bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Pilot Study of Clinical Targeted Next Generation Sequencing for Prostate Cancer: Consequences for Treatment and Genetic Counseling
Authors: Cheng Heather H. , Klemfuss Nola , Montgomery Bruce , Higano Celestia S. , Schweizer Michael T. , Mostaghel Elahe A. , McFerrin Lisa G. , Yu Evan Y. , Nelson Peter S. , Pritchard Colin C. 
Published: June 2016

BACKGROUNDTargeted next generation sequencing (tNGS) is increasingly used in oncology for therapeutic decision‐making, but is not yet widely used for prostate cancer. The objective of this study was to determine current clinical utility of tNGS for prostate cancer management.METHODSSeven academic genitourinary medical oncologists recruited and consented patients with prostate cancer, largely with unusual clinical and/or pathologic features, from 2013 to 2015. UW‐OncoPlex was performed on formalin‐fixed, paraffin‐embedded (FFPE) primary tumors and/or metastatic biopsies. Results were discussed at a multidisciplinary precision tumor board prior to communicating to patients. FFPE tumor DNA was extracted for tNGS analysis of 194 cancer‐associated genes. Results, multidisciplinary discussion, and treatment changes were recorded.RESULTSForty‐five patients consented and 42 had reportable results. Findings included mutations in genes frequently observed in prostate cancer. We also found alterations in genes where targeted treatments were available and/or in clinical trials. 4/42 (10%) cases, change in treatment directly resulted from tNGS and multidisciplinary discussion. In 30/42 (71%) cases additional options were available but not pursued and/or were pending. Notably, 10/42 (24%) of patients harbored suspected germline mutations in moderate or high‐penetrance cancer risk genes, including BRCA2, TP53, ATM, and CHEK2. One patient's tumor had bi‐allelic MSH6 mutation and microsatellite instability. In total, 34/42 (81%) cases resulted in some measure of treatment actionability. Limitations include small size and limited clinical outcomes.CONCLUSIONSTargeted NGS tumor sequencing may help guide immediate and future treatment options for men with prostate cancer. A substantial subset had germline mutations in cancer predisposition genes with potential clinical management implications for men and their relatives. Prostate 76:1303–1311, 2016. © 2016 Wiley Periodicals, Inc.
A Genetic Variation of SOD2 Does Not Determine Duration of Response to Androgen Deprivation Therapy for Prostate Cancer
Authors: Xie Wanling , Drouin Sarah , Nakabayashi Mari , Pomerantz Mark , Lee Gwo‐Shu Mary , Kantoff Philip W. , Sharifi Nima 
Published: June 2016

BACKGROUNDSilencing SOD2 expression upregulates androgen receptor (AR) signaling and expression of SOD2 is downregulated in CRPC, compared with untreated tumors. The decreased SOD2 activity could lead to AR gain‐of‐function and the development of castration‐resistance.METHODSWe genotyped SOD2‐rs4880 in a cohort of 753 prostate cancer patients receiving androgen deprivation therapy (ADT) between 1996 and 2010. The rs4880 encodes Ala16Val in SOD2 and the Val variant has been demonstrated to be functionally less efficient than the Ala variant. We assessed the impact of SOD2‐rs4880 variants on the time to progression (TTP) and overall survival (OS) on ADT using multivariable Cox regression.RESULTSFour hundred thirty‐two out of 753 (57%) had metastases at the time of ADT initiation. Overall, median TTP on ADT was 18.4 (95%CI: 15.8, 20.9) months and median overall survival (OS) from ADT initiation was 6.3 (95%CI: 5.8, 6.8) years. In unadjusted and adjusted analyses, there was no association between SOD‐rs4880 and TTP or OS on ADT (P > 0.05). Results were similarly negative among patients with and without metastatic disease at ADT initiation.CONCLUSIONSOur result suggests that a functional genetic variant in SOD2 does not determine the efficacy of ADT for prostate cancer. It is possible that the drastic downregulation of SOD2 in advanced prostate cancer cells may have overridden any influence of the genetic variation of SOD2. This study suggests the need for careful consideration about timing if the application of SOD2 mimetics for prostate cancer therapy is considered. Prostate 76:1338–1341, 2016. © 2016 Wiley Periodicals, Inc.
Turbulence generation by mountain wave breaking in flows with directional wind shear
Authors: Guarino Maria‐Vittoria , Teixeira Miguel A. C. , Ambaum Maarten H. P. 
Published: June 2016

