bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of sequential S-1 and cyclophosphamide therapy in patients with metastatic breast cancer
Authors: Yanai Keiko , Fujii Takaaki , Horiguchi Jun , Nakazawa Yuko , Kurozumi Sasagu , Obayashi Sayaka , Yajima Reina , Shirabe Ken 
Published: September 2020

Abstract
Background: S-1 and cyclophosphamide (CPA) can be given orally, and their combination may have great potential for treating metastatic breast cancer (MBC). A phase I study of sequential S-1 and CPA therapy was conducted in patients with MBC; the recommended doses that were determined for this regimen were 80 mg/m2/day for S-1 and 100 mg/m2/day for CPA. We then conducted a phase II study of this oral S-1 and CPA regimen. Methods: This was a single-arm, open-label, single-center prospective phase II study to evaluate the efficacy of a sequential S-1 and CPA regimen for MBC. S-1 was administered orally 2´/day for 14 consecutive days, and then CPA was administered orally 2´/day for 14 consecutive days in a repeating 4-week cycle (S-1 for 2 weeks, CPA for 2 weeks). The primary endpoint was the overall response rate (ORR). Secondary endpoints included the overall survival (OS), progression-free survival (PFS), clinical benefit rate (CBR) and safety. Results: Thirty-six patients were enrolled in this study. The overall response was complete response in 0 (0%), partial response in 12 (33.3%), stable disease in 12 (33.3%), and progressive disease in 11 (30.1%) patients. The ORR was 33.3% (12/36). The CBR was 66.7% (24/36). The median PFS was 9.5 months (95%CI: 7.8–12.6 months). The median OS was 20.2 months (95%CI: 15.0–25.4 months) Grade 3/4 adverse events included leukopenia in seven patients (19.4%). Dose reductions because of adverse events occurred in 12 patients (33.3%). There was no treatment-related mortality. Conclusion: The combination of sequential therapy with S-1 and CPA was tolerable and had efficacy with good disease control. Sequential therapy with S-1 and CPA may be a feasible new treatment option for patients with MBC, however, further study is warranted to explore the efficacy of this therapy.Trial registration: JRCT, JRCTs 031180296. Registered 2 December 2019 – Retrospectively registered, https://jrct.hiph.go.jp/latest-detail.jrcts031180296
Involving Research Participants in a Pan-European Research Initiative: The EPAD Participant Panel Experience
Authors: Gregory Sarah , Bunnik Eline M , Callado Ana Belén , Carrie Isabelle , De Boer Casper , Duffus Julie , Fauria Karine , Forster Shona , Gove Dianne , Knezevic Iva , Laquidain Alejandro , Pennetier Delphine , Saunders Stina , Sparks Sarah , Rice J. , Ritchie Craig W , Milne Richard 
Published: September 2020

Abstract
Background: Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts. Methods: In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer’s disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs. Results: The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings. Conclusions: The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations.
Genetically-regulated transcriptomics &amp; copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry
Authors: Pathak Gita A , Polimanti Renato , Silzer Talisa K , Wendt Frank R , Chakraborty Ranajit , Phillips Nicole R 
Published: September 2020

Abstract
BACKGROUND: Proctitis is an inflammation of the rectum and may be induced by radiation treatment for cancer. The genetic heritability of developing radiotoxicity and prior role of genetic variants as being associated with side-effects of radiotherapy necessitates further investigation for underlying molecular mechanisms. In this study, we investigated gene expression regulated by genetic variants, and copy number variation in prostate cancer survivors with radiotoxicity. METHODS: We investigated proctitis as a radiotoxic endpoint in prostate cancer patients who received radiotherapy (n=222). We analyzed the copy number variation and genetically regulated gene expression profiles of whole-blood and prostate tissue associated with proctitis. The SNP and copy number data were genotyped on Affymetrix® Genome-wide Human SNP Array 6.0. Following QC measures, the genotypes were used to obtain gene expression by leveraging GTEx, a reference dataset for gene expression association based on genotype and RNA-seq information for prostate (n= 132) and whole-blood tissue (n=369). RESULTS: In prostate tissue, 62 genes were significantly associated with proctitis, and 98 genes in whole-blood tissue. Six genes - CABLES2, ATP6AP1L, IFIT5, ATRIP, TELO2, and PARD6G were common to both tissues. The copy number analysis identified seven regions associated with proctitis, one of which (ALG1L2) was also associated with proctitis based on transcriptomic profiles in the whole-blood tissue. The genes identified via transcriptomics and copy number variation association were further investigated for enriched pathways and gene ontology. Some of the enriched processes were DNA repair, mitochondrial apoptosis regulation, cell-to-cell signaling interaction processes for renal and urological system, and organismal injury.CONCLUSIONS: We report gene expression changes based on genetic polymorphisms. Integrating gene-network information identified these genes to relate to canonical DNA repair genes and processes. This investigation highlights genes involved in DNA repair processes and mitochondrial malfunction possibly via inflammation. Therefore, it is suggested that larger studies will provide more power to infer the extent of underlying genetic contribution for an individual’s susceptibility to developing radiotoxicity.
Artificial neural networks improve LDCT lung cancer screening: A comparative validation study
Authors: Hsu Yin-Chen , Tsai Yuan-Hsiung , Weng Hsu-Huei , Hsu Li-Sheng , Tsai Ying-Huang , Lin Yu-Ching , Hung Ming-Szu , Fang Yu-Hung , Chen Chien-Wei 
Published: September 2020

