bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electronic cigarette use in restaurants and workplaces where combustible tobacco smoking is not allowed: an Internet survey in Japan
Authors: Kiyohara Kosuke , Tabuchi Takahiro 
Published: June 2017

BackgroundThe present study aimed to examine the experience of actual electronic cigarette (e-cigarette) use in smoke-free areas of restaurants and workplaces and to explore the determinants associated with such use among Japanese adults who reported any experience using e-cigarettes (e-cigarette ever-users).MethodsAn Internet-based self-reported questionnaire survey was conducted in 2015 on Japanese e-cigarette ever-users. The proportion of the respondents who had ever used or frequently used e-cigarettes in smoke-free restaurants and/or workplaces was calculated. Potential factors associated with e-cigarette use in those smoke-free areas were also examined by using multivariable logistic regression analyses.ResultsIn total, 1243 e-cigarette ever-users (662 current and 581 former e-cigarette users) were analysed. The majority of them (1020/1243, 82.1%) were male and their mean age ± SD was 47.0±10.4 years. The proportion of those who had ever used e-cigarettes in smoke-free restaurants was 28.8% (358/1243) and that in smoke-free workplaces was 25.5% (317/1243), respectively. The proportion of those who had frequently used e-cigarettes in smoke-free restaurants was 18.5% (230/1243) and that in smoke-free workplaces was 16.3% (202/1243), respectively. In general, the proportion of e-cigarette use in those smoke-free areas was higher among those having a higher educational level than those having a lower educational level.ConclusionAmong adult Japanese e-cigarette ever-users, approximately 26%–29% had ever used and 16%–19% had frequently used e-cigarettes in restaurants and/or workplaces where combustible tobacco smoking is not allowed. Policy-makers may need to establish explicit rules as to e-cigarette use in smoke-free environments.
Generalized Rogers–Ramanujan identities for twisted affine algebras
Authors: Genish Arel , Gepner Doron 
Published: June 2017

The characters of parafermionic conformal field theories are given by the string functions of affine algebras, which are either twisted or untwisted algebras. Expressions for these characters as generalized Rogers–Ramanujan algebras have been established for the untwisted affine algebras. However, we study the identities for the string functions of the twisted affine Lie algebras. A conjecture for the string functions was proposed by Hatayama et al., for the unit fields, which expresses the string functions as Rogers–Ramanujan type sums. Here we propose to check the Hatayama et al. conjecture, using Lie algebraic theoretic methods. We use Freudenthal’s formula, which we computerized, to verify the identities for all the algebras at low rank and low level. We find complete agreement with the conjecture.
Obstacles, Opportunities and Priorities for Advancing Metastatic Breast Cancer Research
Authors: Flowers Margaret , Birkey Reffey Stephanie , Mertz Shirley A. , Hurlbert Marc 
Published: June 2017

Abstract
In January 2016, the Metastatic Breast Cancer Alliance (the Alliance) convened a think tank of stakeholders from academia, government, industry, and patient advocacy to discuss gaps and opportunities in clinical and translational research in metastatic breast cancer. Priorities that emerged from the meeting included the following: the need for innovative preclinical model systems to study metastatic disease; increased sharing of resources and data; collaboration across cancer care teams and scientists; biorepositories for studies to identify biomarkers for treatment response; creation of patient registries to increase access to clinical trials and tissue procurement; and redesign of clinical trials in metastatic breast cancer. Cancer Res; 77(13); 3386–90. ©2017 AACR.
Germline Genetic Variants and Lung Cancer Survival in African Americans
Authors: Jones Carissa C. , Bush William S. , Crawford Dana C. , Wenzlaff Angela S. , Schwartz Ann G. , Wiencke John K. , Wrensch Margaret R. , Blot William J. , Chanock Stephen J. , Grogan Eric L. , Aldrich Melinda C. 
Published: June 2017

Abstract
Background: African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases.
Methods: Incident non–small cell lung cancer cases (N = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies (N = 316 and 298) were used for replication.
Results: One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54–0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71–0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33–0.66).
Conclusions: We identified an association between rs1878022 in CMKLR1 and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene–environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival.
Impact: We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. Cancer Epidemiol Biomarkers Prev; 26(8); 1288–95. ©2017 AACR.
Inhibition of Hsp90 Suppresses PI3K/AKT/mTOR Signaling and Has Antitumor Activity in Burkitt Lymphoma
Authors: Giulino-Roth Lisa , van Besien Herman J. , Dalton Tanner , Totonchy Jennifer E. , Rodina Anna , Taldone Tony , Bolaender Alexander , Erdjument-Bromage Hediye , Sadek Jouliana , Chadburn Amy , Barth Matthew J. , Dela Cruz Filemon S. , Rainey Allison , Kung Andrew L. , Chiosis Gabriela , Cesarman Ethel 
Published: June 2017

