bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I manage peripheral T‐cell lymphoma, not otherwise specified and angioimmunoblastic T‐cell lymphoma: current practice and a glimpse into the future
Authors: Schmitz Norbert , de Leval Laurence 
Published: December 2016

SummaryPeripheral T‐cell lymphoma (PTCL), not otherwise specified (NOS) and angioimmunoblastic T‐cell lymphoma (AITL) are the most frequent of more than 20 mature PTCL entities featuring a broad spectrum of morphological, immunophenotypic, molecular and clinical characteristics. Unfortunately, recent progress in understanding the (epi)genetic background of PTCL has not been met with similar advances in treatment. Thus, CHO(E)P [cyclophosphamide, doxorubicin, vincristine, and prednisone (plus etoposide)] remains standard first‐line therapy. Patients without comorbidities achieving complete or partial remission proceed to autologous stem cell transplantation. With this approach about 50% of patients survive long‐term. Patients relapsing after or progressing during first‐line therapy have a dismal prognosis. They receive salvage gemcitabine‐therapy followed by allogeneic transplantation whenever possible. After allografting, approximately half of the patients survive long‐term; any other treatment is palliative. New drugs investigated in phase II studies achieved response rates between 10% and 30%; long‐term remissions are the exception to the rule. While most new drugs are not licensed and not readily available, a plethora of other innovative drugs targeting (epi‐)genetic abnormalities are in early development. These, together with combinations of new and old drugs, will hopefully increase response to first‐line therapy, bridge more patients to transplantation, and finally improve prognosis for all patients with PTCL.
Clinical impact of 68Ga‐prostate‐specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer with rising prostate‐specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach
Authors: Albisinni Simone , Artigas Carlos , Aoun Fouad , Biaou Ibrahim , Grosman Julien , Gil Thierry , Hawaux Eric , Limani Ksenija , Otte Francois‐Xavier , Peltier Alexandre , Sideris Spyridon , Sirtaine Nicolas , Flamen Patrick , van Velthoven Roland 
Published: December 2016

ObjectiveTo assess the impact of a novel molecular imaging technique, 68Ga‐(HBED‐CC)‐prostate‐specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), in the clinical management of patients with prostate cancer with rising prostate‐specific antigen (PSA) after treatment with curative intent.Patients and MethodsIn all, 131 consecutive patients were referred to our centre for a 68Ga‐PSMA PET/CT in the setting of recurring prostate cancer. Of these patients, 11/131(8%) presented with persistent PSA after radical prostatectomy, while 120/131 (92%) were referred for biochemical recurrence after surgery, radiotherapy or both. The images where taken 1 h after injection of 2 MBq/kg of the 68Ga‐(HBED‐CC)‐PSMA ligand. All examinations were interpreted by two experienced nuclear medicine specialists. Using the results of the examination, a multidisciplinary oncology committee (MOC) reported on the treatment strategy. A positive impact on clinical management was considered if the examination determined a modification in the treatment strategy compared to the MOC decision before PSMA imaging.ResultsAll patients completed the examination with no adverse reactions. The median (interquartile range) PSA level at the time of the examination was 2.2 (0.72–6.7) ng/mL. Overall, 68Ga‐PSMA PET/CT detected at least one lesion suspicious for prostate cancer in 98/131 (75%) patients. There was an impact on subsequent management in 99/131 patients (76%). The main modifications included continuing surveillance (withholding hormonal therapy), hormonal manipulations, stereotaxic radiotherapy, salvage radiotherapy, salvage node dissection or salvage local treatment (prostatectomy, high‐intensity focussed ultrasound).ConclusionOur preliminary experience suggests that performing 68Ga‐PSMA PET/CT in patients with prostate cancer with rising PSA after treatment with curative intent can be clinically useful as it changes the treatment strategy in a significant proportion of patients. However, larger prospective trials are needed to validate our present findings.
Sorafenib dose escalation in treatment‐naïve patients with metastatic renal cell carcinoma: a non‐randomised, open‐label, Phase 2b study
Authors: Gore Martin E. , Jones Robert J. , Ravaud Alain , Kuczyk Markus , Demkow Tomasz , Bearz Alessandra , Shapiro JoAnn , Strauss Uwe Phillip , Porta Camillo 
Published: December 2016

