bluuebunny/crossref_metadata_2025_split huggingface dataset:
MELK is a prognostic biomarker and correlated with immune infiltration in glioma
Authors: Yang Haiyan , Zhou Huandi , Wang Guohui , Tian Lei , Li Haonan , Zhang Yufeng , Xue Xiaoying 
Published: October 2022

ObjectiveGlioma accounts for the vast majority of primary brain tumors with inevitable recurrence and poor prognosis. Maternal embryonic leucine zipper kinase (MELK) is overexpressed in multiple human tumors and could activate a variety of oncogenic-associated signal pathways. However, its role in the glioma microenvironment is still largely unknown.MethodsWe collected the RNA sequence data and clinical information of gliomas from the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases, and investigated MELK expression and its correlation with clinicopathologic features and prognosis in glioma. Moreover, the relationship between MELK expression and immune cell infiltration in the tumor microenvironment of gliomas was explored through single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. In addition, gene set enrichment analysis (GSEA) and Metascape online analysis were performed to find out signaling pathways enriched by differentially expressed genes (DEGs) between high- and low-MELK expression groups. Finally, immunohistochemistry was performed to validate our findings.ResultsData analysis of CGGA and GEO datasets showed that MELK was significantly upregulated in gliomas than in normal brain tissues, and MELK expression was obviously correlated with clinicopathologic features, including age, WHO grade, histological subtype, IDH mutant status, 1p19q codeletion status, and PRS type. Stratified analysis, Cox regression analysis, and nomogram model revealed that high expression of MELK predicted poor survival; hence, MELK could serve as an independent prognostic biomarker for glioma. Moreover, results from enrichment pathway analysis indicated that the immune system process, angiogenesis, apoptosis, cell cycle, and other oncogenic-related signal pathways were significantly enriched between high- and low-MELK expression groups. Immune infiltration analysis demonstrated that increased MELK expression was significantly correlated with higher immune scores, higher fractions of immunocytes (T cells, NK cells resting, macrophages, resting mast cells, and neutrophils), and higher expression levels of immune checkpoints (B7-H3, CTLA4, LAG3, PD-1, PD-L1, and TIM3). Finally, immunohistochemistry analysis validated our findings that high expression of MELK relates to increased malignancy and poor prognosis of glioma.ConclusionOur findings identified that MELK could act as an independent prognostic indicator and potential immunotherapy target for glioma. In conclusion, these findings suggested that DDOST mediated the immunosuppressive microenvironment of gliomas and could be an important biomarker in diagnosing and treating gliomas.
A cross-sectional study on the effect of dietary zinc intake on the relationship between serum vitamin D3 and HOMA-IR
Authors: Hu Biao , Lin Zheng-yang , Cai Yuan , Sun Yue-xin , Yang Shu-qi , Guo Jiang-long , Zhang Shi , Sun Dong-lin 
Published: October 2022

IntroductionSerum vitamin D3 concentration is associated with the risk of insulin resistance. Zinc has also been reported to be associated with a lower risk of insulin resistance. In addition, zinc is an essential cofactor in the activation of vitamin D3. However, the effect of dietary zinc intake on the relationship between vitamin D3 and insulin resistance risk has not been fully studied. Therefore, we designed this cross-sectional study to assess the impact of changes in zinc intake on the relationship between vitamin D3 and insulin resistance risk.Study design and methodsThis study analyzed data from the national Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, involving 9,545 participants. Participants were stratified by zinc intake category (low zinc intake &lt;9.58 mg/ day; High zinc intake: ≥9.58 mg/ day).ResultsIn this cross-sectional study, serum vitamin D3 levels were independently associated with the risk of insulin resistance in both the low and high Zinc intakes (β: −0.26, 95%Cl: −0.56~0.04 vs. β: −0.56, 95%Cl: −1.01~-0.11). In addition, this association was influenced by different dietary zinc intakes (interaction P &lt; 0.05).ConclusionsOur results suggest that zinc intake may influence the association between serum vitamin D3 and the risk of insulin resistance. Further randomized controlled trials are needed to provide more evidence of this finding.
Gallbladder cancer during pregnancy treated with surgery and adjuvant gemcitabine: A case report and review of the literature
Authors: Diciolla A. , Gianoni M. , Fleury M. , Szturz P. , Demartines N. , Peters S. , Duran R. , Desseauve D. , Panchaud Monnat A. , Fasquelle F. , Digklia A. 
Published: October 2022

