bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship of Soluble Interleukin-6 Receptors With Asthma: A Mendelian Randomization Study
Authors: Raita Yoshihiko , Zhu Zhaozhong , Camargo Carlos A. , Freishtat Robert J. , Ngo Debby , Liang Liming , Hasegawa Kohei 
Published: April 2021

Purpose: Emerging evidence suggests a potential role of interleukin-6 pathways—trans-signaling with soluble interleukin-6 receptors—in the asthma pathobiology. Despite the evidence for their associations with asthma, the causal role of soluble interleukin-6 receptors remains uncertain. We investigated the relations of soluble interleukin-6 receptors with asthma and its major phenotypes.Methods: We conducted a two-sample Mendelian randomization study. As genetic instruments, we selected 33 independent cis-acting variants strongly associated with the level of plasma soluble interleukin-6 receptor in the INTERVAL study. To investigate the association of variants with asthma and its phenotypes, we used genome-wide association study data from the UK Biobank. We combined variant-specific causal estimates by the inverse-variance weighted method for each outcome.Results: Genetically-instrumented soluble interleukin-6 receptor level was associated with a significantly higher risk of overall asthma (OR per one standard deviation increment in inverse-rank normalized soluble interleukin-6 receptor level, 1.02; 95%CI, 1.01–1.03; P = 0.004). Sensitivity analyses demonstrated consistent results and indicated no directional pleiotropy—e.g., MR-Egger (OR, 1.03; 95%CI, 1.01–1.05; P = 0.002; Pintercept =0.37). In the stratified analysis, the significant association persisted across asthma phenotypes—e.g., childhood asthma (OR, 1.05; 95%CI, 1.02–1.08; P &lt; 0.001) and obese asthma (OR, 1.02; 95%CI 1.01–1.03; P = 0.007). Sensitivity analysis using 16 variants selected with different thresholds also demonstrated significant associations with overall asthma and its phenotypes.Conclusion: Genetically-instrumented soluble interleukin-6 receptor level was causally associated with modestly but significantly higher risks of asthma and its phenotypes. Our observations support further investigations into identifying specific endotypes in which interleukin-6 pathways may play major roles.
LncRNA ST7-AS1 is a Potential Novel Biomarker and Correlated With Immune Infiltrates for Breast Cancer
Authors: Zhang Ziwen , Zhang Han , Li Dongbo , Zhou Xiaoping , Wang Jinlu , Zhang Qingyuan 
Published: April 2021

Background: Long noncoding RNA (lncRNA) ST7-AS1 can be observed in various cancers, but its role in breast cancer (BRC) remains unclear. Our aim is to, on the basis of The Cancer Genome Atlas (TCGA) database, prove the correlation between lncRNA ST7-AS1 and BRC.Methods: The lncRNA ST7-AS1 expression and its roles in the prognosis of BRC were explored using data from the TCGA database. The expression level of lncRNA ST7-AS1 in BRC samples was detected using RT-PCR. The 1-, 3-, or 5-year survival rate was predicted using a nomogram established through Cox proportional hazard regression. At last, the biological function was explored through gene ontology (GO) analysis and gene set enrichment analysis (GSEA). The hallmark pathways significantly involved in hub genes were described through functional enrichment analysis. The correlation between lncRNA ST7-AS1 expression and immune infiltration was analyzed through single-sample GSEA (ssGSEA).Results: LncRNA ST7-AS1 expression was downregulated in BRC. Decreased lncRNA ST7-AS1 expression in BRC was correlated with advanced clinical pathologic characteristics (high grade, histological type, age, menopause status, and HER2 status), survival time, and poor prognosis. The nomogram was established for using lncRNA ST7-AS1 to predict 1-, 3-, or 5-year survival in patients with BRC. In addition, GO and pathway analyses suggested the involvement of lncRNA ST7-AS1 in cell cycle, DNA repair, and immune cell infiltration in the BRC immune microenvironment. We found the correlation of lncRNA ST7-AS1 with T helper cells and DC cells.Conclusion: Low expression of lncRNA ST7-AS1 indicates poor prognosis and has an impact on cell cycle, DNA repair, and proportion of infiltrating immune cells in the BRC microenvironment. Therefore, lncRNA ST7-AS1 can be used as a protective prognostic marker and a potential treatment target for BRC.
Evaluation of the Direct Effect of Bilateral Deep Brain Stimulation of the Subthalamic Nucleus on Levodopa-Induced On-Dyskinesia in Parkinson's Disease
Authors: Li Jiping , Mei Shanshan , Jia Xiaofei , Zhang Yuqing 
Published: April 2021

