bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pagoda
Authors: Yeh Tsung Tai , Sabne Amit , Sakdhnagool Putt , Eigenmann Rudolf , Rogers Timothy G. 
Published: November 2019

Massively multithreaded GPUs achieve high throughput by running thousands of threads in parallel. To fully utilize the their hardware, contemporary workloads spawn work to the GPU in bulk by launching large tasks, where each task is a kernel that contains thousands of threads that occupy the entire GPU.
GPUs face severe underutilization and their performance benefits vanish if the tasks are narrow, i.e., they contain less than 512 threads. Latency-sensitive applications in network, signal, and image processing that generate a large number of tasks with relatively small inputs are examples of such limited parallelism.
This article presents Pagoda, a runtime system that virtualizes GPU resources, using an OS-like daemon kernel called MasterKernel. Tasks are spawned from the CPU onto Pagoda as they become available, and are scheduled by the MasterKernel at the warp granularity. This level of control enables the GPU to keep scheduling and executing tasks as long as free warps are found, dramatically reducing underutilization. Experimental results on real hardware demonstrate that Pagoda achieves a geometric mean speedup of 5.52X over PThreads running on a 20-core CPU, 1.76X over CUDA-HyperQ, and 1.44X over GeMTC, the state-of-the-art runtime GPU task scheduling system.
CD47 Deficiency Attenuates Isoproterenol-Induced Cardiac Remodeling in Mice
Authors: Zuo Zhi , Ji Ming-Yue , Zhao Kun , Su Zhong-Ping , Li Peng , Hou Dao-Rong , Li Yong 
Published: November 2019

In this study, we investigated whether CD47 deficiency attenuates isoproterenol- (ISO-) induced cardiac remodeling in mice. Cardiac remodeling was induced by intraperitoneal (i.p.) injection of ISO (60 mg·kg-1·d-1 in 100 μl of sterile normal saline) daily for 14 days and was confirmed by increased levels of lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB), increased heart weight to body weight (HW/BW) ratios, and visible cardiac fibrosis. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were found to be significantly higher in the ISO group than in the control group, while superoxide dismutase (SOD) levels were suppressed in the ISO group. However, CD47 knockout significantly limited ISO-induced increases in LDH, CK-MB, and HW/BW ratios, cardiac fibrosis, oxidative stress, and apoptosis in the heart. In addition, CD47 deficiency also increased p-AMPK and LAMP2 expression and decreased HDAC3, cleaved Caspase-3, cleaved Caspase-9, LC3II, and p62 expression in cardiac tissues. In conclusion, CD47 deficiency reduced i.p. ISO-induced cardiac remodeling probably by inhibiting the HDAC3 pathway, improving AMPK signaling and autophagy flux, and rescuing autophagic clearance.
Molecular Profiles of Matched Primary and Metastatic Tumor Samples Support a Linear Evolutionary Model of Breast Cancer
Authors: Chen Runpu , Goodison Steve , Sun Yijun 
Published: November 2019

Abstract

The interpretation of accumulating genomic data with respect to tumor evolution and cancer progression requires integrated models. We developed a computational approach that enables the construction of disease progression models using static sample data. Application to breast cancer data revealed a linear, branching evolutionary model with two distinct trajectories for malignant progression. Here, we used the progression model as a foundation to investigate the relationships between matched primary and metastasis breast tumor samples. Mapping paired data onto the model confirmed that molecular breast cancer subtypes can shift during progression and supported directional tumor evolution through luminal subtypes to increasingly malignant states. Cancer progression modeling through the analysis of available static samples represents a promising breakthrough. Further refinement of a roadmap of breast cancer progression will facilitate the development of improved cancer diagnostics, prognostics, and targeted therapeutics.

