bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer
Authors: Wu Pingping , Pan Xuan , Lu Kecen , Gu Ning 
Published: November 2022

Background: Colon cancer is one of the most common malignant tumors in the world. FOLFIRI (leucovorin, fluorouracil, and irinotecan) is a common combination in chemotherapy regimens. However, insensitivity to FOLFIRI is an important factor in the effectiveness of the treatment for advanced colon cancer. Our study aimed to explore precise molecular targets associated with chemotherapy responses in colon cancer.Methods: Gene expression profiles of 21 patients with advanced colorectal cancer who received chemotherapy based on FOLFIRI were obtained from the Gene Expression Omnibus (GEO) database. The gene co-expression network was constructed by the weighted gene co-expression network analysis (WGCNA) and functional gene modules were screened out. Clinical phenotypic correlation analysis was used to identify key gene modules. Gene Ontology and pathway enrichment analysis were used to screen enriched genes in key modules. Protein–protein interaction (PPI) analysis was used to screen out key node genes. Based on the Gene Expression Profiling Interactive Analysis (GEPIA) database, the correlation between the expression levels of these genes and the overall survival (OS) and disease-free survival (DFS) of colon cancer patients was investigated, and the hub genes were screened out. Immunohistochemistry of candidate hub genes was identified using the Human Protein Atlas database. Finally, clinical information and RNA sequencing data of colon cancer were obtained from The Cancer Genome Atlas project database (TCGA), the GEPIA, and the Human Atlas databases for validation.Results: The WGCNA revealed that three hub genes were closely related to chemotherapy insensitivity of colon cancer: AEBP1, BGN, and TAGLN. The protein expression levels of AEBP1, BGN, and TAGLN in tumor tissues were higher than those in normal tissues. In addition, the gene expression levels of AEBP1, BGN, and TAGLN were negatively correlated with OS and DFS in colon cancer patients. Therefore, AEBP1, BGN, and TAGLN have been identified as potential biomarkers related to the response to FOLFIRI treatment of colon cancer.Conclusion: We found that AEBP1, BGN, and TAGLN, as potential predictive biomarkers, may play an important role in the response to FOLFIRI treatment of colon cancer and as a precise molecular target associated with chemotherapy response in colon cancer.
Educational attainment and endometrial cancer: A Mendelian randomization study
Authors: Wang Qixia , Wang Runchen , Chen Chao , Feng Yi , Ye Zhiming , Zhan Miaorong , Wen Hao , Guo Kaimin 
Published: November 2022

Background: Low educational attainment has been reported as a risk factor for many diseases. However, conclusion on the association between educational attainment and endometrial cancer (EC) are inconsistent in previous observational studies. This study aims to explore the potential causal association between educational attainment and EC.Methods: A Mendelian Randomization analysis was performed using publicly summary-level data sets of genome-wide association studies (GWAS). A total of 306 single-nucleotide polymorphisms (SNPs) were extracted as instrumental variables for the exposure of educational attainment from the Social Science Genetic Association Consortium GWAS summary data of 1,131,881 participants of European ancestry. SNPs of EC were obtained from the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium and the UK Biobank involving 121,885 people. We conducted inverse variance weighted (IVW) to estimate the causal effect as our primary outcome. And we perform several sensitivity analyses, including MR-Egger regression, weighted median method, MR-PRESSO (Mendelian Randomization Pleiotropy Residual Sum and Outlier) global test, and leave-one-out sensitivity analysis, to evaluate the effect of pleiotropism on the causal estimates.Results: Genetic predisposition towards 4.2 years of additional educational attainment was associated with 38% lower risk of EC. (odds ratio 0.72, 95% confidence interval 0.62 to 0.83; p = 1.65*10−5). The consistent results of sensitivity analyses indicated our causal estimates were reliable. Genetic predisposition towards longer educational attainment was associated with lower risk of obesity, high waist-to-hip ratio (WHR), and diabetes.Conclusion: This study indicated that low educational attainment was a causal risk factor for EC, especially for EC with endometrioid histology. Low educational attainment might lead to EC through the mediator of obesity, high WHR, and diabetes.
Development of a copper metabolism-related gene signature in lung adenocarcinoma
Authors: Chang Wuguang , Li Hongmu , Zhong Leqi , Zhu Tengfei , Chang Zenghao , Ou Wei , Wang Siyu 
Published: November 2022

