bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lungworm Eucoleus aerophilus (Capillaria aerophila) infection in a feline immunodeficiency virus-positive cat in France
Authors: Elhamiani Khatat Sarah , Rosenberg Dan , Benchekroun Ghita , Polack Bruno 
Published: June 2016

Case summary A 2-year-old domestic shorthair female outdoor cat living in France was diagnosed with a lungworm infection due to Eucoleus aerophilus. The history and clinical signs, in association with bronchoscopic examination, suggested chronic upper respiratory disease. Cytological examination of bronchoalveolar lavage fluid (BALF) was consistent with suppurative bronchitis. Direct microscopic examination of BALF enabled the identification of E aerophilus ova. Relevance and novel information The cat was positive for feline immunodeficiency virus and had been treated with steroids for a suspected allergic bronchitis, suggesting that immunodeficiency was probably a facilitating factor for E aerophilus infection, as described in previous cases. This case report emphasises the importance of considering eucoleosis (capillariosis) in the differential diagnosis of respiratory disease in cats. To our knowledge, this is the first clinical case of E aerophilus infection described in a domestic cat in France.
Influence of phyllosilicates and fluid–rock interaction on the deformation style and mechanical behaviour of quartz-rich rocks in the Carboneras and Palomares fault areas (SE Spain)
Authors: Jiménez-Millán J. , Abad I. , Hernández-Puentes P. , Jiménez-Espinosa R. 
Published: June 2016

AbstractDeformed quartzitic rocks from the Carboneras and Palomares fault areas (SE Spain) are enriched in phyllosilicates compared to their respective protoliths. Deformation is mainly localized in highly foliated chlorite-rich bands. Quartz-rich bands show brittle deformation developing dolomite-rich cross-cutting veins re-cementing microcataclasite areas. Undamaged lenses within the cataclastic rocks contain patches of phyllosilicates with randomly oriented chlorite and mica. Mg, Fe, water, As and Zn enrichment of the damaged rocks suggests a process of hydrothermal chloritization associated with the Cabo de Gata volcanism. Petrographic characteristics indicate that hydrothermal alteration that produced chlorite and mica-enrichment occurred before faulting. Phyllosilicates provided lubricating properties to the quartzitic rocks, favouring the predominance of creep over seismic stick-slip and reducing the possibility of large seismogenic events. Dolomite cementation as a consequence of fluid–rock interaction processes would have a limited effect, due to the presence of weak phyllosilicate surfaces.
If the shoe fits: development of an on‐line tool to aid practitioner/patient discussions about ‘healthy footwear’
Authors: Farndon Lisa , Robinson Victoria , Nicholls Emily , Vernon Wesley 
Published: June 2016

AbstractBackgroundA previous study highlighted the importance of footwear to individuals' sense of their identity, demonstrating that shoes must ‘fit’ someone socially, as well as functionally. However, unhealthy shoes can have a detrimental effect on both foot health and mobility. This project utilises qualitative social science methods to enable podiatrists to understand the broader contribution of footwear to patients' sense of themselves and from this an online toolkit was developed to aid footwear education.MethodSemi‐structured interviews were conducted with six podiatrists/shoe‐fitters and 13 people with foot pathologies, some of whom also completed shoe diaries. These were supplemented with some follow‐up interviews and photographs of participants' own shoes were taken to allow in‐depth discussions.ResultsFour areas related to ‘fit’ were identified; practicalities, personal, purpose and pressures, all of which need to be considered when discussing changes in footwear. These were incorporated into an online toolkit which was further validated by service users and practitioners in a focus group.ConclusionThis toolkit can support podiatrists in partnership with patients to identify and address possible barriers to changing footwear towards a more suitable shoe. Enabling patients to make healthier shoe choices will help contribute to improvements in their foot health and mobility.
Gigwa—Genotype investigator for genome-wide analyses
Authors: Sempéré Guilhem , Philippe Florian , Dereeper Alexis , Ruiz Manuel , Sarah Gautier , Larmande Pierre 
Published: June 2016

Abstract

Background
Exploring the structure of genomes and analyzing their evolution is essential to understanding the ecological adaptation of organisms. However, with the large amounts of data being produced by next-generation sequencing, computational challenges arise in terms of storage, search, sharing, analysis and visualization. This is particularly true with regards to studies of genomic variation, which are currently lacking scalable and user-friendly data exploration solutions.

