bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells
Authors: Casimiro Mathew C. , Di Sante Gabriele , Ju Xiaoming , Li Zhiping , Chen Ke , Crosariol Marco , Yaman Ismail , Gormley Michael , Meng Hui , Lisanti Michael P. , Pestell Richard G. 
Published: November 2015

AbstractTherapy resistance and poor outcome in prostate cancer is associated with increased expression of cyclin D1. Androgens promote DNA double-strand break repair to reduce DNA damage, and cyclin D1 was also shown to enhance DNA damage repair (DDR). In this study, we investigated the significance of cyclin D1 in androgen-induced DDR using established prostate cancer cells and prostate tissues from cyclin D1 knockout mice. We demonstrate that endogenous cyclin D1 further diminished the dihydrotestosterone (DHT)-dependent reduction of γH2AX foci in vitro. We also show that cyclin D1 was required for the androgen-dependent DNA damage response both in vitro and in vivo. Furthermore, cyclin D1 was required for androgen-enhanced DDR and radioresistance of prostate cancer cells. Moreover, microarray analysis of primary prostate epithelial cells from cyclin D1-deficient and wild-type mice demonstrated that most of the DHT-dependent gene expression changes are also cyclin D1 dependent. Collectively, our findings suggest that the hormone-mediated recruitment of cyclin D1 to sites of DDR may facilitate the resistance of prostate cancer cells to DNA damage therapies and highlight the need to explore other therapeutic approaches in prostate cancer to prevent or overcome drug resistance. Cancer Res; 76(2); 329–38. ©2015 AACR.
An Open-Label, Randomized Phase II Trial of Personalized Peptide Vaccination in Patients with Bladder Cancer that Progressed after Platinum-Based Chemotherapy
Authors: Noguchi Masanori , Matsumoto Kazumasa , Uemura Hirotsugu , Arai Gaku , Eto Masatoshi , Naito Seiji , Ohyama Chikara , Nasu Yasutomo , Tanaka Masatoshi , Moriya Fukuko , Suekane Shigetaka , Matsueda Satoko , Komatsu Nobukazu , Sasada Tetsuro , Yamada Akira , Kakuma Tatsuyuki , Itoh Kyogo 
Published: November 2015

AbstractPurpose: The prognosis of platinum-based chemotherapy–resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity.Experimental Design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity.Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4–1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34–0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5–12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8–6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions.Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results. Clin Cancer Res; 22(1); 54–60. ©2015 AACR.
A First-in-Human Phase I Study of the Oral p38 MAPK Inhibitor, Ralimetinib (LY2228820 Dimesylate), in Patients with Advanced Cancer
Authors: Patnaik Amita , Haluska Paul , Tolcher Anthony W. , Erlichman Charles , Papadopoulos Kyriakos P. , Lensing Janet L. , Beeram Muralidhar , Molina Julian R. , Rasco Drew W. , Arcos Rebecca R. , Kelly Claudia S. , Wijayawardana Sameera R. , Zhang Xuekui , Stancato Louis F. , Bell Robert , Shi Peipei , Kulanthaivel Palaniappan , Pitou Celine , Mulle Lynette B. , Farrington Daphne L. , Chan Edward M. , Goetz Matthew P. 
Published: November 2015

Abstract
Purpose: p38 MAPK regulates the production of cytokines in the tumor microenvironment and enables cancer cells to survive despite oncogenic stress, radiotherapy, chemotherapy, and targeted therapies. Ralimetinib (LY2228820 dimesylate) is a selective small-molecule inhibitor of p38 MAPK. This phase I study aimed to evaluate the safety and tolerability of ralimetinib, as a single agent and in combination with tamoxifen, when administered orally to patients with advanced cancer.
Experimental Design: The study design consisted of a dose-escalation phase performed in a 3+3 design (Part A; n = 54), two dose-confirmation phases [Part B at 420 mg (n = 18) and Part C at 300 mg (n = 8)], and a tumor-specific expansion phase in combination with tamoxifen for women with hormone receptor–positive metastatic breast cancer refractory to aromatase inhibitors (Part D; n = 9). Ralimetinib was administered orally every 12 hours on days 1 to 14 of a 28-day cycle.
Results: Eighty-nine patients received ralimetinib at 11 dose levels (10, 20, 40, 65, 90, 120, 160, 200, 300, 420, and 560 mg). Plasma exposure of ralimetinib (Cmax and AUC) increased in a dose-dependent manner. After a single dose, ralimetinib inhibited p38 MAPK–induced phosphorylation of MAPKAP-K2 in peripheral blood mononuclear cells. The most common adverse events, possibly drug-related, included rash, fatigue, nausea, constipation, pruritus, and vomiting. The recommended phase II dose was 300 mg every 12 hours as monotherapy or in combination with tamoxifen. Although no patients achieved a complete response or partial response,19 patients (21.3%) achieved stable disease with a median duration of 3.7 months, with 9 of these patients on study for ≥6 cycles.
Conclusions: Ralimetinib demonstrated acceptable safety, tolerability, and pharmacokinetics for patients with advanced cancer. Clin Cancer Res; 22(5); 1095–102. ©2015 AACR.
Identification of an “Exceptional Responder” Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted Therapy
Authors: Gannon Hugh S. , Kaplan Nathan , Tsherniak Aviad , Vazquez Francisca , Weir Barbara A. , Hahn William C. , Meyerson Matthew 
Published: November 2015

