bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Construction and Validation of an RNA-Binding Protein-Associated Prognostic Model for Acute Myeloid Leukemia
Authors: Luo Hongwei , Zhang Yingchun , Hu Nan , He Yancheng , He Chengcheng 
Published: September 2021

Background: The abnormal expression of RNA-binding proteins (RBPs) in various malignant tumors is closely related to the occurrence and development of tumors. However, the role of RBPs in acute myeloid leukemia (AML) is unclear.Methods: We downloaded harmonized RNA-seq count data and clinical data for AML from UCSC Xena, including The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) cohorts. R package edgeR was used for differential expression analysis of 337 whole-blood data and 173 AML data. The prognostic value of these RBPs was systematically investigated by using univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO)–Cox regression analysis, and multivariate Cox regression analysis. C-index and calibration diagram were used to judge the accuracy of the model, and decision curve analysis (DCA) was used to judge the net benefit. The biological pathways involved were revealed by gene set enrichment analysis (GSEA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and the protein–protein interaction (PPI) network performed lateral verification on the selected gene set and LASSO results.Results: A prognostic model of 12-RBP signature was established. In addition, the net benefit and prediction accuracy of the prognostic model and the mixed model based on it were significantly higher than that of cytogenetics. It is verified in the TARGET cohort and shows good prediction effect. Both the selection of our gene set and the LASSO results have high credibility. Most of these pathways are involved in the development of the disease, and they also accumulate in leukemia and RNA-related pathways.Conclusion: The prognosis model of the 12-RBP signature found in this study is an optimized biomarker that can effectively stratify the risk of AML patients. Nomogram based on this prognostic model is a reliable method to predict the median survival time of patients. This study expands our current understanding of the role of RBPs in the occurrence of AML and may lay the foundation for future treatment of the disease.
Tofacitinib Suppresses Several JAK-STAT Pathways in Rheumatoid Arthritis In Vivo and Baseline Signaling Profile Associates With Treatment Response
Authors: Palmroth Maaria , Kuuliala Krista , Peltomaa Ritva , Virtanen Anniina , Kuuliala Antti , Kurttila Antti , Kinnunen Anna , Leirisalo-Repo Marjatta , Silvennoinen Olli , Isomäki Pia 
Published: September 2021

ObjectiveCurrent knowledge on the actions of tofacitinib on cytokine signaling pathways in rheumatoid arthritis (RA) is based on in vitro studies. Our study is the first to examine the effects of tofacitinib treatment on Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathways in vivo in patients with RA.MethodsSixteen patients with active RA, despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), received tofacitinib 5 mg twice daily for three months. Levels of constitutive and cytokine-induced phosphorylated STATs in peripheral blood monocytes, T cells and B cells were measured by flow cytometry at baseline and three-month visits. mRNA expression of JAKs, STATs and suppressors of cytokine signaling (SOCS) were measured from peripheral blood mononuclear cells (PBMCs) by quantitative PCR. Association of baseline signaling profile with treatment response was also investigated.ResultsTofacitinib, in csDMARDs background, decreased median disease activity score (DAS28) from 4.4 to 2.6 (p &lt; 0.001). Tofacitinib treatment significantly decreased cytokine-induced phosphorylation of all JAK-STAT pathways studied. However, the magnitude of the inhibitory effect depended on the cytokine and cell type studied, varying from 10% to 73% inhibition following 3-month treatment with tofacitinib. In general, strongest inhibition by tofacitinib was observed with STAT phosphorylations induced by cytokines signaling through the common-γ-chain cytokine receptor in T cells, while lowest inhibition was demonstrated for IL-10 -induced STAT3 phosphorylation in monocytes. Constitutive STAT1, STAT3, STAT4 and STAT5 phosphorylation in monocytes and/or T cells was also downregulated by tofacitinib. Tofacitinib treatment downregulated the expression of several JAK-STAT pathway components in PBMCs, SOCSs showing the strongest downregulation. Baseline STAT phosphorylation levels in T cells and monocytes and SOCS3 expression in PBMCs correlated with treatment response.ConclusionsTofacitinib suppresses multiple JAK-STAT pathways in cytokine and cell population specific manner in RA patients in vivo. Besides directly inhibiting JAK activation, tofacitinib downregulates the expression of JAK-STAT pathway components. This may modulate the effects of tofacitinib on JAK-STAT pathway activation in vivo and explain some of the differential findings between the current study and previous in vitro studies. Finally, baseline immunological markers associate with the treatment response to tofacitinib.
Malnutrition Is an Independent Risk Factor for Low Health-Related Quality of Life Among Centenarians
Authors: Yang Shanshan , Wang Shengshu , Liu Wei , Han Ke , Jia Wangping , Liu Miao , He Yao 
Published: September 2021

