bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of a second-line treatment and prognostic factors in patients with advanced malignant peritoneal mesothelioma: a retrospective study
Authors: Kitadai rui , Shimoi Tatsunori , Sudo Kazuki , Noguchi Emi , Nagata Yusuke , Sawada Ryoichi , Takashima Atsuo , Boku Narikazu , Yonemori Kan 
Published: January 2021

Abstract
Background
A standard treatment for malignant peritoneal mesothelioma has not been established, and systemic chemotherapy is administered according to malignant pleural mesothelioma. We previously reported the efficacy of cisplatin plus pemetrexed as first-line chemotherapy; however, the efficacy of second-line chemotherapy remains unknown.
Methods
We retrospectively evaluated patients with malignant peritoneal mesothelioma who started first-line systemic chemotherapy with platinum plus pemetrexed between March 2007 and February 2019 at the National Cancer Center Hospital. Patients who received second-line chemotherapy after failure of platinum plus pemetrexed were identified. We evaluated the efficacy of first- and second-line chemotherapy, and explored the prognostic factors. Survival outcomes were determined using Kaplan-Meier estimation, and between-group differences were assessed using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazard models.
Results
A total of 54 and 26 patients received platinum plus pemetrexed as first- and second-line chemotherapy, respectively (gemcitabine in 12 patients; taxane, 6; nivolumab, 3; and others, 5). In all patients, the median overall survival and progression-free survival after first-line chemotherapy were 16.6 and 7.3 months, respectively. Among patients who received second-line chemotherapy, the median overall survival, progression-free survival, and second-line overall survival were 16.9, 3.2, and 9.9 months, respectively. Patients who received 6 or more cycles of platinum plus pemetrexed as first-line chemotherapy had longer overall survival after second-line chemotherapy than those who did not (hazard ratio, 0.23; 95% confidence interval: 0.06–0.82; p = 0.02).
Conclusions
Second-line chemotherapy can be an option for refractory malignant peritoneal mesothelioma, especially for patients who have completed 6 cycles of platinum plus pemetrexed as a first-line chemotherapy.
Formation and Activity Enhancement of Surface Hydrides by the Metal-Oxide Interface
Authors: Wang Beibei , Zhang Lunjia , Cai Jun , Peng Zheng , Cheng Peihong , Li Xiaobao , Zhang Hui , Yang Fan , Liu Zhi 
Published: January 2021

Abstract
The observation of hydride species in reduced ceria has triggered recent interest, because the formation of hydrides in solid catalysts has been limited although hydrides are widely explored in homogeneous catalysis as active species for hydrogenation reactions. Here, we proposed a strategy to enhance the formation and activity of surface hydrides on oxide-based catalysts via the construction of metal-oxide interface. Specifically, during the reaction with H2, Cu supported on CeO2 nano-rods (NRs) were found to enhance the formation of hydride species, with the capacity more than an order of magnitude higher than that of CeO2 NRs. Moreover, sub-nanometer clusters (sub-NCs) of Cu supported on CeO2 NRs could enhance the formation and activity of surface hydrides, much more superior than that of Cu nanoparticles (NPs) on CeO2 NRs. A combination of ambient pressure photoelectron spectroscopy (AP-PES) techniques has enabled in-situ measurements of hydrogen interaction and as such, to correlate directly the electronic structures of solid catalysts with their activity. A strong metal-support interaction between under-saturated Cu clusters with CeO2 was found to account for the enhanced stability and reactivity of surface hydrides at the (sub-NCs) Cu-CeO2 interface, which provides insight for the design of highly efficient catalysts for catalytic hydrogenation reactions.
Identification of NTRK3 as a potential prognostic biomarker associated with tumor mutation burden and immune infiltration in bladder cancer
Authors: Zhang Zhao , Yu Yongbo , Zhang Pengfei , Ma Guofeng , Zhang Mingxin , Liang Ye , Jiao Wei , Niu Haitao 
Published: January 2021