Abstract
Background: This study proposes a prediction model for the automatic assessment of lung cancer risk based on an artificial neural network (ANN) with a data-driven approach to the low-dose computed tomography (LDCT) standardized structure report. Methods: This comparative validation study analysed a prospective cohort from Chiayi Chang Gung Memorial Hospital, Taiwan. In total, 836 asymptomatic patients who had undergone LDCT scans between February 2017 and August 2018 were included, comprising 27 lung cancer cases and 809 controls. A derivation cohort of 602 participants (19 lung cancer cases and 583 controls) was collected to construct the ANN prediction model. A comparative validation of the ANN and Lung-RADS was conducted with a prospective cohort of 234 participants (8 lung cancer cases and 226 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. Results: At the cut-off of category 3, the Lung-RADS had a sensitivity of 12.5%, specificity of 96.0%, positive predictive value of 10.0%, and negative predictive value of 96.9%. At its optimal cut-off value, the ANN had a sensitivity of 75.0%, specificity of 85.0%, positive predictive value of 15.0%, and negative predictive value of 99.0%. The area under the ROC curve was 0.764 for the Lung-RADS and 0.873 for the ANN ( P =0.01). The two most important predictors used by the ANN for predicting lung cancer were the documented sizes of partially solid nodules and ground-glass nodules. Conclusions: Compared to the Lung-RADS, the ANN provided better sensitivity for the detection of lung cancer in an Asian population. In addition, the ANN provided a more refined discriminative ability than the Lung-RADS for lung cancer risk stratification with population-specific demographic characteristics. When lung nodules are detected and documented in a standardized structured report, ANNs may better provide important insights for lung cancer prediction than conventional rule-based criteria.
Determinants of participation in a post-hospitalization physical exercise program for older adults
Authors: Urquiza Miriam , Echeverria Iñaki , Besga Ariadna , Amasene Maria , Labayen Idoia , Rodriguez Ana , Barroso Julia , Aldamiz Mikel , Irazusta Jon 
Published: September 2020

Abstract
BACKGROUND: Older patients often experience a decline in physical function and cognitive status after hospitalization. Although interventions involving physical exercise are effective in improving functional performance, participation in physical exercise interventions among older individuals is low. We aimed to identify factors that contribute to exercise refusal among post-hospitalized older patients.METHODS: A cross-sectional study of recruitment data from a randomized controlled trial was conducted involving 495 hospitalized people ≥70 years old. Sociodemographic and clinical data were obtained from the Basque Public Health System database. We determined physical function with the Short Physical Performance Battery (SPPB), nutritional status with the Mini-Nutritional Assessment, frailty according to the Fried phenotype criteria, and cognitive function with the Short Portable Mental Status Questionnaire (SPMSQ). Student’s t, Mann-Whitney U, or chi-squared tests were applied for bivariate analysis. Parameters significantly associated with participation were introduced in a logistic multivariate regression model.RESULTS: Among the analyzed patients, 88.8% declined participation in the physical exercise program. Multivariate regression revealed that older age (OR: 1.13; 95% CI: 1.07 - 1.19), poor nutritional status (OR: 0.81; 95% CI: 0.69 - 0.95), and reduced home accessibility (OR: 0.27; 95% CI: 0.08 - 0.94) were predictors of participation refusal. Moreover, patients who declined participation had worse performance on the SPPB (P < 0.05) and its tests of balance, leg strength, and walking speed (P < 0.05). No differences were found between groups in other variables. CONCLUSIONS: This study confirms low participation of older adults in a post-hospitalization physical exercise program. Non-participation was associated with increased age, poor nutritional status, and reduced home accessibility. Our findings support the need for intervention design that accounts for these factors to increase older patient participation in beneficial exercise programs.
Cancer in Moroccan elderly: The first multicenter transverse study exploring the sociodemographic characteristics, clinical profile and quality of life of elderly Moroccan cancer patients
Authors: Amzerin Mounia , Laayachi Mohamed , Bazine Aziz , Aassab Rachid , Arifi Samia , Benbrahim Zineb , Khmamouche Mohamed Reda , Kairouani Mouna , Raiss Hanan , Majid Noura , Ouaouch Saloua , Ichou Mohammed , Afqir Said , Mellas Nawfal , Fetohi Mohamed , Razine Rachid , Errihani Hassan 
Published: September 2020

