bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Efficacy and Safety of Janus Kinase Inhibitors for Patients With COVID-19: A Living Systematic Review and Meta-Analysis
Authors: Zhang Xueyang , Shang Lianhan , Fan Guohui , Gu Xiaoying , Xu Jiuyang , Wang Yeming , Huang Lixue , Cao Bin 
Published: January 2022

BackgroundCytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19.MethodsDatabases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR).ResultsOf 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis (n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51–0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41–0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42–0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49–0.78) with no increase in the risk of adverse events.ConclusionBaricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414, identifier: CRD42021261414.
COVID GEAS: COVID-19 National Survey in Patients With Systemic Autoimmune Diseases
Authors: Gracia Borja Del Carmelo , Sáez Luis , Pallarés Lucio , Velilla Jose , Marín Adela , Martinez-Lostao Luis , Simeón Carmen Pilar , Fanlo Patricia 
Published: January 2022

ObjectivesCOVID-19 outcomes in population with systemic autoimmune diseases (SAD) remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 infection in people with rheumatic disease.MethodsTwo phases cross-sectional survey of individuals with rheumatic disease in April 2020 and October 2020. COVID infection, severity of disease, age, sex, smoking status, underlying rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analyzed.ResultsA total of 1,529 individuals with autoimmunity disease diagnosis were included. Out of 50 positive patients, 21 required telephone medical assistance, 16 received assessment by primary care physician, 9 were evaluated in Emergency Department and 4 patient required hospitalization. Multivariate analysis was performed without obtaining differences in any of the systemic autoimmune diseases. Regarding the treatments, significant differences were found (p 0.011) in the treatment with anti-TNF-alpha agents with OR 3.422 (1.322–8.858) and a trend to significance (p 0.094) was observed in patients receiving mycophenolate treatment [OR 2.016 (0.996–4-081)].ConclusionsAnti-TNF-alpha treatment was associated with more than 3-fold risk of suffering from SARS-CoV-2 infection, although in all cases infection was mild. Cumulative incidence in patients with SAD was up to 5 times higher than general population but with great differences between autoimmune diseases.
Serum Inflammatory Biomarkers Contribute to the Prognosis Prediction in High-Grade Glioma
Authors: Chen Xiao-Yong , Pan Ding-Long , Xu Jia-Heng , Chen Yue , Xu Wei-Feng , Chen Jin-Yuan , Wu Zan-Yi , Lin Yuan-Xiang , You Hong-Hai , Ding Chen-Yu , Kang De-Zhi 
Published: January 2022

BackgroundTo evaluate the prognostic value of serum inflammatory biomarkers and develop a risk stratification model for high-grade glioma (HGG) patients based on clinical, laboratory, radiological, and pathological factors.Materials and MethodsA retrospective study of 199 patients with HGG was conducted. Patients were divided into a training cohort (n = 120) and a validation cohort (n = 79). The effects of potential associated factors on the overall survival (OS) time were investigated and the benefits of serum inflammatory biomarkers in improving predictive performance was assessed. Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, and support vector machines (SVM) were used to select variables for the final nomogram model.ResultsAfter multivariable Cox, LASSO, and SVM analysis, in addition to 3 other clinico-pathologic factors, platelet-to-lymphocyte ratio (PLR) &gt;144.4 (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.25–3.38; P = 0.005) were left for constructing the predictive model. The model with PLR exhibited a better predictive performance than that without them in both cohorts. The nomogram based on the model showed an excellent ability of discrimination in the entire cohort (C-index, 0.747; 95%CI, 0.706–0.788). The calibration curves showed good consistency between the predicted and observed survival probability.ConclusionOur study confirmed the prognostic value of serum inflammatory biomarkers including PLR and established a comprehensive scoring system for the OS prediction in HGG patients.
Identification of Circular RNA-Based Immunomodulatory Networks in Colorectal Cancer
Authors: Feng Zongfeng , Li Leyan , Tu Yi , Shu Xufeng , Zhang Yang , Zeng Qingwen , Luo Lianghua , Wu Ahao , Chen Wenzheng , Cao Yi , Li Zhengrong 
Published: January 2022