Description
Here we present Gigwa, a web-based tool that provides an easy and intuitive way to explore large amounts of genotyping data by filtering it not only on the basis of variant features, including functional annotations, but also on genotype patterns. The data storage relies on MongoDB, which offers good scalability properties. Gigwa can handle multiple databases and may be deployed in either single- or multi-user mode. In addition, it provides a wide range of popular export formats.

Conclusions
The Gigwa application is suitable for managing large amounts of genomic variation data. Its user-friendly web interface makes such processing widely accessible. It can either be simply deployed on a workstation or be used to provide a shared data portal for a given community of researchers.
Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group
Authors: Pieters Rob , de Groot-Kruseman Hester , Van der Velden Vincent , Fiocco Marta , van den Berg Henk , de Bont Evelien , Egeler R. Maarten , Hoogerbrugge Peter , Kaspers Gertjan , Van der Schoot Ellen , De Haas Valerie , Van Dongen Jacques 
Published: June 2016

Purpose Outcome of childhood acute lymphoblastic leukemia (ALL) improved greatly by intensifying chemotherapy for all patients. Minimal residual disease (MRD) levels during the first months predict outcome and may select patients for therapy reduction or intensification. Methods Patients 1 to 18 years old with ALL were stratified on the basis of MRD levels after the first and second course of chemotherapy. Thereafter, therapy was substantially reduced in patients with undetectable MRD (standard risk) and intensified in patients with intermediate (medium risk) and high (high risk) levels of MRD. Seven hundred seventy-eight consecutive patients were enrolled. The method of analysis was intention-to-treat. Outcome was compared with historical controls. Results In MRD-based standard-risk patients, the 5-year event-free survival (EFS) rate was 93% (SE 2%), the 5-year survival rate was 99% (SE 1%), and the 5-year cumulative incidence of relapse rate was 6% (SE 2%). The safety upper limit of number of observation years was reached and therapy reduction was declared safe. MRD-based medium-risk patients had a significantly higher 5-year EFS rate (88%, SE 2%) with therapy intensification (including 30 weeks of asparaginase exposure and dexamethasone/vincristine pulses) compared with historical controls (76%, SE 6%). Intensive chemotherapy and stem cell transplantation in MRD-based high-risk patients resulted in a significantly better 5-year EFS rate (78%, SE 8% v 16%, SE 8% in controls). Overall outcome improved significantly (5-year EFS rate 87%, 5-year survival rate 92%, and 5-year cumulative incidence of relapse rate 8%) compared with preceding Dutch Childhood Oncology Group protocols. Conclusion Chemotherapy was substantially reduced safely in one-quarter of children with ALL who were selected on the basis of undetectable MRD levels, without jeopardizing the survival rate. Outcomes of patients with intermediate and high levels of MRD improved with therapy intensification.
Evaluation of the Risk of Relapse in Classical Hodgkin Lymphoma at Event-Free Survival Time Points and Survival Comparison With the General Population in British Columbia
Authors: Hapgood Greg , Zheng Yvonne , Sehn Laurie H. , Villa Diego , Klasa Richard , Gerrie Alina S. , Shenkier Tamara , Scott David W. , Gascoyne Randy D. , Slack Graham W. , Parsons Christina , Morris James , Pickles Tom , Connors Joseph M. , Savage Kerry J. 
Published: June 2016

