bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participant acceptability of exercise in kidney disease (PACE-KD): a feasibility study protocol in renal transplant recipients
Authors: Bishop Nicolette C , Billany Roseanne , Smith Alice C 
Published: September 2017

IntroductionCardiovascular disease (CVD) is a major cause of mortality in renal transplant recipients (RTRs). General population risk scores for CVD underestimate the risk in patients with chronic kidney disease (CKD) suggesting additional non-traditional factors. Renal transplant recipients also exhibit elevated inflammation and impaired immune function. Exercise has a positive impact on these factors in patients with CKD but there is a lack of rigorous research in RTRs, particularly surrounding the feasibility and acceptability of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) in this population. This study aims to explore the feasibility of three different supervised aerobic exercise programmes in RTRs to guide the design of future large-scale efficacy studies.Methods and analysisRenal transplant recipients will be randomised to HIIT A (16 min interval training with 4, 2 and 1 min intervals at 80%–90% of peak oxygen uptake (VO2 peak)), HIIT B (4×4 min interval training at 80%–90% VO2peak) or MICT (~40 min cycling at 50%–60% VO2peak) where they will undertake 24 supervised sessions (approximately thrice weekly over 8 weeks). Assessment visits will be at baseline, midtraining, immediate post-training and 3 months post-training. The study will evaluate the feasibility of recruitment, randomisation, retention, assessment procedures and the implementation of the interventions. A further qualitative sub-study QPACE-KD (Qualitative Participant Acceptability of Exercise in Kidney Disease) will explore patient experiences and perspectives through semistructured interviews and focus groups.Ethics and disseminationAll required ethical and regulatory approvals have been obtained. Findings will be disseminated through conference presentations, public platforms and academic publications.Trial registration numberProspectively registered;ISRCTN17122775.
Maternal ambient air pollution, preterm birth and markers of fetal growth in Rhode Island: results of a hospital-based linkage study
Authors: Kingsley Samantha L , Eliot Melissa N , Glazer Kimberly , Awad Yara Abu , Schwartz Joel D , Savitz David A , Kelsey Karl T , Marsit Carmen J , Wellenius Gregory A 
Published: September 2017

BackgroundMaternal exposure to ambient air pollution has been associated with higher risk of preterm birth and reduced fetal growth, but heterogeneity among prior studies suggests that additional studies are needed in diverse populations and settings. We examined the associations between maternal ambient air pollution levels, risk of preterm birth and markers of fetal growth in an urban population with relatively low exposure to air pollution.MethodsWe linked 61 640 mother–infant pairs who delivered at a single hospital in Providence, Rhode Island, from 2002 to 2012 to birth certificate and hospital discharge data. We used spatial-temporal models and stationary monitors to estimate exposure to fine particulate matter (PM2.5) and black carbon (BC) during pregnancy. Using generalised linear models, we evaluated the association between pollutant levels, risk of preterm birth and markers of fetal growth.ResultsIn adjusted models, an IQR (2.5 µg/m3) increase in pregnancy-average PM2.5was associated with ORs of preterm birth of 1.04 (95% CI 0.94 to 1.15) and 0.86 (0.76 to 0.98) when considering modelled and monitored PM2.5, respectively. An IQR increase in modelled and monitored PM2.5was associated with a 12.1 g (95% CI −24.2 to –0.1) and 15.9 g (95% CI −31.6 to –0.3) lower birth weight. Results for BC were highly sensitive to choice of exposure metric.ConclusionIn a population with relatively low exposures to ambient air pollutants, PM2.5was associated with reduced birth weight but not with risk of preterm birth.
Geochronology, geochemistry and isotope systematics of a mafic–intermediate dyke complex in the İstanbul Zone. New constraints on the evolution of the Black Sea in NW Turkey
Authors: Aysal Namık , Keskin Mehmet , Peytcheva Irena , Duru Olgun 
Published: September 2017

Abstract

We report new U–Pb zircon ages, major and trace element data, mineral chemistry, and Sr–Nd isotopic analyses of the mafic–intermediate dykes and intrusions in the İstanbul Zone. Mafic dykes are represented by calc-alkaline to alkaline lamprophyre and diabase. Intermediate dykes and subvolcanics are andesitic to dacitic in composition and calc-alkaline in character, while intrusive rocks (stocks and small plutons) are granodioritic and dioritic in composition. New zircon U–Pb laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) dating yielded ages from 72.49 ± 0.79 (Upper Cretaceous–Campanian) to 65.44 ± 0.93 Ma (Lower Paleocene–Danian) for the intermediate dykes, and 58.9 ± 1.8 Ma (Upper Paleocene–Thanetian) for a small granodiorite stock.
87
Sr/
86
Sr
(i)
values of the mafic and intermediate dykes and small stocks span a range from 0.703508 to 0.706311, while their
143
Nd/
144
Nd
(i)
values vary from 0.512614 to 0.512812 and eNd
(i)
values from 5.09 to 1.24. Nd
TDM
model ages range between 0.46 and 0.77 Ga.

