bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tapering and discontinuation of methotrexate in patients with RA treated with TNF inhibitors: data from the DREAM registry
Authors: Manders Sofie H M , van de Laar Mart A F J , Rongen-van Dartel Sanne A A , Bos Reinhard , Visser Henk , Brus Herman L , Jansen Tim , Vonkeman Harald E , van Riel Piet L C M , Kievit Wietske 
Published: October 2015

ObjectivesTo study the number of patients that taper or discontinue concomitant methotrexate (MTX) in daily practice in patients with rheumatoid arthritis (RA) treated with tumour necrosis factor inhibitor (TNFi) and to analyse the effects of that adaption on disease activity and drug survival.MethodsData were collected from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. Patients who started their first TNFi were included in the study. Treatment effectiveness after MTX tapering or discontinuation was analysed using Disease Activity Score of 28 joints (DAS28). Drug survival of the TNFi was analysed using the Cox proportional hazard model with a time-dependent covariate.ResultsIn 458 patients (34%), MTX was tapered, 126 patients (10%) discontinued MTX and 747 patients (56%) continued MTX at the same dose. On average, DAS28 improved after tapering MTX (−0.40, −0.45) and after stopping MTX (−0.28, −0.12) at 6 and 12 months. In the taper group, 21% of the patients relapsed (DAS28 increase >0.6), and in the discontinuation group this was 21% and 24% at 6 and 12 months, respectively. Patients who taper and discontinue MTX have a similar DAS28 score over time as patients who continue MTX. Moreover, there was no influence of tapering or discontinuation of MTX on long-term drug survival of TNFi.ConclusionsIn daily practice, tapering or discontinuation of concomitant MTX in patients with RA treated with TNFi frequently occurs and it does not seem to influence the average DAS28 over time or the long-term TNFi drug survival. It appears that in daily clinical practice the correct patients are selected to taper or discontinue MTX.
Dual Roles of RNF2 in Melanoma Progression
Authors: Rai Kunal , Akdemir Kadir C. , Kwong Lawrence N. , Fiziev Petko , Wu Chang-Jiun , Keung Emily Z. , Sharma Sneha , Samant Neha S. , Williams Maura , Axelrad Jacob B. , Shah Amiksha , Yang Dong , Grimm Elizabeth A. , Barton Michelle C. , Milton Denai R. , Heffernan Timothy P. , Horner James W. , Ekmekcioglu Suhendan , Lazar Alexander J. , Ernst Jason , Chin Lynda 
Published: October 2015

Abstract
Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic. Mechanistically, RNF2-mediated invasive behavior is dependent on its ability to monoubiquitinate H2AK119 at the promoter of LTBP2, resulting in silencing of this negative regulator of TGFβ signaling. In contrast, RNF2′s oncogenic activity does not require its catalytic activity nor does it derive from its canonical gene repression function. Instead, RNF2 drives proliferation through direct transcriptional upregulation of the cell-cycle regulator CCND2. We further show that MEK1-mediated phosphorylation of RNF2 promotes recruitment of activating histone modifiers UTX and p300 to a subset of poised promoters, which activates gene expression. In summary, RNF2 regulates distinct biologic processes in the genesis and progression of melanoma via different molecular mechanisms.
Significance: The role of epigenetic regulators in cancer progression is being increasingly appreciated. We show novel roles for RNF2 in melanoma tumorigenesis and metastasis, albeit via different mechanisms. Our findings support the notion that epigenetic regulators, such as RNF2, directly and functionally control powerful gene networks that are vital in multiple cancer processes. Cancer Discov; 5(12); 1314–27. ©2015 AACR.
See related commentary by Black and Whetstine, p. 1241.
This article is highlighted in the In This Issue feature, p. 1225
White Matter Lesion Progression
Authors: Hofer Edith , Cavalieri Margherita , Bis Joshua C. , DeCarli Charles , Fornage Myriam , Sigurdsson Sigurdur , Srikanth Velandai , Trompet Stella , Verhaaren Benjamin F.J. , Wolf Christiane , Yang Qiong , Adams Hieab H.H. , Amouyel Philippe , Beiser Alexa , Buckley Brendan M. , Callisaya Michele , Chauhan Ganesh , de Craen Anton J.M. , Dufouil Carole , van Duijn Cornelia M. , Ford Ian , Freudenberger Paul , Gottesman Rebecca F. , Gudnason Vilmundur , Heiss Gerardo , Hofman Albert , Lumley Thomas , Martinez Oliver , Mazoyer Bernard , Moran Chris , Niessen Wiro J. , Phan Thanh , Psaty Bruce M. , Satizabal Claudia L. , Sattar Naveed , Schilling Sabrina , Shibata Dean K. , Slagboom P. Eline , Smith Albert , Stott David J. , Taylor Kent D. , Thomson Russell , Töglhofer Anna M. , Tzourio Christophe , van Buchem Mark , Wang Jing , Westendorp Rudi G.J. , Gwen Windham B. , Vernooij Meike W. , Zijdenbos Alex , Beare Richard , Debette Stéphanie , Ikram M. Arfan , Jukema J. Wouter , Launer Lenore J. , Longstreth W. T. , Mosley Thomas H. , Seshadri Sudha , Schmidt Helena , Schmidt Reinhold 
Published: October 2015

