bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embolic strokes of undetermined source: Prevalence and patient features in the ESUS Global Registry
Authors: Perera Kanjana S , Vanassche Thomas , Bosch Jackie , Giruparajah Mohana , Swaminathan Balakumar , Mattina Katie R , Berkowitz Scott D , Arauz Antonio , O’Donnell Martin J , Ameriso Sebastian F , Hankey Graeme J , Yoon Byung-Woo , Lavallee Philippa , Cunha Luis , Shamalov Nikolay , Brouns Raf , Gagliardi Rubens J , Kasner Scott E , Pieroni Alessio , Vermehren Philipp , Kitagawa Kazuo , Wang Yongjun , Muir Keith , Coutinho Jonathan , Vastagh Ildiko , Connolly Stuart J , Hart Robert G 
Published: April 2016

Background Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). Aims We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. Methods Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. Results Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years; SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p ≤ 0.001). Excluding patients with atrial fibrillation ( n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years ( p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2–8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. Conclusions This cross-sectional global sample of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions.
Safety of Repeated Injections of Sodium Hyaluronate (SUPARTZ) for Knee Osteoarthritis
Authors: Bannuru Raveendhara R. , Brodie Christopher R. , Sullivan Matthew C. , McAlindon Timothy E. 
Published: April 2016

Objective Though there is no consensus on its efficacy, knee osteoarthritis is symptomatically managed with intra-articular hyaluronic acid (IAHA). Recent reports suggest that IAHA may delay the need for total knee replacement, with the magnitude of delay proportional to the number of injection series. However, the safety of repeated injection series is reported to vary between commercial products. This report describes a systematic review of safety data on repeated treatment courses of SUPARTZ. Design We performed a systematic search of MEDLINE, Cochrane database, EMBASE, Web of Science, Google Scholar, and unpublished data. We included all human randomized controlled trials or observational studies with adverse event (AE) data for SUPARTZ in knee osteoarthritis. Two independent reviewers extracted data and evaluated study quality. Data were analyzed separately for the first and subsequent series of injections. Results The primary sources for repeated-injection data on SUPARTZ were a postmarket registry ( N = 7404), 4 prospective studies ( N = 127 total), and a retrospective study ( N = 220). None of the sources reported increased frequency or severity of AEs with repeated injections. In the registry, 95% of multiple-injection-series patients who reported an AE did so during the first series. None of the AEs was serious, and most resolved spontaneously without medical intervention. The overall adverse event rate after repeat courses of SUPARTZ was 0.008 (95% confidence interval: 0.001-0.055). Conclusions Multiple courses of SUPARTZ injections appear to be at least as safe, and probably safer, than the first course. This study supports the safety of repeat courses of SUPARTZ injections for knee osteoarthritis.
Patient perceptions of implantable cardioverter-defibrillator deactivation discussions: A qualitative study
Authors: MacIver Jane , Tibbles Alana , Billia Filio , Ross Heather 
Published: April 2016

Background: There is a class I recommendation for implantable cardioverter-defibrillator deactivation discussions to occur between physicians and heart failure patients. Few studies have reported the patient’s perspective on the timing of implantable cardioverter-defibrillator deactivation discussions. Aim: To determine patient awareness, preferences and timing of implantable cardioverter-defibrillator deactivation discussions. Design: Grounded theory was used to collect and analyze interview data from 25 heart failure patients with an implantable cardioverter-defibrillator. Setting and participants: Patients with an implantable cardioverter-defibrillator, from the Heart Function Clinic at University Health Network (Toronto, Canada). Results: The sample (n = 25) was predominately male (76%) with an average age of 62 years. Patients identified three stages where they felt implantable cardioverter-defibrillator deactivation should be discussed: (1) prior to implantation, (2) with any significant deterioration but while they were of sound mind to engage in and communicate their preferences and (3) at end of life, where patients wished further review of their previously established preferences and decisions about implantable cardioverter-defibrillator deactivation. Most patients (n = 17, 68%) said they would consider deactivation, six (24%) were undecided and two (8%) were adamant they would never turn it off. Conclusion: The patient preferences identified in this study support the need to include information on implantable cardioverter-defibrillator deactivation at implant, with change in clinical status and within broader discussions about end-of-life treatment preferences. Using this process to help patients determine and communicate their implantable cardioverter-defibrillator deactivation preferences may reduce the number of patients experiencing distressing implantable cardioverter-defibrillator shocks at end of life.
Association of Androgen Deprivation Therapy With Depression in Localized Prostate Cancer
Authors: Dinh Kathryn T. , Reznor Gally , Muralidhar Vinayak , Mahal Brandon A. , Nezolosky Michelle D. , Choueiri Toni K. , Hoffman Karen E. , Hu Jim C. , Sweeney Christopher J. , Trinh Quoc-Dien , Nguyen Paul L. 
Published: April 2016

