bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Targeting of KDM1A/LSD1 in Ewing Sarcoma with SP-2509 Engages the Endoplasmic Reticulum Stress Response
Authors: Pishas Kathleen I. , Drenberg Christina D. , Taslim Cenny , Theisen Emily R. , Johnson Kirsten M. , Saund Ranajeet S. , Pop Ioana L. , Crompton Brian D. , Lawlor Elizabeth R. , Tirode Franck , Mora Jaume , Delattre Olivier , Beckerle Mary C. , Callen David F. , Sharma Sunil , Lessnick Stephen L. 
Published: July 2018

Abstract
Multi-agent chemotherapeutic regimes remain the cornerstone treatment for Ewing sarcoma, the second most common bone malignancy diagnosed in pediatric and young adolescent populations. We have reached a therapeutic ceiling with conventional cytotoxic agents, highlighting the need to adopt novel approaches that specifically target the drivers of Ewing sarcoma oncogenesis. As KDM1A/lysine-specific demethylase 1 (LSD1) is highly expressed in Ewing sarcoma cell lines and tumors, with elevated expression levels associated with worse overall survival (P = 0.033), this study has examined biomarkers of sensitivity and mechanisms of cytotoxicity to targeted KDM1A inhibition using SP-2509 (reversible KDM1A inhibitor). We report, that innate resistance to SP-2509 was not observed in our Ewing sarcoma cell line cohort (n = 17; IC50 range, 81 –1,593 nmol/L), in contrast resistance to the next-generation KDM1A irreversible inhibitor GSK-LSD1 was observed across multiple cell lines (IC50 &gt; 300 μmol/L). Although TP53/STAG2/CDKN2A status and basal KDM1A mRNA and protein levels did not correlate with SP-2509 response, induction of KDM1B following SP-2509 treatment was strongly associated with SP-2509 hypersensitivity. We show that the transcriptional profile driven by SP-2509 strongly mirrors KDM1A genetic depletion. Mechanistically, RNA-seq analysis revealed that SP-2509 imparts robust apoptosis through engagement of the endoplasmic reticulum stress pathway. In addition, ETS1/HIST1H2BM were specifically induced/repressed, respectively following SP-2509 treatment only in our hypersensitive cell lines. Together, our findings provide key insights into the mechanisms of SP-2509 cytotoxicity as well as biomarkers that can be used to predict KDM1A inhibitor sensitivity in Ewing sarcoma. Mol Cancer Ther; 17(9); 1902–16. ©2018 AACR.
Positive Association between Preoperative Total Testosterone Levels and Risk of Positive Surgical Margins by Prostate Cancer: Results in 476 Consecutive Patients Treated Only by Radical Prostatectomy
Authors: Porcaro Antonio Benito , Tafuri Alessandro , Sebben Marco , Corsi Paolo , Pocessali Tania , Pirozzi Marco , Amigoni Nelia , Rizzetto Riccardo , Mariotto Arianna , Inverardi Davide , Brunelli Matteo , Iacovelli Roberto , Romano Mario , Siracusano Salvatore , Artibani Walter 
Published: July 2018

<b><i>Objective:</i></b> To evaluate preoperative total testosterone (TT) as a predictor of positive surgical margins (PSM) in prostate cancer (PCA). <b><i>Patients and methods:</i></b> During the period from November 2014 to July 2017, preoperative TT was measured in 476 PCA patients undergoing only radical prostatectomy (RP) and including all risk classes. Surgical margins were stated negative, focal positive (single and less than 1 mL), and multifocal positive (more than 1). The risk of TT and clinical factors associated with the risk of PSM (focal or multifocal versus negative) was evaluated by the multinomial logistic regression model. <b><i>Results:</i></b> Overall, PSM were detected in 149 cases (31.3%), which included 99 patients with focal cancer invasion (20.8%) and 50 subjects with multifocal cancer invasion (10.5%). In univariate analysis, PSM associated with higher median levels of TT and prostate-specific antigen than controls. Multifocal PSM associated with higher rates of high-risk PCA (42%) than focal (22.2%) or control cases (18.3%). In multivariate analysis, TT was the only independent factor positively associated with the risk of focal PSM when compared to controls (OR 1.002; <i>p</i> = 0.035). TT (OR 1.003; <i>p</i> = 0.002) and high-risk PCA (OR 1.002; <i>p</i> = 0.047) were independent factors, which positively associated with the risk of multifocal PSM when compared to controls. Risk models were computed. <b><i>Conclusions:</i></b> In a large and contemporary cohort of patients elected to primary RP, TT was an ­independent positive factor associated with the risk of focal and multifocal PSM. TT associated with aggressive PCA biology.
Importance of Considering Competing Risks in Time-to-Event Analyses
Authors: Abdel-Qadir Husam , Fang Jiming , Lee Douglas S. , Tu Jack V. , Amir Eitan , Austin Peter C. , Anderson Geoffrey M. 
Published: July 2018

