20.4]) than that in the Chemo group (median 7.7 months [95% CI 6.8-8.6]; hazard ratio [HR] 0.48 [95% CI 0.31-0.74]; P=0.001). ORR was 74.5% (95% CI, 63.0-86.1) in the IO-Chemo group and 34.6% (95% CI, 24.1-45.2) in the Chemo group (P&lt;0.001). The median OS was not reached in the IO-Chemo group versus 35.7 months (95% CI 26.7-44.8) in the Chemo group (HR 0.47 [95% CI 0.20-1.07]; P=0.065). Multivariate analysis revealed that PD-1/PD-L1 inhibitor combination was independently associated with longer PFS (HR 0.40 [95% CI 0.25-0.63]; P&lt;0.001). Grade 3 or higher AEs occurred in 36 (65.5%) patients in the IO-Chemo group and 56 (71.8%) patients in the Chemo group, respectively.ConclusionsIn patients with advanced PLELC, adding PD-1/PD-L1 inhibitor to platinum-based chemotherapy significantly increased PFS and ORR with a tolerable safety profile.
Comparative efficacy and safety of JAK inhibitors as monotherapy and in combination with methotrexate in patients with active rheumatoid arthritis: A systematic review and meta-analysis
Authors: Liu Li , Yan Yi-Dan , Shi Fang-Hong , Lin Hou-Wen , Gu Zhi-Chun , Li Jia 
Published: September 2022

BackgroundWe aim to evaluate the efficacy and tolerability of Janus kinase inhibitors (JAKi) as monotherapy and in combination with methotrexate (MTX) in active rheumatoid arthritis (RA).MethodsMedline, EMBASE, and Cochrane Library were systematically searched to identify relevant randomized controlled trials (RCTs). Pooled analysis was conducted using random-effects model, along with the risk difference (RD) and 95% confidence intervals (CIs).ResultsThree RCTs, including 2,290 patients, were included. JAKi (tofacitinib, baricitinib, and filgotinib) plus MTX displayed a higher proportion of patients meeting the American College of Rheumatology (ACR) criteria than JAKi alone at week 52 (ACR20 RD 0.032; 95% CI −0.027 to 0.091; ACR50 RD 0.050; 95% CI 0.003 to 0.097; ACR70 RD 0.056; 95% CI 0.012 to 0.100). Similar results were observed for ACR20/50/70 at week 24. No significant difference was found between two regimens for the proportion of patients achieving Health Assessment Questionnaire disability index (HAQ-DI) improvement ≥ 0.22 at weeks 24 and 52. Regarding low disease activity and remission achievement, JAKi in combination with MTX, contributed higher response rates than JAKi alone at weeks 24 and 52. Compared with JAKi monotherapy, combination therapy had a higher risks of treatment-emergent adverse events (TEAEs) and adverse events (AEs) leading to study discontinuation.ConclusionJAKi combined with MTX demonstrated superiority to JAKi monotherapy in terms of ACR responses, low disease activity and remission achievement. The two regimens presented comparable physical functioning measured by HAQ-DI improvement and similar tolerability, except for high risks of TEAEs and AEs leading to study discontinuation in combination therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288907.
Exposure to silica and systemic sclerosis: A retrospective cohort study based on the Canadian Scleroderma Research Group
Authors: Muntyanu Anastasiya , Milan Raymond , Rahme Elham , LaChance Avery , Ouchene Lydia , Cormier Maxime , Litvinov Ivan V. , Hudson Marie , Baron Murray , Netchiporouk Elena ,   the Canadian Scleroderma Research Group
Published: September 2022

IntroductionSystemic sclerosis (SSc) is thought to be induced by an environmental trigger in genetically predisposed individuals. This study assessed the demographic and clinical characteristics and disease severity of silica exposed SSc patients.MethodsData was obtained from the Canadian Scleroderma Research Group (CSRG) cohort, containing 1,439 patients (2004–2019). Univariate and multivariate logistic regression analyses were performed, to determine the phenotype and severity of silica-exposed SSc patients. Mortality was assessed using Cox Survival Regression and Kaplan-Meier analyses.ResultsAmong 1,439 patients (86.7% females), 95 patients reported exposure to silica. Those exposed were younger, of male sex and with more severe disease. Sex differences were observed where male patients exposed to silica were more likely to be Caucasian and smokers whereas female patients were younger at SSc diagnosis compared to unexposed. Multivariate regression, controlled for multiple confounders, showed that silica exposure was associated with a younger age at diagnosis and worse disease severity and mortality.ConclusionExposure to silica was reported in ∼7% of CSRG cohort and ∼20% of male patients and was associated with a worse prognosis in terms of age of diagnosis, organ involvement and mortality. Hence, screening for silica exposure among higher risk individuals may be beneficial and these patients may require closer monitoring for systemic disease.
TARDBP mutations in a cohort of Italian patients with Parkinson’s disease and atypical parkinsonisms
Authors: Tiloca Cinzia , Goldwurm Stefano , Calcagno Narghes , Verde Federico , Peverelli Silvia , Calini Daniela , Zecchinelli Anna Lena , Sangalli Davide , Ratti Antonia , Pezzoli Gianni , Silani Vincenzo , Ticozzi Nicola 
Published: September 2022

