bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal Association Between Tea Consumption and Bone Health: A Mendelian Randomization Study
Authors: Chen Song , Chen Tianlai , Chen Yibin , Huang Dianhua , Pan Yuancheng , Chen Shunyou 
Published: September 2022

BackgroundMuch observational research reported that tea consumption decreases the risk of osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP) which are the three major bone disorders. However, the observed correlation is inconclusive. To determine the causal relationship between genetically predicted tea intake and OA, RA, and OP, we performed a two-sample Mendelian randomization (MR) study based on large samples.MethodsThe European population’s genome-wide association meta-analysis (GWAS) dataset identified SNPs associated with tea consumption was obtained from Neale Lab’s analysis of UK Biobank data that comprised 349,376 participants of European ancestry. We extracted genetic data for knee OA (17,885 controls and 4,462 cases), hip OA (50,898 controls and 12,625 cases), and RA (43,923 controls and 14,361 cases) from the UK Biobank and OP cases (93083 controls and 1,175 cases) from FinnGen Data Freeze 2. A MR study was conducted to examine the effect of selected single nucleotide polymorphisms (SNPs) and OA, RA, and OP risk. Several sensitivity analyses were performed with weighted median and inverse-variance weighted methods for estimating the causal effects.ResultsIn this MR study, the genetically predicted per one cup increase of tea consumption was not associated with knee OA (OR 1.11,95% CI: 0.79–1.55) using IVW with random effect. Genetic predisposition to tea consumption was not associated with hip OA (OR: 1.20, 95% CI: 0.84–1.71), RA (OR: 1.24 95% CI: 0.81–1.91), and OP (OR: 1.11, 95% CI: 0.89, 1.39). Following the sensitivity analysis, there was no potential pleiotropy.ConclusionAccording to our study, According to our study, there was no statistical power to confirm a causal relationship between tea consumption and the risk of knee OA, hip OA, RA, and OP.
Dietary meat mutagens intake and cancer risk: A systematic review and meta-analysis
Authors: Reng Qie , Zhu Ling Ling , Feng Li , Li Yong Jie , Zhu Yan Xing , Wang Ting Ting , Jiang Feng 
Published: September 2022

BackgroundClinical and preclinical studies suggested that certain mutagens occurring as a reaction of creatine, amino acids, and sugar during the high temperature of cooking meat are involved in the pathogenesis of human cancer. Here we conducted a systematic review and meta-analysis to examine whether meat mutagens [PhIP, MeIQx, DiMeIQx, total HCA, and B(a)P] present a risk factor for human cancer.MethodsWe searched the following databases for relevant articles published from inception to 10 Oct 2021 with no language restrictions: Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Baidu Academic, Zhejiang Digital Library. Two independent researchers screened all titles and obtained eligible texts for further screening. Independent data extraction was conducted, and meta-analysis was carried out using random-effects models to calculate the risk ratio of the meat mutagens exposure.ResultsA total of 1,786,410 participants and 70,653 cancer cases were identified. Among these, there were 12 different types of cancer at various sites, i.e., breast, bladder, colorectal, colon, rectum, prostate, lung, Non-Hodgkin lymphoma, kidney, gastric, esophagus, pancreatic, hepatocellular carcinoma. Cancer risk was significantly increased by intake of PhIP (OR = 1.13;95% CI 1.07–1.21; p &lt; 0.001), MeIQx (OR = 1.14; 95% CI: 1.07–1.21; p &lt; 0.001), DiMeIQx (OR = 1.07; 95% CI: 1.01–1.13; p = 0.013), total HCA (OR = 1.20; 95% CI: 1.03–1.38; p = 0.016), and cancer risk was not significantly increased by intake of B(a)P (OR = 1.04; 95% CI: 0.98–1.10; p = 0.206).ConclusionMeat mutagens of PhIP, MeIQx, DiMeIQx, and total HCA have a positive association with the risk of cancer.Systematic review registration[www.crd.york.ac.uk/prospero], identifier [CRD42022148856].
Diagnostic accuracy and prognostic significance of Glypican-3 in hepatocellular carcinoma: A systematic review and meta-analysis
Authors: Jiang Donglei , Zhang Yingshi , Wang Yinuo , Xu Fu , Liang Jun , Wang Weining 
Published: September 2022