Abstract
The identification of somatic genetic alterations that confer sensitivity to pharmacologic inhibitors has led to new cancer therapies. To identify mutations that confer an exceptional dependency, shRNA-based loss-of-function data were analyzed from a dataset of numerous cell lines to reveal genes that are essential in a small subset of cancer cell lines. Once these cell lines were determined, detailed genomic characterization from these cell lines was utilized to ascertain the genomic aberrations that led to this extreme dependency. This method, in a large subset of lung cancer cell lines, yielded a single lung adenocarcinoma cell line, NCI-H1437, which is sensitive to RNA interference of MAP2K1 expression. Notably, NCI-H1437 is the only lung cancer cell line included in the dataset with a known activating mutation in MAP2K1 (Q56P). Subsequent validation using shRNA and CRISPR-Cas9 confirmed MAP2K1 dependency. In vitro and in vivo inhibitor studies established that NCI-H1437 cells are sensitive to MEK1 inhibitors, including the FDA-approved drug trametinib. Like NCI-H1437 cells, the MAP2K1-mutant cell lines SNU-C1 (colon) and OCUM-1 (gastric) showed decreased viability after MAP2K1 depletion via Cas9-mediated gene editing. Similarly, these cell lines were particularly sensitive to trametinib treatment compared with control cell lines. On the basis of these data, cancers that harbor driver mutations in MAP2K1 could benefit from treatment with MEK1 inhibitors. Furthermore, this functional data mining approach provides a general method to experimentally test genomic features that confer dependence in tumors.
Implications: Cancers with an activated RAS/MAPK pathway driven by oncogenic MAP2K1 mutations may be particularly sensitive to MEK1 inhibitor treatments. Mol Cancer Res; 14(2); 207–15. ©2015 AACR.
The prevalence and predictors of self-stigma of individuals with mental health illness in two Chinese cities
Authors: Young Daniel Kim-Wan , Ng Petrus Yat-Nam 
Published: November 2015

Background: Although self-stigma is found to have adverse effects on the lives of persons with mental illness, little is known on the self-stigma of these individuals in Chinese societies. Objective: This research study explores the prevalence rate and predicting factors of self-stigma of consumers in two Chinese cities, Hong Kong and Guangzhou. Methods: A cross-sectional research design is adopted which involves a random sample of 266 consumers from Hong Kong and a convenient sample of 208 consumers from Guangzhou. These individuals have been assessed in terms of their self-stigma, recovery, self-esteem and quality of life by using standardized assessment scales. Results: In all, 38.3% of the Hong Kong participants and 49.5% of the Guangzhou participants report to have self-stigma. Also, self-stigma is found to be negatively related to self-esteem and quality of life. A logistic regression analysis shows that hope and well-being are predicting factors of self-stigma. Conclusion: Self-stigma is found to be higher in Guangzhou, probably due to the influence of traditional cultural values. Also, as hope and well-being are found to be predicting factors of self-stigma, suitable recovery-orientated interventions that facilitate hope and well-being should be developed so as to reduce self-stigma of consumers in Chinese societies.
Current challenges in diagnostic imaging of venous thromboembolism
Authors: Huisman Menno V. , Klok Frederikus A. 
Published: November 2015