Background: To explore the association and understand gender disparities between nutritional status and quality of life among centenarians.Methods: It was a full-sample survey of centenarians conducted in Hainan that included a total of 1,002 eligible centenarians whose age had been verified. The Mini Nutritional Assessment – Short Form (MNA-SF) questionnaire and the EuroQol five dimensions visual analog scale (EQ-5D-VAS) were used to measure participants' nutritional status and quality of life, respectively.Findings: In the 1002 centenarians (822 women and 180 men), 797 (79.5%) (79.5%) reported multimorbidity. The adjusted standardized β estimate association between the MNA-SF and EQ-5D scores was 0.508 in the complete sample. With reference to the normal nutrition group, the standardized β estimate of the association between EQ-5D score and nutritional status were −0.179 and −0.583 for the at risk of malnutrition and malnutrition groups, respectively (both P &lt;0.001). Nutritional status significantly affected the five dimensions of quality of life, particularly mobility and self-care. Compared with the normal nutrition group, the malnutrition group had greater odds of low mobility [Odds ratio (OR)=23.15; 95% CI: 9.81–54.64] and low self-care (OR=24.58; 95% CI: 12.62–47.89). Among males, nutritional status was significantly associated with the usual activities and anxiety/depression dimensions after adjustment. Female participants had results similar to the general population.Interpretation: Malnutrition and being at risk of malnutrition is prevalent among centenarians. Maintaining normal nutritional status is an important protective factor and should receive more attention to improve centenarians' quality of life.
Endoscopic Endonasal Resection of Symptomatic Rathke Cleft Cysts: Total Resection or Partial Resection
Authors: Zhang Xiejun , Yang Jihu , Huang Yan , Liu Yufei , Chen Lei , Chen Fanfan , Huang Guodong 
Published: September 2021

Objective: Rathke cleft cysts (RCC) are benign sellar lesions, and endoscopic endonasal surgery (EES) for symptomatic RCC is becoming increasingly popular, but total resection or partial resection (TR or PR) of the cyst wall is still inconclusive. The aim of this study was to review the complications and clinical prognoses associated with total and partial resection of the cyst wall by EES.Methods: We retrospectively analyzed a series of 72 patients with symptomatic RCC treated by EES from -January 2011 to June 2019 at Shenzhen University First Affiliated Hospital. For these 72 cases, 30 were treated with TR and 42 were treated with PR. Intra- and post-operative complications and clinical prognosis were investigated.Results: All 72 patients underwent a pure EES. In the TR group, 10 patients (33.3%) had intraoperative cerebrospinal fluid leakage (CSF leak), three patients (10%) had postoperative CSF leak, eight patients (26.7%) had postoperative diabetes insipidus (DI), eight patients (26.7%) had postoperative electrolyte disturbance, and 12 patients (40%) had temporary hypopituitarism postoperatively. While in the PR group, three patients (7.1%) had intraoperative CSF leak, two patients (4.8%) had postoperative DI, three patients (7.1%) had postoperative electrolyte disturbance, four patients (9.5%) had temporary hypopituitarism postoperatively, and no cases experienced postoperative CSF leak. The intra- and post-operative complications were significantly higher in TR group then PR group (P IntraoperativeCSFleak = 0.004, P Post−operativeCSFleak =0.036, P TransientDI = 0.008, P Temporaryhypopituitarism = 0.002, P Permanenthypopituitarism = 0.036, P Electrolytedisturbance = 0.023). No significant differences in post-operative improvement and recurrence.Conclusions: EES is a safe and effective approach for the treatment of symptomatic RCC. Complete sucking out the cyst contents and partial resection of the cyst wall may be sufficient for treatment, and total resection of the cyst wall is associated with a higher incidence of complications.
Stability of MDS-UPDRS Motor Subtypes Over Three Years in Early Parkinson's Disease
Authors: Kohat Abhijeet K. , Ng Samuel Y. E. , Wong Aidan S. Y. , Chia Nicole S. Y. , Choi Xinyi , Heng Dede L. , Li Wei , Ng Hwee-Lan , Chua Shu-Ting , Neo Shermyn X. M. , Xu Zheyu , Tay Kay-Yaw , Au Wing-Lok , Tan Eng-King , Tan Louis C. S. 
Published: September 2021