Dykes are enriched in large ion lithophile elements (LILEs) and light rare earth elements (LREEs) relative to high field strength elements (HFSEs). Normal-type mid-ocean ridge basalt (N-MORB)-normalized multi-element spidergrams of the majority of the mafic and intermediate dykes display a clear subduction signature, except a subset, which cut the Palaeozoic of İstanbul and the upper part of the Upper Cretaceous volcanics in the north of İstanbul (i.e. feeder dykes of the Kısırkaya Formation) and show a clear ocean island basalt (OIB) signature indicating that the melts feeding the dyke system during the Upper Cretaceous–Paleocene period were derived from two contrasting mantle sources: (1) initially a lithospheric mantle modified by subducted slab-derived melts which sourced the magmas with a clear subduction signature; and (2) followed by an asthenospheric mantle from which basic magmas with OIB signature. Petrological models indicate the interaction of these two discrete magma series via magma-mixing processes.

Geothermometric calculations based on the composition of amphiboles are in the range of 769–953 and 938–994°C. Geobarometric calculations indicate crystallization depths ranging over an interval between 3.0 and 20.2 km, implying a polybaric crystallization. The oxygen fugacity (logƒO
2
) values vary between −10.10 and −13.07 bar in the dykes cutting the Upper Cretaceous volcanics, and from −8.71 to −10.33 bar in intermediate dykes cutting the İstanbul Palaeozoic unit. H
2
O
melt
contents change between 4.91–6.89 and 4.82–7.51%, respectively implying that the dykes were emplaced at mid to shallow crustal levels. Dyke complexes of the İstanbul zone are interpreted to have been emplaced in a rifted volcanic arc margin related to the opening of the Black Sea during the Late Cretaceous–Paleocene period.
PD-1 Expression in Head and Neck Squamous Cell Carcinomas Derives Primarily from Functionally Anergic CD4+ TILs in the Presence of PD-L1+ TAMs
Authors: Mattox Austin K. , Lee Jina , Westra William H. , Pierce Robert H. , Ghossein Ronald , Faquin William C. , Diefenbach Thomas J. , Morris Luc G. , Lin Derrick T. , Wirth Lori J. , Lefranc-Torres Armida , Ishida Eiichi , Chakravarty Patrick D. , Johnson Lauren , Zeng Yang C. , Chen Huabiao , Poznansky Mark C. , Iyengar Neil M. , Pai Sara I. 
Published: September 2017

Abstract
Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cavity tumor. In this study, we examined the basis for the activity of programmed cell death protein (PD-1)-based immune checkpoint therapy that is being explored widely in head and neck cancers. Using multispectral imaging, we systematically investigated the OTSCC tumor microenvironment (TME) by evaluating the frequency of PD-1 expression in CD8+, CD4+, and FoxP3+ tumor-infiltrating lymphocytes (TIL). We also defined the cellular sources of PD-1 ligand (PD-L1) to evaluate the utility of PD-1:PD-L1 blocking antibody therapy in this patient population. PD-L1 was expressed in 79% of the OTSCC specimens examined within the TME. Expression of PD-L1 was associated with moderate to high levels of CD4+ and CD8+ TILs. We found that CD4+ TILs were present in equal or greater frequencies than CD8+ TILs in 94% of OTSCC and that CD4+FOXP3neg TILs were colocalized with PD-1/PD-L1/CD68 more frequently than CD8+ TILs. Both CD4+PD1+ and CD8+PD1+ TILs were anergic in the setting of PD-L1 expression. Overall, our results highlight the importance of CD4+ TILs as pivotal regulators of PD-L1 levels and in determining the responsiveness of OTSCC to PD1-based immune checkpoint therapy. Cancer Res; 77(22); 6365–74. ©2017 AACR.
Mesenchymal Stem Cells Promote Hepatocarcinogenesis via lncRNA–MUF Interaction with ANXA2 and miR-34a
Authors: Yan Xinlong , Zhang Dongdong , Wu Wei , Wu Shuheng , Qian Jingfeng , Hao Yajing , Yan Fang , Zhu Pingping , Wu Jiayi , Huang Guanling , Huang Yinghui , Luo Jianjun , Liu Xinhui , Liu Benyu , Chen Xiaomin , Du Ying , Chen Runsheng , Fan Zusen 
Published: September 2017