Abstract
Background: Moroccan incidence of cancer is increasing with the lengthening of life expectancy. Data regarding elderly Moroccan cancer patients are lacking. In the context of our project aiming to develop an adapted version of the Comprehensive Geriatric Assessment CGA to the Moroccan population, we launched the first Moroccan multicenter transverse study to explore the characteristics of elderly Moroccan cancer patients.Methods: The study was conducted in nine Moroccan medical oncology departments. Patients were enrolled over 4 months. Inclusion criteria were patients aged 65 years or over with verified solid cancer. The questionnaire included four sections: socio-demographic and economic data, clinical data, vulnerability and EORTC-QLQ C30. We explored the entire included population. Then, we compared the results according to age (65-70 years old and ≥71 years old) and sex. We also explored the correlation between G8 scores and the ability to practice religion as an indicator of fitness level. Results: In total, 164 patients were enrolled. The mean age was 73.18± 6.01 years. The majority of patients were married, lived with their children and received their financial income from them. Fifteen percent of families asked to hide the diagnosis from the patient. Breast (23%), colorectal (15.9%) and lung (14%) cancers were the most frequent, and 83.5% had an abnormal G8. The majority of the patients were independent for basic daily activities. Female patients had poorer social and economic conditions. Abnormal G8 was correlated with religious practice and quality of life scores. Conclusion: This is the first multicenter prospective study designed to collect data on the lifestyle and clinical profiles of elderly Moroccan cancer patients as an Arab and Muslim population. Our study shows that it is a well-cared-for population with strong social ties. However, there is deep economic vulnerability, especially among women, requiring urgent care. Religious practice is an important daily activity for our elderly patients and should be included in the Moroccan CGA.
Role of Circulating Free DNA in Evaluating Clinical Tumor Burden and Predicting Survival in Chinese Metastatic Colorectal Cancer Patients
Authors: xu xiaojing , yu yiyi , shen minna , liu menglin , wu shengchao , liang li , huang fei , zhang chenlu , guo wei , liu tianshu 
Published: September 2020

Abstract
Background: The aim of this study was to explore the utility of circulating free DNA (cfDNA) in the evaluation of clinical tumor burden and survival in Chinese patients with metastatic colorectal cancer (mCRC) and to preliminarily summarize some metastatic characteristics associated with mutational status.Methods: A panel covering a total of 197 hotspot mutations of KRAS, NRAS, BRAF and PIK3CA was used to evaluate the mutational status in plasma by next-generation sequencing (NGS) technology in 126 patients with mCRC. An amplification-refractory mutation system (ARMS) was used to analyze genomic DNA from matched tissue samples. Clinical markers including carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) in serum and the sum of all tumor diameters on CT or PET/CT were collected to indicate clinical tumor burden. The correlations between cfDNA and clinical tumor burden were analyzed using Pearson correlation and linear regression models. The median progression-free survival (PFS) and 1-year overall survival (OS) rates were calculated by Kaplan-Meier (K-M) survival analysis.Results: If the 126 enrolled patients, patients who were tested positive for mutations in plasma accounted for 45.2% (57/126). Mutations in KRAS, NRAS, BRAF and PIK3CA were detected in 37.3% (47/126), 1.6% (2/126), 3.2% (4/126) and 13.5% (17/126) of patients, respectively. The overall concordance rate of mutational status between plasma and matched tissues was 78.6% (99/126). Sixteen patients had mutations in plasma that were not detected in tissue, including some rare hotspot mutations. The cfDNA concentration was significantly correlated with the levels of clinical markers, especially CEA (P<0.0001, Pearson r = 0.81), LDH (P<0.0001, Pearson r = 0.84) and the sum of tumor diameters (P<0.0001, Pearson r = 0.80). Patients with a high cfDNA concentration (>17.91 ng/ml) had shorter median progression-free survival (6.6 versus 11.7 months, P<0.0001) and lower 1-year overall survival rate (56% versus 94%, P<0.0001) than those with a low cfDNA concentration (≤17.91 ng/ml). The most common metastatic site was the liver (77.8%), followed by the lymph nodes (62.7%), lung (40.5%), peritoneum (14.3%) and bone (10.3%), in all patients. There was no significant difference in metastasis between different mutational statuses.Conclusion: Analyzing mutations in plasma could provide a more comprehensive overview of the mutational landscape than analyzing mutations in tissue. The cfDNA concentration could be a quantitative biomarker of tumor burden and could predict survival in Chinese patients with mCRC.
Characterization of poplar growth-regulating factors and analysis of their function in leaf size control
Authors: Wang Jinnan , Zhou Houjun , Zhao Yanqiu , Sun Pengbo , Tang Fang , Song Xueqin , Lu Mengzhu 
Published: September 2020

