bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer
Authors: Zhang Yang , Chen Xiaoyi , Wang Huamin , Gordon-Mitchell Shanisha , Sahu Srabani , Bhagat Tushar D. , Choudhary Gaurav , Aluri Srinivas , Pradhan Kith , Sahu Plabani , Carbajal Milagros , Zhang Hui , Agarwal Beamon , Shastri Aditi , Martell Robert , Starczynowski Daniel , Steidl Ulrich , Maitra Anirban , Verma Amit 
Published: May 2022

AbstractAdvanced pancreatic ductal adenocarcinoma (PDAC) is usually an incurable malignancy that needs newer therapeutic targets. Interleukin-1 receptor accessory protein (IL1RAP) is an innate immune mediator that regulates activation of pro-inflammatory and mitogenic signaling pathways. Immunohistochemistry on tissue microarrays demonstrated expression of IL1RAP in majority of human PDAC specimens and in murine pancreatic tumors from K-RasG122D/p53R172H/PDXCre (KPC) mice. Single cell RNA-Seq analysis of human primary pre-neoplastic lesions and adenocarcinoma specimens indicated that overexpression occurs during carcinogenesis. IL1RAP overexpression was associated with worse overall survival. IL1RAP knockdown significantly reduced cell viability, invasiveness, and clonogenic growth in pancreatic cancer cell lines. Inhibition of the downstream interleukin-1 receptor-associated kinase 4 (IRAK4) using two pharmacologic inhibitors, CA-4948 and PF06650833, resulted in reduced growth in pancreatic cancer cell lines and in xenograft models.
The effect of Rosa canina L. and a polyherbal formulation syrup in patients with attention-deficit/hyperactivity disorder: a study protocol for a multicenter randomized controlled trial
Authors: Golsorkhi Haide , Qorbani Mostafa , Kamalinejad Mohammad , Sabbaghzadegan Saeideh , Bahrami Mohsen , Vafaee-Shahi Mohammad , Montazerlotfelahi Hadi , Abniki Elham , Dadmehr Majid 
Published: May 2022

Abstract
Background
Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood and adolescence. A number of these patients do not respond to the current pharmacological treatments and there may also be drug side effects. This study aims to determine the efficacy and safety of two herbal medicine products, including Rosa canina L. (RC) and a polyherbal formulation (PHF) syrup, on the clinical manifestations of ADHD in children and adolescents.

Methods
Ninety ADHD patients based on DSM-5 diagnostic criteria will be randomly assigned equally into three groups: (1) RC syrup + methylphenidate (MP), (2) PHF syrup + MP, and (3) placebo + MP according to the inclusion criteria (30 subjects in each group). The syrup dosage is 5cc every 8 h, and MP will have a stabilized dose for 8 weeks during the study. Moreover, Conner’s questionnaires will be completed by the teacher and parents before the intervention and then every 4 weeks. Also, the Child Symptom Inventory-fourth edition (CSI-4) and temperament questionnaires will be completed before the intervention and every 4 weeks until 2 months.

Discussion
This trial is the first experiment to determine the effects of RC and PHF syrups on the clinical manifestations of ADHD in children and adolescents. Our findings provide new insight into the effect of these herbal products on the clinical manifestations of ADHD.

Trial registration
Iranian Registry of Clinical Trials IRCT20190923044855N1. Registered on 14 January 2020. The trial was registered at https://www.irct.ir/.
Evolocumab administration prior to Coronary Artery Bypass Grafting in patients with multivessel coronary artery disease (EVOCABG): study protocol for a randomized controlled clinical trial
Authors: Na Hye Rim , Kwon O Sung , Kang Joon Kyu , Kim Yong Han , Lim Ju Yong 
Published: May 2022

Abstract
Background
Despite advances in surgical and postoperative care, myocardial injury or infarction (MI) is still a common complication in patients undergoing coronary artery bypass surgery (CABG). Several studies that aimed to reduce postoperative myocardial injury, including those investigating statin loading, have been conducted but did not indicate any clear benefits. Evolocumab, a PCSK9 inhibitor, has been reported to lower lipids and prevent ischemic events in various medical conditions. However, the effect of evolocumab in cardiovascular surgery has not been evaluated. The objective of this trial is to evaluate the cardioprotective effects of evolocumab in elective CABG patients with multivessel coronary artery disease.

