bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based Apoptosis Regulator Nrh/BCL2L10
Authors: Nougarede Adrien , Popgeorgiev Nikolay , Kassem Loay , Omarjee Soleilmane , Borel Stephane , Mikaelian Ivan , Lopez Jonathan , Gadet Rudy , Marcillat Olivier , Treilleux Isabelle , Villoutreix Bruno O. , Rimokh Ruth , Gillet Germain 
Published: January 2018

Abstract
Drug resistance and metastatic relapse remain a top challenge in breast cancer treatment. In this study, we present preclinical evidence for a strategy to eradicate advanced breast cancers by targeting the BCL-2 homolog Nrh/BCL2L10, which we discovered to be overexpressed in &gt;45% of a large cohort of breast invasive carcinomas. Nrh expression in these tumors correlated with reduced metastasis-free survival, and we determined it to be an independent marker of poor prognosis. Nrh protein localized to the endoplasmic reticulum. Mechanistic investigations showed that Nrh made BH4 domain–dependent interactions with the ligand-binding domain of the inositol-1,4,5-triphosphate receptor (IP3R), a type 1/3 Ca2+ channel, allowing Nrh to negatively regulate ER-Ca2+ release and to mediate antiapoptosis. Notably, disrupting Nrh/IP3R complexes by BH4 mimetic peptides was sufficient to inhibit the growth of breast cancer cells in vitro and in vivo. Taken together, our results highlighted Nrh as a novel prognostic marker and a candidate therapeutic target for late stage breast cancers that may be addicted to Nrh.
Significance: These findings offer a comprehensive molecular model for the activity of Nrh/BCL2L10, a little studied antiapoptotic molecule, prognostic marker, and candidate drug target in breast cancer. Cancer Res; 78(6); 1404–17. ©2018 AACR.
Demethylation-Induced Overexpression of Shc3 Drives c-Raf–Independent Activation of MEK/ERK in HCC
Authors: Liu Yun , Zhang Xinran , Yang Baicai , Zhuang Hao , Guo Hua , Wei Wen , Li Yuan , Chen Ruibing , Li Yongmei , Zhang Ning 
Published: January 2018

Abstract
Invasion and intrahepatic metastasis are major factors of poor prognosis in patients with hepatocellular carcinoma (HCC). In this study, we show that increased Src homolog and collagen homolog 3 (Shc3) expression in malignant HCC cell lines associate with HCC invasion and metastasis. Shc3 (N-Shc) was significantly upregulated in tumors of 33 HCC patient samples as compared with adjacent normal tissues. Further analysis of 52 HCC patient samples showed that Shc3 expression correlated with microvascular invasion, cancer staging, and poor prognosis. Shc3 interacted with major vault protein, resulting in activation of MEK1/2 and ERK1/2 independently of Shc1 and c-Raf; this interaction consequently induced epithelial–mesenchymal transition and promoted HCC cell proliferation and metastasis. The observed increase in Shc3 levels was due to demethylation of its upstream promoter, which allowed c-Jun binding. In turn, Shc3 expression promoted c-Jun phosphorylation in a positive feedback loop. Analysis of metastasis using a tumor xenograft mouse model further confirmed the role of Shc3 in vivo. Taken together, our results indicate the importance of Shc3 in HCC progression and identify Shc3 as a novel biomarker and potential therapeutic target in HCC.
Significance: Ectopic expression of Shc3 forms a complex with MVP/MEK/ERK to potentiate ERK activation and plays an important role in sorafinib resistance in HCC. Cancer Res; 78(9); 2219–32. ©2018 AACR.
Clinical Utility of a STAT3-Regulated miRNA-200 Family Signature with Prognostic Potential in Early Gastric Cancer
Authors: Yu Liang , Wu Di , Gao Hugh , Balic Jesse J. , Tsykin Anna , Han Tae-Su , Liu You Dong , Kennedy Catherine L. , Li Ji Kun , Mao Jie Qi , Tan Patrick , Oshima Masanobu , Goodall Gregory J. , Jenkins Brendan J. 
Published: January 2018