Abstract
Background: Growth-regulating factors (GRFs) are plant-specific transcription factors that control organ size. Nineteen GRF genes were identified in the Populus trichocarpa genome and one was reported to control leaf size by regulating cell expansion. In this study, we further characterize the roles of the other poplar GRFs in leaf size control in a similar manner.Results: The 19 poplar GRF genes were clustered into six groups according to their phylogenetic relationship with Arabidopsis GRFs. Bioinformatic analysis, degradome, and transient transcription assays showed that 18 poplar GRFs were regulated by miR396, with GRF12b the only exception. The functions of PagGRF6b (Pag, Populus alba × P. glandulosa), PagGRF7a, PagGRF12a, and PagGRF12b, representing three different groups, were investigated. The results show that PagGRF6b may have no function on leaf size control, while PagGRF7a functions as a negative regulator of leaf size by regulating cell expansion. By contrast, PagGRF12a and PagGRF12b may function as positive regulators of leaf size control by regulating both cell proliferation and expansion, primarily cell proliferation.Conclusions: The diversity of poplar GRFs in leaf size control may facilitate the specific, coordinated regulation of poplar leaf development through fine adjustment of cell proliferation and expansion.
The Axin2-Snail axis promotes bone invasion by activating cancer-associated fibroblasts in oral squamous cell carcinoma
Authors: An Yin-Zhe , Cho Eunae , ling Junqi , Zhang Xianglan 
Published: September 2020

Abstract
Background: In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC.Methods: The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo.Results: Axin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro. Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro. Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model.Conclusions: Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC.
Effect of Transcranial Direct Current Stimulation and Reaction Time Training on Cognition and Choice Reaction Time in Recreational Soccer Players (FAST Trial): A Protocol for A Randomized Clinical Trial
Authors: Neto Eduaro de Moura , Luvizutto Gustavo José , Souza Luciane Aparecida Pascucci Sande de 
Published: September 2020

Abstract
Background: Studies examining the effects of transcranial direct current stimulation (tDCS) and reaction time (RT) training on choice RT in the lower limb during a specific task linked to soccer practice, such as kicking, are lacking. Accordingly, this proposal aimed to evaluate the efficacy and safety of tDCS and RT training in choice RT and cognitive function during recreational soccer. Methods: In this single-center, randomized, placebo-controlled, double-blind, parallel-group study of 30 recreational soccer players, tDCS will be applied in the primary motor cortex (M1). Participants will be divided into (1) anodal tDCS plus RT training and (2) sham tDCS plus RT training. The investigator will be blinded to patient treatment before the first session, last session, and 1 day after the last tDCS session. In total, 15 sessions will be performed using a schedule of three times a week for 5 weeks. The RT training protocol will be delivered during tDCS and will comprise kicking a ball from a platform, placed on either the right or the left side, depending on a light cue, during a 10-min interval (between minute 5 and minute 15 after 20-min stimulation). Changes in choice RT in the upper and lower limbs will be considered primary outcome measures, and changes in Trail Making Test and Digit Span Test will be considered secondary outcome measures. Any adverse effects during the study period will be reported. To detect changes in continuous outcomes, a the anodal tDCS and the sham mode will be compared using a t-test for normal distribution, or the nonparametric Mann-Whitney test for non-normal distribution; changes will be considered significant at p < 0.05. Discussion: The FAST trial is a new proposal that uses a novel method of evaluation and training of choice RT in soccer players through a functional task. The anodal tDCS along with choice RT training with a functional task can be an efficient tool for athletes to prevent injuries. Our findings may be useful for soccer athletes to have enhanced responses during a game, and to improve performances in championships. Trial Registration: Registro Brasileiro de Ensaios Clínicos (Rebec) - RBR-9bjttcDate of registration: 02/28/2020Last Update: 04/20/2020