Methods
EVOCABG is a prospective, randomized, open, controlled, multicenter, superiority, phase III clinical trial. Patients with multivessel coronary artery disease without initial cardiac enzyme elevation will be recruited (n=100). Participants will be randomly allocated into two groups: a test group (evolocumab (140mg) administration once within 72 h before CABG) and a control group (no administration). The primary outcome is the change in peak levels of serum cardiac marker (troponin-I) within 3 days of CABG surgery compared to the baseline. Secondary outcomes include post-operative clinical events including death, myocardial infarction, heart failure, stroke, and atrial fibrillation.

Discussion
This trial is the first prospective randomized controlled trial to demonstrate the efficacy of evolocumab in reducing ischemic-reperfusion injury in patients undergoing CABG. This trial will provide the first high-quality evidence for preoperative use of evolocumab in mitigating or preventing ischemic-reperfusion-related myocardial injury during the surgery.

Trial registration
Clinical Research Information Service (CRIS) of the Republic of Korea KCT0005577. Registered on 4 November 2020.
Zinc supplementation and COVID-19 mortality: a meta-analysis
Authors: Tabatabaeizadeh Seyed-Amir 
Published: May 2022

Abstract
Background and aims
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a pneumonia outbreak and was called 2019 novel coronavirus disease (COVID-19). COVID-19 emerged in December 2019 and now considered a pandemic. Zinc supplementation can reduce mortality in patients with severe pneumonia. This study aimed at meta-analysis of the results of related studies and evaluate the effect of zinc supplementation on COVID-19 mortality.

Methods
A systematic search has conducted for manuscripts through PUBMED/Medline and Google Scholar (Cochrane guideline has considered it as the gray literature) up to September 2021. This meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Guideline for evaluation of the effect zinc supplementation on COVID-19 mortality. Based on the heterogeneity a fixed-effect or random-effect model, the OR and 95% CI were used to assess the combined risk.

Results
After assessment, five studies with 1506 participants in case and control groups were included in meta-analysis. The OR for one study was not estimable, and the pool OR was estimated for other studies with 1398 participants. The meta-analysis showed that zinc supplementation in cases led to a significant lower risk of mortality when it was compared with the control group; pooled OR (95% CI) was 0.57 [0.43, 0.77] (P < 0.001).

Conclusion
This meta-analysis has suggested that zinc supplementation is associated with a lower mortality rate in COVID-19 patients. Zinc supplementation could be considered as a simple way and cost benefit approach for reduction of mortality in COVID-19 patients.
Leveraging farm production diversity for dietary diversity: evidence from national level panel data
Authors: Khandoker Sayla , Singh Alka , Srivastava Shivendra Kumar 
Published: May 2022

AbstractDietary diversity is the key to improved health and nutrition. Farm production diversity has the potential of enhancing dietary diversity but this interrelationship varies and is ambiguous in many societies. To examine the effect of farm production diversity on household dietary diversity using nationally representative panel data of Bangladesh we have used Bangladesh Integrated Household Survey (BIHS) data collected by International Food Policy Research Institute (IFPRI) in 2011/12, 2015 and 2018/19. Total sample size is 11,720. For assessing dietary diversity we have used different indicators namely household dietary diversity score (HDDS) and food variety score (FVS). We have also used multiple methods for measuring farm production diversity including production diversity score, crop diversity score and Simpson diversification index. Poisson regression model has been used. Results revealed a strong positive association among farm production diversity, income and dietary diversity though the extent of the association is small. The variables such as market orientation, access to market, age and education are also found to influence on household dietary diversity. Our results propose that for increasing dietary diversity efforts should be taken to increase farm production diversity combined with diverse income and market access.
Eavesdropping on the brain at sea: development of a surface-mounted system to detect weak electrophysiological signals from wild animals
Authors: Kendall-Bar Jessica M. , Mukherji Ritika , Nichols Jordan , Lopez Catherine , Lozano Daniel A. , Pitman Julie K. , Holser Rachel R. , Beltran Roxanne S. , Schalles Matt , Field Cara L. , Johnson Shawn P. , Vyssotski Alexei L. , Costa Daniel P. , Williams Terrie M. 
Published: May 2022