PurposeGlypican-3 (GPC-3) expression is abnormal in the occurrence and development of hepatocellular carcinoma (HCC). To explore whether GPC-3 has diagnostic accuracy and prognostic significance of HCC, we did a systematic review and meta-analysis.MethodPubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure were searched with keywords “GPC-3” and “HCC” and their MeSH terms from inception to July 2022. We applied the hierarchical summary receiver operating characteristic model and evaluated the diagnostic value of GPC-3 alone and combination, and the correlation between high and low GPC-3 expression on clinicopathological features and survival data in prognosis.ResultsForty-one original publications with 6,305 participants were included, with 25 of them providing data for diagnostic value and 18 records were eligible for providing prognostic value of GPC-3. GPC-3 alone got good diagnostic value in patients with HCC when compared with healthy control and moderate diagnostic value when compared with patients with cirrhosis. In addition, combination of GPC-3 + AFP and GPC-3 + GP73 got great diagnostic value in HCC versus cirrhosis groups; the combination of GPC-3 can also improve the diagnostic accuracy of biomarkers. Moreover, we discovered that overexpression of GPC-3 was more likely found in HBV infection, late tumor stage, and microvascular invasion groups and causes shorter overall survival and disease free survival, which means poor prognosis.ConclusionGCP-3 could be used as a biomarker in HCC diagnosis and prognosis, especially in evaluated diagnostic value in combination with AFP or GP73, and in forecasting worse survival data of overexpression GPC-3Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42022351566].
Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients
Authors: Mariani Stefano , Puzzoni Marco , Giampieri Riccardo , Ziranu Pina , Pusceddu Valeria , Donisi Clelia , Persano Mara , Pinna Giovanna , Cimbro Erika , Parrino Alissa , Spanu Dario , Pretta Andrea , Lai Eleonora , Liscia Nicole , Lupi Alessio , Giglio Enrica , Palomba Grazia , Casula Milena , Pisano Marina , Palmieri Giuseppe , Scartozzi Mario 
Published: September 2022

BackgroundRechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently, the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy-driven cetuximab rechallenge in a RAS and BRAF WT selected population.MethodsCRC patients with RAS and BRAF WT both on tumor tissue and on ct-DNA at baseline receiving rechallenge with cetuximab were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing and nucleotide sequencing assays. Real-time PCR and droplet digital PCR were performed to confirm the RAS-BRAF mutational status.ResultsA total of 26 patients were included in our analysis. In the global population, RR was 25.0%, median overall survival (mOS) was 5.0 months, and median progression-free survival (mPFS) was 3.5 months. Previous response to anti-EGFR was associated with improved mPFS (5.0 vs. 2.0 months, HR: 0.26, p = 0.048); anti-EGFR free interval &gt; 14 months and anti-EGFR free interval &gt; 16 months were associated with improved mPFS (respectively 7.0 vs. 3.0 months, HR: 0.27, p = 0.013 and not reached vs. 3.0 months, HR: 0.20, p = 0.002) and with improved mOS (respectively 13.0 vs. 5.0 months, HR: 0.27, p = 0.013 and 13.0 vs. 5.0 months, HR: 0.20, p = 0.002). Previous lines &gt;2 were correlated with improved mPFS (4.0 vs. 1.0 month, HR: 0.05, p = 0.041) and with improved mOS (7.0 vs. 1.0 month, HR: 0.045, p = 0.034). In a multiple logistic regression model, only the anti-EGFR free interval was confirmed to be a significant predictor for mOS and mPFS.ConclusionsLiquid biopsy-driven cetuximab rechallenge was confirmed to be effective. The clinical outcome was consistent with available results from phase II studies. In addition to the molecular selection through the analysis of ct-DNA for RAS, the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option.
Evolution of research trends in artificial intelligence for breast cancer diagnosis and prognosis over the past two decades: A bibliometric analysis
Authors: Syed Asif Hassan , Khan Tabrej 
Published: September 2022

