bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing doctors’ competencies using multisource feedback: validating a Japanese version of the Sheffield Peer Review Assessment Tool (SPRAT)
Authors: Sasaki Hatoko , Archer Julian , Yonemoto Naohiro , Mori Rintaro , Nishida Toshihiko , Kusuda Satoshi , Nakayama Takeo 
Published: June 2015

ObjectiveTo assess the validity and reliability of the Sheffield Peer Review Assessment Tool (SPRAT) Japanese version for evaluating doctors’ competencies using multisource feedback.MethodsSPRAT, originally developed in the UK, was translated and validated in three phases: (1) an existing Japanese version of SPRAT was back-translated into English; (2) two expert panel meetings were held to develop and assure content validity in a Japanese setting; (3) the newly devised Japanese SPRAT instrument was tested by a multisource feedback survey, validity was tested using principal component factor analysis, and reliability was assessed using generalisability and decision studies based on generalisability theory.Results86 doctors who had been practising for between 2 and 33 years participated as assessees and were evaluated with the SPRAT tool. First, the doctors identified 1019 potential assessors who were each sent SPRAT forms (response rate, 81%). The mean number of assessors per doctor was 9.7 (SD=2.5). The decision study showed that 95% CIs of ±0.5 were achieved with only 5 assessors. 85 of the 86 doctors achieved scores that could be placed with 95% CI above the 4 expected standard. Doctors received lower scores from more senior assessors (p<0.001) and higher scores from those they had known longer (p<0.001). Scores also varied with the job role (p<0.05).ConclusionsFollowing translation and content validation, the Japanese instrument behaved similarly to the UK tool. Assessor selection remains a primary concern, as the assessment scores are affected by the seniority of the assessor, the length of the assessor–assessee working relationship, and the assessor's job role. Users of the SPRAT tool need to be aware of these limitations when administering the instrument.
Association between androgen receptor expression, Ki-67 and the 21-gene recurrence score in non-metastatic, lymph node-negative, estrogen receptor-positive and HER2-negative breast cancer
Authors: Vera-Badillo Francisco E , Chang Martin C , Kuruzar Gordana , Ocana Alberto , Templeton Arnoud J , Seruga Bostjan , Goldstein Robyn , Bedard Philippe L , Tannock Ian F , Amir Eitan 
Published: June 2015

BackgroundThe mechanisms underlying the favourable prognosis of androgen receptor (AR) expression in breast cancer are unknown.MethodsThe associations between the 21-gene recurrence score (RS), AR, grade, mitotic score, Ki-67 and estrogen receptor (ER) and progesterone receptor (PgR) expression were explored in sequential women with lymph node-negative, ER-positive and HER2-negative breast cancer. Statistical significance of this exploratory study was defined as p<0.10.ResultsAnalysis comprised 70 women. Most tumours had high AR expression (97% had scores >3). Median RS was 15 (range 1–53). AR expression showed a minimally significant positive correlation with ER (R=0.37), but no correlation with Ki-67 (R=−0.18). In univariable analysis, AR (p=0.01), ER (p<0.001) and PgR (p<0.001) had significant negative associations with RS. Ki-67 (p=0.16), grade (p=0.40) and mitotic score (p=0.23) showed no association with RS. Multivariable analysis showed similar associations.ConclusionsAR is associated with lower RS, but not with Ki-67.
The value of protective head cap and glasses in neurointerventional radiology
Authors: Sans Merce Marta , Korchi Amine M , Kobzeva Lisa , Damet Jérôme , Erceg Gorislav , Marcos Gonzalez Ana , Lovblad Karl-Olof , Mendes Pereira Vitor 
Published: June 2015