Abstract
Hsp90 is a molecular chaperone that protects proteins, including oncogenic signaling complexes, from proteolytic degradation. PU-H71 is a next-generation Hsp90 inhibitor that preferentially targets the functionally distinct pool of Hsp90 present in tumor cells. Tumors that are driven by the MYC oncoprotein may be particularly sensitive to PU-H71 due to the essential role of Hsp90 in the epichaperome, which maintains the malignant phenotype in the setting of MYC. Burkitt lymphoma (BL) is an aggressive B-cell lymphoma characterized by MYC dysregulation. In this study, we evaluated Hsp90 as a potential therapeutic target in BL. We found that primary BL tumors overexpress Hsp90 and that Hsp90 inhibition has antitumor activity in vitro and in vivo, including potent activity in a patient-derived xenograft model of BL. To evaluate the targets of PU-H71 in BL, we performed high-affinity capture followed by proteomic analysis using mass spectrometry. We found that Hsp90 inhibition targets multiple components of PI3K/AKT/mTOR signaling, highlighting the importance of this pathway in BL. Finally, we found that the anti-lymphoma activity of PU-H71 is synergistic with dual PI3K/mTOR inhibition in vitro and in vivo. Overall, this work provides support for Hsp90 as a therapeutic target in BL and suggests the potential for combination therapy with PU-H71 and inhibitors of PI3K/mTOR. Mol Cancer Ther; 16(9); 1779–90. ©2017 AACR.
CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest
Authors: Francis Ashleigh M. , Alexander Angela , Liu Yanna , Vijayaraghavan Smruthi , Low Kwang Hui , Yang Dong , Bui Tuyen , Somaiah Neeta , Ravi Vinod , Keyomarsi Khandan , Hunt Kelly K. 
Published: June 2017

Abstract
Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (&gt;5 cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow. Here we describe the development of a synergistic combination treatment strategy that may be applicable in both soft tissue sarcomas as well as sarcomas of bone that takes advantage of targeting the cell cycle. We show that Rb-positive cell lines treated with the CDK4/6 inhibitor palbociclib reversibly arrest in the G1 phase of the cell cycle, and upon drug removal cells progress through the cell cycle as expected within 6–24 hours. Using a long-term high-throughput assay that allows us to examine drugs in different sequences or concurrently, we found that palbociclib-induced cell-cycle arrest poises Rb-positive sarcoma cells (SK-LMS1 and HT-1080) to be more sensitive to agents that work preferentially in S–G2 phase such as doxorubicin and Wee1 kinase inhibitors (AZD1775). The synergy between palbociclib and AZD1775 was also validated in vivo using SK-LMS1 xenografts as well as Rb-positive patient-derived xenografts (PDX) developed from leiomyosarcoma patients. This work provides the necessary preclinical data in support of a clinical trial utilizing this treatment strategy. Mol Cancer Ther; 16(9); 1751–64. ©2017 AACR.
Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma
Authors: Grommes Christian , Pastore Alessandro , Palaskas Nicolaos , Tang Sarah S. , Campos Carl , Schartz Derrek , Codega Paolo , Nichol Donna , Clark Owen , Hsieh Wan-Ying , Rohle Dan , Rosenblum Marc , Viale Agnes , Tabar Viviane S. , Brennan Cameron W. , Gavrilovic Igor T. , Kaley Thomas J. , Nolan Craig P. , Omuro Antonio , Pentsova Elena , Thomas Alissa A. , Tsyvkin Elina , Noy Ariela , Palomba M. Lia , Hamlin Paul , Sauter Craig S. , Moskowitz Craig H. , Wolfe Julia , Dogan Ahmet , Won Minhee , Glass Jon , Peak Scott , Lallana Enrico C. , Hatzoglou Vaios , Reiner Anne S. , Gutin Philip H. , Huse Jason T. , Panageas Katherine S. , Graeber Thomas G. , Schultz Nikolaus , DeAngelis Lisa M. , Mellinghoff Ingo K. 
Published: June 2017

