bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative and population genomic landscape of Phellinus noxius: A hypervariable fungus causing root rot in trees
Authors: Chung Chia‐Lin , Lee Tracy J. , Akiba Mitsuteru , Lee Hsin‐Han , Kuo Tzu‐Hao , Liu Dang , Ke Huei‐Mien , Yokoi Toshiro , Roa Marylette B. , Lu Mei‐Yeh J. , Chang Ya‐Yun , Ann Pao‐Jen , Tsai Jyh‐Nong , Chen Chien‐Yu , Tzean Shean‐Shong , Ota Yuko , Hattori Tsutomu , Sahashi Norio , Liou Ruey‐Fen , Kikuchi Taisei , Tsai Isheng J. 
Published: September 2017

AbstractThe order Hymenochaetales of white rot fungi contain some of the most aggressive wood decayers causing tree deaths around the world. Despite their ecological importance and the impact of diseases they cause, little is known about the evolution and transmission patterns of these pathogens. Here, we sequenced and undertook comparative genomic analyses of Hymenochaetales genomes using brown root rot fungus Phellinus noxius, wood‐decomposing fungus Phellinus lamaensis, laminated root rot fungus Phellinus sulphurascens and trunk pathogen Porodaedalea pini. Many gene families of lignin‐degrading enzymes were identified from these fungi, reflecting their ability as white rot fungi. Comparing against distant fungi highlighted the expansion of 1,3‐beta‐glucan synthases in P. noxius, which may account for its fast‐growing attribute. We identified 13 linkage groups conserved within Agaricomycetes, suggesting the evolution of stable karyotypes. We determined that P. noxius has a bipolar heterothallic mating system, with unusual highly expanded ~60 kb A locus as a result of accumulating gene transposition. We investigated the population genomics of 60 P. noxius isolates across multiple islands of the Asia Pacific region. Whole‐genome sequencing showed this multinucleate species contains abundant poly‐allelic single nucleotide polymorphisms with atypical allele frequencies. Different patterns of intra‐isolate polymorphism reflect mono‐/heterokaryotic states which are both prevalent in nature. We have shown two genetically separated lineages with one spanning across many islands despite the geographical barriers. Both populations possess extraordinary genetic diversity and show contrasting evolutionary scenarios. These results provide a framework to further investigate the genetic basis underlying the fitness and virulence of white rot fungi.
iDNA screening: Disease vectors as vertebrate samplers
Authors: Kocher Arthur , de Thoisy Benoit , Catzeflis François , Valière Sophie , Bañuls Anne‐Laure , Murienne Jérôme 
Published: September 2017

AbstractIn the current context of global change and human‐induced biodiversity decline, there is an urgent need for developing sampling approaches able to accurately describe the state of biodiversity. Traditional surveys of vertebrate fauna involve time‐consuming and skill‐demanding field methods. Recently, the use of DNA derived from invertebrate parasites (leeches and blowflies) was suggested as a new tool for vertebrate diversity assessment. Bloodmeal analyses of arthropod disease vectors have long been performed to describe their feeding behaviour, for epidemiological purposes. On the other hand, this existing expertise has not yet been applied to investigate vertebrate fauna per se. Here, we evaluate the usefulness of hematophagous dipterans as vertebrate samplers. Blood‐fed sand flies and mosquitoes were collected in Amazonian forest sites and analysed using high‐throughput sequencing of short mitochondrial markers. Bloodmeal identifications highlighted contrasting ecological features and feeding behaviour among dipteran species, which allowed unveiling arboreal and terrestrial mammals of various body size, as well as birds, lizards and amphibians. Additionally, lower vertebrate diversity was found in sites undergoing higher levels of human‐induced perturbation. These results suggest that, in addition to providing precious information on disease vector host use, dipteran bloodmeal analyses may represent a useful tool in the study of vertebrate communities. Although further effort is required to validate the approach and consider its application to large‐scale studies, this first work opens up promising perspectives for biodiversity monitoring and eco‐epidemiology.
Seasonal rather than spatial variability drives planktonic and benthic bacterial diversity in a microtidal lagoon and the adjacent open sea
Authors: Quero Grazia Marina , Perini Laura , Pesole Graziano , Manzari Caterina , Lionetti Claudia , Bastianini Mauro , Marini Mauro , Luna Gian Marco 
Published: September 2017