BackgroundCircular RNAs (circRNAs) have been recently proposed as hub molecules in various diseases, especially in tumours. We found that circRNAs derived from ribonuclease P RNA component H1 (RPPH1) were highly expressed in colorectal cancer (CRC) samples from Gene Expression Omnibus (GEO) datasets.ObjectiveWe sought to identify new circRNAs derived from RPPH1 and investigate their regulation of the competing endogenous RNA (ceRNA) and RNA binding protein (RBP) networks of CRC immune infiltration.MethodsThe circRNA expression profiles miRNA and mRNA data were extracted from the GEO and The Cancer Genome Atlas (TCGA) datasets, respectively. The differentially expressed (DE) RNAs were identified using R software and online server tools, and the circRNA–miRNA–mRNA and circRNA–protein networks were constructed using Cytoscape. The relationship between targeted genes and immune infiltration was identified using the GEPIA2 and TIMER2 online server tools.ResultsA ceRNA network, including eight circRNAs, five miRNAs, and six mRNAs, was revealed. Moreover, a circRNA–protein network, including eight circRNAs and 49 proteins, was established. The targeted genes, ENOX1, NCAM1, SAMD4A, and ZC3H10, are closely related to CRC tumour-infiltrating macrophages.ConclusionsWe analysed the characteristics of circRNA from RPPH1 as competing for endogenous RNA binding miRNA or protein in CRC macrophage infiltration. The results point towards the development of a new diagnostic and therapeutic paradigm for CRC.
Case Report: Durable Clinical Response to Third-Line Pyrotinib After Resistance to Trastuzumab in a Gastric Cancer Patient
Authors: Wu Junyi , Li Lei , Qin Jun , Yan Zhengqing , Chen Shiqing , Jin Tao , Xu Junming 
Published: January 2022

BackgroundTrastuzumab plus chemotherapy remains the standard first-line treatment strategy for HER2-positive gastric cancer (GC). Trastuzumab resistance, on the other hand, remains a significant issue. There are a few effective anti-HER2 agents for patients who develop resistance to trastuzumab.Case PresentationA 49-year-old female was diagnosed with stage IV GC with liver and lung metastasis in July 2017. She underwent gastrostomy, and the immunohistochemistry (IHC) result of postoperative tissue demonstrated HER2 (3+). She received first-line treatment of trastuzumab (440 mg), oxaliplatin (200 mg), and S-1 (40 mg). After treatment for 6 months, the patient achieved complete response (CR) with PFS up to 21 months. After progression, she subsequently received trastuzumab (440 mg) plus oxaliplatin (200 mg) as second-line treatment. However, the patient developed resistance to trastuzumab after 12 months of treatment. She started to receive third-line treatment of irinotecan (200 mg d1) and capecitabine (60 mg bid) plus pyrotinib (400 mg/day). After 2 months of treatment, the tumor is evaluated as partial response with PFS of 12 months.ConclusionsWe presented a patient with HER2-positive GC who benefited from the pyrotinib-based treatment after two lines of trastuzumab-based therapies failed. Further research is required to validate such conclusions.
Feasibility of Shear Wave Elastography Imaging for Evaluating the Biological Behavior of Breast Cancer
Authors: Liu Chaoxu , Zhou Jin , Chang Cai , Zhi Wenxiang 
Published: January 2022