Purpose Studies in classical Hodgkin lymphoma (cHL) typically measure the time to events from diagnosis. We evaluated the risk of relapse at event-free survival time points in cHL and compared the risk of death to expected mortality rates in British Columbia (BC). Methods The BC Cancer Agency Lymphoid Cancer Database was screened to identify all patients age 16 to 69 years diagnosed with cHL between 1989 and 2012 treated with the chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (or equivalent). We compared the observed mortality to the general population using age-, sex-, and calendar period–generated expected mortality rates from BC life-tables. Relative survival was calculated using a conditional approach and expressed as a standardized mortality ratio of observed-to-expected deaths. Results One thousand four hundred two patients were identified; 749 patients were male (53%), the median age was 32 years, and 68% had advanced-stage disease. The median follow-up time was 8.4 years. Seventy-two percent of relapses occurred within the first 2 years of diagnosis. For all patients, the 5-year risk of relapse from diagnosis was 18.1% but diminished to 5.6% for patients remaining event free at 2 years. For advanced-stage patients who were event free at 2 years, the 5-year risk of relapse was only 7.6%, and for those who were event free at 3 years, it was comparable to that of limited-stage patients (4.1% v 2.5%, respectively; P = .07). Furthermore, international prognostic score ≥ 4 and bulky disease were no longer prognostic in patients who were event free at 1 year. Although the relative survival improved as patients remained in remission, it did not normalize compared with the general population. Conclusion Patients with cHL who are event free at 2 years have an excellent outcome regardless of baseline prognostic factors. All patients with cHL had an enduring increased risk of death compared with the general population.
Double-Blind, Placebo-Controlled, Randomized Phase III Trial Evaluating Pertuzumab Combined With Chemotherapy for Low Tumor Human Epidermal Growth Factor Receptor 3 mRNA–Expressing Platinum-Resistant Ovarian Cancer (PENELOPE)
Authors: Kurzeder Christian , Bover Isabel , Marmé Frederik , Rau Joern , Pautier Patricia , Colombo Nicoletta , Lorusso Domenica , Ottevanger Petronella , Bjurberg Maria , Marth Christian , Barretina-Ginesta Pilar , Vergote Ignace , Floquet Anne , del Campo Josep M. , Mahner Sven , Bastière-Truchot Lydie , Martin Nicolas , Oestergaard Mikkel Z. , Kiermaier Astrid , Schade-Brittinger Carmen , Polleis Sandra , du Bois Andreas , Gonzalez-Martin Antonio 
Published: June 2016

Purpose The AGO-OVAR 2.29/ENGOT-ov14/PENELOPE prospectively randomized phase III trial evaluated the addition of pertuzumab to chemotherapy in patients with platinum-resistant ovarian carcinoma with low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression. We report the results of the primary efficacy analysis. Patients and Methods Eligible patients had ovarian carcinoma that progressed during or within 6 months of completing four or more platinum cycles, centrally tested low tumor HER3 mRNA expression (concentration ratio ≤ 2.81 by quantitative reverse transcriptase polymerase chain reaction on cobas z480 [Roche Molecular Diagnostics, Pleasanton, CA]), and no more than two prior lines of chemotherapy. After investigators’ selection of the chemotherapy backbone (single-agent topotecan, weekly paclitaxel, or gemcitabine), patients were randomly assigned to also receive either placebo or pertuzumab (840-mg loading dose followed by 420 mg every 3 weeks). Stratification factors were selected chemotherapy, prior antiangiogenic therapy, and platinum-free interval. The primary end point was independent review committee–assessed progression-free survival (PFS). Additional end points included overall survival, investigator-assessed PFS, objective response rate, safety, patient-reported outcomes, and translational research. Results Overall, 156 patients were randomly assigned. Adding pertuzumab to chemotherapy did not significantly improve independent review committee–assessed PFS for the primary analysis (stratified hazard ratio, 0.74; 95% CI, 0.50 to 1.11; P = .14; median PFS, 4.3 months for pertuzumab plus chemotherapy v 2.6 months for placebo plus chemotherapy). Sensitivity analyses and secondary efficacy end point results were consistent with the primary analysis. The effect on PFS favoring pertuzumab was more pronounced in the gemcitabine and paclitaxel cohorts. No new safety signals were seen. Conclusion Although the primary objective was not met, subgroup analyses showed trends in PFS favoring pertuzumab in the gemcitabine and paclitaxel cohorts, meriting further exploration of pertuzumab in ovarian cancer.
Lack of Effectiveness of Neutropenic Diet and Social Restrictions as Anti-Infective Measures in Children With Acute Myeloid Leukemia: An Analysis of the AML-BFM 2004 Trial
Authors: Tramsen Lars , Salzmann-Manrique Emilia , Bochennek Konrad , Klingebiel Thomas , Reinhardt Dirk , Creutzig Ursula , Sung Lillian , Lehrnbecher Thomas 
Published: June 2016