ObjectiveTo assess the efficacy and safety of sorafenib dose escalation in metastatic renal cell carcinoma (mRCC).Patients and MethodsIntra‐patient dose escalation may enhance the clinical benefit of targeted anticancer agents in metastatic disease. In this non‐randomised, open‐label, Phase 2b study, treatment‐naïve patients with mRCC were initially treated with the standard oral sorafenib dose [400 mg twice daily (BID)]. Two dose escalations were planned, each 200 mg BID after 28 days at the prior level. Dose reductions, interruptions, or delayed escalations were used to manage adverse events (AEs). The primary endpoint was objective response rate (ORR) in the modified intent‐to‐treat (mITT) population, which comprised patients with ≥6 months of treatment including ≥4 months of therapy at their highest tolerated dose. Secondary endpoints included progression‐free survival (PFS) and safety.ResultsIn all, 83 patients received sorafenib. The dose received for the longest duration was 400, 600, and 800 mg BID in 48.2%, 15.7%, and 24.1% of patients, respectively. The ORR was 44.4% [n = 8/18; 95% confidence interval (CI) 21.5–69.2] and 17.9% (n = 12/67; 95% CI 9.6–29.2) in the mITT and ITT populations, respectively. The median (95% CI) PFS was 7.4 (6.0–11.7) months (ITT). The most common AEs of any grade were hand–foot skin reaction (66.3%) and diarrhoea (63.9%).ConclusionSorafenib demonstrated clinical benefit in treatment‐naïve patients with mRCC. However, relatively few patients could sustain doses of >400 mg BID. There was evidence that, where tolerated, escalation from the standard sorafenib dose may have enhanced clinical benefit. However, this study does not support dose escalation for most patients with treatment‐naïve mRCC. Alternative protocols for sorafenib dose escalation could be explored.
Development, validation and clinical application of Pelvic Lymphadenectomy Assessment and Completion Evaluation: intraoperative assessment of lymph node dissection after robot‐assisted radical cystectomy for bladder cancer
Authors: Hussein Ahmed A. , Hinata Nobuyuki , Dibaj Shiva , May Paul R. , Kozlowski Justen D. , Abol‐Enein Hassan , Abaza Ronney , Eun Daniel , Khan Mohamed S. , Mohler James L. , Agarwal Piyush , Pohar Kamal , Sarle Richard , Boris Ronald , Mane Sridhar S. , Hutson Alan , Guru Khurshid A. 
Published: December 2016

ObjectivesTo develop a scoring tool, Pelvic Lymphadenectomy Appropriateness and Completion Evaluation (PLACE), to assess the intraoperative completeness and appropriateness of pelvic lymph node dissection (PLND) following robot‐assisted radical cystectomy (RARC).Patients, Subjects and MethodsA panel of 11 open and robotic surgeons developed the content and structure of PLACE. The PLND template was divided into three zones. In all, 21 de‐identified videos of bilateral robot‐assisted PLNDs were assessed by the 11 experts using PLACE to determine inter‐rater reliability. Lymph node (LN) clearance was defined as the proportion of cleared LNs from all PLACE zones. We investigated the correlation between LN clearance and LN count. Then, we compared the LN count of 18 prospective PLNDs using PLACE with our retrospective series performed using the extended template (No PLACE).ResultsA significant reliability was achieved for all PLACE zones among the 11 raters for the 21 bilateral PLND videos. The median (interquartile range) for LN clearance was 468 (431–545). There was a significant positive correlation between LN clearance and LN count (R2 = 0.70, P < 0.01). The PLACE group yielded similar LN counts when compared to the No PLACE group.ConclusionsPelvic Lymphadenectomy Appropriateness and Completion Evaluation is a structured intraoperative scoring system that can be used intraoperatively to measure and quantify PLND for quality control and to facilitate training during RARC.
Co‐occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma
Authors: Pagès Mélanie , Beccaria Kevin , Boddaert Nathalie , Saffroy Raphaël , Besnard Aurore , Castel David , Fina Frédéric , Barets Doriane , Barret Emilie , Lacroix Ludovic , Bielle Franck , Andreiuolo Felipe , Tauziède‐Espariat Arnault , Figarella‐Branger Dominique , Puget Stéphanie , Grill Jacques , Chrétien Fabrice , Varlet Pascale 
Published: December 2016

