bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Interaction between the Matrix Protein of Vesicular Stomatitis Virus and the Immunoproteasome Subunit LMP2
Authors: Beilstein Frauke , Obiang Linda , Raux Hélène , Gaudin Yves 
Published: August 2015

ABSTRACT
The matrix protein (M) of vesicular stomatitis virus (VSV) is involved in virus assembly, budding, gene regulation, and cellular pathogenesis. Using a yeast two-hybrid system, the M globular domain was shown to interact with LMP2, a catalytic subunit of the immunoproteasome (which replaces the standard proteasome catalytic subunit PSMB6). The interaction was validated by coimmunoprecipitation of M and LMP2 in VSV-infected cells. The sites of interaction were characterized. A single mutation of M (I96A) which significantly impairs the interaction between M and LMP2 was identified. We also show that M preferentially binds to the inactive precursor of LMP2 (bearing an N-terminal propeptide which is cleaved upon LMP2 maturation). Furthermore, taking advantage of a sequence alignment between LMP2 and its proteasome homolog, PSMB6 (which does not bind to M), we identified a mutation (L45R) in the S1 pocket where the protein substrate binds prior to cleavage and a second one (D17A) of a conserved residue essential for the catalytic activity, resulting in a reduction of the level of binding to M. The combination of both mutations abolishes the interaction. Taken together, our data indicate that M binds to LMP2 before its incorporation into the immunoproteasome. As the immunoproteasome promotes the generation of major histocompatibility complex (MHC) class I-compatible peptides, a feature which favors the recognition and the elimination of infected cells by CD8 T cells, we suggest that M, by interfering with the immunoproteasome assembly, has evolved a mechanism that allows infected cells to escape detection and elimination by the immune system.

IMPORTANCE
The immunoproteasome promotes the generation of MHC class I-compatible peptides, a feature which favors the recognition and the elimination of infected cells by CD8 T cells. Here, we report on the association of vesicular stomatitis virus (VSV) matrix protein (M) with LMP2, one of the immunoproteasome-specific catalytic subunits. M preferentially binds to the LMP2 inactive precursor. The M-binding site on LMP2 is facing inwards in the immunoproteasome and is therefore not accessible to M after its assembly. Hence, M binds to LMP2 before its incorporation into the immunoproteasome. We suggest that VSV M, by interfering with the immunoproteasome assembly, has evolved a mechanism that allows infected cells to escape detection and elimination by the immune system. Modulating this M-induced immunoproteasome impairment might be relevant in order to optimize VSV for oncolytic virotherapy.
A prediction model to estimate completeness of electronic physician claims databases
Authors: Lix Lisa M , Yao Xue , Kephart George , Quan Hude , Smith Mark , Kuwornu John Paul , Manoharan Nitharsana , Kouokam Wilfrid , Sikdar Khokan 
Published: August 2015

ObjectivesElectronic physician claims databases are widely used for chronic disease research and surveillance, but quality of the data may vary with a number of physician characteristics, including payment method. The objectives were to develop a prediction model for the number of prevalent diabetes cases in fee-for-service (FFS) electronic physician claims databases and apply it to estimate cases among non-FFS (NFFS) physicians, for whom claims data are often incomplete.DesignA retrospective observational cohort design was adopted.SettingData from the Canadian province of Newfoundland and Labrador were used to construct the prediction model and data from the province of Manitoba were used to externally validate the model.ParticipantsA cohort of diagnosed diabetes cases was ascertained from physician claims, insured resident registry and hospitalisation records. A cohort of FFS physicians who were responsible for the diagnosis was ascertained from physician claims and registry data.Primary and secondary outcome measuresA generalised linear model with a γ distribution was used to model the number of diabetes cases per FFS physician as a function of physician characteristics. The expected number of diabetes cases per NFFS physician was estimated.ResultsThe diabetes case cohort consisted of 31 714 individuals; the mean cases per FFS physician was 75.5 (median=49.0). Sex and years since specialty licensure were significantly associated (p<0.05) with the number of cases per physician. Applying the prediction model to NFFS physician registry data resulted in an estimate of 18 546 cases; only 411 were observed in claims data. The model demonstrated face validity in an independent data set.ConclusionsComparing observed and predicted disease cases is a useful and generalisable approach to assess the quality of electronic databases for population-based research and surveillance.
Association of worker characteristics and early reimbursement for physical therapy, chiropractic and opioid prescriptions with workers’ compensation claim duration, for cases of acute low back pain: an observational cohort study
Authors: Busse Jason W , Ebrahim Shanil , Heels-Ansdell Diane , Wang Li , Couban Rachel , Walter Stephen D 
Published: August 2015

