bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of lenalidomide in mantle cell lymphoma can be explained by NK cell‐mediated cytotoxicity
Authors: Hagner Patrick R. , Chiu Hsiling , Ortiz Maria , Apollonio Benedetta , Wang Maria , Couto Suzana , Waldman Michelle F. , Flynt Erin , Ramsay Alan G. , Trotter Matthew , Gandhi Anita K. , Chopra Rajesh , Thakurta Anjan 
Published: August 2017

SummaryLenalidomide is an immunomodulatory agent that has demonstrated clinical benefit for patients with relapsed or refractory mantle cell lymphoma (MCL); however, despite this observed clinical activity, the mechanism of action (MOA) of lenalidomide has not been characterized in this setting. We investigated the MOA of lenalidomide in clinical samples from patients enrolled in the CC‐5013‐MCL‐002 trial (NCT00875667) comparing single‐agent lenalidomide versus investigator's choice single‐agent therapy and validated our findings in pre‐clinical models of MCL. Our results revealed a significant increase in natural killer (NK) cells relative to total lymphocytes in lenalidomide responders compared to non‐responders that was associated with a trend towards prolonged progression‐free survival and overall survival. Clinical response to lenalidomide was independent of baseline tumour microenvironment expression of its molecular target, cereblon, as well as genetic mutations reported to impact clinical response to the Bruton tyrosine kinase inhibitor ibrutinib. Preclinical experiments revealed lenalidomide enhanced NK cell‐mediated cytotoxicity against MCL cells via increased lytic immunological synapse formation and secretion of granzyme B. In contrast, lenalidomide exhibited minimal direct cytotoxic effects against MCL cells. Taken together, these data provide the first insight into the clinical activity of lenalidomide against MCL, revealing a predominately immune‐mediated MOA.
Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T‐lineage acute lymphoblastic leukaemia or T‐lineage lymphoblastic lymphoma: results of a phase 4 study
Authors: Zwaan Christian Michel , Kowalczyk Jerzy , Schmitt Claudine , Bielorai Bella , Russo Mark W. , Woessner Mary , Ranganathan Sulabha , Leverger Guy 
Published: August 2017

SummaryNelarabine is an antineoplastic agent approved for the treatment of relapsed/refractory T‐lineage acute lymphoblastic leukaemia (T‐ALL) or T‐lineage acute lymphoblastic lymphoma (T‐LBL). The purpose of this phase 4, multicentre, single‐arm, observational, open‐label trial was to provide additional data on the safety and efficacy of nelarabine under licensed conditions of use in children and young adults ≤21 years of age. Patients (N = 28) had a mean ± standard deviation age of 11·5 ± 4·6 years; 71% were male and 61% had a diagnosis of T‐ALL. Adverse events (AEs) and treatment‐related AEs were experienced by 46% and 21%, respectively, and included few haematological AEs and no haematological serious AEs. Neurological AEs from one of four predefined categories (peripheral and central nervous systems, mental status change and uncategorized) were reported in four patients. There were no AE‐related treatment discontinuations/withdrawals. The overall response rate was 39.3%: complete response (CR), 35.7%; CR without full haematological recovery (CR*), 3.6%. Post‐treatment stem cell transplantation was performed for 46% of the cohort. Median overall survival (OS) was 3·35 months for non‐responders and not reached for responders (CR + CR*). The response rate, median OS, and safety profile of nelarabine in this disease setting and population were consistent with those reported previously.
Intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity incontinence: do we need urodynamic investigation for outcome assessment?
Authors: Koschorke Miriam , Leitner Lorenz , Sadri Helen , Knüpfer Stephanie C. , Mehnert Ulrich , Kessler Thomas M. 
Published: August 2017