Objective: This study aimed to evaluate the direct anti-dyskinesia effect of deep brain stimulation (DBS) of subthalamic nucleus (STN) on levodopa-induced on-dyskinesia in Parkinson's disease (PD) patients during the early period after surgery without reducing the levodopa dosage.Methods: We retrospectively reviewed PD patients who underwent STN-DBS from January 2017 to October 2019 and enrolled patients with levodopa-induced on-dyskinesia before surgery and without a history of thalamotomy or pallidotomy. The Unified Dyskinesia Rating Scale (UDysRS) parts I+III+IV and the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) were monitored prior to surgery, and at the 3-month follow-up, the location of active contacts was calculated by postoperative CT–MRI image fusion to identify stimulation sites with good anti-dyskinesia effect.Results: There were 41 patients enrolled. The postoperative levodopa equivalent daily dose (LEDD) (823.1 ± 201.5 mg/day) was not significantly changed from baseline (844.6 ± 266.1 mg/day, P = 0.348), while the UDysRS on-dyskinesia subscores significantly decreased from 24 (10–58) to 0 (0–18) [median (range)] after STN stimulation (P &lt; 0.0001). The levodopa-induced on-dyskinesia recurred in stimulation-off/medication-on state in all the 41 patients and disappeared in 39 patients when DBS stimulation was switched on at 3 months of follow-up. The active contacts which correspond to good effect for dyskinesia were located above the STN, and the mean coordinate was 13.05 ± 1.24 mm lateral, −0.13 ± 1.16 mm posterior, and 0.72 ± 0.78 mm superior to the midcommissural point.Conclusions: High-frequency electrical stimulation of the area above the STN can directly suppress levodopa-induced on-dyskinesia.
Case Report: Autoimmune Encephalitis Associated With Anti-glutamic Acid Decarboxylase Antibodies: A Pediatric Case Series
Authors: Ren Changhong , Ren Haitao , Ren Xiaotun , Zhang Weihua , Li Jiuwei , Dai Lifang , Guan Hongzhi , Fang Fang 
Published: April 2021

Background: Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extralimbic encephalitis. There have been some case reports and investigations regarding anti-GAD65 antibody-associated encephalitis in adult populations, but pediatric cases are rare. We retrospectively analyzed the clinical data of three anti-GAD65 antibody-positive patients to explore the diversity and clinical features of anti-GAD65 antibody-associated pediatric autoimmune encephalitis.Methods: The clinical data of a series of three patients positive for anti-GAD65 antibody were retrospectively analyzed. GAD65 antibodies were determined in serum and CSF using a cell-based assay.Results: All three patients were female, and the onset ages were 4 years and 9 months, 6 years, and 16 years old. Their clinical phenotypes included autoimmune limbic encephalitis, extralimbic encephalitis, and encephalitis combining limbic and extralimbic encephalitis. The clinical symptoms included seizures, memory deficits, drowsiness, dysautonomia, and headache. All patients had abnormal carinal MRI and EEG. All patients received immunotherapy and had transiently good responsiveness, but one patient then experienced relapse. In follow-up, one patient with extralimbic encephalitis recovered completely, while two patients with limbic involvement had poor outcomes with refractory focal epilepsy.Conclusion: In addition to limbic encephalitis, extralimbic encephalitis is also an important phenotype in patients who are positive for anti-GAD65 antibodies. Early diagnosis and immunotherapy can improve the symptoms. However, patients with limbic encephalitis often have refractory epilepsy in the chronic phase and have a poor long-term outcome.
Optimization of Early Mobilization Program for Patients With Acute Ischemic Stroke: An Orthogonal Design
Authors: Zhang Min , Wang Qing , Jiang Yuanyuan , Shi Huiling , Peng Tiantian , Wang Mengyue 
Published: April 2021