Background and Purpose—
White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.

Methods—
Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies.

Results—

A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (
P
<5×10
−8
). Four loci were suggestive (
P
<1×10
−5
) of an association with WML progression: 10q24.32 (rs10883817,
P
=1.46×10
−6
); 12q13.13 (rs4761974,
P
=8.71×10
−7
); 20p12.1 (rs6135309,
P
=3.69×10
−6
); and 4p15.31 (rs7664442,
P
=2.26×10
−6
). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden.

Conclusions—
Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors.
Carotid Plaque Morphology Is Significantly Associated With Sex, Age, and History of Neurological Symptoms
Authors: Wendorff Carina , Wendorff Heiko , Pelisek Jaroslav , Tsantilas Pavlos , Zimmermann Alexander , Zernecke Alma , Kuehnl Andreas , Eckstein Hans-Henning 
Published: October 2015

Background and Purpose—
The purpose of this study was to analyze the association between morphological characteristics of human carotid plaques and patient’s sex, age, and history of neurological symptoms.

Methods—
The study included 763 atherosclerotic plaques from patients treated surgically for carotid stenosis between 2004 and 2013. Histological analyses of carotid plaques were performed to assess the type of plaque (American Heart Association classification), the stability of the plaque, the extent of calcification, inflammation, and neovascularization, as well as the deposition of collagen and elastin. According to the scale of outcome measurement, logistic regression, ordinal regression, and multinomial regression analyses were applied. All results were adjusted for common risk factors of atherosclerosis.

Results—

Male sex was associated with more cellularity (odds ratio [OR], 1.56;
P
=0.003), more inflammatory infiltrates (OR, 1.75;
P
<0.001), and more neovascularization (OR, 1.47;
P
=0.010), but less calcification (OR, 0.78;
P
=0.090). Symptomatic patients were more likely to have a lower amount of elastin (OR, 0.71;
P
=0.057). Higher age was associated with increased calcification (OR, 1.23;
P
=0.009). Unstable plaques were found more frequently in symptomatic patients (OR, 1.60; 95% confidence interval, 1.14–2.25;
P
=0.007). A multinomial regression model revealed that age, sex, and history of neurological symptoms were significantly associated with specific plaque types (
P
=0.009,
P
<0.001, and
P
=0.017, respectively).