AbstractCoastal lagoons are highly productive ecosystems, which are experiencing a variety of human disturbances at increasing frequency. Bacteria are key ecological players within lagoons, yet little is known about the magnitude, patterns and drivers of diversity in these transitional environments. We carried out a seasonal study in the Venice Lagoon (Italy) and the adjacent sea, to simultaneously explore diversity patterns in different domains (pelagic, benthic) and their spatio‐temporal variability, and test the role of environmental gradients in structuring assemblages. Community composition differed between lagoon and open sea, and between domains. The dominant phyla varied temporally, with varying trends for the two domains, suggesting different environmental constraints on the assemblages. The percentage of freshwater taxa within the lagoon increased during higher river run‐off, pointing at the lagoon as a dynamic mosaic of microbial taxa that generate the metacommunity across the whole hydrological continuum. Seasonality was more important than spatial variability in shaping assemblages. Network analyses indicated more interactions between several genera and environmental variables in the open sea than the lagoon. Our study provides evidences for a temporally dynamic nature of bacterial assemblages in lagoons and suggests that an interplay of seasonally influenced environmental drivers shape assemblages in these vulnerable ecosystems.
Barriers to and enablers of healthy lifestyle behaviours in adolescents with obesity: a scoping review and stakeholder consultation
Authors: Kebbe M. , Damanhoury S. , Browne N. , Dyson M. P. , McHugh T.‐L. F. , Ball G. D. C. 
Published: September 2017

SummaryHealthy lifestyle behaviours are key to successful weight management, but have proven to be challenging to attain for adolescents with obesity. The purpose of our scoping review was to (i) describe barriers and enablers that adolescents with obesity encounter for healthy nutrition, physical activity, sedentary behaviour and sleep habits and (ii) identify gaps in the literature. We adhered to established methodology for scoping reviews. Six databases were searched (1980–June 2016) for original articles published in English or French that focused on lifestyle behaviours of 13‐ to 17‐year‐olds in paediatric weight management. Following screening and data extraction, findings of selected articles were synthesized thematically using a social ecological framework. Stakeholder consultation (n = 20) with adolescents with obesity and health professionals was completed to enhance methodological rigour. Our search yielded 17 articles for inclusion, including 546 unique participants. Barriers to healthy nutrition and physical activity were more consistently related to individual‐level and interpersonal‐level factors; enablers tended to be linked with interpersonal‐level factors. Knowledge gaps identified related to sedentary behaviour and sleep as well as environmental and policy levels of influence. Our review revealed that some barriers and enablers were unique to adolescents with obesity, which were either within or beyond their control. These findings highlight the importance of multilevel interventions to enable healthy lifestyle behaviours for weight management.
The Moral Depth of Human Dignity
Authors: Coghlan Simon 
Published: September 2017

AbstractIn 1971, Herbert Spiegelberg challenged philosophers to refine and deepen the vivid idea of human dignity to prevent its degeneration. Although philosophers, including Michael Rosen and Jeremy Waldron, have responded with valuable insights, the full moral depth of dignity has remained philosophically elusive. Furthermore, many philosophers still think human dignity a limited ethical concept. By integrating important alienable and inalienable dimensions of human dignity, this essay attempts to do justice to our vivid contemporary experience of dignity's moral depth. It seeks to illuminate the profound, universal worth of all humans, and the ethical force of human rights protections.
ACA Exchange Competitiveness In Michigan
Authors: Foster Friedman Megan , Fangmeier Joshua , Baum Nancy , Udow‐Phillips Marianne 
Published: September 2017