Background and purpose: Early mobilization is considered to have favorable outcomes for stroke patients, but there is currently a lack of specific data to guide this early mobilization, including the initiation time, intensity, frequency, and duration of each activity. Therefore, the optimal strategy for early mobilization is unclear. In this study, we investigated the best combination of different factors to achieve early mobilization, to develop the optimal program.Methods: We conducted an L9 (33) orthogonal experiment with a blinded follow-up assessment. Patients with ischemic stroke, admitted to a stroke unit within 24–72 h of its onset, were recruited. Eligible subjects were randomly assigned to one of nine different programs of early mobilization. The outcomes were assessed at baseline, discharge, and 1 and 3 months after discharge to observe the changes in various efficacy indicators and determine the main factors affecting outcome.Results: We analyzed 57 of 63 patients, after six were excluded for poor compliance, failure to cooperate with the study, or worsening of the disease. The initiation time, intensity, and frequency of mobilization were the main factors affecting outcome (all P &lt; 0.05), and the duration of each activity was a secondary factor (P &gt; 0.05). A comprehensive analysis of the various parameters showed that the optimal level of the early mobilization program was an initiation time: 24–48 h after stroke; intensity: bed and chair transfer, sitting out of bed, standing and walking or climbing stairs when mobility permitted; frequency: 2–3 times/day; duration of each mobilization: determined according to the actual situation of the patient.Conclusions: Early rehabilitation with high-intensity physical exercise at 24–48 h after the onset of stroke, 2–3 times/day, may benefit stroke patients. Applying the optimized program of early mobilization to stroke patients effectively alleviated their symptoms of neurological deficit, improved their capacity for self-care, restored their self-efficacy, improved their quality of life and social participation, and reduced post-stroke fatigue at 3 months.
Repetitive Transcranial Magnetic Stimulation for Tinnitus Treatment in Vestibular Schwannoma: A Pilot Study
Authors: Leao Maria Teresa , Machetanz Kathrin , Sandritter Joey , Liebsch Marina , Stengel Andreas , Tatagiba Marcos , Naros Georgios 
Published: April 2021

Background: Vestibular schwannomas (VS) are brain tumors affecting the vestibulocochlear nerve. Thus, VS patients suffer from tinnitus (TN). While the pathophysiology is mainly unclear, there is an increasing interest in repetitive transcranial magnetic stimulation (rTMS) for TN treatment. However, the results have been divergent. In addition to the methodological aspects, the heterogeneity of the patients might affect the outcome. Yet, there is no study evaluating rTMS exclusively in VS-associated tinnitus. Thus, the present pilot study evaluates low-frequency rTMS to the right dorsolateral pre-frontal cortex (DLPFC) in a VS-associated tinnitus.Methods: This prospective pilot study enrolled nine patients with a monoaural VS-associated tinnitus ipsilateral to the tumor. Patients were treated with a 10-day rTMS regime (1 Hz, 100% RMT, 1,200 pulses, right DLPFC). The primary endpoint of the study was the reduction of TN distress (according to the Tinnitus Handicap Inventory, THI). The secondary endpoint was a reduction of TN intensity (according to the Tinnitus Matching Test, TMT) and the evaluation of factors predicting tinnitus outcome (i.e., hearing impairment, TN duration, type of tinnitus).Results: No complications or side effects occurred. There was one drop-out due to a non-responsiveness of the complaint. There was a significant acute effect of rTMS on the THI and TMT. However, there was no significant long-term effect after 4 weeks. While the THI failed to detect any clinically relevant acute effect of rTMS in 56% of the patients, TMT revealed a reduction of TN intensity for more than 20 in 89% and for more than 50 in 56% of the patients. Notably, the acute effect of rTMS was influenced by the TN type and duration. In general, patients with a tonal TN and shorter TN duration showed a better response to the rTMS therapy.Conclusion: The present pilot study is the first one to exclusively evaluate the effect of low-frequency rTMS to the right DLPFC in a VS-associated tinnitus. Our results prove the feasibility and the efficacy of rTMS in this patient cohort. There is a significant acute but a limited long-term effect. In addition, there is evidence that patients with a tonal tinnitus and shorter tinnitus duration might have the strongest benefit. A larger, randomized controlled study is necessary to prove these initial findings.
Alteration in Resting-State EEG Microstates Following 24 Hours of Total Sleep Deprivation in Healthy Young Male Subjects
Authors: Ke Ming , Li Jianpan , Wang Lubin 
Published: April 2021