BackgroundProtection of the head and eyes of the neurointerventional radiologist is a growing concern, especially after recent reports on the incidence of brain cancer among these personnel, and the revision of dose limits to the eye lens. The goal of this study was to determine typical occupational dose levels and to evaluate the efficiency of non-routine radiation protective gear (protective eyewear and cap). Experimental correlations between the dosimetric records of each measurement point and kerma area product (KAP), and between whole body doses and eye lens doses were investigated.MethodsMeasurements were taken using thermoluminescent dosimeters placed in plastic bags and worn by the staff at different places. To evaluate the effective dose, whole body dosimeters (over and under the lead apron) were used.ResultsThe mean annual effective dose was estimated at 0.4 mSv. Annual eye lens exposure was estimated at 17 mSv when using a ceiling shield but without protective glasses. The protective glasses reduced the eye lens dose by a factor of 2.73. The mean annual dose to the brain was 12 mSv; no major reduction was observed when using the cap. The higher correlation coefficients with KAP were found for the dosimeters positioned between the eyes (R2=0.84) and above the apron, and between the eye lens (R2=0.85) and the whole body.ConclusionsUnder the specific conditions of this study, the limits currently applicable were respected. If a new eye lens dose limit is introduced, our results indicate it could be difficult to comply with, without introducing additional protective eyewear.
Arteriovenous malformation embocure score: AVMES
Authors: Lopes Demetrius K , Moftakhar Roham , Straus David , Munich Stephan A , Chaus Fahad , Kaszuba Megan C 
Published: June 2015

BackgroundCerebral arteriovenous malformations (CAVMs) may be treated with microsurgery, radiosurgery, endovascular surgery, or a combination of these modalities. Grading scales are available to aid the assessment of curative risk for microsurgery and radiosurgery. No grading system has been developed to assess the curative risk of endovascular surgery.ObjectiveTo report our retrospective application of the AVM embocure score to patients treated at our institution between 2005 and 2011MethodsWe performed a retrospective review of 39 patients with CAVM treated at our institution between 2005 and 2011 with the primary aim of achieving a curative embolization. After reviewing all the different variables associated with the conventional Onyx embolization technique for CAVMs, we identified the following as the most relevant characteristics influencing the chances for complete angiographic embolization and complication risk: the number of arterial pedicles and draining veins, size of AVM nidus, and vascular eloquence. We sought to develop a scoring system to assess the complication risk for a curative embolization of CAVM with liquid embolic Onyx (Covidien, Irvine, California, USA). We developed the AVM embocure score (AVMES). This scoring system ranges from 3 to 10 and is the arithmetic sum of the number of arterial pedicles feeding the AVM (≤3, 4–6, >6), the number of draining veins (≤3, 4–6, >6), the size of the AVM nidus in centimeters (≤3, 4–6, >6), and the vascular eloquence (0–1). We applied AVMES to the same cohort of patients and validated the predictability of complete angiographic embolization and expected clinical risk of complication.ResultsIn lesions with an AVMES of 3 (n=8), there was a 100% rate of complete AVM obliteration and 0% rate of major complications. In AVMES 4 (n=12) lesions, there was 75% complete obliteration rate, with 8% major morbidity. In AVMES 5 (n=9) lesions, there was 78% complete obliteration and 11% major morbidity. In AVMES >5 (n=10) there was 20% complete obliteration and 30% major morbidity. Receiver-operator curve analysis showed that this scoring system was robust in its discriminative ability, with an area under the curve (AUC) of 0.8356 for complete obliteration without complication, AUC=0.8240 for complete obliteration regardless of the presence of major morbidity, and AUC=0.7529 for major morbidity.ConclusionsThe AVMES complements existing scoring systems for microsurgery and radiosurgery. It provides a valuable tool for risk assessment during the complex decision-making process in treating AVMs that accounts for angioarchitectural features of particular relevance to endovascular surgeons.
Predictors and risk factors for the intestinal shedding of Escherichia coli O157 among working donkeys (Equus asinus) in Nigeria
Authors: Jedial Jesse T. , Shittu Aminu , Tambuwal Faruk M. , Abubakar Mikail B. , Garba Muhammed K. , Kwaga Jacob P. , Fasina Folorunso O. 
Published: June 2015

