bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Osteoarthritis Thumb Therapy (OTTER) II Trial: a study protocol for a three-arm multi-centre randomised placebo controlled trial of the clinical effectiveness and efficacy and cost-effectiveness of splints for symptomatic thumb base osteoarthritis
Authors: Adams Jo , Barratt Paula , Arden Nigel K , Barbosa Bouças Sofia , Bradley Sarah , Doherty Michael , Dutton Susan , Dziedzic Krysia , Gooberman-Hill Rachael , Hislop Lennie Kelly , Hutt Greenyer Corinne , Jansen Victoria , Luengo-Fernandez Ramon , Meagher Claire , White Peter , Williams Mark 
Published: October 2019

IntroductionThe economic cost of osteoarthritis (OA) is high. At least 4.4 million people have hand OA in the UK. Symptomatic thumb base OA affects 20% of people over 55 years, causing more pain, work and functional disability than OA elsewhere in the hand. Most evidence-based guidelines recommend splinting for hand OA. Splints that support or immobilise the thumb base are routinely used despite there being limited evidence on their effectiveness. The potential effects of placebo interventions in OA are acknowledged, but few studies investigate the clinical efficacy of rehabilitation interventions nor the impact of any placebo effects associated with splints.Methods and analysisParticipants aged 30 years and over with symptomatic thumb base OA will be recruited into the trial from secondary care occupational therapy and physiotherapy centres. Following informed consent, participants will complete a baseline questionnaire and then be randomised into one of three treatment arms: a self-management programme, a self-management programme plus a verum thumb splint or a self-management programme plus a placebo thumb splint. The primary outcome is the Australian Canadian Osteoarthritis Hand Index (AUSCAN) hand pain scale. The study endpoint is 8 weeks after baseline. Baseline assessments will be carried out prior to randomisation and outcomes collected at 4, 8 and 12 weeks. Cost-effectiveness analysis will be conducted and individual qualitative interviews conducted with up to 40 participants after 8 weeks to explore perceptions and outcome expectations of verum and placebo splints and exercise.Ethics and disseminationSouth Central—Oxford C Research Ethics Committee approved this study (16/SC/0188). The findings will be disseminated to health professional conferences, journals and lay publications for patient organisations. The research will contribute to improving the management of thumb base OA and help clinicians and patients make informed decisions about the value of different interventions.Trial registration numberISRCTN54744256.
Mainstreaming of genomic medicine in gastroenterology, present and future: a nationwide survey of UK gastroenterology trainees
Authors: Al Bakir Ibrahim , Sebepos-Rogers Gregory Malcolm , Burton Hilary , Monahan Kevin J 
Published: October 2019

ObjectiveGenomics and personalised medicine are increasingly relevant for patients with gastroenterological conditions. We aim to capture the current state of genomics training in gastroenterology to review current understanding, clinical experience and long-term educational needs of UK trainees.Design and settingA web-based nationwide survey of all UK gastroenterology specialty trainees was conducted in 2017.Results100 trainees (14% of UK gastroenterology trainees) completed this survey. Only 9% and 16% of respondents believe that their local training programme adequately prepares them for the future clinical practice using genomic medicine and personalised medicine, respectively. Barriers identified include the need for greater trainee education (95%), inadequate clinical guidance to base interventions on the results of genomic testing (53%), concerns over misinterpretation by patients (43%) and overuse/misuse of testing by clinicians (34%).Survey respondents felt prepared to perform HFE genotyping (98%), assess TPMT status (97%) and interpret HLA subtyping for suspected coeliac disease (85%). However, only a minority felt prepared to perform the following investigations: polyposis screening (34%), hereditary pancreatitis screening (30%), testing for Lynch yndrome (33%) and KRAS testing for colorectal cancer (20%).Most respondents would support holding dedicated training days on genomic medicine (83%), formal training provisions for the mainstreaming of genomic testing (64%), an update to the UK gastroenterology specialty training curriculum and examinations (57%) and better-defined referral pathways for local genomic services (91%).ConclusionMost gastroenterology trainees in this survey feel ill equipped to practise genomic and personalised medicine as consultants. We propose specific revisions to the UK gastroenterology specialty curriculum that addresses trainees needs.
Frequency and format of clinical trial results dissemination to patients: a survey of authors of trials indexed in PubMed
Authors: Schroter Sara , Price Amy , Malički Mario , Richards Tessa , Clarke Mike 
Published: October 2019

