bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer
Authors: Blute Michael L. , Zorn Kristin , Grimes Matthew , Shi Fangfang , Downs Tracy M. , Jarrard David F. , Best Sara L. , Richards Kyle , Nakada Stephen Y. , Abel E. Jason 
Published: November 2015

ObjectiveTo assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m2) is associated with peri‐operative outcomes, overall survival (OS), cancer‐specific survival (CSS), or recurrence‐free survival (RFS) after surgical treatment for renal cell carcinoma (RCC).Patients and MethodsAfter institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan–Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables.ResultsIn all, 100 patients (11.9%) with a BMI ≥ 40 kg/m2 and 743 patients (88.1%) with a BMI < 40 kg/m2 who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587–1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3–6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30‐day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m2 was not a predictor of major complications (OR 0.58, 95% CI 0.227–1.47; P = 0.251) or 90‐day mortality (P = 0.4067). BMI ≥ 40 kg/m2 was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m2 was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5‐year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/m2 and BMI ≥ 40 kg/m2, respectively (P = 0.69). The 5‐year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m2 and BMI ≥ 40 kg/m2, respectively. The 5‐year RFS rates for BMI < 40 kg/m2 and BMI ≥ 40 kg/m2 were 84.1 and 90.6%, respectively (P = 0.48).ConclusionsExtreme obesity is not associated with worse peri‐operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.
What should dental services for people with disabilities in Ireland be like? Agreed priorities from a focus group of people with learning disabilities
Authors: Mac Giolla Phadraig Caoimhin , Dougall Alison , Stapleton Siobhan , McGeown Danielle , Nunn June , Guerin Suzanne 
Published: November 2015

Accessible summaryThis study asked a group of people with learning disabilities in Ireland what was important to them about their dental services.The group easily ordered their priorities according to five topics:Access, Cost, Information, Quality of Care and Treatment.The group's discussion revealed a disempowered group who had little control over how they interacted with dental services.We suggest ways to empower people with learning disabilities in their interactions with dental services.AbstractBackground:In Ireland, people with learning disabilities have poor oral health. This is in part due to inappropriate oral health services. Recognising the value of inclusive approaches to research and healthcare planning, this study sought to include a group of people with learning disabilities in priority setting for oral health services in Ireland. This study discusses the feasibility of the methods used to promote inclusive approaches in oral healthcare planning.Materials and Methods:A single focus group of six participants with communication and cognitive impairments agreed priorities for dental services using evidence‐based research tools across five topics:Access, Cost, Information, Quality of Care and Treatment. Sorting was recorded photographically and discussion was video‐recorded, transcribed and analysed using deductive content analysis.Results:The group ranked priorities within each topic but found it difficult to meaningfully rank between topics. Across topics, issues of control, empowerment and choice were observed.Conclusions:Participants were largely disempowered in their interactions with dental services. The method used in this study to empower potential service users with disabilities was successful and can be used by others who have an interest in inclusive healthcare priority setting.
Molecular mechanism of positive allosteric modulation of the metabotropic glutamate receptor 2 by JNJ‐46281222
Authors: Doornbos Maarten L J , Pérez‐Benito Laura , Tresadern Gary , Mulder‐Krieger Thea , Biesmans Ilse , Trabanco Andrés A , Cid Jose María , Lavreysen Hilde , IJzerman Adriaan P , Heitman Laura H 
Published: November 2015