PurposeThe dysregulation of copper metabolism is closely related to the occurrence and progression of cancer. This study aims to investigate the prognostic value of copper metabolism-related genes (CMRGs) in lung adenocarcinoma (LUAD) and its characterization in the tumor microenvironment (TME).MethodsThe differentially expressed CMRGs were identified in The Cancer Genome Atlas (TCGA) of LUAD. The least absolute shrinkage and selection operator regression (LASSO) and multivariate Cox regression analysis were used to establish the copper metabolism-related gene signature (CMRGs), which was also validated in Gene Expression Omnibus (GEO) database (GSE72094). The expression of key genes was verified by quantitative real-time PCR (qRT-PCR). Then, the CMRGS was used to develop a nomogram to predict the 1-year, 3-year, and 5-year overall survival (OS). In addition, differences in tumor mutation burden (TMB), biological characteristics and immune cell infiltration between high-risk and low-risk groups were systematically analyzed. Immunophenoscore (IPS) and an anti-PD-L1 immunotherapy cohort (IMvigor210) were used to verify whether CMRGS can predict the response to immunotherapy in LUAD.Results34 differentially expressed CMRGs were identified in the TCGA dataset, 11 of which were associated with OS. The CMRGS composed of 3 key genes (LOXL2, SLC31A2 and SOD3) had showed good clinical value and stratification ability in the prognostic assessment of LUAD patients. The results of qRT-PCR confirmed the expression of key CMRGs in LUAD and normal tissues. Then, all LUAD patients were divided into low-risk and high-risk groups based on median risk score. Those in the low-risk group had a significantly longer OS than those in the high-risk group (P&lt;0.0001). The area under curve (AUC) values of the nomogram at 1, 3, and 5 years were 0.734, 0.735, and 0.720, respectively. Calibration curves comparing predicted and actual OS were close to ideal model, indicating a good consistency between prediction and actual observation. Functional enrichment analysis showed that the low-risk group was enriched in a large number of immune pathways. The results of immune infiltration analysis also confirmed that there were a variety of immune cell infiltration in the low-risk group. In addition, multiple immune checkpoints were highly expressed in the low-risk group and may benefit better from immunotherapy.ConclusionCMRGS is a promising biomarker to assess the prognosis of LUAD patients and may be serve as a guidance on immunotherapy.
Temporal variations, distribution, ecological risks, and sources of antibiotics in the marine ecosystem of Dapeng Cove, Shenzhen, South China
Authors: Su Haochang , Li Wenjun , Hu Xiaojuan , Xu Wujie , Xu Yu , Wen Guoliang , Cao Yucheng 
Published: November 2022

IntroductionAntibiotics are widely used in medical and health services, as well as livestock farming. High concentrations of antibiotics are eventually discarded into rivers due to incomplete metabolism and removal. Bays connect rivers to the sea, and have important ecological functions. Although the occurrence, concentrations, and distribution of antibiotics in bays have been widely studied, the temporal variations in the concentration, contamination indicators and sources of antibiotics, as well as related ecological risk factors, remain unclear.MethodsWithin this context, we investigate the sources, concentrations, temporal variations, and ecological risks associated with antibiotics in water and sediment samples from Dapeng Cove, Shenzhen, South China, in three rainy seasons.ResultsEight and ten different antibiotics were detected in the water and sediment samples, respectively. Of these, the detection rates of erythromycin-H2O (ETM) and clarithromycin were highest in both sample types (100%), while trimethoprim (TMP) and ETM were the most abundant antibiotics in the water and sediment samples, respectively. The total concentration (TC) of antibiotics was highest in water and sediment samples from a local domestic sewage site, at 301.96 ng/L and 18.67 ng/g, respectively. Several environmental factors and the concentrations of the predominant antibiotics TMP and ETM were positively correlated. Multiple linear regression analysis revealed TMP and ETM to be the predominant antibiotics influencing the TC of the target antibiotics, with partial regression coefficients of 1.28 and 1.136, respectively (p &lt; 0.01). Notably, ETM had risk quotients of 0.43–7.91, indicating medium to high risk, while samples from the inner bay and domestic sewage outlet had high ecological risk levels. Redundancy analysis showed that the domestic sewage and inner bay samples were clustered closely but separately from the other samples.DiscussionThe results of our study indicate that domestic sewage is the dominant source of antibiotics in the bay.
Destination of New Guinea Coastal Undercurrent in the western tropical Pacific: Variability and linkages
Authors: Azminuddin Fuad , Jang Chan Joo , Jeon Dongchull 
Published: November 2022

