bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progression
Authors: Borghesan Michela , Fusilli Caterina , Rappa Francesca , Panebianco Concetta , Rizzo Giovanni , Oben Jude A. , Mazzoccoli Gianluigi , Faulkes Chris , Pata Illar , Agodi Antonella , Rezaee Farhad , Minogue Shane , Warren Alessandra , Peterson Abigail , Sedivy John M. , Douet Julien , Buschbeck Marcus , Cappello Francesco , Mazza Tommaso , Pazienza Valerio , Vinciguerra Manlio 
Published: January 2016

AbstractAging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, and were robust immunohistochemical markers of human cirrhosis and HCC. In response to the chemotherapeutic and DNA-demethylating agent 5-aza-deoxycytidine (5-aza-dC), transgenic expression of macroH2A1 isoforms in HCC cell lines prevented the emergence of a senescent-like phenotype and induced synergistic global DNA hypomethylation. Conversely, macroH2A1 depletion amplified the antiproliferative effects of 5-aza-dC in HCC cells, but failed to enhance senescence. Senescence-associated secretory phenotype and whole-transcriptome analyses implicated the p38 MAPK/IL8 pathway in mediating macroH2A1-dependent escape of HCC cells from chemotherapy-induced senescence. Furthermore, chromatin immunoprecipitation sequencing revealed that this hepatic antisenescence state also required active transcription that could not be attributed to genomic occupancy of these histones. Collectively, our findings reveal a new mechanism by which drug-induced senescence is epigenetically regulated by macroH2A1 and DNA methylation and suggest macroH2A1 as a novel biomarker of hepatic senescence that could potentially predict prognosis and disease progression. Cancer Res; 76(3); 594–606. ©2016 AACR.
A Breakthrough: Macrophage-Directed Cancer Immunotherapy
Authors: Mills Charles D. , Lenz Laurel L. , Harris Robert A. 
Published: January 2016

AbstractSuccessful immunotherapy of cancer is becoming a reality aided by the realization that macrophages play an important role in the growth or regression of tumors. Specifically, M2/repair-type macrophages predominate in human cancers and produce growth-promoting molecules that actively stimulate tumor growth in much the same way they help wounds heal. However, modulating M2/repair-type macrophages to M1/kill-type can slow or stop cancer growth. The effects involve direct activity of M1 kill-type as well as the ability of M1-type macrophages to stimulate Th1-type cytotoxic T cells and other effector cells. Macrophage responses can also predict cancer susceptibility; individuals with a high M1/kill to M2/repair ratio are less prone. That macrophages/innate immunity can be modulated to play a central role in directly or indirectly combating cancer is a breakthrough that seems likely to finally make successful immunotherapy of cancer a reality. Cancer Res; 76(3); 513–6. ©2016 AACR.
RON Nuclear Translocation under Hypoxia Potentiates Chemoresistance to DNA Double-Strand Break–Inducing Anticancer Drugs
Authors: Chang Hong-Yi , Chang Ting-Chia , Huang Wen-Ya , Lee Chung-Ta , Yen Chia-Jui , Tsai Yuh-Shyan , Tzai Tzong-Shin , Chen Shu-Hui , Chow Nan-Haw 
Published: January 2016

Abstract
Tumor hypoxia is associated with radioresistance, chemoresistance, and metastasis, which eventually lead to cancer progression and a poor patient prognosis. RON [also known as macrophage-stimulating protein receptor (MST1R)] belongs to the c-MET [also known as hepatocyte growth factor receptor (HGFR)] receptor tyrosine kinase (RTK) superfamily. To identify the interaction partners of RON nuclear translocation in response to hypoxia, the nuclear extract of TSGH8301 bladder cancer cells was immunoprecipitated for tandem mass profiling analysis. Nuclear RON interacted with adenosine triphosphate (ATP)-dependent DNA helicase 2 (Ku70) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to activate nonhomologous end joining (NHEJ) DNA repair. The interaction was time dependent, extending 3 to 24 hours posthypoxia or until the components had been exposed to the chemotherapeutic drugs doxorubicin and epirubicin. Stable knockdown experiments in vitro suggest the importance of RON for the chemoresistance of cancer cells under hypoxia. In addition, the tyrosine kinase domain of nuclear RON is crucial for interaction with Ku70 under hypoxia. J82 cells transfected with RON showed a survival advantage in the presence of epirubicin and hypoxia. This suggests that nuclear RON activates NHEJ repair by interacting with Ku70/DNA-PKcs and inhibiting RON activity to increase cancer cell chemosensitivity. Mol Cancer Ther; 15(2); 276–86. ©2016 AACR.
Inhibition of Class I Histone Deacetylases 1 and 2 Promotes Urothelial Carcinoma Cell Death by Various Mechanisms
Authors: Pinkerneil Maria , Hoffmann Michèle J. , Deenen René , Köhrer Karl , Arent Tanja , Schulz Wolfgang A. , Niegisch Günter 
Published: January 2016

