bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Causal Relationship Between Human Blood Metabolites and Five Neurodegenerative Diseases With GWAS Summary Statistics
Authors: Chen Haimiao , Qiao Jiahao , Wang Ting , Shao Zhonghe , Huang Shuiping , Zeng Ping 
Published: December 2021

Background: Neurodegenerative diseases (NDDs) are the leading cause of disability worldwide while their metabolic pathogenesis is unclear. Genome-wide association studies (GWASs) offer an unprecedented opportunity to untangle the relationship between metabolites and NDDs.Methods: By leveraging two-sample Mendelian randomization (MR) approaches and relying on GWASs summary statistics, we here explore the causal association between 486 metabolites and five NDDs including Alzheimer’s Disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson’s disease (PD), and multiple sclerosis (MS). We validated our MR results with extensive sensitive analyses including MR-PRESSO and MR-Egger regression. We also performed linkage disequilibrium score regression (LDSC) and colocalization analyses to distinguish causal metabolite-NDD associations from genetic correlation and LD confounding of shared causal genetic variants. Finally, a metabolic pathway analysis was further conducted to identify potential metabolite pathways.Results: We detected 164 metabolites which were suggestively associated with the risk of NDDs. Particularly, 2-methoxyacetaminophen sulfate substantially affected ALS (OR = 0.971, 95%CIs: 0.961 ∼ 0.982, FDR = 1.04E-4) and FTD (OR = 0.924, 95%CIs: 0.885 ∼ 0.964, FDR = 0.048), and X-11529 (OR = 1.604, 95%CIs: 1.250 ∼ 2.059, FDR = 0.048) and X-13429 (OR = 2.284, 95%CIs: 1.457 ∼ 3.581, FDR = 0.048) significantly impacted FTD. These associations were further confirmed by the weighted median and maximum likelihood methods, with MR-PRESSO and the MR-Egger regression removing the possibility of pleiotropy. We also observed that ALS or FTD can alter the metabolite levels, including ALS and FTD on 2-methoxyacetaminophen sulfate. The LDSC and colocalization analyses showed that none of the identified associations could be driven by genetic correlation or confounding by LD with common causal loci. Multiple metabolic pathways were found to be involved in NDDs, such as “urea cycle” (P = 0.036), “arginine biosynthesis” (P = 0.004) on AD and “phenylalanine, tyrosine and tryptophan biosynthesis” (P = 0.046) on ALS.Conclusion: our study reveals robust bidirectional causal associations between servaral metabolites and neurodegenerative diseases, and provides a novel insight into metabolic mechanism for pathogenesis and therapeutic strategies of these diseases.
Association Between Dietary Patterns and Plasma Lipid Biomarker and Female Breast Cancer Risk: Comparison of Latent Class Analysis (LCA) and Factor Analysis (FA)
Authors: Cao Shang , Liu Linchen , Zhu Qianrang , Zhu Zheng , Zhou Jinyi , Wei Pingmin , Wu Ming 
Published: December 2021

Background: Diet research focuses on the characteristics of “dietary patterns” regardless of the statistical methods used to derive them. However, the solutions to these methods are both conceptually and statistically different.Methods: We compared factor analysis (FA) and latent class analysis (LCA) methods to identify the dietary patterns of participants in the Chinese Wuxi Exposure and Breast Cancer Study, a population-based case-control study that included 818 patients and 935 healthy controls. We examined the association between dietary patterns and plasma lipid markers and the breast cancer risk.Results: Factor analysis grouped correlated food items into five factors, while LCA classified the subjects into four mutually exclusive classes. For FA, we found that the Prudent-factor was associated with a lower risk of breast cancer [4th vs. 1st quartile: odds ratio (OR) for 0.70, 95% CI = 0.52, 0.95], whereas the Picky-factor was associated with a higher risk (4th vs. 1st quartile: OR for 1.35, 95% CI = 1.00, 1.81). For LCA, using the Prudent-class as the reference, the Picky-class has a positive association with the risk of breast cancer (OR for 1.42, 95% CI = 1.06, 1.90). The multivariate-adjusted model containing all of the factors was better than that containing all of the classes in predicting HDL cholesterol (p = 0.04), triacylglycerols (p = 0.03), blood glucose (p = 0.04), apolipoprotein A1 (p = 0.02), and high-sensitivity C-reactive protein (p = 0.02), but was weaker than that in predicting the breast cancer risk (p = 0.03).Conclusion: Factor analysis is useful for understanding which foods are consumed in combination and for studying the associations with biomarkers, while LCA is useful for classifying individuals into mutually exclusive subgroups and compares the disease risk between the groups.
Efficacy and Safety of Brucea javanica Oil Emulsion Injection in the Treatment of Gastric Cancer: A Systematic Review and Meta-Analysis
Authors: Wang Xinmiao , Wang Heping , Cao Luchang , Wu Jingyuan , Lu Taicheng , Li Shixin , Li Jie 
Published: December 2021