BackgroundAggregates of TAR DNA-binding protein of 43 kDa (TDP-43) represent the pathological hallmark of most amyotrophic lateral sclerosis (ALS) and of nearly 50% of frontotemporal dementia (FTD) cases but were also observed to occur as secondary neuropathology in the nervous tissue of patients with different neurodegenerative diseases, including Parkinson’s disease (PD) and atypical parkinsonism. Mutations of TARDBP gene, mainly in exon 6 hotspot, have been reported to be causative of some forms of ALS and FTD, with clinical signs of parkinsonism observed in few mutation carriers.MethodsDirect DNA sequencing of TARDBP exon 6 was performed in a large Italian cohort of 735 patients affected by PD (354 familial and 381 sporadic) and 142 affected by atypical parkinsonism, including 39 corticobasal syndrome (CBS) and 103 progressive sopranuclear palsy (PSP). Sequencing data from 1710 healthy, ethnically matched controls were already available.ResultsFour TARDBP missense variants (p.N267S, p. G294A, p.G295S, p.S393L) were identified in four patients with typical PD and in two individuals with atypical parkinsonism (1 CBS and 1 PSP). None of the detected mutations were found in healthy controls and only the variant p.N267S was previously described in association to idiopathic familial and sporadic PD and to CBS.ConclusionIn this study we provide further insight into the clinical phenotypic heterogeneity associated with TARDBP mutations, which expands beyond the classical ALS and FTD diseases to include also PD and atypical parkinsonism, although with a low mutational frequency, varying considerably in different Caucasian populations. In addition, our study extends the spectrum of TARDBP pathogenetic mutations found in familial and sporadic PD.
Synergistic multi-joint kinematic strategies to reduce tripping risks during obstacle-crossing in older long-term Tai-Chi Chuan practitioners
Authors: Huang Hsing-Po , Kuo Chien-Chung , Lu Shiuan-Huei , Chen Sheng-Chang , Ho Tsung-Jung , Lu Tung-Wu 
Published: September 2022

IntroductionLosing balance or tripping over obstacles is considered one of the most common causes of falls in the elderly. Tai-Chi Chuan (TCC) has been shown to improve muscle strength, inter-joint coordination and balance control in the elderly. This study aimed to determine whether older long-term TCC practitioners would show multi-joint kinematic strategies that would reduce the risk of tripping during obstacle-crossing compared to peers without TCC experience.MethodsThree-dimensional motions of the pelvis and lower extremities were measured using a motion capture system in fifteen older long-term TCC practitioners (TCC group) and 15 healthy controls without TCC experience during walking and crossing obstacles of three different heights. Crossing angles of the pelvis and lower limbs and toe-obstacle clearances were obtained and analyzed using two-way analyses of variance to study the between-subject (group) and within-subject (height) effects. A multi-link system approach was used to reveal the relationship between joint angular changes and toe-obstacle clearances.ResultsCompared to the controls, the TCC group showed increased leading and trailing toe-obstacle clearances (p &lt; 0.05) with increased pelvic hiking and hip flexion but decreased hip adduction on the swing side and decreased knee flexion on the stance side during leading-limb crossing (p &lt; 0.05), and increased pelvic hiking and anterior tilt but decreased hip adduction on the swing side, and decreased knee flexion on the stance side during trailing limb crossing (p &lt; 0.05). All significant joint angular changes contributed to the increases in the toe-obstacle clearances.ConclusionThe current study identified the kinematic changes of the pelvis and the lower limb joints and revealed a specific synergistic multi-joint kinematic strategy to reduce tripping risks during obstacle-crossing in older long-term TCC practitioners as compared to non-TCC controls. The observed multi-joint kinematic strategies and the associated increases in toe-obstacle clearances appeared to be related to the training characteristics of TCC movements. Long-term TCC practice may be helpful for older people in reducing the risk of tripping and the subsequent loss of balance.
Levels of adhesion molecules and clinical outcomes in patients with ischemic stroke after mechanical thrombectomy
Authors: Zhang Xiaohao , Zhou Feng , Wang Wei , E Yan , Chen Shuaiyu , Cao Haiming , Lian Huiwen , Jiang Teng , Zhang Yingdong , Shi Hongchao , Zhou Junshan 
Published: September 2022

