bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of dual phosphoinositol‐3‐kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma
Authors: Seront Emmanuel , Rottey Sylvie , Filleul Bertrand , Glorieux Philippe , Goeminne Jean‐Charles , Verschaeve Vincent , Vandenbulcke Jean‐Marie , Sautois Brieuc , Boegner Petra , Gillain Aline , van Maanen Aline , Machiels Jean‐Pascal 
Published: January 2016

ObjectiveTo assess, in a multicentre phase II trial, the safety and efficacy of BEZ235, an oral pan‐class I phosphoinositol‐3‐kinase (PI3K) and mammalian target of rapamycin (mTOR) complex1/2 inhibitor, in locally advanced or metastatic transitional cell carcinoma (TCC) after failure of platinum‐based therapy.Patients and MethodsPatients with locally advanced or metastatic TCC progressing after platinum therapy were prospectively stratified by PI3K/Akt/mTOR pathway alterations, defined as PTEN loss and PIK3CA mutation. All patients received BEZ235 until progressive disease or unacceptable toxicity. The primary endpoint was the progression‐free survival (PFS) rate at 16 weeks. This study was, however, closed prematurely because BEZ235 was withdrawn from further development.ResultsA total of 20 patients (18 without and two with PI3K/Akt/mTOR alterations) were enrolled and received BEZ235. One partial response (5%) and two cases of stable disease (10%) were observed, all in patients without PI3K/mTOR pathway alterations. The PFS rate at 8 and 16 weeks was 15 and 10%, respectively; the median (range) PFS was 62 (38–588) days (95% confidence interval [CI] 53–110); and the median (range) overall survival was 127 (41–734) days (95% CI 58–309). Among the 90% of patients who experienced drug‐related adverse events of any grade, 50% experienced grade 3–4 adverse events, including stomatitis (15%), fatigue (5%), nausea (5%), diarrhoea (5%), renal failure (5%), cutaneous rash (5%), hepatotoxicity (5%) and hypertension (5%).ConclusionBEZ235 showed modest clinical activity and an unfavourable toxicity profile in patients with advanced and pretreated TCC; however, a minority of patients experienced a clinical benefit, suggesting that a complete blockade of the PI3K/mTOR axis could improve outcome in some specific patients. Furthermore, this study showed that molecular stratification of patients for personalized medicine before treatment is feasible.
Prevalence of the HOXB13 G84E mutation in Danish men undergoing radical prostatectomy and its correlations with prostate cancer risk and aggressiveness
Authors: Storebjerg Tine M. , Høyer Søren , Kirkegaard Pia , Bro Flemming ,   the LuCamp Study Group, Ørntoft Torben F. , Borre Michael , Sørensen Karina D. 
Published: January 2016

ObjectivesTo determine the prevalence of the HOXB13 G84E mutation (rs138213197) in Danish men with or without prostate cancer (PCa) and to investigate possible correlations between HOXB13 mutation status and clinicopathological characteristics associated with tumour aggressiveness.Materials and MethodsWe conducted a case–control study including 995 men with PCa (cases) who underwent radical prostatectomy (RP) between 1997 and 2011 at the Department of Urology, Aarhus University Hospital, Denmark. As controls, we used 1622 healthy men with a normal prostate specific antigen (PSA) level.ResultsThe HOXB13 G84E mutation was identified in 0.49% of controls and in 2.51% of PCa cases. The mutation was associated with a 5.12‐fold increased relative risk (RR) of PCa (95% confidence interval [CI] 2.26–13.38; P = 13 × 10−6). Furthermore, carriers of the risk allele were significantly more likely to have a higher PSA level at diagnosis (mean PSA 19.9 vs 13.6 ng/mL; P = 0.032), a pathological Gleason score ≥7 (83.3 vs 60.9%; P = 0.032), and positive surgical margins (56.0 vs 28.5%; P = 0.006) than non‐carriers. Risk allele carriers were also more likely to have aggressive disease (54.2 vs 28.6%; P = 0.011), as defined by a preoperative PSA ≥20 ng/mL, pathological Gleason score ≥ (4+3) and/or presence of regional/distant disease. At a mean follow‐up of 7 months, we found no significant association between HOXB13 mutation status and biochemical recurrence in this cohort of men who underwent RP.ConclusionsThis is the first study to investigate the HOXB13 G84E mutation in Danish men. The mutation was detected in 0.49% of controls and in 2.51% of cases, and was associated with 5.12‐fold increased RR of being diagnosed with PCa. In our RP cohort, HOXB13 mutation carriers were more likely to develop aggressive PCa. Further studies are needed to assess the potential of HOXB13 for future targeted screening approaches.
New In Vitro Models to Study Amyotrophic Lateral Sclerosis
Authors: Myszczynska Monika , Ferraiuolo Laura 
Published: January 2016