Conclusions—
Plaque morphology differed between men and women and varied with age. Certain types of plaques (VI and VI/VII) as well as unstable plaques were significantly associated with a history of neurological symptoms. Thus, individual approaches (eg, in detection of plaque hemorrhage or thin fibrous caps) especially based on sex and age should be considered to identify patients at increased risk of stroke.
Visualizing Rayleigh Scattering through UV Photography
Authors: Lindfors Anders V. , Ylianttila Lasse 
Published: October 2015

Abstract
A tailored camera setup has been used to take photographs of the atmosphere and the environment as seen in the ultraviolet (UV) wavelength band. These photographs make visible what the human eye cannot normally perceive—in particular, the effects of the increasingly strong scattering of UV radiation by the molecular atmosphere. This scattering of sunlight by air molecules is commonly known as Rayleigh scattering, and its scattering efficiency is inversely proportional to the fourth power of the wavelength; the shorter the wavelength, the stronger the scattering. The blue color of the cloud-free sky is a well-known consequence of this, while it is also known that radiation in the UV band is even more diffuse than blue light. The UV photographs presented here demonstrate these effects of Rayleigh scattering. They show, for example, how clouds are much harder to distinguish from the background (the sky) in the UV than in the visible band, and how shadows tend to disappear in the UV. Thereby, these photographs provide intuitive insight into the physics of Rayleigh scattering, and help connect the typically abstract and theoretical information of textbooks and scientific articles with a more concrete understanding of the effects of Rayleigh scattering.
Storm-Scale Data Assimilation and Ensemble Forecasting with the NSSL Experimental Warn-on-Forecast System. Part I: Radar Data Experiments
Authors: Wheatley Dustan M. , Knopfmeier Kent H. , Jones Thomas A. , Creager Gerald J. 
Published: October 2015

AbstractThis first part of a two-part study on storm-scale radar and satellite data assimilation provides an overview of a multicase study conducted as part of the NOAA Warn-on-Forecast (WoF) project. The NSSL Experimental WoF System for ensembles (NEWS-e) is used to produce storm-scale analyses and forecasts of six diverse severe weather events from spring 2013 and 2014. In this study, only Doppler reflectivity and radial velocity observations (and, when available, surface mesonet data) are assimilated into a 36-member, storm-scale ensemble using an ensemble Kalman filter (EnKF) approach. A series of 1-h ensemble forecasts are then initialized from storm-scale analyses during the 1-h period preceding the onset of storm reports. Of particular interest is the ability of these 0–1-h ensemble forecasts to reproduce the low-level rotational characteristics of supercell thunderstorms, as well as other convective hazards. For the tornado-producing thunderstorms considered in this study, ensemble probabilistic forecasts of low-level rotation generally indicated a rotating thunderstorm approximately 30 min before the time of first observed tornado. Displacement errors (often to the north of tornado-affected areas) associated with vorticity swaths were greatest in those forecasts launched 30–60 min before the time of first tornado. Similar forecasts were produced for a tornadic mesovortex along the leading edge of a bow echo and, again, highlighted a well-defined vorticity swath as much as 30 min prior to the first tornado.
The Role of Collective Efficacy in Climate Change Adaptation in India
Authors: Thaker Jagadish , Maibach Edward , Leiserowitz Anthony , Zhao Xiaoquan , Howe Peter 
Published: October 2015

Abstract
Research on adaptive capacity often focuses on economics and technology, despite evidence from the social sciences finding that socially shared beliefs, norms, and networks are critical in increasing individuals’ and communities’ adaptive capacity. Drawing upon social cognitive theory, this paper builds on the first author’s Ph.D. dissertation and examines the role of collective efficacy—people’s shared beliefs about their group’s capabilities to accomplish collective tasks—in influencing Indians’ capacity to adapt to drinking water scarcity, a condition likely to be exacerbated by future climate change. Using data from a national survey (N = 4031), individuals with robust collective efficacy beliefs were found to be more likely to participate in community activities intended to ensure the adequacy of water supplies, and this relationship was found to be stronger in communities with high levels of community collective efficacy compared to communities with low levels of community collective efficacy. In addition, community collective efficacy was positively associated with self-reported community adaptation responses. Public education campaigns aimed at increasing collective efficacy beliefs are likely to increase adaptive capacity.
Trends in diagnosis of bipolar disorder: Have the boundaries changed?
Authors: Sara Grant E , Malhi Gin S 
Published: October 2015