Abstract
Background
Bladder cancer (BLCA) is a common malignant tumor of urinary system with high morbidity and mortality. In recent years, immunotherapy plays a significant role in the treatment of BLCA. Tumor mutation burden (TMB) has been reported to be a powerful biomarker to predict tumor prognosis and efficacy of immunotherapy. Our study aimed to explore the relationship between TMB, prognosis and immune infiltration to excavate the key genes in BLCA.
Methods
Clinical information, somatic mutation and gene expression data of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA) database. According to the calculated TMB scores, patients were divided into high and low TMB groups. Gene Set Enrichment Analysis (GSEA) was performed to screen significantly enriched pathways. Differentially expressed genes (DEGs) between the two groups were identified. Univariate cox analysis and Kaplan-Meier survival analysis were applied for screening key genes. Immune infiltration was performed for TMB groups and NTRK3.
Results
Higher TMB scores were related with poor survival in BLCA. After filtering, 36 DEGs were identified. NTRK3 had the highest hazard ratio and significant prognostic value. Co-expressed genes of NTRK3 were mainly involved in several pathways, including DNA replication, basal transcription factors, complement and coagulation cascades, and ribosome biogenesis in eukaryotes. There was a significant correlation among TMB scores, NTRK3 expression and immune infiltration.
Conclusions
Our results suggest that NTRK3 is a TMB-related prognostic biomarker, which lays the foundation for further research on the immunomodulatory effect of NTRK3 in BLCA.
SFRP2 Promotes Peritoneal Metastasis of Ovarian Cancer within Phosphorylation of GSK3β
Authors: Zhang Tengfei , Qin Shimin Chen , Yuan Jianrong , Zhao Jianlong , Wang Yutong , Jin Jianqiang , Guo Xiaping 
Published: January 2021

Abstract
BackgroundThe aim was to study further the molecular mechanism of ovarian cancer peritoneal metastasis and the corresponding prognostic markers.MaterialsWe analysed the sequencing data of 10 pairs of primary ovarian cancer and peritoneal metastasis from GSE98281 to determine SFRP2 through GO, KEGG and GSEA analysis. Western blot, invasion and migration experiments were used to detect the biological effects of SFRP2 on ovarian cancer cells. Immunohistochemistry was used to detect ovarian cancer in tissue samples from a TCGA-Ovarian Cancer cohort, and the survival analysis of SFRP2 was then performed.ResultsSFRP2 affected the phosphorylation level of GSK3β and upregulated the expression level of β-catenin. The high expression of SFRP2 in ovarian cancer cells improves cell invasion and migration capabilities. In histology studies, high expression of SFRP2 has increased the positive expression of β-catenin in the nucleus, and patients with high expression of SFRP2 had a worse prognosis. Similar results also appeared in ovarian cancer cases with high expression of SFRP2 mRNA in the TCGA data set.ConclusionSFRP2 activates the β-Catenin/Wnt signalling pathway through phosphorylation of GSK3β, which promotes the metastasis of ovarian cancer that leads to poor prognosis.
The Associations of Serum S100A9 with the Severity and Prognosis In Patients With Community-Acquired Pneumonia: A Retrospective Cohort Study
Authors: Liu Hong-Yan , Xiang Hui-Xian , Xiang Ying , Xu Zheng , Feng Chun-Mei , Fei Jun , Fu Lin , Zhao Hui 
Published: January 2021

Abstract
Background: Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 in the CAP was unclear. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a retrospective cohort study.Methods: A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were extracted. Serum S100A9 and inflammatory cytokines were measured.Results: Serum S100A9 was elevated in CAP patients on admission. Furthermore, serum S100A9 was gradually elevated parallelly with CAP severity scores. Inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Furtherly, logistical regression demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage was positively correlated with the death of risk and hospital stay among CAP patients. Conclusion: Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain function in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.
USP9X promotes apoptosis in cholangiocarcinoma by modulation expression of KIF1Bβ via deubiquitinating EGLN3
Authors: Chen Weiqian , Song Jingjing , Liu Siyu , Tang Bufu , Shen Lin , Zhu Jinyu , Fang Shiji , Wu Fazong , Zheng Liyun , Qiu Rongfang , Chen Chunmiao , Gao Yang , Tu Jianfei , Zhao Zhongwei , Ji Jiansong 
Published: January 2021