Background and purposeData on adhesion molecule levels in patients treated with mechanical thrombectomy (MT) are scarce. We aimed to evaluate the association among adhesion molecule levels, symptomatic intracranial hemorrhage (sICH), and clinical outcome and to determine whether the sICH influences the association of adhesion molecules with functional outcome.MethodsPatients with large artery occlusion in the anterior circulation and treated with MT were prospectively recruited. Adhesion molecules, such as soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) were tested. An unfavorable outcome was defined as a 90-day modified Rankin Scale (mRS) score of 3–6. The sICH was diagnosed according to the Heidelberg Bleeding Classification within 72 h of endovascular treatment (EVT).ResultsOf the 310 enrolled patients (mean age, 68.5 years; 198 men), 46 (14.8%) experienced sICH and 173 (55.8%) experienced an unfavorable outcome at 90 days. After adjusting for potential confounders, patients with higher sVCAM-1 and sE-selectin levels had an increasing trend of sICH [4th quartile vs. 1st quartile for sVCAM-1; odds ratio (OR), 2.766, p = 0.085; sE-selectin; OR, 2.422, p = 0.086] and poor outcome (4th quartile vs. 1st quartile for sVCAM-1; OR, 2.614, p = 0.025; sE-selectin; OR, 2.325, p = 0.046). Furthermore, the sICH might partially mediate the worse functional outcome in patients with higher adhesion molecules levels (Sobel test, p &lt; 0.001 for sVCAM-1 and p = 0.007 for sE-selectin).ConclusionsThere were significant relationships between levels of adhesion molecules and a 90-day poor outcome in patients with ischemic stroke treated with MT, which was partially mediated by sICH.
Differences in treatment for Alzheimer's disease between urban and rural areas in China
Authors: Li Bei , Liu Dejun , Wan Qiaoqin , Sheng Can , Wang Xiting , Leng Fangda , Peng Qing , Wang Ting , Du Ailian , Zhu Feiqi , Mima Dunzhu , Wang Huali , Xie Hengge , Wang Zhaoxia , Jin Haiqiang , Sun Yongan 
Published: September 2022

IntroductionIn China, the increasing number of people with Alzheimer's disease (AD) poses a great challenge to families and the country. Economic and cultural differences cause a urban-rural gap in medical resources. This multicenter survey aimed to investigate the real-world practice of disease treatment among people with AD.MethodsPeople with AD and their caregivers from 30 provincial regions in mainland China were enrolled from October 2020 to December 2020 to be surveyed for their treatment experience. Logistic regression was used to explore the factors that influence medication adherence in all areas, urban areas, and rural areas.ResultsIn this survey, 1,427 participants came from urban areas, and 539 participants came from rural areas. Patients in urban areas were older (mean age 74 vs. 70, p = 0.001), less frequently had mild AD (36.0 vs. 52.1%, p &lt; 0.001), and more often were cared for at professional institutions (8.8 vs. 3.2%, p &lt; 0.001). In terms of pharmacotherapy, 77.8% of people accepted taking lifelong medication, whereas 61.3% of patients insisted on taking medications. Although 72.0% of rural people believed in taking lifelong medication, only 30.0% adhered to drug use. The major factors that influenced medication adherence for all patients with AD were regional distribution (p &lt; 0.001, OR = 6.18, 95% CI: 4.93–7.74) and family earnings (p = 0.003, OR = 1.22, 95% CI: 1.07–1.38). In rural areas, family earnings (p = 0.008, OR = 1.44, 95% CI: 1.10–1.89) and severity of AD (p = 0.033, OR = 1.31, 95% CI: 1.02–1.68) were the main factors. Family earnings (p = 0.038, OR = 1.16, 95% CI: 1.01–1.34) was the only factor among urban areas. Among all non-pharmaceutical activities except for cognitive intervention, the participation rates of rural patients were significantly higher than those of urban patients (p &lt; 0.05).ConclusionAlthough national progress has been made in the public awareness of disease treatment, adequate diagnosis and medication adherence need to be prompted, especially in rural areas. Furthermore, lifelong treatment should be improved based on regional characteristics through the joint efforts of the government, health workers, and social volunteers.
Is frontoparietal electroencephalogram activity related to the level of functional disability in patients emerging from a minimally conscious state? A preliminary study
Authors: Wu Wanchun , Xu Chengwei , Huang Xiyan , Xiao Qiuyi , Zheng Xiaochun , Zhong Haili , Liang Qimei , Xie Qiuyou 
Published: September 2022

