bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting cancer resistance to therapies with cell-type-specific dynamic logic models
Authors: Eduati Federica , Doldàn-Martelli Victoria , Klinger Bertram , Cokelaer Thomas , Sieber Anja , Kogera Fiona , Dorel Mathurin , Garnett Mathew J , Blüthgen Nils , Saez-Rodriguez Julio 
Published: December 2016

AbstractTherapies targeting specific molecular processes, in particular kinases, are major strategies to treat cancer. Genomic features are commonly used as biomarkers for drug sensitivity, but our ability to stratify patients based on these features is still limited. As response to kinase inhibitors is a dynamic process affecting largely signal transduction, we investigated the association between cell-specific dynamic signaling pathways and drug sensitivity. We measured 14 phosphoproteins under 43 different perturbed conditions (combination of 5 stimuli and 7 inhibitors) for 14 colorectal cancer cell-lines, and built cell-line-specific dynamic logic models of the underlying signaling network. Model parameters, representing pathway dynamics, were used as features to predict sensitivity to a panel of 27 drugs. This analysis revealed associations between cell-specific signaling pathways and drug sensitivity for 14 of the drugs, 9 of which have no genomic biomarker. Following one of these associations, we validated a drug combination predicted to overcome resistance to MEK inhibitors by co-blockade of GSK3. These results underscore the value of perturbation-based studies to find biomarkers and combination therapies complementing those based on a static genomic characterization.
Combining familiarity and landscape features helps break down the barriers between movements and home ranges in a non‐territorial large herbivore
Authors: Marchand Pascal , Garel Mathieu , Bourgoin Gilles , Duparc Antoine , Dubray Dominique , Maillard Daniel , Loison Anne 
Published: December 2016

Summary

Recent advances in animal ecology have enabled identification of certain mechanisms that lead to the emergence of territories and home ranges from movements considered as unbounded. Among them, memory and familiarity have been identified as key parameters in cognitive maps driving animal navigation, but have been only recently used in empirical analyses of animal movements.

At the same time, the influence of landscape features on movements of numerous species and on space division in territorial animals has been highlighted. Despite their potential as exocentric information in cognitive maps and as boundaries for home ranges, few studies have investigated their role in the design of home ranges of non‐territorial species.

Using step selection analyses, we assessed the relative contribution of habitat characteristics, familiarity preferences and linear landscape features in movement step selection of 60 GPS‐collared Mediterranean mouflon Ovis gmelini musimon × Ovis sp. monitored in southern France. Then, we evaluated the influence of these movement‐impeding landscape features on the design of home ranges by testing for a non‐random distribution of these behavioural barriers within sections of space differentially used by mouflon.

We reveal that familiarity and landscape features are key determinants of movements, relegating to a lower level certain habitat constraints (e.g. food/cover trade‐off) that we had previously identified as important for this species. Mouflon generally avoid crossing both anthropogenic (i.e. roads, tracks and hiking trails) and natural landscape features (i.e. ridges, talwegs and forest edges) while moving in the opposite direction, preferentially toward familiar areas. These specific behaviours largely depend on the relative position of each movement step regarding distance to the landscape features or level of familiarity in the surroundings. We also revealed cascading consequences on the design of home ranges in which most landscape features were excluded from cores and relegated to the peripheral areas.

These results provide crucial information on landscape connectivity in a context of marked habitat fragmentation. They also call for more research on the role of landscape features in the emergence of home ranges in non‐territorial species using recent methodological developments bridging the gap between movements and space use patterns.
Trait‐associated loss of frugivores in fragmented forest does not affect seed removal rates
Authors: Farwig Nina , Schabo Dana G. , Albrecht Jörg 
Published: December 2016

Summary

Seed dispersal by frugivorous animals forms the basis for regeneration of numerous plant species. Habitat fragmentation has been found to be one major factor perturbing frugivore communities and dependent plant species. Yet, community‐wide consequences of fragmentation for both frugivore and plant communities are still hardly understood.