The New Guinea Coastal Undercurrent (NGCUC) is considered a bottleneck in the western tropical Pacific (WTP), carrying upper-to-intermediate waters from the south to the northwestern Pacific, thereby playing a fundamen	tal role in the interhemispheric water mass exchange. However, how the NGCUC links to the circulation in the WTP was insufficiently studied. This work explores the destination of NGCUC waters, its spatiotemporal changes, and possible physical processes linked with the downstream NGCUC using ocean reanalysis for 22 years (1994 – 2015). Lagrangian particle tracking discloses eight major destinations of the NGCUC: The Equatorial Undercurrent (EUC, 35.26%), the North Equatorial Countercurrent (NECC, 12.3%), the North (13.33%) and South (8.85%) Subsurface Countercurrents, the Equatorial Deep Jet (11.49%), the Mindanao Undercurrent (13.24%), and the Indonesian (3.47%) and Halmahera (0.86%) Throughflows. The NGCUC waters are distributed mainly to the east (81.65%) and their dissemination varies markedly with depth. These destinations exhibit significant variations on seasonal and interannual time scales. The NGCUC strengthens (weakens) during summer (winter) and more NGCUC waters are distributed westward and northeastward (eastward). Interannually, the distribution of the NGCUC water is influenced by El Niño-Southern Oscillation, in which most of its eastward-distributed waters shift northward (equatorward) in El Niño (La Niña) phase joining the strengthened NECC (EUC). Changes in the NGCUC water destination can transform the water mass properties in the WTP. The findings of this study also emphasize the fundamental role of eddies in trapping and redistributing the NGCUC waters and linking the currents in the WTP.
The efficacy and safety of Sacubitril/Valsartan on pulmonary hypertension in hemodialysis patients
Authors: Zhao Cong , Guo Yanhong , Wang Yulin , Wang Liuwei , Yu Lu , Liang Yan , Zhai Zihan , Tang Lin 
Published: November 2022

BackgroundPulmonary hypertension (PH) is a common complication of end-stage renal disease which is associated with adverse outcomes including all-cause mortality and cardiovascular events. Recent studies have demonstrated that Sacubitril/Valsartan (Sac/Val) as an enkephalinase inhibitor and angiotensin II receptor blocker could reduce pulmonary artery systolic pressure (PASP) and improve the prognosis of patients with heart failure. However, whether Sac/Val is effective in hemodialysis (HD) patients with PH is essentially unknown. In this retrospective study, we aimed to evaluate the efficacy and safety of Sac/Val in the treatment of PH in HD patients.MethodsA total of 122 HD patients with PH were divided into Sac/Val group (n = 71) and ARBs group (n = 51) based on the treatment regimen. The PASP, other cardiac parameters measured by echocardiography, and cardiac biomarkers including N-terminal fragment of BNP (NT-proBNP) and cardiac troponin I (cTnI) were observed at baseline and 3 months after treatment.ResultsThere were no significant differences in the baseline characteristics between the two groups. PASP decreased significantly from 45(38, 54) to 28(21, 40) mmHg in Sac/Val group (p &lt; 0.001). PASP reduced from 41(37, 51) to 34(27, 44) mmHg in ARBs group (p &lt; 0.001), and the decrease was more pronounced in the Sac/Val group (p &lt; 0.001). In addition, improvements in the right atrial diameter (RAD), left ventricular diameter (LVD), left ventricular posterior wall thickness (LVPWT), left atrial diameter (LAD), pulmonary artery diameter (PAD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and fractional shortening (FS) were found in Sac/Val group (ps &lt; 0.05). After 3 months, LVD, LAD, LVEDV, LVESV, LVEF, SV, and PASP were significantly improved in Sac/Val group compared with ARBs group (ps &lt;0.05). Significant reduction in NT-proBNP [35,000 (15,000, 70,000) pg/ml vs. 7,042 (3,126, 29,060) pg/ml, p &lt; 0.001] and cTnI [0.056(0.031, 0.085) ng/ml vs. 0.036 (0.012, 0.056) ng/ml, p &lt; 0.001) were observed in Sac/Val group. No significant differences were observed in adverse events between the two groups (ps &gt; 0.05).ConclusionSac/Val seems to be an efficacious regimen in PH with favorable safety and has huge prospects for treating PH in HD patients.
Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection
Authors: Yan Ying , Sun Huizhen , Chang Le , Ji Huimin , Jiang Xinyi , Song Shi , Xiao Yingzi , Feng Kaihao , Nuermaimaiti Abudulimutailipu , Lu Zhuoqun , Wang Lunan 
Published: November 2022