Background: Various classifications have been proposed to subtype Parkinson's disease (PD) based on their motor phenotypes. However, the stability of these subtypes has not been properly evaluated.Objective: The goal of this study was to understand the distribution of PD motor subtypes, their stability over time, and baseline factors that predicted subtype stability.Methods: Participants (n = 170) from two prospective cohorts were included: the Early PD Longitudinal Singapore (PALS) study and the National Neuroscience Institute Movement Disorders Database. Early PD patients were classified into tremor-dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate subtypes according to the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) criteria and clinically evaluated for three consecutive years.Results: At baseline, 60.6% patients were TD, 12.4% patients were indeterminate, and 27.1% patients were PIGD subtypes (p &lt; 0.05). After 3 years, only 62% of patients in TD and 50% of patients in PIGD subtypes remained stable. The mean levodopa equivalent daily dose (LEDD) was higher in the PIGD subtype (276.92 ± 232.91 mg; p = 0.01). Lower LEDD [p &lt; 0.05, odds ratio (OR) 0.99, 95% confidence interval (CI): 0.98–0.99] and higher TD/PIGD ratios (p &lt; 0.05, OR 1.77, 95% CI: 1.29–2.43) were independent predictors of stability of TD subtype with an area under the curve (AUC) of 0.787 (95%CI: 0.669–0.876), sensitivity = 57.8%, and specificity = 89.7%.Conclusion: Only 50–62% of PD motor subtypes as defined by MDS-UPDRS remained stable over 3 years. TD/PIGD ratio and baseline LEDD were independent predictors for TD subtype stability over 3 years.
The Function of Tranexamic Acid to Prevent Hematoma Expansion After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis From Randomized Controlled Trials
Authors: Yan Zeya , Chen Shujun , Xue Tao , Wu Xin , Song Zhaoming , Wang Zongqi , Chen Zhouqing , Wang Zhong 
Published: September 2021

Objectives: The clinical results caused by spontaneous intracerebral hemorrhage (ICH) are disastrous to most patient. As tranexamic acid (TXA) has been proved to decrease the influence of ICH, we conducted this research to explore the function of TXA for the prognosis of ICH compared with placebo.Methods: We searched MEDLINE, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials (RCTs) that were performed to evaluate TXA vs. placebo for ICH up to February 2021. The data were assessed by Review Manager 5.3 software. The risk ratio (RR) and mean difference were analyzed using dichotomous outcomes and continuous outcomes, respectively, with a fixed effect model.Results: We collected 2,479 patients from four RCTs. Then, we took the change of hematoma volume, modified Rankin Scale (mRS), and adverse events as evaluation standard of the treatment for ICH. Through statistical analysis, we found that there is no obvious hematoma expansion effect after the application of TXA (RR = 1.05), and we proceeded the quantitative analysis of percentage change in hematoma volume from baseline, indicating that TXA could inhibit the expansion of hematoma volume (RR = −2.02) compared with placebo. However, according to the outcomes of mRS (0–1, RR = 1.04; 0–2, RR = 0.96), TXA cannot improve neurological functional prognosis. As for the security outcomes—mortality (RR = 1.02), thromboembolic events (RR = 0.99), neurological deterioration (RR = 0.92), infection (RR = 0.86), and craniotomy (RR = 0.41), there seems exist no statistical difference between TXA and placebo.Conclusions: TXA has an advantage in the aspect of preventing hematoma expansion compared with placebo for ICH, but cannot illustrate the efficacy of TXA in improving neurological functional prognosis, which still needs more researches with large sample sizes. Moreover, for safety, we did not find obvious statistical difference between TXA and placebo.
Pathology and Protein Changes of the Spinal Dural Arteriovenous Fistula Arterial Draining Vein Under Sustained High Vascular Pressure
Authors: Liu Peixi , Shi Yuan , Li Sichen , Liu Yingjun , Zhou Yingjie , Song Yaying , Zhu Wei , An Qingzhu 
Published: September 2021

