bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of high bednet usage from a list randomization experiment in rural Gambia
Authors: Brew Joe , Pinder Margaret , Dalessandro Umberto , Lindsay Steven W , Jones Carloine , Sicuri Elisa 
Published: November 2019

Abstract
Background Recording behaviours that have the potential to impact health can be doubly challenging if the behaviour takes place in private spaces that cannot be observed directly and where there is potential for social desirability bias, i.e. where the respondent may give an answer that they think the recorder wants to hear. Sleeping under a long-lasting insecticidal net (LLIN) is an important intervention for malaria prevention, yet it is difficult to gauge the extent to which coverage (how many nets are in the community) differs from usage (how many people sleep under a net). We employed a novel method, list randomization, which partially obscures respondents' answers to sensitive questions, as a mean to provide an accurate estimate of LLIN usage in The Gambia.Methods We surveyed 196 residents from 196 households recruited into a randomised controlled trial assessing the effect of a housing intervention on malaria. In the current experiment, 98 of the 196 study participants were randomly assigned to the control group and received a four-question list about non-sensitive behaviours; the other participants in the intervention group, received the same list, with the addition of one question on a sensitive behaviour; whether or not they had used a bednet the previous night. Participants were read the list of questions and then said how many of the statements were true. We estimated bednet usage by calculating the difference in means between the total number of affirmative items between the two groups, and quantified uncertainty using a t-test.Results The mean number of affirmative responses in the control group was 2.60 of four statements (95% confidence interval, 95% CI, = 2.50-2.70), compared with 3.68 (95% CI = 3.59-3.78) in the intervention group. Such difference (1.08; 95% CI = 94.9-100%) suggests approximately 100% bednet usage.Conclusions Our findings suggest complete universal bednet usage in the study area. Further validation of the list randomization method in areas with lower net coverage is required.
MicroRNA-20a mediates the cytotoxicity of natural killer cells in endometriosis via ERG/HLX/STAT4/perforin axis
Authors: Chen Li-Juan , Hu Bin , Han Zhi-Qiang , Ni Jian , Zhou Yong-Ming , Chen Xue-Xing , Zhou Hao 
Published: November 2019

Abstract
Background: Intriguingly, microRNA-20a (miR-20a) has been recently witnessed to be involved in the pathogenesis of endometriosis (EMS) but the molecular mechanism controlled by miR-20a is to be undefined. The present study is designed to probe into how miR-20a acts to regulate the cytotoxicity of natural killer (NK) cells. Methods: Most of all, consistent with the clinical determination in EMS patients, miR-20a was determined to be down-regulated in NK cells isolated from nude mice. miR-20a could specifically bind to ERG and negatively regulates its expression in NK cells. Additionally, shRNA-mediated silencing of ERG decreased the expression of HLX. HLX up-regulated STAT4 by inducing proteasome degradation and inhibited NK cell cytotoxicity. Results: Of great importance, forced expression of miR-20a consequently induced NK cell cytotoxicity in vitro by increasing perforin expression via enhancement of STAT4 that was caused by impairing the binding of ERG to HLX enhancer. The in vivo experiments further confirmed the promoting role of miR-20a in the cytotoxicity of NK cells isolated from EMS nude mice and subsequent protective role of miR-20a against EMS-induced endometrial injury. Conclusion: The aforementioned data suggest that miR-20a potentiates the cytotoxicity of NK via up-regulating perforin mediated by ERG/HLX/STAT4, highlighting potential novel mechanisms associated with EMS progression.
Preoperative predictive factor analysis of ovarian malignant involvement in premenopausal patients with clinical stage I endometrioid endometrial carcinoma
Authors: Chen Qin , Feng Yan , Wang Wenwen , Lv Weiguo , Li Baohua 
Published: November 2019