IntroductionOccult hepatitis B virus infection (OBI) is an HBsAg negative state in HBV infection with usually inactive HBV replication. However, there were a minority of individuals with positive HBeAg and anti-HBs among OBI blood donors and few studies have focused on this unusual serological pattern.Methods2022 plasma of blood donors that preliminary screened reactive for HBV DNA and non-reactive for HBsAg were collected from 16 provinces in China from 2015 to 2018. HBV DNA and HBsAg in these samples were retested using the Cobas TaqScreen MPX test and ARCHITECT HBsAg Quantitative II assay. Lumipulse HBsAg-HQ assay and polyethylene glycol (PEG)-double precipitation following HCl and trypsin digestion were performed to detect HBsAg from HBsAg-anti-HBs circulating immune complexes (CICs).Results1487 of 2022 samples were positive for Cobas HBV DNA test and non-reactive for ARCHITECT HBsAg assay, while 404 of them were positive using Lumipulse HBsAg-HQ assay. 10 HBsAg-/anti-HBs+/HBeAg+ OBI blood donor samples were further dissociated and HBsAg-CICs were detected in 7 samples. Sequencing analysis showed that D44N, N98T, G73S, Del 56-116, and I161T occurred in the pre-S region, and immune escape mutations such as P127T, F134L, G145R, V168A, and I126T/S in the S region were found.DiscussionIn conclusion, there were a minority of HBsAg-/anti-HBs+/HBeAg+ individuals in OBI blood donors. The undetectable HBsAg in these individuals was mainly due to HBsAg-CICs. Immune escape-associated mutations also happened under the host’s selective pressure. HBsAg dissociation methods or Lumipulse HBsAg-HQ assay is recommended to distinguish these individuals.
Detection of differentially expressed genes in spatial transcriptomics data by spatial analysis of spatial transcriptomics: A novel method based on spatial statistics
Authors: Qiu Zhihua , Li Shaojun , Luo Ming , Zhu Shuanggen , Wang Zhijian , Jiang Yongjun 
Published: November 2022

BackgroundSpatial transcriptomics (STs) simultaneously obtains the location and amount of gene expression within a tissue section. However, current methods like FindMarkers calculated the differentially expressed genes (DEGs) based on the classical statistics, which should abolish the spatial information.Materials and methodsA new method named spatial analysis of spatial transcriptomics (saSpatial) was developed for both the location and the amount of gene expression. Then saSpatial was applied to detect DEGs in both inter- and intra-cross sections. DEGs detected by saSpatial were compared with those detected by FindMarkers.ResultsSpatial analysis of spatial transcriptomics was founded on the basis of spatial statistics. It was able to detect DEGs in different regions in the normal brain section. As for the brain with ischemic stroke, saSpatial revealed the DEGs for the ischemic core and penumbra. In addition, saSpatial characterized the genetic heterogeneity in the normal and ischemic cortex. Compared to FindMarkers, a larger number of valuable DEGs were found by saSpatial.ConclusionSpatial analysis of spatial transcriptomics was able to effectively detect DEGs in STs data. It was a simple and valuable tool that could help potential researchers to find more valuable genes in the future research.
Case report: Spontaneous remission of synchronous endometrial and ovarian cancers following pregnancy
Authors: Daley Diandra , Padwick Malcolm , Mistry Sabina , Malhotra Vivek , Vikram Radhika Selvi , Stanciu Paul 
Published: November 2022

