bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Pan-Cancer Analysis of Heat Shock Protein 110, 90, 70, and 60 Families
Authors: Yan Li-rong , Shen Shi-xuan , Wang Ang , Ding Han-xi , Liu Ying-nan , Yuan Yuan , Xu Qian 
Published: October 2021

Background:Here we carried out a panoramic analysis of the expression and prognosis of HSP110, HSP90, HSP70, and HSP60 families in 33 types of cancer, with the aim of deepening the systematic understanding of heat shock proteins (HSPs) in cancer.Materials and Methods:Next-generation sequencing data of multiple tumors were downloaded from TCGA, CCLE and Oncomine databases. RStudio 3.6.1 was used to analyze HSP110, HSP90, HSP70 and HSP60 families based on their expression in 33 types of cancer. The validationsin vivo(stomach adenocarcinoma and colon adenocarcinoma tissues) were performed by qRT-PCR.Results:HSPs were differentially expressed in different cancers. The results revealed mainly positive correlations among the expressions of HSPs in different cancers. Expressions of HSP family members were generally associated with poor prognosis in respiratory, digestive, urinary and reproductive system tumors and associated with good prognosis in cholangiocarcinoma, pheochromocytoma and paraganglioma. TCGA mutation analysis showed that HSP gene mutation rate in cancers was 0–23%. CCLE mutation analysis indicated that HSP gene mutation rate in 828 cell lines from 15 tumors was 0–17%. CNV analysis revealed that HSPs have different degrees of gene amplifications and deletions in cancers. Gene mutations of 15 HSPs influenced their protein expressions in different cancers. Copy number amplifications and deletions of 22 HSPs also impacted protein expression levels in pan-cancer. HSP gene mutation was generally a poor prognosis factor in cancers, except for uterine corpus endometrial carcinoma. CNVs in 14 HSPs showed varying influences on survival status in different cancers. HSPs may be involved in the activation and inhibition of multiple cancer-related pathways. HSP expressions were closely correlated with 22 immune cell infiltrations in different cancers. The qRT-PCR validation resultsin vivoshowed that HSPA2 was down-regulated in stomach adenocarcinoma and colon adenocarcinoma; HSPA7 and HSPA1A also were down-regulated in colon adenocarcinoma. HSPA2-HSPA7 (r = 0.031,p= 0.009) and HSPA1A-HSPA7 (r = 0.516,p&lt; 0.001) were positive correlation in colon adenocarcinoma.Conclusion:These analysis and validation results show that HSP families play an important role in the occurrence and development of various tumors and are potential tumor diagnostic and prognostic biomarkers as well as anti-cancer therapeutic targets.
Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma
Authors: Lin Guofu , Chen Luyang , Lin Lanlan , Lin Hai , Guo Zhifeng , Xu Yingxuan , Hu Chanchan , Fu Jinglan , Lin Qinhui , Chen Wenhan , Zeng Yiming , Xu Yuan 
Published: October 2021

Background: Lung adenocarcinoma (LUAD) is the most predomintnt lung cancer subtype with increasing morbidity and mortality. Previous studies have shown that aquaporin (AQP) family genes were correlated with tumor progression and metastasis in several kinds of malignancies. However, their biological behaviors and prognostic values in LUAD have not been comprehensively elucidated.Methods: RNA sequencing and real-time reverse transcription PCR (RT-PCR) were used to assess AQP1/3/4/5 gene expressions in LUAD patients using GEPIA and UALCAN databases. And then Kaplan–Meier analysis, cBioPortal, Metascape, GeneMANIA, TISIDB, and TIMER were utilized to determine the prognostic value, mutation frequency, and immune cell infiltration of AQP family members in LUAD.Results: We found that AQP3 expression was significantly elevated and AQP1 expression was markedly reduced in LUAD patients, whereas the expression levels of AQP4 and AQP5 exhibited no significant changes. The Kaplan–Meier survival analysis indicated that the higher expressions of AQP1/4/5 were related to longer overall survival (OS). Of interest, AQP3 was significantly correlated with the clinical tumor stage and lower AQP3 expression showed favorable prognosis in stage I LUAD patients, which indicated that AQP3 may be a potential prognostic biomarker for patients. Through functional enrichment analysis, the functions of these four AQPs genes were mainly involved in the passive transport by aquaporins, water homeostasis, and protein tetramerization. Moreover, AQP1/3/4/5 expression was strongly associated with tumor-infiltrating lymphocytes (TILs) in LUAD.Conclusion: AQP3 can be used as a prognosis and survival biomarker for stage I LUAD. These findings may provide novel insights into developing molecular targeted therapies in LUAD.
Effectiveness and Safety of Rituximab for Refractory Myasthenia Gravis: A Systematic Review and Single-Arm Meta-Analysis
Authors: Zhao Cong , Pu Meng , Chen Dawei , Shi Jin , Li Zhuyi , Guo Jun , Zhang Guangyun 
Published: October 2021