Abstract
Background Earlier literature suggests that ovarian preservation in young premenopausal clinical stage I endometrioid endometrial carcinoma patients does not negatively impact prognosis and is a more suitable choice for management of the disease. The main purpose of this study was to clarify the incidence of ovarian malignant involvement in premenopausal clinical stage I endometrioid endometrial carcinoma and further identify potential preoperative predictive factors of ovarian malignant involvement.Methods Premenopausal patients (≤50 years) with clinical stage I endometrioid endometrial carcinoma subjected to total hysterectomy and bilateral salpingo-oophorectomy with or without pelvic and/or para-aortic lymph node dissection at Women’s Hospital, Zhejiang University School of Medicine between 2002 and 2016 were enrolled for study. Patients were excluded in cases of gross extra pelvic disease on examination or imaging and family history of colon or gastrointestinal carcinoma. The included patient population was examined for incidence of ovarian malignant involvement and potential preoperative clinical predictive factors.Results A total of 511 premenopausal (age≤50 years) patients diagnosed with clinical stage I endometrioid endometrial carcinoma were included for the study. Ovarian malignant involvements were detected in 23 of the patients (4.5%). Kaplan-Meier analysis showed poorer prognoses of patients with ovarian malignant involvement than those without ovarian involvement. Univariate logistic analysis revealed significant association of preoperative imaging of myometrial invasion depth and serum CA125 with prediction of ovarian malignant involvement in patients. Multivariate logistic analysis further validated preoperative imaging of myometrial invasion depth and serum CA125 as independent risk predictors of postoperative ovarian malignant involvement. Receiver operating characteristic (ROC) curves were individually generated for preoperative myometrial invasion depth and serum CA125 as well as a combination of the two factors. The area under the curve (AUC) was 0.772 (95% confidence interval [CI], 0.661–0.884) for combined preoperative myometrial invasion depth and serum CA125.Conclusions The incidence of ovarian malignant involvement in premenopausal patients with clinical stage I endometrioid endometrial carcinoma was relatively minimal. Preoperative imaging of myometrial invasion depth and serum CA125 were independent risk predictors of ovarian malignant involvement. These findings may facilitate preoperative counseling of patients and informed clinical decision-making on ovarian preservation in these patients.
The Clinical Characteristics and Prognosis of Chinese Patients With Primary Light-Chain Amyloidosis: A Retrospective Multicenter Analysis
Authors: He Donghua , Guan Fangshu , Hu Minli , Zheng Gaofeng , Hong Pan , Wang Gang , He Jingsong , Han Xiaoyan , Wu Wenjun , Zhao Yi , Yang Yang , Cai Zhen 
Published: November 2019

Abstract
Objective To retrospectively identify the critical characteristics and prognostic factors of primary light-chain amyloidosis. Patients and Methods: Data were collected and compared from 91 patients who were diagnosed with primary light-chain amyloidosis at four hospitals between January 2010 and November 2018. We analyzed the clinical characteristics and performed an overall survival (OS) analysis. Results: Patients (median age, 60 years) were diagnosed with organ involvement of the kidney (91.2%), heart (56%), liver (14.3%), soft tissue (18.7%), or gastrointestinal tract (15.4%), and 68.1% of patients had more than two organs involved. Patients were most commonly treated with bortezomib-based regimens (56%), and only one patient had autologous stem cell transplantation (auto-ASCT). The median OS was 36.33 months and was affected by the ECOG score, renal involvement, cardiac involvement, hepatic involvement and negative immunofixation in the serum and urine after treatment. Multivariate analysis indicated that cardiac involvement and negative immunofixation in the serum and urine after treatment were independent prognostic factors for OS. Conclusion: Cardiac involvement and the hematologic response to treatment were independent prognostic factors for OS in primary light-chain amyloidosis patients. The type and number of organs involved is more important than the number of organs involved for the OS.
Albumin to alkaline phosphatase ratio: does it predict survival in grade 1 and grade 2 neuroendocrine tumors?
Authors: Acikgoz Yusuf , Bal Öznur , Doğan Mutlu 
Published: November 2019