Background: Gastric cancer (GC) is one of the most common digestive tract cancers and ranks fifth in the incidence of malignant tumors worldwide. Brucea javanica oil emulsion injection (BJOEI), a Chinese patent medicine extracted from Brucea javanica (Yadanzi in Chinese Pinyin), is widely used as an adjuvant treatment for GC in China. This systematic review and meta-analysis aimed to evaluate the available data on the efficacy and safety of BJOEI in the treatment of GC and assess the quality of the synthesized evidence.Methods: A comprehensive search was performed on PubMed, EMBASE, CENTRAL, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and Chinese Scientific Journals Database (VIP database), and other potential resources, such as the Chinese Clinical Trial Registry (ChiCTR) and ClinicalTrials.gov from their inception to July 31, 2021. Randomized controlled trials (RCTs) comparing the therapeutic effects of BJOEI combined with conventional therapy to those of conventional therapy alone were included. We used RevMan 5.3 for data analysis and quality evaluation of the included studies and assessed the evidence quality based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.Results: Eighteen RCTs involving 1,210 patients were included, and the meta-analysis results demonstrated that compared with the control group (conventional therapy), the experimental group (BJOEI combined with conventional therapy) showed a significantly improved overall response rate (ORR) (risk ratio [RR] = 1.52, 95% CI: 1.36–1.69, P &lt; 0.00001), clinical benefit rate (CBR) (RR = 1.17, 95% CI: 1.11–1.23, P &lt; 0.00001), performance status (RR = 1.72, 95% CI: 1.46–2.01, P &lt; 0.00001), and reduced incidence of the following adverse drug reactions (ADRs): neutropenia, leukopenia, nausea and vomiting, diarrhea, liver damage, hand-foot syndrome, and peripheral sensory nerve toxicity. Subgroup analysis showed that the BJOEI intervention could significantly improve the ORR and CBR in patients with GC when combined with FOLFOX4, XELOX, and other chemotherapeutics.Conclusion: The evidence presented in this study supports the fact that BJOEI combined with conventional chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, CBR, performance status, and ADR reduction in patients with GC. To further support this conclusion, more rigorously designed, large-scale, and multicenter RCTs are needed in the future.
Lobectomy Versus Sublobectomy in Stage IIIA/N2 Non-Small Cell Lung Cancer: A Population-Based Study
Authors: Wang Suyu , Zhang Zhiyuan , Gu Yang , Lv Xin , Shi Xuan , Liu Meiyun 
Published: December 2021

BackgroundThe role lobectomy plays in stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial for a long time. What’s more, no previous study concentrates on whether sublobectomy can improve survival outcome for these patients, so we performed this population-based study to investigate whether stage IIIA/N2 NSCLC can benefit from these two surgery types and compare survival outcomes after lobectomy and sublobectomy.MethodsA total of 21,638 patients diagnosed with stage IIIA/N2 NSCLC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database matched our selection criteria. The study cohort included patients who received no surgery (n = 15,951), sublobectomy (n = 628) and lobectomy (n = 5,059). Kaplan–Meier method, Cox regression analyses, and inverse probability of treatment weighting (IPTW)-adjusted Cox regression were used to illustrate the influence of sublobectomy and lobectomy on overall survival (OS) rates in the study cohort and compare these two surgery types.ResultsMultivariable Cox regression analysis showed sublobectomy [HR: 0.584 (95%CI: 0.531–0.644), P-value &lt;0.001; IPTW-adjusted HR: 0.619 (95%CI: 0.605–0.633), P-value &lt;0.001] and lobectomy [HR: 0.439 (95%CI: 0.420–0.459), P-value &lt;0.001; IPTW-adjusted HR: 0.441 (95%CI: 0.431–0.451), P-value &lt;0.001] were both related to better OS rates compared with no surgery, and lobectomy exhibited better survival than sublobectomy [HR: 0.751 (95%CI: 0.680–0.830), P-value &lt;0.001; IPTW-adjusted HR: 0.713 (95%CI: 0.696–0.731), P-value &lt;0.001]. Moreover, the results in subgroup analyses based on age, tumor size and radiotherapy and chemotherapy strategy in all study cohort were consistent.ConclusionStage IIIA/N2 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provided better OS rates than sublobectomy.
Predictive and Prognostic Effects of Primary Tumor Size on Colorectal Cancer Survival
Authors: Alese Olatunji B. , Zhou Wei , Jiang Renjian , Zakka Katerina , Huang Zhonglu , Okoli Chimuanya , Shaib Walid L. , Akce Mehmet , Diab Maria , Wu Christina , El-Rayes Bassel F. 
Published: December 2021