Background and Objective: Myasthenia gravis (MG) is an autoimmune neuromuscular disease. Nearly 10–30% of patients with MG are refractory to conventional therapy. Rituximab (RTX), a monoclonal antibody targeting CD20, is increasingly used in autoimmune disorders. We performed a systematic review and meta-analysis to evaluate the effectiveness and safety of RTX for refractory MG.Methods: Studies published between January 1, 2000 and January 17, 2021 were searched in PubMed, EMBASE, Cochrane Library, and ClincalTrails.gov. Primary outcomes included proportion of patients achieving minimal manifestation status (MMS) or better and quantitative MG (QMG) score change from baseline. Secondary outcomes were glucocorticoids (GC) doses change from baseline and proportion of patients discontinuing oral immunosuppressants.Results: A total of 24 studies involving 417 patients were included in the meta-analysis. An overall 64% (95% confidence interval, 49–77%) of patients achieved MMS or better. The estimated reduction of QMG score was 1.55 (95% confidence interval, 0.88–2.22). The mean reduction of GC doses was 1.46 (95% confidence interval, 1.10–1.82). The proportion of patients discontinuing oral immunosuppressants was 81% (95% confidence interval, 66–93%). Subgroup analyses showed that the proportion of patients achieving MMS or better and discontinuing oral immunosuppressants was higher in MuSK-MG group than those in AChR-MG group. Improvement was more pronounced in patients with mild to moderate MG compared to those with severe MG. Moreover, the efficacy appeared to be independent of the dose of RTX. 19.6% of patients experienced adverse events, most of which were mild to moderate. Only one patient developed progressive multifocal leukoencephalopathy.Conclusions: RTX can alleviate the symptom of weakness, decrease QMG score and reduce the doses of steroids and non-steroid immunosuppressive agents in refractory MG. It is well-tolerated with few severe adverse events. Randomized controlled trials are urgently needed to study the efficacy of RTX in treating refractory MG and to identify the characteristics of patients who might respond well to RTX.
Bioinformatics Identification of Ferroptosis-Related Biomarkers and Therapeutic Compounds in Ischemic Stroke
Authors: Chen Guozhong , Li Lin , Tao Hongmiao 
Published: October 2021

Background: Stroke is one of the most common deadly diseases with an estimated 780,000 new cases globally, of which ischemic stroke accounts for over 80% of all cases. Ferroptosis is a new form of programmed cell death that plays a vital role in many diseases, including ischemic stroke and heart diseases. The role of the ferroptosis-related gene in the diagnosis, prognosis, or therapy of ischemic stroke was not fully clarified.Methods: Ferroptosis-related differentially expressed genes (DEGs) in ischemic stroke were identified by bioinformatic analysis of the GSE16561 and GSE22255 datasets. Subsequently, receiver operator characteristic (ROC) monofactor analysis was performed to evaluate the diagnostic value of ferroptosis-related biomarkers in ischemic stroke.Results: A total of 10 ferroptosis-related DEGs were identified in ischemic stroke vs. normal control. GO and KEGG analysis revealed that these 10 ferroptosis-related DEGs were mainly enriched in response to oxidative stress, HIF-1 signaling pathway, ferroptosis, lipid, and atherosclerosis. Moreover, the random forest model suggested three ferroptosis-related biomarkers, namely, PTGS2, MAP1LC3B, and TLR4, for ischemic stroke. Interestingly, the expression of PTGS2, MAP1LC3B, and TLR4 was upregulated in ischemic stroke. ROC monofactor analysis demonstrated a good performance of MAP1LC3B, PTGS2, and TLR4 in the diagnosis of ischemic stroke. The expression and diagnostic value of MAP1LC3B, PTGS2, and TLR4 in ischemic stroke were also verified using GSE22255. We also revealed the transcription factor regulation network and co-expressed protein network of ferroptosis-related biomarkers. Several potential therapeutic compounds corresponding to MAP1LC3B, PTGS2, and TLR4 were also identified for ischemic stroke, including Zinc12503187 (Conivaptan), Zinc3932831 (Avodart), Zinc64033452 (Lumacaftor), Zinc11679756 (Eltrombopag), Zinc100378061 (Naldemedine), and Zinc3978005 (Dihydroergotamine).Conclusion: Our results suggested MAP1LC3B, PTGS2, and TLR4 as potential diagnostic biomarkers for ischemic stroke, providing more evidence about the vital role of ferroptosis in ischemic stroke.
Selenium-Binding Protein 1 (SELENBP1) as Biomarker for Adverse Clinical Outcome After Traumatic Spinal Cord Injury
Authors: Seelig Julian , Heller Raban Arved , Haubruck Patrick , Sun Qian , Georg Klingenberg Jochen , Hackler Julian , Crowell Helena Lucia , Daniel Volker , Moghaddam Arash , Schomburg Lutz , Biglari Bahram 
Published: October 2021