Mountain wave breaking, and the resulting potential for the generation of turbulence in the atmosphere, are investigated using numerical simulations of idealized, nearly hydrostatic, atmospheric flows with directional wind shear over an axisymmetric isolated mountain. These simulations, which use the WRF‐ARW model, differ in degree of flow nonlinearity and shear intensity, quantified through the dimensionless mountain height and the Richardson number of the incoming flow, respectively. The aim is to diagnose wave breaking based on large‐scale flow variables.The simulation results have been used to produce a regime diagram giving a description of the wave breaking behaviour in Richardson number–dimensionless mountain height parameter space. By selecting flow overturning occurrence as a discriminating factor, it was possible to split the regime diagram into sub‐regions with and without wave breaking.When mountain waves break, the associated convective instability leads to turbulence generation (which is one of the known forms of clear air turbulence (CAT)). Thus, regions within the simulation domain where wave breaking and the development of CAT are expected have been identified. The extent of these regions increases with terrain elevation and background wind shear intensity.Analysis of the model output, supported by theoretical arguments, suggests the existence of a link between wave breaking and the relative orientations of the incoming wind vector and the horizontal velocity perturbation vector. More specifically, in a wave breaking event, due to the effect of critical levels, the background wind vector and the wavenumber vector of the dominant mountain waves are perpendicular. It is shown that, at least for the wind profile employed in the present study, this corresponds to a situation where the background wind vector and the velocity perturbation vector are also approximately perpendicular.
Concise Review: Fate Determination of Stem Cells by Deubiquitinating Enzymes
Authors: Chandrasekaran Arun Pandian , Suresh Bharathi , Kim Hyongbum (Henry) , Kim Kye-Seong , Ramakrishna Suresh 
Published: June 2016

AbstractPost-translational modification by ubiquitin molecules is a key regulatory process for stem cell fate determination. Ubiquitination and deubiquitination are the major cellular processes used to balance the protein turnover of several transcription factors that regulate stem cell differentiation. Deubiquitinating enzymes (DUBs), which facilitate the processing of ubiquitin, significantly influence stem cell fate choices. Specifically, DUBs play a critical regulatory role during development by directing the production of new specialized cells. This review focuses on the regulatory role of DUBs in various cellular processes, including stem cell pluripotency and differentiation, adult stem cell signaling, cellular reprogramming, spermatogenesis, and oogenesis. Specifically, the identification of interactions of DUBs with core transcription factors has provided new insight into the role of DUBs in regulating stem cell fate determination. Thus, DUBs have emerged as key pharmacologic targets in the search to develop highly specific agents to treat various illnesses.
Outcome of fetal ovarian cysts diagnosed on prenatal ultrasound examination: systematic review and meta‐analysis
Authors: Bascietto F. , Liberati M. , Marrone L. , Khalil A. , Pagani G. , Gustapane S. , Leombroni M. , Buca D. , Flacco M. E. , Rizzo G. , Acharya G. , Manzoli L. , D'Antonio F. 
Published: June 2016