AbstractAmyotrophic Lateral Sclerosis (ALS) is a complex multifactorial disorder, characterized by motor neuron loss with involvement of several other cell types, including astrocytes, oligodendrocytes and microglia. Studies in vivo and in in vitro models have highlighted that the contribution of non‐neuronal cells to the disease is a primary event and ALS pathogenesis is driven by both cell‐autonomous and non‐cell autonomous mechanisms. The advancements in genetics and in vitro modeling of the past 10 years have dramatically changed the way we investigate the pathogenic mechanisms involved in ALS. The identification of mutations in transactive response DNA‐binding protein gene (TARDBP), fused in sarcoma (FUS) and, more recently, a GGGGCC‐hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) and their link with familial ALS have provided new avenues of investigation and hypotheses on the pathophysiology of this devastating disease. In the same years, from 2007 to present, in vitro technologies to model neurological disorders have also undergone impressive developments. The advent of induced pluripotent stem cells (iPSCs) gave the field of ALS the opportunity to finally model in vitro not only familial, but also the larger part of ALS cases affected by sporadic disease. Since 2008, when the first human iPS‐derived motor neurons from patients were cultured in a petri dish, several different techniques have been developed to produce iPSC lines through genetic reprogramming and multiple direct conversion methods have been optimised. In this review, we will give an overview of how human in vitro models have been used so far, what discoveries they have led to since 2007, and how the recent advances in technology combined with the genetic discoveries, have tremendously widened the horizon of ALS research.
New ALS‐Related Genes Expand the Spectrum Paradigm of Amyotrophic Lateral Sclerosis
Authors: Sabatelli Mario , Marangi Giuseppe , Conte Amelia , Tasca Giorgio , Zollino Marcella , Lattante Serena 
Published: January 2016

AbstractAmyotrophic Lateral Sclerosis (ALS) is characterized by the degeneration of upper and lower motor neurons. Clinical heterogeneity is a well‐recognized feature of the disease as age of onset, site of onset and the duration of the disease can vary greatly among patients. A number of genes have been identified and associated to familial and sporadic forms of ALS but the majority of cases remains still unexplained. Recent breakthrough discoveries have demonstrated that clinical manifestations associated with ALS‐related genes are not circumscribed to motor neurons involvement. In this view, ALS appears to be linked to different conditions over a continuum or spectrum in which overlapping phenotypes may be identified. In this review, we aim to examine the increasing number of spectra, including ALS/Frontotemporal Dementia and ALS/Myopathies spectra. Considering all these neurodegenerative disorders as different phenotypes of the same spectrum can help to identify common pathological pathways and consequently new therapeutic targets in these incurable diseases.
Spatial Ecology of the Fungal Genus Xylaria in a Tropical Cloud Forest
Authors: Thomas Daniel C. , Vandegrift Roo , Ludden Ashley , Carroll George C. , Roy Bitty A. 
Published: January 2016