Background and PurposeAllosteric modulation of the mGlu2 receptor is a potential strategy for treatment of various neurological and psychiatric disorders. Here, we describe the in vitro characterization of the mGlu2 positive allosteric modulator (PAM) JNJ‐46281222 and its radiolabelled counterpart [3H]‐JNJ‐46281222. Using this novel tool, we also describe the allosteric effect of orthosteric glutamate binding and the presence of a bound G protein on PAM binding and use computational approaches to further investigate the binding mode.Experimental ApproachWe have used radioligand binding studies, functional assays, site‐directed mutagenesis, homology modelling and molecular dynamics to study the binding of JNJ‐46281222.Key ResultsJNJ‐46281222 is an mGlu2‐selective, highly potent PAM with nanomolar affinity (KD = 1.7 nM). Binding of [3H]‐JNJ‐46281222 was increased by the presence of glutamate and greatly reduced by the presence of GTP, indicating the preference for a G protein bound state of the receptor for PAM binding. Its allosteric binding site was visualized and analysed by a computational docking and molecular dynamics study. The simulations revealed amino acid movements in regions expected to be important for activation. The binding mode was supported by [3H]‐JNJ‐46281222 binding experiments on mutant receptors.Conclusion and ImplicationsOur results obtained with JNJ‐46281222 in unlabelled and tritiated form further contribute to our understanding of mGlu2 allosteric modulation. The computational simulations and mutagenesis provide a plausible binding mode with indications of how the ligand permits allosteric activation. This study is therefore of interest for mGlu2 and class C receptor drug discovery.
The high frequency relationship: implications for torsadogenic hERG blockers
Authors: Champeroux P , Le Guennec J Y , Jude S , Laigot C , Maurin A , Sola M L , Fowler J S L , Richard S , Thireau J 
Published: November 2015

Background and PurposeVentricular arrhythmias induced by human ether‐a‐go‐go related gene (hERG; Kv11.1 channel) blockers are a consequence of alterations in ventricular repolarisation in association with high‐frequency (HF) oscillations, which act as a primary trigger; the autonomic nervous system plays a modulatory role. In the present study, we investigated the role of β1‐adrenoceptors in the HF relationship between magnitude of heart rate and QT interval changes within discrete 10 s intervals (sorted into 5 bpm heart rate increments) and its implications for torsadogenic hERG blockers.Experimental ApproachThe HF relationship was studied under conditions of autonomic blockade with atenolol (β1‐adrenoceptor blocker) in the absence or presence of five hERG blockers in beagle dogs. In total, the effects of 14 hERG blockers on the HF relationship were investigated.Key ResultsAll the torsadogenic hERG blockers tested caused a vertical shift in the HF relationship, while hERG blockers associated with a low risk of Torsades de Pointes did not cause any vertical shift. Atenolol completely prevented the effects four torsadogenic agents (quinidine, thioridazine, risperidone and terfenadine) on the HF relationship, but only partially reduced those of dofetilide, leading to the characterization of two types of torsadogenic agent.Conclusions and ImplicationsAnalysis of the vertical shift in the HF relationship demonstrated that signs of transient sympathetic activation during HF oscillations in the presence of torsadogenic hERG blockers are mediated by β1‐adrenoceptors. We suggest the HF relationship as a new biomarker for assessing Torsades de pointes liability, with potential implications in both preclinical studies and the clinic.
Post‐breakup burial and exhumation of the southern margin of Africa
Authors: Green Paul F. , Duddy Ian R. , Japsen Peter , Bonow Johan M. , Malan Jean A. 
Published: November 2015