Objective: There are concerns that the diagnostic boundaries of bipolar disorder have expanded. This study seeks evidence of change in diagnostic practice at three boundaries: the ‘lower’ boundary with subclinical mood conditions, the ‘lateral’ boundary with other mental health conditions (psychotic, anxiety, substance and personality disorders) and the ‘internal’ boundary within affective disorders. Methods: Diagnoses recorded in health system administrative data collections were used as a measure of clinician diagnostic behaviour. We examined all diagnoses made by public (state operated) inpatient and community mental health services in New South Wales, Australia, from 2003 to 2014. Results: A total of 31,746 people had at least one recorded diagnosis of bipolar disorder in the period. There was a significant upward trend in the age-standardised population rate of diagnosis of bipolar disorder. Bipolar disorders made up an increasing proportion of psychosis diagnoses. There was no increase in the rate of comorbid diagnosis of bipolar disorders with non-psychotic disorders or in the likelihood of diagnosis of bipolar disorder at first or subsequent episodes of depression. There were significant reductions in diagnoses of schizophrenia, particularly in younger people. Conclusion: There may be some increase in diagnoses of bipolar disorder in New South Wales public mental health services. However, some changes in diagnosis, particularly in younger adults, may reflect movement away from diagnoses of schizophrenia towards a range of other diagnoses, rather than specific movement towards bipolar disorder. Expansion of bipolar disorder may have been more marked in private practice settings and may have involved the poorly defined bipolar II subtype.
Sodium-Glucose Cotransporter 2 Inhibitors in the Treatment of Type 2 Diabetes Mellitus
Authors: Vivian Eva 
Published: October 2015

Purpose The purpose of this review article is to provide guidance to clinicians and diabetes educators regarding the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as a therapeutic option for the treatment of patients with type 2 diabetes mellitus (T2DM). Methods The PubMed database was searched through February 2015 to identify clinical trials and meta-analyses evaluating the use of the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin administered as monotherapy or in combination with other oral antidiabetes drugs or with insulin. Results SGLT2 inhibitors reduce hyperglycemia in an insulin-independent manner by inhibiting the reabsorption of glucose into the systemic circulation by the kidneys. In patients with T2DM, SGLT2 inhibitors provide consistent reductions in glycated hemoglobin, fasting plasma and postprandial glucose, body weight, and blood pressure when used as monotherapy or in combination with other oral antidiabetes agents or with insulin. SGLT2 inhibitors are associated with a low risk of hypoglycemia, except when used with agents known to be associated with a higher risk of hypoglycemia, such as sulfonylureas or insulin. Conclusions The unique renal-specific mechanism of action and favorable efficacy and safety profile of SGLT2 inhibitors support consideration of these antidiabetes agents as a treatment option for patients with T2DM.
Effects of therapeutic ultrasound on pain, physical functions and safety outcomes in patients with knee osteoarthritis: a systematic review and meta-analysis
Authors: Zhang Chi , Xie Yujie , Luo Xiaotian , Ji Qiaodan , Lu Chunlan , He Chengqi , Wang Pu 
Published: October 2015

Objective: To explore the effects of therapeutic ultrasound with sham or no intervention on pain, physical function and safety outcomes in patients with knee osteoarthritis. Data sources: This systematic review was searched on CENTRAL, EMBASE, MEDLINE, CINAHL, Physiotherapy Evidence Database, Open Gray on 4 September 2015. Trials included randomized controlled trials that compared therapeutic ultrasound with a sham or no intervention in patients with osteoarthritis of the knee. Review methods: Eligible trials and extracted data were identified by two independent investigators. Standardized mean differences (SMDs) and 95% confidence interval (CI) were calculated for pain and physical function outcomes. Heterogeneity was assessed by the I2 test and inverse-variance random-effects analysis was applied to all trials. Results: Ten randomized controlled trials (645 patients) met the inclusion criteria. Therapeutic ultrasound showed a positive effect on pain (SMD = −0.93, 95%, CI = −1.22 to −0.64, p < 0.01, p for heterogeneity = 0.12, I2 = 42%). For physical function, therapeutic ultrasound was advantageous for reducingWestern Ontario and McMaster Universities physical function score (SMD = −0.37, 95% CI = −0.73 to −0.01, p = 0.04, p for heterogeneity = 0.94, I2 = 0%). In terms of safety, no occurrence of adverse events caused by therapeutic ultrasound was reported in any trial. Conclusion: The authors suggested that therapeutic ultrasound is beneficial for reducing knee pain and improving physical functions in patients with knee osteoarthritis and could be a safe treatment.
A Rasch analysis of the model of human occupation screening tool single observation form (MOHOST-SOF) in mental health
Authors: Maciver Donald , Morley Mary , Forsyth Kirsty , Bertram Nick , Edwards Tracey , Heasman David , Rennison Jane , Rush Robert , Willis Suzie 
Published: October 2015