ObjectiveTo explore the feasibility of shear wave elastography (SWE) parameters for assessing the biological behavior of breast cancer.Materials and MethodsIn this prospective study, 224 breast cancer lesions in 216 female patients were examined by B-mode ultrasound and shear wave elastography in sequence. The maximum size (Smax) of the lesion was measured by B-mode ultrasound, and then shear wave elastography was performed on this section to obtain relevant parameters, including maximum elasticity (Emax), mean elasticity (Emean), standard deviation of elasticity (SD), and the area ratio of shear wave elastography to B-mode ultrasound (AR). The relationship between SWE parameters and pathological type, histopathological classification, histological grade, lymphovascular invasion status (LVI), axillary lymph node status (ALN), and immunohistochemistry of breast cancer lesions was performed according to postoperative pathology.ResultsIn the univariate analysis, the pathological type and histopathological classification of breast cancer were not significantly associated with SWE parameters; with an increase in the histological grade of invasive ductal carcinoma (IDC), SD (p = 0.016) and Smax (p = 0.000) values increased. In the ALN-positive group, Smax (p = 0.004) was significantly greater than in the ALN-negative group; Smax (p = 0.003), Emax (p = 0.034), and SD (p = 0.045) were significantly higher in the LVI-positive group than in the LVI-negative group; SD (p = 0.043, p = 0.047) and Smax (p = 0.000, p = 0.000) were significantly lower in the ER+ and PR+ groups than in the ER- and PR- groups, respectively; AR (p = 0.032) was significantly higher in the ER+ groups than in the ER- groups, and Smax (p = 0.002) of the HER2+ group showed higher values than that of the HER2- group; Smax (p = 0.000), SD (p = 0.006), and Emax (p = 0.004) of the Ki-67 high-expression group showed significantly higher values than those of the Ki-67 low-expression group. In the multivariate analysis, Ki-67 was an independent factor of Smax (p = 0.005), Emax (p = 0.004), and SD (p = 0.006); ER was an independent influencing factor of Smax (p = 0.000) and AR (p = 0.032). LVI independently influences Smax (p = 0.006).ConclusionsThe SWE parameters Emax, SD, and AR can be used to evaluate the biological behavior of breast cancer.
Chromosomal Aberrations in Blood Lymphocytes as Predictors of Respiratory Function After Stereotactic Lung Irradiation
Authors: Kocsis Zsuzsa S. , Farkas Gyöngyi , Bajcsay András , Kun-Gazda Márta , Lövey József , Ostoros Gyula , Pócza Tamás , Herein András , Ladányi Katalin , Székely Gábor , Markóczy Zsolt , Takácsi-Nagy Zoltán , Polgár Csaba , Juranyi Zsolt 
Published: January 2022

Due to the profound difference in radiosensitivity of patients and various side effects caused by this phenomenon, a radiosensitivity marker is needed. Prediction by a marker may help personalise the treatment. In this study, we tested chromosomal aberrations (CA) of in vitro irradiated blood as predictor of pulmonary function decrease of nonsmall cell lung cancer (NSCLC) patients and also compared it with the CAs in the blood of irradiated patients. Peripheral blood samples were taken from 45 lung cancer patients before stereotactic radiotherapy (SBRT) and immediately after the last fraction and 3, 6, 9, 12, 15, 18, 21, and 24 months later. Respiratory function measurements were performed at the same time. Diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1s), and FEV1s/FVC (FEV1%) were monitored. Metaphase preparations of lymphocytes were made with standard procedures, and chromosome aberrations were analysed. In our cohort, the 36-month local relapse-free survival was 97.4%, and the distant metastasis-free survival was 71.5% at 36 months. There was no change in the mean of the pulmonary function tests (PFTs) after the therapy. However, there was a considerable variability between the patients. Therefore, we subtracted the baseline and normalised the PFT values. There were significant decreases at 12–24 months in relative FEV1s and relative FEV1%. The tendentious decrease of the PFTs could be predicted by the in vitro chromosome aberration data. We also found connections between the in vitro and in vivo CA values (i.e., dicentrics plus rings after 3 Gy irradiation predicts dicentric-plus-ring value directly after the radiotherapy/V54 Gy (p = 0.001 24.2%)).We found that—after further validation—chromosome aberrations resulted from in vitro irradiation before radiotherapy can be a predictive marker of pulmonary function decrease after lung irradiation.
CA9-Related Acidic Microenvironment Mediates CD8+ T Cell Related Immunosuppression in Pancreatic Cancer
Authors: Yin Lingdi , Lu Yichao , Cao Cheng , Lu Zipeng , Wei Jishu , Zhu Xiaole , Chen Jianmin , Guo Feng , Tu Min , Xi Chunhua , Zhang Kai , Wu Junli , Gao Wentao , Jiang Kuirong , Miao Yi , Li Qiang , Peng Yunpeng 
Published: January 2022