AbstractDespite many years of study, the processes involved in the development of the continental margin of southern Africa and the distinctive topography of the hinterland remain poorly understood. Previous thermochronological studies carried out within a monotonic cooling framework have failed to take into account constraints provided by Mesozoic sedimentary basins along the southern margin. We report apatite fission track analysis and vitrinite reflectance data in outcrop samples from the Late Jurassic to Early Cretaceous sedimentary fill of the Oudtshoorn, Gamtoos and Algoa Basins (Uitenhage Group), as well as isolated sedimentary remnants further west, plus underlying Paleozoic rocks (Cape Supergroup) and Permian‐Triassic sandstones from the Karoo Supergroup around the Great Escarpment. Results define a series of major regional cooling episodes. Latest Triassic to Early Jurassic cooling which began between 205 and 180 Ma is seen dominantly in basement flanks to the Algoa and Gamtoos Basins. This episode may have affected a wider region but in most places any effects have been overprinted by later events. The effects of Early Cretaceous (beginning between 145 and 130 Ma) and Early to mid‐Cretaceous (120–100 Ma) cooling are both delimited by major structures, while Late Cretaceous (85–75 Ma) cooling appears to have affected the whole region. These cooling events are all interpreted as dominantly reflecting exhumation. Higher Late Cretaceous paleotemperatures in samples from the core of the Swartberg Range, coupled with evidence for localised Cenozoic cooling, are interpreted as representing Cenozoic differential exhumation of the mountain range. Late Cretaceous paleotemperatures between 60°C and 90°C in outcropping Uitenhage Group sediments from the Oudtshoorn, Gamtoos and Algoa Basins require burial by between 1.2 and 2.2 km prior to Late Cretaceous exhumation. Because these sediments lie in depositional contact with underlying Paleozoic rocks in many places, relatively uniform Late Cretaceous paleotemperatures across most of the region, in samples of both basin fill and underlying basement, suggest the whole region may have been buried prior to Late Cretaceous exhumation. Cenozoic cooling (beginning between 30 and 20 Ma) is focussed mainly in mountainous regions and is interpreted as representing denudation which produced the modern‐day relief. Features such as the Great Escarpment are not related to continental break up, as is often supposed, but are much younger (post‐30 Ma). This history of post‐breakup burial and subsequent episodic exhumation is very different from conventional ideas of passive margin evolution, and requires a radical re‐think of models for development of continental margins.
Silica diagenesis in Cenozoic mudstones of the North Viking Graben: physical properties and basin modelling
Authors: Wrona Thilo , Jackson Christopher A.‐L. , Huuse Mads , Taylor Kevin G. 
Published: November 2015

AbstractSilica diagenesis can significantly change physical properties of the host strata and release large volumes of water. Predicting these changes and their timing is essential to understanding compaction, fluid flow and rock deformation in sedimentary basins. In this paper, the influence of silica diagenesis (opal‐A/CT transformation) on physical properties is determined, the sediment volume affected by these changes is mapped, and a new technique to model silica diagenesis is introduced. A petrophysical analysis of 16 exploration wells shows that the opal‐A/CT transformation leads to a porosity reduction of c.20% (from 49 to 29%) in Cenozoic mudstones of the North Viking Graben. Using three‐dimensional seismic reflection data, it is shown that the c.50 m thick opal‐A/CT transformation zone covers an area of >1500 km2, equating to a minimum volume of 75 km3. The spatial and temporal evolution of opal‐A/CT transformation is simulated using an innovative basin modelling approach, the results of which indicate that the transformation started around Middle‐to‐Late Eocene times and then migrated upwards until it gradually fossilised between the Miocene and present. These findings are important, as they help understanding how these sediments compact and when fluids are released by diagenesis.
Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy
Authors: Chan Jean L. , Koda Joy , Heilig Joseph S. , Cochran Elaine K. , Gorden Phillip , Oral Elif A. , Brown Rebecca J. 
Published: November 2015

