bluuebunny/crossref_metadata_2025_split huggingface dataset:
comeNgo
Authors: Zhang Tianyang , Cui Peng , Faloutsos Christos , Lu Yunfei , Ye Hao , Zhu Wenwu , Yang Shiqiang 
Published: July 2017

How do social groups, such as Facebook groups and Wechat groups, dynamically evolve over time? How do people join the social groups, uniformly or with burst? What is the pattern of people quitting from groups? Is there a simple universal model to depict the come-and-go patterns of various groups?In this article, we examine temporal evolution patterns of more than 100 thousands social groups with more than 10 million users. We surprisingly find that the evolution patterns of real social groups goes far beyond the classic dynamic models like SI and SIR. For example, we observe both diffusion and non-diffusion mechanism in the group joining process, and power-law decay in group quitting process, rather than exponential decay as expected in SIR model. Therefore, we propose a new modelcomeNgo, a concise yet flexible dynamic model for group evolution. Our model has the following advantages: (a) Unification power: it generalizes earlier theoretical models and different joining and quitting mechanisms we find from observation. (b) Succinctness and interpretability: it contains only six parameters with clear physical meanings. (c) Accuracy: it can capture various kinds of group evolution patterns preciously, and the goodness of fit increases by 58% over baseline. (d) Usefulness: it can be used in multiple application scenarios, such as forecasting and pattern discovery. Furthermore, our model can provide insights about different evolution patterns of social groups, and we also find that group structure and its evolution has notable relations with temporal patterns of group evolution.
Novel Gene and Network Associations Found for Acute Lymphoblastic Leukemia Using Case–Control and Family-Based Studies in Multiethnic Populations
Authors: Nakka Priyanka , Archer Natalie P. , Xu Heng , Lupo Philip J. , Raphael Benjamin J. , Yang Jun J. , Ramachandran Sohini 
Published: July 2017

Abstract
Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, suggesting that germline variants influence ALL risk. Although multiple genome-wide association (GWA) studies have identified variants predisposing children to ALL, it remains unclear whether genetic heterogeneity affects ALL susceptibility and how interactions within and among genes containing ALL-associated variants influence ALL risk.
Methods: Here, we jointly analyzed two published datasets of case–control GWA summary statistics along with germline data from ALL case–parent trios. We used the gene-level association method PEGASUS to identify genes with multiple variants associated with ALL. We then used PEGASUS gene scores as input to the network analysis algorithm HotNet2 to characterize the genomic architecture of ALL.
Results: Using PEGASUS, we confirmed associations previously observed at genes such as ARID5B, IKZF1, CDKN2A/2B, and PIP4K2A, and we identified novel candidate gene associations. Using HotNet2, we uncovered significant gene subnetworks that may underlie inherited ALL risk: a subnetwork involved in B-cell differentiation containing the ALL-associated gene CEBPE, and a subnetwork of homeobox genes, including MEIS1.
Conclusions: Gene and network analysis uncovered loci associated with ALL that are missed by GWA studies, such as MEIS1. Furthermore, ALL-associated loci do not appear to interact directly with each other to influence ALL risk, and instead appear to influence leukemogenesis through multiple, complex pathways.
Impact: We present a new pipeline for post hoc analysis of association studies that yields new insight into the etiology of ALL and can be applied in future studies to shed light on the genomic underpinnings of cancer. Cancer Epidemiol Biomarkers Prev; 26(10); 1531–9. ©2017 AACR.
Rural–Urban Differences in Cancer Incidence and Trends in the United States
Authors: Zahnd Whitney E. , James Aimee S. , Jenkins Wiley D. , Izadi Sonya R. , Fogleman Amanda J. , Steward David E. , Colditz Graham A. , Brard Laurent 
Published: July 2017