ABSTRACTObjectiveTo explore the outcome of fetuses with a prenatal diagnosis of ovarian cyst.MethodsThe electronic databases MEDLINE and EMBASE were searched using keywords and word variants for ‘ovarian cysts’, ‘ultrasound’ and ‘outcome’. The following outcomes in fetuses with a prenatal diagnosis of ovarian cyst were explored: resolution of the cyst, change of ultrasound pattern of the cyst, occurrence of ovarian torsion and intracystic hemorrhage, need for postnatal surgery, need for oophorectomy, accuracy of prenatal ultrasound examination in correctly identifying ovarian cyst, type of ovarian cyst at histopathological analysis and intrauterine treatment. Meta‐analyses using individual data random‐effects logistic regression and meta‐analyses of proportions were performed. Quality assessment of the included studies was performed using the Newcastle–Ottawa Scale.ResultsThirty‐four studies (954 fetuses) were included. In 53.8% (95% CI, 46.0–61.5%) of cases for which resolution of the cyst was evaluated (784 fetuses), the cyst regressed either during pregnancy or after birth. The likelihood of resolution was significantly lower in complex vs simple cysts (odds ratio (OR), 0.15 (95% CI, 0.10–0.23)) and in cysts measuring ≥ 40 mm vs < 40 mm (OR, 0.03 (95% CI, 0.01–0.06)). Change in ultrasound pattern of the cyst was associated with an increased risk of ovarian loss (surgical removal or autoamputation) (pooled proportion, 57.7% (95% CI, 42.9–71.8%)). The risk of ovarian torsion was significantly higher for cysts measuring ≥ 40 mm compared with < 40 mm (OR, 30.8 (95% CI, 8.6–110.0)). The likelihood of having postnatal surgery was higher in patients with cysts ≥ 40 mm compared with < 40 mm (OR, 64.4 (95% CI, 23.6–175.0)) and in complex compared with simple cysts, irrespective of cyst size (OR, 14.6 (95% CI, 8.5–24.8)). In cases undergoing prenatal aspiration of the cyst, rate of recurrence was 37.9% (95% CI, 14.8–64.3%), ovarian torsion and intracystic hemorrhage were diagnosed after birth in 10.8% (95% CI, 4.4–19.7%) and 12.8% (95% CI, 3.8–26.0%), respectively, and 21.8% (95% CI, 0.9–40.0%) had surgery after birth.ConclusionSize and ultrasound appearance are the major determinants of perinatal outcome in fetuses with ovarian cysts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Comparison of characterization and microbial communities in rice straw- and wheat straw-based compost forAgaricus bisporusproduction
Authors: Wang Lin , Mao Jiugeng , Zhao Hejuan , Li Min , Wei Qishun , Zhou Ying , Shao Heping 
Published: June 2016

AbstractRice straw (RS) is an important raw material for the preparation of Agaricus bisporus compost in China. In this study, the characterization of composting process from RS and wheat straw (WS) was compared for mushroom production. The results showed that the temperature in RS compost increased rapidly compared with WS compost, and the carbon (C)/nitrogen (N) ratio decreased quickly. The microbial changes during the Phase I and Phase II composting process were monitored using denaturing gradient gel electrophoresis (DGGE) and phospholipid fatty acid (PLFA) analysis. Bacteria were the dominant species during the process of composting and the bacterial community structure dramatically changed during heap composting according to the DGGE results. The bacterial community diversity of RS compost was abundant compared with WS compost at stages 4–5, but no distinct difference was observed after the controlled tunnel Phase II process. The total amount of PLFAs of RS compost, as an indicator of microbial biomass, was higher than that of WS. Clustering by DGGE and principal component analysis of the PLFA compositions revealed that there were differences in both the microbial population and community structure between RS- and WS-based composts. Our data indicated that composting of RS resulted in improved degradation and assimilation of breakdown products by A. bisporus, and suggested that the RS compost was effective for sustaining A. bisporus mushroom growth as well as conventional WS compost.
Family obligations and individuation among immigrant youth: Do generational status and age at immigration matter?
Authors: Oznobishin Olga , Kurman Jenny 
Published: June 2016

ABSTRACTImmigrant children and adolescents often assume parental roles in their families and may feel guilty about psychologically separating and individuating from the family. However, little is known about this phenomenon and youth' generational status and age at immigration. We investigated various aspects of family obligations (instrumental and emotional roles, language and culture brokering, perceived unfairness) and individuation among 302 immigrants from the former Soviet Union in Israel: first‐generation (n = 44) and second‐generation immigrant adolescents (n = 56); young adults who had arrived in Israel before the age of nine (n = 72) and from this age onward (n = 130). Immigrants who had arrived at age nine and older reported adopting more family obligations than other groups. Among the second‐generation immigrants, family obligations were related to lower individuation compared to the first‐generation immigrants. Possible explanations for the relations between family obligations and individuation according to generational status are suggested.
APOE and MS4A6A interact with GnRH signaling in Alzheimer's disease: Enrichment of epistatic effects
Authors: Cáceres Alejandro , Vargas José E. , González Juan R. 
Published: June 2016

IntroductionIt is unknown if risk loci, identified by genome‐wide association studies of late‐onset Alzheimer's disease (LOAD), are linked to common molecular mechanisms through epistatic effects.MethodsWe performed genome‐wide interaction studies of five risk variants for LOAD followed by enrichment analyses to find if there are pathways that simultaneously interact with more than one variant. This novel approach was applied to four independent cohorts (5393 cases and 3746 controls).ResultsWe found enrichment of epistasis in gonadotropin‐releasing hormone signaling with risk single‐nucleotide polymorphisms in APOE and MS4A6A (P value = 3.7 × 10−5, P value = 5.6 × 10−6); vascular smooth muscle contraction pathway was also enriched in epistasis with these loci (P value = 9.6 × 10−5, P value = 2.4 × 10−7). MS4A6A risk variant also interacted with dilated cardiomyopathy pathway (P value = 3.1 × 10−7).DiscussionIn addition to APOE, MS4A6A polymorphisms should be considered in hormone trials targeting gonadotropins. Interactions of risk variants with neurovascular pathways may also be important in LOAD pathology.
Severity of Menopausal Symptoms and Nicotine Dependence amongst Postmenopausal Women Smokers
Authors: Copeland Amy L. , Peltier MacKenzie R. , Geiselman Paula J. 
Published: June 2016