ObjectiveTo assess the association between early reimbursement for physiotherapy, chiropractic and opioid prescriptions for acute low back pain (LBP) with disability claim duration.DesignObservational cohort study.Setting and participantsFrom a random sample of 6665 claims for acute, uncomplicated LBP approved by the Ontario Workplace Safety and Insurance Board (WSIB) in 2005, we analysed 1442 who remained on full benefits at 4 weeks after claim approval.Primary outcome measureOur primary outcome was WSIB claim duration.ResultsWe had complete data for all but 3 variables, which had <15% missing data, and we included missing data as a category for these factors. Our time-to-event analysis was adjusted for demographic, workplace and treatment factors, but not injury severity, although we attempted to include a sample with very similar, less-severe injuries. Regarding significant factors and treatment variables in our adjusted analysis, older age (eg, HR for age ≥55 vs <25=0.52; 99% CI 0.36 to 0.74) and WSIB reimbursement for opioid prescription in the first 4 weeks of a claim (HR=0.68; 99% CI 0.53 to 0.88) were associated with longer claim duration. Higher predisability income was associated with longer claim duration, but only among persistent claims (eg, HR for active claims at 1 year with a predisability income >$920 vs ≤$480/week=0.34; 99% CI 0.17 to 0.68). Missing data for union membership (HR=1.27; 99% CI 1.01 to 1.59), and working for an employer with a return-to-work programme were associated with fewer days on claim (HR=1.78; 99% CI 1.45 to 2.18). Neither reimbursement for physiotherapy (HR=1.01; 99% CI 0.86 to 1.19) nor chiropractic care (HR for active claims at 60 days=1.15; 99% CI 0.94 to 1.41) within the first 4 weeks was associated with claim duration. Our meta-analysis of 3 studies (n=51 069 workers) confirmed a strong association between early opioid use and prolonged claim duration (HR=0.57, 95% CI 0.48 to 0.69; low certainty evidence).ConclusionsOur analysis found that early WSIB reimbursement for physiotherapy or chiropractic care, in claimants fully off work for more than 4 weeks, was not associated with claim duration, and that early reimbursement for opioids predicted prolonged claim duration. Well-designed randomised controlled trials are needed to verify our findings and establish causality between these variables and claim duration.
Treatment of experimental aneurysms with a new liquid embolic agent and a retrievable stent: proof of concept and feasibility study
Authors: Berenstein Alejandro 
Published: August 2015