ObjectiveIn recent years, among the available tools, the concurrent application of Artificial Intelligence (AI) has improved the diagnostic performance of breast cancer screening. In this context, the present study intends to provide a comprehensive overview of the evolution of AI for breast cancer diagnosis and prognosis research using bibliometric analysis.MethodologyTherefore, in the present study, relevant peer-reviewed research articles published from 2000 to 2021 were downloaded from the Scopus and Web of Science (WOS) databases and later quantitatively analyzed and visualized using Bibliometrix (R package). Finally, open challenges areas were identified for future research work.ResultsThe present study revealed that the number of literature studies published in AI for breast cancer detection and survival prediction has increased from 12 to 546 between the years 2000 to 2021. The United States of America (USA), the Republic of China, and India are the most productive publication-wise in this field. Furthermore, the USA leads in terms of the total citations; however, hungry and Holland take the lead positions in average citations per year. Wang J is the most productive author, and Zhan J is the most relevant author in this field. Stanford University in the USA is the most relevant affiliation by the number of published articles. The top 10 most relevant sources are Q1 journals with PLOS ONE and computer in Biology and Medicine are the leading journals in this field. The most trending topics related to our study, transfer learning and deep learning, were identified.ConclusionThe present findings provide insight and research directions for policymakers and academic researchers for future collaboration and research in AI for breast cancer patients.
CDK7 is a prognostic biomarker for non-small cell lung cancer
Authors: Kuempers Christiane , Jagomast Tobias , Heidel Carsten , Paulsen Finn-Ole , Bohnet Sabine , Schierholz Stefanie , Dreyer Eva , Kirfel Jutta , Perner Sven 
Published: September 2022

AimNon-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death globally despite promising progress of personalized therapy approaches. Cyclin-dependent kinase 7 (CDK7) is a kinase involved in transcription, overexpressed in a broad spectrum of cancer types and found to be associated with an unfavourable prognosis. In this study, we aimed to investigate the protein expression of CDK7 in a large cohort of NSCLC incorporating adenocarcinomas (adNSCLC) and squamous cell carcinomas (sqNSCLC) and to correlate its expression with clinicopathological data.MethodsWe performed immunohistochemical staining of CDK7 on our cohort of NSCLC including 258 adNSCLC and 101 sqNSCLC and measured protein expression via a semi-automated read out. According to the median value of CDK7 the cohort was stratified in a CDK7 high and low expressing group, respectively, and results were correlated with clinico-pathological data.ResultsCDK7 was significantly higher expressed in sqNSCLC than in adNSCLC. In the group of sqNSCLC, CDK7 expression was significantly higher in sqNSCLC with lymph node metastases than in sqNSCLC with N0 stage. We found a significantly worse overall survival and disease-free survival for patients with CDK7 high expressing NSCLC.ConclusionSince a high CDK7 expression seems to be linked with a poor prognosis it might serve as a promising novel prognostic biomarker and its assessment could be implied in future routine diagnostic workup of NSCLC samples. Considering that CDK7 inhibitors are currently tested in several trials for advanced solid malignancies, it may also be a new target for future anti-cancer therapy.
Antitumor effects of Chinese herbal medicine compounds and their nano-formulations on regulating the immune system microenvironment
Authors: Sun Kexiang , Wu Linguangjin , Wang Shuyun , Deng Wanli 
Published: September 2022