AbstractFungal symbioses with plants are ubiquitous, ancient, and vital to both ecosystem function and plant health. However, benefits to fungal symbionts are not well explored, especially in non‐mycorrhizal fungi. The Foraging Ascomycete hypothesis proposes that some wood‐decomposing fungi may shift life‐history strategies to endophytism to bridge gaps in time and space between suitable substrates. To test this hypothesis we examine spatial relationships of Xylaria endophytic fungi in the forest canopy with Xylaria decomposer fungi on the forest floor. We sampled for fungi of the genus Xylaria using a spatially explicit sampling scheme in a remote Ecuadorian cloud forest, and concurrently carried out an extensive culture‐based sampling of fungal foliar endophytes. We found 36 species of Xylaria in our 0.5 ha plot, 31 of which were found to only occur as fruiting bodies. All five species of Xylaria found as endophytes were also found as fruiting bodies. We also tested the relationships of both stages of these fungi to environmental variables. Decomposer fungi were differentiated by species‐specific habitat preferences, with three species being found closer to water than expected by chance. In contrast, endophytes displayed no sensitivity to environmental conditions, such as host, moisture, or canopy cover. We found evidence of spatial linkage between life stages in two species. We also demonstrate that direct transmission of endophytes from leaves to woody substrates is possible. These results indicate that endophytism may represent one way for decomposer fungi to escape moisture limitation, and that endophytic fungi may act as sources of dispersal for decomposer fungi consistent with predictions of the Foraging Ascomycete hypothesis.
Bird Communities in Amazonian White‐Sand Vegetation Patches: Effects of Landscape Configuration and Biogeographic Context
Authors: Borges Sergio H. , Cornelius Cintia , Moreira Marcelo , Ribas Camila C. , Conh‐Haft Mario , Capurucho João M. , Vargas Claudeir , Almeida Ricardo 
Published: January 2016

AbstractVegetation growing on white‐sand soils is patchily distributed across the Amazon and is characterized by scrublands or open vegetation types (white‐sand campinas) and by forests (white‐sand forests) surrounded by contrasting habitat types. We studied birds in patches of white‐sand campinas in contrasting landscapes in four regions located in distinct biogeographic units delimited by major rivers. Our aim was to investigate the contribution of landscape configuration and biogeographic context to patterns of species diversity and distribution. Aracá and Viruá landscapes (on opposite sides of Rio Branco) are composed by large and continuous patches of white‐sand campinas, while Jaú, Novo Airão and Uatumã landscapes (on opposite sides of Rio Negro) are composed by small patches of white‐sand campinas isolated by continuous terra firme forests. Birds were sampled using mist‐nets and qualitative censuses, and were classified as white‐sand vegetation specialists or non‐specialists. Bird species diversity was significantly different among studied regions, and composition was significantly different for both, specialists and non‐specialists birds. Local variability in species diversity and composition was best explained by white‐sand campina area, patch proximity, and distance to major rivers. We conclude that landscape configuration and biogeographical context influence patterns of bird diversity, abundance, and composition in Amazonian white‐sand campinas.
Low Phylogenetic Beta Diversity and Geographic Neo‐endemism in Amazonian White‐sand Forests
Authors: Guevara Juan Ernesto , Damasco Gabriel , Baraloto Christopher , Fine Paul V. A. , Peñuela María Cristina , Castilho Carolina , Vincentini Alberto , Cárdenas Dairón , Wittmann Florian , Targhetta Natalia , Phillips Oliver , Stropp Juliana , Amaral Ieda , Maas Paul , Monteagudo Abel , Jimenez Eliana M. , Thomas Rachel , Brienen Roel , Duque Álvaro , Magnusson William , Ferreira Cid , Honorio Eurídice , de Almeida Matos Francisca , Arevalo Freddy R. , Engel Julien , Petronelli Pascal , Vasquez Rodolfo , ter Steege Hans 
Published: January 2016

AbstractOver the past three decades, many small‐scale floristic studies of white‐sand forests across the Amazon basin have been published. Nonetheless, a basin‐wide description of both taxonomic and phylogenetic alpha and beta diversity at regional scales has never been achieved. We present a complete floristic analysis of white‐sand forests across the Amazon basin including both taxonomic and phylogenetic diversity. We found strong regional differences in the signal of phylogenetic community structure with both overall and regional Net Relatedness Index and Nearest Taxon Index values found to be significantly positive leading to a pattern of phylogenetic clustering. Additionally, we found high taxonomic dissimilarity but low phylogenetic dissimilarity in pairwise community comparisons. These results suggest that recent diversification has played an important role in the assembly of white‐sand forests causing geographic neo‐endemism patterns at the regional scale.
The White‐sand Vegetation of Acre, Brazil
Authors: Daly Douglas C. , Silveira Marcos , Medeiros Herison , Castro Wendeson , Obermüller Flávio A. 
Published: January 2016