AbstractClass I histone deacetylases HDAC1 and HDAC2 contribute to cell proliferation and are commonly upregulated in urothelial carcinoma. To evaluate whether specific inhibition of these enzymes might serve as an appropriate therapy for urothelial carcinoma, siRNA-mediated knockdown and specific pharmacologic inhibition of HDAC1 and HDAC2 were applied in urothelial carcinoma cell lines (UCC) with distinct HDAC1 and HDAC2 expression profiles. HDACs and response marker proteins were followed by Western blotting and qRT-PCR. Effects of class I HDAC suppression on UCCs were analyzed by viability, colony forming, and caspase-3/7 assays; flow cytometry, senescence and lactate dehydrogenase cytotoxicity assays; and immunofluorescence staining. Whereas single knockdowns of HDAC1 or HDAC2 were impeded by compensatory upregulation of the other isoenzyme, efficient double knockdown of HDAC1 and HDAC2 reduced proliferation by up to 80% and induced apoptosis-like cell death in all UCCs. Clonogenic growth was cell line– and HDAC-dependently reduced, with double knockdown of HDAC1 and HDAC2 being usually most efficient. Class I HDAC-specific inhibitors, especially the more specific HDAC1/2 inhibitors romidepsin and givinostat, significantly reduced proliferation of all UCCs (IC50, 3.36 nmol/L–4.59 μmol/L). Romidepsin and givinostat also significantly inhibited clonogenic growth of UCCs, with minor effects on nontumorigenic controls. Intriguingly, these compounds induced primarily S-phase disturbances and nonapoptotic cell death in UCCs. Thus, although both ways of inhibiting HDAC1/2 share mechanisms and efficaciously inhibit cell proliferation, their modes of action differ substantially. Regardless, combined inhibition of HDAC1/2 appears to represent a promising strategy for urothelial carcinoma therapy. Mol Cancer Ther; 15(2); 299–312. ©2016 AACR.
Hydrolutos piaroa sp.n. (Orthoptera: Anostostomatidae), a new semiaquatic Lutosini species from south-western Venezuelan lowland streams
Authors: DERKA Tomáš , SVITOK MAREK , FEDOR PETER 
Published: January 2016

Hydrolutos piaroa, a new species of Lutosini (Orthoptera: Anostostomatidae) from Tobogán de la Selva (Puerto Ayacucho region, SW Venezuela) is described and figured. Inhabiting aquatic environment it represents an unusual orthopteran with sternal and pleural area covered by fine microtrichia, forming a plastron. This is the first known Hydrolutos species sampled in lowland streams of Venezuelan Guayana.
Adherence to a depression self-care intervention among primary care patients with chronic physical conditions: A randomised controlled trial
Authors: McCusker Jane , Cole Martin G. , Yaffe Mark , Strumpf Erin , Sewitch Maida , Sussman Tamara , Ciampi Antonio , Lavoie Kim , Belzile Eric 
Published: January 2016