ObjectiveDissemination of research findings is central to research integrity and promoting discussion of new knowledge and its potential for translation into practice and policy. We investigated the frequency and format of dissemination to trial participants and patient groups.DesignSurvey of authors of clinical trials indexed in PubMed in 2014–2015.ResultsQuestionnaire emailed to 19 321 authors; 3127 responses received (16%). Of these 3127 trials, 2690 had human participants and 1818 enrolled individual patients. Among the 1818, 498 authors (27%) reported having disseminated results to participants, 238 (13%) planned to do so, 600 (33%) did not plan to, 176 (10%) were unsure and 306 (17%) indicated ‘other’ or did not answer. Of the 498 authors who had disseminated, 198 (40%) shared academic reports, 252 (51%) shared lay reports, 111 (22%) shared both and 164 (33%) provided individualised study results. Of the 1818 trials, 577 authors (32%) shared/planned to share results with patients outside their trial by direct contact with charities/patient groups, 401 (22%) via patient communities, 845 (46%) via presentations at conferences with patient representation, 494 (27%) via mainstream media and 708 (39%) by online lay summaries. Relatively few of the 1818 authors reported dissemination was suggested by institutional bodies: 314 (17%) of funders reportedly suggested dissemination to trial participants, 252 (14%) to patient groups; 333 (18%) of ethical review boards reportedly suggested dissemination to trial participants, 148 (8%) to patient groups. Authors described many barriers to dissemination.ConclusionFewer than half the respondents had disseminated to participants (or planned to) and only half of those who had disseminated shared lay reports. Motivation to disseminate results to participants appears to arise within research teams rather than being incentivised by institutional bodies. Multiple factors need to be considered and various steps taken to facilitate wide dissemination of research to participants.
E-Cigarettes: Unstandardized, Under-Regulated, Understudied, and Unknown Health and Cancer Risks
Authors: Hawk Ernest T. , Colbert Maresso Karen 
Published: October 2019

Abstract

E-cigarettes have the ability to deliver nicotine in a manner that is similar to, and, theoretically, safer than, combusted tobacco. However, these devices are extremely heterogeneous and regulation has struggled to keep up with their rapid evolution. A compilation of early data suggest that e-cigarettes may contain numerous toxic substances, including known carcinogens. However, there are few data available on the short- and long-term health effects of e-cigarettes, including any potential effect on cancer risk. Until more is known, e-cigarettes should not be considered a safe alternative to combusted tobacco use.
Uma abordagem semiótica da messianidade de Portugal em Mensagem, de Fernando Pessoa
Authors: Brito Clebson Luiz de , Lara Glaucia Muniz Proença 
Published: October 2019

À luz de contribuições provenientes tanto da Semiótica Narrativa quanto da Semiótica Tensiva, este trabalho aborda a obra Mensagem, do poeta português Fernando Pessoa. Tomando como unidade de sentido o conjunto de poemas que integram a referida obra, nosso objetivo é examinar como se estrutura a elaboração poética do messianismo português na retomada da história de Portugal por Pessoa. Nesse sentido, pretendemos demonstrar que o discurso do poeta esteia-se sobre um contrato transcendente entre Portugal e a instância divina, contrato esse que se revela, seja no uso reiterado das etapas narrativas da manipulação e da sanção, seja no apelo a um processo de triagem, que distingue Portugal das demais nações.
Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase–Dependent Inhibition of a Ubiquitin Proteasome System
Authors: Paredes Felipe , Williams Holly C. , Quintana Raymundo A. , San Martin Alejandra 
Published: October 2019

Rationale:
The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle. As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity. Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation. Thus, we hypothesize that the metabolic reprograming induced by Poldip2 deficiency controls VSMC differentiation.

Objective:
To determine the role of Poldip2-mediated metabolic reprograming in phenotypic modulation of VSMC.