BackgroundGallbladder cancer (GBC) represents the most common biliary tract cancer. Prognosis remains poor with 5-year overall survival rates less than 5% in advanced stages. GBCs are diagnosed more frequently in women, supposedly due to endocrine factors.CaseA 35-year-old woman, diagnosed with a non-metastatic GBC in the 22nd week of gestation, underwent a complete surgical resection 5 weeks later. Adjuvant gemcitabine was administered without complications, temporarily discontinued in the 32nd week to allow childbirth. The patient was disease-free for more than 3 years with ongoing remission at the last visit in July 2022. During the follow-up period, the child had no developmental, cognitive, or other health issues.ConclusionMalignant tumors occur in about 0.1% of pregnant women, many are treated with chemotherapy. In oncology, the need to deliver optimal treatment in these patients represents a major concern. Both surgery and adjuvant chemotherapy of locally advanced GBC can be performed safely, with certain considerations, in the second trimester of pregnancy.
A novel diagnostic model for differentiation of lung metastasis from primary lung cancer in patients with colorectal cancer
Authors: Guo Rui , Yan Shi , Wang Fei , Su Hua , Xie Qing , Zhao Wei , Yang Zhi , Li Nan , Yu Jiangyuan 
Published: October 2022

ObjectiveThis study aimed to evaluate the 18F-FDG PET/CT in differentiating lung metastasis(LM) from primary lung cancer(LC) in patients with colorectal cancer (CRC).MethodsA total of 120 CRC patients (80 male, 40 female) who underwent 18F-FDG PET/CT were included. The diagnosis of primary lung cancer or lung metastasis was based on histopathology The patients were divided into a training cohort and a validation cohort randomized 1:1. Independent risk factors were extracted through the clinical information and 18F-FDG PET/CT imaging characteristics of patients in the validation cohort, and then a diagnostic model was constructed and a nomograms was made. ROC curve, calibration curve, cutoff, sensitivity, specificity, and accuracy were used to evaluate the prediction performance of the diagnostic model.ResultsOne hundred and twenty Indeterminate lung lesions (ILLs) (77 lung metastasis, 43 primary lung cancer) were analyzed. No significant difference in clinical characteristics and imaging features between the training and the validation cohorts (P &gt; 0. 05). Using uni-/multivariate analysis, pleural tags and contour were identified as independent predictors. These independent predictors were used to establish a diagnostic model with areas under the receiver operating characteristic curves (AUCs) of 0.92 and 0.89 in the primary and validation cohorts, respectively. The accuracy rate of the diagnostic model for differentiating LM from LC were higher than that of subjective diagnosis (P &lt; 0.05).ConclusionsPleural tags and contour were identified as independent predictors. The diagnostic model of ILLs in patients with CRC could help differentiate between LM and LC.
Bevacizumab increases the risk of anastomosis site leakage in metastatic colorectal cancer
Authors: Kim Seijong , Shin Jung Kyong , Park Yoonah , Huh Jung Wook , Kim Hee Cheol , Yun Seong Hyeon , Lee Woo Yong , Cho Yong Beom 
Published: October 2022

BackgroundBevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor and is used in combination with first-line chemotherapy in the treatment of metastatic colorectal cancer. One of the side effects of bevacizumab is gastrointestinal perforation. This study was designed to identify the effect of bevacizumab in intestinal anastomosis site healing.MethodsFrom January 2010 to December 2020, patients diagnosed with stage IV colorectal cancer treated with palliative chemotherapy or chemoradiotherapy followed by radical surgery were retrospectively reviewed. Clinical signs or symptoms and computed tomography were tools used for diagnosing anastomosis site leakage. The patients were divided into two groups, the bevacizumab group (n = 136) and the non-bevacizumab group (n = 124).ResultsAmong the 260 patients 14 (5.4%) patients were diagnosed with anastomosis site leakage. In the bevacizumab group, 13 (9.6%) patients were diagnosed with anastomotic leakage. In the non-bevacizumab group, 1 (0.8%) patient was diagnosed with anastomotic leakage. Anastomosis site leakage was significantly higher in the bevacizumab treatment group (P &lt; 0.001). In the bevacizumab group, period of drug discontinuation before surgery was factor associated with anastomosis site leakage in multivariable analysis (P = 0.031).ConclusionStage IV colorectal patients treated with bevacizumab before radical surgery for primary cancer should be carefully observed of anastomosis site leakage after surgery, and the period of drug discontinuation before surgery should be longer than 5 weeks to avoid anastomosis site leakage.
Neoadjuvant immunotherapy combined with chemotherapy significantly improved patients’ overall survival when compared with neoadjuvant chemotherapy in non-small cell lung cancer: A cohort study
Authors: Dai Fuqiang , Wu Xiaoli , Wang Xintian , Li Kunkun , Wang Yingjian , Shen Cheng , Zhou Jinghai , Niu Huijun , Deng Bo , Tan Qunyou , Wang Ruwen , Guo Wei 
Published: October 2022