Abstract
Purpose: The majority of gastric cancer patients are diagnosed with late-stage disease, for which distinct molecular subtypes have been identified that are potentially amenable to targeted therapies. However, there exists no molecular classification system with prognostic power for early-stage gastric cancer (EGC) because the molecular events promoting gastric cancer initiation remain ill-defined.
Experimental Design: miRNA microarrays were performed on gastric tissue from the gp130F/F preclinical EGC mouse model, prior to tumor initiation. Computation prediction algorithms were performed on multiple data sets and independent gastric cancer patient cohorts. Quantitative real-time PCR expression profiling was undertaken in gp130F/F-based mouse strains and human gastric cancer cells genetically engineered for suppressed activation of the oncogenic latent transcription factor STAT3. Human gastric cancer cells with modulated expression of the miR-200 family member miR-429 were also assessed for their proliferative response.
Results: Increased expression of miR-200 family members is associated with both tumor initiation in a STAT3-dependent manner in gp130F/F mice and EGC (i.e., stage IA) in patient cohorts. Overexpression of miR-429 also elicited contrasting pro- and antiproliferative responses in human gastric cancer cells depending on their cellular histologic subtype. We also identified a miR-200 family–regulated 15-gene signature that integrates multiple key current indicators of EGC, namely tumor invasion depth, differentiation, histology, and stage, and provides superior predictive power for overall survival compared with each EGC indicator alone.
Conclusions: Collectively, our discovery of a STAT3-regulated, miR-200 family–associated gene signature specific for EGC, with predictive power, provides a molecular rationale to classify and stratify EGC patients for endoscopic treatment. Clin Cancer Res; 24(6); 1459–72. ©2018 AACR.
Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease
Authors: Arya Shipra , Khakharia Anjali , Binney Zachary O. , DeMartino Randall R. , Brewster Luke P. , Goodney Philip P. , Wilson Peter W.F. 
Published: January 2018

Background:
Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality.

Methods:
Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003–2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate–intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score–matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding.

Results:

In 155 647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy–only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy–only users (hazard ratio, 0.67; 95% confidence interval, 0.61–0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70–0.77, respectively). Low-to-moderate–intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75– 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81–0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins (
P
<0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score–matched, sensitivity, and subgroup analyses.

Conclusions:
Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate–intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.
Maternal knowledge of pertussis and Tdap vaccine and the use of a vaccine information statement
Authors: Payakachat Nalin , Hadden Kristie B , Hanner Jeremy , Ragland Denise 
Published: January 2018

Objective: This study explored maternal knowledge of pertussis and Tdap vaccine and the use of a Tdap Vaccine Information Statement (VIS) to improve that knowledge. Design: Prospective cohort study. Setting: Two outpatient obstetric clinics at a US academic medical centre. Methods: An electronic survey was administered to pregnant women who received care at the clinics. The survey included a test of knowledge of pertussis and Tdap vaccine, a health literacy instrument and demographic questions. A chart review was conducted to determine Tdap vaccination status. The knowledge test was administered before and immediately after participants read the VIS. Differences between pre- and post-knowledge test scores were determined using the Wilcoxon signed-rank test. The effects of two different versions of the VIS on participants’ knowledge gained and associated factors were examined using a repeated-measures mixed model with random effects. Results: In total, 279 participants were analysed with an average age of 26.4 ± 5.7 years. The average post-test knowledge score was higher than the pre-test score (6.4 vs 4.2, p < .001). Health literacy score ( p < .001), White race/ethnicity ( p = .007) and higher education level ( p < .001) were positively associated with improved knowledge scores. Both VIS versions improved participants’ knowledge scores to a similar degree. However, knowledge scores were not a predictor of Tdap vaccination in our population. Conclusion: A Tdap VIS improved maternal knowledge and is an economical and easily accessible educational tool in clinical practice for promoting Tdap vaccine to pregnant women.
Civil Citation
Authors: Nadel Melissa R. , Pesta George , Blomberg Thomas , Bales William D. , Greenwald Mark 
Published: January 2018

Objectives: The primary objective of this study is to assess potential variation across Florida’s counties of their implementation of civil citation and the outcomes associated with that implementation. Methods: Interrupted time-series analysis is used to determine whether the trends in juvenile arrests and the total delinquent population referred to the juvenile justice system (either through arrests or through civil citation) were significantly affected by the implementation of civil citation in each county. Results: There were immediate and gradual diversion effects of the civil citation program in a number of Florida’s counties. As a result, there is evidence of successful implementation with a few cases of net widening. Conclusions: While there was variation between counties in their implementation of civil citation, overall, Florida’s civil citation program was found to provide a diversion from arrest rather than a net-widening outcome. The study concludes with the identification of county-specific factors that characterized the local jurisdictions that were able to successfully overcome the major impediments associated with diversion and other reform programs’ implementation fidelity.
Measuring attitudes towards the dying process: A systematic review of tools
Authors: Groebe Bernadette , Strupp Julia , Eisenmann Yvonne , Schmidt Holger , Schlomann Anna , Rietz Christian , Voltz Raymond 
Published: January 2018