Significance:
Analysis of matched primary and metastatic tumor samples supports a unidirectional, linear cancer evolution process and sheds light on longstanding issues regarding the origins of molecular subtypes and their progression relationships.
Targeting the MET Receptor Tyrosine Kinase as a Strategy for Radiosensitization in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma
Authors: Nisa Lluís , Francica Paola , Giger Roland , Medo Matúš , Elicin Olgun , Friese-Hamim Manja , Wilm Claudia , Stroh Christopher , Bojaxhiu Beat , Quintin Aurélie , Caversaccio Marco D. , Dettmer Matthias S. , Buchwalder Mélanie , Brodie Tess M. , Aebersold Daniel M. , Zimmer Yitzhak , Carey Thomas E. , Medová Michaela 
Published: November 2019

AbstractRadiotherapy (RT) along with surgery is the mainstay of treatment in head and neck squamous cell carcinoma (HNSCC). Radioresistance represents a major source of treatment failure, underlining the urgent necessity to explore and implement effective radiosensitization strategies. The MET receptor widely participates in the acquisition and maintenance of an aggressive phenotype in HNSCC and modulates the DNA damage response following ionizing radiation (IR). Here, we assessed MET expression and mutation status in primary and metastatic lesions within a cohort of patients with advanced HNSCC. Moreover, we investigated the radiosensitization potential of the MET inhibitor tepotinib in a panel of cell lines, in vitro and in vivo, as well as in ex vivo patient-derived organotypic tissue cultures (OTC). MET was highly expressed in 62.4% of primary tumors and in 53.6% of lymph node metastases (LNM), and in 6 of 9 evaluated cell lines. MET expression in primaries and LNMs was significantly associated with decreased disease control in univariate survival analyses. Tepotinib abrogated MET phosphorylation and to distinct extent MET downstream signaling. Pretreatment with tepotinib resulted in variable radiosensitization, enhanced DNA damage, cell death, and G2–M-phase arrest. Combination of tepotinib with IR led to significant radiosensitization in one of two tested in vivo models. OTCs revealed differential patterns of response toward tepotinib, irradiation, and combination of both modalities. The molecular basis of tepotinib-mediated radiosensitization was studied by a CyTOF-based single-cell mass cytometry approach, which uncovered that MET inhibition modulated PI3K activity in cells radiosensitized by tepotinib but not in the resistant ones.
ERK Inhibitor LY3214996 Targets ERK Pathway–Driven Cancers: A Therapeutic Approach Toward Precision Medicine
Authors: Bhagwat Shripad V. , McMillen William T. , Cai Shufen , Zhao Baohui , Whitesell Matthew , Shen Weihua , Kindler Lisa , Flack Robert S. , Wu Wenjuan , Anderson Bryan , Zhai Yan , Yuan Xiu-Juan , Pogue Meghann , Van Horn Robert D. , Rao Xi , McCann Denis , Dropsey Andrew J. , Manro Jason , Walgren Jennie , Yuen Eunice , Rodriguez Michael J. , Plowman Gregory D. , Tiu Ramon V. , Joseph Sajan , Peng Sheng-Bin 
Published: November 2019

AbstractThe ERK pathway is critical in oncogenesis; aberrations in components of this pathway are common in approximately 30% of human cancers. ERK1/2 (ERK) regulates cell proliferation, differentiation, and survival and is the terminal node of the pathway. BRAF- and MEK-targeted therapies are effective in BRAF V600E/K metastatic melanoma and lung cancers; however, responses are short-lived due to emergence of resistance. Reactivation of ERK signaling is central to the mechanisms of acquired resistance. Therefore, ERK inhibition provides an opportunity to overcome resistance and leads to improved efficacy. In addition, KRAS-mutant cancers remain an unmet medical need in which ERK inhibitors may provide treatment options alone or in combination with other agents. Here, we report identification and activity of LY3214996, a potent, selective, ATP-competitive ERK inhibitor. LY3214996 treatment inhibited the pharmacodynamic biomarker, phospho-p90RSK1, in cells and tumors, and correlated with LY3214996 exposures and antitumor activities. In in vitro cell proliferation assays, sensitivity to LY3214996 correlated with ERK pathway aberrations. LY3214996 showed dose-dependent tumor growth inhibition and regression in xenograft models harboring ERK pathway alterations. Importantly, more than 50% target inhibition for up to 8 to 16 hours was sufficient for significant tumor growth inhibition as single agent in BRAF- and KRAS-mutant models. LY3214996 also exhibited synergistic combination benefit with a pan-RAF inhibitor in a KRAS-mutant colorectal cancer xenograft model. Furthermore, LY3214996 demonstrated antitumor activity in BRAF-mutant models with acquired resistance in vitro and in vivo. Based on these preclinical data, LY3214996 has advanced to an ongoing phase I clinical trial (NCT02857270).
AMPK-Independent LKB1 Activity Is Required for Efficient Epithelial Ovarian Cancer Metastasis
Authors: Buensuceso Adrian , Ramos-Valdes Yudith , DiMattia Gabriel E. , Shepherd Trevor G. 
Published: November 2019