Here, we studied the effects of habitat fragmentation on the seed removal by frugivorous birds and mammals from nine fleshy‐fruited plant species in Białowieża Forest (Eastern Poland). This last relict of old‐growth lowland forest in Europe poses an exceptional reference site for studying the impact of habitat fragmentation on seed dispersal processes in temperate forest ecosystems.

In particular, (i) we tested for associations between forest fragmentation and response traits of frugivores, that is forest specialization and body mass; (ii) we studied the relationship between frugivore response and effect traits, that is centrality (number of consumed plant species) and interaction type (mutualistic vs. antagonistic); and (iii) we assessed the feedback of fragmentation‐induced changes on plant–frugivore interactions and seed removal rates.

We found that fragmentation led to shifts in the frugivore community, associated with the response traits forest specialization and body mass, with fewer forest specialists and large‐bodied frugivores in fragmented than in continuous forests. However, forest generalists and small‐bodied frugivores were more central in the plant–frugivore associations than forest specialists and large‐bodied frugivores. Therefore, the loss of vulnerable species did not result in reduced seed removal rates in fragmented compared with continuous forest.

Synthesis. These results indicate that seed removal may be relatively robust in spite of shifts in the frugivore community in forest fragments. The correlation between response and effect traits of frugivores highlights the importance of forest generalists and small‐bodied frugivores for maintaining dispersal processes in fragmented forests in temperate regions. Yet, future studies should aim at quantifying the consequences of seed disperser loss on other aspects of dispersal, such as long‐distance dispersal, spatial patterns of seed deposition, seed germination and plant regeneration.
Temporal change and determinants of maternal reproductive success in an expanding oak forest stand
Authors: Gerzabek Gabriel , Oddou‐Muratorio Sylvie , Hampe Arndt 
Published: December 2016

Summary

Global change is generating widespread local‐scale expansions of tree populations. During demographic expansions, even small differences in individual reproductive success can generate large differences in the genetic composition of the resulting population. Colonizing tree populations almost invariably show highly skewed distributions of seed production, but the evolution of this reproductive skew during plant recruitment remains understudied.

We examine how recruit mortality modifies initial patterns of acorn dispersal and maternal reproductive success in a recently established, expanding Pedunculate oak (Quercus robur) forest stand and test different predictors of successful recruit establishment.

We mapped and genotyped a cohort of seedlings (n = 809) emerging within and around the stand (n = 254 adult trees), identified their habitats and monitored their fate until an age of 3 years. Their mother trees were inferred by Bayesian parentage analysis, and the number of assigned descendants was used as a proxy for tree maternal fertility. We examined temporal trends in tree fertility and patterns of dispersal, and tested effects of seed number‐quality trade‐offs, dispersal failure, dispersal distance and habitat of propagule arrival on the probability of seedling establishment.

We observed marked inequality in maternal reproductive success at the time of seedling emergence. A positive relationship between tree fertility and the proportion of non‐dispersed seedlings pointed to disperser satiation. An overall seedling mortality of 69% generated considerable reshuffling in the fertility ranking of individual trees. Non‐dispersal more than doubled seedling mortality. The establishment success of actually dispersed seedlings was independent of mother fertility and dispersal distance but strongly related to the habitat of arrival. Recruit survival was markedly higher in pine plantations or non‐forested areas than in broadleaved forest.

Synthesis. A few highly fertile trees dominated reproduction in the stand. Differential recruitment success tended to reduce their initial advantage, however, suggesting that reproductive inequality might rapidly decline as more trees start to reproduce along the expansion process. Our results also suggest that field estimates of size or seed production are unlikely to provide reliable estimates of lifetime reproductive success in trees.
Estimating contemporary migration rates: effect and joint inference of inbreeding, null alleles and mistyping
Authors: Robledo‐Arnuncio Juan J. , Gaggiotti Oscar E. 
Published: December 2016

Summary

Microsatellite‐based genetic assignment is used broadly to monitor contemporary effective dispersal among populations. The need to investigate the robustness of this method to common genotyping errors was emphasized more than a decade ago, but it remains unaddressed.