AbstractFor vegetation on white sand in Amazonia, the topography, soil nutrients, level of the water table, and rainfall combine to result in distinct formations, each with a characteristic physiognomy and each with a rather distinct floristic composition and very distinct dominants. We describe the physiognomies and present the floristic composition of nine formations, based on intensive fieldwork in NW Acre state, Brazil, where on six sites we have documented 222 species; 170 of them are woody plants or trunked palms ≥5 cm diam. Herbaceous species are good indicators for some of the formations. Distribution patterns and habitat specialization can be difficult to interpret because they often require familiarity with the localities and local terminologies involved. Many of the species show disjunct distributions congruent with the occurrence of other white‐sand areas in northern South America. The nine formations within Acre are strongly dissimilar, with only two pairwise comparisons showing >50 percent similarity. Comparison of the Acre white‐sand flora with datasets from Peruvian and Central + Eastern Amazonia show striking differences in composition and in taxonomic dominance, with more than 95 percent dissimilarity. White‐sand formations in Acre and elsewhere are gravely affected by expanding human settlement; little is known about the regeneration and recovery of the degraded white‐sand habitats. This complex sector of Acre's biological diversity is still virtually unrepresented in conservation units anywhere in Brazil's part of southwestern Amazonia, so it should be made an immediate conservation priority.
Pre‐settlement vegetation maps generated using Ontario early survey: An online database providing enhanced map access for researchers
Authors: Karrow Thomas , Suffling Roger 
Published: January 2016

Key MessagesEarly survey data from Ontario and elsewhere in Canada are vastly under‐utilized research resources.Pre‐settlement vegetation data embedded in early survey notes provide reliable baseline data sets for vegetation mapping.Existing vegetation maps derived from early survey data are largely unknown and inaccessible, but are now inventoried and available online through the University of Waterloo Library's Geospatial Centre.
Utility of FDG‐PET imaging in screening for succinate dehydrogenase B and D mutation‐related lesions
Authors: Kornaczewski E.R. , Pointon O.P. , Burgess J.R. 
Published: January 2016

SummaryObjectiveMutations of the genes encoding succinate dehydrogenase B and D (SDHB, SDHD) are associated with highly penetrant phenotypes, including paragangliomas and phaeochromocytomas. Patients with these mutations require lifelong surveillance; however, there is currently ambiguity regarding the optimal screening regimen. We sought to determine the utility of fluorodeoxyglucose (18F) positron emission tomography (18F‐FDG PET) imaging, compared to other modalities for detecting SDHB and SDHD mutation‐related lesions.DesignA retrospective audit of patients with SDHB or SDHD mutation.PatientsAll adult patients with confirmed SDHB and SDHD mutations who underwent 18F‐FDG PET/CT at our institution between 1 July 2011 and 30 May 2015.Measurements18F‐FDG PET/computed tomography (CT) performed during surveillance of patients with SDHB and SDHD mutations. Lesion numbers and locations detected by 18F‐FDG PET were compared to those identified on the CT component, as well as other imaging modalities and histology when available.ResultsThirty‐one 18F‐FDG PET/CT studies were completed on 22 patients. For SDHB (20 patients), there were five positive and 21 negative studies. There were no false‐negative 18F‐FDG PET studies. Positive 18F‐FDG PET findings correlated with magnetic resonance imaging (MRI), CT and [68 Ga]‐DOTA(0)‐Tyr(3)‐octreotate (68 Ga DOTATATE PET/CT) imaging with no missed lesions; the only potential false‐positive result relating to nonspecific postoperative changes (sensitivity 100·0%, specificity 95·5%).For SDHD (two patients), lesions were detected on 18F‐FDG PET and correlated with other imaging in three of five studies. Metastatic lesions were incompletely visualized on 18F‐FDG PET but were detected on the noncontrast fusion CT.Conclusions18F‐FDG PET/CT is suitable for detecting SDHB and SDHD mutation‐related lesions and may be considered effective for periodic surveillance of patients with these mutations.
Adrenal surgery in England: better outcomes in high‐volume practices
Authors: Palazzo Fausto , Dickinson Andrew , Phillips Barbara , Sahdev Anju , Bliss Richard , Rasheed Ashraf , Krukowski Zygmunt , Newell‐Price John 
Published: January 2016