Abstract

Epithelial ovarian cancer (EOC) spreads by direct dissemination of malignant cells and multicellular clusters, known as spheroids, into the peritoneum followed by implantation and growth on abdominal surfaces. Using a spheroid model system of EOC metastasis, we discovered that Liver kinase B1 (LKB1), encoded by the STK11 gene, and its canonical substrate AMP-activated protein kinase (AMPK) are activated in EOC spheroids, yet only LKB1 is required for cell survival. We have now generated STK11-knockout cell lines using normal human FT190 cells and three EOC cell lines, OVCAR8, HeyA8, and iOvCa147. STK11KO did not affect growth and viability in adherent culture, but it decreased anchorage-independent growth of EOC cells. EOC spheroids lacking LKB1 had markedly impaired growth and viability, whereas there was no difference in normal FT190 spheroids. To test whether LKB1 loss affects EOC metastasis, we performed intraperitoneal injections of OVCAR8-, HeyA8-, and iOvCa147-STK11KO cells, and respective controls. LKB1 loss exhibited a dramatic reduction on tumor burden and metastatic potential; in particular, OVCAR8-STK11KO tumors had evidence of extensive necrosis, apoptosis, and hypoxia. Interestingly, LKB1 loss did not affect AMPKα phosphorylation in EOC spheroids and tumor xenografts, indicating that LKB1 signaling to support EOC cell survival in spheroids and metastatic tumor growth occurs via other downstream mediators. We identified the dual-specificity phosphatase DUSP4 as a commonly upregulated protein due to LKB1 loss; indeed, DUSP4 knockdown in HeyA8-STK11KO cells partially restored spheroid formation and viability.

Implications:
LKB1 possesses key tumor-promoting activity independent of downstream AMPK signaling during EOC metastasis.
Prevalence and Electronic Health Record-Based Phenotype of Loss-of-Function Genetic Variants in Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Genes
Authors: Carruth Eric D. , Young Wilson , Beer Dominik , James Cynthia A. , Calkins Hugh , Jing Linyuan , Raghunath Sushravya , Hartzel Dustin N. , Leader Joseph B. , Kirchner H. Lester , Smelser Diane T. , Carey David J. , Kelly Melissa A. , Sturm Amy C. , Alsaid Amro , Fornwalt Brandon K. , Haggerty Christopher M. 
Published: November 2019

Background:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with variants in desmosome genes. Secondary findings of pathogenic/likely pathogenic variants, primarily loss-of-function (LOF) variants, are recommended for clinical reporting; however, their prevalence and associated phenotype in a general clinical population are not fully characterized.

Methods:

From whole-exome sequencing of 61 019 individuals in the DiscovEHR cohort, we screened for putative loss-of-function variants in
PKP2
,
DSC2
,
DSG2
, and
DSP
. We evaluated measures from prior clinical ECG and echocardiograms, manually over-read to evaluate ARVC diagnostic criteria, and performed a PheWAS (phenome-wide association study). Finally, we estimated expected penetrance using Bayesian inference.

Results:

One hundred forty individuals (0.23%; 59±18 years old at last encounter; 33% male) had an ARVC variant (G
+
). None had an existing diagnosis of ARVC in the electronic health record, nor significant differences in prior ECG or echocardiogram findings compared with matched controls without variants. Several G
+
individuals satisfied major repolarization (n=4) and ventricular function (n=5) criteria, but this prevalence matched controls. PheWAS showed no significant associations of other heart disease diagnoses. Combining our best genetic and disease prevalence estimates yields an estimated penetrance of 6.0%.