Objective: Among primary care patients with chronic physical conditions and comorbid depressive symptoms, to assess (1) the effect of lay telephone coaching on adherence to a psycho-educational intervention for depression, (2) demographic characteristics that predict adherence and (3) the association between adherence and 6-month outcomes. Design: Single blind randomised pragmatic trial of a lay telephone-supported depression self-care intervention compared to an unsupported intervention. Methods: All patients received a multimedia toolkit of paper and audiovisual materials on depression that provided education on depression and on self-care for depression. Core tools included a cognitive-behavioural therapy (CBT)-based workbook and a mood monitoring notebook, with opportunities for written exercises and notes, and a video. Intervention group patients were additionally offered telephone coaching. Self-reported use of the materials was assessed at 3 and 6 months post-randomisation; 6-month outcomes were patient satisfaction and change from baseline in depression severity. Results: In all, 223 patients were randomised; 165 (74.0%) completed follow-up. Coached versus uncoached patients reported significantly greater use of the workbook, but not of other tools. Men used more audiovisual tools; women used more paper tools. Self-reported completion of written exercises and a greater number of coach contacts were associated with greater satisfaction, but not with improvement in depression. Conclusion: Telephone coaching can increase adherence to CBT-based tools for depression self-care; however, use of these tools may not improve depression outcomes. Many patients are capable of self-directed use of self-care educational materials. Sex differences in patterns of tool use may be helpful in the targeting of tools.
Time Sharing Between Robotics and Process Control
Authors: Wickens Christopher Dow , Gutzwiller Robert S. , Vieane Alex , Clegg Benjamin A. , Sebok Angelia , Janes Jess 
Published: January 2016

Objective: The aim of this study was to validate the strategic task overload management (STOM) model that predicts task switching when concurrence is impossible. Background: The STOM model predicts that in overload, tasks will be switched to, to the extent that they are attractive on task attributes of high priority, interest, and salience and low difficulty. But more-difficult tasks are less likely to be switched away from once they are being performed. Method: In Experiment 1, participants performed four tasks of the Multi-Attribute Task Battery and provided task-switching data to inform the role of difficulty and priority. In Experiment 2, participants concurrently performed an environmental control task and a robotic arm simulation. Workload was varied by automation of arm movement and both the phases of environmental control and existence of decision support for fault management. Attention to the two tasks was measured using a head tracker. Results: Experiment 1 revealed the lack of influence of task priority and confirmed the differing roles of task difficulty. In Experiment 2, the percentage attention allocation across the eight conditions was predicted by the STOM model when participants rated the four attributes. Model predictions were compared against empirical data and accounted for over 95% of variance in task allocation. More-difficult tasks were performed longer than easier tasks. Task priority does not influence allocation. Conclusions: The multiattribute decision model provided a good fit to the data. Applications: The STOM model is useful for predicting cognitive tunneling given that human-in-the-loop simulation is time-consuming and expensive.
Mega-project meltdown: Post-politics, neoliberal urban regeneration and Valencia’s fiscal crisis
Authors: Tarazona Vento Amparo 
Published: January 2016

Drawing on the literature of post-politics and post-democracy, the literature of neoliberalism as mode of governance and the study of the city of Valencia’s long-standing emphasis on the development of prestige mega-projects of iconic architecture as a means to achieve economic regeneration and urban revitalisation, this paper evaluates the social and economic effects of urban mega-projects and analyses them as conduits of neoliberal globalisation and de-politicisation of the public sphere. On the one hand, an urban policy based on the use of mega-projects represents a turn from welfarism to entrepreneurialism which, beyond the evident urban transformation and re-imaging, results in an increase in social inequality, the creation of precarious jobs, and an underinvestment in social services. On the other hand, the mechanisms used to implement mega-projects – including both exceptionality measures and privatisation of management through the creation of semi-public delivery bodies – result in a lack of transparency and democratic control, which in turn lead to more authoritative and privatised forms of decision-making. Moreover, mega-projects – through their focus on expertise and technocracy and a populist politics and discourse constructed around them – play a crucial role in the erosion of democracy and the establishment of a consensual politics where ideological struggle does not exist.
Risk of Secondary Injury in Younger Athletes After Anterior Cruciate Ligament Reconstruction
Authors: Wiggins Amelia J. , Grandhi Ravi K. , Schneider Daniel K. , Stanfield Denver , Webster Kate E. , Myer Gregory D. 
Published: January 2016