We evaluate here for the first time the effect of mistaken and null alleles on estimates of contemporary seed and pollen migration rates obtained with genetic assignment methods. We also introduce a novel Bayesian approach to jointly estimate seed and pollen migration rates, genotyping error rates and null allele frequencies, not requiring independent reference or duplicate genotypic data.

Unaccounted‐for mistaken alleles caused positive bias and increased the root mean square error (RMSE) of pollen migration rate estimates, whereas seed migration rate estimates were weakly sensitive to mistyping. Jointly estimating mistyping rates minimized the bias and RMSE they introduce on pollen migration estimates, while yielding seed migration rate estimates with similar or slightly larger bias and RMSE than those obtained when ignoring mistyping.

Ignoring genotyping errors can be especially problematic when there is no actual migration, because it can lead to the wrong conclusion that there is statistically significant exchange of pollen and/or seeds among populations that are actually isolated.

Unaccounted‐for null alleles are problematic when among‐population pollen dispersal is present, leading to underestimation of pollen migration rates and overestimation of seed migration rates. Jointly estimating null allele frequencies minimized these two biases, reduced the RMSE of seed migration rate estimates and produced relatively small changes in the RMSE of pollen dispersal estimates.

Synthesis. Disregarding genotyping errors and null alleles can produce biased and less accurate estimates of the rates at which present‐day plant populations are exchanging seed and pollen. An approach is proposed here to minimize the effect of genotyping problems on contemporary migration rate estimates, which should help avoiding erroneous migration inference, monitoring and management, especially when dealing with low migration rates and their associated uncertainty.
Maternal and neonatal outcomes of pregnancies in women with Addison's disease: a population‐based cohort study on 7.7 million births
Authors: Schneiderman M , Czuzoj‐Shulman N , Spence AR , Abenhaim HA 
Published: December 2016

ObjectiveTo assess if pregnancies among women with Addison's disease (AD) are at higher risk of adverse maternal and neonatal outcomes.DesignPopulation‐based retrospective cohort study.Setting/PopulationAll births in the United States’ Healthcare Cost and Utilization Project‐Nationwide Inpatient Sample from 2003 to 2011.MethodsBaseline characteristics were compared between women with AD and those without, and prevalence over time was measured. Logistic regression was used to estimate the effect of AD on maternal and neonatal outcomes by calculating the crude and adjusted odds ratios (OR) and corresponding 95% confidence intervals (95% CI).ResultsWe calculated a prevalence of AD in pregnancy of 5.5/100 000, increasing from 5.6 to 9.6/100 000 (P = 0.0001) over the 9‐year study period. Compared with women without AD, women with AD were more likely to deliver preterm (OR 1.50, 95% CI 1.16–1.95), deliver by caesarean section (OR 1.32, 95% CI 1.08–1.61), have impaired wound healing (OR 4.28, 95% CI 2.55–7.18), develop infections (OR 2.44, 95% CI 1.66–3.58) and develop thromboembolism (OR 5.21, 95% CI 2.15–12.63), require transfusions (OR 6.69, 95% CI 4.69–9.54), and have prolonged postpartum hospital admissions (OR 5.71, 95% CI 4.37–7.47). Maternal mortality was significantly higher than in the comparison group (OR 22.30, 95% CI 6.82–72.96). Congenital anomalies (OR 3.62, 95% CI 2.05–6.39) and small‐for‐gestational age infants (OR 1.78, 95% CI 1.15–2.75) were more likely in these pregnancies.ConclusionsAddison's disease significantly increases the risk of severe adverse maternal and neonatal outcomes, so pregnant women with AD are best managed in tertiary‐care centres.Tweetable abstractPregnancies complicated by Addison's disease have an increased risk of adverse maternal and neonatal outcomes.
Lesbian and bisexual women's likelihood of becoming pregnant: a systematic review and meta‐analysis
Authors: Hodson K , Meads C , Bewley S 
Published: December 2016