Abstract
Cholangiocarcinoma represents the second most common primary liver malignancy. The incidence rate has constantly increased over the last decades. Cholangiocarcinoma silent nature limits early diagnosis and prevents efficient treatment. Here we demonstrated that USP9X is downregulated in cholangiocarcinoma which contributes to tumorigenesis. The expression of USP9X in cholangiocarcinoma inhibited cell proliferation and colony formation in vitro as well as xenograft tumorigenicity in vivo. Clinical data demonstrated that expression levels of USP9X were positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that USP9X was involved in the deubiquitination of EGLN3, a member of 2-oxoglutarate and iron-dependent dioxygenases. USP9X elicited tumor suppressor role by preventing degradation of EGLN3. Importantly, knockdown of EGLN3 impaired USP9X-mediated suppression of proliferation. USP9X positively regulated the expression level of apoptosis pathway genes KIF1Bβ through EGLN3 thus involved in apoptosis of cholangiocarcinoma. Together, these findings help to understand that USP9X alleviates the malignant potential of cholangiocarcinoma through upregulation of EGLN3. Consequently, we provided novel insight into that USP9X is a potential biomarker or serves as a therapeutic or diagnostic target for cholangiocarcinoma.
Functional Analysis of SARS-CoV-2 Proteins in Drosophila Identifies Orf6-induced Pathogenicity Attenuated by Selinexor
Authors: Zhu Jun-yi , Lee Jin-Gu , de Leemput Joyce van , Lee Hangnoh , Han Zhe 
Published: January 2021

Abstract
Background: SARS-CoV-2 causes COVID-19 with a widely diverse disease profile that affect many different tissues. The mechanisms underlying its pathogenicity in host organisms remain unclear. Animal models for study the pathogenicity of SARS-CoV-2 proteins are lacking. Methods: Using bioinformatic analysis, we showed that the majority of the virus-host interacting proteins are conserved in Drosophila. Therefore, we generated a series of transgenic lines for individual SARS-CoV-2 genes and used the Gal4-UAS system to express them in various tissues to study their pathogenicity. Results: We found that the Nsp6, Orf6 and Orf7a transgenic flies displayed reduced trachea branching and muscle deficits resulting in “held-up” wing phenotype and poor climbing ability. Furthermore, muscle tissue in these flies showed dramatically reduced mitochondria. Since Orf6 was found to bind nucleopore proteins XPO1, we tested Selinexor, a drug that inhibits XPO1, and found that it could attenuated the Orf6-induced lethality and tissue-specific phenotypes in flies. Conclusions: Our studies here established new Drosophila models for studying the function of SARS-CoV2 genes, identified Orf6 as a highly pathogenic protein in various tissues, and demonstrated the effects of Selinexor for inhibiting Orf6 toxicity with an in vivo model system.
Family Doctor Contract Services and Health-Related Quality of Life Among Patients With Chronic Diseases in Rural China: What Is the Role of Socioeconomic Status?
Authors: Li Zhixian , Li Jie , Fu Peipei , Chen Yan , Jing Zhengyue , Yuan Yemin , Yang Shijun , Yan Chen , Li Wenjuan , Li Jie , Gui Zhen , Zhou Chengchao 
Published: January 2021