Abstract
Accumulating evidence suggests that cancer-associated mesenchymal stem cells (MSC) contribute to the development and metastasis of hepatocellular carcinoma (HCC). Aberrant expression of long noncoding RNAs (lncRNA) has been associated with these processes but cellular mechanisms are obscure. In this study, we report that HCC-associated mesenchymal stem cells (HCC-MSC) promote epithelial–mesenchymal transition (EMT) and liver tumorigenesis. We identified a novel lncRNA that we termed lncRNA–MUF (MSC-upregulated factor) that is highly expressed in HCC tissues and correlated with poor prognosis. Depleting lncRNA–MUF in HCC cells repressed EMT and inhibited their tumorigenic potential. Conversely, lncRNA–MUF overexpression accelerated EMT and malignant capacity. Mechanistic investigations showed that lncRNA–MUF bound Annexin A2 (ANXA2) and activated Wnt/β-catenin signaling and EMT. Furthermore, lncRNA-MUF acted as a competing endogenous RNA for miR-34a, leading to Snail1 upregulation and EMT activation. Collectively, our findings establish a lncRNA-mediated process in MSC that facilitates hepatocarcinogenesis, with potential implications for therapeutic targeting. Cancer Res; 77(23); 6704–16. ©2017 AACR.
Skp2-Mediated Stabilization of MTH1 Promotes Survival of Melanoma Cells upon Oxidative Stress
Authors: Wang Jia Yu , Liu Guang Zhi , Wilmott James S. , La Ting , Feng Yu Chen , Yari Hamed , Yan Xu Guang , Thorne Rick F. , Scolyer Richard A. , Zhang Xu Dong , Jin Lei 
Published: September 2017

Abstract
MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA; however, there is little understanding of how MTH1 itself is regulated. Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination. In melanoma cell lines and patient specimens, we observed a positive correlation of Skp2 and MTH1 expression. Mechanistic investigations showed that Skp2 limited DNA damage and apoptosis triggered by oxidative stress and that MAPK upregulated Skp2 and MTH1 to render cells more resistant to such stress. Collectively, our findings identify Skp2-mediated K63-linked polyubiquitination as a critical regulatory mechanism responsible for MTH1 upregulation in melanoma, with potential implications to target the MAPK/Skp2/MTH1 pathway to improve its treatment. Cancer Res; 77(22); 6226–39. ©2017 AACR.
Combined CDK4/6 and PI3Kα Inhibition Is Synergistic and Immunogenic in Triple-Negative Breast Cancer
Authors: Teo Zhi Ling , Versaci Stephanie , Dushyanthen Sathana , Caramia Franco , Savas Peter , Mintoff Chris P. , Zethoven Magnus , Virassamy Balaji , Luen Stephen J. , McArthur Grant A. , Phillips Wayne A. , Darcy Phillip K. , Loi Sherene 
Published: September 2017

AbstractNew treatments for triple-negative breast cancer (TNBC) are urgently needed. Despite there being little evidence of clinical activity as single-agent therapies, we show that dual blockade of PI3Kα and CDK4/6 is synergistically effective against multiple RB1-wild-type TNBC models. Combined PI3Kα and CDK4/6 inhibition significantly increased apoptosis, cell-cycle arrest, and tumor immunogenicity and generated immunogenic cell death in human TNBC cell lines. Combination treatment also significantly improved disease control in human xenograft models compared with either monotherapy. Combined PI3Kα and CDK4/6 inhibition significantly increased tumor-infiltrating T-cell activation and cytotoxicity and decreased the frequency of immunosuppressive myeloid-derived suppressor cells in a syngeneic TNBC mouse model. Notably, combined PI3Kα and CDK4/6 inhibition, along with inhibition of immune checkpoints PD-1 and CTLA-4, induced complete and durable regressions (&gt;1 year) of established TNBC tumors in vivo. Overall, our results illustrate convergent mechanisms of PI3Kα and CDK4/6 blockade on cell-cycle progression, DNA damage response, and immune-modulation and may provide a novel therapeutic approach for TNBC. Cancer Res; 77(22); 6340–52. ©2017 AACR.
NY-ESO-1 Vaccination in Combination with Decitabine Induces Antigen-Specific T-lymphocyte Responses in Patients with Myelodysplastic Syndrome
Authors: Griffiths Elizabeth A. , Srivastava Pragya , Matsuzaki Junko , Brumberger Zachary , Wang Eunice S. , Kocent Justin , Miller Austin , Roloff Gregory W. , Wong Hong Yuen , Paluch Benjamin E. , Lutgen-Dunckley Linda G. , Martens Brandon L. , Odunsi Kunle , Karpf Adam R. , Hourigan Christopher S. , Nemeth Michael J. 
Published: September 2017