Rationale: Cigarette smoking has antiestrogenic properties, which may worsen the symptoms and health risks associated with menopause.Objectives: In the present study, it was hypothesised that menopausal symptoms would improve with smoking abstinence.Methods: Postmenopausal smokers (n = 76) were assessed with the Kupperman Index (KI) of menopausal symptoms and smoking-related indices of nicotine dependence, cotinine level, cigarettes per day (CPD), and number of years smoking.Results: Participants were 67% Caucasian, 33% African-American, 52.3(SD = 7.8) mean years of age, follicle stimulating hormone (FSH) level, m = 42.6(SD = 25.7) mlU/ml, mean number of months since last menses was 145.1(SD = 118.9), and mean body mass index (BMI) was 27.4(SD = 6.2). Mean cigarettes smoked per day (CPD) was 20.3(SD = 11.5), for m = 29.4(SD = 10.7) years; m = 6.4(SD = 2.1) Fagerström Test for Nicotine Dependence (FTND), m = 23.8(SD = 13.0) ppm carbon monoxide, and m = 19.7(SD = 12.5) KI total score. Most participants (78.9%) were currently taking hormone therapy (HT). Hierarchical linear regression analyses revealed that FTND (β = 0.48, p = 0.001) and cotinine level (β = −0.27, p = 0.02) predicted KI scores at baseline. Amongst participants (n = 65) who achieved abstinence for 2 weeks, number of years smoking predicted KI scores (β = 0.38, p = 0.01). At 8 weeks postcessation, CPD significantly predicted of KI scores (β = −0.74), p = 0.04).Conclusions: With abstinence from smoking, the overall severity of menopausal symptoms decreased and shared variance with different smoking-related variables. The temporal and cessation-related symptom course identified in this study will be important in informing cessation interventions with this population of smokers.
MATERNAL HEALTH-SEEKING BEHAVIOUR AND UNDER-FIVE MORTALITY IN ZIMBABWE
Authors: Chadoka-Mutanda Nyasha , Odimegwu Clifford O. 
Published: June 2016

SummaryUnder-five mortality remains a major public health challenge in sub-Saharan Africa. Zimbabwe is one of the countries in the region that failed to achieve Millennium Developmental Goal 4 in 2015. The objective of this study was to examine the extent to which maternal health-seeking behaviour prior to and during pregnancy and post-delivery influences the likelihood of under-five mortality among Zimbabwean children. The study was cross-sectional and data were extracted from the 2010/11 Zimbabwe Demographic and Health Survey (ZDHS). The study sample comprised 5155 children who were born five years preceding the 2010/11 ZDHS to a sample of 4128 women of reproductive age (15–49 years). Cox Proportional Hazard regression modelling was used to examine the relationship between maternal health-seeking behaviour and under-five mortality. The results showed that maternal health-seeking behaviour factors are associated with the risk of dying during childhood. Children born to mothers who had ever used contraceptives (HR: 0.38, CI 0.28–0.51) had a lower risk of dying during childhood compared with children born to mothers who had never used any contraceptive method. The risk of under-five mortality among children who had a postnatal check-up within two months after birth (HR: 0.36, CI 0.23–0.56) was lower than that of children who did not receive postnatal care. Small birth size (HR: 1.70, CI 1.20–2.41) and higher birth order (2+) increased the risk of under-five mortality. Good maternal health-seeking behaviour practices at the three critical stages around childbirth have the potential to reduce under-five mortality. Therefore, public health programmes should focus on influencing health-seeking behaviour among women and removing obstacles to effective maternal health-seeking behaviour in Zimbabwe.
On some theoretical problems of laser wake-field accelerators
Authors: Bulanov S. V. , Esirkepov T. Zh. , Hayashi Y. , Kiriyama H. , Koga J. K. , Kotaki H. , Mori M. , Kando M. 
Published: June 2016