AbstractGanglioglioma (GG) is a grade I tumor characterized by alterations in the MAPK pathway, including BRAF V600E mutation. Recently, diffuse midline glioma with an H3 K27M mutation was added to the WHO 2016 classification as a new grade IV entity. As co‐occurrence of H3 K27M and BRAF V600E mutations has been reported in midline tumors and anaplastic GG, we searched for BRAF V600E and H3 K27M mutations in a series of 54 paediatric midline grade I GG (midline GG) to determine the frequency of double mutations and its relevance for prognosis. Twenty‐seven patients (50%) possessed the BRAF V600E mutation. The frequency of the co‐occurrence of H3F3A/BRAF mutations at diagnosis was 9.3%. No H3 K27M mutation was detected in the absence of the BRAF V600E mutation. Double‐immunostaining revealed that BRAF V600E and H3 K27M mutant proteins were present in both the glial and neuronal components. Immunopositivity for the BRAF V600E mutant protein correlated with BRAF mutation status as detected by massARRAY or digital droplet PCR. The median follow‐up of patients with double mutation was 4 years. One patient died of progressive disease 8 years after diagnosis, whereas the four other patients were all alive with stable disease at the last clinical follow‐up (at 9 months, 1 year and 7 years) without adjuvant therapy. We demonstrate in this first series of midline GGs that the H3 K27M mutation can occur in association with the BRAF V600E mutation in grade I glioneuronal tumors. Despite the presence of H3 K27M mutations, these cases should not be graded and treated as grade IV tumors because they have a better spontaneous outcome than classic diffuse midline H3 K27M‐mutant glioma. These data suggest that H3 K27M cannot be considered a specific hallmark of grade IV diffuse gliomas and highlight the importance of integrated histomolecular diagnosis in paediatric brain tumors.
Mitochondrial activity in the frontal cortex area 8 and angular gyrus in Parkinson's disease and Parkinson's disease with dementia
Authors: Garcia‐Esparcia Paula , Koneti Anusha , Rodríguez‐Oroz M. Cruz , Gago Belen , del Rio José Antonio , Ferrer Isidro 
Published: December 2016

AbstractAltered mitochondrial function is characteristic in the substantia nigra in Parkinson's disease (PD). Information about mitochondria in other brain regions such as the cerebral cortex is conflicting mainly because most studies have not contemplated the possibility of variable involvement depending on the region, stage of disease progression and clinical symptoms such as the presence or absence of dementia. RT‐qPCR of 18 nuclear mRNAs encoding subunits of mitochondrial complexes and 12 mRNAs encoding energy metabolism‐related enzymes; western blotting of mitochondrial proteins; and analysis of enzymatic activities of complexes I, II, II, IV and V of the respiratory chain were assessed in frontal cortex area 8 and the angular gyrus of middle‐aged individuals (MA), and those with incidental PD (iPD), long‐lasting PD with parkinsonism without dementia (PD) and long‐lasting PD with dementia (PDD). Up‐regulation of several genes was found in frontal cortex area 8 in PD when compared with MA and in the angular gyrus in iPD when compared with MA. Marked down‐regulation of genes encoding mitochondrial subunits and energy metabolism‐related enzymes occurs in frontal cortex but only of genes coding for energy metabolism‐related enzymes in the angular gyrus in PDD. Significant decrease in the protein expression levels of several mitochondrial subunits encoded by these genes occurs in frontal cortex area 8 and angular gyrus in PDD. Moreover, expression of MT‐ND1 which is encoded by mitochondrial DNA is also reduced in PDD. Reduced enzymatic activity of complex III in frontal cortex area 8 and angular gyrus is observed in PD, but dramatic reduction in the activity of complexes I, II, II and IV in both regions characterizes PDD. Dementia in the context of PD is linked to region‐specific deregulation of genomic genes encoding subunits of mitochondrial complexes and to marked reduction in the activity of mitochondrial complexes I, II, III and IV.
Development of endometrioid adenocarcinoma despite Levonorgestrel‐releasing intrauterine system: a case report with discussion and review of the RCOG/BSGE Guideline on the Management of Endometrial Hyperplasia
Authors: van der Meer A. C. L. , Hanna L. S. 
Published: December 2016