Purpose Androgen deprivation therapy (ADT) may contribute to depression, yet several studies have not demonstrated a link. We aimed to determine whether receipt of any ADT or longer duration of ADT for prostate cancer (PCa) is associated with an increased risk of depression. Methods We identified 78,552 men older than age 65 years with stage I to III PCa using the SEER-Medicare–linked database from 1992 to 2006, excluding patients with psychiatric diagnoses within the prior year. Our primary analysis was the association between pharmacologic ADT and the diagnosis of depression or receipt of inpatient or outpatient psychiatric treatment using Cox proportional hazards regression. Drug data for treatment of depression were not available. Our secondary analysis investigated the association between duration of ADT and each end point. Results Overall, 43% of patients (n = 33,882) who received ADT, compared with patients who did not receive ADT, had higher 3-year cumulative incidences of depression (7.1% v 5.2%, respectively), inpatient psychiatric treatment (2.8% v 1.9%, respectively), and outpatient psychiatric treatment (3.4% v 2.5%, respectively; all P < .001). Adjusted Cox analyses demonstrated that patients with ADT had a 23% increased risk of depression (adjusted hazard ratio [AHR], 1.23; 95% CI, 1.15 to 1.31), 29% increased risk of inpatient psychiatric treatment (AHR, 1.29; 95% CI, 1.17 to 1.41), and a nonsignificant 7% increased risk of outpatient psychiatric treatment (AHR, 1.07; 95% CI, 0.97 to 1.17) compared with patients without ADT. The risk of depression increased with duration of ADT, from 12% with ≤ 6 months of treatment, 26% with 7 to 11 months of treatment, to 37% with ≥ 12 months of treatment (P trend < .001). A similar duration effect was seen for inpatient (P trend < .001) and outpatient psychiatric treatment (P trend < .001). Conclusion Pharmacologic ADT increased the risk of depression and inpatient psychiatric treatment in this large study of elderly men with localized PCa. This risk increased with longer duration of ADT. The possible psychiatric effects of ADT should be recognized by physicians and discussed with patients before initiating treatment.
Disparities in Use of Human Epidermal Growth Hormone Receptor 2–Targeted Therapy for Early-Stage Breast Cancer
Authors: Reeder-Hayes Katherine , Peacock Hinton Sharon , Meng Ke , Carey Lisa A. , Dusetzina Stacie B. 
Published: April 2016

Purpose Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab. Methods We examined a national cohort of Medicare beneficiaries with incident stage I to III HER2-positive breast cancer diagnosed in 2010 and 2011 (n = 1,362). We used insurance claims data to track any use of trastuzumab in the 12 months after diagnosis as well as to identify chemotherapy drugs used in partnership with trastuzumab. We used modified Poisson regression analysis to evaluate the independent effect of race on likelihood of receiving trastuzumab by controlling for clinical need, comorbidity, and community-level socioeconomic status. Results Overall, 50% of white women and 40% of black women received some trastuzumab therapy. Among women with stage III disease, 74% of whites and 56% of blacks received trastuzumab. After adjustment for tumor characteristics, poverty, and comorbidity, black women were 25% less likely to receive trastuzumab within 1 year of diagnosis than white women (risk ratio, 0.745; 95% CI, 0.60 to 0.93). Conclusion Approxemately one half of patients 65 years of age and older with stage I to III breast cancer do not receive trastuzumab-based therapy, which includes many with locally advanced disease. Significant racial disparities exist in the receipt of this highly effective therapy. Further research that identifies barriers to use and increases uptake of trastuzumab could potentially improve recurrence and survival outcomes in this population, particularly among minority women.
PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome
Authors: Roemer Margaretha G.M. , Advani Ranjana H. , Ligon Azra H. , Natkunam Yasodha , Redd Robert A. , Homer Heather , Connelly Courtney F. , Sun Heather H. , Daadi Sarah E. , Freeman Gordon J. , Armand Philippe , Chapuy Bjoern , de Jong Daphne , Hoppe Richard T. , Neuberg Donna S. , Rodig Scott J. , Shipp Margaret A. 
Published: April 2016