Abstract
PurposeThe relationship between family doctor contract services (FDCS) and health-related quality of life (HRQOL) among patients with chronic diseases in rural China was unknown. This study aims to explore the relationship between status of signing on FDCS and HRQOL among patients with chronic diseases and examine whether there are differences in the relationship between different socioeconomic status (SES).MethodsA total of 1,210 respondents were included in this study. HRQOL was measured by EQ-5D-3L. The contracting status was divided into uncontracted and contracted. Tobit regression and Logistic regression were employed to explore the association between contracting status and HRQOL. The interaction terms were included to explore the differences in the association among different SES status.ResultsContracting with family doctors was associated with HRQOL (coefficient = 0.042; 95%CI 0.008 to 0.075). The association was different among different socioeconomic levels that the contracting status was only associated with HRQOL in low-income (P < 0.01) and highly educated patients (P < 0.05). Compared with uncontracted patients, contracted patients reported higher ED-5D-3L utility value in the low-income group (coefficient = 0.116; 95%CI 0.039 to 0.194) and high educational attainment (coefficient = 0.236; 95%CI 0.095 to 0.377).Conclusions﻿This study found a significant association between FDCS and HRQOL among chronic patients in rural Shandong, China. This relationship varied by income levels and educational attainment. The government should take efforts to formulate a variety of measures to encourage chronic patients to contract with family doctors, with special attention to people with low SES.
Barriers in Adult Vitamin D Service Provision by Health Care Workers: a Qualitative Study in Three Ecologies of Ethiopia
Authors: Mekonnen Wubegzier , Feleke Yeweyenhareg , Asnake Wubetsh , Haidar Jemal , Lambisso Biruk , Zewdie Tewabech , Desalegn Yakob 
Published: January 2021

Abstract
Background: Adult vitamin D deficiency, a public health problem in low-income countries, is correlated with increased mortality. Although health care workers (HCWs) in Ethiopia are educated on minerals counseling on the benefits of vitamin D and its sources is not witnessed since their knowledge is low. The main aim of this study is to explore barriers to good knowledge, positive attitude, and practice of health care providers on adult vitamin D.Methods: An exploratory qualitative study is done in three ecologies covering highland, midland, and lowland. The size of 27 participants was fixed by saturation of ideas. In-depth interviews were conducted among leaders and HCWs of different professional groups in health centers and hospitals. Moderators were Ph.D. holders. An interview guide was developed after reviewing research that was translated into the local language. Interviews were audio-taped, transcribed and, translated. Open Code software was used to code and categorize the data. Thematic analysis is presented using themes and sub-themes.Result: The main barriers are related to health systems, HCWs’ understandings, health facilities, and the educational system. Lack of attention by the health systems’ leadership, missing adult vitamin D as a priority in health programs, and the absence of adult vitamin D management and treatment guidelines are barriers related to the health system. On the other hand, health care professionals believed that the prevalence of adult vitamin D deficiency is insignificant and vitamin D deficiency is only an issue related to children. Besides, the inadequacy of laboratory investigation and limited in-service training are barriers related to health facilities while the absence of studies and the focus of the medical curriculum on child vitamin D are barriers related to the education system. Conclusion: Adult vitamin D deficiency is a neglected public health problem with many barriers related to diagnosis and treatment. Barriers are related to the professionals themselves, their leadership, health facilities, and the education system. The government should give attention to adult vitamin D management and treatment, continuous on the job training, development of guidelines, purchase of laboratory equipment, the inclusion of adult vitamin D in pre-service and, in-service training curriculums.
Extrarenal Testicle Wilms Tumor Followed the Operation of Left Hernia Sac High Ligation and Right Cryptorchidism Descent Fixation: A Case Report
Authors: Wang Jinjing , Li Yao , Luo Shuai , Zheng Hong 
Published: January 2021

Abstract
Background:The extrarenal Wilms tumor is a rare malignancy in the pediatric population. So far, no extrarenal testicle Wilms tumor followed the operation of left hernia sac high ligation and right cryptorchidism descent fixation has been reported in the literature. Case presentation: We researched an exceptionally unheard case of the extrarenal testicular Wilms tumor after the surgery of left hernia sac high ligation and right cryptorchidism descent fixation in a 2.8 years old boy. The patient was admitted to a hospital due to the evidence of huge scrotum mass six months after the operation of left hernia sac high ligation and right cryptorchidism descent fixation. A huge tumor ascending from the right testicular was found. Conclusions: Histology examination revealed the typical triphasic Wilms tumor elements such as epithelial, mesenchymal, and blastemal areas. This study revealed histopathological, clinical, diagnostic, prognostic, and therapeutic characteristics of this infrequent tumor.
Association of Empirically Derived Food-based Inflammatory Potential of the Diet and Breast Cancer: A Hospital Based Case-control Study
Authors: Ghanbari Mahtab , Imani Hossein , Shahinfar Hossein , Shab-Bidar Sakineh 
Published: January 2021