Methods and Results:
We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4). Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor). Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation. Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.

Conclusions:
Our data show that Poldip2 deficiency induces a highly differentiated phenotype in VSMCs through a mechanism that involves regulation of metabolism and proteostasis. Additionally, our study positions mitochondria-initiated signaling as key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases.
Early and Late Effects of Cardiac Resynchronization Therapy in Adult Congenital Heart Disease
Authors: Yin Yanrong , Dimopoulos Konstantinos , Shimada Eriko , Lascelles Karen , Griffiths Samuel , Wong Tom , Gatzoulis Michael A. , Babu‐Narayan Sonya V. , Li Wei 
Published: October 2019

Background

There are limited data about cardiac resynchronization therapy (
CRT
) in adult congenital heart disease. We aimed to assess early and late outcomes of
CRT
among patients with adult congenital heart disease.

Methods and Results

We retrospectively studied 54 patients with adult congenital heart disease (median age, 46 years; range, 18–73 years; 74% men) who received
CRT
implantation (biventricular paced >90%) between 2004 and 2017. Clinical and echocardiographic data were analyzed at baseline and early (mean±SD: 1.8±0.8 years) and late (4.7±0.8 years) follow‐up after
CRT
. Compared with baseline,
CRT
was associated with significant improvement at early follow‐up in New York Heart Association functional class,
QRS
duration, and cardiothoracic ratio (
P
<0.05 for all); improvement in New York Heart Association class was sustained at late follow‐up. Among patients with a systemic left ventricle (
LV
; n=39), there was significant increase in
LV
ejection fraction and reduction in
LV
end‐systolic volume at early and late follow‐up (
P
<0.05 for both). For patients with a systemic right ventricle (n=15), there was a significant early but not late reduction in systemic right ventricular basal and longitudinal diameters. Eleven patients died, and 2 had heart transplantation unrelated to systemic ventricular morphological characteristics. Thirty‐five patients (65%) responded positively to
CRT
, but only baseline
QRS
duration was predictive of a positive response.

Conclusions

CRT
results in sustained improvement in functional class, systemic
LV
size, and function. Patients with a systemic
LV
and prolonged
QRS
duration, independent of
QRS
morphological characteristics, were most likely to respond to
CRT
.
Linking ITCZ Migrations to the AMOC and North Atlantic/Pacific SST Decadal Variability
Authors: Moreno-Chamarro E. , Marshall J. , Delworth T. L. 
Published: October 2019

AbstractWe examine the link between migrations in the intertropical convergence zone (ITCZ) and changes in the Atlantic meridional overturning circulation (AMOC), Atlantic multidecadal variability (AMV), and Pacific decadal oscillation (PDO). We use a coupled climate model that allows us to integrate over climate noise and assess underlying mechanisms. We use an ensemble of ten 300-yr-long simulations forced by a 50-yr oscillatory North Atlantic Oscillation (NAO)-derived surface heat flux anomaly in the North Atlantic, and a 4000-yr-long preindustrial control simulation performed with GFDL CM2.1. In both setups, an AMV phase change induced by a change in the AMOC’s cross-equatorial heat transport forces an atmospheric interhemispheric energy imbalance that is compensated by a change in the cross-equatorial atmospheric heat transport due to a meridional ITCZ shift. Such linkages occur on decadal time scales in the ensemble driven by the imposed forcing, and internally on multicentennial time scales in the control. Regional precipitation anomalies differ between the ensemble and the control for a zonally averaged ITCZ shift of similar magnitude, which suggests a dependence on time scale. Our study supports observational evidence of an AMV–ITCZ link in the twentieth century and further links it to the AMOC, whose long-time-scale variability can influence the phasing of ITCZ migrations. In contrast to the AMV, our calculations suggest that the PDO does not drive ITCZ migrations, because the PDO does not modulate the interhemispheric energy balance.
Extended-Range Probabilistic Fire-Weather Forecasting Based on Ensemble Model Output Statistics and Ensemble Copula Coupling
Authors: Worsnop Rochelle P. , Scheuerer Michael , Hamill Thomas M. 
Published: October 2019