Background:
Ignoring competing risks in time-to-event analyses can lead to biased risk estimates, particularly for elderly patients with multimorbidity. We aimed to demonstrate the impact of considering competing risks when estimating the cumulative incidence and risk of stroke among elderly atrial fibrillation patients.

Methods and Results:

Using linked administrative databases, we identified patients with atrial fibrillation aged ≥66 years discharged from hospital in ON, Canada between January 1, 2007, and March 31, 2011. We estimated the cumulative incidence of stroke hospitalization using the complement of the Kaplan–Meier function and the cumulative incidence function. This was repeated after stratifying the cohort by presence of prespecified comorbidities: chronic kidney disease, chronic obstructive pulmonary disease, cancer, or dementia. The full cohort was used to regress components of the CHA
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VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, sex) score on the hazard of stroke hospitalization using the Fine-Gray and Cox methods. These models were subsequently used to predict the 5-year risk of stroke hospitalization. Among 136 156 patients, the median CHA
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DS
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VASc score was 4 and 84 728 patients (62.2%) had ≥1 prespecified comorbidity. The 5-year cumulative incidence of stroke was 5.4% (95% confidence interval, 5.3%–5.5%), whereas that of death without stroke was 48.8% (95% confidence interval, 48.5%–49.1%). The incidence of both events was overestimated by the Kaplan–Meier method; stroke incidence was overestimated by a relative factor of 39%. The degree of overestimation was larger among patients with non-CHA
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DS
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VASc comorbidity because of higher incidence of death without stroke. The Fine-Gray model demonstrated better calibration than the Cox model, which consistently overpredicted stroke incidence.

Conclusions:
The incidence of death without stroke was 9-fold higher than that of stroke, leading to biased estimates of stroke risk with traditional time-to-event methods. Statistical methods that appropriately account for competing risks should be used to mitigate this bias.
Le Profil des AVQ adapté au rôle de parent : Une étude exploratoire
Authors: Major Sabrina , Gilbert Véronique , Dutil Elisabeth , Pituch Evelina , Bottari Carolina 
Published: July 2018

Description. Devenir parent implique plusieurs défis quotidiens, particulièrement pour les parents ayant des incapacités physiques et cognitives. Néanmoins, aucun outil d’évaluation n’existe pour soutenir les ergothérapeutes dans l’évaluation de l’indépendance à prendre soin d’un bébé. But. Cette étude visait à (a) développer des activités spécifiques à l’évaluation des habiletés parentales auprès de bébés à l’intérieur du Profil des AVQ et (b) réaliser une étude pilote pour explorer les besoins des parents avec incapacités. Méthodologie. Les activités ont été sélectionnées par une approche participative avec des ergothérapeutes experts ( n = 3) et l’évaluation a été expérimentée auprès de parents ( n = 4) avec incapacités physiques et cognitives. Résultats. Six activités parentales ont été développées et celles-ci ont permis de conclure sur l'indépendance d’un parent à prendre soin de son bébé. Conséquences. Par l’ajout d’activités parentales, le Profil des AVQ a le potentiel d’outiller les ergothérapeutes dans leurs recommandations reliées au rôle de parent.
Microbiological monitoring of heater-cooler unit to keep free of Mycobacterium chimaera infection
Authors: Chan Tanee , Ling Moi Lin , Teng Siew Yan , Chiu Kit Yi , James Esther Magdalane 
Published: July 2018