ObjectiveTo evaluate if urinary continence in patients with refractory neurogenic detrusor overactivity (NDO) incontinence after intradetrusor onabotulinumtoxinA injections is sufficient for appropriate outcome assessment or if urodynamic investigation (UDI) is needed.Patients and MethodsA consecutive series of 148 patients undergoing intradetrusor onabotulinumtoxinA injections for refractory NDO incontinence were prospectively evaluated. Patients underwent UDI before and at 6 weeks after onabotulinumtoxinA injections. The primary outcome was the prevalence of maximum storage detrusor pressure (Pdetmax storage) of >40 cmH2O in continent patients at 6 weeks after treatment. The secondary outcomes were treatment effects on other clinical and video‐urodynamic variables.ResultsAt 6 weeks after intradetrusor onabotulinumtoxinA injections, 98 of the 148 patients (66%) with NDO incontinence were continent. Of these patients, 18 (18%, confidence interval 12–27%) had a Pdetmax storage of >40 cmH2O. Gender, underlying neurological disorder, and high Pdetmax storage before treatment appear to increase the risk of poor urodynamic outcomes.ConclusionsUrinary continence is not sufficient for outcome assessment after intradetrusor onabotulinumtoxinA injections, as high intravesical pressures threatening the upper urinary tract may be missed in a relevant proportion of continent patients. Therefore, we strongly recommend UDI as a routine part of the follow‐up.
Sediment routing evolution in the North Alpine Foreland Basin, Austria: interplay of transverse and longitudinal sediment dispersal
Authors: Sharman Glenn R. , Hubbard Stephen M. , Covault Jacob A. , Hinsch Ralph , Linzer Hans‐Gert , Graham Stephan A. 
Published: August 2017

AbstractIntegration of detrital zircon geochronology and three‐dimensional (3D) seismic‐reflection data from the Molasse basin of Austria yields new insight into Oligocene‐early Miocene palaeogeography and patterns of sediment routing within the Alpine foreland of central Europe. Three‐dimensional seismic‐reflection data show a network of deep‐water tributaries and a long‐lived (>8 Ma) foredeep‐axial channel belt that transported Alpine detritus greater than 100 km from west to east. We present 793 new detrital zircon ages from 10 sandstone samples collected from subsurface cores located within the seismically mapped network of deep‐water tributaries and the axial channel belt. Grain age populations correspond with major pre‐Alpine orogenic cycles: the Cadomian (750–530 Ma), the Caledonian (490–380 Ma) and the Variscan (350–250 Ma). Additional age populations correspond with Eocene‐Oligocene Periadriatic magmatism (40–30 Ma) and pre‐Alpine, Precambrian sources (>750 Ma). Although many samples share the same age populations, the abundances of these populations vary significantly. Sediment that entered the deep‐water axial channel belt from the west (Freshwater Molasse) and southwest (Inntal fault zone) is characterized by statistically indistinguishable age distributions that include populations of Variscan, Caledonian and Cadomian zircon at modest abundances (15–32% each). Sandstone from a shallow marine unit proximal to the northern basin margin consists of >75% Variscan (350–300 Ma) zircon, which originated from the adjacent Bohemian Massif. Mixing calculations based on the Kolmogorov–Smirnoff statistic suggest that the Alpine fold‐thrust belt south of the foreland was also an important source of detritus to the deep‐water Molasse basin. We interpret evolving detrital zircon age distributions within the axial foredeep to reflect a progressive increase in longitudinal sediment input from the west (Freshwater Molasse) and/or southwest (Inntal fault zone) relative to transverse sediment input from the fold‐thrust belt to the south. We infer that these changes reflect a major reorganization of catchment boundaries and denudation rates in the Alpine Orogen that resulted in the Alpine foreland evolving to dominantly longitudinal sediment dispersal. This change was most notably marked by the development of a submarine canyon during deposition of the Upper Puchkirchen Formation that promoted sediment bypass eastward from Freshwater Molasse depozones to the Molasse basin deep‐water axial channel belt. The integration of 3D seismic‐reflection data with detrital zircon geochronology illustrates sediment dispersal patterns within a continental‐scale orogen, with implications for the relative role of longitudinal vs. transverse sediment delivery in peripheral foreland basins.
What Develops in Infants’ Spatial Categorization? Korean Infants’ Categorization of Containment and Tight‐Fit Relations
Authors: Casasola Marianella , Ahn Yeojin A. 
Published: August 2017

Korean‐learning infants’ categorization of two spatial categories, one consistent and one inconsistent with the Korean semantic category of “kkita,” was examined. Infants of 10 months (n = 32) and 18 months (n = 49) were tested on their categorization of containment or tight fit spatial relations. At 10 months, infants only formed a category of containment, but at 18 months, their categorization of tight fit was significantly stronger than containment. The results suggest that Korean infants benefit from their language environment in forming a category of tight fit when the exemplars are perceptually diverse. In particular, infants’ language environment may bolster their ability to generalize across diverse exemplars to form abstract categorical representations of spatial relations.
Biomechanical behavior of titanium and zirconia frameworks for implant‐supported full‐arch fixed dental prosthesis
Authors: Tiossi Rodrigo , Gomes Érica Alves , Faria Adriana Cláudia Lapria , Rodrigues Renata Cristina Silveira , Ribeiro Ricardo Faria 
Published: August 2017