Background: Injury to the ipsilateral graft used for reconstruction of the anterior cruciate ligament (ACL) or a new injury to the contralateral ACL are disastrous outcomes after successful ACL reconstruction (ACLR), rehabilitation, and return to activity. Studies reporting ACL reinjury rates in younger active populations are emerging in the literature, but these data have not yet been comprehensively synthesized. Purpose: To provide a current review of the literature to evaluate age and activity level as the primary risk factors in reinjury after ACLR. Study Design: Systematic review and meta-analysis. Methods: A systematic review of the literature was conducted via searches in PubMed (1966 to July 2015) and EBSCO host (CINAHL, Medline, SPORTDiscus [1987 to July 2015]). After the search and consultation with experts and rating of study quality, 19 articles met inclusion for review and aggregation. Population demographic data and total reinjury (ipsilateral and contralateral) rate data were recorded from each individual study and combined using random-effects meta-analyses. Separate meta-analyses were conducted for the total population data as well as the following subsets: young age, return to sport, and young age + return to sport. Results: Overall, the total second ACL reinjury rate was 15%, with an ipsilateral reinjury rate of 7% and contralateral injury rate of 8%. The secondary ACL injury rate (ipsilateral + contralateral) for patients younger than 25 years was 21%. The secondary ACL injury rate for athletes who return to a sport was also 20%. Combining these risk factors, athletes younger than 25 years who return to sport have a secondary ACL injury rate of 23%. Conclusion: This systematic review and meta-analysis demonstrates that younger age and a return to high level of activity are salient factors associated with secondary ACL injury. These combined data indicate that nearly 1 in 4 young athletic patients who sustain an ACL injury and return to high-risk sport will go on to sustain another ACL injury at some point in their career, and they will likely sustain it early in the return-to-play period. The high rate of secondary injury in young athletes who return to sport after ACLR equates to a 30 to 40 times greater risk of an ACL injury compared with uninjured adolescents. These data indicate that activity modification, improved rehabilitation and return-to-play guidelines, and the use of integrative neuromuscular training may help athletes more safely reintegrate into sport and reduce second injury in this at-risk population.
The mental health benefits of employment: Results of a systematic meta-review
Authors: Modini Matthew , Joyce Sadhbh , Mykletun Arnstein , Christensen Helen , Bryant Richard A , Mitchell Philip B , Harvey Samuel B 
Published: January 2016

Objective: The literature on mental health in the workplace largely focuses on the negative impacts of work and how work may contribute to the development of mental disorders. The potential mental health benefits of employment have received less attention. Method: A systematic search of reviews or meta-analyses that consider the benefits of work in regards to mental health was undertaken using academic databases. All relevant reviews were subjected to a quality appraisal. Results: Eleven reviews were identified as meeting the inclusion criteria, with four deemed to be of at least moderate quality. The available evidence supports the proposition that work can be beneficial for an employee’s well-being, particularly if good-quality supervision is present and there are favourable workplace conditions. The benefits of work are most apparent when compared with the well-documented detrimental mental health effects of unemployment. Conclusions: The potential positive effects of good work and the role work can play in facilitating recovery from an illness and enhancing mental well-being need to be highlighted and promoted more widely. Future research should aim to further investigate what constitutes a ‘good’ workplace or a ‘good’ job in terms of mental health outcomes.
Fatigue Alters Landing Shock Attenuation During a Single-Leg Vertical Drop Jump
Authors: Tamura Akihiro , Akasaka Kiyokazu , Otsudo Takahiro , Sawada Yutaka , Okubo Yu , Shiozawa Jyunya , Toda Yuka , Yamada Kaori 
Published: January 2016