Purpose Classical Hodgkin lymphomas (cHLs) include small numbers of malignant Reed-Sternberg cells within an extensive but ineffective inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1/PD-L1/PD-L2 alterations increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and their further induction through Janus kinase 2–signal transducers and activators of transcription signaling. The unique composition of cHL limits its analysis with high-throughput genomic assays. Therefore, the precise incidence, nature, and prognostic significance of PD-L1/PD-L2 alterations in cHL remain undefined. Methods We used a fluorescent in situ hybridization assay to evaluate CD274/PD-L1 and PDCD1LG2/PD-L2 alterations in 108 biopsy specimens from patients with newly diagnosed cHL who were treated with the Stanford V regimen and had long-term follow-up. In each case, the frequency and magnitude of 9p24.1 alterations—polysomy, copy gain, and amplification—were determined, and the expression of PD-L1 and PD-L2 was evaluated by immunohistochemistry. We also assessed the association of 9p24.1 alterations with clinical parameters, which included stage (early stage I/II favorable risk, early stage unfavorable risk, advanced stage [AS] III/IV) and progression-free survival (PFS). Results Ninety-seven percent of all evaluated cHLs had concordant alterations of the PD-L1 and PD-L2 loci (polysomy, 5% [five of 108]; copy gain, 56% [61 of 108]; amplification, 36% [39 of 108]). There was an association between PD-L1 protein expression and relative genetic alterations in this series. PFS was significantly shorter for patients with 9p24.1 amplification, and the incidence of 9p24.1 amplification was increased in patients with AS cHL. Conclusion PD-L1/PD-L2 alterations are a defining feature of cHL. Amplification of 9p24.1 is more common in patients with AS disease and associated with shorter PFS in this series. Further analyses of 9p24.1 alterations in patients treated with standard cHL induction regimens or checkpoint blockade are warranted.
Prioritizing US Cervical Cancer Prevention With Results From a Geospatial Model
Authors: Kish Jonathan K. , Rolin Alicia I. , Zou Zhaohui , Cucinelli James E. , Tatalovich Zaria , Saraiya Mona , Altekruse Sean F. 
Published: April 2016

PurposeTo determine if differences in screening and vaccination patterns across the population may accentuate ethnic and geographic variation in future burden of disease.MethodsUsing Cancer in North America data provided by the North American Association of Central Cancer Registries, county cervical cancer incidence trends from 1995 to 2009 were modeled for the entire United States using ecologic covariates. Rates for health service areas were also modeled by ethnicity. State-level incidence was mapped together with Papanicolaou (Pap) screening, past 3 years (women ≥ 18 years old), and three-dose human papillomavirus (HPV) vaccine coverage (girls 13 to 17 years old) to identify potential priority areas for preventive services.ResultsUS cervical cancer incidence decreased more during the periods 1995 to 1999 and 2000 to 2004 than during the period 2005 to 2009. During these 15 years, the most affected areas became increasingly confined to Appalachia, the lower Mississippi Valley, the Deep South, Texas, and Florida. Hispanic and black women experienced a higher incidence of cervical cancer than both white and Asian and Pacific Islander women during each period. Women in 10 of 17 states/districts with a high incidence (≥ 8.14/100,000) reported low Pap testing (< 78.5%), HPV vaccine coverage (< 33.9%), or both prevention technologies.ConclusionThe decline in cervical cancer incidence has slowed in recent years. Access to HPV vaccination, targeted screening, and treatment in affected populations is needed to reduce cervical cancer disparities in the future.
Experience of the National Cancer Institute Community Cancer Centers Program on Community-Based Cancer Clinical Trials Activity
Authors: Hirsch Bradford R. , Locke Susan C. , Abernethy Amy P. 
Published: April 2016