AbstractProbabilistic fire-weather forecasts provide pertinent information to assess fire behavior and danger of current or potential fires. Operational fire-weather guidance is provided for lead times fewer than seven days, with most products only providing day 1–3 outlooks. Extended-range forecasts can aid in decisions regarding placement of in- and out-of-state resources, prescribed burns, and overall preparedness levels. We demonstrate how ensemble model output statistics and ensemble copula coupling (ECC) postprocessing methods can be used to provide locally calibrated and spatially coherent probabilistic forecasts of the hot–dry–windy index (and its components). The univariate postprocessing fits the truncated normal distribution to data transformed with a flexible selection of power exponents. Forecast scenarios are generated via the ECC-Q variation, which maintains their spatial and temporal coherence by reordering samples from the univariate distributions according to ranks of the raw ensemble. A total of 20 years of ECMWF reforecasts and ERA-Interim reanalysis data over the continental United States are used. Skill of the forecasts is quantified with the continuous ranked probability score using benchmarks of raw and climatological forecasts. Results show postprocessing is beneficial during all seasons over CONUS out to two weeks. Forecast skill relative to climatological forecasts depends on the atmospheric variable, season, location, and lead time, where winter (summer) generally provides the most (least) skill at the longest lead times. Additional improvements of forecast skill can be achieved by aggregating forecast days. Illustrations of these postprocessed forecasts are explored for a past fire event.
Adverse Events Associated with Balloon Sinuplasty: A MAUDE Database Analysis
Authors: Hur Kevin , Ge Marshall , Kim Jeehong , Ference Elisabeth H. 
Published: October 2019

ObjectiveBalloon sinuplasty utilization has increased significantly since its introduction over a decade ago. However, the most common associated complications are still unknown. The objective of this study was to analyze adverse events related to balloon sinuplasty.Study DesignRetrospective cross‐sectional analysis.SettingFood and Drug Administration’s MAUDE database (Manufacturer and User Facility Device Experience; 2008‐2018).Subjects and MethodsThe MAUDE database was searched for all reports on adverse events involving balloon sinuplasty devices from the 3 leading manufacturers: Acclarent, Entellus, and Medtronic. Reported events were reviewed and categorized.ResultsDuring the study period, there were 211 adverse events from 208 reports divided into the following categories: patient related (n = 102, 48.3%), device related (n = 101, 47.9%), and packaging related (n = 8, 3.8%). Four periprocedural deaths were reported but were not clearly associated with technical complications. The most common device‐related complications were guide catheter malfunction (39.6%), balloon malfunction (38.6%), and imprecise navigation (17.8%). The most common patient‐related complications were cerebrospinal fluid leak (36.3%), eye swelling (29.4%), and epistaxis (11.8%). A lateral canthotomy was performed in 30.0% of eye‐swelling complications. Sixty percent of eye complications occurred during balloon dilation of the maxillary sinus. The years 2014 (n = 48) and 2012 (n = 32) had the highest number of adverse events reported as compared with all other years.ConclusionThe most common adverse events associated with balloon sinuplasty include balloon malfunction, guide catheter malfunction, cerebrospinal fluid leak, and significant eye swelling. Health care providers should discuss these possible complications when consenting patients for balloon sinuplasty.
The Association Between a Hindfoot Deformity Assessed by Weightbearing CT and the Full Leg Alignment
Authors: Burssens Arne , Buedts Kristian , Barg Alexej , Vluggen Elizabeth , Demey Patrick , Saltzman Charles , Victor Jan 
Published: October 2019