Abstract
Because the clinical diagnosis of deep-vein thrombosis and pulmonary embolism is nonspecific, integrated diagnostic approaches for patients with suspected venous thromboembolism have been developed over the years, involving both non-invasive bedside tools (clinical decision rules and D-dimer blood tests) for patients with low pretest probability and diagnostic techniques (compression ultrasound for deep-vein thrombosis and computed tomography pulmonary angiography for pulmonary embolism) for those with a high pretest probability. This combination has led to standardized diagnostic algorithms with proven safety for excluding venous thrombotic disease. At the same time, it has become apparent that, as a result of the natural history of venous thrombosis, there are special patient populations in which the current standard diagnostic algorithms are not sufficient. In this review, we present 3 evidence-based patient cases to underline recent developments in the imaging diagnosis of venous thromboembolism.
Complement in hemolytic anemia
Authors: Brodsky Robert A. 
Published: November 2015

Abstract
Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.
Large scale patterns of genetic variation and differentiation in sugar maple from tropical Central America to temperate North America
Authors: Vargas-Rodriguez Yalma L. , Platt William J. , Urbatsch Lowell E. , Foltz David W. 
Published: November 2015

AbstractBackgroundGeological events in the latter Cenozoic have influenced the distribution, abundance and genetic structure of tree populations in temperate and tropical North America. The biogeographical history of temperate vegetation that spans large ranges of latitude is complex, involving multiple latitudinal shifts that might have occurred via different migration routes. We determined the regional structuring of genetic variation of sugar maple (Acer saccharumsubsp.saccharum) and its only subspecies in tropical America (Acer saccharumsubsp.skutchii) using nuclear and chloroplast data. The studied populations span a geographic range from Maine, USA (46°N), to El Progreso, Guatemala (15°N). We examined genetic subdivisions, explored the locations of ancestral haplotypes, analyzed genetic data to explore the presence of a single or multiple glacial refugia, and tested whether genetic lineages are temporally consistent with a Pleistocene or older divergence.ResultsNuclear and chloroplast data indicated that populations in midwestern USA and western Mexico were highly differentiated from populations in the rest of the sites. The time of the most recent common ancestor of the western Mexico haplotype lineage was dated to the Pliocene (5.9 Ma, 95 % HPD: 4.3–7.3 Ma). Splits during the Pleistocene separated the rest of the phylogroups. The most frequent and widespread haplotype occurred in half of the sites (Guatemala, eastern Mexico, southeastern USA, and Ohio). Our data also suggested that multiple Pleistocene refugia (tropics-southeastern USA, midwestern, and northeastern USA), but not western Mexico (Jalisco), contributed to post-glacial northward expansion of ranges. Current southern Mexican and Guatemalan populations have reduced population sizes, genetic bottlenecks and tend toward homozygosity, as indicated using nuclear and chloroplast markers.ConclusionsThe divergence of western Mexican populations from the rest of the sugar maples likely resulted from orographic and volcanic barriers to gene flow. Past connectivity among populations in the southeastern USA and eastern Mexico and Guatemala possible occurred through gene flow during the Pleistocene. The time to the most common ancestor values revealed that populations from the Midwest and Northeast USA represented different haplotype lineages, indicating major divergence of haplotypes lineages before the Last Glacial Maximum and suggesting the existence of multiple glacial refugia.
Strong convergence theorem for totally quasi-ϕ-asymptotically nonexpansive multi-valued mappings under relaxed conditions
Authors: Qian Shanguang 
Published: November 2015

AbstractWe construct a relaxed hybrid shrinking iteration algorithm for approximating common fixed points of a countable family of totally quasi-ϕ-asymptotically nonexpansive multi-valued mappings. A strong convergence theorem for solving generalized mixed equilibrium problems is established in the framework of Banach spaces under relaxed conditions. Since there is no need to impose a uniformity assumption on the involved mappings and no need to compute complex series in the iteration process, the results improve those of the authors with related interests.
Genome sequence and description of the anaerobic lignin-degrading bacterium Tolumonas lignolytica sp. nov.
Authors: Billings Andrew F. , Fortney Julian L. , Hazen Terry C. , Simmons Blake , Davenport Karen W. , Goodwin Lynne , Ivanova Natalia , Kyrpides Nikos C. , Mavromatis Konstantinos , Woyke Tanja , DeAngelis Kristen M. 
Published: November 2015