Purpose: The cognitive effects of total sleep deprivation (TSD) on the brain remain poorly understood. Electroencephalography (EEG) is a very useful tool for detecting spontaneous brain activity in the resting state. Quasi-stable electrical distributions, known as microstates, carry useful information about the dynamics of large-scale brain networks. In this study, microstate analysis was used to study changes in brain activity after 24 h of total sleep deprivation.Participants and Methods: Twenty-seven healthy volunteers were recruited and underwent EEG scans before and after 24 h of TSD. Microstate analysis was applied, and six microstate classes (A–F) were identified. Topographies and temporal parameters of the microstates were compared between the rested wakefulness (RW) and TSD conditions.Results: Microstate class A (a right-anterior to left-posterior orientation of the mapped field) showed lower global explained variance (GEV), frequency of occurrence, and time coverage in TSD than RW, whereas microstate class D (a fronto-central extreme location of the mapped field) displayed higher GEV, frequency of occurrence, and time coverage in TSD compared to RW. Moreover, subjective sleepiness was significantly negatively correlated with the microstate parameters of class A and positively correlated with the microstate parameters of class D. Transition analysis revealed that class B exhibited a higher probability of transition than did classes D and F in TSD compared to RW.Conclusion: The observation suggests alterations of the dynamic brain-state properties of TSD in healthy young male subjects, which may serve as system-level neural underpinnings for cognitive declines in sleep-deprived subjects.
Systemic Chemotherapy Including Ramucirumab in Combination With Pressurized Intra-Peritoneal Aerosol Chemotherapy Is a Safe Treatment Option for Peritoneal Metastasis of Gastric Cancer
Authors: Feldbrügge Linda , Gronau Felix , Brandl Andreas , Auer Timo Alexander , Oeff Alan , Thuss-Patience Peter , Pratschke Johann , Rau Beate 
Published: April 2021

BackgroundPressurized intraperitoneal aerosol chemotherapy (PIPAC) is a laparoscopic technique for local chemotherapy. It has been used for treatment of peritoneal metastasis of gastric cancer (PM GC) in combination with systemic therapy. VEGFR2 antagonist ramucirumab is a second-line therapy for GC, and has been suspected to cause wound healing disorders.MethodsThis is a retrospective single center cohort study of patients with PM GC, who received PIPAC treatment in combination with systemic chemotherapy with and without ramucirumab. Data on patients’ characteristics and their perioperative courses were collected and complication rates were compared with regard to preoperative use of ramucirumab and time between last dose of systemic therapy and PIPAC treatment.ResultsFifty patients underwent 90 PIPAC treatments for PM GC in 3 years. Overall postoperative morbidity was 11% with 6% severe complications. The mean interval between systemic therapy and PIPAC was 20 days. Neither the length of interval nor the use of ramucirumab had an effect on complication rates.ConclusionOur study suggests that addition of ramucirumab to pre-PIPAC systemic therapy, irrespective of the length of the treatment-free interval before PIPAC, does not increase the risk of postoperative complications and is therefore a safe option for treatment of PM GC.
Prognostic Modeling of Patients Undergoing Surgery Alone for Esophageal Squamous Cell Carcinoma: A Histopathological and Computed Tomography Based Quantitative Analysis
Authors: Wu Lei-Lei , Wang Jin-Long , Huang Wei , Liu Xuan , Huang Yang-Yu , Zeng Jing , Cui Chun-Yan , Lu Jia-Bin , Lin Peng , Long Hao , Zhang Lan-Jun , Wei Jun , Lu Yao , Ma Guo-Wei 
Published: April 2021

ObjectiveTo evaluate the effectiveness of a novel computerized quantitative analysis based on histopathological and computed tomography (CT) images for predicting the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients.MethodsWe retrospectively reviewed the medical records of 153 ESCC patients who underwent esophagectomy alone and quantitatively analyzed digital histological specimens and diagnostic CT images. We cut pathological images (6000 × 6000) into 50 × 50 patches; each patient had 14,400 patches. Cluster analysis was used to process these patches. We used the pathological clusters to all patches ratio (PCPR) of each case for pathological features and we obtained 20 PCPR quantitative features. Totally, 125 computerized quantitative (20 PCPR and 105 CT) features were extracted. We used a recursive feature elimination approach to select features. A Cox hazard model with L1 penalization was used for prognostic indexing. We compared the following prognostic models: Model A: clinical features; Model B: quantitative CT and clinical features; Model C: quantitative histopathological and clinical features; and Model D: combined information of clinical, CT, and histopathology. Indices of concordance (C-index) and leave-one-out cross-validation (LOOCV) were used to assess prognostic model accuracy.ResultsFive PCPR and eight CT features were treated as significant indicators in ESCC prognosis. C-indices adjusted for LOOCV were comparable among four models, 0.596 (Model A) vs. 0.658 (Model B) vs. 0.651 (Model C), and improved to 0.711with Model D combining information of clinical, CT, and histopathology (all p&lt;0.05). Using Model D, we stratified patients into low- and high-risk groups. The 3-year overall survival rates of low- and high-risk patients were 38.0% and 25.0%, respectively (p&lt;0.001).ConclusionQuantitative prognostic modeling using a combination of clinical data, histopathological, and CT images can stratify ESCC patients with surgery alone into high-risk and low-risk groups.
High TIL, HLA, and Immune Checkpoint Expression in Conventional High-Grade and Dedifferentiated Chondrosarcoma and Poor Clinical Course of the Disease
Authors: Nota Sjoerd P. F. T. , Al-Sukaini Ahmad , Patel Shalin S. , Sabbatino Francesco , Nielsen G. Petur , Deshpande Vikram , Yearley Jennifer H. , Ferrone Soldano , Wang Xinhui , Schwab Joseph H. 
Published: April 2021