AbstractThe expansion of Medicaid and the creation of the Health Insurance Marketplace has provided greater access to health insurance coverage for many Michigan residents. To date, Michigan's Health Insurance Marketplace has seen relative success, in part due to the presence of multiple regional insurance carriers and the state's embrace of managed care in its Medicaid program in the 1990s. This report examines the conditions in Michigan's exchange market and analyzes its experience to date with carrier participation, pricing, and provider networks.
ACA Exchange Competitiveness In California
Authors: Weinberg Micah , Kallerman Patrick 
Published: September 2017

AbstractCalifornia's implementation of the Affordable Care Act (ACA) has been the most successful in the nation and is, in many ways, a model of how a managed competition marketplace is expected to work. In particular, the state's decision to structure its marketplace as an active purchaser has contributed to premium increases that are lower than in almost all other states. This report on the performance of the ACA marketplace in California examines the effects of concentration and consolidation factors, the breadth of enrollment, and the impact of competition on the cost of health insurance and the options available to consumers across the many diverse regions of the state, in the context of an active purchaser exchange structure interacting with the regulations of federal law and with local market dynamics. It concludes that the relative concentrations of insurers and particularly of providers in the different rating regions of the state are the fundamentals that matter most in the effort to bend the health insurance cost curve.
Controlled Human Malaria Infection: Applications, Advances, and Challenges
Authors: Stanisic Danielle I. , McCarthy James S. , Good Michael F. 
Published: September 2017

ABSTRACT

Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or parasitized erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of antimalarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development, where it is used to evaluate products in well-controlled early-phase proof-of-concept clinical studies, thus facilitating progression of only the most promising candidates for further evaluation in areas where malaria is endemic. Controlled infections have also been used to immunize against malaria infection. Historically, CHMI studies have been restricted by the need for access to insectaries housing infected mosquitoes or suitable malaria-infected individuals. Evaluation of vaccine and drug candidates has been constrained in these studies by the availability of a limited number of
Plasmodium falciparum
isolates. Recent advances have included cryopreservation of sporozoites, the manufacture of well-characterized and genetically distinct cultured malaria cell banks for blood-stage infection, and the availability of
Plasmodium vivax
-specific reagents. These advances will help to accelerate malaria vaccine and drug development by making the reagents for CHMI more widely accessible and also enabling a more rigorous evaluation with multiple parasite strains and species. Here we discuss the different applications of CHMI, recent advances in the use of CHMI, and ongoing challenges for consideration.
Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease
Authors: Flaherty Kevin R , Brown Kevin K , Wells Athol U , Clerisme-Beaty Emmanuelle , Collard Harold R , Cottin Vincent , Devaraj Anand , Inoue Yoshikazu , Le Maulf Florence , Richeldi Luca , Schmidt Hendrik , Walsh Simon , Mezzanotte William , Schlenker-Herceg Rozsa 
Published: September 2017

600 patients aged ≥18 years will be randomised in a 1:1 ratio to nintedanib or placebo. Patients with diagnosis of IPF will be excluded. The study population will be enriched with two-thirds having a usual interstitial pneumonia-like pattern on HRCT. The primary endpoint is the annual rate of decline in forced vital capacity over 52 weeks. The main secondary endpoints are the absolute change from baseline in King’s Brief Interstitial Lung Disease Questionnaire total score, time to first acute interstitial lung disease exacerbation or death and time to all-cause mortality over 52 weeks.Ethics and disseminationThe trial is conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Tripartite Guideline for Good Clinical Practice (GCP) and Japanese GCP regulations.Trial registration numberNCT02999178.
Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab
Authors: Burmester Gerd R , Kaeley Gurjit S , Kavanaugh Arthur F , Gabay Cem , MacCarter Daryl K , Nash Peter , Takeuchi Tsutomu , Goss Sandra L , Rodila Ramona , Chen Kun , Kupper Hartmut , Kalabic Jasmina 
Published: September 2017