AbstractTolumonas lignolytica BRL6-1T sp. nov. is the type strain of T. lignolytica sp. nov., a proposed novel species of the Tolumonas genus. This strain was isolated from tropical rainforest soils based on its ability to utilize lignin as a sole carbon source. Cells of Tolumonas lignolytica BRL6-1T are mesophilic, non-spore forming, Gram-negative rods that are oxidase and catalase negative. The genome for this isolate was sequenced and returned in seven unique contigs totaling 3.6Mbp, enabling the characterization of several putative pathways for lignin breakdown. Particularly, we found an extracellular peroxidase involved in lignin depolymerization, as well as several enzymes involved in β-aryl ether bond cleavage, which is the most abundant linkage between lignin monomers. We also found genes for enzymes involved in ferulic acid metabolism, which is a common product of lignin breakdown. By characterizing pathways and enzymes employed in the bacterial breakdown of lignin in anaerobic environments, this work should assist in the efficient engineering of biofuel production from lignocellulosic material.
The expression of the T-box selector genemidlinein the leg imaginal disc is controlled by both transcriptional regulation and cell lineage
Authors: Svendsen Pia C. , Ryu Jae-Ryeon , Brook William J. 
Published: November 2015

ABSTRACTThe Drosophila Tbx20 homologs midline and H15 act as selector genes for ventral fate in Drosophila legs. midline and H15 expression defines the ventral domain of the leg and the two genes are necessary and sufficient for the development of ventral fate. Ventral-specific expression of midline and H15 is activated by Wingless (Wg) and repressed by Decapentaplegic (Dpp). Here we identify VLE, a 5 kb enhancer that drives ventral specific expression in the leg disc that is very similar to midline expression. Subdivision of VLE identifies two regions that mediate both activation and repression and third region that only mediates repression. Loss- and gain-of-function genetic mosaic analysis shows that the activating and repressing regions respond to Wg and Dpp signaling respectively. All three repression regions depend on the activity of Mothers-against-decapentaplegic, a Drosophila r-Smad that mediates Dpp signaling, and respond to ectopic expression of the Dpp target genes optomoter-blind and Dorsocross 3. However, only one repression region is responsive to loss of schnurri, a co-repressor required for direct repression by Dpp-signaling. Thus, Dpp signaling restricts midline expression through both direct repression and through the activation of downstream repressors. We also find that midline and H15 expression are both subject to cross-repression and feedback inhibition. Finally, a lineage analysis indicates that ventral midline-expressing cells and dorsal omb-expressing cells do not mix during development. Together this data indicates that the ventral-specific expression of midline results from both transcriptional regulation and from a lack of cell-mixing between dorsal and ventral cells.
Factors associated with non-adherence to oral IBD medication: a systematic review of the literature 1980–2013
Authors: Peel Adam , Thorpe Gabrielle , Deane Katherine Helen O'Leary 
Published: November 2015

Background Non-adherence to oral medication for inflammatory bowel disease (IBD) has been estimated to be 30–45%. Factors found to be associated with non-adherence, while frequently reported, are often conflicting. Methods Databases Embase, Medline, CINAHL and PsycINFO were used to identify studies between 2008 and 2013. Results were summarised through vote count, with reference to study quality and participant number. Results Seventeen records met the inclusion criteria and were analysed alongside another 15 identified by a previous literature review ( Jackson et al, 2010 ). Factors related to adherence were grouped into four themes: demographic, psychosocial, clinical and medication. Only the factors of attitudes towards and beliefs about treatment, barriers to taking medication, and membership of a patient support group were found to be consistently associated with adherence Conclusions Many factors reported to be associated with adherence to oral IBD medication are not supported with any consistency. Further research is needed in areas shown to be consistently associated with adherence.
Misogynoir and antiblack racism: What The Walking Dead teaches us about the limits of Speculative Fiction fandom
Authors: Johnson Dominique Deirdre 
Published: November 2015

Abstract
Antiblack racial antagonisms manifest in discourse through audience engagement with characters in Speculative Fiction (SF). This article addresses the ways that a fictional black woman in a popular SF series gets constructed in the public imaginaries of a popular fandom community. The character Michonne from the dystopian comic book series and television drama, The Walking Dead, provides an excellent occasion to examine audience engagement that distinctly operates within a recognizable cultural frame. The character’s reception between has sparked much debate and criticism due to the ways that she is understood and dramatized in relation to other characters in the series. While a majority of fan content regarding the character recognizes her skill and abilities for survival with relative positivity, she is routinely regarded as an outsider, perpetually unfeeling or emotionally inept. The result is a broad lack of empathy mitigated by antiblack misogyny. It is as though her character is regarded as a functional object (a weapon) and less than human, which bears the weight of the question of black non-ontology as a requirement for social order. This is particularly interesting within an imagined world of the undead. This article interrogates the ways in which fandom communities actively cite, circulate and produce discourses that sustain structural antagonisms, as well as how they contribute to, respond, or engage particularly problematic tropes regarding black female subjectivities.