BackgroundPathologic staging is crucial in colorectal cancer (CRC). Unlike the majority of solid tumors, the current staging model does not use tumor size as a criterion. We evaluated the predictive and prognostic impact of primary tumor size on all stages of CRC.MethodsUsing the National Cancer Database (NCDB), we conducted an analysis of CRC patients diagnosed between 2010 and 2015 who underwent resection of their primary cancer. Univariate and multivariate analyses were used to identify predictive and prognostic factors, Kaplan-Meier analysis and Cox proportional hazards models for association between tumor size and survival.ResultsAbout 61,000 patients met the inclusion criteria. Median age was 63 years and majority of the tumors were colon primary (82.7%). AJCC stage distribution was: I - 20.1%; II - 32.1%; III - 34.7% and IV - 13.1%. The prognostic impact of tumor size was strongly associated with survival in stage III disease. Compared to patients with tumors &lt;2cm; those with 2-5cm (HR 1.33; 1.19-1.49; p&lt;0.001), 5-10cm (HR 1.51 (1.34-1.70; p&lt;0.001) and &gt;10cm (HR 1.95 (1.65-2.31; p&lt;0.001) had worse survival independent of other variables. Stage II treated without adjuvant chemotherapy had comparable survival outcomes (HR 1.09; 0.97-1.523; p=0.148) with stage III patients who did, while Stage II patients who received adjuvant chemotherapy did much better than both groups (HR 0.76; 0.67-0.86; p&lt;0.001). Stage III patients who did not receive adjuvant chemotherapy had the worst outcomes among the non-metastatic disease subgroups (HR 2.66; 2.48-2.86; p&lt;0.001). Larger tumors were associated with advanced stage, MSI high, non-rectal primary and positive resection margins.ConclusionsFurther studies are needed to clarify the role of tumor size in prognostic staging models, and how to incorporate it into therapy decisions.
miR-616-5p Promotes Invasion and Migration of Bladder Cancer via Downregulating NR2C2 Expression
Authors: Ren Wenbiao , Hu Jiao , Li Huihuang , Chen Jinbo , Ding Jian , Zu Xiongbing , Fan Benyi 
Published: December 2021

BackgroundMicroRNAs, small non-coding RNA molecules with about 22 nucleotides in length, play a significant role in the development of bladder cancer. Previous studies found that miR-616-5p could promote the progress of cancers. However, its role in bladder cancer remains unclear. In the study, we aimed to demonstrate how miR-616-5p impacts the invasion and migration of bladder cancer and its potential downstream targets.MethodsFirstly, qRT-PCR was used to detect the expression of miR-616-5p in normal bladder uroepithelial cell lines and bladder cancer cell lines. Then, chamber–transwell invasion and wound healing migration assays were used to detect the roles of miR-616-5p and NR2C2 in invasion and migration. Subsequently, Western blot was used to evaluate the regulation effects of miR-616-5p and NR2C2. Finally, luciferase assays were performed to manifest the mechanism of miR-616-5p and NR2C2 regulation.ResultsWe found that miR-616-5p was upregulated in bladder cancer, and it could promote the invasion and migration of bladder cancer in vitro. Moreover, we demonstrated that NR2C2 was a downstream target of miR-616-5p. miR-616-5p could inhibit the expression of NR2C2 by binding to the 3′UTR of NR2C2 mRNA. Importantly, patients with a high expression of NR2C2 showed better prognoses in bladder cancer.ConclusionsThis study identifies that miR-616-5p can promote bladder cancer progression via altering the expression of NR2C2. Therefore, identifying miR-616-5p expression levels might be a useful strategy for developing potential therapeutic targets in bladder cancer.
EUS-FNA Biopsies to Guide Precision Medicine in Pancreatic Cancer: Results of a Pilot Study to Identify KRAS Wild-Type Tumours for Targeted Therapy
Authors: Lundy Joanne , Harris Marion , Zalcberg John , Zimet Allan , Goldstein David , Gebski Val , Borsaru Adina , Desmond Christopher , Swan Michael , Jenkins Brendan J. , Croagh Daniel 
Published: December 2021