Purpose: A goal of the National Cancer Institute Community Cancer Centers Program (NCCCP) was to improve cancer research capacity in community settings. We examined research capacity development during the pilot phase of the NCCCP within the context of national trends in clinical trial activity with respect to the number and phase of trials, total accrual, and accrual of underserved populations. Materials and Methods: We examined self-reported data from NCCCP sites during 2007 to 2010, supplemented with data from the National Cancer Institute Cancer Therapy Evaluation Program. Results: Trial availability and accrual improved more quickly at NCCCP sites compared with national trends. Phase III trial availability increased 8% nationally versus 16% across NCCCP sites, and accrual increased 30% nationally versus 133% across NCCCP sites. Accrual of racial and ethnic minorities rose 82%, from 83 to 151 patients, and accrual of patients age ≥ 65 years rose by 221%, from 200 to 641 patients. Change in trial portfolio and accrual differed by sophistication of the site and by prior experience in conducting clinical trials at the site. Conclusion: Despite the short duration, the NCCCP pilot resulted in an increase in the number of open trials as well as patient accrual at a faster rate than that observed nationally. These results, coupled with insights into the relative success of sites with varying sophistication at the outset, provide promise that lessons learned can be applied more broadly to increase research participation.
Olfactory organ ofOctopus vulgaris: morphology, plasticity, turnover and sensory characterization
Authors: Polese Gianluca , Bertapelle Carla , Di Cosmo Anna 
Published: April 2016

ABSTRACTThe cephalopod olfactory organ was described for the first time in 1844 by von Kölliker, who was attracted to the pair of small pits of ciliated cells on each side of the head, below the eyes close to the mantle edge, in both octopuses and squids. Several functional studies have been conducted on decapods but very little is known about octopods. The morphology of the octopus olfactory system has been studied, but only to a limited extent on post-hatching specimens, and the only paper on adult octopus gives a minimal description of the olfactory organ. Here, we describe the detailed morphology of young male and female Octopus vulgaris olfactory epithelium, and using a combination of classical morphology and 3D reconstruction techniques, we propose a new classification for O. vulgaris olfactory sensory neurons. Furthermore, using specific markers such as olfactory marker protein (OMP) and proliferating cell nuclear antigen (PCNA) we have been able to identify and differentially localize both mature olfactory sensory neurons and olfactory sensory neurons involved in epithelium turnover. Taken together, our data suggest that the O. vulgaris olfactory organ is extremely plastic, capable of changing its shape and also proliferating its cells in older specimens.
Reciprocal regulation of actin cytoskeleton remodelling and cell migration by Ca2+ and Zn2+: role of TRPM2 channels
Authors: Li Fangfang , Abuarab Nada , Sivaprasadarao Asipu 
Published: April 2016

ABSTRACT
Cell migration is a fundamental feature of tumour metastasis and angiogenesis. It is regulated by a variety of signalling molecules including H2O2 and Ca2+. Here, we asked whether the H2O2-sensitive transient receptor potential melastatin 2 (TRPM2) Ca2+ channel serves as a molecular link between H2O2 and Ca2+. H2O2-mediated activation of TRPM2 channels induced filopodia formation, loss of actin stress fibres and disassembly of focal adhesions, leading to increased migration of HeLa and prostate cancer (PC)-3 cells. Activation of TRPM2 channels, however, caused intracellular release of not only Ca2+ but also of Zn2+. Intriguingly, elevation of intracellular Zn2+ faithfully reproduced all of the effects of H2O2, whereas Ca2+ showed opposite effects. Interestingly, H2O2 caused increased trafficking of Zn2+-enriched lysosomes to the leading edge of migrating cells, presumably to impart polarisation of Zn2+ location. Thus, our results indicate that a reciprocal interplay between Ca2+ and Zn2+ regulates actin remodelling and cell migration; they call for a revision of the current notion that implicates an exclusive role for Ca2+ in cell migration.
Bryophyte diversity in the Sacred Groves, with special reference to Vallikkattukavu of Kozhikode district in Western Ghats
Authors: Jyothilakshmi G R , Nair Manju C , Venugopal Mithun , Chandini V K 
Published: April 2016

