bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Dietary Intake and Biomarker of α-Linolenic Acid With Incident Colorectal Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies
Authors: Dai Ze-Bin , Ren Xiao-Li , Xue Yi-Lang , Tian Ya , He Bing-Bing , Xu Chang-Long , Yang Bo 
Published: July 2022

Background and ObjectiveThere is keen interest in better understanding the impacts of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, in ameliorating the development of cancer; however, results of several prospective cohorts present an inconsistent association between ALA intake and the incident colorectal cancer (CRC). We aimed to investigate the summary association of dietary intake and biomarkers of ALA with CRC risk based on the prospective cohorts.MethodsPertinent prospective cohorts were identified in Cochrane Library, PubMed, and EMBASE from inception to February 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) for comparing the top with the bottom quartiles of ALA levels were combined using a random-effects model. Nonlinear dose-response relationships of ALA levels in diet and blood with CRC risk were assessed using the restricted cubic spline models, respectively.ResultsOver the duration of follow-up with a median of 9.3 years ranging from 1 to 28 years, 12,239 CRC cases occurred among 861,725 participants from 15 cohorts (11 studies on diet and 5 studies on biomarkers including 4 on blood and 1 on adipose tissue). The summary RR was 1.03 (95% CI: 0.97, 1.10; I2: 0.00%) for dietary intake and 0.83 (95% CI: 0.69, 0.99; I2: 0.00%) for biomarker. Each 0.1% increase in the levels of ALA in blood was associated with a 10% reduction in risk of CRC (summary RR: 0.90, 95% CI: 0.80, 0.99; I2: 38.60%), whereas no significant dose-response association was found between dietary intake of ALA and the incident CRC (p for non-linearity = 0.18; p for linearity = 0.24).ConclusionsBlood levels of ALA were inversely and linearly associated with the risk of CRC, which suggested that increased intake of ALA to improve circulating levels was beneficial for CRC prevention.
Risk Stratification in Oral Cancer: A Novel Approach
Authors: Tu Irene Wen-Hui , Shannon Nicholas Brian , Thankappan Krishnakumar , Balasubramanian Deepak , Pillai Vijay , Shetty Vivek , Rangappa Vidyabhushan , Chandrasekhar Naveen Hedne , Kekatpure Vikram , Kuriakose Moni Abraham , Krishnamurthy Arvind , Mitra Arun , Pattatheyil Arun , Jain Prateek , Iyer Subramania , Subramaniam Narayana , Iyer N. Gopalakrishna 
Published: July 2022

BackgroundOral squamous cell carcinoma (OSCC) is a common head and neck cancer with high morbidity and mortality. Currently, treatment decisions are guided by TNM staging, which omits important negative prognosticators such as lymphovascular invasion, perineural invasion (PNI), and histologic differentiation. We proposed nomogram models based on adverse pathological features to identify candidates suitable for treatment escalation within each risk group according to the National Comprehensive Cancer Network (NCCN) guidelines.MethodsAnonymized clinicopathologic data of OSCC patients from 5 tertiary healthcare institutions in Asia were divided into 3 risk groups according to the NCCN guidelines. Within each risk group, nomograms were built to predict overall survival based on histologic differentiation, histologic margin involvement, depth of invasion (DOI), extranodal extension, PNI, lymphovascular, and bone invasion. Nomograms were internally validated with precision–recall analysis and the Kaplan–Meier survival analysis.ResultsLow-risk patients with positive pathological nodal involvement and/or positive PNI should be considered for adjuvant radiotherapy. Intermediate-risk patients with gross bone invasion may benefit from concurrent chemotherapy. High-risk patients with positive margins, high DOI, and a high composite score of histologic differentiation, PNI, and the American Joint Committee on Cancer (AJCC) 8th edition T staging should be considered for treatment escalation to experimental therapies in clinical trials.ConclusionNomograms built based on prognostic adverse pathological features can be used within each NCCN risk group to fine-tune treatment decisions for OSCC patients.
Efficacy and Safety of Capecitabine for Triple-Negative Breast Cancer: A Meta-Analysis
Authors: Xun Xueqiong , Cao Qinguang , Hong Pan , Rai Saroj , Zhou Yeming , Liu Ruikang , Hu Huiyong 
Published: July 2022

BackgroundTriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited treatment options and poor prognosis. Capecitabine, as a novel adjuvant chemotherapy for TNBCs, remains controversial. Therefore, we conducted this meta-analysis to assess the efficacy and safety of capecitabine for early-stage TNBCs combined with neo-/adjuvant chemotherapy.MethodsWe searched Medline, Embase, Web of Science, and Cochrane databases updated on Mar 18, 2022 for relevant RCTs. In all, 11 RCTs with 5,175 patients were included. We used hazard ratios (HRs) and odds ratios (ORs) to assess the differences between disease-free survival (DFS), overall survival (OS), and adverse events.ResultsOur study demonstrated significance differences in both DFS and OS (DFS: HR=0.77; 95% CI 0.68–0.86; OS: HR=0.73, 95% CI 0.63–0.85). In subgroup analysis, the lower dosage group showed higher DFS (HR=0.79, 95% CI 0.69–0.91), higher frequency (HR=0.72, 95%CI 0.62–0.83), and adjuvant chemotherapy (HR=0.74, 95% CI 0.65–0.84). However, capecitabine was also associated with a higher risk of diarrhea (OR=3.10, 95% CI 2.32–4.15), hand–foot syndrome (OR=25.79, 95% CI 15.32–43.42), and leukopenia (OR=2.08, 95% CI 1.13–3.84).ConclusionThe addition of capecitabine to early-stage TNBC patients receiving standard adjuvant chemotherapy showed significant DFS and OS improvement with tolerable adverse events. The lower dosage and higher frequency of capecitabine combined with adjuvant chemotherapy demonstrated a better survival outcome.
Case Report: Clinical Characteristics and Outcomes of HIV Positive Patients With Metastatic Prostate Cancer Treated With Immunotherapy: A Case Series and Literature Review
Authors: Idossa Dame , Friedlander Terence , Paller Channing J. , Ryan Charles J. , Borno Hala T. 
Published: July 2022

BackgroundThe treatment of metastatic prostate cancer has been revolutionized with the advent of many targeted therapies, including immunotherapy. Pembrolizumab has demonstrated benefit in the treatment of certain patients with docetaxel-refractory metastatic castrate-resistant prostate cancer (mCRPC). However, extrapolation of these data to patients with HIV is limited, as these patients are conventionally excluded from therapeutic clinical trials. This study aims to develop a better understanding of the clinical outcomes of HIV positive patients with prostate cancer treated with immunotherapy. A review of the literature is conducted on the use of immunotherapy in HIV positive patients with prostate cancer, and a summary is presented of two clinical cases from a single institution.MethodsThis is a retrospective case report of 2 patients diagnosed with prostate cancer and HIV who received treatment with pembrolizumab. Quantitative analysis was performed to summarize patient demographics, clinical history, and outcomes.ResultsTwo patients with mCRPC and HIV on highly active antiretroviral therapy were identified. Both individuals had biochemical and radiographic response to treatment with pembrolizumab. The duration of response for individual 1 is &gt;31 months and 14 months for individual 2. Neither patient had immune-related adverse events or decreased suppression of their HIV infection. One patient died from disease progression after 14 months of treatment and the other remains on treatment with pembrolizumab to date.ConclusionIn this small case series, pembrolizumab appears to be a safe and effective treatment option for HIV positive patients with metastatic prostate cancer.
Association of Mu-Opioid Receptor Expression With Long-Term Survival and Perineural Nerve Invasion in Patients Undergoing Surgery for Ovarian Cancer
Authors: Zhang Hao , Qu Mengdi , Sun Caihong , Wang Yanghanzhao , Li Ting , Xu Wei , Sun Zhirong , Zhang Xiaoguang , Guo Kefang , Chen Wankun , Sun Minli , Miao Changhong 
Published: July 2022