SummaryObjectiveRecombinant human leptin (metreleptin) improves glycaemia and hypertriglyceridaemia in patients with generalized lipodystrophy; antibody development with in vitro neutralizing activity has been reported. We aimed to characterize antimetreleptin antibody development, including in vitro neutralizing activity.DesignTwo randomized controlled studies in patients with obesity (twice‐daily metreleptin ± pramlintide for 20–52 weeks; 2006–2009); two long‐term, open‐label studies in patients with lipodystrophy (once‐daily or twice‐daily metreleptin for 2 months to 12·3 years; 2000–2014).PatientsA total of 579 metreleptin‐treated patients with obesity and 134 metreleptin‐treated patients with lipodystrophy (antibody/neutralizing activity data: n = 105).MeasurementsAntimetreleptin antibodies, in vitro neutralizing activity.ResultsAntimetreleptin antibodies developed in most patients (obese: 96–100%; lipodystrophy: 86–92%). Peak antibody titers (approximately 1:125 to 1:3125) generally occurred within 4–6 months and decreased with continued therapy (lipodystrophy). Antibody development did not adversely impact efficacy or safety (patients with obesity), except for inflammatory injection site reactions, but was associated with elevated leptin concentrations. Three patients with obesity developed in vitro neutralizing activity coincident with weight gain. Weight later returned to baseline in one patient despite persistent neutralizing activity. Four patients with generalized lipodystrophy developed in vitro neutralizing activity concurrent with worsened metabolic control; two with confounding comorbidities had sepsis. One patient with lipodystrophy had resolution of neutralizing activity on metreleptin.ConclusionsDevelopment of in vitro neutralizing activity could be associated with loss of efficacy but has not been consistently associated with adverse clinical consequences. Whether neutralization of endogenous leptin with clinical consequences occurs remains unclear.
Ellipsoid zone on optical coherence tomography: a review
Authors: Tao Lingwei William , Wu Zhichao , Guymer Robyn H , Luu Chi D 
Published: November 2015

AbstractEmergence of the high‐resolution optical coherence tomography has allowed better delineation of retinal layers, and many of the anatomical correlations of these layers have now been agreed upon. However, some anatomical correlates still remain contentious, such as the second hyper‐reflective band, which is now termed ellipsoid zone. Despite the lack of consensus of the actual origin of the ellipsoid zone, there has been much interest in evaluating its integrity and intensity in different disease processes. This review paper aims to provide an overview of the ellipsoid zone and its clinical and research applications.
A re‐appraisal of publication rates of scientific papers presented at the Otorhinolaryngology Research Society meetings
Authors: Lau A.S. , Krishnan M. , Williams S.P. , Mamais C. , Sweed A. , Bhat J. , Somashekar S. , Leong S.C. 
Published: November 2015

ObjectivesTo review the rate of publication of papers in peer‐reviewed journals after oral presentations at the Otorhinolaryngology Research Society meetings between 1996 and 2013 and to compare trends with the previous review (1979–1995).DesignLiterature review.SettingMerseyside ENT Research Collaborative.ParticipantsThe abstracts of presentations at Otorhinolaryngology Research Society meetings are published in Clinical Otolaryngology. A structured search of PubMed was undertaken to identify published Otorhinolaryngology Research Society presentations.Main outcome measuresPublication rates.ResultsA total of 460 abstracts were identified. The interobserver reliability among reviewers was 98%. Of the total, 259 (56.3%) abstracts were published in peer‐reviewed journals. The average time from Otorhinolaryngology Research Society presentation to publication was 27.7 months (median 23), which was not significantly different from the previous review. Publication by subspeciality was as follows: head and neck (45.6%), otology (30.5%), rhinology (22%) and others (1.9%). Most published Otorhinolaryngology Research Society presentations were published in Clinical Otolaryngology (22.4%), followed by the Journal of Laryngology and Otology (8.1%) and the Laryngoscope (7.3%). Clinical research was the most common category of abstracts being presented at Otorhinolaryngology Research Society meetings, followed by laboratory‐based research. Over half (56.5%) of laboratory research presented were head and neck themed, while otology and rhinology predominated clinical research presentations. Over half (52.1%) of Otorhinolaryngology Research Society abstracts originated from units in the North of England. Bristol presented the most abstracts (30.1%), followed by Newcastle (25.1%).ConclusionsThe publication rate of Otorhinolaryngology Research Society presentations remains high and many are subsequently published in high‐impact factor otolaryngology journals. More Otorhinolaryngology Research Society presentations are now published in American and European journals.
Long‐term outcomes of locally or radically resected T1 colorectal cancer
Authors: Nam M. J. , Han K. S. , Kim B. C. , Hong C. W. , Sohn D. K. , Chang H. J. , Kim M. J. , Kim S. Y. , Baek J. Y. , Park S. C. , Oh J. H. 
Published: November 2015