The bryophyte diversity in the Vallikkattu kavu of Kozhikode district is enumerated along with the conservation of bryophytes in the sacred grove is discussed. This report represents many interesting finds such as Bryum retusifolium var. heterophyllum Card. ex Gangulee a new record to Kerala and Ditrichum tortuloides Grout. is a new record for Peninsular India. The endemic species Fissidens kammadensis Manju et al. and the rare species Calymperes palisotti Schwaegr. could be collected from this sacred grove.
BCC
Authors: Yuan Yuan , Wang Kaibo , Lee Rubao , Ding Xiaoning , Xing Jing , Blanas Spyros , Zhang Xiaodong 
Published: April 2016

The Optimistic Concurrency Control (OCC) method has been commonly used for in-memory databases to ensure transaction serializability --- a transaction will be aborted if its read set has been changed during execution. This simple criterion to abort transactions causes a large proportion of false positives, leading to excessive transaction aborts. Transactions aborted false-positively (i.e. false aborts) waste system resources and can significantly degrade system throughput (as much as 3.68x based on our experiments) when data contention is intensive.
Modern in-memory databases run on systems with increasingly parallel hardware and handle workloads with growing concurrency. They must efficiently deal with data contention in the presence of greater concurrency by minimizing false aborts. This paper presents a new concurrency control method named Balanced Concurrency Control (BCC) which aborts transactions more carefully than OCC does. BCC detects data dependency patterns which can more reliably indicate unserializable transactions than the criterion used in OCC. The paper studies the design options and implementation techniques that can effectively detect data contention by identifying dependency patterns with low overhead. To test the performance of BCC, we have implemented it in Silo and compared its performance against that of the vanilla Silo system with OCC and two-phase locking (2PL). Our extensive experiments with TPC-W-like, TPC-C-like and YCSB workloads demonstrate that when data contention is intensive, BCC can increase transaction throughput by more than 3x versus OCC and more than 2x versus 2PL; meanwhile, BCC has comparable performance with OCC for workloads with low data contention.
Effects of vaccination against Yersinia ruckeri on oxidative stress biomarkers and liver and heart biochemistry in rainbow trout (Oncorhynchus mykiss)
Authors: Tkachenko Halyna , Grudniewska Joanna , Pękala Agnieszka , Paździor Ewa 
Published: April 2016

Abstract
To determine the effects of vaccination against Yersinia ruckeri on the health condition of rainbow trout, Oncorhynchus mykiss (Walbaum) in general, and oxidative stress biomarkers and metabolic parameters specifically, as well as to identify mechanisms that underpin the susceptibility of fish to vaccination, we compared the liver and heart function, and the oxidative mechanism underlying those effects, by detecting relevant lipid peroxidation and protein oxidation biomarkers, as well as aerobic-anaerobic metabolism in trout immunized against Y. ruckeri at 30 days post-vaccination and in healthy individuals. In our study, hepatic aminotransferase activities were positively associated with the oxidative stress biomarkers in the trout vaccinated against Y. ruckeri. Moreover, similar associations were observed in the cardiac tissue of the immunized trout. Decreased aldehydic and ketonic derivatives of oxidatively modified proteins and the reduction of aminotransferase and lactate dehydrogenase activities were sensitive to the vaccination of trout against Y. ruckeri and may potentially be used as biomarkers in evaluating vaccine effects in the liver of rainbow trout. Understanding the role of biochemical changes in the tissues of vaccinated trout has important implications for understanding of the complex physiological changes that occur in immunization, and also for improving aquaculture practices to maximize tissue growth and the health of vaccinated trout.