BackgroundOpioids are widely used during primary debulking surgery (PDS) for ovarian cancers, and a high mu-opioid receptor (MOR) expression predicts worse cancer outcomes. However, the impact of MOR expression on survival outcomes in ovarian cancers is still not clear.MethodsA retrospective cohort study was conducted in patients who underwent PDS in ovarian cancer patients. MOR expression was measured in tumor and normal tissue. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Secondary outcomes included perineural invasion (PNI), intraoperative sufentanil consumption, length of stay (LOS), and verbal numerical rating scale (VNRS) on postoperative day 1 (POD1), POD3, and POD5.ResultsAfter propensity score matching, a total of 366 patients were finally enrolled in this study. There were no significant differences in OS rates in patients with high versus low levels of MOR (1-year OS: 82.9% versus 83.3%, 3-year: 57.8% versus 59.1%, 5-year: 22.4% versus 23.1%,respectively) in the ovarian cancers. There were no significant differences in DFS between the groups. Intraoperative sufentanil consumption was higher in the MOR high-expression group compared with the MOR low-expression group. Tumors expressing high levels of MOR showed higher rates of PNI. VNRS in the MOR high-expression group was higher on POD1.ConclusionMOR is not an independent predictor of worse survival in ovarian cancers but is associated with high rates of perineural invasion.
Prognostic Significance of the Systemic Immune-Inflammation Index in Patients With Cholangiocarcinoma: A Meta-Analysis
Authors: Liu Xue-chun , Jiang Yue-ping , Sun Xue-guo , Zhao Jian-jian , Zhang Ling-yun , Jing Xue 
Published: July 2022

BackgroundThe systemic immune-inflammation index (SII) is a significant prognostic factor for neoplastic diseases. However, the prognostic value of SII in patients with cholangiocarcinoma (CCA) remains unclear. This meta-analysis aimed to investigate the prognostic value of preoperative SII in patients with CCA.MethodWe systematically searched for relevant studies in PubMed, Scopus, EMBASE, Web of Science, PROSPERO, and Cochrane Library databases up to March 22, 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association between SII and survival outcomes, including overall survival (OS) and recurrence-free survival.ResultsFive studies with 1402 patients were included in this meta-analysis to determine the prognostic value of preoperative SII. The results showed that a higher SII was associated with poor OS in patients with CCA who underwent invasive surgery (HR=1.916; 95% CI, 1.566–2.343; Z=6.329; P&lt;0.001). The results were reliable in the subgroup analysis according to country, age, sample size, SII cutoff values, and treatment methods.ConclusionsA high preoperative SII appears to be an effective and practical method for monitoring survival in patients with CCA.Systematic Review RegistrationInternational Platform of Registered Systematic. Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202240015.
Comprehensive Analysis of TRP Channel–Related Genes in Patients With Triple-Negative Breast Cancer for Guiding Prognostic Prediction
Authors: Zhang Haojie , Zhang Xiangsheng , Wang Xiaohong , Sun Hongguang , Hou Changran , Yu Yue , Wang Song , Yin Fangxu , Yang Zhenlin 
Published: July 2022

BackgroundTriple-negative breast cancer (TNBC) is a special subtype of breast cancer. Transient Receptor Potential (TRP) channel superfamily has emerged as a novel and interesting target in a variety of tumors. However, the association of TRP channel–related genes with TNBC is still unclear.MethodsThe The Cancer Genome Atlas (TCGA)-TNBC and GSE58812 datasets were downloaded from the public database. The differentially expressed TRP channel–related genes (DETGs) were screened by limma package, and mutations of the above genes were analyzed. Subsequently, new molecular subtypes in TNBC-based DETGs were explored by consensus clustering analysis. In addition, Lasso–Cox regression analysis was used to divide it into two robust risk subtypes: high-risk group and low-risk group. The accuracy and distinguishing ability of above models were verified by a variety of methods, including Kaplan–Meier survival analysis, ROC analysis, calibration curve, and PCA analysis. Meanwhile, CIBERSORT algorithm was used to excavate status of immune-infiltrating cells in TNBC tissues. Last, we explored the therapeutic effect of drugs and underlying mechanisms of risk subgroups by pRRophetic package and GSEA algorithm, respectively.ResultsA total of 19 DETGs were identified in 115 TNBC and 113 normal samples from TCGA database. In addition, missense mutation and SNP were the most common variant classification. According to Lasso–Cox regression analysis, the risky formula performed best when nine genes were used: TRPM5, TRPV2, HTR2B, HRH1, P2RY2, MAP2K6, NTRK1, ADCY6, and PRKACB. Subsequently, Kaplan–Meier survival analysis, ROC analysis, calibration curve, and Principal Components Analysis (PCA) analysis showed an excellent accuracy for predicting OS using risky formula in each cohort (P &lt; 0.05). Specifically, high-risk group had a shorter OS compared with low-risk group. In addition, T-cell CD4 memory activated and macrophages M1 were enriched in normal tissues, whereas Tregs were increased in tumor tissues. Note that the low-risk group was better therapeutic effect to docetaxel, doxorubicin, cisplatin, paclitaxel, and gemcitabine than the high-risk group (P &lt; 0.05). Last, in vitro assays, Quantitative Real-time PCR (qRT-PCR) indicated that TRPM5 was significantly highly expressed in MDA-MB-231 and MDA-MB-468 cells compared with that in MCF-10A cells (P &lt; 0.01).ConclusionWe identified a risky formula based on expression of TRP channel–related genes that can predict prognosis, therapeutic effect, and status of tumor microenvironment for patients with TNBC.
Surveillance of Acute SARS-CoV-2 Infections in Elementary Schools and Daycare Facilities in Bavaria, Germany (09/2020–03/2021)
Authors: Kern Anna , Kuhlmann Pia H. , Matl Stefan , Ege Markus , Maison Nicole , Eckert Jana , von Both Ulrich , Behrends Uta , Anger Melanie , Frühwald Michael C. , Gerstlauer Michael , Woelfle Joachim , Neubert Antje , Melter Michael , Liese Johannes , Goettler David , Sing Andreas , Liebl Bernhard , Hübner Johannes , Klein Christoph ,   the COVID Kids Bavaria Consortium
Published: July 2022