Enhancement of the quality of laser wake-field accelerated (LWFA) electron beams implies the improvement and controllability of the properties of the wake waves generated by ultra-short pulse lasers in underdense plasmas. In this work we present a compendium of useful formulas giving relations between the laser and plasma target parameters allowing one to obtain basic dependences, e.g. the energy scaling of the electrons accelerated by the wake field excited in inhomogeneous media including multi-stage LWFA accelerators. Consideration of the effects of using the chirped laser pulse driver allows us to find the regimes where the chirp enhances the wake field amplitude. We present an analysis of the three-dimensional effects on the electron beam loading and on the unlimited LWFA acceleration in inhomogeneous plasmas. Using the conditions of electron trapping to the wake-field acceleration phase we analyse the multi-equal stage and multiuneven stage LWFA configurations. In the first configuration the energy of fast electrons is a linear function of the number of stages, and in the second case, the accelerated electron energy grows exponentially with the number of stages. The results of the two-dimensional particle-in-cell simulations presented here show the high quality electron acceleration in the triple stage injection–acceleration configuration.
Conservation status and management insights from tracking a cryptic and Critically Endangered species of Orchidaceae
Authors: Kraaij T. , Baard J. A. , Crain B. J. 
Published: June 2016

AbstractNinety-five percent of orchid species associated with fynbos shrublands of South Africa's Cape Floristic Kingdom have been assessed for the IUCN Red List, yet aspects of their demography and population biology remain poorly understood. We conducted a 6-year demographic study of the Critically Endangered Disa procera, a cryptic, terrestrial species from South Africa with a global population of c. 50 individuals known from a single location. We aimed to provide management recommendations that would facilitate its persistence. Our findings indicate that the population of D. procera is larger than previously thought, and the species occurs at two distinct locations. These orchids exhibit high interannual variation in population size and turnover of individuals, potentially indicative of a species with a short life span, and still meet the criteria for Critically Endangered status. The species benefits from disturbances, such as brush cutting along trails, or fire, which open up clearances in the vegetation. However, physical damage to plants during their aboveground growing season (September–January) is particularly detrimental and should be avoided in habitat management for the species. Fire had beneficial effects at the population and individual levels and is recommended at 10–25-year intervals, outside the orchid's growing season. The species exhibited comparatively high rates of fruit set (68%), suggesting that pollination limitation does not currently constrain its performance. Its patchy distribution may, however, indicate constraints on dispersal or recruitment. We recommend that management strategies should include continued protection and monitoring of both populations, studies on pollination, habitat requirements and mycorrhizal associates, and a prescribed disturbance regime.
‘It's in my blood now’: the satisfaction of rangers working in Queen Elizabeth National Park, Uganda
Authors: Moreto William D. , Lemieux Andrew M. , Nobles Matt R. 
Published: June 2016

AbstractInvestigating the human dimension of conservation science warrants an interdisciplinary approach. Criminologists and criminal justice scholars have begun to empirically examine various issues that are directly related to conservation, including wildlife law enforcement. This qualitative study of job satisfaction among law enforcement rangers in a protected area in Uganda contributes to both criminal justice and conservation science. Based on interviews and participant observation we identified four main themes that contributed positively to the job satisfaction of rangers: their role in aiding Uganda's conservation efforts and national development; financial stability and familial support; conducting frontline work and establishing ownership of the Park; and opportunities for personal and social development. We discuss the implications of our findings for Park management capacity building as well as for future interdisciplinary and qualitative scholarship in conservation science.
Love and Transience in Proust
Authors: Kubala Robbie 
Published: June 2016

AbstractOne strand of recent philosophical attention to Marcel Proust's novel À la Recherche du Temps Perdu, exemplified by Martha Nussbaum and Rae Langton, claims that romantic love is depicted in the text as self-regarding and solipsistic. I aim to challenge this reading. First, I demonstrate that the text contains a different view, overlooked by these recent interpreters, according to which love is directed at the partially knowable reality of another. Second, I argue that a better explanation for Proust's narrator's ultimate renunciation of romantic love appeals not to his impossible epistemic standard for knowledge of another person, but to his demanding evaluative standard for the permanence of love. This interpretation takes into account the broader scope of the novel, connecting with its larger themes of lost time and the desire for stability, and is more charitable, connecting to familiar worries about transience and constancy in loving relationships.