Object: Spinal dural arteriovenous fistula (SDAVF) is the most common spinal vascular shunt lesion. Although pathological changes in the SDAVF draining vein (SDAVF-DV) have been elucidated, protein changes remain enigmatic. We investigated the pathology and protein changes in the SDAVF-DV under sustained high vascular pressure.Methods: Three SDAVF-DV samples were compared with superficial temporal artery (STA) and superficial temporal vein (STV) samples as controls. Vascular structure was revealed by hematoxylin and eosin (H&amp;E) and Masson staining; and cell distribution, extracellular matrix, and inflammation infiltration were observed by immunohistochemistry. Label-free quantitative proteomics was performed, and the peptide mixture was fractionated and analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins. Bioinformatics analysis of the differentially expressed proteins was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) networks.Results: H&amp;E and Masson staining showed an artery-like structure of the SDAVF-DV. Immunostaining showed that vWF+ cells were not continuous in the SDAVF-DV. Although α-SMA+ and AT1+ cells were more abundant in the STV than in the SDAVF-DV, piezo-1 expression was lower in the SDAVF-DV. The SDAVF-DV showed different distributions of elastin, COL I, and COL III. COL IV and COL VI were decreased in the SDAVF-DV, while CD45+ cells and COX-1 were increased compared with those in the controls. No differences in CD68 expression and COX-2 staining were observed between the SDAVF-DV and controls. Compared with the STA, 95 proteins were upregulated and 303 proteins were downregulated in the SDAVF-DV. The most differential GO terms in each category were the adenylate cyclase-modulating G protein-coupled receptor signaling pathway, U6 snRNP, and SH3 domain binding. The most differentially expressed KEGG protein pathway was focal adhesion. Compared with the STV, the SDAVF-DV had 158 upregulated proteins and 362 downregulated proteins. The most differential GO terms in each category were lamellipodium assembly, U6 snRNP, and SH3 domain binding; and the most differentially expressed KEGG protein pathway was dilated cardiomyopathy. PPI analysis revealed PPIs among the top 300 proteins.Conclusions: The SDAVF-DV exhibits specific pathology and protein expression changes under sustained high vascular pressure. The results of the present study provide insights into the pathogenesis of SDAVF formation at the protein level as well as a scientific foundation for further exploration of the pathophysiological mechanism of the SDAVF.
A Study Protocol for an Open-Label Feasibility Treatment Trial of Visual Snow Syndrome With Transcranial Magnetic Stimulation
Authors: Grande Marissa , Lattanzio Lucas , Buard Isabelle , McKendrick Allison M. , Chan Yu Man , Pelak Victoria S. 
Published: September 2021

Background: Visual Snow (VS) syndrome is believed to be due to aberrant central visual processing. Positron Emission Tomography (PET) brain imaging and visual evoked potential studies provide evidence for excessive neuronal activity in the medial temporal lobe, specifically the lingual gyrus, and suggest the VS syndrome is a hyperexcitability syndrome. These data provide the basis for consideration of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for the VS syndrome.Objective: To publish the study protocol for a pilot study underway at the University of Colorado School of Medicine to investigate the use of rTMS intervention to improve symptoms and visual dysfunction associated with VS. The study aims to determine the adverse events and drop-out rate, evaluate performance of outcome measures, including a novel VS symptom scale, and describe changes in outcomes associated with treatment.Methods and Design: Up to 10 participants meeting criteria for VS syndrome, age 19–65 years, will undergo an open-label intervention consisting of 10 rTMS sessions, occurring 5 days a week over a 2-week period. Participants will complete pre-treatment and post-treatment assessments that include: the Colorado Visual Snow Scale (CVSS), the National Eye Institute Visual Functional Questionnaire—25 (VFQ-25), the General Anxiety Disorder—7 scale (GAD-7), and three psychophysical visual processing tasks.Discussion: Knowledge gained from this pilot study will inform future study planning and provide valuable lessons for future investigation of rTMS for the VS syndrome. An overview of study proceedings thus far demonstrates recruitment challenges associated with the COVID-19 pandemic, and additional challenges that are unique to the VS syndrome and to treatment schedules associated with TMS.Registration: This study has been approved by the Colorado Multiple Institutional Review Board. ClinicalTrials.gov Identifier: NCT04925232.
Cerebral Venous Sinus Thrombosis, Pulmonary Embolism, and Thrombocytopenia After COVID-19 Vaccination in a Taiwanese Man: A Case Report and Literature Review
Authors: Lin Wei , Ko Chien-An , Sung Yueh-Feng , Chen Yeu-Chin , Lee Jiunn-Tay , Lin Yun-Qian , Lin Yu-Kai 
Published: September 2021