IntroductionHere we report our results of a multi-center, open cohort study (“COVID-Kids-Bavaria”) investigating the distribution of acute SARS-CoV-2 infections among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany.Materials and MethodsOverall, 2,568 children (1,337 school children, 1,231 preschool children) and 1,288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7,062 throat swabs were analyzed for SARS-CoV-2 by commercial RT-PCR kits.ResultsIn phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. Correlation of a positive PCR test result with the local-7-day incidence values showed a strong association of a 7-day-incidence of more than 100/100,000 as compared to &lt;100/100,000 (OR = 10.3 [1.5–438], p &lt; 0.005). After phase III, antibody testing was offered to 713 study participants in elementary schools. A seroprevalence rate of 7.7% (students) and 4.5% (teachers) was determined.DiscussionDuring the initial waves of the SARS-CoV-2 pandemic, the risk of a positive SARS-CoV-2 result correlated positively with the local 7-day incidence. Hence, the occurrence of SARS-CoV-2 infections were reflected in schools and daycare facilities. An increased risk of SARS-CoV-2 transmission in the setting of daycare and elementary schooling was unlikely.
Effect of Threshold Inspiratory Muscle Training on Functional Fitness and Respiratory Muscle Strength Compared to Incentive Spirometry in Children and Adolescents With Obesity: A Randomized Controlled Trial
Authors: Kaeotawee Phatthareeda , Udomittipong Kanokporn , Nimmannit Akarin , Tovichien Prakarn , Palamit Apinya , Charoensitisup Pawinee , Mahoran Khunphon 
Published: July 2022

BackgroundTo determine the effect of threshold inspiratory muscle training (IMT) on functional fitness and respiratory muscle strength (RMS) compared to incentive spirometry (IS) in children/adolescents with obesity.MethodsA total of 60 obese children/adolescents aged 8–15 years were randomized into the threshold IMT group (n= 20), the IS group (n= 20), or the control group (n= 20). The IMT group performed 30 inspiratory breaths with the intensity set at 40% of baseline maximal inspiratory pressure (MIP) twice daily for 8 weeks; the IS group performed 30 breaths with sustained maximum inspiration twice daily for 8 weeks; and, the control group was assigned no training device for 8 weeks. Six-min walk test (6-MWT), RMS, and spirometry were compared between baseline and 8 weeks.ResultsSix-MWT distance (528.5 ± 36.2 vs. 561.5 ± 35.2 m,p= 0.002) and MIP (121.2 ± 26.8 vs. 135.3 ± 32.1%Predicted,p= 0.03) were significantly improved after 8 weeks of IMT training. There was no significant difference in any evaluated pulmonary function parameters between baseline and 8 weeks in the IS or control groups; however, 6-MWT distance demonstrated a trend toward significant improvement in the IS group (526.9 ± 59.1 vs.549.0 ± 50.6 m,p= 0.10). No significant difference among groups was found for any variable relative to change from baseline to post-training.ConclusionEight weeks of threshold IMT training significantly improved both inspiratory muscle strength (MIP) and functional fitness (6-MWT) in children/adolescents with obesity. Eight weeks of IS training yielded a trend toward significantly improved functional fitness.
Chronic Administration of COVID-19 Drugs Fluvoxamine and Lopinavir Shortens Action Potential Duration by Inhibiting the Human Ether‐à‐go‐go–Related Gene and Cav1.2
Authors: Zheng Zequn , Cai Dihui , Fu Yin , Wang Ying , Song Yongfei , Lian Jiangfang 
Published: July 2022