AbstractDespite rapid advances in sensor development and technological miniaturization, it remains challenging to non-invasively record small-amplitude electrophysiological signals from an animal in its natural environment. Many advances in ecophysiology and biologging have arisen through sleep studies, which rely on detecting small signals over multiple days and minimal disruption of natural animal behavior. This paper describes the development of a surface-mounted system that has allowed novel electrophysiological recordings of sleep in wild marine mammals. We discuss our iterative design process by providing sensor-comparison data, detailed technical illustrations, and material recommendations. We describe the system’s performance over multiple days in 12 freely moving northern elephant seals (Mirounga angustirostris) sleeping on land and in water in captivity and the wild. We leverage advances in signal processing by applying independent components analysis and inertial motion sensor calibrations to maximize signal quality across large (> 10 gigabyte), multi-day datasets. Our study adds to the suite of biologging tools available to scientists seeking to understand the physiology and behavior of wild animals in the context in which they evolved.
Controlling risky behavior associated with AIDS: the role of social support, family functioning, self-efficacy and AIDS risk perception
Authors: Zakiei Ali , Norouzi‬ Ebrahim , Ghasemi Seyed Ramin , Komasi Saeid , Rostampour Masoumeh , Khazaie Habibolah 
Published: May 2022

Abstract
Objectives
We believe that major steps can be taken towards Acquired Immunodeficiency Syndrome (AIDS) prevention through identifying the relevant factors that are apt to predict risky behavior. The main purpose of the present study was to analyze and evaluate the relationship of social support, family functioning, self-efficacy and AIDS risk perception to controlling risky behavior associated with AIDS.

Methods
To conduct this cross-sectional study, 765 subjects (59% female) were selected from the youth inhabiting the western provinces of Iran through cluster sampling. Five questionnaires were used: AIDS risk perception, self-efficacy in controlling risky behavior associated with AIDS, controlling risky behavior associated with AIDS, the multidimensional scale of perceived social support, and the family assessment device.

Results
The results demonstrated that all two models enjoyed acceptable fitness, and the mediating roles of self-efficacy and AIDS risk perception were confirmed. Moreover, family functioning and perceived social support together could predict 20% of the variance of controlling risky behavior associated with AIDS. The results also indicated that family functioning with a standardized coefficient of − 0.24 and self-efficacy in controlling risky behavior associated with AIDS with a standardized coefficient of 0.58 could predict the controlling risky behavior associated with AIDS (p < 0.01).

Conclusions
Our findings suggest that self-efficacy and AIDS risk perception play major roles in controlling risky behavior associated with AIDS. Therefore, it is recommended that families and psychologists promote self-efficacy in order to prevent the occurrence of high-risk behaviors.
Improving predictability of IgE-high type 2 chronic sinusitis with nasal polyps in the biologic era
Authors: Heffernan Austin , Phulka Jobanjit , Thamboo Andrew 
Published: May 2022

Background Chronic rhinosinusitis (CRS) is an inflammatory disease that may require biological therapy. Omalizumab is an anti-IgE biologic that was recently approved by the FDA and Health Canada for use in severe CRS with nasal polyps (CRSwNP) recalcitrant to intranasal corticosteroids. Dosing is based on weight and pre-treatment serum IgE, with elevated levels of the latter being an indication for biologic treatment according to EPOS and EUFOREA guidelines. The goal of this study was to identify variables that predict IgE-high type 2 inflammation and serve as indicators for biologic treatment in CRS. Methods Patients ≥ 19 yo diagnosed with CRS undergoing functional endoscopic sinus surgery were included retrospectively. Demographics, past medical history, preoperative blood work, Lund-Mackay (LM), Lund Kennedy (LK), and SNOT-22 scores were extracted. Descriptive statistics and binary logistic regression analyses were conducted. Model superiority was based on Nagelkerke R2 scores and receiver operating characteristic curves. Results Sixty-five patients, average age 49.96 ± 13.59 years, were included. Sixty-one binary logistic regression models for elevated serum IgE were created. Among the top 3 models, the best model had sensitivity, specificity, positive predictive value and negative predictive values of 82.1, 69.2, 80.0, and 72.0. All performance measures except sensitivity exceeded the Canadian Biologics Guideline model. Serum eosinophils ≥ 300 cell/uL, CRSwNP and LM ≥ 17 increased the odds of elevated IgE. Conclusions IgE-high type-2 inflammation can be predicted by a model that includes eosinophil ≥ 300 cell/uL, CRSwNP, LM ≥ 17, asthma diagnosis and SNOT-22 ≥ 40. Patients meeting these parameters have a high pretest probability for elevated IgE and would benefit from IgE serology to determine qualification for omalizumab. This could reduce unwarranted IgE serology in patients with CRSwNP but also target a patient population for further workup that will lead to optimization of resource allocation and improve healthcare equity in rural and remote areas within Canada.
Unique characteristics of G719X and S768I compound double mutations of epidermal growth factor receptor (EGFR) gene in lung cancer of coal-producing areas of East Yunnan in Southwestern China
Authors: Wang Jun-Ling , Fu Yu-Dong , Gao Yan-Hong , Li Xiu-Ping , Xiong Qian , Li Rui , Hou Bo , Huang Ruo-Shan , Wang Jun-Feng , Zhang Jian-Kun , Lv Jia-Ling , Zhang Chao , Li Hong-Wei 
Published: May 2022