BackgroundProgrammed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors displayed considerable advantages in neoadjuvant therapy of non-small cell lung cancer (NSCLC), but the specific application of neoadjuvant immunotherapy has not been well determined, and the long-term prognostic data of neoadjuvant immunochemotherapy combined with surgical resection of NSCLC remains limited. In this study, we intended to assess the efficacy of the neoadjuvant therapy of the PD-1 inhibitor and long-term prognosis in patients with resectable NSCLC.MethodsWe retrospectively analyzed NSCLC surgical patients treated with neoadjuvant therapy in our hospital, and divided them into a neoadjuvant chemotherapy group and a neoadjuvant immunotherapy combined with chemotherapy group. The propensity score matching method was used to evaluate the effectiveness of immunotherapy combined with chemotherapy in the treatment of resectable lung cancer, and the long-term prognosis of these two groups was compared.ResultsA total of 62 cases were enrolled, including 20 patients (20/62, 32.26%) in the immunotherapy group and 42 patients (42/62, 67.74%) in the chemotherapy group. The clinical baseline data of these two groups were balanced. In the immunotherapy group, all patients had tumor regression in imaging finding (tumor regression ratio: 11.88% - 75.00%). In the chemotherapy group, 30 patients had tumor regression (tumor regression ratio: 2.70% - 58.97%). The R0 removal rates of cancers were comparable between the immunotherapy group and chemotherapy group (19/20, 95.00% vs. 39/42, 92.86%, P=1.000). The two groups were balanced in complete minimally invasive surgery, pneumonectomy, operative duration, blood loss, postoperative complications, and hospital stay. The immunotherapy group had more sleeve resection (36.84% vs. 10.26%, p=0.039) including bronchial sleeve and vascular sleeve, higher pathological complete response (pCR) rate (57.89% vs. 5.13%, P&lt;0.001) and major pathologic response (MPR) rate (78.95% vs. 10.26%, P&lt;0.001). There were no differences in survival curves for: smoker and non-smoker, squamous cell carcinoma and adenocarcinoma, or right lung cancer and left lung cancer. Moreover, patients who achieved MPR (including pCR) had significantly better overall survival (OS) and disease-free survival (DFS). Patients in immunotherapy group had significantly better OS and longer DFS than those in chemotherapy group.ConclusionsIn conclusion, neoadjuvant immunotherapy combined with chemotherapy can provide better OS and DFS and improving pCR and MPR rates by shrinking tumors.This study has been registered in the Chinese Clinical Trial Registry, number ChiCTR2200060433. http://www.chictr.org.cn/edit.aspx?pid=170157&amp;htm=4.
Expression of basement membrane genes and their prognostic significance in clear cell renal cell carcinoma patients
Authors: Tao Junyue , Li Xiao , Liang Chaozhao , Liu Yi , Zhou Jun 
Published: October 2022