ObjectivesEscherichia coli are an important group of bacteria in the normal gastrointestinal system but can sometimes cause infections in domestic animals and man. Donkeys are routinely used as multipurpose animal but details of burdens of potentially infectious bacteria associated with it are limited. The prevalence and associations between intestinal shedding of E. coli O157 and animal characteristics and management factors were studied among 240 randomly selected working donkeys in north‐western Nigeria.DesignFour local government areas, of Sokoto State in north‐western Nigeria were recruited in this study. A multistage randomised cluster design was used to select subjects and donkey owners within selected zones. Confirmation of infection was based on bacterial culture, isolation and biochemical test for E. coli O157 from faecal samples.ResultsOf the total bacteria isolated, 203 of the 329 (61.70 per cent) were E. coli, 76 of which was E. coli serotype O157. A multivariable logistic regression model was used to examine the relation between intestinal shedding of E. coli O157 and selected variables. The analysis yielded five potential predictors of shedding: soft faeces in donkeys, Akaza and Fari ecotypes of donkey were positive predictors while maize straw as feed and sampling during the cold dry period were negative predictors.ConclusionsThis study concludes that controlling intestinal shedding of E. coli O157 among working donkeys in Nigeria is possible using the identified predictors in planning appropriate interventions to reduced human risk of infection.
Keap1–Nrf2 Interaction Suppresses Cell Motility in Lung Adenocarcinomas by Targeting the S100P Protein
Authors: Chien Ming-Hsien , Lee Wei-Jiunn , Hsieh Feng-Koo , Li Chia-Feng , Cheng Tsu-Yao , Wang Ming-Yang , Chen Jin-Shing , Chow Jyh-Ming , Jan Yi-Hua , Hsiao Michael , Hua Kuo-Tai , Kuo Min-Liang 
Published: June 2015

Abstract
Purpose: Kelch-like ECH-associated protein 1 (Keap1) is an E3 ligase participated in the cellular defense response against oxidative stress through nuclear factor erythroid-2–related factor 2 (Nrf2). However, the role of Keap1 in regulating cancer motility is still controversial. We investigated the contribution of the Keap1–Nrf2 axis in the progression of non–small cell lung cancer (NSCLC).
Experimental Design: The expression of Keap1 and Nrf2 was examined via immunohistochemistry, real-time PCR, and Western blot analysis in a cohort of NSCLC tissues and cells. A series of in vivo and in vitro assays was performed to elucidate the contribution of the Keap1–Nrf2 axis in lung cancer mobility and progression.
Results: Keap1 expression was decreased in specimens from NSCLC patients with lymph node metastasis compared with patients without metastasis. Higher Keap1 expression levels were correlated with the survival of NSCLC patients. Moreover, manipulation of Keap1 expression affected cell migration/invasion abilities. Depletion of Nrf2 relieved the migration promotion imposed by Keap1 suppression. Mechanistic investigations found that S100P was downregulated in both Keap1-overexpressing and Nrf2-knockdown NSCLC cells. Overexpression of Keap1 and knockdown of Nrf2 both suppressed S100P expression in NSCLC cells. Knockdown of S100P inhibited cell migration in highly invasive NSCLC cells and also relieved the migration promotion imposed by Keap1 suppression in weakly invasive NSCLC cells.
Conclusions: Our findings suggest that Keap1 functions as a suppressor of tumor metastasis by targeting the Nrf2/S100P pathway in NSCLC cells. In addition, overexpression of Keap1 may be a novel NSCLC treatment strategy and/or useful biomarker for predicting NSCLC progression. Clin Cancer Res; 21(20); 4719–32. ©2015 AACR.
Selective Inhibition of SIN3 Corepressor with Avermectins as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer
Authors: Kwon Yeon-Jin , Petrie Kevin , Leibovitch Boris A. , Zeng Lei , Mezei Mihaly , Howell Louise , Gil Veronica , Christova Rossitza , Bansal Nidhi , Yang Shuai , Sharma Rajal , Ariztia Edgardo V. , Frankum Jessica , Brough Rachel , Sbirkov Yordan , Ashworth Alan , Lord Christopher J. , Zelent Arthur , Farias Eduardo , Zhou Ming-Ming , Waxman Samuel 
Published: June 2015