Introduction This study examined the psychometric properties of the model of human occupation screening tool single observation form. Method Clinical records were extracted pre- and post-treatment for 152 mental health service users. Data were model of human occupation screening tool single observation form scores and demographics. We investigated the form using Rasch analysis; we also present an analysis of change over time. Results We identified four misfitting items and evidence of instability with respect to change over time. After anchoring to adjust for unstable estimates, it was possible to measure client change, and there were significant differences in form scores pre–post treatment indicating client improvement in ability. Conclusion The study provides initial psychometric assessment of this version of the model of human occupation screening tool.
Pial Synangiosis Ameliorates Movement Disorders in the Absence of Prior Stroke in Moyamoya Disease
Authors: Greene Stephanie , Bansal Lalit , Coffman Keith A. , Nardone Raffaele , Zuccoli Giulio 
Published: October 2015

Background: Moyamoya disease is a rare cerebrovascular disease characterized by progressive stenosis of the bilateral distal internal carotid arteries and their proximal branches. Both chorea and dystonia have been reported as the initial presentation of moyamoya disease. Objective: The objective was to define the clinical presentation and describe the disease course following pial synangiosis of 3 patients with dyskinesias. Methods: A retrospective chart review of 3 cases of patients presenting with movement disorders and ultimately diagnosed with moyamoya disease was performed. Results: The authors present a case series of 1 patient with dystonia and 2 patients with chorea, all diagnosed with moyamoya disease. All patients experienced resolution of their movement disorders following pial synangiosis. Magnetic resonance imaging disclosed moyamoya disease-related basal ganglia anomalies in all patients. Conclusions: Moyamoya disease is an important and surgically treatable cause of movement disorders.
End-of-Life Care of Patients With Amyotrophic Lateral Sclerosis and Other Nonmalignant Diseases
Authors: Tiirola Anna , Korhonen Tarja , Surakka Tiina , Lehto Juho T. 
Published: October 2015

Background: Palliative care services extend to meet the needs of patients with nonmalignant diseases. Aim: To explore the diagnoses, symptoms, and treatment of patients dying in hospice due to nonmalignant diseases, with special emphasis on amyotrophic lateral sclerosis (ALS). Design: A retrospective study based on a detailed analysis of patient records. Setting/Participants: All patients with nonmalignant diseases who died in Pirkanmaa Hospice during the period 2004 to 2013 were included. Results: Of the 67 patients studied, 48% had ALS, and the remaining had pulmonary (18%), cardiovascular (13%), neurologic (10%), and other (10%) diseases. Dyspnea, followed by pain and fatigue, was the most common symptom reported, increasing in frequency from admission to the last day of life (31% vs 48%; P < .05). Compared with ALS, patients with other diseases had more comorbidities (3.8% vs 1.4%, P < .001) and were more likely to have very short (≤3 days) final care periods (31% vs 9%; P < .05). During the last day of life, patients with ALS were more frequently unable to swallow (87% vs 31%, P < .001) and received significantly more antidepressants, antibiotics, and laxatives but less corticosteroids and oxygen compared to other patients. Noninvasive ventilation was used in 31% of all patients. Conclusion: Respiratory symptoms are important in the management of nonmalignant diseases in hospice. Especially, units taking care of ALS should be prepared to meet the special needs involved in ventilation support. In contrast to ALS, late referrals to hospice are common in patients with other nonmalignant diseases.