Purpose Although nonpharmacologic anti-infective measures are widely used in children treated for acute myeloid leukemia (AML), there is little evidence of their effectiveness. Patients and Methods We analyzed infectious complications in children during intensive treatment of AML according to the AML-BFM 2004 trial and surveyed sites on institutional standards regarding recommended restrictions of social contacts (six items), pets (five items), and food (eight items). A scoring system was developed with a restriction score for each item. Multivariable Poisson regression adjusted for sex, age, weight group, risk stratification, and prophylactic antibiotics was used to estimate the impact of the restrictions on the incidence ratios of fever of unknown origin, bacteremia, pneumonia, and gastroenteritis. Results Data on recommendations of nonpharmacologic anti-infective measures and infectious complications were available in 339 patients treated in 37 institutions. Analyses did not demonstrate a significant benefit of any of the restrictions regarding food, social contacts, and pets on the risk of fever, bacteremia, pneumonia, and gastroenteritis. In contrast, age, weight group, risk stratification, and nonabsorbable antibiotics had some influence on infections complications. Conclusion The lack of effectiveness of dietary restrictions and restrictions regarding social contacts and pets should result in reconsideration of anti-infective policies.
Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer
Authors: Fribbens Charlotte , O’Leary Ben , Kilburn Lucy , Hrebien Sarah , Garcia-Murillas Isaac , Beaney Matthew , Cristofanilli Massimo , Andre Fabrice , Loi Sherene , Loibl Sibylle , Jiang John , Bartlett Cynthia Huang , Koehler Maria , Dowsett Mitch , Bliss Judith M. , Johnston Stephen R.D. , Turner Nicholas C. 
Published: June 2016

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.
Comparative Effectiveness of Treatment Strategies for Bladder Cancer With Clinical Evidence of Regional Lymph Node Involvement
Authors: Galsky Matthew D. , Stensland Kristian , Sfakianos John P. , Mehrazin Reza , Diefenbach Michael , Mohamed Nihal , Tsao Che-Kai , Boffetta Paolo , Wiklund Peter , Oh William K. , Mazumdar Madhu , Ferket Bart 
Published: June 2016

Purpose Patients with bladder cancer with clinical lymph node involvement (cN+) are at high risk for distant metastases, but are potentially curable. Such patients are excluded from neoadjuvant chemotherapy trials and pooled with patients with distant metastases in first-line chemotherapy trials not suited to define the role of combined-modality therapy. To address this evidence void, we performed a comparative effectiveness analysis. Methods We included cTanyN1-3M0 bladder cancer patients from the National Cancer Data Base (2003-2012) treated with chemotherapy and/or cystectomy. We used multistate survival analysis, allowing for delayed entry, to assess overall survival (OS) according to various treatment strategies. Effectiveness was estimated with multivariable adjustment for tumor-, patient-, and facility-level characteristics. Results Among 1,739 patients (cN1, 48%; cN2, 45%; cN3, 7%), 1,104 underwent cystectomy and 635 were treated with chemotherapy alone. Of the cystectomy patients, 363 received preoperative and 328 received adjuvant chemotherapy. The crude 5-year OS for chemotherapy alone, cystectomy alone, preoperative chemotherapy followed by cystectomy, and cystectomy followed by adjuvant chemotherapy was 14% (95% CI, 11% to 17%), 19% (95% CI, 15% to 24%), 31% (95% CI, 25% to 38%), and 26% (95% CI, 21% to 34%), respectively. Compared with cystectomy alone, preoperative chemotherapy was associated with a significant improvement in OS (hazard ratio, 0.80; 95% CI, 0.66 to 0.97). Adjuvant chemotherapy was also associated with a significant improvement in survival compared with cystectomy alone. The survival of patients treated with chemotherapy alone was worse than those treated with cystectomy alone. Conclusion A subset of patients with cN+ bladder cancer achieves long-term survival. Combined-modality therapy, with chemotherapy and cystectomy, is associated with the best outcomes.
PRKACA Somatic Mutations Are Rare Findings in Aldosterone-Producing Adenomas
Authors: Rhayem Yara , Perez-Rivas Luis G. , Dietz Anna , Bathon Kerstin , Gebhard Christian , Riester Anna , Mauracher Brigitte , Gomez-Sanchez Celso , Eisenhofer Graeme , Schwarzmayr Thomas , Calebiro Davide , Strom Tim M. , Reincke Martin , Beuschlein Felix 
Published: June 2016