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death and lacks effective treatment options. Diagnostic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies represent an appealing source of material for molecular analysis to inform targeted therapy, as they are often the only available tissue for patients presenting with PDAC irrespective of disease stage. However, EUS-FNA biopsies are typically not used to screen for precision medicine studies due to concerns about low tissue yield and quality. Epidermal growth factor receptor (EGFR) inhibition has shown promise in clinical trials of unselected patients with advanced pancreatic cancer, but has not been prospectively tested in KRAS wild-type patients. Here, we examine the clinical utility of EUS-FNA biopsies for molecular screening of KRAS wild-type PDAC patients for targeted anti-EGFR therapy to assess the feasibility of this approach.Patients and MethodsFresh frozen EUS-FNA or surgical biopsies from PDAC patient tumours were used to screen for KRAS mutations. Eligible patients with recurrent, locally advanced, or metastatic KRAS wild-type status who had received at least one prior line of chemotherapy were enrolled in a pilot study (ACTRN12617000540314) and treated with panitumumab at 6mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was 4-month progression-free survival (PFS).Results275 patient biopsies were screened for KRAS mutations, which were detected in 88.3% of patient samples. 8 eligible KRAS wild-type patients were enrolled onto the interventional study between November 2017 and December 2020 and treated with panitumumab. 4-month PFS was 14.3% with no objective tumour responses observed. The only grade 3/4 treatment related toxicity observed was hypomagnesaemia.ConclusionsThis study demonstrates proof-of-principle feasibility to molecularly screen patients with pancreatic cancer for targeted therapies, and confirms diagnostic EUS-FNA biopsies as a reliable source of tumour material for molecular analysis. Single agent panitumumab was safe and tolerable but led to no objective tumour responses in this population.
The Incidence Rate and Risk Factors of Malignancy in Elderly-Onset Inflammatory Bowel Disease: A Chinese Cohort Study From 1998 to 2020
Authors: Wang Zheng , Zhang Huimin , Yang Hong , Zhang Mengmeng , Qian Jiaming 
Published: December 2021

BackgroundPatients suffering from inflammatory bowel disease (IBD) have an increased risk of cancer. However, the risk of malignancy in patients with elderly-onset IBD (≥60 years) remains controversial. Hence, we aimed to identify and compare the dissimilarities in morbidity and related risk factors between patients with elderly-onset and adult-onset (18–59 years) IBD in a Chinese cohort.MethodsPatients with confirmed IBD, diagnosed at age ≥18 years, between January 1998 and December 2020 at the Peking Union Medical College Hospital were enrolled. The yearly incidence rates (IRs) for cancer were calculated, and the characteristics were analyzed in these patients.ResultsA total of 1,480 patients suffering from adult-onset IBD and 129 patients suffering from elderly-onset IBD with a median follow-up period of 4.9 years and 4.8 years, respectively, were included. Patients in the elderly-onset IBD group demonstrated an increased overall incidence of cancer than that demonstrated by patients in the adult-onset group (IR 26.9 versus 9.51, respectively, per 1,000 person-years; relative risk [RR], 2.83). Colorectal cancer was the most common malignancy in the two groups, and patients suffering from elderly-onset IBD demonstrated a higher incidence of the malignancy (IR, 7.07 versus 3.34, respectively, per 1,000 person-years; RR, 2.12). Among the extraintestinal cancers, hematological malignancies and urinary tract cancers (including renal and urinary bladder carcinoma) were common in the elderly-onset group (IR, 4.24 and 4.24 per 1,000 person-years, respectively), whereas thyroid cancer was more common in the adult-onset group (IR, 1.36 per 1,000 person-years). Analysis of clinical characteristics revealed that patients with elderly-onset IBD who developed cancer were more likely to have diabetes and urinary lithiasis (p = 0.041 and 0.035, respectively). In addition, patients in the elderly-onset group had a shorter course from IBD to cancer, less exposure to immunosuppressants, less extraintestinal manifestations, and higher cancer-related mortality. Cox proportional risk regression analysis in the elderly-onset IBD group revealed that diabetes was an independent risk factor for the progression to cancer (hazard ratio [HR], 12.53 [2.379–65.994], P = 0.003).ConclusionThe risk of malignancy in patients suffering from elderly-onset IBD increased significantly as compared with those with adult-onset disease. Therefore, cancer monitoring should be initiated earlier for patients in the elderly-onset group.
Giant Ovarian Cysts Treated by Single-Port Laparoscopic Surgery: A Case Series
Authors: Jiang Lili , Zhao Xinyu , Han Yue , Liu Kuiran , Meng Xinyue 
Published: December 2021