BackgroundFew data exist regarding pregnancy in lesbian and bisexual (LB) women.ObjectivesTo determine the likelihood of LB women becoming pregnant, naturally or assisted, in comparison with heterosexual womenSearch strategySystematic review of papers published 1 January 2000 to 23 June 2015.Selection criteriaStudies contained details of pregnancy rates among LB women compared with heterosexual women. No restriction on study design.Data collection and analysisInclusion decisions, data extraction and quality assessment were conducted in duplicate. Meta‐analyses were carried out, with subgroups as appropriate.Main resultsOf 6859 papers identified, 104 full‐text articles were requested, 30 papers (28 studies) were included. The odds ratio (OR) of ever being pregnant was 0.19 (95% CI 0.18–0.21) in lesbian women and 1.22 (95% CI 1.15–1.29) in bisexual women compared with heterosexual women. In the general population, the odds ratio for pregnancy was nine‐fold lower among lesbian women and over two‐fold lower among bisexual women (0.12 [95% CI 0.12–0.13] and 0.50 [95% CI 0.45–0.55], respectively). Odds ratios for pregnancy were higher for both LB adolescents (1.37 [95% CI 1.18–1.59] and 1.98 [95% CI 1.85, 2.13], respectively). There were inconsistent results regarding abortion rates. Lower rates of previous pregnancies were found in lesbian women undergoing artificial insemination (OR 0.17 [95% CI 0.11–0.26]) but there were higher assisted reproduction success rates compared with heterosexual women (OR 1.56 [95% CI 1.24–1.96]).ConclusionsHeterosexuality must not be assumed in adolescents, as LB adolescents are at greater risk of unwanted pregnancies and terminations. Clinicians should provide appropriate information to all women, without assumptions about LB patients’ desire for, or rejection of, fertility and childbearing.Tweetable abstractReview of likelihood of LB women becoming pregnant: LB teenagers at greater risk of unwanted pregnancies.
Examining Interobserver Reliability of Metric and Morphoscopic Characteristics of the Mandible
Authors: Byrnes Jennifer F. , Kenyhercz Michael W. , Berg Gregory E. 
Published: December 2016

AbstractMandibular metric and morphological characteristics have long been used for sex and ancestry estimation. Currently, there are no large‐scale studies examining interobserver agreement, particularly examining the role of observer experience. This study examines the interobserver agreement of six morphoscopic and eleven metric mandibular variables. Four observers with varied levels of experience scored 183 mandibles from the William M. Bass Donated Skeletal Collection. Absolute agreement and consistency were evaluated with the intraclass correlation coefficient (ICC). Additionally, technical error of measurement (TEM) and relative TEM (%TEM) were calculated for each metric variable. All analyses were conducted twice—once with all observers and again with only experienced observers. Results show mean morphoscopic agreement of 0.543 among all observers and 0.615 for experienced observers, and mean metric agreement of 0.886 among all observers and 0.911 for experienced observers. Further, no TEM exceeded 2 mm. All results were significant (p < 0.001).
Efficacy and safety of high‐dose dual therapy for Helicobacter pylori rescue therapy: A systematic review and meta‐analysis
Authors: Gao Cai Ping , Zhou Zhou , Wang Jia Zhen , Han Sheng Xi , Li Liang Ping , Lu Hong 
Published: December 2016

AbstractObjectiveAlthough some studies have reported >90% success with high‐dose dual proton pump inhibitor (PPI)–amoxicillin dual therapy for Helicobacter pylori (H. pylori) eradication, the efficacy of this therapy remains controversial. We aimed to re‐evaluate the efficacy and safety of high‐dose dual therapy on H. pylori eradication.MethodsWe searched PubMed, the Cochrane Library, and EMBASE for randomized clinical trials (RCTs) evaluating the efficacy of high‐dose PPI–amoxicillin dual therapy as the rescue therapy on H. pylori eradication. Treatment effect was determined with a fixed‐effect model using the inverse variance method and was expressed as risk ratio (RR) with 95% confidence interval (CI).ResultsBecause of significant statistical heterogeneity (χ2 15.98, I2 = 69%) among the six studies that qualified, four RCTs that included 473 patients with H. pylori infection after eradication failure were assessed. The meta‐analysis showed that high‐dose dual therapy and guideline‐recommended rescue therapies achieved similar efficacy (81.3% vs 81.5%, RR 1.00 [95% CI 0.93–1.08], intention‐to‐treat analysis), compliance (95.3% vs 95.4%, RR 1.00 [95% CI 0.97–1.03]), and side effects (17.9% vs 19.7%, RR 0.88 [95% CI 0.62–1.25]).ConclusionsHigh‐dose PPI–amoxicillin dual therapy is comparable to recommended rescue therapies for H. pylori infection. More researches are needed to determine the efficacy of high‐dose dual therapy as a first‐line therapy.
In‐gantry MRI guided prostate biopsy diagnosis of prostatitis and its relationship with PIRADS V.2 based score
Authors: Jyoti Rajeev , Jina Noel Hamesh , Haxhimolla Hodo Z 
Published: December 2016