Background: Old drugs for new indications in the novel coronavirus disease of 2019 (COVID-19) pandemic have raised concerns regarding cardiotoxicity, especially the development of drug-induced QT prolongation. The acute blocking of the cardiac hERG potassium channel is conventionally thought to be the primary mechanism of QT prolongation induced by COVID-19 drugs fluvoxamine (FLV) and lopinavir (LPV). The chronic impact of these medications on the hERG expression has yet to be determined.Methods: To investigate the effect of long-term incubation of FLV and LPV on the hERG channel, we used electrophysiological assays and molecular experiments, such as Western blot, RT-qPCR, and immunofluorescence, in HEK-293 cells stably expressing hERG and human-induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs).Results: Compared to the acute effects, chronic incubation for FLV and LPV generated much lower half-maximal inhibitory concentration (IC50) values, along with a left-shifted activation curve and retarded channel activation. Inconsistent with the reduction in current, we unexpectedly found that the chronic effects of drugs promoted the maturation of hERG proteins, accompanied by the high expression of Hsp70 and low expression of Hsp90. Targeting Hsp70 using siRNA was able to reverse the effects of these drugs on hERG proteins. In addition, FLV and LPV resulted in a significant reduction of APD90 and triggered the early after-depolarizations (EADs), as well as inhibited the protein level of the L-type voltage–operated calcium channel (L-VOCC) in hiPSC-CMs.Conclusion: Chronic incubation with FLV and LPV produced more severe channel-blocking effects and contributed to altered channel gating and shortened action potential duration by inhibiting hERG and Cav1.2.
CYP2A6 and GABRA2 Gene Polymorphisms are Associated With Dexmedetomidine Drug Response
Authors: Fang Chao , Ouyang Wen , Zeng Youjie , Pei Qi , Xia Yuhao , Luo Siwan , Chen Minghua 
Published: July 2022

Background: Dexmedetomidine is a commonly used clinical sedative; however, the drug response varies among individuals. Thus, the purpose of this study was to explore the association between dexmedetomidine response and gene polymorphisms related to drug-metabolizing enzymes and drug response (CYP2A6, UGT2B10, UGT1A4, ADRA2A, ADRA2B, ADRA2C, GABRA1, GABRB2, and GLRA1).Methods: This study was a prospective cohort study. A total of 194 female patients aged 18–60 years, American Society of Anesthesiologists (ASA) score I-II, who underwent laparoscopy at the Third Xiangya Hospital of Central South University, were included. The sedative effect was assessed every 2 min using the Ramsay score, and the patient’s heart rate decrease within 20 min was recorded. Peripheral blood was collected from each participant to identify genetic variants in the candidate genes of metabolic and drug effects using the Sequenom MassARRAY® platform. Furthermore, additional peripheral blood samples were collected from the first 99 participants at multiple time points after dexmedetomidine infusion to perform dexmedetomidine pharmacokinetic analysis by Phoenix® WinNonlin 7.0 software.Results: Carriers of the minor allele (C) of CYP2A6 rs28399433 had lower metabolic enzyme efficiency and higher plasma concentrations of dexmedetomidine. In addition, the participants were divided into dexmedetomidine sensitive or dexmedetomidine tolerant groups based on whether they had a Ramsay score of at least four within 20 min, and CYP2A6 rs28399433 was identified to have a significant influence on the dexmedetomidine sedation sensitivity by logistic regression with Plink software [p = 0.003, OR (95% CI): 0.27 (0.11–0.65)]. C allele carriers were more sensitive to the sedative effects of dexmedetomidine than A allele carriers. GABRA2 rs279847 polymorphism was significantly associated with the degree of the heart rate decrease. In particular, individuals with the GG genotype had a 4-fold higher risk of heart rate abnormality than carriers of the T allele (OR = 4.32, 95% CI: 1.96–9.50, p = 0.00027).Conclusion:CYP2A6 rs28399433 polymorphism affects the metabolic rate of dexmedetomidine and is associated with susceptibility to the sedative effects of dexmedetomidine; GABRA2 rs279847 polymorphism is significantly associated with the degree of the heart rate decrease.