Context:Somatic mutations have been found causative for endocrine autonomy in aldosterone-producing adenomas (APAs). Whereas mutations of PRKACA (catalytic subunit of protein kinase A) have been identified in cortisol-producing adenomas, the presence of PRKACA variants in APAs is unknown, especially in those that display cosecretion of cortisol.Objective:The objective of the study was to investigate PRKACA somatic variants identified in APA cases.Design:Identification of PRKACA somatic variants in APAs by whole-exome sequencing followed by in vitro analysis of the enzymatic activity of PRKACA variants and functional characterization by double immunofluorescence of CYP11B2 and CYP11B1 expression in the corresponding tumor tissues.Setting and Patients:APA tissues were collected from 122 patients who underwent unilateral adrenalectomy for primary aldosteronism between 2005 and 2015 at a single institution.Results:PRKACA somatic mutations were identified in two APA cases (1.6%). One APA carried a newly identified p.His88Asp variant, whereas in a second case, a p.Leu206Arg mutation was found, previously described only in cortisol-producing adenomas with overt Cushing's syndrome. Functional analysis showed that the p.His88Asp variant was not associated with gain of function. Although CYP11B2 was strongly expressed in the p.His88Asp-mutated APA, the p.Leu206Arg carrying APA predominantly expressed CYP11B1. Accordingly, biochemical Cushing's syndrome was present only in the patient with the p.Leu206Arg mutation. After adrenalectomy, both patients improved with a reduced number of antihypertensive medications and normalized serum potassium levels.Conclusions:We describe for the first time PRKACA mutations as rare findings associated with unilateral primary aldosteronism. As cortisol cosecretion occurs in a subgroup of APAs, other molecular mechanisms are likely to exist.
Signaling pathways controlling activity-dependent local translation of BDNF and their localization in dendritic arbors
Authors: Baj Gabriele , Pinhero Vera , Vaghi Valentina , Tongiorgi Enrico 
Published: June 2016

ABSTRACT
Brain-derived neurotrophic factor (BDNF) is encoded by multiple mRNA variants whose differential subcellular distribution constitutes a ‘spatial code’ for local translation of BDNF and selective morphological remodeling of dendrites. Here, we investigated where BDNF translation takes place and what are the signaling pathways involved. Cultured hippocampal neurons treated with KCl showed increased BDNF in the soma, proximal and distal dendrites, even in quaternary branches. This activity-dependent increase of BDNF was abolished by cycloheximide, suggesting local translation, and required activation of glutamate and Trk receptors. Our data showed that BDNF translation was regulated by multiple signaling cascades including RAS–Erk and mTOR pathways, and CaMKII–CPEB1, Aurora-A–CPEB1 and Src–ZBP1 pathways. Aurora-A, CPEB1, ZBP1 (also known as IGF2BP1), eiF4E, S6 (also known as rpS6) were present throughout the dendritic arbor. Neuronal activity increased the levels of Aurora-A, CPEB1 and ZBP1 in distal dendrites whereas those of eiF4E and S6 were unaffected. BDNF-6, the main dendritic BDNF transcript, was translated in the same subcellular domains and in response to the same pathways as total BDNF. In conclusion, we identified the signaling cascades controlling BDNF translation and we describe how the translational machinery localization is modulated in response to electrical activity.