BackgroundOcclusion of canine bifurcation and sidewall aneurysms was undertaken with a new liquid embolic agent (PHIL 35) assisted by a high-density partially retrievable stent (FRED) with preservation of the carotid artery.MethodsThree dogs were used as acute preparations for development of the technique and two were used for chronic studies lasting 90 days. In one animal we intentionally did not completely fill the aneurysm to determine the long-term results of incomplete treatment. The degree of occlusion, carotid artery compromise, and dislodgement and/or migration of embolic material in treated aneurysms were assessed.ResultsAll aneurysms planned for complete obliteration were totally occluded successfully. By design, we partially occluded one aneurysm. In this aneurysm, angiography performed at 30 days revealed less filling, but at 90 days it had persistent small residual filling. We did not detect any distal embolization during the injection and no angiographic occlusions, change in configuration, or delayed migration of the embolic material were found. In the inspected stent, no foreign material was noted. In four animals we successfully removed the stent with preservation of the integrity of the carotid artery. In the fifth we intentionally left both stents deployed.ConclusionsWe have developed a new treatment for cerebral aneurysms using a combination of a retrievable stent and a new liquid embolic agent.
Seribantumab, an Anti-ERBB3 Antibody, Delays the Onset of Resistance and Restores Sensitivity to Letrozole in an Estrogen Receptor–Positive Breast Cancer Model
Authors: Curley Michael D. , Sabnis Gauri J. , Wille Lucia , Adiwijaya Bambang S. , Garcia Gabriela , Moyo Victor , Kazi Armina A. , Brodie Angela , MacBeath Gavin 
Published: August 2015

Abstract
Heregulin-driven ERBB3 signaling has been implicated as a mechanism of resistance to cytotoxic and antiendocrine therapies in preclinical breast cancer models. In this study, we evaluated the effects of seribantumab (MM-121), a heregulin-blocking anti-ERBB3 monoclonal antibody, alone and in combination with the aromatase inhibitor letrozole, on cell signaling and tumor growth in a preclinical model of postmenopausal estrogen receptor–positive (ER+) breast cancer. In vitro, heregulin treatment induced estrogen receptor phosphorylation in MCF-7Ca cells, and long-term letrozole-treated (LTLT-Ca) cells had increased expression and activation levels of EGFR, HER2, and ERBB3. Treatment with seribantumab, but not letrozole, inhibited basal and heregulin-mediated ERBB receptor phosphorylation and downstream effector activation in letrozole-sensitive (MCF-7Ca) and -refractory (LTLT-Ca) cells. Notably, in MCF-7Ca–derived xenograft tumors, cotreatment with seribantumab and letrozole had increased antitumor activity compared with letrozole alone, which was accompanied by downregulated PI3K/MTOR signaling both prior to and after the development of resistance to letrozole. Moreover, the addition of an MTOR inhibitor to this treatment regimen did not improve antitumor activity and was not well tolerated. Our results demonstrate that heregulin-driven ERBB3 signaling mediates resistance to letrozole in a preclinical model of ER+ breast cancer, suggesting that heregulin-expressing ER+ breast cancer patients may benefit from the addition of seribantumab to antiendocrine therapy. Mol Cancer Ther; 14(11); 2642–52. ©2015 AACR.
Onset of optimal P2Y12-ADP receptor blockade after ticagrelor and prasugrel intake in Non-ST elevation acute coronary syndrome
Authors: Laine Marc , Camoin-Jau Laurence , Noirot Frederic , Guieu Régis , Dignat-George Françoise , Paganelli Franck , Frere Corinne , Bonello Laurent 
Published: August 2015

SummaryPretreatment with a loading dose (LD) of clopidogrel or ticagrelor before percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is supported by the guidelines, but debated following a recent meta-analysis on clopidogrel pretreatment and the ACCOAST trial. In this trial prasugrel pretreatment failed to reduce ischaemic events. The timing of optimal platelet reactivity (PR) inhibition of ticagrelor and prasugrel in non ST-elevation ACS (NSTE ACS) is yet undetermined. In the present study, we aimed to investigate the delay required to reach optimal PR inhibition in NSTE ACS following a LD of ticagrelor or prasugrel. Consecutive patients undergoing PCI for NSTE ACS were randomised in this monocentre study. The Vasodilatorphosphoprotein index (VASP) was used to measure PR before the LD and then at 30 minutes, 1, 2, 4 and 24 hours (h) post-LD. Optimal PR inhibition was defined as a VASP< 50 %. We randomised 24 patients to ticagrelor or prasugrel LD. One hour after the LD, 29 % of patients had a VASP > 50 % (ticagrelor and prasugrel: 25 vs 33 %; p=0.7). Optimal PR inhibition was obtained 2 h after the LD in both groups (12/12 with ticagrelor and 11/12 with prasugrel). At that time, the mean VASP index was 19 ± 16 % (95 %CI: 12–25). Maximal PR inhibition was reached after 4 h: 11 ± 10 % (95 %CI: 6–15). In NSTE ACS undergoing PCI a LD of ticagrelor or prasugrel given during the procedure provides optimal P2Y12-ADP receptor blockade in 2 h and maximal inhibition within 4 h.
Relation of Smoking With Total Mortality and Cardiovascular Events Among Patients With Diabetes Mellitus
Authors: Pan An , Wang Yeli , Talaei Mohammad , Hu Frank B. 
Published: August 2015