Abstract
Background: Cancer incidence and mortality rates in the United States are declining, but this decrease may not be observed in rural areas where residents are more likely to live in poverty, smoke, and forego cancer screening. However, there is limited research exploring national rural–urban differences in cancer incidence and trends.
Methods: We analyzed data from the North American Association of Central Cancer Registries' public use dataset, which includes population-based cancer incidence data from 46 states. We calculated age-adjusted incidence rates, rate ratios, and annual percentage change (APC) for: all cancers combined, selected individual cancers, and cancers associated with tobacco use and human papillomavirus (HPV). Rural–urban comparisons were made by demographic, geographic, and socioeconomic characteristics for 2009 to 2013. Trends were analyzed for 1995 to 2013.
Results: Combined cancers incidence rates were generally higher in urban populations, except for the South, although the urban decline in incidence rate was greater than in rural populations (10.2% vs. 4.8%, respectively). Rural cancer disparities included higher rates of tobacco-associated, HPV-associated, lung and bronchus, cervical, and colorectal cancers across most population groups. Furthermore, HPV-associated cancer incidence rates increased in rural areas (APC = 0.724, P &lt; 0.05), while temporal trends remained stable in urban areas.
Conclusions: Cancer rates associated with modifiable risks—tobacco, HPV, and some preventive screening modalities (e.g., colorectal and cervical cancers)—were higher in rural compared with urban populations.
Impact: Population-based, clinical, and/or policy strategies and interventions that address these modifiable risk factors could help reduce cancer disparities experienced in rural populations. Cancer Epidemiol Biomarkers Prev; 27(11); 1265–74. ©2017 AACR.
Pediatric Phase I Trial and Pharmacokinetic Study of Trebananib in Relapsed Solid Tumors, Including Primary Tumors of the Central Nervous System ADVL1115: A Children's Oncology Group Phase I Consortium Report
Authors: Leary Sarah E.S. , Park Julie R. , Reid Joel M. , Ralya Andrew T. , Baruchel Sylvain , Wu Bing , Roberts Timothy P.L. , Liu Xiaowei , Minard Charles G. , Fox Elizabeth , Weigel Brenda , Blaney Susan 
Published: July 2017

Abstract
Purpose: Trebananib is a first-in-class antiangiogenic peptibody (peptide–Fc fusion protein) that inhibits Angiopoietin 1 and 2. A pediatric phase 1 trial was performed to define trebananib dose-limiting toxicities (DLT), recommended phase 2 dose (RP2D), and pharmacokinetics (PK).
Experimental Design: Trebananib was administered by weekly infusion. Three dose levels (10, 15, or 30 mg/kg/dose) were evaluated using a rolling-six design. Part 2 evaluated a cohort of subjects with primary central nervous system (CNS) tumors. Pharmacokinetic sampling and analysis of peripheral blood biomarkers was performed during the first 4 weeks. Response was evaluated after 8 weeks. Correlative studies included angiogenic protein expression and DCE-MRI.
Results: Thirty-seven subjects were enrolled (31 evaluable for toxicity) with median age 12 years (range, 2 to 21). Two of 19 evaluable non-CNS subjects developed DLT at the 30 mg/kg dose level, including venous thrombosis and pleural effusion. In the CNS cohort, 3/12 subjects developed DLT, including decreased platelet count, transient ischemic attack, and cerebral edema with headache and hydrocephalus. Other grade 3 or 4 toxicities included lymphopenia (n = 4), anemia, thrombocytopenia, neutropenia, vomiting, and hypertension (n = 1 each). Response included stable disease in 7 subjects, no partial or complete responses. Two subjects continued study treatment with prolonged stable disease for 18 cycles (neuroblastoma) and 26 cycles (anaplastic astrocytoma). Pharmacokinetics appeared linear over 3 dose levels. Correlative studies demonstrated increased PlGF and sVCAM-1, but no change in endoglin or perfusion by DCE-MRI.
Conclusions: Trebananib was well tolerated in pediatric patients with recurrent or refractory solid or CNS tumors. RP2D is 30 mg/kg. Clin Cancer Res; 23(20); 6062–9. ©2017 AACR.
Numb−/low Enriches a Castration-Resistant Prostate Cancer Cell Subpopulation Associated with Enhanced Notch and Hedgehog Signaling
Authors: Guo Yanjing , Zhang Kai , Cheng Chaping , Ji Zhongzhong , Wang Xue , Wang Minglei , Chu Mingliang , Tang Dean G. , Zhu Helen He , Gao Wei-Qiang 
Published: July 2017