Abstract
Triple-negative breast cancers (TNBC) lacking estrogen, progesterone, and HER2 receptors account for 10% to 20% of breast cancer and are indicative of poor prognosis. The development of effective treatment strategies therefore represents a pressing unmet clinical need. We previously identified a molecularly targeted approach to target aberrant epigenetics of TNBC using a peptide corresponding to the SIN3 interaction domain (SID) of MAD. SID peptide selectively blocked binding of SID-containing proteins to the paired α-helix (PAH2) domain of SIN3, resulting in epigenetic and transcriptional modulation of genes associated with epithelial–mesenchymal transition (EMT). To find small molecule inhibitor (SMI) mimetics of SID peptide, we performed an in silico screen for PAH2 domain–binding compounds. This led to the identification of the avermectin macrocyclic lactone derivatives selamectin and ivermectin (Mectizan) as candidate compounds. Both selamectin and ivermectin phenocopied the effects of SID peptide to block SIN3–PAH2 interaction with MAD, induce expression of CDH1 and ESR1, and restore tamoxifen sensitivity in MDA-MB-231 human and MMTV-Myc mouse TNBC cells in vitro. Treatment with selamectin or ivermectin led to transcriptional modulation of genes associated with EMT and maintenance of a cancer stem cell phenotype in TNBC cells. This resulted in impairment of clonogenic self-renewal in vitro and inhibition of tumor growth and metastasis in vivo. Underlining the potential of avermectins in TNBC, pathway analysis revealed that selamectin also modulated the expression of therapeutically targetable genes. Consistent with this, an unbiased drug screen in TNBC cells identified selamectin-induced sensitization to a number of drugs, including those targeting modulated genes. Mol Cancer Ther; 14(8); 1824–36. ©2015 AACR.
Edge‐Detected Common Carotid Artery Intima–Media Thickness and Incident Coronary Heart Disease in the Multi‐Ethnic Study of Atherosclerosis
Authors: Polak Joseph F. , O'Leary Daniel H. 
Published: June 2015

Background

Common carotid artery intima–media thickness (
IMT
) can be measured either by hand or with an automated edge detector. We performed a direct comparison of these 2 approaches and studied their respective associations with coronary heart disease outcomes.

Methods and Results

We studied 5468 participants of the Multi‐Ethnic Study of Atherosclerosis, composed of white, Chinese, Hispanic, and black participants with an average age of 61.9 years (47.8% men) and who were free of
coronary heart disease
at baseline. Manual‐traced and edge‐detected
IMT
measurements were made in the same location on ultrasound images of the right common carotid artery far wall in an area free of plaque.
Manual‐traced
and
edge‐detected common carotid artery IMT measurements
were added separately to multivariable Cox proportional hazards models with time to incident
coronary heart disease
as the outcome and adjusted for traditional
coronary heart disease
Framingham risk factors, lipid‐lowering therapy, blood pressure–lowering therapy, and race or ethnicity. Additional models were generated after adding clinic site and reader. There were 349 events during a median follow‐up of 10.2 years. In adjusted models, the hazard ratio was not significant (1.31; 95%
CI
0.84 to 2.06) for each millimeter increase in manual‐traced
IMT
but was significant for edge‐detected
IMT
(hazard ratio 1.63; 95%
CI
1.12 to 2.37). Edge‐detected
IMT
remained statistically associated with outcomes after additional adjustment for clinic site and reader performing the
IMT
measurement (hazard ratio 1.59; 95%
CI
1.07 to 2.35).