PurposeThis study aims to integrate pancreatic cancer TCGA, GEO, and single-cell RNA-sequencing (scRNA-seq) datasets, and explore the potential prognostic markers and underlying mechanisms of the immune microenvironment of pancreatic cancer through bioinformatics methods, in vitro and in vivo assays.MethodsExpression data and clinicopathological data of pancreatic cancer TCGA, GEO (GSE131050), single cell sequencing (PAAD_CRA001160) dataset were downloaded. We used R/Bioconductor edgeR for differential expression analysis. ClusterProfiler was utilized to perform GO enrichment analysis on differentially expressed genes. The online software CIBERSORT was used to reanalyze the mRNA expression data of pancreatic cancer. CellRanger, RunPCA, FindNeighbors, FindClusters, RunTSNE and RunUMAP were used to perform preprocessing, cell clustering and expression profile analysis on single-cell sequencing data sets. We analyzed intracellular pH with or without CA9 inhibitor SLC-0111. Indirect co-culture model of human pancreatic cancer cell lines and healthy individual-derived PBMCs were used to determine the effect of CA9-related Acidic Microenvironment on CD8+ T cells.ResultsThe CIBERSORT analysis of TCGA pancreatic cancer transcriptome sequencing data showed that among the 22 immune microenvironment components, CD8+ T cell infiltration was significantly correlated with the prognosis of pancreatic cancer patients. The differential expression analysis of the TCGA data grouped by the level of CD8+ T cell infiltration indicates that the expression of carbonic anhydrase 9 (CA9) is the most significant, and the survival analysis suggests that CA9 is associated with the overall survival of pancreatic cancer. TCGA data and GEO data set GSE131050 expression correlation analysis suggests that CA9 and CD8 expression are closely related. Pancreatic cancer single-cell sequencing data set PAAD_CRA001160 analysis results show that CA9 is mainly expressed in pancreatic cancer cell clusters, and the expression of the cancer cell subgroup CA9 in the single-cell data set is correlated with CD8+ T cell infiltration.ConclusionPancreatic cancer cells may inhibit the infiltration of CD8+ T cells through CA9. Further exploration of its related mechanisms can be used to explore the immune escape pathway of pancreatic cancer and provides new perspectives immune targeted therapy.
Treatment Stratification in First-Line Recurrent or Metastatic Head and Neck Cancer, on Behalf of the EORTC Young Investigator Head and Neck Cancer Group
Authors: Klinghammer Konrad , Lorini Luigi , Nevens Daan , Simon Christian , Machiels Jean-Pascal , Bossi Paolo 
Published: January 2022

Multiple factors differentially influence treatment decisions in the first line treatment of recurrent/metastatic HNSCC. The EORTC Young investigator group launched a survey among treating physicians to explore the main influencing factors for treatment stratification. The questionnaire was posted as a web-survey link from May to August 2020. Next to defining the factors that mostly influence therapeutic decision the survey was complemented by a clinical case discussion of five patient cases. A total of 118 responses from 19 countries were collected. The key factors identified to guide treatment decision were performance status, PD-L1 Expression, time from last systemic treatment above or below 6 months, and disease burden.Prospective evaluation of patient characteristics and additional potential predictive biomarkers for novel treatment options remains an important question to stratify personalized treatment for RM HNSCC.
Cancer Genomic Alterations Can Be Potential Biomarkers Predicting Microvascular Invasion and Early Recurrence of Hepatocellular Carcinoma
Authors: Xin Zhaodan , Li Jin , Zhang Haili , Zhou Yi , Song Jiajia , Chen Piaopiao , Bai Ling , Chen Hao , Zhou Juan , Chen Jie , Ying Binwu 
Published: January 2022