Background—
The prevalence of smoking in diabetic patients remains high, and reliable quantification of the excess mortality and morbidity risks associated with smoking is important for diabetes management. We performed a systematic review and meta-analysis of prospective cohort studies to evaluate the relation of active smoking with risk of total mortality and cardiovascular events among diabetic patients.

Methods and Results—
We searched Medline and Embase databases through May 2015, and multivariate-adjusted relative risks were pooled by using random-effects models. A total of 89 cohort studies were included. The pooled adjusted relative risk (95% confidence interval) associated with smoking was 1.55 (1.46–1.64) for total mortality (48 studies with 1 132 700 participants and 109 966 deaths), and 1.49 (1.29–1.71) for cardiovascular mortality (13 studies with 37 550 participants and 3163 deaths). The pooled relative risk (95% confidence interval) was 1.44 (1.34–1.54) for total cardiovascular disease (16 studies), 1.51 (1.41–1.62) for coronary heart disease (21 studies), 1.54 (1.41–1.69) for stroke (15 studies), 2.15 (1.62–2.85) for peripheral arterial disease (3 studies), and 1.43 (1.19–1.72) for heart failure (4 studies). In comparison with never smokers, former smokers were at a moderately elevated risk of total mortality (1.19; 1.11–1.28), cardiovascular mortality (1.15; 1.00–1.32), cardiovascular disease (1.09; 1.05–1.13), and coronary heart disease (1.14; 1.00–1.30), but not for stroke (1.04; 0.87–1.23).

Conclusions—
Active smoking is associated with significantly increased risks of total mortality and cardiovascular events among diabetic patients, whereas smoking cessation is associated with reduced risks in comparison with current smoking. The findings provide strong evidence for the recommendation of quitting smoking among diabetic patients.
Characteristics of the Springtime Alpine Valley Atmospheric Boundary Layer Using Self-Organizing Maps
Authors: Katurji Marwan , Noonan Bob , Zawar-Reza Peyman , Schulmann Tobias , Sturman Andrew 
Published: August 2015

AbstractVertical profiles of wind velocity and air temperature from a sound detection and ranging (sodar) radio acoustic sounding system (RASS)-derived dataset within an alpine valley of the New Zealand Southern Alps were analyzed. The data covered the month of September 2013, and self-organizing maps (SOM; a data-clustering approach that is based on an unsupervised machine-learning algorithm) are used to detect topological relationships between profiles. The results of the SOM were shown to reflect the physical processes within the valley boundary layer by preserving valley boundary layer dynamics and its response to wind shear. By examining the temporal evolution of ridgetop wind speed and direction and SOM node transitions, the sensitivity of the valley boundary layer to ridgetop weather conditions was highlighted. The approach of using a composite variable (wind speed and potential temperature) with SOM was successful in revealing the coupling of dynamics and atmospheric stability. The results reveal the capabilities of SOM in analyzing large datasets of atmospheric boundary layer measurements and elucidating the connectivity of ridgetop wind speeds and valley boundary layers.
Dynamics of the Northern Annular Mode at Weekly Time Scales
Authors: Rivière Gwendal , Drouard Marie 
Published: August 2015