Objective: Coronavirus disease (COVID-19) vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but fatal complication observed within 2 weeks of adenovirus-vectored vaccination.Case Report: A 52-year-old male patient, with a family history of autoimmune diseases, presented with a new onset of worsening headache with nausea and vomiting post-vaccination. The patient was diagnosed with VITT based on laboratory findings demonstrating thrombocytopenia, elevated D-dimer, and dural sinus thrombosis identified on neuroimaging. The patient was successfully treated with high-dose immunoglobulin, steroids, and non-heparin anticoagulants, without any neurologic sequelae. Finally, a confirmatory test with anti-platelet factor 4 antibody was strongly positive.Conclusion: Physicians should be vigilant when treating patients presenting with new-onset thunderclap headache, progressive worsening headache, and awakening headache accompanied by nausea or vomiting after vaccination, even if no definite clinical neurological deficits are identified. Emergency laboratory test results for demonstrating elevated D-dimer levels, decreased platelet count, and neuroimaging correlation are integral for diagnosis and must be the standard protocol. Treatment with non-heparin anticoagulants, high-dose intravenous immunoglobulin, and steroids that halt or slow the immune-mediated prothrombotic process should be initiated immediately. Considering the high mortality rate of VITT, treatment should be initiated prior to confirmatory test results.
Targeted Next-Generation Sequencing of Cancer-Related Genes in a Norwegian Patient Cohort With Head and Neck Squamous Cell Carcinoma Reveals Novel Actionable Mutations and Correlations With Pathological Parameters
Authors: Dongre Harsh N. , Haave Hilde , Fromreide Siren , Erland Fredrik A. , Moe Svein Erik Emblem , Dhayalan Sophia Manueldas , Riis Rasmus Kopperud , Sapkota Dipak , Costea Daniela Elena , Aarstad Hans Jorgen , Vintermyr Olav K. 
Published: September 2021

BackgroundTargeted next-generation sequencing (NGS) is increasingly applied in clinical oncology to advance personalized treatment. Despite success in many other tumour types, use of targeted NGS panels for assisting diagnosis and treatment of head and neck squamous cell carcinomas (HNSCC) is still limited.AimThe focus of this study was to establish a robust NGS panel targeting most frequent cancer mutations in long-term preserved formalin-fixed paraffin-embedded (FFPE) tissue samples of HNSCC from routine diagnostics.Materials and MethodsTumour DNA obtained from archival FFPE tissue blocks of HNSCC patients treated at Haukeland University Hospital between 2003-2016 (n=111) was subjected to mutational analysis using a custom made AmpliSeq Library PLUS panel targeting 31 genes (Illumina). Associations between mutational burden and clinical and pathological parameters were investigated. Mutation and corresponding clinicopathological data from HNSCC were extracted for selected genes from the Cancer Genome Atlas (TCGA) and used for Chi-square and Kaplan-Meier analysis.ResultsThe threshold for sufficient number of reads was attained in 104 (93.7%) cases. Although the specific number of PCR amplified reads detected decreased, the number of NGS-annotated mutations did not significantly change with increased tissue preservation time. In HPV-negative carcinomas, mutations were detected mainly in TP53 (73.3%), FAT1 (26.7%) and FLG (16.7%) whereas in HPV-positive, the common mutations were in FLG (24.3%) FAT1 (17%) and FGFR3 (14.6%) genes. Other less common pathogenic mutations, including well reported SNPs were reproducibly identified. Presence of at least one cancer-specific mutations was found to be positively associated with an extensive desmoplastic stroma (p=0.019), and an aggressive type of invasive front (p=0.035), and negatively associated with the degree of differentiation (p=0.041). Analysis of TCGA data corroborated the association between cancer-specific mutations and tumour differentiation and survival analysis showed that tumours with at least one mutation had shorter disease-free and overall survival (p=0.005).ConclusionsA custom made targeted NGS panel could reliably detect several specific mutations in archival samples of HNSCCs preserved up to 17 years. Using this method novel associations between mutational burden and clinical and pathological parameters were detected and actionable mutations in HPV-positive HNSCC were discovered.