Background: Landings in fatigue conditions are considered to be one of the factors that cause noncontact anterior cruciate ligament (ACL) injury. Additionally, it is known that fatigue alters lower extremity landing strategies and decreases the ability to attenuate shock during landing. Purpose: To determine characteristics of knee kinematics and shock attenuation during the landing phase of a single-leg vertical drop jump in a fatigued condition. The hypothesis was that knee kinematics during the landing phase of a single-leg vertical drop jump would demonstrate a significant difference between before and after fatigue. Study Design: Controlled laboratory study. Methods: Thirty-four college females participated in this experiment. They were randomly assigned to either the fatigue (n = 17) or control group (n = 17). The fatigue group performed the single-leg vertical drop jump before and after the fatigue protocol, which was performed on a bike ergometer. Knee kinematics data were obtained from the 3-dimensional motion analysis system. The ratio of each variable (%) was calculated, comparing the pre- to postfatigue protocol. Unpaired t tests were used to compare changes in kinematic variables between the fatigue-induced group and control group. Results: Peak knee flexion angular velocity increased significantly in the fatigue group (106.1% ± 8.0%) in comparison with the control group (100.7% ± 6.6%) ( P < .05). However, peak knee flexion angle and acceleration had no differences between each group. Peak knee adduction/abduction angle, velocity, and acceleration also had no differences between each group. Conclusion: Fatigue decreased the ability to attenuate shock by increasing angular velocity in the direction of knee flexion during single-leg drop jump landing. These findings indicate the need to evaluate the ability to attenuate shock by measuring knee flexion angular velocity when fatigue is considered. Clinical Relevance: Measuring knee angular velocity during landings might be an important evaluation parameter in the consideration of the knee injury prevention.
Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1
Authors: Gu Shengqing , Chan Wayne W. , Mohi Golam , Rosenbaum Joel , Sayad Azin , Lu Zhibin , Virtanen Carl , Li Shaoguang , Neel Benjamin G. , Van Etten Richard A. 
Published: January 2016

Key Points
Scaffolding adaptor protein GAB2 is required for BCR-ABL1–evoked myeloid and lymphoid leukemogenesis. SHP2 and p85 binding to GAB2 activate distinct signaling pathways and are required differentially for myeloid and lymphoid leukemogenesis.
Polycomb-dependent epigenetic landscape in adult T-cell leukemia
Authors: Fujikawa Dai , Nakagawa Shota , Hori Makoto , Kurokawa Naoya , Soejima Ai , Nakano Kazumi , Yamochi Tadanori , Nakashima Makoto , Kobayashi Seiichiro , Tanaka Yuetsu , Iwanaga Masako , Utsunomiya Atae , Uchimaru Kaoru , Yamagishi Makoto , Watanabe Toshiki 
Published: January 2016

Key PointsATL involves genome-wide reprogramming of the H3K27me3 pattern that is distinct from other cell types. Druggable epigenetic mechanisms are associated with ATL cell development and HTLV-1–mediated transformation.
Deletion of Pten in CD45-expressing cells leads to development of T-cell lymphoblastic lymphoma but not myeloid malignancies
Authors: Mirantes Cristina , Dosil Maria Alba , Hills David , Yang Jian , Eritja Núria , Santacana Maria , Gatius Sònia , Vilardell Felip , Medvinsky Alexander , Matias-Guiu Xavier , Dolcet Xavier 
Published: January 2016

Key Points
CD45-driven expression of Cre generates the first mouse model that allows specific and exclusive deletion of Pten in hematopoietic cells. Pten deletion in CD45-expressing cells causes T-cell acute lymphoblastic leukemia, but no other hematologic malignancies.
Diffuse large B-cell lymphoma patient-derived xenograft models capture the molecular and biological heterogeneity of the disease
Authors: Chapuy Bjoern , Cheng Hongwei , Watahiki Akira , Ducar Matthew D. , Tan Yuxiang , Chen Linfeng , Roemer Margaretha G. M. , Ouyang Jing , Christie Amanda L. , Zhang Liye , Gusenleitner Daniel , Abo Ryan P. , Farinha Pedro , von Bonin Frederike , Thorner Aaron R. , Sun Heather H. , Gascoyne Randy D. , Pinkus Geraldine S. , van Hummelen Paul , Wulf Gerald G. , Aster Jon C. , Weinstock David M. , Monti Stefano , Rodig Scott J. , Wang Yuzhuo , Shipp Margaret A. 
Published: January 2016

Key Points
Our generated PDX models reflect the immunophenotypic, transcriptional, genetic, and functional heterogeneity of primary DLBCL. The experimental and analytical approach will inform the development of additional PDX models and facilitate preclinical drug discovery.