Abstract
Rapid onsets of positive and negative tropospheric northern annular mode (NAM) events during boreal winters are studied using ERA-Interim datasets. The NAM anomalies first appear in the North Pacific from low-frequency Rossby wave propagation initiated by anomalous convection in the western tropical Pacific around 2 weeks before the peak of the events. For negative NAM, the enhanced convection leads to a zonal acceleration of the Pacific jet, while for positive NAM, the reduced convection leads to a poleward-deviated jet in its exit region. The North Atlantic anomalies, which correspond to North Atlantic Oscillation (NAO) anomalies, are formed in close connection with the North Pacific anomalies via downstream propagation of low-frequency planetary-scale and high-frequency synoptic waves, the latter playing a major role during the last onset week. Prior to positive NAM, the generation of synoptic waves in the North Pacific and their downstream propagation is strong. The poleward-deviated Pacific jet favors a southeastward propagation of the waves across North America and anticyclonic breaking in the North Atlantic. The associated strong poleward eddy momentum fluxes push the Atlantic jet poleward and form the positive NAO phase. Conversely, prior to negative NAM, synoptic wave propagation across North America is significantly reduced and more zonal because of the more zonally oriented Pacific jet. This, together with a strong eddy generation in the North Atlantic, leads to equatorward eddy momentum fluxes, cyclonic wave breaking, and the formation of the negative NAO phase. Even though the stratosphere may play a role in some individual cases, it is not the main driver of the composited tropospheric NAM events.
Experiences of discrimination and positive treatment in people with mental health problems: Findings from an Australian national survey
Authors: Reavley Nicola J , Jorm Anthony F 
Published: August 2015

Objective: Stigma and discrimination are central concerns for people with mental health problems. The aim of the study was to carry out a national survey in order to assess experiences of avoidance, discrimination and positive treatment in people with mental health problems. Methods: In 2014, telephone interviews were carried out with 5220 Australians aged 18+, 1381 of whom reported a mental health problem or scored highly on a symptom screening questionnaire. Questions covered experiences of avoidance, discrimination and positive treatment by friends, spouse, other family, workplace, educational institution and others in the community. Results: In most domains, respondents reported more positive treatment experiences than avoidance or discrimination. Friends and family were more likely to avoid the person than to discriminate. Conclusion: The results can provide input into the design of anti-discrimination interventions and further empower people with mental health problems as they advocate for change in the area of discrimination.
Patients’ experiences of a new integrated breathlessness support service for patients with refractory breathlessness: Results of a postal survey
Authors: Reilly Charles C , Bausewein Claudia , Pannell Caty , Moxham John , Jolley Caroline J , Higginson Irene J 
Published: August 2015

Background: We developed a new single point of access to integrated palliative care, respiratory medicine and physiotherapy: the breathlessness support service for patients with advanced disease and refractory breathlessness. This study aimed to describe patients’ experiences of the service and identify the aspects valued. Design: We attempted to survey all patients who had attended and completed the 6-week breathlessness support service intervention by sending them a postal questionnaire to self-complete covering experience, composition, effectiveness of the BSS and about participation in research. Data were analysed using descriptive statistics and thematic analysis of free text comments. Results: Of the 70 postal questionnaires sent out, 25 (36%) returned. A total of 21 (84% (95% confidence interval: 69%–98%)) responding patients reported that they definitely found the breathlessness support service helpful and 13 (52% (95% confidence interval: 32%–72%)) rated the breathlessness support service as excellent. A total of 21 (84% (95% confidence interval: 69%–98%)) patients reported that the breathlessness support service helped with their management of their breathlessness along with additional symptoms and activities (e.g. mood and mobility). Four key themes were identified: (1) personalised care, (2) caring nature of the staff, (3) importance of patient education to empower patients and (4) effectiveness of context-specific breathlessness interventions. These were specific aspects that patients valued. Conclusion: Patients’ satisfaction with the breathlessness support service was high, and identified as important to this was a combination of personalised care, nature of staff, education and empowerment, and use of specific interventions. These components would be important in any future breathlessness service.