Graphical AbstractThe pathophysiology of traumatic spinal cord injury (TSCI) can be divided into two major phases. (A) The mechanical trauma is followed within minutes by a secondary phase consisting of local complex and intertwined acute responses, intercellular signaling and cell activity regulating pathways. Inflammatory processes, oxidative stress and hypoxia, leading to cell damage and death, and specific cell contents are released into the circulation (B). The motor and sensory deficits upon TSCI are assessed by using the American Spinal Injury Association (ASIA) impairment scale (AIS), ranging from AIS A as a complete absence of any motor and sensory functions under the lesion site, to AIS E with complete preservation of motor and sensory functions. (C) The concentrations of serum SELENBP1 were elevated in patients classified as AIS A as compared to less severely affected patients classified as AIS B, C or D. A cut-off was deduced [(SELENBP1) &gt; 30.2 μg/L], reliably predicting whether a patient belongs to the group showing neurological recovery (G1) or not (G0) within 3 months after the trauma. The figure was created by using https://biorender.com.
Role of the Aryl Hydrocarbon Receptor and Gut Microbiota-Derived Metabolites Indole-3-Acetic Acid in Sulforaphane Alleviates Hepatic Steatosis in Mice
Authors: Xu Xiuxiu , Sun Siyuan , Liang Ling , Lou Chenxi , He Qijin , Ran Maojuan , Zhang Lu , Zhang Jingyue , Yan Chen , Yuan Hengjie , Zhou Lu , Chen Xin , Dai Xin , Wang Bangmao , Zhang Jie , Zhao Jingwen 
Published: October 2021

Scope: Gut microbiome-derived metabolites are the major mediators of diet-induced host-microbial interactions. Aryl hydrocarbon receptor (AHR) plays a crucial role in glucose, lipid, and cholesterol metabolism in the liver. In this study, we aimed to investigate the role of indole-3-acetic acid (IAA) and AHR in sulforaphane (SFN) alleviates hepatic steatosis in mice fed on a high-fat diet (HFD).Methods and Results: The HFD-fed male C57BL/6 mice were intervened with SFN for 6 weeks. HFD-mice showed classical pathophysiological characteristics of hepatic steatosis. The results showed that SFN significantly reduced body weight, liver inflammation and hepatic steatosis in HFD-fed mice. SFN reduced hepatic lipogenesis by activating AHR/SREBP-1C pathway, which was confirmed in HepG2 cell experiments. Moreover, SFN increased hepatic antioxidant activity by modulating Nrf-2/NQO1 expression. SFN increased serum and liver IAA level in HFD mice. Notably, SFN manipulated the gut microbiota, resulting in reducing Deferribacteres and proportions of the phylum Firmicutes/Bacteroidetes and increasing the abundance of specific bacteria that produce IAA. Furthermore, SFN upregulated Ahr expression and decreased the expression of inflammatory cytokines in Raw264.7 cells.Conclusions: SFN ameliorated hepatic steatosis not only by modulating lipid metabolism via AHR/SREBP-1C pathway but regulating IAA and gut microbiota in HFD-induced NAFLD mice.
Risk Factors of Lymph Node Metastasis and Its Prognostic Significance in Early Gastric Cancer: A Multicenter Study
Authors: Wang Jinfeng , Wang Liang , Li Sha , Bai Fei , Xie Hailong , Shan Hanguo , Liu Zhuo , Ma Tiexiang , Tang Xiayu , Tang Haibing , Qin Ang , Lei Sanlin , Zuo Chaohui 
Published: October 2021