Abstract
BACKGROUND: Neuroendocrine tumors (NETs) are very heterogeneous tumors. Although it is classified according to Ki-67 proliferation index and mitotic count, their behavior may greatly vary even in the same group. Therefore, more accurate prognostic markers are required to predict prognosis in patients with well differentiated NETs. This study is aimed to evaluate prognostic value of albumin to alkaline phosphatase ratio (AAPR) in patients with well differentiated neuroendocrine tumors. PATIENTS AND METHODS: A total of 110 patients included in this study. Patients' data were obtained from registration data-base of the hospital and reviewed retrospectively. AAPR was calculated by dividing albumin concentration (g/dl) to alkaline phosphatase level (U/L). Cut off value for AAPR was determined by Receiver Operating Characteristic (ROC) analysis. Survival analysis was performed by Kaplan-Meier method with the Long-rank test. We reported two-sided p value and p<0.05 was considered statistically significant.RESULT: The calculated optimum cut-off value for AAPR was 0.028. Patients were divided into two groups as patients with AAPR ≤0.028 (n:22, 20%) and, with AAPR >0.028 (n:88, 80%). Patients with AAPR >0.028 had statistically longer overall survival (OS) compared with patients with ≤0.028 ( NR vs 96,8 months, p=0.001). Additionally, AAPR has been shown to be an independent prognostic factor for OS in in multivariate analysis (HR=4.942, 95% CI=1.693-14.420, p=0.003).CONCLUSION: Patients with higher AAPR had more favourable prognosis compared to patients with lower AAPR. We demonstrated that AAPR can be of prognostic value in well-differentiated NETs.
Meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.
Authors: Tanaka Kazuhiro , Kawano Masanori , Iwasaki Tatsuya , Itonaga Ichiro , Tsumura Hiroshi 
Published: November 2019

Abstract
Background In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the surrogacy of EFS for OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach. Methods We identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated by weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2). Results A total of 3,612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis demonstrated that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929). Conclusions Overall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. Given the rare occurrence of ES and difficulty in conducting large-scale RCTs, EFS may be useful as a surrogate endpoint in RCTs of ES. The surrogacy of EFS is worth verifying using individual data.
Prognostic value of Ki-67 and prediction in patients with hypertension and prostate cancer: A Real-World Study of Chinese Group for Prostate Cancer Party
Authors: Cao Zhijun , Xiang Mengqi , Zhang Zhiyu , Zhang Jianglei , Jiang Minjun , Shen Gang , Zhou Yongqiang , Ouyang Jun , Chen Jianjun 
Published: November 2019

Abstract
Purpose Prostate cancer is the second most common malignancy with high mortality among males around the world, especially combine with hypertension. Ki-67 is one of the most reliable markers for growth fraction of neoplastic human cell populations. However, the prognostic value and prediction of Ki-67 in patients with hypertension and prostate cancer remain unclear. Materials and methods We launched a retrospective analysis of 296 patients with hypertension and prostate cancer from May 1, 2012, to Oct 1, 2015. The overall survival was evaluated using Cox regression models and Kaplan-Meier analysis. A nomogram was established. The accuracy of the model was assessed by calibration curve. Results Multivariate analysis showed that the Ki-67 (+) class was associated with an over 5-fold increase in the risk of death (HR 5.83, 95% CI 3.35-10.14, p<0.001) and a 2-fold increase in the risk of progression (HR 2.06, 95% CI 1.37-3.10, p<0.001). Multivariate Lasso regression showed that smoking, heart failure, ACS, Ki-67 expression, serum albumin, prognostic nutritional index, surgery, Gealson score, and stage were positively associated with prognosis in patients with prostate cancer. To quantify the contribution of each covariate to the prognosis, a nomogram of the Cox model was generated and displayed. The nomogram demonstrated excellent accuracy in estimating the risk of death, with a bootstrap-corrected C index of 0.829. There was also a suitable calibration curve for risk estimation.Conclusions Ki-67(+) predicts worsened outcomes of OM. A cross-validated multivariate score, including Ki-67(+), showed excellent concordance and efficacy of predicting prostate cancer.
Candidate methylation sites associated with endocrine therapy resistance in the TCGA ER+/HER2- breast cancer cohort
Authors: Soleimani Maryam , Borgoni Simone , Sofyalı Emre , Verschure Pernette J. , Wiemann Stefan , Moerland Perry , Kampen Antoine H.C. van 
Published: November 2019