Abstract
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor–associated protein CD79B. CD79B-mutant PCNSLs showed enrichment of mammalian target of rapamycin (mTOR)-related gene sets and increased staining with PI3K/mTOR activation markers. Inhibition of the PI3K isoforms p110α/p110δ or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells.
Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS. Response rates in PCNSL were considerably higher than reported for diffuse large B-cell lymphoma outside the CNS, suggesting a divergent molecular pathogenesis. Combined inhibition of BTK and PI3K/mTOR may augment the ibrutinib response in CD79B-mutant human PCNSLs. Cancer Discov; 7(9); 1018–29. ©2017 AACR.
See related commentary by Lakshmanan and Byrd, p. 940.
This article is highlighted in the In This Issue feature, p. 920
A Four-Factor Immunoscore System That Predicts Clinical Outcome for Stage II/III Gastric Cancer
Authors: Wen Ti , Wang Zhenning , Li Yi , Li Zhi , Che Xiaofang , Fan Yibo , Wang Shuo , Qu Jinglei , Yang Xianghong , Hou Kezuo , Zhou Wenyang , Xu Ling , Li Ce , Wang Jin , Liu Jing , Chen Liqun , Zhang Jingdong , Qu Xiujuan , Liu Yunpeng 
Published: June 2017

Abstract
The American Joint Committee on Cancer (AJCC) staging system is insufficiently prognostic for operable gastric cancer patients; therefore, complementary factors are under intense investigation. Although the focus is on immune markers, the prognostic impact of a single immune factor is minimal, due to complex antitumor immune responses. A more comprehensive evaluation may engender more accurate predictions. We analyzed immune factors by immunohistochemical staining in two independent cohorts. The association with patients' survival was analyzed by the Kaplan–Meier method. Our immunoscore system was constructed using Cox proportional hazard analysis. PD-L1+ immune cells (IC), PD-L1+ tumor cells (TC), PD-1hi, and CD8More were found among 33.33%, 31.37%, 33.33%, and 49%, respectively, of patients from the discovery cohort, and 41.74%, 17.4%, 38.26%, and 30.43% from the validation cohort. PD-L1+ ICs and PD-1hi ICs correlated with poorer overall survival (OS), but PD-L1+ TCs correlated with better OS and clinical outcomes and infiltration of more CD8+ T cells. These four factors were independently prognostic after tumor/lymph nodes/metastasis (TNM) stage adjustment. An immunoscore system based on hazard ratios of the four factors further separated gastric cancer patients with similar TNM staging into low-, medium-, or high-risk groups, with significantly different survival. Our prognostic model yielded an area under the receiver operating characteristic curve (AUC) of 0.856 for prediction of mortality at 5 years, superior to that of TNM staging (AUC of 0.676). Thus, this more comprehensive immunoscore system can provide more accurate prognoses and is an essential complement to the AJCC staging system for operable gastric cancer patients. Cancer Immunol Res; 5(7); 524–34. ©2017 AACR.
Impact of Relative Conditional Survival Estimates on Patient Prognosis After Percutaneous Coronary Intervention
Authors: Baart Sara J. , van Domburg Ron T. , Janssen-Heijnen Maryska L.G. , Deckers Jaap W. , Akkerhuis K. Martijn , Daemen Joost , van Geuns Robert-Jan , Boersma Eric , Kardys Isabella 
Published: June 2017

Background—
Some aspects of prognosis are not reflected by cumulative survival estimates. These aspects include information on the time already survived by the patient and the patient’s survival compared with the general population. Conditional survival (ie, conditional on having survived a certain period of time already) and relative conditional survival (ie, compared with the general population) do incorporate these aspects. We investigated these measures of prognosis in patients undergoing percutaneous coronary intervention.

Methods and Results—
We studied 17 903 consecutive patients undergoing percutaneous coronary intervention between 2000 and 2014. Cumulative survival was estimated for patients with ST-segment–elevation myocardial infarction (n=5996, 853 deaths), non–ST-segment–elevation myocardial infarction (n=5371, 901 deaths), and stable angina pectoris (n=6536, 965 deaths) in 4 age categories. One-year conditional and relative conditional survival up to 10 years post–percutaneous coronary intervention was calculated. The results demonstrated that 1-year cumulative survival for patients with ST-segment–elevation myocardial infarction aged ≥76 years was 83%. One-year conditional survival, conditional on surviving the first month, was 92% in this group, and relative conditional survival (relative to the general population) was 99%. In younger age categories and in patients with non–ST-segment–elevation myocardial infarction and stable angina pectoris , similar patterns were found albeit less pronounced. Five-year relative conditional rendered similar results.