Abstract
Background
The principal objective of this project was to investigate the Epidermal Growth Factor Receptor (EGFR) gene mutation characteristics of lung cancer patients, which can provide a molecular basis for explaining the clinicopathological features, epidemiology and use of targeted therapy in lung cancer patients in the coal-producing areas of East Yunnan.

Methodology
We collected 864 pathologically confirmed lung cancer patients’ specimens in First People’s Hospital of Qujing City of Yunnan Province from September 2016 to September 2021. We thereafter employed Next Generation Sequencing (NGS) technology to detect all exons present in the EGFR gene.

Results
The overall mutation frequency of the EGFR gene was 47.22%. The frequency of EGFR gene mutations in the tissue, plasma, and cytology samples were found to be 53.40%, 23.33%, and 62.50%, respectively. Univariate analysis indicated that the coal-producing areas and Fuyuan county origin were significantly associated with relatively low EGFR gene mutation frequency. Female, non-smoking history, adenocarcinoma, non-brain metastasis, and tissue specimens were found to be related to high EGFR gene mutation frequency. Multivariate logistic regression analysis suggested the lung cancer patients in the central area of Qujing City, stage Ia, non-coal-producing areas, non-Fuyuan origin, and non-Xuanwei origin were more likely to develop EGFR gene mutations. The most common mutations were L858R point mutation (33.09%) and exon 19 deletion (19-del) (21.32%). Interestingly, the mutation frequency of G719X (p = 0.001) and G719X + S768I (p = 0.000) in the coal-producing areas were noted to be more significant than those in non-coal-producing regions.

Conclusion
This findings of this study might be important in establishing the correlation between routine using NGS for EGFR gene mutation diagnosis and clinical practice in the lung cancer patients.
AMPLIFY-NEOVAC: a randomized, 3-arm multicenter phase I trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with an immune checkpoint inhibitor targeting programmed death-ligand 1 in isocitrate dehydrogenase 1 mutant gliomas
Authors: Bunse Lukas , Rupp Anne-Kathleen , Poschke Isabel , Bunse Theresa , Lindner Katharina , Wick Antje , Blobner Jens , Misch Martin , Tabatabai Ghazaleh , Glas Martin , Schnell Oliver , Gempt Jens , Denk Monika , Reifenberger Guido , Bendszus Martin , Wuchter Patrick , Steinbach Joachim P , Wick Wolfgang , Platten Michael 
Published: May 2022

Abstract
Introduction
Isocitrate dehydrogenase (IDH) mutations are disease-defining mutations in IDH-mutant astrocytomas and IDH-mutant and 1p/19q-codeleted oligodendrogliomas. In more than 80% of these tumors, point mutations in IDH type 1 (IDH1) lead to expression of the tumor-specific protein IDH1R132H. IDH1R132H harbors a major histocompatibility complex class II (MHCII)-restricted neoantigen that was safely and successfully targeted in a first-in human clinical phase 1 trial evaluating an IDH1R132H 20-mer peptide vaccine (IDH1-vac) in newly diagnosed astrocytomas concomitant to standard of care (SOC).

Methods
AMPLIFY-NEOVAC is a randomized, 3-arm, window-of-opportunity, multicenter national phase 1 trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with avelumab (AVE), an immune checkpoint inhibitor (ICI) targeting programmed death-ligand 1 (PD-L1). The target population includes patients with resectable IDH1R132H-mutant recurrent astrocytoma or oligodendroglioma after SOC. Neoadjuvant and adjuvant immunotherapy will be administered to 48 evaluable patients. In arm 1, 12 patients will receive IDH1-vac; in arm 2, 12 patients will receive the combination of IDH1-vac and AVE, and in arm 3, 24 patients will receive AVE only. Until disease progression according to immunotherapy response assessment for neuro-oncology (iRANO) criteria, treatment will be administered over a period of maximum 43 weeks (primary treatment phase) followed by facultative maintenance treatment.