Abstract
Purpose: To elucidate the role and molecular mechanism of Numb in prostate cancer and the functional contribution of Numb−/low prostate cancer cells in castration resistance.
Experimental Design: The expression of Numb was assessed using multiple Oncomine datasets and prostate cancer tissues from both humans and mice. The biological effects of the overexpression and knockdown of Numb in human prostate cancer cell lines were investigated in vitro and in vivo. In addition, we developed a reliable approach to distinguish between prostate cancer cell populations with a high or low endogenous expression of Numb protein using a Numb promoter–based lentiviral reporter system. The difference between Numb−/low and Numbhigh prostate cancer cells in the response to androgen-deprivation therapy (ADT) was then tested. The likely downstream factors of Numb were analyzed using luciferase reporter assays, immunoblotting, and quantitative real-time PCR.
Results: We show here that Numb was downregulated and negatively correlated with prostate cancer advancement. Functionally, Numb played an inhibitory role in xenograft prostate tumor growth and castration-resistant prostate cancer development by suppressing Notch and Hedgehog signaling. Using a Numb promoter–based lentiviral reporter system, we were able to distinguish Numb−/low prostate cancer cells from Numbhigh cells. Numb−/low prostate cancer cells were smaller and quiescent, preferentially expressed Notch and Hedgehog downstream and stem-cell–associated genes, and associated with a greater resistance to ADT. The inhibition of the Notch and Hedgehog signaling pathways significantly increased apoptosis in Numb−/low cells in response to ADT.
Conclusions: Numb−/low enriches a castration-resistant prostate cancer cell subpopulation that is associated with unregulated Notch and Hedgehog signaling. Clin Cancer Res; 23(21); 6744–56. ©2017 AACR.
Head and Neck Carcinoma Immunotherapy: Facts and Hopes
Authors: Whiteside Theresa L. 
Published: July 2017

Abstract
Cancer of the head and neck (HNC) is a heterogeneous disease of the upper aerodigestive tract, encompassing distinct histologic types, different anatomic sites, and human papillomavirus (HPV)–positive as well as HPV-negative cancers. Advanced/recurrent HNCs have poor prognosis with low survival rates. Tumor-mediated inhibition of antitumor immune responses and a high mutational burden are common features of HNCs. Both are responsible for the successful escape of these tumors from the host immune system. HNCs evolve numerous mechanisms of evasion from immune destruction. These mechanisms are linked to genetic aberrations, so that HNCs with a high mutational load are also highly immunosuppressive. The tumor microenvironment of these cancers is populated by immune cells that are dysfunctional, inhibitory cytokines, and exosomes carrying suppressive ligands. Dysfunctional immune cells in patients with recurrent/metastatic HNC can be made effective by the delivery of immunotherapies in combination with conventional treatments. With many promising immune-based strategies available, the future of immune therapies in HNC is encouraging, especially as methods for genetic profiling and mapping the immune landscape of the tumor are being integrated into a personalized approach. Efficiency of immune therapies is expected to rapidly improve with the possibility for patients' selection based on personal immunogenomic profiles. Noninvasive biomarkers of response to therapy will be emerging as a better understanding of the various molecular signals co-opted by the tumors is gained. The emerging role of immunotherapy as a potentially beneficial addition to standard treatments for recurrent/metastatic HNC offers hope to the patients for whom no other therapeutic options exist. Clin Cancer Res; 24(1); 6–13. ©2017 AACR.
FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation–Associated Advanced Ovarian Cancer
Authors: Balasubramaniam Sanjeeve , Beaver Julia A. , Horton Sara , Fernandes Laura L. , Tang Shenghui , Horne Hisani N. , Liu Jinzhong , Liu Chao , Schrieber Sarah J. , Yu Jingyu , Song Pengfei , Pierce William , Robertson Kim J. , Palmby Todd R. , Chiu Haw-Jyh , Lee Eunice Y. , Philip Reena , Schuck Robert , Charlab Rosane , Banerjee Anamitro , Chen Xiao Hong , Wang Xing , Goldberg Kirsten B. , Sridhara Rajeshwari , Kim Geoffrey , Pazdur Richard 
Published: July 2017