Background: At the end of life, anxious attitudes concerning the dying process are common in patients in Palliative Care. Measurement tools can identify vulnerabilities, resources and the need for subsequent treatment to relieve suffering and support well-being. Aim: To systematically review available tools measuring attitudes towards dying, their operationalization, the method of measurement and the methodological quality including generalizability to different contexts. Design: Systematic review according to the PRISMA Statement. Methodological quality of tools assessed by standardized review criteria. Data sources: MEDLINE, PsycINFO, PsyndexTests and the Health and Psychosocial Instruments were searched from their inception to April 2017. Results: A total of 94 identified studies reported the development and/or validation of 44 tools. Of these, 37 were questionnaires and 7 alternative measurement methods (e.g. projective measures). In 34 of 37 questionnaires, the emotional evaluation (e.g. anxiety) towards dying is measured. Dying is operationalized in general items ( n = 20), in several specific aspects of dying ( n = 34) and as dying of others ( n = 14). Methodological quality of tools was reported inconsistently. Nine tools reported good internal consistency. Of 37 tools, 4 were validated in a clinical sample (e.g. terminal cancer; Huntington disease), indicating questionable generalizability to clinical contexts for most tools. Conclusion: Many tools exist to measure attitudes towards the dying process using different endpoints. This overview can serve as decision framework on which tool to apply in which contexts. For clinical application, only few tools were available. Further validation of existing tools and potential alternative methods in various populations is needed.
Evaluation of an iterative model-based CT reconstruction algorithm by intra-patient comparison of standard and ultra-low-dose examinations
Authors: Noël Peter B , Engels Stephan , Köhler Thomas , Muenzel Daniela , Franz Daniela , Rasper Michael , Rummeny Ernst J , Dobritz Martin , Fingerle Alexander A 
Published: January 2018

Background The explosive growth of computer tomography (CT) has led to a growing public health concern about patient and population radiation dose. A recently introduced technique for dose reduction, which can be combined with tube-current modulation, over-beam reduction, and organ-specific dose reduction, is iterative reconstruction (IR). Purpose To evaluate the quality, at different radiation dose levels, of three reconstruction algorithms for diagnostics of patients with proven liver metastases under tumor follow-up. Material and Methods A total of 40 thorax–abdomen–pelvis CT examinations acquired from 20 patients in a tumor follow-up were included. All patients were imaged using the standard-dose and a specific low-dose CT protocol. Reconstructed slices were generated by using three different reconstruction algorithms: a classical filtered back projection (FBP); a first-generation iterative noise-reduction algorithm (iDose4); and a next generation model-based IR algorithm (IMR). Results The overall detection of liver lesions tended to be higher with the IMR algorithm than with FBP or iDose4. The IMR dataset at standard dose yielded the highest overall detectability, while the low-dose FBP dataset showed the lowest detectability. For the low-dose protocols, a significantly improved detectability of the liver lesion can be reported compared to FBP or iDose4 ( P = 0.01). The radiation dose decreased by an approximate factor of 5 between the standard-dose and the low-dose protocol. Conclusion The latest generation of IR algorithms significantly improved the diagnostic image quality and provided virtually noise-free images for ultra-low-dose CT imaging.
CKD Patients and Erythropoietin: Do We Need Evidence-Based Informed Consent?
Authors: Mezza E. , Consiglio V. , Soragna G. , Putaggio S. , Burdese M. , Perrotta L. , Jeantet A. , Segoloni G.P. , Piccoli G.B. 
Published: January 2018

Background Consent to therapy is increasingly requested in the form of “informed consent”. Objective To validate an evidence-based informed consent form for erythropoietin (EPO) therapy and to evaluate patient opinions about the informed consent approach. Methods An evidence-based informed consent form was developed as part of the Evidence-Based-Medicine course at the Medical School of Turin, Italy. It was validated by anonymous questionnaires (0–10 analogical scales and open answers) administered to patients at different stages of CKD (19 pre-ESRD, 26 hemodialysis, 12 transplant patients) attending an outpatient unit of the University of Turin, to 8 nurses, and to 26 medical students. Results All individuals filled in the questionnaire. Interest in a detailed explanation of the therapy was high (median 9), as was comprehension (median 9), with no differences between patients with regard to disease stage (pre-ESRD vs. RRT) or educational level. Prior knowledge of the therapy was affected by the educational level (p=0.013 for the advantages and p=0.004 for the side effects) and the professional role (patients vs caregivers: p=0.009 for the advantages and p<0.001 for side affects); patient knowledge of the advantages (median 6) tended to increase as the disease progressed (p=0.015). The most common response by patients was that informed consent was necessary for all drugs (35.1%); 73.1% of the caregivers considered it necessary only for severe side effects. The preferred modality of consent was discussion with the caregiver during the clinical controls (42% of all cases). Conclusions Patient interest in and comprehension of an informed consent form with a detailed explanation of the therapy was high; the caregiver's opinion was still the most valued teaching tool.
Rheological Characterization of an Artificial Synovial Fluid
Authors: Casentini G. , Di Paola L. , Marrelli L. , Palma F. 
Published: January 2018