Perspective
IDH1R132H 20-mer peptide is a shared clonal driver mutation-derived neoepitope in diffuse gliomas. IDH1-vac safely targets IDH1R132H in newly diagnosed astrocytomas. AMPLIFY-NEOVAC aims at (1) demonstrating safety of enhanced peripheral IDH1-vac-induced T cell responses by combined therapy with AVE compared to IDH1-vac only and (2) investigating intra-glioma abundance and phenotypes of IDH1-vac induced T cells in exploratory post-treatment tissue analyses. In an exploratory analysis, both will be correlated with clinical outcome.

Trial registration

NCT03893903.
Genetic polymorphisms and gene expression of one-carbon metabolizing enzymes and their relation to breast cancer
Authors: Eldeeb Mona Kamal , Shoaib Mai Maher Abd-Elaziz , Abd-Elmonem Esraa Ahmed , Saeed Hesham Mahmoud Sayd , Embaby Amira Mohammad , Farouk Ayman Mohamed , Rashad Radwa Mohammed 
Published: May 2022

Abstract
Background
Breast cancer is considered the leading cause of cancer-related death among Egyptian women (15.41%). One of the common BC risk factors is the genetic factor. One-carbon metabolism is one of the pathways reported to increase BC risk by influencing DNA synthesis and methylation. Methyl tetrahydrofolate reductase (MTHFR), thymidylate synthase (TYMS) and DNA methyltransferase (DNMT) enzymes are key enzymes in one-carbon metabolism directly and through influencing folate metabolism. We aimed to study the association of the gene expression level and polymorphisms of MTHER C677T (rs1801133), TYMS (rs45445694), TYMS 3′UTR 1494del6 and ΔDNMT3B − 149C>T with breast cancer risk in a sample of Egyptian women.

Methods
This study was conducted on one hundred female breast cancer patients. Genotyping and gene expression of the MTHFR and TYMS (1494del6, rs45445694) and DNMT3B genes were performed.

Results
There was no significant difference (OR 1.493; 95% CI 0.78–2.84; P = 0.288) in the frequency of the MTHFR (C677T) genotypes between breast cancer patients and control subjects and no significant difference in the frequency of the MTHFR mutant T allele. TYMS tandem repeats showed a significant difference (OR 2.232; CI 1.21–4.12; P = 0.01) in the frequency of the genotype 2R/3R among breast cancer patients and control subjects; however, the frequency of the 2R allele was not significantly different from that of the 3R allele (OR 1.461; 95% CI 0.96–2.21; P = 0.073). TYMS 3′-UTR 1494del6 showed a significant difference in the distribution of (+ 6/ + 6), (+ 6/− 6) and (− 6/− 6) genotypes between the patient and control groups (P ≤ 0.001*), and its corresponding mutant allele showed P value ≤ 0.001, 95% CI = 1.64–3.76 and OR = 2.483. The expression of MTHFR was downregulated by 0.62-fold in all malignant tissues compared to normal adjacent tissues (0.57 ± 0.20, P < 0.001*). On the other hand, no significant difference (P = 0.143) in the expression level of TYMS was found. Gene expression of DNMT3B was upregulated by 1.65-fold in all breast cancerous tissue samples compared with the control normal adjacent tissue with mean ± SD of 1.81 ± 0.63. (P ≤ 0.001*).

Conclusion
The current study showed that the 2R/3R TYMS allele and DNMT3B (− 149C>T) SNP are associated with a high risk of breast cancer and that there is a correlation between the 3′-UTR 1494del6 polymorphism (genotype − 6/− 6) and breast cancer risk. A significant reduction was found in the MTHFR gene expression level in BC compared with control tissues, and the DNMT3B (− 149C>T) SNP did affect the DNMT3B expression level.
Do related party transactions affect the relationship between political connections and firm value? Evidence from Egypt
Authors: Ismail Tariq H. , El-Deeb Mohamed , Halim Yasser Tawfik 
Published: May 2022

AbstractThis paper aims to (i) investigate the impact of political connections (PC) and related party transactions (RPTs) on the firm value (FV), and (ii) test the moderating effect of RPTs on such relationship, while controlling for the firms’ corporate governance mechanisms. Based on 315 observations from publicly listed firms in Egypt, our results reveal that (i) there is a positive relationship between PC and the FV, (ii) there is a negative relationship between RPTs and the FV, and (iii) the existing of RPTs as a moderating variable enhances the impact of the politically connected companies on the FV. The findings suggest that the Egyptian firms are much affected by the politically connected board of directors or owners, and this significantly exists when associated with related party transactions, despite that, the corporate governance practices could mitigate such effects.