BackgroundEarly gastric cancer (EGC) is invasive gastric cancer that invades no deeper than the submucosa, regardless of lymph node metastasis (LNM). It is mainly treated by surgery. Recently, the resection range of EGC has been minimized, but cancer recurrence and overall survival in some patients should be given high status. LNM is an important indicator of prognosis and treatment in gastric cancer. The law of the number and location of metastatic lymph nodes in EGC is not yet clear. Therefore, we aimed to identify the risk factors of LNM in radically resected EGC and guide treatment.MethodsThe clinicopathological factors of 611 patients with EGC were retrospectively analyzed in six hospitals between January 2010 and December 2016. The relationship between clinicopathological factors and LNM, as well as their prognostic significance, were analyzed by univariate and multivariate analyses.ResultsThe rate of LNM was 20.0% in the 611 EGC patients. The depth of invasion, differentiation type, tumor diameter, morphological ulceration, and lymphovascular invasion were independent risk factors for LNM (P&lt;0.05) by logistic regression analysis. Tumor location in the proximal third of the stomach and morphological ulceration were significant factors for group 2 LNM. Moreover, the 5-year survival rate was 94.9% for patients with no positive nodes, 88.5% for patients with 1-2 positive nodes, 64.3% for patients with 3-6 positive nodes, and 41.8% for patients with &gt;6 metastatic nodes. Interestingly, the 7-year risk of relapse diminished for patients with no LNM or retrieved no less than 15 lymph nodes.ConclusionsFifteen lymph node dissection and D2 radical operation are the surgical options in case of high risk factors for LNM. Extended lymph node dissection (D2+) is recommended for morphological ulceration or disease located in the proximal third of the stomach due to their high rate of group 2 LNM. Furthermore, LNM is a significant prognostic factor of EGC. Moreover, lymph nodes can also play a significant role in the chemotherapeutic and radiotherapy approach for non-surgical patients with EGC.
Controlling Nutritional Status Score Before Receiving Treatment as a Prognostic Indicator for Patients With Urothelial Cancer: An Exploration Evaluation Methods
Authors: Peng Lei , Du Chunxiao , Meng Chunyang , Li Jinze , You Chengyu , Li Xianhui , Zhao Pan , Cao Dehong , Li Yunxiang 
Published: October 2021

IntroductionThis meta-analysis aims to assess whether the Controlling nutritional status (CONUT) score before treatment can be an independent predictor of the prognosis of patients with urothelial cancer (UC).MethodsThe system searches Web of Science, PubMed, MEDLINE, China National Knowledge Infrastructure (CNKI), and Cochrane Library, and the search time is up to April 2021. Use STATA 16.0 and Engauge Digitizer 4.1 software for data processing and statistical analysis.ResultsA total of 8 studies were included in this meta-analysis. The meta-analysis results show that compared with the low CONUT group, the high CONUT group has worse over survival (OS) [HR=1.58, 95%CI (1.34, 1.86), P=0.001], cancer-specific survival (CSS) [HR=2.03, 95%CI (1.25-3.29), P=0.04] and recurrence-free survival (RFS) [HR=1.97, 95%CI (1.15, 3.40), P=0.014]; for progression-free survival (PFS), or disease-free survival (DFS), the difference between the two groups was not statistically significant [HR=2.30, 95%CI (0.72, 7.32), P=0.158]. According to different carcinoma types, cut-off value, and region, subgroup analysis of OS was performed, and similar results were obtained.ConclusionsBased on current evidence, this meta-analysis proves that the CONUT score of UC patients before treatment is an independent prognostic predictor. It performs well on OS, CSS, and RFS, but the conclusions on DFS/PFS need to be treated with caution.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021251890, identifier CRD42021251890.
SARS-CoV-2 Infection in Cancer Patients: A Population-Based Study
Authors: Zorzi Manuel , Guzzinati Stefano , Avossa Francesco , Fedeli Ugo , Calcinotto Arianna , Rugge Massimo 
Published: October 2021