SummaryObesity is a significant risk factor for the development of endometrial hyperplasia and cancer. More conservative prevention and management strategies are attractive due to the increased surgical risk and complication rates associated with obesity. The Levonorgestrel‐releasing intrauterine system (LNG‐IUS, Mirena) has been shown to reduce the risk of developing endometrial cancer. The recent joint Green Top Guideline on the Management of Endometrial Hyperplasia published by the Royal College of Obstetricians and Gynaecologists (RCOG) with the British Society for Gynaecological Endoscopy (BSGE) recommends the LNG‐IUS for the medical management of endometrial hyperplasia without atypia. This case study reports on the development of endometrioid adenocarcinoma despite the presence of an LNG‐IUS following a negative hysteroscopy in a 56‐year‐old woman with morbid obesity. This report highlights the need for patients and clinicians to remain vigilant to the early warning signs of developing endometrial cancer, especially in those at an increased risk secondary to obesity.
Consistency of effects of tropical‐forest disturbance on species composition and richness relative to use of indicator taxa
Authors: Stork N.E. , Srivastava D.S. , Eggleton P. , Hodda M. , Lawson G. , Leakey R.R.B. , Watt A.D. 
Published: December 2016

AbstractLawton et al. (1998) found, in a highly cited study, that the species richness of 8 taxa each responds differently to anthropogenic disturbance in Cameroon forests. Recent developments in conservation science suggest that net number of species is an insensitive measure of change and that understanding which species are affected by disturbance is more important. It is also recognized that all disturbance types are not equal in their effect on species and that grouping species according to function rather than taxonomy is more informative of responses of biodiversity to change. In a reanalysis of most of the original Cameroon data set (canopy and ground ants, termites, canopy beetles, nematodes, and butterflies), we focused on changes in species and functional composition rather than richness and used a more inclusive measure of forest disturbance based on 4 component drivers of change: years since disturbance, tree cover, soil compaction, and degree of tree removal. Effects of disturbance on compositional change were largely concordant between taxa. Contrary to Lawton et al.’s findings, species richness for most groups did not decline with disturbance level, providing support for the view that trends in species richness at local scales do not reflect the resilience of ecosystems to disturbance. Disturbance affected species composition more strongly than species richness for butterflies, canopy beetles, and litter ants. For these groups, disturbance caused species replacements rather than just species loss. Only termites showed effects of disturbance on species richness but not composition, indicating species loss without replacement. Although disturbance generally caused changes in composition, the strength of this relationship depended on the disturbance driver. Butterflies, litter ants, and nematodes were correlated with amount of tree cover, canopy beetles were most strongly correlated with time since disturbance, and termites were most strongly correlated with degree of soil disturbance. There were moderately divergent responses to disturbance between functional feeding groups. Disturbance was most strongly correlated with compositional differences of herbivores within beetles and nematodes and humus feeders within termites. Our results suggest that consideration of the impact of different forms of disturbance on species and functional composition, rather than on net numbers of species, is important when assessing the impacts of disturbance on biodiversity.
What do Parents and Children talk about at a Natural History Museum?
Authors: To Cheryl , Tenenbaum Harriet R. , Wormald Daniel 
Published: December 2016

AbstractThis study investigated the ways in which families constructed an understanding of evolution exhibits at a natural history museum. We examined museum visitors’ use of exhibit text and the types of evolution‐related talk in parent‐child conversations while visiting the chimp/human and the artiodactyl exhibits. Participants were 52 families with children aged 2‐ to 11‐years who agreed to be digitally recorded. Analyses of parent‐child conversations indicated that families who read exhibit text were more likely to stay longer at the exhibits and to encounter the intended content of the exhibits than families who did not read the text. On‐topic conversations tended to focus on labelling and describing the exhibit content rather than talking about evolutionary concepts. Physical descriptions of exhibit displays allowed children to make inferences about novel entities (i.e., those in the exhibits) based on prior knowledge.
Developing a Research Agenda Aimed at Understanding the Teaching and Learning of Science at a Natural History Museum
Authors: Hammerness Karen , MacPherson Anna , Gupta Preeti 
Published: December 2016