Abstract
Background: Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, about 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of the mechanisms through which therapy resistance develops. Therefore, we aimed to identify methylation loci associated with endocrine therapy resistance. Methods: We used genome-wide DNA methylation profiles of primary ER+ tumors from The Cancer Genome Atlas in combination with curated data on survival and treatment to predict development of endocrine resistance. Association of individual DNA methylation markers with survival was assessed using Cox proportional hazards models in a cohort of ER+/HER2- tumours (N=552) and two sub-cohorts corresponding to the endocrine treatment (AIs or TAM) that patients received (N=210 and N=172, respectively). Models were adjusted for clinical variables tumour stage, age, and AI treatment. We also identified signatures of multiple methylation loci associated with survival using Cox proportional hazards models with elastic net regularization. Individual markers and multivariable signatures were compared with DNA methylation profiles generated in a time course experiment using the T47D ER+ breast cancer cell line treated with tamoxifen or deprived from estrogen. Results: We identified 132, 9 and 1 CpGs for which DNA methylation is significantly associated with survival in the ER+/HER2-, TAM and AI cohorts respectively. Corresponding multi-locus signatures consisted of 171, 50 and 160 CpGs and showed a large overlap with the corresponding single-locus signatures. The methylation signatures were associated with survival independently of luminal status. Single-locus signatures for the ER+/HER2- and TAM cohorts were conserved among the loci that were differentially methylated in endocrine-resistant T47D cells. Similarly, multi-locus signatures for the ER+/HER2- and AI cohorts were conserved in endocrine-resistant T47D cells. Conclusions: We identified individual and multivariable DNA methylation markers associated with therapy resistance independently of luminal status. Our results suggest that these markers identified from primary tumours and prior to any endocrine treatment are associated with development of endocrine resistance.
Enhanced antitumor efficacy on colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perﬂuorocarbon
Authors: Wu Pingping , Zhou Qing , Zhu Huayun , Zhuang Yan , Bao Jun 
Published: November 2019

Abstract
Recurrence and metastasis are the shortcomings of the clinical treatment of colon cancer. Finding an efficacy strategy for the treatment of colon cancer is important. In recent years, PLGA has been shown to have potential as a broad therapeutic drug delivery system. this study aimed to design a dual-loaded nanoparticles drug delivery system to overcome the limitations of chemotherapeutic drugs in colon cancer therapy. We developed epidermal growth factor (EGF) functionalized poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perﬂuorocarbon (PFC) (EGF-PLGA@5Fu/PFC) for target therapy of colon cancer. EGF-PLGA@5Fu /PFC NPs were estimated to have an average size of 200 nm with a 5Fu-loading efficiency of 7.29%. In vitro release profile exhibited a pH-responsive release. CCK-8, Hoechst33342 staining and flow cytometry assays were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Targeted EGF-PLGA@5Fu/PFC NPs also exhibited higher cellular uptake than non-targeted NPs in colon cancer cells. EGF-PLGA@5Fu/PFC NPs were found to have the best efficiency on cell viability suppression and apoptosis induction in SW620 cells. In xenograft mice, EGF-PLGA@5Fu/PFC NPs had the best suppressive effects on tumor growth compared with 5Fu, PLGA@5Fu and PLGA@5Fu/PFC NPs. The results of histopathological analysis further indicated that EGF-targeted NPs were the most efficient on tumor growth inhibition. Mechanically, the data demonstrated the improved therapeutic outcomes were owing to the fact that PFC could relieve tumor hypoxia via transporting oxygen to the tumor. We creatively constructed a biocompatible nanodrug delivery system and functionalized nanoparticles may provide new potential for selective delivery of chemotherapy drugs to cancers.
Immunohistochemical Expression of Vitamin D Receptor and Forkhead Box P3 in Classic Hodgkin Lymphoma: Correlation with Clinical and Pathologic Findings
Authors: Gupta Gaurav , Agrawal Tanupriya , Pilichowska Monika 
Published: November 2019