BackgroundHigh recurrence incidence and poor survival after hepatectomy are enormous threats to hepatocellular carcinoma (HCC) patients, which can be caused by microvascular invasion (MVI). However, it is difficult to predict preoperative MVI status. In this study, we focus on cancer genomic alterations to comprehensively explore potential MVI and early recurrence biomarkers and provide clues to the mechanisms of HCC invasion and metastasis.MethodsForty-one patients with initially suspected HCC who were undergoing hepatectomy were finally enrolled. High-throughput targeted sequencing was performed on genomic alterations in their preoperative plasma and surgical fresh tumor tissues utilizing the 1,021-gene panel.ResultsHCC patients without MVI had longer RFS than MVI ones (p &lt; 0.0001). The mutant incidence of genes like KEAP1, TP53, HIST1H3D, NFKBIA, PIK3CB, and WRN was higher in both MVI and early-recurrence patients than their counterparts. Besides, the alteration rates of Rap1 and Ras signaling pathways were significantly higher in MVI patients than NMVI ones (p &lt; 0.05), and a similar trend of differences was also found in early-recurrence/non-recurrence comparison. The maximal variant allele frequency (VAF) of circulating tumor DNA (ctDNA) was statistically higher in MVI patients than NMVI ones (0.038 vs. 0.012, p = 0.0048). With the cutoff value of 0.018, ctDNA maximal VAF could potentially predict the presence of MVI with an AUC of 0.85 (95% CI 0.693–0.998, p = 0.0062).ConclusionThe integration of a panel containing specific mutated genes and ctDNA maximal VAF for predicting MVI and early recurrence of HCC may achieve better performance.
A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification
Authors: Wu Jiyue , Sun Zejia , Bi Qing , Wang Wei 
Published: January 2022

IntroductionClear cell renal cell carcinoma (ccRCC) is a malignant tumor characterized by poor prognosis and difficult treatment. Ferroptosis is a relatively new form of programmed cell death that involved in cancer development and therapy resistance. Studies have shown that targeted ferroptosis may be a novel option for the treatment of ccRCC, but key genes and their roles between ferroptosis and ccRCC are limited so far. This study aims to develop a ccRCC stratified model based on ferroptosis-related genes to provide a reference for the prognosis prediction and the individualized treatment of ccRCC.Materials and MethodsThe mRNAs expression data of ccRCC and FRGs were obtained from TCGA and FerrDb database, respectively. Through multiple analysis, a 4-FRG based prognostic stratified model was constructed and its predictive performance was validated through various methods. Then, a nomogram based on the model was constructed and ccRCC patients stratified by the model were analyzed for tumor microenvironment, immune infiltration, sensitivity for immune checkpoint inhibitors (ICIs)/traditional anti-tumor therapy and tumor mutation burden (TMB). Functional enrichment analysis was performed to explore potential biological pathways. Finally, we verified our model by RT-qPCR, siRNA transfection, scratch assay and CCK-8 assay.ResultsIn this study, the stratified model and a model-based nomogram can accurately predict the prognosis of ccRCC patients in TCGA database. The patients stratified by the model showed different tumor microenvironments, immune infiltration, TMB, resistance to traditional and ICIs therapy, and sensitivity to ferroptosis. Functional enrichment analysis suggested several biological pathways related to the process and prognosis of ccRCC. RT-qPCR confirmed the differential expression of ferroptosis-related genes. Scratch assay and CCK-8 assay indicated the promotion effects of CD44 on the proliferation and migration of ccRCC.ConclusionIn this study, we established a novel ccRCC stratified model based on FRGs, which can accurately predict the prognosis of ccRCC patients and provide a reference for clinical individualized treatment.