AbstractBackgroundThe biomechanical behavior of implant‐supported titanium and zirconia full‐arch fixed dental prosthesis (FAFDP) frameworks require further investigation.PurposeStrains transferred by implant‐supported titanium (Ti) and zirconia (Zr) FAFDP frameworks were analyzed.Materials and MethodsMaxillary 14‐unit FAFDPs supported by 6 implants and 12‐unit FAFDPs supported by 4 implants were tested. One‐piece frameworks were fabricated by computer‐aided design/computer‐aided manufacturing. Four groups were divided (n = 3): G1, Ti‐6 implants; G2, Zr‐6 implants; G3, Ti‐4 implants; G4, Zr‐4 implants. A 250 N single‐point load was applied on the second premolar. A three‐dimensional digital image correlation system recorded framework and maxilla model surface deformation.ResultsThe following strains (μS) averaged over the length of the second premolar were calculated: frameworks, G1 (321.82 ± 111.29), G2 (638.87 ± 108.64), G3 (377.77 ± 28.64), G4 (434.18 ± 132.21); model surface, G1 (473.99 ± 48.69), G2 (653.93 ± 45.26), G3 (1082.50 ± 71.14), G4 (1218.26 ± 230.37). Zirconia frameworks supported by 6 implants (G2) presented higher surface strains (P < .05). FAFDPs with titanium frameworks transferred significantly lower strains to the supporting maxilla when 6 implants were used (G1) (P < .05). Both framework materials transferred similar strains when supported by 4 implants (G3 and G4) (P > .05).ConclusionsZirconia frameworks supported by 6 implants showed higher strains. FAFDPs supported by 6 implants transferred less strains to the supporting maxilla, irrespective of framework material.
Cellular behaviours of bone marrow‐derived mesenchymal stem cells towards pristine graphene oxide nanosheets
Authors: Wei Changbo , Liu Zifeng , Jiang Fangfang , Zeng Binghui , Huang Mingdi , Yu Dongsheng 
Published: August 2017

AbstractObjectivesGraphene oxide (GO), the derivative of graphene with unique properties, has attracted much attention for applications in dental implants. The aim of this study was, by two biomimetic cell culture methods, to investigate the quantitative relationship between the concentration of pristine GO nanosheets and their cellular behaviours towards bone marrow‐derived mesenchymal stem cells (BMSCs).Materials and methodsThe cells were firstly characterized according to their morphology, self‐renewal capabilities and multipotency. Subsequently, adhesion density, proliferation, alkaline phosphatase activity and mineralization of BMSCs treated with various concentrations of GO were analysed. In addition, osteogenic‐related proteins were measured for further verification of the GO‐induced osteogenic differentiation.ResultsPristine GO nanosheets inhibited the proliferation of BMSCs at a high concentration of 10 μg/mL during the first 3 days with two seeding methods and facilitated proliferation of BMSCs at a low concentration of 0.1 μg/mL after 5 days with a sequential‐seeding method compared to a co‐seeding method. Analogously, osteogenic differentiation was promoted when BMSCs were treated with 0.1 μg/mL of GO. Both the proliferation and differentiation showed concentration‐dependent behaviour. Interestingly, Wnt/β‐catenin signalling pathway appeared to be involved in osteogenic differentiation induced by pristine GO nanosheets.ConclusionsPristine GO nanosheets at a concentration of 0.1 μg/mL provide benefits to promote BMSCs proliferation and osteogenesis under a sequential‐seeding method, contributing to the use of GO for dental implantation.
Dapagliflozin is associated with lower risk of cardiovascular events and all‐cause mortality in people with type 2 diabetes (CVD‐REAL Nordic) when compared with dipeptidyl peptidase‐4 inhibitor therapy: A multinational observational study
Authors: Persson Frederik , Nyström Thomas , Jørgensen Marit E. , Carstensen Bendix , Gulseth Hanne L. , Thuresson Marcus , Fenici Peter , Nathanson David , Eriksson Jan W. , Norhammar Anna , Bodegard Johan , Birkeland Kåre I. 
Published: August 2017