Abstract
On December 19, 2016, the FDA granted accelerated approval to rucaparib (RUBRACA; Clovis Oncology, Inc.) for the treatment of patients with deleterious BRCA mutation (germline and/or somatic)–associated advanced ovarian cancer who have been treated with two or more chemotherapies. The FDA also approved the FoundationFocus CDxBRCA test (Foundation Medicine, Inc.), the first next-generation sequencing-based companion diagnostic, for identifying patients with advanced ovarian cancer eligible for treatment with rucaparib based on detection of deleterious BRCA1 and/or BRCA2 mutations in tumor tissue. Rucaparib's approval was based primarily on efficacy data from 106 patients with BRCA mutation–associated ovarian cancer who had prior treatment with two or more chemotherapies and safety data from 377 patients with ovarian cancer treated with rucaparib 600 mg orally twice daily on two open-label, single-arm trials. Investigator-assessed objective response rate was 54% [57/106; 95% confidence interval (CI), 44–64], and median duration of response was 9.2 months (95% CI, 6.6–11.7). The approved companion diagnostic verified tumor BRCA mutation status retrospectively in 96% (64/67) of patients. Common adverse reactions (≥20%) to rucaparib were nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. This article summarizes the FDA review and data supporting rucaparib's accelerated approval. Clin Cancer Res; 23(23); 7165–70. ©2017 AACR.
See related commentary by Kohn et al., p. 7155
Angiotensin II Type 1 Receptor‐Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin
Authors: Uneda Kazushi , Wakui Hiromichi , Maeda Akinobu , Azushima Kengo , Kobayashi Ryu , Haku Sona , Ohki Kohji , Haruhara Kotaro , Kinguchi Sho , Matsuda Miyuki , Ohsawa Masato , Minegishi Shintaro , Ishigami Tomoaki , Toya Yoshiyuki , Atobe Yoshitoshi , Yamashita Akio , Umemura Satoshi , Tamura Kouichi 
Published: July 2017

Background

The kidney is easily affected by aging‐associated changes, including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly, renal tubulointerstitial fibrosis is a final common pathway in most forms of progressive renal disease. Angiotensin
II
type 1 receptor (
AT
1R)‐associated protein (
ATRAP
), which was originally identified as a molecule that binds to
AT
1R, is highly expressed in the kidney. Previously, we have shown that
ATRAP
suppresses hyperactivation of
AT
1R signaling, but does not affect physiological
AT
1R signaling.

Methods and Results

We hypothesized that
ATRAP
has a novel functional role in the physiological age‐degenerative process, independent of modulation of
AT
1R signaling.
ATRAP
‐knockout mice were used to study the functional involvement of
ATRAP
in the aging.
ATRAP
‐knockout mice exhibit a normal age‐associated appearance without any evident alterations in physiological parameters, including blood pressure and cardiovascular and metabolic phenotypes. However, in
ATRAP
‐knockout mice compared with wild‐type mice, the following takes place: (1) age‐associated renal function decline and tubulointerstitial fibrosis are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent increases in the production of reactive oxygen species are more advanced; and (3) life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key mechanism, age‐related pathological changes in the kidney of
ATRAP
‐knockout mice correlated with decreased expression of the prosurvival gene,
Sirtuin1
. On the other hand, chronic angiotensin
II
infusion did not affect renal sirtuin1 expression in wild‐type mice.