Conclusions

Edge‐detected common carotid artery far wall
IMT
has similar if not stronger associations with coronary heart disease outcomes when compared with manual‐traced
IMT
.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov/
. Unique identifier: NCT00063440.
Efficiency and Safety of Proprotein Convertase Subtilisin/Kexin 9 Monoclonal Antibody on Hypercholesterolemia: A Meta‐Analysis of 20 Randomized Controlled Trials
Authors: Li Chuanwei , Lin Ling , Zhang Wen , Zhou Liang , Wang Hongyong , Luo Xiaoli , Luo Hao , Cai Yue , Zeng Chunyu 
Published: June 2015

Background

Proprotein convertase subtilisin/kexin9 (
PCSK
9) monoclonal antibody significantly reduces low‐density lipoprotein cholesterol level in patients with hypercholesterolemia. The goal of this study was to review recently reported randomized controlled trials to investigate the therapeutic effects and safety of
PCSK
9 inhibitors.

Methods and Results

The clinical randomized controlled trials published from inception to March 19, 2015 were identified from The Cochrane Library databases,
PUBMED
, and
EBASE
. Randomized controlled trials of at least 8 weeks duration using
PCSK
9 inhibitors in treating patients with hypercholesterolemia were included. Mean difference (
MD
) with a 95%
CI
was used to calculate the continuous data, the standardized mean difference with a 95%
CI
was used when the unit was not unified, and risk ratio with a 95%
CI
was used for dichotomous data. After screening, 20 trials fulfilled the inclusion criteria.
PCSK
9 inhibitors significantly decreased the levels of low‐density lipoprotein cholesterol (
MD
=−65.29 mg/dL, 95%
CI
: −72.08 to −58.49), total cholesterol (
MD
=−60.04 mg/dL, 95%
CI
: −69.95 to −50.13), triglycerides (
MD
=−12.21 mg/dL, 95%
CI
: −16.21 to −8.22) and apolipoprotein‐B (
MD
=−41.01 mg/dL, 95%
CI
: −46.07 to −35.94), lipoprotein(a) (standardized mean difference=−0.94, 95%
CI
: −1.12 to −0.77) and increased the levels of high‐density lipoprotein cholesterol (
MD
=3.40 mg/dL, 95%
CI
: 3.12 to 3.68) and apolipoprotein‐A1 (
MD
=6.75 mg/dL, 95%
CI
: 4.64 to 8.86). There was no significant difference in the incidence of treatment‐emergent adverse events (risk ratio=1.01, 95%
CI
: 0.98 to 1.04), serious treatment‐emergent adverse events (risk ratio=1.01, 95%
CI
: 0.88 to 1.17), and the discontinuation of treatment between the 2 groups (risk ratio=1.07, 95%
CI
: 0.86 to 1.34).

Conclusions

The meta‐analysis indicated that
PCSK
9 inhibitors had a strong effect in lowering low‐density lipoprotein cholesterol and other lipid levels with satisfactory safety and tolerability in patients with hypercholesterolemia.
Competitive STDP Learning of Overlapping Spatial Patterns
Authors: Krunglevicius Dalius 
Published: June 2015

Spike-timing-dependent plasticity (STDP) is a set of Hebbian learning rules firmly based on biological evidence. It has been demonstrated that one of the STDP learning rules is suited for learning spatiotemporal patterns. When multiple neurons are organized in a simple competitive spiking neural network, this network is capable of learning multiple distinct patterns. If patterns overlap significantly (i.e., patterns are mutually inclusive), however, competition would not preclude trained neuron’s responding to a new pattern and adjusting synaptic weights accordingly. This letter presents a simple neural network that combines vertical inhibition and Euclidean distance-dependent synaptic strength factor. This approach helps to solve the problem of pattern size-dependent parameter optimality and significantly reduces the probability of a neuron’s forgetting an already learned pattern. For demonstration purposes, the network was trained for the first ten letters of the Braille alphabet.
Active but asocial: exploration and activity is linked to social behaviour in a colonially breeding finch
Authors: McCowan Luke S.C. , Griffith Simon C. 
Published: June 2015