Introduction: The association of Mycobacterium chimaera infection in patients undergoing cardiopulmonary bypass (CPB) with the use of heater-cooler units (HCU) has been reported in various literature. We described microbiological monitoring and the extent of microbiological contamination of HCUs utilized in our centre and strategies employed to reduce the high microbial load. Methods: Since August 2016, we have been following the new Instructions for Use from the manufacturer for the cleaning and disinfection of three units of Stöckert 3T and four units of Stöckert 1T HCU at the National Heart Centre Singapore. Microbiological monitoring began in January 2017 and included acid-fast bacilli (AFB) culture, Pseudomonas aeruginosa, total colony and total coliform count. Methods, such as increasing disinfection frequency and making the HCU inactive by keeping it empty in storage, were used to reduce the high colony count. Results: All three units of Stöckert 3T and two units of Stöckert 1T were contaminated with Mycobacterium chimaera. Pseudomonas aeruginosa and total coliform count were consistently <1 colony-forming unit (CFU)/100 mL in every water sample of each HCU. High colony counts were encountered initially in all units. Step-up frequency of disinfection was found to be not as effective as keeping the HCU inactive in bringing the total colony count to an acceptable level. Conclusions: All monitoring and maintenance measures of HCUs need to be established and maintained to mitigate potential infection risks to patients. Strict adherence to all cleaning and disinfection processes and keeping the HCU inactive maintained the water quality of the HCU at acceptable levels.
Towards a biomarker model for cognitive improvement: No change in memory-related prefrontal engagement following a negative cognitive remediation trial in bipolar disorder
Authors: Macoveanu Julian , Demant Kirsa M , Vinberg Maj , Siebner Hartwig R , Kessing Lars V , Miskowiak Kamilla W 
Published: July 2018

Background: Cognitive deficits are prevalent in bipolar disorder during remission but effective cognition treatments are lacking due to insufficient insight into the neurobiological targets of cognitive improvement. Emerging data suggest that dorsal prefrontal cortex target engagement is a key neurocircuitry biomarker of pro-cognitive treatment effects. Aims: In this randomized controlled functional magnetic resonance imaging study, we test this hypothesis by investigating the effects of an ineffective cognitive remediation intervention on dorsal prefrontal response during strategic memory encoding and working memory engagement. Methods: Bipolar disorder patients in partial remission with subjective cognitive difficulties were randomized to receive 12-week group-based cognitive remediation ( n = 13) or to continue their standard treatment ( n = 14). The patients performed a strategic episodic picture encoding task and a spatial n-back working memory task under functional magnetic resonance imaging at baseline and following cognitive remediation or standard treatment. Results: The right dorsolateral prefrontal cortex was commonly activated by both strategic memory tasks across all patients. The task-related prefrontal engagement was not altered by cognitive remediation relative to standard treatment. The dorsolateral prefrontal cortex response was not significantly associated with recall accuracy or working memory performance. Conclusions: As hypothesized, no task-related change in prefrontal activity was observed in a negative cognitive remediation trial in remitted bipolar disorder patients. By complementing previous findings linking cognitive improvement with increased dorsolateral prefrontal cortex engagement, our negative findings provide additional validity evidence to the dorsal prefrontal target engagement biomarker model of cognitive improvement by strengthening the proposed causality between modulation of dorsolateral prefrontal cortex engagement and pro-cognitive effects.
The fate of abstracts presented at international ophthalmology meetings: 2- and 5-year publication rates
Authors: Villani Edoardo , Vujosevic Stela , Specchia Claudia , Tresca Carducci Filippo , De Cillà Stefano , Nucci Paolo 
Published: July 2018