Abstract
Expression of forkhead box P3 (FOXP3), a key regulator of T-cell function, in the tumor immune microenvironment is related to survival in classic Hodgkin lymphoma (CHL). Vitamin D receptor (VDR), a transcription factor, agonists have been shown to induce FOXP3 expression in T-cells and enhance recruitment of these cells to the inflammatory sites. VDR expression is CHL is described. However, there is no data on expression of VDR in context of quantity of FOXP3 expressing cells in CHL. We examined and correlated immunohistochemical expression of VDR and FOXP3 with clinical and pathology findings in 29 cases of CHL. VDR was expressed in Hodgkin Reed-Sternberg (HRS) cells and background lymphocytes and FOXP3 was expressed in background lymphocytes. 82% of CHL cases, regardless of the subtype, expressed VDR and in majority of the cases, VDR expression was directly proportional to the quantity of FOXP3 expressing lymphocytes in the tumor microenvironment. In cases with higher clinical stage (III/IV), only 28.5% of cases diffusely expressed VDR and FOXP3 compared to 71.4% showing focal positivity. Whereas in cases with lower clinical stages (I/II), the expression pattern of VDR and FOXP3 was almost similar (41.6% diffuse versus 33.3% focal). Interestingly, focal VDR and FOXP3 expression pattern was significantly higher among males. Mixed cellularity cases showed predilection for focal VDR and FOXP3 expression (80% cases); whereas nodular sclerosis subtype had focal and diffuse VDR and FOXP3 expression patterns in similar proportion. Cases with diffuse VDR and FOXP3 expression were less likely to have bone marrow involvement. Epstein Barr virus- encoded small RNA (EBER) positive cases were predominantly focally positive (80%) for VDR and FOXP3. In summary, quantity of FOXP3 positive T-cells in CHL microenvironment seems to correlate with VDR expression. Clinical stage show a trend of inverse correlation with expression of VDR and quantity of FOXP3 positive T-cells. These findings suggest that VDR could be a possible prognostic and therapeutic target in CHL.
Comparison of the touch-screen and traditional versions of the Corsi block-tapping test in patients with psychosis and healthy controls.
Authors: Siddi Sara , Preti Antonio , Lara Elvira , Brébion Gildas , Vila Regina , Iglesias Maria , Cuevas-Esteban Jorge , López-Carrilero Regina , Butjosa Anna , Haro Josep Maria 
Published: November 2019

Abstract
Working memory (WM) refers to the capacity system for temporary storage and processing of information, which is known to depend on the integrity of the prefrontal cortex. Impairment in working memory is a core cognitive deficit among individuals with psychotic disorders. The Corsi block-tapping test is a widely used instrument to assess visuospatial working memory. The traditional version is composed of 9 square blocks positioned on a physical board. In recent years, the number of digital instruments has increased significantly; several advantages might derive from the use of a digital version of the Corsi test.
This study aimed to compare the digital and traditional versions of the Corsi test in 45 patients with psychotic disorders and 45 healthy controls. Both groups completed a neuropsychological assessment involving attention and working memory divided into two conditions. Results were consistent between the traditional and digital versions of the Corsi test. Overall, patients performed worse relative to the healthy comparison group. The traditional Corsi test was positively related to intelligence and verbal working memory, probably due to a more significant effort to execute the test. The digital version is able to discriminate between patients with psychosis and healthy controls. It would be of use in determining who is at risk of developing a psychotic disorder, and in those already with psychosis, it might provide a prognostic marker for future functional outcome. Further, it is easy to administer while ensuring a standard procedure.