Traditional Chinese medicine (TCM), including herbal medicine, acupuncture and meditation, has a wide range of applications in China. In recent years, herbal compounding and active ingredients have been used to control tumor growth, reduce suffering, improve quality of life, and prolong the life span of cancer patients. To reduce side effects, herbal medicine can be used in conjunction with radiotherapy and chemotherapy or can be used as an adjuvant to strengthen the immune effect of anticancer vaccines. In particular, in the immunosuppressed tumor microenvironment, herbal medicine can have antitumor effects by stimulating the immune response. This paper reviews the advances in research on antitumor immunomodulation in Chinese herbal medicine, including the regulation of the innate immune system, which includes macrophages, MDSCs, and natural killer cells, and the adaptive immune system, which includes CD4+ T cells, CD8+ T cells, and regulatory T cells (Tregs), to influence tumor-associated inflammation. In addition, a combination of active ingredients of herbal medicine and modern nanotechnology alter the tumor immune microenvironment. In recent years, immunological antitumor therapy in TCM has been applied on a reasonably large scale both nationally and internationally, and there is potential for further clinical expansion. Investigation of immune modulation mechanisms in Chinese herbal medicine will provide novel perspectives of how herbal medicine controls tumor growth and metastasis, which will contribute to the evolution of tumor research.MethodologyExperimental research between the years of 2012-2022, meta-analysis and reviews for the period 2002-2022 found on the Databases including PubMed, Embase, and the Cochrane database were used. The inclusion criteria were experimental research literature addressing the anti-tumor immunological effects of active ingredients and nanoparticles in Chinese herbal medicine. Exclusion criteria were articles that addressed Chinese herbal medicine and nano-formulations without discussing anti-tumor immunological effects in innate, adaptive immune cells, MDSCs, and nuclear factors.
Identification of cuproptosis-related patterns and construction of a scoring system for predicting prognosis, tumor microenvironment-infiltration characteristics, and immunotherapy efficacy in breast cancer
Authors: Li Wei , Zhang Xingda , Chen Yanbo , Pang Da 
Published: September 2022

BackgroundCuproptosis, a recently discovered refreshing form of cell death, is distinct from other known mechanisms. As copper participates in cell death, the induction of cancer cell death with copper ionophores may emerge as a new avenue for cancer treatment. However, the role of cuproptosis in tumor microenvironment (TME) cell infiltration remains unknown.MethodsWe systematically evaluated the cuproptosis patterns in The Cancer Genome Atlas (TCGA) database in breast cancer (BRCA) samples based on 10 cuproptosis-related genes (CRGs), and correlated these patterns with the prognosis and characteristics of TME cell infiltration. A principal component analysis algorithm was used to construct a cuproptosis score to quantify the cuproptosis pattern in individual tumors. Further, the relationships between the cuproptosis score and transcription background, clinical features, characteristics of TME cell infiltration, drug response, and efficacy of immunotherapy were assessed.ResultsTwo distinct cuproptosis patterns with distinct prognoses were identified; their TME characteristics were found to be consistent with the immune-excluded and immune-inflamed phenotypes, respectively. The cuproptosis patterns in individual patients were evaluated using the cuproptosis score based on the cuproptosis phenotype-related genes, contributing to distinguishing biological processes, clinical outcome, immune cell infiltration, genetic variation, and drug response. Univariate and multivariate Cox regression analyses verified this score as an independent prognostic predictor in BRCA. A high cuproptosis score, characterized by immune activation, suggests an inflamed tumor and immune-inflamed phenotype with poor survival and a low cuproptosis score, characterized by immune suppression, indicates a non-inflamed tumor and immune-excluded phenotype with better survival. Significant differences were observed in the IC50 between the high and low cuproptosis score groups receiving chemotherapy and targeted therapy drugs. In the two immunotherapy cohorts, patients with a higher cuproptosis score experienced considerable therapeutic advantages and clinical benefits.ConclusionsThis study is the first to elucidate the prominent role of cuproptosis in the clinical outcome and the formation of TME diversity and complexity in BRCA. Estimating cuproptosis patterns in tumors could help predict the prognosis and characteristics of TME cell infiltration and guide more effective chemotherapeutic and immunotherapeutic strategies.
Phytochemical and toxicological evaluation of Zephyranthes citrina
Authors: Rehman Muhammad Haseeb Ur , Saleem Uzma , Ahmad Bashir , Rashid Memoona 
Published: September 2022