AimsTo compare the sodium‐glucose‐cotransporter‐2 (SGLT‐2) inhibitor dapagliflozin with dipeptidyl peptidase‐4 (DPP‐4) inhibitors with regard to risk associations with major adverse cardiovascular (CV) events (MACE; non‐fatal myocardial infarction, non‐fatal stroke or cardiovascular mortality), hospitalization for heart failure (HHF), atrial fibrillation and severe hypoglycaemia in patients with type 2 diabetes (T2D) in a real‐world setting.MethodsAll patients with T2D prescribed glucose‐lowering drugs (GLDs) during 2012 to 2015 were identified in nationwide registries in Denmark, Norway and Sweden. Patients were divided into two groups: new users of dapagliflozin and new users of DPP‐4 inhibitors, matched 1:3 by propensity score, calculated by patient characteristics, comorbidities and drug treatment. Cox survival models were used to estimate hazard ratio (HR) per country separately, and a weighted average was calculated.ResultsAfter matching, a total of 40 908 patients with T2D were identified as new users of dapagliflozin (n = 10 227) or a DPP‐4 inhibitor (n = 30 681). The groups were well balanced at baseline; their mean age was 61 years and 23% had CV disease. The mean follow‐up time was 0.95 years, with a total of 38 760 patient‐years. Dapagliflozin was associated with a lower risk of MACE, HHF and all‐cause mortality compared with DPP‐4 inhibitors: HRs 0.79 (95% confidence interval [CI] 0.67‐0.94), 0.62 (95% CI 0.50‐0.77), and 0.59 (95% CI 0.49‐0.72), respectively. Numerically lower, but non‐significant HRs were observed for myocardial infarction (0.91 [95% CI 0.72‐1.16]), stroke (0.79 [95% CI 0.61‐1.03]) and CV mortality (0.76 [95% CI 0.53‐1.08]) Neutral associations with atrial fibrillation and severe hypoglycaemia were observed.ConclusionsDapagliflozin was associated with lower risks of CV events and all‐cause mortality compared with DPP‐4 inhibitors in a real‐world clinical setting and a broad T2D population.
Predictive factors for successful renal denervation: should we use them in clinical trials?
Authors: Barber‐Chamoux Nicolas , Esler Murray D. 
Published: August 2017

AbstractRenal denervation (RDN) is facing various challenges to its initial claimed value in hypertension treatment. Major concerns are the choice of the patients and the technical efficacy of the RDN. Different factors have been described as predicting the capacity of RDN to decrease blood pressure. These factors are related to the patients, the procedure and the tools to confirm successful neural ablation. Their use in future trials should help to improve RDN trials understanding and outcomes. This review summarizes the different predictive factors available and their potential benefits in patient selection and in procedure guidance.
Influences of dissolved oxygen on juvenile largemouth bass foraging behaviour
Authors: French Christopher G. , Wahl David H. 
Published: August 2017

AbstractSummer stratification often leads to large areas of hypolimnetic hypoxia in lakes and reservoirs. These areas of hypoxia alter fish behaviours and distributions as well as restrict access to valuable prey resources, yet few studies have examined foraging behaviour of fish in response to low dissolved oxygen (DO) concentrations. We observed foraging behaviour of juvenile largemouth bass, Micropterus salmoides, in response to varying DO concentrations in tanks that simulated a stratified lake water column during the summer: 28°C oxygenated epilimnion, 15°C deoxygenated hypolimnion. Compared with saturated concentrations (8.0–9.0 mg/L), hypolimnetic oxygen concentrations of 3.0 mg/L and 1.5 mg/L resulted in a drastic decrease in prey consumption, handling efficiency and time spent below the thermocline mainly due to avoidance behaviour of hypoxic conditions. However, we found at high hypolimnetic prey densities, individual fish were more willing to venture into reduced oxygen concentrations. Several unique behaviours including transporting prey above the oxycline for consumption, aquatic surface respiration and gill flaring were employed by largemouth bass foraging in low oxygen environments. Reduced hypolimnetic oxygen concentrations may influence and alter feeding strategies, especially for fish that rely on benthic prey resources.
Caring for transgender patients with epilepsy
Authors: Johnson Emily L. , Kaplan Peter W. 
Published: August 2017