BackgroundOvarian cysts are very common diseases of the female reproductive system. Giant ovarian cysts refer to the tumors with diameters greater than 10 cm. In recent years, due to the development of clinical diagnosis, imaging modalities, and the improvement of patients’ cognition of the diseases, the occurrence of giant ovarian cysts has become rare. The purpose of this study was to show a new operation method of single-port laparoscopy to treat giant ovarian cysts.MethodsWe report a case series of five patients with giant ovarian cysts who underwent single-port laparoscopic surgery in the gynecology department of the Shengjing Hospital of China Medical University between June 2020 and March 2021. The inclusion criteria were ovarian cysts at least 20 cm in diameter, and cases when the tumor might be malignant were excluded.ResultsThe patients’ mean age was 26.2years. The most common clinical presentation was progressive abdominal distension. Median size of the cysts at imaging was 39.2 cm (range 21–63 cm). All patients underwent single-port laparoscopic surgery, and none of them converted to laparotomy. On final pathological reports, two cysts were serous cystadenomas, and three were mucinous cystadenomas. All patients recovered well and were discharged on time.ConclusionGiant ovarian cysts can be treated by single-port laparoscopic surgery. In addition to the well-known advantages of laparoscopic surgery (e.g., small pelvic interference, fast postoperative recovery), it can also play the role of perfect cosmetic results, which has more advantages for young women.
Ameliorative Effects of Dietary Ellagic Acid Against Severe Malaria Pathogenesis by Reducing Cytokine Storms and Oxidative Stress
Authors: Mohanty Shilpa , Gupta Amit Chand , Maurya Anil Kumar , Shanker Karuna , Pal Anirban , Bawankule Dnyaneshwar Umrao 
Published: December 2021

Ellagic acid (EA), a fruit- and vegetable-derived flavonoid, has been reported for multiple pharmacological activities, which encouraged us to examine its useful effect in severe malaria pathogenesis, especially malaria-induced cytokine storms and oxidative stress linked to damage in major organs. Malaria was induced by injecting Plasmodium berghei–infected RBCs intraperitoneally into the mice. EA was given orally (5, 10, and 20 mg/kg) following Peter’s 4-day suppression test. EA exhibited the suppression of parasitemia, production of inflammatory cytokine storms and oxidative stress marker level quantified from vital organs significantly and an increase in hemoglobin, blood glucose, and mean survival time compared to the vehicle-treated infected group. EA administration also restored the blood–brain barrier integrity evidenced through Evans blue staining. Furthermore, we demonstrated the protecting effect of EA in LPS-induced inflammatory cytokine storms and oxidative stress in glial cells. The present study conclude that ellagic acid is able to alleviate severe malaria pathogenesis by reducing cytokine storms and oxidative stress–induced by malarial parasites. It also attributed promising antimalarial activity and afforded to improve the blood glucose and hemoglobin levels in treated mice. These research findings suggested the suitability of ellagic acid as a useful bioflavonoid for further study for the management of severe malaria pathogenesis.