Drugs obtained from medicinal plants have always played a pivotal role in the field of medicine and to identify novel compounds. Safety profiling of plant extracts is of utmost importance during the discovery of new biologically active compounds and the determination of their efficacy. It is imperative to conduct toxicity studies before exploring the pharmacological properties and perspectives of any plant. The present work aims to provide a detailed insight into the phytochemical and toxicological profiling of methanolic extract of Zephyranthes citrina (MEZ). Guidelines to perform subacute toxicity study (407) and acute toxicity study (425) provided by the organization of economic cooperation and development (OECD) were followed. A single orally administered dose of 2000 mg/kg to albino mice was used for acute oral toxicity testing. In the subacute toxicity study, MEZ in doses of 100, 200, and 400 mg/kg was administered orally, consecutive for 28 days. Results of each parameter were compared to the control group. In both studies, the weight of animals and their selected organs showed consistency with that of the control group. No major toxicity or organ damage was recorded except for some minor alterations in a few parameters such as in the acute study, leukocyte count was increased and decreased platelet count, while in the subacute study platelet count increased in all doses. In the acute toxicity profile liver enzymes Alanine aminotransferase (ALT), as well as, aspartate aminotransferase (AST) were found to be slightly raised while alkaline phosphatase (ALP) was decreased. In subacute toxicity profiling, AST and ALT were not affected by any dose while ALP was decreased only at doses of 200 and 400 mg/kg. Uric acid was raised at a dose of 100 mg/kg. In acute toxicity, at 2000 mg/kg, creatinine and uric acid increased while urea levels decreased. Therefore, it is concluded that the LD50 of MEZ is more than 2000 mg/kg and the toxicity profile of MEZ was generally found to be safe.
Pharmacological treatments of fibromyalgia in adults; overview of phase IV clinical trials
Authors: Alorfi Nasser M. 
Published: September 2022

Background: Fibromyalgia is a chronic neurological condition characterized by widespread pain. The effectiveness of current pharmacological treatments is limited. However, several medications have been approved for phase IV trials in order to evaluate them.Aim: To identify and provide details of drugs that have been tested in completed phase IV clinical trials for fibromyalgia management in adults, including the primary endpoints and treatment outcomes. This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology.Method: Publicly available and relevant phase IV trials registered at ClinicalTrials.gov were analyzed. The uses of the trialed drugs for fibromyalgia were reviewed.Results: As of 8 August 2022, a total of 1,263 phase IV clinical trials were identified, of which 121 were related to fibromyalgia. From these, 10 clinical trials met the inclusion criteria for the current study. The drugs used in phase IV trials are milnacipran, duloxetine, pregabalin, a combination of tramadol and acetaminophen, and armodafinil. The effectiveness of the current pharmacological treatments is apparently limited.Conclusion: Due to its complexity and association with other functional pain syndromes, treatment options for fibromyalgia only are limited and they are designed to alleviate the symptoms rather than to alter the pathological pathway of the condition itself. Pain management specialists have numerous pharmacologic options available for the management of fibromyalgia.
Association of necrotizing enterocolitis with antimicrobial exposure in preterm infants <32 weeks gestational age:A multicenter prospective case-control study
Authors: Pei Xiaojing , Gao Yujun , Kou Yan , Ding Yanjie , Li Dan , Lei Peng , Zuo Lili , Liu Qiongyu , Miao Naiying , Reddy Simmy , Yu Yonghui , Sun Xuemei 
Published: September 2022

Objective: To assess the risk of necrotizing enterocolitis (NEC) and explore the relationship between antibiotic overexposure and disease occurrence in a large prospective birth cohort.Methods: Based on a prospective birth cohort, the study collected hospitalization data of very preterm infants (VPIs) having gestational age of less than 32 weeks from January 1, 2018, to June 30, 2021 via the China Northern Neonatal Network. Infants diagnosed with NEC ≥ stage II were included in the case group, and each case was matched for GA and birth weight for the control group. Furthermore, the risk factors for NEC were determined by statistical analyses.Results: A total of 6425 VPIs were included in this study, and 167 (2.6%) of these subjects were diagnosed with NEC ≥ stage II. The study also included 984 extremely preterm infants (gestational age &lt;28 weeks), including 50 (5.1%) infants diagnosed with NEC ≥ stage II. In the matched case-control study, subjects had a total of antibiotic days-of-therapy for 9015 days, of which broad-spectrum antibiotics (BSAs) accounted for 77%. The antibiotic spectrum index per antibiotic day in the case group was significantly higher and was an independent risk factor for the occurrence of NEC (p = 0.001, OR = 1.13).Conclusion: The cohort of VPIs was overexposed to antiboitics. Unreasonable combination of antibiotics and overexposure to BSAs may increase the risk of NEC in preterm infants.