One largely neglected area of personality research is an individual’s propensity to move and feed alongside others. We monitored the foraging behaviour of captive zebra finches in social groups in large enclosures using a PIT-tag system, and also separately assayed activity levels in a home cage with a social partner. We found that more active individuals found novel feeders more quickly (explored faster). Furthermore, we found that more active males fed less socially than inactive males. Our findings suggest that variation in foraging behaviour in the zebra finch is driven by both personality and social factors. This work suggests that degrees of sociality — the intrinsic propensity with which individuals interact and coordinate their activity with other conspecifics — is an important component of personality, and needs to be accounted for in future work.
Local Synthesis of Pepsin in Barrett’s Esophagus and the Role of Pepsin in Esophageal Adenocarcinoma
Authors: Samuels Tina , Hoekzema Craig , Gould Jon , Goldblatt Matthew , Frelich Matthew , Bosler Matthew , Lee Sang-Hyuk , Johnston Nikki 
Published: June 2015

Objective: Despite widespread use of proton pump inhibitors (PPIs), the incidence of esophageal adenocarcinoma (EAC) continues to rise. PPIs reduce reflux acidity, but only transiently inactivate gastric enzymes. Nonacid reflux, specifically nonacid pepsin, contributes to carcinogenesis in the larynx. Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated. Methods: Normal and Barrett’s biopsies from 8 Barrett’s esophagus patients were collected for pepsin analysis via Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Human esophageal cells cultured from healthy patients were treated with pepsin (0.01-1 mg/mL; 1-20 hours), acid (pH 4) ± pepsin (5 minutes); real-time RT-PCR, ELISA, and cell migration were assayed. Results: Pepsin was detected in all 8 Barrett’s and 4 of 8 adjacent normal specimens. Pepsinogen mRNA was observed in 22 Barrett’s, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL-1β expression and cell migration in vitro. Conclusions: Pepsin is synthesized by metaplastic, Barrett’s esophageal mucosa. Nonacid pepsin increases metrics of tumorigenicity in esophageal epithelial cells in vitro. These findings implicate refluxed and locally synthesized pepsin in development and progression of EAC and, in part, explain the inefficacy of PPIs in the prevention of EAC.
Vidéosurveillance intelligente et détection des chutes : perception des professionnels et des gestionnaires
Authors: Lapierre Nolwenn , Carpentier Isabelle , St-Arnaud Alain , Ducharme Francine , Meunier Jean , Jobidon Mireille , Rousseau Jacqueline 
Published: June 2015

Description. Les gérontechnologies peuvent être utilisées pour la détection des chutes. Toutefois, les systèmes existants ne répondent pas entièrement aux besoins des usagers. Notre équipe a donc développé un système de vidéosurveillance intelligente pour combler certaines lacunes. Des auteurs préconisent de consulter les utilisateurs potentiels des gérontechnologies dès les premiers stades de la conception pour y intégrer leurs suggestions. But. L’étude vise à explorer l’opinion des acteurs du système de santé concernant la vidéosurveillance intelligente pour la détection des chutes des aînés à domicile. Méthodologie. Une étude qualitative a exploré l’opinion de 31 participants en utilisant la technique de groupe de discussion thématique. Les transcriptions ont été codées à partir de codes prédéfinis, créés à partir du Modèle de compétence. Résultats. Les participants dégagent divers intérêts à la vidéosurveillance intelligente et suggèrent des améliorations au système. Conséquences. Les propositions et réflexions des participants permettront d’améliorer le système pour répondre aux besoins des usagers.