ObjectiveWhen regaining consciousness, patients who emerge from a minimally conscious state (EMCS) present with different levels of functional disability, which pose great challenges for treatment. This study investigated the frontoparietal activity in EMCS patients and its effects on functional disability.Materials and methodsIn this preliminary study, 12 EMCS patients and 12 healthy controls were recruited. We recorded a resting-state scalp electroencephalogram (EEG) for at least 5 min for each participant. Each patient was assessed using the disability rating scale (DRS) to determine the level of functional disability. We analyzed the EEG power spectral density and sensor-level functional connectivity in relation to the patient’s functional disability.ResultsIn the frontoparietal region, EMCS patients demonstrated lower relative beta power (P &lt; 0.01) and higher weighted phase lag index (wPLI) values in the theta (P &lt; 0.01) and gamma (P &lt; 0.01) bands than healthy controls. The frontoparietal theta wPLI values of EMCS patients were positively correlated with the DRS scores (rs = 0.629, P = 0.029). At the whole-brain level, EMCS patients only had higher wPLI values in the theta band (P &lt; 0.01) than healthy controls. The whole-brain theta wPLI values of EMCS patients were also positively correlated with the DRS scores (rs = 0.650, P = 0.022). No significant difference in the power and connectivity between the frontoparietal region and the whole brain in EMCS patients was observed.ConclusionEMCS patients still experience neural dysfunction, especially in the frontoparietal region. However, the theta connectivity in the frontoparietal region did not increase specifically. At the level of the whole brain, the same shift could also be seen. Theta functional connectivity in the whole brain may underlie different levels of functional disability.
Safety of deep brain stimulation in pregnancy: A comprehensive review
Authors: King Caroline , Parker T. Maxwell , Roussos-Ross Kay , Ramirez-Zamora Adolfo , Smulian John C. , Okun Michael S. , Wong Joshua K. 
Published: September 2022

IntroductionDeep brain stimulation (DBS) is increasingly used to treat the symptoms of various neurologic and psychiatric conditions. People can undergo the procedure during reproductive years but the safety of DBS in pregnancy remains relatively unknown given the paucity of published cases. We thus conducted a review of the literature to determine the state of current knowledge about DBS in pregnancy and to determine how eligibility criteria are approached in clinical trials with respect to pregnancy and the potential for pregnancy.MethodsA literature review was conducted in EMBASE to identify articles involving DBS and pregnancy. Two reviewers independently analyzed the articles to confirm inclusion. Data extracted for analysis included conditions treated, complications at all stages of pregnancy, neonatal/pediatric outcomes, and DBS target. A second search was then conducted using www.clinicaltrials.gov. The same two reviewers then assessed whether each trial excluded pregnant individuals, lactating individuals, or persons of childbearing age planning to conceive. Also assessed was whether contraception had to be deemed adequate prior to enrollment.ResultsThe literature search returned 681 articles. Following independent analysis and agreement of two reviewers, 8 pregnancy related DBS articles were included for analysis. These articles described 27 subjects, 29 pregnancies (2 with subsequent pregnancies), and 31 infants (2 twin pregnancies). There was 1 preterm birth at 35 weeks, and 3 patients who experienced discomfort from the DBS battery (i.e., impulse generator) placement site. All 27 patients had a DBS device implanted before they became pregnant, which remained in use throughout their pregnancy. There was exclusion of pregnant individuals from 68% of 135 interventional trials involving DBS. Approximately 44% of these trials excluded persons of childbearing age not on “adequate contraception” or wishing to conceive in the coming years. Finally, 22% excluded breastfeeding persons.ConclusionThe data from 29 pregnancies receiving DBS treatment during pregnancy was not associated with unexpected pregnancy or post-partum complication patterns. Many clinical trials have excluded pregnant individuals. Documentation of outcomes in larger numbers of pregnancies will help clarify the safety profile and will help guide study designs that will safely include pregnant patients.