BackgroundClear cell renal cell carcinoma (ccRCC) is a malignant tumor with limited treatment options. A recent study confirmed the involvement of basement membrane (BM) genes in the progression of many cancers. Therefore, we studied the role and prognostic significance of BM genes in ccRCC.MethodsCo-expression analysis of ccRCC-related information deposited in The Cancer Genome Atlas database and a BM geneset from a recent study was conducted. The differentially expressed BM genes were validated using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Least absolute shrinkage and selection operator regression and univariate Cox regression analyses were performed to identify a BM gene signature with prognostic significance for ccRCC. Multivariate Cox regression, time-dependent receiver operating characteristic, Kaplan–Meier, and nomogram analyses were implemented to appraise the prognostic ability of the signature and the findings were further verified using a Gene Expression Omnibus dataset. Additionally, immune cell infiltration and and pathway enrichment analyses were performed using ImmuCellAI and Gene Set Enrichment Analysis (GSEA), respectively. Finally, the DSIGDB dataset was used to screen small-molecule therapeutic drugs that may be useful in treating ccRCC patients.ResultsWe identified 108 BM genes exhibiting different expression levels compared to that in normal kidney tissues, among which 32 genes had prognostic values. The qRT-PCR analyses confirmed that the expression patterns of four of the ten selected genes were the same as the predicted ones. Additionally, we successfully established and validated a ccRCC patient prediction model based on 16 BM genes and observed that the model function is an independent predictor. GSEA revealed that differentially expressed BM genes mainly displayed significant enrichment of tumor and metabolic signaling cascades. The BM gene signature was also associated with immune cell infiltration and checkpoints. Eight small-molecule drugs may have therapeutic effects on ccRCC patients.ConclusionThis study explored the function of BM genes in ccRCC for the first time. Reliable prognostic biomarkers that affect the survival of ccRCC patients were determined, and a BM gene-based prognostic model was established.
The clinical outcomes of extended resections in patients with IV stage gallbladder cancers: A retrospective study from a large tertiary center
Authors: Zhang Kecheng , Liu Hu , Zhao Yongyang , Zhang Baohua 
Published: October 2022

Background and aimThe role of extended resections in patients with clinical stage IV gallbladder cancer (GBC) remains unclear. This study retrospectively analyzed the clinical outcomes of patients who underwent extended resections for IV GBC.MethodsPatients who were diagnosed with IV stage GBCs and underwent extended resections in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, were retrospectively included in our study. Extended resection was defined as a major hepatectomy (resection of ≥3 liver segments), a pancreatoduodenectomy, or both. The clinical outcomes (baseline characteristics, preoperative variables, intraoperative variables, pathological outcomes, and follow-up data) were obtained and analyzed. The factors associated with major postoperative complications and long-term survival were analyzed by logistic regression analyses.ResultsFrom January 2011 to June 2017, 74 patients were included in our study. There were 33 (44.6%) males and the median age was 62.5 years (interquartile range [IQR], 56.0-67.0 years). According to pathological specimens, the median tumor size was 7cm (IQR, 6-8cm), 73(98.6%) of them received R0 resection and 72 (97.2%) of them were IV A stage GBC. Three perioperative deaths (5.4%) occurred, and major postoperative complications occurred for 15 patients (20.3%). Among them, 61 patients (82.4%) experienced recurrence and 17 patients (23.0%) were still alive after a median follow-up period of 52 months. The disease free survival time was 9 months (95% confidence interval [CI], 7.8-10.2 months) and the overall survival was 18.0 months (95% CI, 15.2-20.8 months). Longer hospital stay days [odds ratio, (OR)=1.979, 95%CI:1.038-1.193, P=0.003), initial symptoms with abdominal pain (OR=21.489, 95%CI=1.22-37.57, P=0.036), more blood transfusion volume during hospitalization (OR=1.036, 95%CI:1.021-1.058, P=0.005), and intraoperative hemorrhage (OR=18.56, 95%C:3.54-47.65, P=0.001) were independently associated with postoperative complications. Moreover, locally recurrence (OR=1.65, 95%CI:1.17-1.96, P=0.015), and more adjuvant chemotherapy cycles (OR=1.46, 95%CI:1.13-1.76, P=0.026) were independently associated with long-term survival.ConclusionOur retrospective study identified that extended resections can be safely and efficaciously performed on stage IV GBC patients in selected cases and performed by experienced surgeons.
Determination of a DNA repair-related gene signature with potential implications for prognosis and therapeutic response in pancreatic adenocarcinoma
Authors: Lai Jinzhi , Chen Weijie , Zhao Aiyue , Huang Jingshan 
Published: October 2022