Conclusions:
The prevalence of ARVC loss-of-function variants is ≈1:435 in a general clinical population of predominantly European descent, but with limited electronic health record-based evidence of phenotypic association in our population, consistent with a low penetrance estimate. Prospective deep phenotyping and longitudinal follow-up of a large sequenced cohort is needed to determine the true clinical relevance of an incidentally identified ARVC loss-of-function variant.
Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden
Authors: Schlemm Ludwig , Endres Matthias , Werring David J. , Nolte Christian H. 
Published: November 2019

Background and Purpose—
Cerebral microbleeds (CMBs) are a risk factor for intracranial hemorrhage. Whether intravenous thrombolysis (IVT) improves functional outcome in acute ischemic stroke patients with CMBs is unknown. We aimed to estimate the treatment effect of IVT in patients with acute ischemic stroke and a high burden (>10) of CMBs.

Methods—
We devised a multistep algorithm to model 90-day modified Rankin Scale scores in patients with ≤10 versus >10 CMBs who do or do not receive IVT. Parameters were extracted from recently published meta-analyses and included pairwise relationships between CMBs, IVT, 3-month functional outcome, and intracranial hemorrhage. Uncertainty was quantified in probabilistic sensitivity analyses.

Results—
In patients with >10 CMBs as compared with ≤10 CMBs, point estimates of the odds ratios for favorable outcome (modified Rankin Scale ≤2) associated with IVT were 7% to 10% lower but still >1 (range, 1.03–1.51). On the other hand, IVT in patients with >10 CMBs significantly increased the odds of mortality. The point estimates for the net treatment effect of IVT (change in the utility-weighted modified Rankin Scale score) in patients with >10 CMBs were in favor of withholding IVT in older patients with more severe strokes and longer treatment delays. However, because the general pretest probability of >10 CMBs is low (0.6%–2.7%), pretreatment magnetic resonance imaging to quantify CMB burden would be justified only if it delayed IVT by <10 minutes.

Conclusions—
High CMB burden modifies the treatment effect of IVT. In patients with >10 CMBs, IVT is associated with higher mortality and, in older patients with severe strokes and longer treatment delays, a net utility loss. Patients with higher-than-average pretest probability of >10 CMB might profit from magnetic resonance imaging screening if it does not increase the treatment time.
Wenzhou Restaurants in Paris’s Chinatowns
Authors: Lipovsky Caroline , Wang (王玮) Wei 
Published: November 2019

Abstract
In light of the large number of Chinese immigrants in Paris originally from the Wenzhou region in China’s Zhejiang Province, this research focuses on two case studies of Wenzhou restaurants situated in different Paris Chinatowns. It seeks to identify the ways in which the Wenzhou owners mark their presence in the Parisian linguistic landscape through the signage of their shopfronts and premises. By infusing existing multimodal analysis with ethnographic linguistic landscape analysis (ELLA), this study examines the ways in which two Wenzhou restaurateurs display their specific cultural and ethnic identity in the linguistic landscape. The analysis of the signage of their premises, combined with ethnographic interviews, unveils the restaurateurs’ strategies to enact their cultural and ethnic Wenzhou identity through their shopfront signs, menus and premise decorations, and how they distinguish themselves from their Chinese competitors.
Redescription of three rare species of Dasypoda bees with first description of D. iberica and D. tibialis females (Hymenoptera, Apoidea, Melittidae)
Authors: RADCHENKO VLADIMIR G. , GHISBAIN GUILLAUME , MICHEZ DENIS 
Published: November 2019

Dasypoda bees are host-specialized solitary species distributed in the Palaearctic Region. In the framework of a global revision of this genus, comprehensive descriptions of three rare species (D. tibialis Morawitz, D. vulpecula Lebedev and D. iberica Warncke) are presented. The detailed morphology of the D. tibialis male and both sexes of D. vulpecula are given for the first time after a very partial original description. The females of D. tibialis and D. iberica are described for the first time and additional morphological characters of the male of D. iberica are provided. The lectotype of Dasypoda tibialis is designated. Host-plants and new localities are also presented.
The Relationships of Extreme Precipitation and Temperature Events with Ethnographic Reports of Droughts and Floods in Nonindustrial Societies
Authors: Felzer B. S. , Ember Carol R. , Cheng R. , Jiang M. 
Published: November 2019