BackgroundTreatment of rheumatoid arthritis (RA) with a combination of methotrexate (MTX)+adalimumab (ADA) is more effective than ADA monotherapy. We assessed the toxicity of different doses of MTX and treatment efficacy of ADA+MTX in two trials.MethodsData originated from CONCERTO, in patients with early RA initiating ADA+ 2.5, 5, 10 or 20 mg/week MTX for 26 weeks; and MUSICA, in patients with an inadequate response to MTX initiating ADA+ 7.5 or 20 mg/week MTX for 24 weeks. Efficacy was assessed by the American College of Rheumatology 50 (ACR50). Patient-reported MTX-related toxicity information was collected at each visit on 18 prespecified MTX-related adverse events (AE) in the MTX label.ResultsIn CONCERTO, ACR50 rates increased over time, ranging from 54% to 68% at week 26, while AE rates remained steady, ranging from 2.4% to 17.8% at week 26. Of 395 patients, 113 (28.6%) reported 345 MTX-related AEs, including one serious AE (SAE, excessive fatigue and/or malaise); 10 AEs (in two patients) led to study discontinuation. In MUSICA, ACR50 rates increased over time, and were 32.3% and 37.5% at week 24, while MTX-related AE rates remained steady and were 6.5% at week 24. Of 309 patients, 71 (23%) reported 185 MTX-related AEs, including 5 SAEs (four infections and one fever/chills); six AEs (in four patients) led to study discontinuation.ConclusionIn patients with RA initiating ADA+MTX combination, treatment efficacy was achieved and increased throughout both trials, while rates of MTX-related AEs remained steady. MTX-related AEs were observed in up to 30% of patients and most were mild. MTX was discontinued by 0.5%–1.3% of patients.Trial registration numberMUSICA (NCT01185288), CONCERTO (NCT01185301), Post results.
Adaptation to TKI Treatment Reactivates ERK Signaling in Tyrosine Kinase–Driven Leukemias and Other Malignancies
Authors: Bruner J. Kyle , Ma Hayley S. , Li Li , Qin Alice Can Ran , Rudek Michelle A. , Jones Richard J. , Levis Mark J. , Pratz Keith W. , Pratilas Christine A. , Small Donald 
Published: September 2017

Abstract
FMS-like tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia (AML). We hypothesized that FLT3/internal tandem duplication (ITD) leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here, we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared with either drug alone. ERK reactivation was also observed following inhibition of other tyrosine kinase–driven cancer cells, including EGFR-mutant lung cancer, HER2-amplified breast cancer, and BCR–ABL leukemia. These studies reveal an adaptive feedback mechanism in tyrosine kinase–driven cancers associated with reactivation of ERK signaling in response to targeted inhibition. Cancer Res; 77(20); 5554–63. ©2017 AACR.
MCT1 Inhibitor AZD3965 Increases Mitochondrial Metabolism, Facilitating Combination Therapy and Noninvasive Magnetic Resonance Spectroscopy
Authors: Beloueche-Babari Mounia , Wantuch Slawomir , Casals Galobart Teresa , Koniordou Markella , Parkes Harold G. , Arunan Vaitha , Chung Yuen-Li , Eykyn Thomas R. , Smith Paul D. , Leach Martin O. 
Published: September 2017

Abstract
Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux. AZD3965 also increased the levels of TCA cycle–related metabolites and 13C-glucose mitochondrial metabolism, enhancing oxidative pyruvate dehydrogenase and anaplerotic pyruvate carboxylase fluxes. Increased mitochondrial metabolism was necessary to maintain cell survival under drug stress. These effects were counteracted by coadministration of the mitochondrial complex I inhibitor metformin and the mitochondrial pyruvate carrier inhibitor UK5099. Improved bioenergetics were confirmed in vivo after dosing with AZD3965 in mouse xenograft models of human lymphoma. Our results reveal new metabolic consequences of MCT1 inhibition that might be exploited for therapeutic and pharmacodynamic purposes. Cancer Res; 77(21); 5913–24. ©2017 AACR.
TET-Mediated Sequestration of miR-26 Drives EZH2 Expression and Gastric Carcinogenesis
Authors: Deng Min , Zhang Ruixin , He Zhengxi , Qiu Qinwei , Lu Xihong , Yin Jiang , Liu Hao , Jia Xiaoting , He Zhimin 
Published: September 2017