Rheological measurements on two classes of artificial synovial fluids have been carried out in the attempt to get a suitable but cheap lubricant for wear tests of prosthetic materials. Fluids of both classes are solutions of hyaluronic acid (HA) that, for one class, is dissolved into a simple Ringer solution whereas, for the other class, into a mixture of human serum and Ringer solution. Similar rheological properties have been observed for both classes of fluids. Experimental results have been interpreted by two classical models that are commonly used in the literature to describe the rheological behavior of colloidal systems and of polymer solutions with high entanglement density, respectively. The quality of correlations shows that, at high HA concentrations, entagled structures are largely present and cannot be neglected.
Determination of VIT 45 (IND#63,243 - American Regent) Removal by Closed Loop in Vitro Hemodialysis System
Authors: Manley H.J. , McClaran M.L. 
Published: January 2018

Background Intravenous iron is typically administered during the hemodialysis (HD) procedure. The extent of VIT 45, a novel intravenous iron formulation, removal by high-flux (HF) or high-efficiency (HE) dialysis membranes at various ultrafiltration rates (UFR) is unknown. Methods An in vitro HD system was constructed to determine the dialyzabiltiy of iron from a normal saline compartment (NSC) containing 1000 mg iron of VIT 45. The in vitro system utilized a 6-L closed-loop SBS system that was subject to 4 different HD conditions conducted over 4 hours: HE membrane + 0 ml/h UFR; HE membrane + 500 ml/h UFR; HF membrane + 0 ml/h UFR; HF membrane + 500 ml/h UFR. Blood flow and dialysate flow rates were 500 ml/min and 800 ml/min, respectively. The dialysate compartment was a 6-L closed-loop system. A volumetric HD machine controlled all blood, dialysate, and ultrafiltration rates. NSC and dialysate compartment samples were taken at various time points and iron elimination rate (khd) and HD clearance (Clhd) was determined. Iron removal from the NSC > 15% was considered clinically significant. Results The percent removal of iron from the NSC was < 0.5% at all time points in the study. Dialysate recovery of iron was negligible: 1.7–5.1 mg. VIT 45 removal elimination rates from NSC were less than -0.001 h −1 (range -0.0002 ± 0.0001 to -0.0001 ± 0.0002 h −1) for all study conditions. Dialyzer type or UFR did not effect iron removal. Conclusion HF or HE dialysis membranes do not remove clinically significant amounts of VIT 45 over a 4-hour in vitro HD session. This effect remained constant even controlling for UFR up to 500 ml/hour. VIT 45 is not dialyzed by HE or HF dialysis membranes irrespective of UFR. (Int J Artif Organs 2006; 29: 1062–6)
Inadequacy of Dialysis, Chronic Inflammation and Malnutrition in Nigerian Patients on Chronic Hemodialysis
Authors: Tzamaloukas A.H. , Vanderjagt D.J. , Agaba E.I. , Ma I. , Lopez A. , Tzamaloukas R.A. , Murata G.H. , Glew R.H. 
Published: January 2018

Purpose To identify the extent of underdialysis, chronic inflammation and malnutrition and their interrelationships in Nigerian hemodialysis patients. Methods In a prospective study including 10 adult patients, (6 men, 4 women) on hemodialysis in North Central Nigeria, malnutrition was assessed by body mass index (BMI), serum albumin and prealbumin, and bioimpedance (BIA) pre-and post dialysis, inflammation was evaluated by C-reactive protein (CRP) and adequacy of dialysis was judged by frequency of the hemodialysis sessions and Kt/V urea. Results Post-dialysis BMI was 21.3 (19.9, 24.3) kg/m2 (< 20 kg/m2 in 4 patients), serum albumin 31.5 (24.0, 32.0) g/L (< 30.0 g/L in 5), serum pre-albumin 25.2 (15.3, 31.1) mg/dL (< 18.0 mg/dL in 4), serum CRP 4.8 (1.2, 11.5) mg/dL (> 1.0 mg/dL in 8), phase angle 4.2 (3.7, 5.1)° (< 3° in 3) and body fat deficit was diagnosed by BIA in 4 patients. Weekly frequency of dialysis was 3 times in 2 patients, twice in 1 and ≤1 time in 7. Single-pool Kt/V urea was 0.81 (0.68, 0.95, <1.2 in 9 patients and > 1.2 in one patient receiving dialysis only twice weekly). By combined frequency of dialysis and Kt/V urea values, no patient received an adequate dose of dialysis and, indeed, all patients had overt symptoms of uremia. Low body weight, low serological and BIA nutrition indices, and high CRP levels occurred in the same patients. Patients on dialysis for > 1 year had worse nutrition indices than those on dialysis for < 1 year. Conclusions Underdialysis was universal, while poor nutrition and chronic malnutrition were found in the majority of the small number of patients studied. These three adverse conditions, which were interlinked, may be common in Nigerian hemodialysis patients, because their underlying socioeconomic causes are widespread. (Int J Artif Organs 2006; 29: 1067–73)