PurposeThe aim of this study was to characterize chondrosarcoma tumor infiltration by immune cells and the expression of immunologically relevant molecules. This information may contribute to our understanding of the role of immunological events in the pathogenesis of chondrosarcoma and to the rational design of immunotherapeutic strategies.Patients and MethodsA tissue microarray (TMA) containing 52 conventional and 24 dedifferentiated chondrosarcoma specimens was analyzed by immunohistochemical staining for the expression of parameters associated with tumor antigen-specific immune responses, namely, CD4+and CD8+tumor infiltrating lymphocytes (TILs) and the expression of HLA class I heavy chain, beta-2 microglobulin (β2m), HLA class II and immune checkpoint molecules, B7-H3 and PD-1/PD-L1. The results were correlated with histopathological characteristics and the clinical course of the disease.ResultsCD8+TILs were present in 21% of the conventional and 90% of the dedifferentiated chondrosarcoma tumors tested. B7-H3 was expressed in 69% of the conventional and 96% of the dedifferentiated chondrosarcoma tumors tested. PD-1 and PD-L1 were expressed 53% and 33% respectively of the dedifferentiated tumors tested. PD-L1 expression was associated with shorter time to metastasis.ConclusionThe tumor infiltration by lymphocytes suggests that chondrosarcoma is immunogenic. Defects in HLA class I antigen and expression of the checkpoint molecules B7-H3 and PD-1/PD-L1 suggest that tumor cells utilize escape mechanisms to avoid immune recognition and destruction. This data implies that chondrosarcoma will benefit from strategies that enhance the immunogenicity of tumor antigens and/or counteract the escape mechanisms.
Rapamycin Antagonizes BCRP-Mediated Drug Resistance Through the PI3K/Akt/mTOR Signaling Pathway in mPRα-Positive Breast Cancer
Authors: Zhang Jing , Hu Jing , Li Weiwei , Zhang Chunyan , Su Peng , Wang Yan , Sun Wei , Wang Xiao , Li Li , Wu Xiaojuan 
Published: April 2021

PurposeOverexpression of breast cancer (BCa) resistance protein (BCRP) is detected in approximately 30% of BCa cases. BCRP indicates a poor response to chemotherapy, and it has become a classic target to overcome drug-resistant tumor cells. In this study, we aimed to explore the mechanism of BCRP overexpression and a strategy to reverse this overexpression in invasive BCa.MethodsBCRP expression in BCa tissues was determined by immunohistochemistry. GSE25066 was downloaded from the NCBI GEO database. Western blot was used to determine the expression of key molecules in vitro. Cell counting kit-8 assays were used to assess the drug response of BCa cells.ResultsOur results suggested that BCRP is an independent risk factor for BCa. We further established that upon 17α-PG binding, membrane progesterone receptor α (mPRα) promoted BCRP expression via the PI3K/Akt/mTOR signaling pathway. mPRα physically interacted with p-Akt1 S473. Moreover, rapamycin, an inhibitor of mTOR complex 1 (mTORC1), downregulated BCRP expression and enhanced the effects of particular drugs, including doxorubicin and paclitaxel.ConclusionBCRP is a potential biomarker of poor prognosis in BCa. BCRP expression is regulated by 17α-PG in mPRα-positive BCa cells through the PI3K/Akt/mTOR signaling pathway. Rapamycin might enhance the therapeutic effect of chemotherapy agents in mPRα-positive MDA-MB-453/BCRP cells and might be a therapeutic option for mPRα-positive invasive BCa with BCRP overexpression.