Abstract
Background: Diet may be a modifiable factor in the prevention of breast cancer (BC) by modulating inflammation. We used a food-based empirical dietary inflammatory index (FDII) to evaluate the association between FDII and odds of breast cancer in Iranian women.Methods: The present case-control study carried out on 150 age-matched women with newly diagnosed breast cancer and controls. Data for dietary intake and anthropometric measures were collected. FDII score was developed according to participants dietary intakes of 21 pre-defined food groups. Multivariate odds ratios (OR) with 95% confidence intervals (CI) were used to investigate the association of empirically derived food-based inflammatory potential of the diet and breast cancer. Results: Our finding indicated that participants in the top tertile of FDII score had a higher odds of breast cancer (OR: 1.73; 95% CI: 1.14 - 2.53, P=0.01) compared with those in the first tertile. . After controlling confounders, multivariate logistic regressions showed in those at the third tertile of FDII chance of breast cancer was 1.7 times higher than those in the first terile (OR: 1.72; 95% CI: 1.12- 2.58, P=0.01). Conclusions: The results of our study suggested that more pro-inflammatory diets (higher FDII scores) are associated with increased breast cancer risk. These findings suggest that developing an effective dietary modification based on FDII may reduce risk of breast cancer.
Attenuated Input to the Primary Somatosensory Cortex is Associated with the Occurrence of Rubber Hand Illusion
Authors: Sakamoto Masanori , Ifuku Hirotoshi 
Published: January 2021

Abstract
The neural representation of the body is easily altered by the integration of multiple sensory signals in the brain. The “rubber hand illusion” (RHI) is one of the most popular experimental paradigms to investigate this phenomenon. During this illusion, ownership of the rubber hand is created. Some studies have shown that somatosensory processing in the brain is attenuated when RHI occurs. However, it is unknown where attenuation of somatosensory inputs occurs. Here, we show that somatosensory input from the hand is attenuated at the primary somatosensory cortex. We found that the early response of somatosensory evoked potential, which is thought to originate from the primary somatosensory cortex, was attenuated during RHI. Furthermore, this attenuation was observed before the occurrence of the illusion. Our results suggest that attenuation of somatosensory inputs from the hand to the brain is one of the factors influencing the occurrence of the RHI.
Familial SYN1 Pathogenic Mutations Related Neurodevelopmental Disorders in Asian Pediatric Patients
Authors: Xiong Juan , Duan Haolin , Chen Shimeng , Kessi Miriam , He Fang , Deng Xiaolu , Zhang Ciliu , Yang Li , Peng Jing , Yin Fei 
Published: January 2021

Abstract
Background: SYN1 encodes synapsin I, which is a neuronal phosphoprotein in relation to the membranes of small synaptic vesicles. Pathogenic variants in the gene have been confirmed as genetic causes of neurodevelopmental disorders. Methods: In our study, we collected clinical information of two male probands with intellectual disability, and performed whole exome sequencing on both patients and their parents. We also reviewed more SYN1 variant cases in pervious publications.Results: Two maternally inherited variants in SYN1 gene (NM_133499:c.C1076A (p.T359K) in proband A and NM_133499:c.C1444T (p. Q482X) in proband B) were found in our patients, which have never been described in detail before. After a literature review, we found that all probands have been reported so far were male, who inherited the significant SYN1 variants from their asymptomatic or mild affected mother. Although the disease encompasses three main clinical presentations: mental deficiency, easily controlled reflex seizure and behavior problems, the phenotypes of family members vary in gender.Conclusion: Here, we firstly report two familial SYN1-related neurodevelopmental disorders in Asian pediatric patients. Our results supported that gender and phenotype differences should be highly valued in this disorder.