AimIn a consecutive series of cancer patients tested for SARS-CoV-2 infection, this retrospective population-based study investigates the risks of viral infection and death.MethodsMalignancies were distinguished as incident or prevalent (active or inactive). Cancer management and vital status were retrieved from institutional regional databases. Comorbidities were recorded, based on Adjusted Clinical Groups (ACG). Six Resource Utilization Bands (RUBs) were also considered. Independent risk factors for SARS-CoV-2 infection and death were identified using multivariable logistic regression, considering sex, age, comorbidities and RUBs, cancer status (active versus prevalent), primary cancer site, and treatments (chemotherapy and/or radiotherapy).ResultsAmong 34,929 cancer patients, 1,090 (3.1%) tested positive for SARS-CoV-2 infection (CoV2+ve). The risk of infection was associated with age (OR per 1-year increase=1.012; 95%CI=1.007-1.017), prevalent-inactive disease, hematologic malignancies (OR=1.33; 95%CI=1.03-1.72) and RUB (OR per 1-level increase=1.14; 95%CI=1.05-1.24). Among CoV2+ve cancer patients, the risk of death was doubled for males, and increased with age (OR per 1-year increase=1.07; 95%CI=1.06-1.09) and comorbidities (renal [OR=3.18; 95%CI=1.58-6.49], hematological [OR=3.08; 95%CI=1.49-6.50], respiratory [OR=2.87; 95%CI=1.61-5.14], endocrine [OR=2.09; 95%CI=1.25-3.51]). Lung and blood malignancies raised the mortality risk (OR=3.55; 95%CI=1.56-8.33, and OR=1.81; 95%CI=1.01-3.25 respectively). Incident or prevalent-active disease and recent chemotherapy and radiotherapy (OR=4.34; 95%CI=1.85-10.50) increased the risk of death.ConclusionIn a large cohort of cancer patients, the risk of SARS-CoV-2 infection was higher for those with inactive disease than in incident or prevalent-active cases. Among CoV2+ve cancer patients, active malignancies and recent multimodal therapy both significantly raised the risk of death, which increased particularly for lung cancer.
Nomogram Combining Radiomics With the American College of Radiology Thyroid Imaging Reporting and Data System Can Improve Predictive Performance for Malignant Thyroid Nodules
Authors: Huang Xingzhi , Wu Zhenghua , Zhou Aiyun , Min Xiang , Qi Qi , Zhang Cheng , Chen Songli , Xu Pan 
Published: October 2021

PurposeTo develop and validate a nomogram combining radiomics of B-mode ultrasound (BMUS) images and the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) for predicting malignant thyroid nodules and improving the performance of the guideline.MethodA total of 451 thyroid nodules referred for surgery and proven pathologically at an academic referral center from January 2019 to September 2020 were retrospectively collected and randomly assigned to training and validation cohorts (7:3 ratio). A nomogram was developed through combining the BMUS radiomics score (Rad-Score) with ACR TI-RADS score (ACR-Score) in the training cohort; the performance of the nomogram was assessed with respect to discrimination, calibration, and clinical application in the validation and entire cohorts.ResultsThe ACR-Rad nomogram showed good calibration and yielded an AUC of 0.877 (95% CI 0.836–0.919) in the training cohort and 0.864 (95% CI 0.799–0.931) in the validation cohort, which were significantly better than the ACR-Score model (p &lt; 0.001 and 0.031, respectively). The significantly improved AUC, net reclassification index (NRI), and integrated discriminatory improvement (IDI) of the nomogram were found for both senior and junior radiologists (all p &lt; 0.001). Decision curve analysis indicated that the nomogram was clinically useful. When cutoff values for 50% predicted malignancy risk (ACR-Rad_50%) were applied, the nomogram showed increased specificity, accuracy and positive predictive value (PPV), and decreased unnecessary fine-needle aspiration (FNA) rates in comparison to ACR TI-RADS.ConclusionThe ACR-Rad nomogram has favorable value in predicting malignant thyroid nodules and improving performance of the ACR TI-RADS for senior and junior radiologists.
Prognostic Factors and Surgery for Breast Cancer Patients With Locoregional Recurrence: An Analysis of 5,202 Consecutive Patients
Authors: Huang Jiahui , Tong Yiwei , Chen Xiaosong , Shen Kunwei 
Published: October 2021

PurposeWith the application of “less extensive surgery” in breast cancer treatment, the pattern of locoregional recurrence (LRR) has significantly changed. This study aims to evaluate the risk and prognostic factors of LRR in a recent large breast cancer cohort.MethodsConsecutive early breast cancer patients who received surgery from January 2009 to March 2018 in Shanghai Ruijin Hospital were retrospectively analyzed. LRR was defined as recurrence at the ipsilateral breast (IBTR), chest wall, or regional lymph nodes and without concurrent distant metastasis (DM). Patients’ characteristics and survival were compared among these groups.ResultsAmong 5,202 patients included, 87 (1.7%) and 265 (5.1%) experienced LRR and DM as first event after a median 47.0 (3.0–122.5) months’ follow-up. LRR was significantly associated with large tumor size and positive lymph node status (p &lt; 0.05). Forty (46.0%) patients received further salvage surgery after LRR and had a significantly better 3-year post-recurrence overall survival than those who did not (94.7% vs. 60.7%, p = 0.012). Multivariate analysis showed that salvage surgery for LRR was independently associated with better survival (HR = 0.12, 95% CI 0.02–0.93, p = 0.043) along with estrogen receptor (ER) positivity (HR = 0.33, 95% CI 0.12–0.91, p = 0.033).ConclusionLRR rate was relatively low in recent era of breast cancer treatment. Tumor size and lymph node status were associated with risk of LRR, and salvage surgery for selected LRR patients achieved an excellent outcome.