Purpose: To investigate the 2- and 5-year publication rates of abstracts presented at major international ophthalmology meetings. Methods: We analyzed a random selection of 20% of free papers and posters presented at the 2010 meeting of the Association for Research in Vision and Ophthalmology, the American Academy of Ophthalmology, the European Association for Vision and Eye Research, the Asia-Pacific Academy of Ophthalmology, and the 2009 European Society of Ophthalmology meeting. The PubMed (MEDLINE) database was searched to identify matching journal articles. Data collection included: topic, geographic origin, presentation type, publication status, and impact factor. A multivariate logistic regression model was used to assess odds of publication and impact factor. Results: Our analysis included 1742 research abstracts. The overall 2- and 5-year publication rates were 33.3% (n = 579) and 47.2% (n = 823), respectively. The highest publication rates were found for Association for Research in Vision and Ophthalmology (36.1% and 51.9%, p < 0.0001), paper presentations (44.5% and 60.5%, p < 0.0001), researches from Oceania (35.8% and 57.1%, p < 0.05) and North America (36.2% and 50.5%, p < 0.05), and Basic science studies (44% and 60.3%, p < 0.01). After adjustments, higher odds of publication were shown by the Association for Research in Vision and Ophthalmology and the American Academy of Ophthalmology meetings (p < 0.0001), papers (p < 0.0001), and Basic science (p < 0.05). The median impact factor was 3.20 (interquartile range = 1.90–3.40). Conclusion: Less than half of abstracts presented at the major ophthalmology meetings reach publication within 5 years of their initial presentation. Professionals attending meetings may consider adopting a more critical approach to the preliminary results reported in presented abstracts. Increasing publication rates and reducing potential publication bias is of interest.
Optical coherence tomography angiography in myopic choroidal neovascularization after intravitreal ranibizumab
Authors: Cennamo Gilda , Amoroso Francesca , Schiemer Stefano , Velotti Nunzio , Alfieri Mariacristina , de Crecchio Giuseppe 
Published: July 2018

Purpose: To describe the optical coherence tomography angiography characteristics of myopic patients with choroidal neovascularization secondary to pathologic myopia during ranibizumab therapy. Methods: Nineteen patients were enrolled in this prospective study (13 females, 6 males, mean age 55.25 ± 9.63 years) for a total of 20 eyes examined (14 right eyes, 6 left eyes). Images were analyzed independently by two examiners. Results: Mean follow-up was 5.75 ± 1.88 months, with a mean intravitreal injections of 1.90 ± 0.44. Mean best-corrected visual acuity at baseline was 0.39 ± 0.18 logMAR versus 0.26 ± 0.16 logMAR 6 months after treatment. The neovascular area (Z = –2.091, p = 0.037) was significantly reduced after treatment, whereas vessel density was not (Z = –1.848, p = 0.065). Moreover, the best-corrected visual acuity was increased (Z = –3.055, p = 0.002). Neovascular area was significantly correlated with best-corrected visual acuity, at both baseline and follow-up (p < 0.05). Conclusion: Our data suggest that optical coherence tomography angiography is a reproducible non-invasive examination with which to monitor changes in the neovascular area in patients with pathologic myopia treated with ranibizumab.
Early reappearance of disappeared ruptured small aneurysm with concomitant vertebral artery dissection
Authors: Enesi Eugen , Rroji Arben , Bilaj Fatmir , Reka Eni , Ndroqi Adrian , Xhumari Artur , Lilamani Ejona , Petrela Mentor 
Published: July 2018

Thrombosis of a previously ruptured intracranial aneurysm is a frequent event and it most commonly occurs in large or giant aneurysms. We present a dynamic short-term follow-up and management of thrombosis in a ruptured small posterior inferior cerebellar artery aneurysm with concomitant vertebral artery dissection (VAD). Clinical and radiological follow-up findings and reviewed literature on thrombosis of small ruptured aneurysms are the focus of this presentation. Early reappearance of a disappeared ruptured small cerebral aneurysm with a concomitant VAD may be attributed to the controlled ovarian hyperstimulation phase of in vitro fertilization and prolonged use of oral contraceptive pills.
Using step counters to promote physical activity and exercise capacity in patients with chronic obstructive pulmonary disease: a meta-analysis
Authors: Qiu Shanhu , Cai Xue , Wang Xuyi , He Can , Zügel Martina , Steinacker Jürgen Michael , Schumann Uwe 
Published: July 2018