AbstractPurpose: Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are first-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that patients with acute myeloid leukemia (AML) receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in patients with MDS receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1–specific MDS-directed cytotoxic T-cell immune response.Experimental Design: In a phase I study, 9 patients with MDS received an HLA-unrestricted NY-ESO-1 vaccine (CDX-1401 + poly-ICLC) in a nonoverlapping schedule every four weeks with standard-dose decitabine.Results: Analysis of samples serially obtained from the 7 patients who reached the end of the study demonstrated induction of NY-ESO-1 expression in 7 of 7 patients and NY-ESO-1–specific CD4+ and CD8+ T-lymphocyte responses in 6 of 7 and 4 of 7 of the vaccinated patients, respectively. Myeloid cells expressing NY-ESO-1, isolated from a patient at different time points during decitabine therapy, were capable of activating a cytotoxic response from autologous NY-ESO-1–specific T lymphocytes. Vaccine responses were associated with a detectable population of CD141Hi conventional dendritic cells, which are critical for the uptake of NY-ESO-1 vaccine and have a recognized role in antitumor immune responses.Conclusions: These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively nonimmunogenic myeloid cancer and highlight the potential for induced antigen-directed immunotherapy in a group of patients with limited options. Clin Cancer Res; 24(5); 1019–29. ©2017 AACR.See related commentary by Fuchs, p. 991
Restricted Delivery of Talazoparib Across the Blood–Brain Barrier Limits the Sensitizing Effects of PARP Inhibition on Temozolomide Therapy in Glioblastoma
Authors: Kizilbash Sani H. , Gupta Shiv K. , Chang Kenneth , Kawashima Ryo , Parrish Karen E. , Carlson Brett L. , Bakken Katrina K. , Mladek Ann C. , Schroeder Mark A. , Decker Paul A. , Kitange Gaspar J. , Shen Yuqiao , Feng Ying , Protter Andrew A. , Elmquist William F. , Sarkaria Jann N. 
Published: September 2017

AbstractPoly ADP-ribose polymerase (PARP) inhibitors, including talazoparib, potentiate temozolomide efficacy in multiple tumor types; however, talazoparib-mediated sensitization has not been evaluated in orthotopic glioblastoma (GBM) models. This study evaluates talazoparib ± temozolomide in clinically relevant GBM models. Talazoparib at 1–3 nmol/L sensitized T98G, U251, and GBM12 cells to temozolomide, and enhanced DNA damage signaling and G2–M arrest in vitro. In vivo cyclical therapy with talazoparib (0.15 mg/kg twice daily) combined with low-dose temozolomide (5 mg/kg daily) was well tolerated. This talazoparib/temozolomide regimen prolonged tumor stasis more than temozolomide alone in heterotopic GBM12 xenografts [median time to endpoint: 76 days versus 50 days temozolomide (P = 0.005), 11 days placebo (P &lt; 0.001)]. However, talazoparib/temozolomide did not accentuate survival beyond that of temozolomide alone in corresponding orthotopic xenografts [median survival 37 vs. 30 days with temozolomide (P = 0.93), 14 days with placebo, P &lt; 0.001]. Average brain and plasma talazoparib concentrations at 2 hours after a single dose (0.15 mg/kg) were 0.49 ± 0.07 ng/g and 25.5±4.1 ng/mL, respectively. The brain/plasma distribution of talazoparib in Bcrp−/− versus wild-type (WT) mice did not differ, whereas the brain/plasma ratio in Mdr1a/b−/− mice was higher than WT mice (0.23 vs. 0.02, P &lt; 0.001). Consistent with the in vivo brain distribution, overexpression of MDR1 decreased talazoparib accumulation in MDCKII cells. These results indicate that talazoparib has significant MDR1 efflux liability that may restrict delivery across the blood–brain barrier, and this may explain the loss of talazoparib-mediated temozolomide sensitization in orthotopic versus heterotopic GBM xenografts. Mol Cancer Ther; 16(12); 2735–46. ©2017 AACR.
Transformation of a New Chinese Immigrant Community in the United States: A Case Study in Flushing, New York (美國新華人移民社區的轉型—以紐約法拉盛為探討中心)
Authors: Chen (陳靜瑜) Christine Chin-yu 
Published: September 2017