Abstract
DNA demethylases of the TET family function as tumor suppressors in various human cancers, but their pathogenic contributions and mechanisms of action in gastric carcinogenesis and progression remain unclear. Here, we report that TET is transcriptionally upregulated in gastric cancer, where it correlates with poor prognosis. Mechanistic investigations revealed that TET facilitated gastric carcinogenesis through a noncoding function of the 3′UTR, which interacted with miR-26. This interaction resulted in sequestration of miR-26 from its target EZH2, which released the suppression on EZH2, and thereby led to EZH2 overexpression in gastric cancer. Our findings uncover a novel noncoding function for TET family proteins in facilitating gastric carcinogenesis. Cancer Res; 77(22); 6069–82. ©2017 AACR.
Upregulation of Cystathionine-β-Synthase in Colonic Epithelia Reprograms Metabolism and Promotes Carcinogenesis
Authors: Phillips Ches'Nique M. , Zatarain John R. , Nicholls Michael E. , Porter Craig , Widen Steve G. , Thanki Ketan , Johnson Paul , Jawad Muhammad U. , Moyer Mary P. , Randall James W. , Hellmich Judith L. , Maskey Manjit , Qiu Suimin , Wood Thomas G. , Druzhyna Nadiya , Szczesny Bartosz , Módis Katalin , Szabo Csaba , Chao Celia , Hellmich Mark R. 
Published: September 2017

Abstract
The trans-sulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells. Differentially expressed metabolites (65 increased and 20 decreased) clustered into the glycolytic pathway, nucleotide sugars, intermediates of the pentose phosphate pathway, and lipogenesis, including primarily phospholipids, sphingolipids, and bile acids. CBS upregulation induced broad changes in the NCM356 cell transcriptome with over 350 differentially expressed genes. These genes overlapped significantly with gene sets related to glycolysis, hypoxia, and a colon cancer cell phenotype, including genes regulated by NF-κB, KRAS, p53, and Wnt signaling, genes downregulated after E-cadherin knockdown, and genes related to increased extracellular matrix, cell adhesion, and epithelial-to-mesenchymal transition. The CBS-induced switch to an anabolic metabolism was associated with increased NCM356 cell bioenergetics, proliferation, invasion through Matrigel, resistance to anoikis, and CBS-dependent tumorigenesis in immunocompromised mice. Genetic ablation of CBS in CBS heterozygous mice (CBS+/−) reduced the number of mutagen-induced aberrant colonic crypt foci. Taken together, these results establish that activation of the CBS/H2S axis promotes colon carcinogenesis. Cancer Res; 77(21); 5741–54. ©2017 AACR.
How Ribosomes Translate Cancer
Authors: Sulima Sergey O. , Hofman Isabel J.F. , De Keersmaecker Kim , Dinman Jonathan D. 
Published: September 2017

AbstractA wealth of novel findings, including congenital ribosomal mutations in ribosomopathies and somatic ribosomal mutations in various cancers, have significantly increased our understanding of the relevance of ribosomes in oncogenesis. Here, we explore the growing list of mechanisms by which the ribosome is involved in carcinogenesis—from the hijacking of ribosomes by oncogenic factors and dysregulated translational control, to the effects of mutations in ribosomal components on cellular metabolism. Of clinical importance, the recent success of RNA polymerase inhibitors highlights the dependence on “onco-ribosomes” as an Achilles' heel of cancer cells and a promising target for further therapeutic intervention.Significance: The recent discovery of somatic mutations in ribosomal proteins in several cancers has strengthened the link between ribosome defects and cancer progression, while also raising the question of which cellular mechanisms such defects exploit. Here, we discuss the emerging molecular mechanisms by which ribosomes support oncogenesis, and how this understanding is driving the design of novel therapeutic strategies. Cancer Discov; 7(10); 1069–87. ©2017 AACR.