SummaryAims and BackgroundAdrenal surgery is performed by a variety of surgical specialities in differing environments and volumes. International data suggest that there is a correlation between adrenal surgery volume and outcomes but there are no UK data to support this or UK surgical guidelines. A multidisciplinary team representing the stakeholders in adrenal disease is preparing a national guidance on adrenal surgery. A review of the outcomes for adrenal surgery in England was performed to correlate outcomes with the volume of surgeon practice.MethodsHospital Episode Statistics (HES) data for the National Health Service (NHS) in England in the tax year 2013–2014 were examined for adrenal surgery. Length of hospital stay and rate of postoperative readmission were assessed as surrogate quality markers and a comparison made between ‘high‐’ and ‘low‐’ volume surgeons.ResultsA total of 795 adult adrenalectomies were performed by 222 different surgeons with a range of between 1 and 34 adrenalectomies performed per surgeon. Only thirty‐six (16%) adrenal surgeons performed 6 or more adrenalectomies. A total of 186 surgeons (84%) performed a median of one adrenalectomy a year. Length of stay and readmission rate within thirty days of operation was 60% longer and 47% higher, respectively, when performed by low‐volume surgeons.ConclusionThe current provision of adrenal surgery in the UK is not in the best interests of patients and is not cost‐effective for the NHS. Adrenal surgery is best performed by higher volume surgeons in centres with dedicated adrenal multidisciplinary teams expert in all aspects of care of the adrenal patient.
Long‐term outcomes of dental implants placed in elderly patients: a retrospective clinical and radiographic analysis
Authors: Park Jung‐Chul , Baek Won‐Sun , Choi Seong‐Ho , Cho Kyoo‐Sung , Jung Ui‐Won 
Published: January 2016

AbstractObjectivesThe aim of this retrospective study was to determine the clinical and the radiographic outcomes of dental implants placed in elderly people older than 65 years.Materials and methodsIn total, 902 implants in 346 patients (age: 65–89 years) were followed up for 2–17 years following the implant surgery. The survival rate of these implants was recorded and analyzed. Changes in marginal bone levels were also analyzed in serial radiographs, and Cox regression analysis for implant loss was performed.ResultsThe survival rates were 95.39% and 99.98% in the implant‐ and patient‐based analyses, respectively (involving a total of 29 implant failures), and the marginal bone loss at the implants was 0.17 ± 0.71 mm (mean ± SD). The number of failures was greatest in patients aged 65–69 years. The Cox regression with shared frailty analysis showed that implant loss was significantly greater in those aged 65–69 years than in those aged 70–74 years (P < 0.05), and it varied between specific implant systems.ConclusionsWithin the limitations of this retrospective study, it was concluded that implant therapy can be successfully provided to elderly patients and that age alone does not seem to affect the implant survival rate.
Brain Region‐Specific Histopathological Effects of Varying Trajectories of Controlled Cortical Impact Injury Model of Traumatic Brain Injury
Authors: Pabón Mibel M. , Acosta Sandra , Guedes Vivian A. , Tajiri Naoki , Kaneko Yuji , Borlongan Cesar V. 
Published: January 2016

SummaryAimsTraumatic brain injury (TBI) occurs when the head is impacted by an external force causing either a closed or penetrating head injury through a direct or accelerating impact. In laboratory research, most of the TBI animal models focus on a specific region to cause brain injury, but traumatic injuries in patients do not always impact the same brain regions. The aim of this study was to examine the histopathological effects of different angles of mechanical injury by manipulating the trajectory of the controlled cortical impact injury (CCI) model in adult Sprague‐Dawley rats.MethodsThe CCI model was manipulated as follows: conventional targeting of the frontal cortex, farthest right angle targeting the frontal cortex, closest right angle targeting the frontal cortex, olfactory bulb injury, and cerebellar injury. Three days after TBI, brains were harvested to analyze cortical and hippocampal cell loss, neuroinflammatory response, and neurogenesis via immunohistochemistry.ResultsResults revealed cell death in the M1 region of the cortex across all groups, and in the CA3 area from olfactory bulb injury group. This observed cell death involved upregulation of inflammation as evidenced by rampant MHCII overexpression in cortex, but largely spared Ki‐67/nestin neurogenesis in the hippocampus during this acute phase of TBI.ConclusionThese results indicate a trajectory‐dependent injury characterized by exacerbation of inflammation and different levels of impaired cell proliferation and neurogenesis. Such multiple brain areas showing varying levels of cell death after region‐specific CCI model may closely mimic the clinical manifestations of TBI.