Category: Hindfoot Introduction/Purpose: The exact relationship between different types of hindfoot deformities and the full leg alignment is currently unclear. Therefore, our aim is to assess hindfoot alignment on a weight-bearing CT (WBCT) and its association with the full leg radiographic alignment. Methods: A retrospective analysis was performed on a study population of 109 patients (mean age of 53 years ± 14.49) with a varus or valgus hindfoot deformity and the presence or absence of ankle osteoarthritis (OA) based on the Takakura classification. The mechanical hindfoot - (mHA) and subtalar vertical angle (SVA) were determined on WBCT, while the mechanical tiba – (mTA) and mechanical tibiofemoral angle (mTFA) were measured on full leg radiographs. Results: In patients with ankle OA, a hindfoot valgus deformity was associated with a significantly higher mean varus alignment of the knee (mTFA = -1.8°±2.1; mTAx= -4.3°±1.9) compared to a valgus alignment of the knee (mTFA = 0.3°±2.6; mTAx= -1.4°±2.2; P <0.001) in patients with a varus hindfoot (Fig1A, B). The opposite relation was found in patients without ankle OA (P <0.001). The SVA was significantly more orientated in valgus (mean=106.9°±8.0) for patients with a hindfoot valgus compared to a higher varus orientation (mean=89.3°±13.9) in patients with a hindfoot varus deformity (P <0.001). The same pattern was found in patients without ankle OA, but not significant (P >0.05). Conclusion: A valgus hindfoot deformity demonstrated a higher varus alignment of the knee when compared to patients with a hindfoot varus deformity, if ankle OA was present. The subtalar joint did not attain an overall compensatory correction towards the hindfoot deformity as opposed to a compensatory orientation of the tibia alignment. In clinical practice, these findings could improve the current understanding of both joint preserving as well as joint replacing procedures of the hindfoot and the knee.
Long-Term Outcomes and Alignment following Isolated Fibular Sesamoidectomy
Authors: Ford Samuel E. , Adair Christopher R. , Cohen Bruce E. , Davis W. Hodges , Ellington J. Kent , Jones Carroll P. , Anderson Robert B. 
Published: October 2019

Category: Bunion, Midfoot/Forefoot, Sesamoid Introduction/Purpose: Potential etiologies of sesamoid related pain include repetitive stresses, fracture, cartilage lesions, arthrosis, and/or osteonecrosis. When patients fail to respond to conservative treatment, surgical intervention may be indicated in the form of sesamoid bone grafting, shaving/debridement, and/or sesamoid excision. Minimal published literature exists regarding the long-term safety and efficacy of fibular sesamoidectomy. The purpose of this study was to evaluate patients following isolated, complete fibular sesamoidectomy for long-term pain relief, functional outcome, and changes in hallux alignment. Methods: A query of a tertiary referral center administrative database was performed using the CPT code 28135 for sesamoidectomy between 10/1/2005 and 9/1/2016. Patients who underwent an isolated fibular sesamoidectomy were identified and contacted by their treating physicians with a recruitment letter, phone call, or e-mail to return for an office visit. The primary outcome measure was preoperative to final postoperative change in ten-point visual analog scale pain score. Secondary measures included satisfaction, hallux flexion strength, change in hallux alignment, and final post-operative functional outcome scores. Patients who met the 2-year clinical or radiographic follow-up minimum were included. Patients who underwent concomitant joint realignment procedures or had a medical history of either diabetes or peripheral neuropathy were excluded. Results: Ninety-three fibular sesamoidectomies were identified. Thirty-six sesamoidectomies (35 patients) met inclusion criteria (median follow-up 60 months). The average patient was 36-years-old with a BMI of 24.7 kg/m2 and underwent sesamoidectomy a mean 1.1 years after initial diagnosis. Median VAS scores improved 5 (6 to 1) points at final follow-up (p<0.0001). Final post- operative hallux valgus angle (HVA) did not differ from pre-operative values (10.5°/8.5°, p=0.12); similarly, intermetatarsal angle (IMA) did not differ (8.0°/7.9°, p=0.53). 88% of patients would have surgery again and 70% were “very satisfied” with their result. Hallux flexion strength (mean 14.7 pounds) did not differ following sesamoidectomy relative to the contralateral foot (mean 16.1 pounds) (p=0.23). Among the full 93 case cohort, 3 patients underwent 4 known reoperations. Conclusion: Fibular sesamoidectomy effectively provides long-term pain relief for patients with sesamoiditis, fracture, nonunion, osteonecrosis, and arthritis at long-term follow-up (median 5 years). Potential long-term sequelae, including hallux flexion weakness, change in hallux alignment, and deterioration of patient satisfaction/function were not encountered.