AbstractAimLittle is known about the long‐term outcome of T1 colorectal cancer (CRC) following curative resection. The present study addressed the long‐term outcome of locally or radically resected T1 CRCs.MethodA total of 430 patients with T1 CRC who underwent local or radical resection were considered. Unfavourable histological factors were defined as positive resection margin, deep submucosal invasion, vascular invasion, Grade 3 and budding. The patients were classified as low‐risk (unfavourable histological factor negative, n = 65) or high‐risk (unfavourable histological factor positive, n = 365).ResultsOver a median follow‐up of 78.4 months, disease recurred in 16 (3.7%) patients in the high‐risk group, and no recurrence in the low‐risk group. Resection type and vascular invasion were significantly associated with recurrence. In the vascular invasion (+) high‐risk group, both 5‐year disease‐free survival rate and 5‐year overall survival rate were significantly associated with resection type (radical 94.6%, local 43.8%, P < 0.001, and radical 99.1%, local 66.7%, P < 0.001). In the vascular invasion (−) high‐risk group, 5‐year disease‐free survival rate was also significantly associated with resection type (radical 98.9%, local 84.7%, P = 0.001). However, 5‐year overall survival rate was not associated with resection type (radical 98.9%, local 95.2%, P = 0.816).ConclusionLocal resection may be effective and oncologically safe in low‐risk T1 CRC. Although additional surgery should be recommended for the locally resected high‐risk T1 CRC cases, intensive surveillance without additional surgery and timely salvage operation may offer another treatment option, if vascular invasion is negative.
Mediastinal schwannoma with atypical localization diagnosed by endobronchial ultrasound
Authors: Çiftci Fatma , Gürün Kaya Aslıhan , Karaçay Ebru , Çiledağ Aydın , Ceyhan Koray , Kaya Akın , Çelik Gökhan 
Published: November 2015

AbstractIntroductionSchwannoma is a peripheral nerve sheath tumor usually originating from the posterior mediastinum. Because schwannomas can exhibit high fluorodeoxyglucose uptake on positron emission tomography, they cannot be distinguished from malignant tumors.ObjectivesWe present this case to stress the importance of endobronchial ultrasonography in the diagnosis of intrapulmonary masses with rare occurrence and different localization.MethodsA patient was referred to our clinic for further workup of a soft tissue mass in the anterior mediastinum and diagnosed with a benign schwannoma by endobronchial ultrasonography.ResultsThe diagnosis is thus largely based on pathological examination. Until today schwannomas have been diagnosed by pathology examination of lesions excised surgically for suspected malignancy.ConclusionThis article was reported since intrapulmonary schwannoma is a very rare tumor and this was the first case of an anterior mediastinal schwannoma diagnosed by endobronchial ultrasonography.
A simple bedside approach to therapeutic goals achievement during the management of deceased organ donors – An adapted version of the “VIP” approach
Authors: Westphal Glauco Adrieno 
Published: November 2015

AbstractThe disproportion between the supply and demand of transplant organs could be alleviated by improving the quality of clinical management of deceased potential donors. As a large number of donor losses by cardiac arrest occur due to hemodynamic instability, without instituting all essential maintenance measures, it is likely that the application of simplified potential donor maintenance protocols will help to decrease potential donor losses and increase the supply of organs for transplantation. The Ventilation, Infusion and Pumping (VIP) strategy is a mnemonic method that brings together key aspects of the restoration of oxygen delivery to tissues during hemodynamic instability: adequate mechanical Ventilation, volume Infusion and evaluation of heart Pump effectiveness. The inclusion of the additional initials, “P” and “S,” refers to Pharmacological treatment and Specificities involved in the etiology of shock. The use of simplified care standards can assist in adhering to essential potential donor management measures. Therefore, using a simplified method as the adapted VIP approach can contribute to improving management standards of potential organ donors and increasing the supply of organs for transplantation.