AbstractOver the past two decades, cultural institutions such as museums are beginning to develop their capacity for engaging in long‐term research on teaching and learning (Rennie et al. 2003; see also Crowley 2014). In this article, we describe one museum's efforts to develop an educational research agenda in relationship to these broader efforts. We explain how we got started; share steps taken; describe the agenda itself; and give examples of some of our current research studies. We end with insights into some of the challenges we've faced in developing this work and how we've addressed them and our next steps.
Investigating the Development of the “Mobile Museum” from the Perspective of Service
Authors: HUang Chia‐Hui , Lin Fang‐Suey 
Published: December 2016

AbstractDuring economic development, modern museums face competition from various leisure activities and entertainment sites, and to achieve sustainable development, museums should reflect on providing high‐quality service to satisfy visitors’ expectations. Based on service design‐related theories, this research team conducted a case study to explore the planning, implementation, and meaning of Mobile Museums. It investigated design development from the perspective of public service design and summarized the policy, design, and service satisfaction results for Mobile Museums. Finally, the similarities in service processes are discussed between Mobile Museums and the general service industry. According to this study, attracting more visitors is the biggest issue facing museums today, as are the ways in which museums must actively provide service and become recognized to compete with others. This study identifies the onstage and backstage support of museums as well as their cultural features and non‐profit services.
Frontal theta activation associated with error detection in toddlers: influence of familial socioeconomic status
Authors: Conejero Ángela , Guerra Sonia , Abundis‐Gutiérrez Alicia , Rueda M. Rosario 
Published: December 2016

AbstractError detection is one of the functions of the executive attention network, a brain system involved in executive control that includes the anterior cingulate cortex and other prefrontal regions. Despite the key role of this function in a wide range of life outcomes, very limited research has examined the early development of the network and whether its functional efficacy is related to environmental factors. Electrophysiological studies with adults have shown oscillatory activity in theta (4–7 Hz) range arising from medial frontal cortex that follows the detection of self‐committed or observed errors. In the current study, we designed a novel experimental procedure that involved a familiarization phase with simple three‐pieces puzzles followed by an experimental phase in which toddlers observed the puzzles being formed either correctly or incorrectly. Observation of incorrect configurations produced increased potentials in midline channels and greater power theta activity for both toddlers (n = 56) and adults (n = 14). In addition, socioeconomic status of the family in general, and parental education in particular, contributed to individual differences in the amplitude of the error‐related signal and associated theta power in toddlers, indicating that children raised in lower SES families show poorer activation of the executive attention network. These data demonstrate the influence of environmental factors at the earliest stages of development of the executive attention network. Importantly, the results show that error‐detection EEG signals can be used as neural markers of the initial development of executive attention, which can be of great help for the early detection of risk for developmental disorders involving deficits in this function.
Attaching meaning to the number words: contributions of the object tracking and approximate number systems
Authors: vanMarle Kristy , Chu Felicia W. , Mou Yi , Seok Jin H. , Rouder Jeffrey , Geary David C. 
Published: December 2016

AbstractChildren's understanding of the quantities represented by number words (i.e., cardinality) is a surprisingly protracted but foundational step in their learning of formal mathematics. The development of cardinal knowledge is related to one or two core, inherent systems – the approximate number system (ANS) and the object tracking system (OTS) – but whether these systems act alone, in concert, or antagonistically is debated. Longitudinal assessments of 198 preschool children on OTS, ANS, and cardinality tasks enabled testing of two single‐mechanism (ANS‐only and OTS‐only) and two dual‐mechanism models, controlling for intelligence, executive functions, preliteracy skills, and demographic factors. Measures of both OTS and ANS predicted cardinal knowledge in concert early in the school year, inconsistent with single‐mechanism models. The ANS but not the OTS predicted cardinal knowledge later in the school year as well the acquisition of the cardinal principle, a critical shift in cardinal understanding. The results support a Merge model, whereby both systems initially contribute to children's early mapping of number words to cardinal value, but the role of the OTS diminishes over time while that of the ANS continues to support cardinal knowledge as children come to understand the counting principles.