AbstractIntroductionThe recent literature has focussed predominantly on prostate cancer detection which has been revolutionized by multiparametric magnetic resonance imaging (mpMRI). Due to an overlap of features, prostatitis may mimic prostate cancer on MRI, especially in patients with chronic prostatitis. We retrospectively analysed our in‐gantry MRI‐guided biopsy (MRGB) results to determine incidental detection rate of prostatitis in Prostate Imaging Reporting and Data System (PIRADS) 3, 4 and 5 foci reported on diagnostic MRI of the prostate.MethodsAbout 137 patients underwent in‐gantry MRGB for lesions with PIRADS score of 3 or above. All the biopsies were performed utilizing the dynaTRIM™ system (Invio Inc, Germany) on a three‐tesla MRI scanner (Ingenia 3.0T, Philips, Netherlands) by a Radiologist and a Urologist.ResultsWe biopsied 228 lesions in 137 patients. There were 55 lesions that returned positive for prostate cancer with a Gleason Score of 3 + 3 = 6 or above. There were 62 lesions that showed inflammation. The distribution of these lesions was 3 (5%) in the central zone, 32 (52%) in the transitional zone and 27 (43%) in the peripheral zone. Inflammation was found in 36 (58%) PIRADS 3 lesions, 24 (39%) PIRADS 4 lesions and 2 (3%) PIRADS 5 lesions on pre biopsy MRI evaluation.ConclusionIn our series, biopsies which showed inflammation had a radiological appearance on mpMRI more likely of a PIRADS 3 or 4 lesions with only 3% of PIRADS 5 biopsies showing inflammation. This would suggest that a higher PIRADS score can more reliably differentiate between prostate cancer and prostatitis.
Breast interest group faculty of radiation oncology: Australian and New Zealand patterns of practice survey on breast radiotherapy
Authors: Nguyen Kimberley , Mackenzie Penny , Allen Angela , Dreosti Marcus , Morgia Marita , Zissiadis Yvonne , Lamoury Gilian , Windsor Apsara 
Published: December 2016

AbstractIntroductionThis patterns of practice study was conducted on behalf of the RANZCR Breast Interest Group in order to document current radiotherapy practices for breast cancer in Australia and New Zealand. The survey identifies variations and highlights potential contentious aspects of radiotherapy management of breast cancer.MethodsA fifty‐eight question survey was disseminated via the Survey Monkey digital platform to 388 Radiation Oncologists in Australia and New Zealand.ResultsIn total, 156 responses were received and collated. Areas of notable consensus among respondents included hypofractionation (77.3% of respondents would ‘always’ or ‘sometimes’ consider hypofractionation in the management of ductal carcinoma in‐situ and 99.3% in early invasive breast cancer); margin status in early breast cancer (73.8% believe a clear inked margin is sufficient and does not require further surgery) and use of bolus in post‐mastectomy radiotherapy (PMRT) (91.1% of participants use bolus in PMRT). Areas with a wider degree of variability amongst respondents included regional nodal irradiation and components of radiotherapy planning and delivery (examples include the technique used for delivery of boost and frequency of bolus application for PMRT).ConclusionThe results of these patterns of practice survey informs radiation oncologists in Australia and New Zealand of the current clinical practices being implemented by their peers. The survey identifies areas of consensus and contention, the latter of which may lead to a development of research trials and/or educational activities to address these areas of uncertainty.