IntroductionEndometrial cancer is one of the most common malignancies affecting women. It is uncommonly diagnosed in young women, particularly in the absence of abnormal vaginal bleeding symptoms.Case presentationA 28-year-old woman was referred to our department with lower abdominal pain. Transvaginal ultrasound showed a complex right adnexal mass with mixed echogenicity. Magnetic resonance imaging (MRI) identified a right-sided, torted, cystic solid ovarian mass, and a polypoid lesion in the uterine cavity.DiagnosisFollowing multidisciplinary team advice, hysteroscopic transcervical resection of endometrial polypoid mass and laparoscopic right salpingo-oophorectomy was performed. Histopathologic assessment of the endometrial tissue showed changes consistent with grade 1 endometrioid endometrial carcinoma, while the right ovarian mass showed a well-differentiated endometrioid carcinoma.InterventionThe patient underwent hormonal treatment and surveillance whilst making a final decision regarding further surgical management. However, the patient stopped hormonal treatment after 2 weeks, went abroad and absconded from treatment for 8 months. On her return, she had conceived naturally and was in the first trimester of pregnancy. Further management was postponed until the patient was 7 weeks postnatal. The patient was not keen on any further surgical management and opted for close surveillance with ultrasound scans and hysteroscopies with endometrial biopsies. All subsequent endometrial biopsies showed normal endometrium, with no evidence of hyperplasia or malignancy.OutcomeTo date, the patient remains on a 6-monthly surveillance plan and is considered to have had complete natural remission of her endometrial and ovarian cancers following pregnancy.ConclusionThis unique case demonstrates a natural phenomenon, in which the complete, natural remission of endometrial and ovarian cancers occurred following pregnancy and childbirth. The aetiology may be related to the high progesterone levels occurring in pregnancy.
Intra-articular injection of placental mesenchymal stromal cells ameliorates pain and cartilage anabolism/catabolism in knee osteoarthritis
Authors: Fan Mengqiang , Zhang Jingwen , Zhou Li , Chen Zuxiang , Bao Ronghua , Zheng Longpo , Tong Peijian , Ma Yuhai , Shan Letian 
Published: November 2022

Background: Knee Osteoarthritis (kOA), the most common joint degenerative disorder, lacks effective therapeutics. Placenta-derived mesenchymal stromal cells (PMSCs) are effective in tissue repairing and generation, which have potential in treating kOA. This study aimed to determine the anti-kOA efficacy of PMSCs and to explore its action mode.Methods: Flow cytometry and three-line differentiation were performed for identification of PMSCs. In vivo, a rat kOA model established by anterior cruciate ligament transection (ACLT) surgery was used to evaluate the efficacy of PMSCs. Histopathological HE and SO staining with Osteoarthritis Research Society International scoring were conducted, and cartilage expressions of MMP13 and Col2 were measured by immunohistochemistry. Pain behavior parameters by mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), were measured. In vitro, wound healing and cell immunofluorescence assays were conducted to detect the proliferation and migration ability of chondrocytes treated with PMSCs conditioned medium (PMSCs-CM). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) assays were applied to explore the molecular action of PMSCs on chondrocytes.Results: The results of flow cytometry indicated that the surface markers of PMSCs (CD73 &gt; 95%, CD90 &gt; 95%, and CD34 &lt; 2%) were consistent with the typical mesenchymal stromal cells. The in vivo data showed that PMSCs significantly reversed the kOA progression by protection of cartilage, regulation of anabolic (Col2) and catabolic (MMP13) expressions, and relief of pain symptoms. The in vitro data showed that PMSCs promoted chondrocyte proliferation and migration and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Mmp13, Adamts4, Adamts5 and Sox9 and also restored the abnormal protein expressions of Col2, Mmp13 and Sox9 of chondrocytes. The molecular actions of PMSCs on chondrocytes in nested co-culture way or in conditioned medium way were similar, confirming a paracrine-based mode of action.Conclusion: This study demonstrated PMSCs’ anti-kOA efficacy and its paracrine-based action mode, providing novel knowledge of PMSCs and suggesting it as a promising cell therapy for treatment of kOA.