Background: Although step counters are popularly employed for physical rehabilitation in chronic obstructive pulmonary disease (COPD) patients, their effectiveness is inconsistent and even questioned. This meta-analysis aimed to investigate whether step counter use increases physical activity or improves exercise capacity in COPD patients. Methods: Electronic databases were searched for randomized controlled trials that assessed the efficacy of step counter use in increasing physical activity or in improving exercise capacity. Data were aggregated using a random-effects model to get the overall effect sizes [standard mean difference (SMD) with 95% confidence interval (CI)], and subgroup analyses were performed. Results: A total of 15 trials enrolling 1316 patients with moderate to severe COPD were included. Step counter use increased physical activity compared with controls (SMD = 0.57, 95% CI 0.31–0.84), which is equal to a magnitude of 1026 steps/day in daily steps. It also enhanced exercise capacity with an effect size of 0.30 (95% CI 0.16–0.45), approximating to a magnitude of 11.6 m in the 6-min walking distance. Step counter use could augment physical activity (SMD = 0.64, 95% CI 0.19–1.08) and exercise capacity (SMD = 0.32, 95% CI 0.01–0.62) for patients receiving pulmonary rehabilitation. Yet it cannot enhance physical activity or exercise capacity in patients with severe COPD or among studies with intervention durations ⩾6 months (both p > 0.50). Conclusions: Step counter use increases physical activity and improves exercise capacity in COPD patients, at least in the short term, which supports the notion of recommending step counter use in COPD management.
Preoperative Mental Health Has a Stronger Association with Baseline Self-Assessed Knee Scores than Defect Morphology in Patients Undergoing Cartilage Repair
Authors: Ackermann Jakob , Ogura Takahiro , Duerr Robert A. , Barbieri Mestriner Alexandre , Gomoll Andreas H. 
Published: July 2018

Objective The purpose of this study was to assess potential correlations between the mental component summary of the Short Form–12 (SF-12 MCS), patient characteristics or lesion morphology, and preoperative self-assessed pain and function scores in patients undergoing autologous chondrocyte implantation (ACI). Design A total of 290 patients underwent ACI for symptomatic cartilage lesions in the knee. One hundred and seventy-eight patients were included in this study as they completed preoperative SF-12, Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores. Age, sex, smoker status, body mass index, Worker’s Compensation, previous surgeries, concomitant surgeries, number of defects, lesion location in the patella, and total defect size were recorded for each patient. Pearson’s correlation and multivariate regression models were used to distinguish associations between these factors and preoperative knee scores. Results The SF-12 MCS showed the strongest bivariate correlation with all KOOS subgroups ( P < 0.001) (except KOOS Symptom; P = 0.557), Tegner ( P = 0.005), Lysholm ( P < 0.001), and IKDC scores ( P < 0.001). In the multivariate regression models, the SF-12 MCS showed the strongest association with all KOOS subgroups ( P < 0.001) (except KOOS Symptom; P = 0.91), Lysholm ( P = 0.001), Tegner ( P = 0.017), and IKDC ( P < 0.001). Conclusion In patients with symptomatic cartilage defects of the knee, preoperative patient mental health has a strong association with self-assessed pain and functional knee scores. Further studies are needed to determine if preoperative mental health management can improve preoperative symptoms and postoperative outcomes.
EUROVISCO Guidelines for the Design and Conduct of Clinical Trials Assessing the Disease-Modifying Effect of Knee Viscosupplementation
Authors: Henrotin Yves , Chevalier Xavier , Raman Raghu , Richette Pascal , Montfort Jordi , Jerosch Jörg , Baron Dominique , Bard Hervé , Carrillon Yannick , Migliore Alberto , Conrozier Thierry 
Published: July 2018

Objectives Hyaluronic acid viscosupplementation is a commonly used intra-articular treatment for osteoarthritis (OA). Some recent preclinical and clinical trials have demonstrated a potential for its disease-modifying effects. The goal of this expert opinion, consensus-driven exercise is to provide guidelines for the design and conduct of clinical trials assessing the disease-modifying effect of viscosupplementation in the knee. Methods The EUROVISCO group constitutes 10 members who had expertise in clinical research methodology in the field of OA and viscosupplementation. They initially drafted issues through an iterative process and had to vote on their degree of agreement on these recommendations. The scores were pooled to generate a median agreement score for each recommendation. Results The document includes 31 recommendations regarding study population, imaging, clinical and biological assessment of disease-modifying effects of viscosupplementation. Agreements were reached on some recommendations. In particular, the experts reached unanimous agreement on double-blind study design, imaging primary outcomes, time interval between 2 radiographs, x-ray procedure standardization, and the combined use of imaging and biological markers. The group did not recommend the use of ultrasonography, computed tomography (CT) scan and CT arthrography as a tool for OA diagnosis or to assess progression over time. Conclusion In summary, the working group identified 31 recommendations that represent the current best practices regarding clinical trials that target the assessment of viscosupplementation disease-modifying effects in patients with knee OA. These recommendations integrate new imaging technologies and soluble biomarkers.