Conclusions—
Relative conditional survival provides a comprehensive picture of patient prognosis, particularly for older patients with ST-segment–elevation myocardial infarction. Although, as expected, their cumulative survival is low, once they survive the first month after percutaneous coronary intervention, their prognosis is comparable to that of the general population. Therefore, relative conditional survival estimates provide an important, meaningful addition when discussing prognosis with patients.
Victims at the Prospective International Criminal Law Section of the African Court of Justice and Human and Peoples’ Rights
Authors: Perez-Leon-Acevedo Juan-Pablo 
Published: June 2017

The introduction of an International Criminal Law Section (icls) to the prospective African Union (au) African Court of Justice and Human and Peoples’ Rights (acjhr) has sparked academic debate. However, discussion of victims’ status at the acjhr-icls has been neglected. Victims’ status as participants and reparation claimants, as provided for in the acjhr Statute, is critically analysed. There are important gaps and limitations, especially concerning the victim participant status, and implementation challenges, particularly regarding the reparation claimant status. Recommendations to address normative problems and face future challenges are provided. The amended acjhr-icls Statute is comparatively tested against inter alia the legal framework and practice of the International Criminal Court (icc). The icc Statute is relevant because the acjhr Statute provisions on victims largely borrow from it. Additionally, despite some deficits, the icc Statute and practice arguably constitute guiding standards to tackle complex victim-related issues at international/hybrid criminal tribunals (ihcts).
A Postprocessing Method for Seasonal Forecasts Using Temporally and Spatially Smoothed Statistics
Authors: Kharin V. V. , Merryfield W. J. , Boer G. J. , Lee W.-S. 
Published: June 2017

AbstractA statistical postprocessing method for seasonal forecasts based on temporally and spatially smoothed climate statistics is introduced. The method uses information available from seasonal hindcasts initialized at the beginning of 12 calendar months. The performance of the method is tested within both deterministic and probabilistic frameworks using output from the ensemble of seasonal hindcasts produced by the Canadian Seasonal to Interannual Prediction System for the 30-yr period 1981–2010. Forecast skill improvements are found to be greater when forecast adjustment parameters estimated for individual seasons and at individual grid points are temporally and spatially smoothed. The greatest skill improvements are typically achieved for seasonally invariant parameters while skill improvements due to additional spatial smoothing are modest.
Modelling water trap seal boundary conditions in building drainage systems: Computational fluid dynamics analysis of unsteady friction to improve accuracy
Authors: Jean NJ , Gormley M 
Published: June 2017

The safe removal of disease-carrying human waste is the objective of all sanitation systems and the limiting of air pressure transients within the system remains a significant part of current codes and regulations. The water trap seal offers fundamental protection and is the system’s sole barrier between the public sewer network and habitable space inside a building. Modelling water trap seal responses to air pressure fluctuations offers an opportunity to analyse whole system performance, but the quality of the data depends on the accuracy of the modelling technique and that of the defining inputs. AIRNET, a 1D Method of Characteristics based model, enables rapid whole system testing; however, the present boundary condition for the water trap seal within the model is based solely on steady state conditions, ignoring system dynamics. Computational fluid dynamics offers an opportunity to numerically evaluate the flow patterns within the trap seal in response to applied air pressure transients. This research confirms the importance of the rate of rise, and hence frequency of air pressure transients incident on water trap seals and relates this to potential vulnerabilities of different device geometries, particularly the ratio between inner and outer wall length. The research led to the development of a dynamic velocity decrement model encapsulating unsteady friction and separation losses linked to device geometry for the first time. The development of a frequency-dependent internal energy term Δ v, suitable for inclusion in AIRNET provides the capability to predict more realistic water trap response to air pressure transients over a range of air pressure transient frequencies likely to cause problems: 1 Hz to 8 Hz.Practical application: Whole system modelling can greatly improve the ability of design engineers to fully simulate the operation of a building drainage system in a realistic way. The work described in this paper improves the accuracy of whole system models by evaluating water dynamic responses to air pressure transients using a range of techniques including computational fluid dynamics and more traditional 1D finite difference method of characteristics models. The work also paves the way for more robust evaluation of building drainage products through in-depth investigation of the fluid mechanics associated with their operation.
Perioperative single-site veno-venous extracorporeal CO2 removal for minimally invasive giant bulla resection
Authors: Redwan Bassam , Biancosino Christian , Giebel Felix , Woebker Gabriele , Eberlein Michael , Bölükbas Servet 
Published: June 2017

Giant pulmonary bullae are rare and surgical management of patients with severe emphysema and advanced chronic obstructive lung disease (COPD) presenting with giant bullae can be very challenging. Previously, perioperative, two-site, high-flow, veno-venous extracorporeal membrane oxygenation (ECMO) was successfully utilized during giant bulla resection. Here we report the perioperative application of single-site, low-flow extracorporeal CO2 removal (ECCO2R) for minimally invasive thoracoscopic giant bulla resection. This approach of low-flow, veno-venous ECCO2R, which is less invasive than conventional ECLS approaches, has enabled the safe performance of surgery and facilitated protective intraoperative single-lung ventilation while avoiding possible complications of aggressive mechanical ventilation.