AbstractOur broad research goal is to understand how human societies adapt to natural hazards, such as droughts and floods, and how their social and cultural structures are shaped by these events. Here we develop meteorological data of extreme dry, wet, cold, and warm indices relative to 96 largely nonindustrial societies in the worldwide Standard Cross-Cultural Sample to explore how well the meteorological data can be used to hindcast ethnographically reported drought and flood events and the global patterns of extremes. We find that the drought indices that are best at hindcasting ethnographically reported droughts [precipitation minus evaporation (P − E) measures] also tend to overpredict the number of droughts, and therefore we propose a combination of these two indices plus the PDSI as an optimal approach. Some wet precipitation indices (R10S and R20S) are more effective at hindcasting ethnographically reported floods than others. We also calculate the predictability of those extreme indices and use factor analysis to reduce the number of variables so as to discern global patterns. This work highlights the ability to use extreme meteorological indices to fill in gaps in ethnographic records; in the future, this may help us to determine relationships between extreme events and societal response over longer time scales than are otherwise available.
The top 100 most influential articles in allergic rhinitis from 1970 to 2018: A bibliometric analysis
Authors: Wu Qingwu , Zheng Rui , Wang Weihao , Qiu Huijun , Huang Xuekun , Yang Qintai 
Published: November 2019

Objective This study aimed to identify the top 100 most influential articles in the field of allergic rhinitis (AR). Methods Web of Science was queried for 1970 to 2018. Articles were sorted in descending order of the citation count. All titles and abstracts were screened to identify the top 100 articles. Results The top 100 most influential articles in AR were identified. The earliest article was published in 1975, and the most recent in 2015. The most prolific decade was the 2000s, with 59 articles published. Twenty-nine journals contributed to the top 100 articles, with the Journal of Allergy and Clinical Immunology contributing most of the articles (n = 34). The top three countries of article origin were the United States (n = 34), followed by the United Kingdom and France (n = 14 each). The type of article covered clinical research (n = 68), reviews (n = 22), and basic research (n = 10). For the clinical research articles, there were 6 studies with level 1 evidence, 25 with level 2 evidence, 11 with level 3 evidence, and 26 with level 4 evidence. Conclusions This study identified the top 100 most influential articles in the area of AR. Recognition of important historical contributions to this field may guide future investigations into AR.
An exploratory study of how young people experience and perceive living with type 1 diabetes during late adolescence and emerging adulthood
Authors: Ingersgaard Marianne Vie , Hoeeg Didde , Willaing Ingrid , Grabowski Dan 
Published: November 2019

Objective Suboptimal glycemic control and psychosocial challenges are significant concerns for adolescents and emerging adults (collectively young people) with type 1 diabetes. Knowledge about young peoples’ attitudes towards living with type 1 diabetes is inadequate, but the issue is important in the development of strategies to improve glycemic control and psychosocial well-being. This study explored young peoples’ perceptions of living with type 1 diabetes. Methods An exploratory, qualitative design was employed. Data were collected through five participatory workshops with 19 young people (age 15–25). Data were thematically analyzed. Results The overall depiction of living with type 1 diabetes was paradoxical; it affected everything and nothing. Living with type 1 diabetes was a balancing act between accommodating a “normal” way of living and self-management tasks of the treatment regimen. Participants’ perceptions reflected shifting accounts that could be divided into five themes: (1) special rules during youth, (2) striving for autonomy, (3) an uncertain future, (4) social support, and (5) stigma and disclosure. Discussion It is important to probe for the multiple and interrelated social contexts that underlie young peoples’ motives for adhering to and deviating from treatment regimens. Future studies should focus on relational aspects, including stigma mechanisms, the role of friends, and facilitation of balanced parental involvement.