Early Chinese immigrants in America centered on the Chinatown, which had fixed blocks and scope of activities. The distinguishing features of its ethnic culture and economy were formed by the ethnic Chinese immigrants who dwelt there. The Chinatown has become identified with the early Chinese immigrants and become one of the most unique residential areas for any ethnic group. Ever since the 1965 amendments to the American Immigration and Nationality Act, however, new Chinese arrivals no longer inhabit Chinatowns after they reach the United States. Without stationary blocks and scopes of activities, new Chinese immigrant communities have become enclaves accommodating multiple ethnic groups instead of one particular ethnicity. These communities are closely connected to a variety of ethnic features and have a tremendously different appearance from that of Chinatown. This transformation is still in progress and has been widely-considered by many scholars researching overseas ethnic Chinese immigrants. Flushing, in New York, is the largest Chinese immigrant community in the twenty-first century. This essay takes it as a case study to look into the evolution of Chinese immigrant communities in the United States.
早期美國華人移民以唐人街為中心，它有固定的街區，一定的活動範圍。老移民住在這個範圍內，形成它鮮明的族裔文化和經濟特色，贏得了早期華人移民的認同，成為美國最具特色的族裔聚居區之一。自1965年新移民法修改後，新移民移入美國，不再以唐人街為居住區域，新華人移民社區無固定的街區，無固定的活動範圍，無單一的族裔聚集區，甚或是多族裔聚集的區域，靠著族裔特色融匯在一起，與過去的唐人街特色迥異，這種改變正在持續中，也是現今研究海外華人的學者關注的課題。本文欲藉由21世紀全球最大的華人移民社區—紐約的法拉盛（Flushing） 為例，探討美國華人移民社區的演變。 (This article is in English).
Subsurface Lateral Heat Flux within the Heterogeneous Surface of a Subtropical Wetland and Its Potential Contribution to Energy Imbalance
Authors: Cui Wenhui , May Chui Ting Fong 
Published: September 2017

AbstractIn the eddy covariance technique, lateral heat fluxes in the atmosphere, surfaces, and subsurfaces are often ignored under the assumption of a homogeneous surface. Among lateral heat fluxes, the surface and subsurface fluxes, which might affect the surface energy balance closure over a heterogeneous surface, are less studied. Many wetlands are heterogeneous, with a mix of vegetated areas and shallow open water. This study examined the subsurface lateral heat fluxes between a reed bed and the adjacent water of a subtropical wetland in Hong Kong, China. An array of temperature and water-level sensors was installed in the soil of the reed bed and in the adjacent water. An eddy covariance system was also set up on the reed bed. The subsurface lateral heat fluxes were largest close to the interface of the reed bed and water and decreased as the distance from the interface increased, as expected. However, the subsurface lateral heat fluxes could not account for the energy imbalance because their magnitudes were relatively small and fluctuated in phase with the energy budget residuals during the winter months. The uncertainties of the turbulent fluxes and the lateral heat fluxes were estimated to be 10%–20% and 10%–30%, respectively. This study explored another potential reason behind the energy imbalance of the eddy covariance technique. The results enhance the understanding of water and energy exchanges between a terrestrial biotope and the surrounding water, which might further generate insights into the biochemical processes in wetlands.
How Much Does “Backing Aloft” Actually Impact a Supercell?
Authors: Parker Matthew D. 
Published: September 2017

Abstract
Among forecasters and storm chasers, there is a common perception that hodographs with counterclockwise curvature or kinking in the midlevels (sometimes called backing aloft or veer–back–veer profiles) are unfavorable for long-lived supercells and tornadoes. This study reviews and then evaluates several possible explanations for the purported negative effect of backing aloft. As a controlled hypothesis test, simulated supercells are initiated within a range of idealized wind profiles, many of which include representative counterclockwise kinks or bends in their hodographs. In these experiments, the short-term, direct impacts of backing aloft upon supercell maintenance are generally small. Backing aloft does modify the component of vertical accelerations linked to updraft–shear interactions, but these changes generally occur well above the level of free convection (LFC), and they are generally offset by substantial upward accelerations attributable to other processes (e.g., within-storm rotation and positive buoyancy). In these simulations, the longevity of isolated supercells seems to be most directly hindered in environments with very low storm-relative helicity (SRH) or else (for a line of supercells) substantial along-line flow in the upper troposphere. Although these two disrupting properties can accompany backing aloft, they are neither universally nor exclusively associated with it. From the perspective of storm dynamics, it seems advisable to focus on SRH and along-line flow in the environment, rather than the presence (or absence) of backing aloft in the wind profile.