SummaryObjectiveApproximately 25 million individuals older than age 15 identify as transgender, representing about 0.3–0.9% of the world's population. The aim of this paper is to identify and describe important medical and social considerations facing transgender persons with epilepsy.MethodsWe performed literature searches on the following terms: transgender AND epilepsy, transgender AND neurology, gender dysphoria AND epilepsy, gender dysphoria AND neurology. We also performed literature searches for common feminizing or masculinizing treatment regimens, and searched for interactions of those treatment regimens with antiepileptic drugs (AEDs) and with seizures.ResultsThere are multiple bidirectional interactions between AEDs and the commonly used treatments for aligning external sex characteristics with identified gender. The scope of the transgender population with epilepsy remains to be elucidated.SignificanceTransgender patients with epilepsy face significant social and medical challenges. Interactions between medical gender‐affirming treatments and AEDs are common, and management must depend on knowledge of these interactions to provide appropriate treatment.
Radiographic, computed tomographic, gross pathological and histological findings with suspected apical infection in 32 equine maxillary cheek teeth (2012–2015)
Authors: Liuti T. , Smith S. , Dixon P. M. 
Published: August 2017

SummaryBackgroundEquine maxillary cheek teeth apical infections are a significant disorder because of frequent spread of infection to the supporting bones. The accuracy of computed tomographic imaging (CT) of this disorder has not been fully assessed.ObjectivesTo compare the radiographic and CT findings in horses diagnosed with maxillary cheek teeth apical infections with pathological findings in the extracted teeth to assess the accuracy of these imaging techniques.Study designObservational clinical study.MethodsThirty‐two maxillary cheek teeth (in 29 horses) diagnosed with apical infections by clinical, radiographic and principally by CT examinations, were extracted orally. The extracted teeth were subjected to further CT, gross pathological and histological examinations. Four normal teeth extracted from a cadaver served as controls.ResultsPulpar and apical changes highly indicative of maxillary cheek teeth apical infection were present in all 32 teeth on CT, but in just 17/32 teeth (53%) radiographically. Gross pulpar/apical abnormalities and histological pulpar/periapical changes were present in 31/32 (97%) extracted teeth. On CT, one tooth contained small gas pockets in the apical aspect of one pulp and adjacent periodontal space, however no pathological changes were found following its extraction.Main limitationsThe study is descriptive and is confined to a small number of cases.ConclusionThis study showed a 97% agreement between CT diagnosis of maxillary cheek teeth apical infection and the presence of pathological changes in the extracted teeth, confirming the diagnostic accuracy of CT compared with radiography for this disorder.
Systematic conservation planning in floodplain fisheries: To what extent are fishers’ needs captured in prioritisation models?
Authors: Chiaravalloti R. M. 
Published: August 2017

AbstractSystematic conservation planning (SCP) is a promising tool underpinned by the idea that multistakeholders’ needs should be considered in any conservation action. However, there is almost no research verifying whether those proposed solutions indeed capture local people's needs. In this article, a SCP exercise was developed in the Pantanal wetland, Brazil, to propose a possible new negotiated solution for environmental protection areas and fisheries zone. To test the validity of the SCP‐delivered solutions, physical maps showing them were presented and discussed with local people. None of the proposed possible SCP scenarios was accepted locally as workable. The fixed solutions proposed by SCP do not map onto the spatial–temporal flexibility of floodplain fisheries. Current, SCP approaches seem far from being able to incorporate the livelihood uncertainties of floodplain fisheries into mathematical models in a way that encompasses people's needs and, therefore remains only a theoretical tool for sustainability.
Modelling pasture production and soil temperature, water and carbon fluxes in Mediterranean grassland systems with the Pasture Simulation model
Authors: Pulina A. , Lai R. , Salis L. , Seddaiu G. , Roggero P. P. , Bellocchi G. 
Published: August 2017

AbstractGrasslands play important roles in agricultural production and provide a range of ecosystem services. Modelling can be a valuable adjunct to experimental research in order to improve the knowledge and assess the impact of management practices in grassland systems. In this study, the PaSim model was assessed for its ability to simulate plant biomass production, soil temperature, water content, and total and heterotrophic soil respiration in Mediterranean grasslands. The study site was the extensively managed sheep grazing system at the Berchidda‐Monti Observatory (Sardinia, Italy), from which two data sets were derived for model calibration and validation respectively. A new model parameterization was derived for Mediterranean conditions from a set of eco‐physiological parameters. With the exception of heterotrophic respiration (Rh), for which modelling efficiency (EF) values were negative, the model outputs were in agreement with observations (e.g., EF ranging from ~0.2 for total soil respiration to ~0.7 for soil temperature). These results support the effectiveness of PaSim to simulate C cycle components in Mediterranean grasslands. The study also highlights the need of further model development to provide better representation of the seasonal dynamics of Mediterranean annual species‐rich grasslands and associated peculiar Rh features, for which the modelling is only implicitly being undertaken by the current PaSim release.