BackgroundPancreatic adenocarcinoma (PAAD) is one of the leading causes of cancer death worldwide. Alterations in DNA repair-related genes (DRGs) are observed in a variety of cancers and have been shown to affect the development and treatment of cancers. The aim of this study was to develop a DRG-related signature for predicting prognosis and therapeutic response in PAAD.MethodsWe constructed a DRG signature using least absolute shrinkage and selection operator (LASSO) Cox regression analysis in the TCGA training set. GEO datasets were used as the validation set. A predictive nomogram was constructed based on multivariate Cox regression. Calibration curve and decision curve analysis (DCA) were applied to validate the performance of the nomogram. The CIBERSORT and ssGSEA algorithms were utilized to explore the relationship between the prognostic signature and immune cell infiltration. The pRRophetic algorithm was used to estimate sensitivity to chemotherapeutic agents. The CellMiner database and PAAD cell lines were used to investigate the relationship between DRG expression and therapeutic response.ResultsWe developed a DRG signature consisting of three DRGs (RECQL, POLQ, and RAD17) that can predict prognosis in PAAD patients. A prognostic nomogram combining the risk score and clinical factors was developed for prognostic prediction. The DCA curve and the calibration curve demonstrated that the nomogram has a higher net benefit than the risk score and TNM staging system. Immune infiltration analysis demonstrated that the risk score was positively correlated with the proportions of activated NK cells and monocytes. Drug sensitivity analysis indicated that the signature has potential predictive value for chemotherapy. Analyses utilizing the CellMiner database showed that RAD17 expression is correlated with oxaliplatin. The dynamic changes in three DRGs in response to oxaliplatin were examined by RT-qPCR, and the results show that RAD17 is upregulated in response to oxaliplatin in PAAD cell lines.ConclusionWe constructed and validated a novel DRG signature for prediction of the prognosis and drug sensitivity of patients with PAAD. Our study provides a theoretical basis for further unraveling the molecular pathogenesis of PAAD and helps clinicians tailor systemic therapies within the framework of individualized treatment.
A domain knowledge enhanced yield based deep learning classifier identifies perineural invasion in oral cavity squamous cell carcinoma
Authors: Lee Li-Yu , Yang Cheng-Han , Lin Yu-Chieh , Hsieh Yu-Han , Chen Yung-An , Chang Margaret Dah-Tsyr , Lin Yen-Yin , Liao Chun-Ta 
Published: October 2022

BackgroundPerineural invasion (PNI), a form of local invasion defined as the ability of cancer cells to invade in, around, and through nerves, has a negative prognostic impact in oral cavity squamous cell carcinoma (OCSCC). Unfortunately, the diagnosis of PNI suffers from a significant degree of intra- and interobserver variability. The aim of this pilot study was to develop a deep learning-based human-enhanced tool, termed domain knowledge enhanced yield (Domain-KEY) algorithm, for identifying PNI in digital slides.MethodsHematoxylin and eosin (H&amp;E)-stained whole-slide images (WSIs, n = 85) were obtained from 80 patients with OCSCC. The model structure consisted of two parts to simulate human decision-making skills in diagnostic pathology. To this aim, two semantic segmentation models were constructed (i.e., identification of nerve fibers followed by the diagnosis of PNI). The inferred results were subsequently subjected to post-processing of generated decision rules for diagnostic labeling. Ten H&amp;E-stained WSIs not previously used in the study were read and labeled by the Domain-KEY algorithm. Thereafter, labeling correctness was visually inspected by two independent pathologists.ResultsThe Domain-KEY algorithm was found to outperform the ResnetV2_50 classifier for the detection of PNI (diagnostic accuracy: 89.01% and 61.94%, respectively). On analyzing WSIs, the algorithm achieved a mean diagnostic accuracy as high as 97.50% versus traditional pathology. The observed accuracy in a validation dataset of 25 WSIs obtained from seven patients with oropharyngeal (cancer of the tongue base, n = 1; tonsil cancer, n = 1; soft palate cancer, n = 1) and hypopharyngeal (cancer of posterior wall, n = 2; pyriform sinus cancer, n = 2) malignancies was 96%. Notably, the algorithm was successfully applied in the analysis of WSIs to shorten the time required to reach a diagnosis. The addition of the hybrid intelligence model decreased the mean time required to reach a diagnosis by 15.0% and 23.7% for the first and second pathologists, respectively. On analyzing digital slides, the tool was effective in supporting human diagnostic thinking.ConclusionsThe Domain-KEY algorithm successfully mimicked human decision-making skills and supported expert pathologists in the routine diagnosis of PNI.