Conclusions

These results indicate that
ATRAP
plays an important role in inhibiting kidney aging, possibly through sirtuin1‐mediated mechanism independent of blocking
AT
1R signaling, and further protecting normal life span.
Mediation as Politics: How Nations Leverage Peace Engagements?
Authors: Beriker Nimet 
Published: July 2017

AbstractThis study proposes a conceptual model that depicts middle power mediation as a foreign policy strategy in the context of asymmetric alliance dynamics. It expands on Touval’s (2003) mediation-as-foreign policy perspective and argues that once mediation is conceived of as a viable political option in the conduct of foreign policy, engaging in mediation activity enables middle powers to create an extra space of political power not otherwise available. The article introduces an analytical model that explains the dynamics of mediation-as-foreign policy approach and the mechanisms that translate mediation engagement into political leverage. The analysis focuses on aspects of Turkish mediation efforts between 2002 and 2009 in the context of Turkish-us/eurelations.
Diurnal Cycle of Rainfall Associated with Landfalling Tropical Cyclones in China from Rain Gauge Observations
Authors: Hu Hao , Duan Yihong , Wang Yuqing , Zhang Xinghai 
Published: July 2017

AbstractThe diurnal variation of rainfall over China associated with landfalling tropical cyclones (TCs) is investigated using hourly rain gauge observations obtained from 2425 conventional meteorological stations in China. Records between 12 h prior to landfall and 12 h after landfall of 450 landfalling TCs in China from 1957 to 2014 are selected as samples. The harmonic analysis shows an obvious diurnal signal in TC rainfall with a rain-rate peak in the early morning and a minimum in the afternoon. The diurnal cycle in the outer region (between 400- and 900-km radii from the storm center) is found to be larger than in the core region (within 400 km of the storm center). This could be attributed to the effect of land on the inner core of the storms as the diurnal cycle is distinct in the core region well before landfall. As the result of this diurnal cycle, TCs making landfall at night tend to have cumulative precipitation, defined as the precipitation cumulated from the time at landfall to 12 h after landfall, about 30% larger than those making landfall around noon or afternoon. Moreover, the radial propagation of the diurnal cycle in TC rain rate, which has been a controversial phenomenon in some previous studies with remote sensing observations, was not present in this study that is based on rain gauge observations. Results also show that the diurnal signal has little dependence on the storm intensity 12 h prior to landfall.
Human skin gene expression: Natural (trans) resveratrol versus five resveratrol analogs for dermal applications
Authors: Lephart Edwin D , Andrus Merritt B 
Published: July 2017

Resveratrol (RV) is a polyphenolic compound naturally produced by plants. Polyphenolic compounds incorporated into medicinal products are beneficial but, RV is rapidly metabolized with an associated decline in biological activity. This study tested RV as the standard and compared five structurally modified RV analogs: butyrate, isobutyrate, palmitoate, acetate, and diacetate (to improve functionality) at 1% concentration(s) for 24 h in epiderm full thickness cultures by gene array/qPCR mRNA analysis. When silent mating type information regulation 2 homolog 1, extracellular elements (collagen1A1, 3A1, 4A1; elastin, tissue inhibitor of matrix metalloproteinase 1, fibrillin 1 laminin beta1 and matrix metalloproteinase 9), anti-aging and aging genes, inflammatory biomarkers (interleukin-1A [IL1A], IL1R2, IL-6 and IL-8), nerve growth factor, and the antioxidants (proliferating cell nuclear antigen, catalase, superoxide dismutase and metallothionein 1H/2H) were evaluated, ranking each from highest-to-lowest for gene expression: butyrate > isobutyrate > diacetate > acetate > palmitoate. This study showed that the butyrate and isobutyrate analogs are more biologically active compared to resveratrol and have potential use in topical applications to improve dermal and other health applications. Impact statement Resveratrol has been reported to have a wide variety of health benefits but its rapid metabolism especially after oral ingestion results in very low bioavailability. Notably, the first human skin gene expression study of resveratrol was not published until 2014. The purpose of this study was to determine if increased stability and biological activity could be obtained by modifying the chemical structure of natural (trans) resveratrol and quantifying human gene expression by qPCR of skin biomarkers that enhance dermal health. Five resveratrol analogs were synthesized that increased their lipophilic index to enhance tissue penetration and augment biological activities on the measured parameters that expand the current knowledge of structure/function relationships. The butyrate and isobutyrate modifications displayed gene expression values significantly above resveratrol and suggest that oral application of these and potentially other resveratrol analogs may yield similar results to improve stability and biological activity to benefit/address various disorders/diseases.
Evaluating 17 years of latent tuberculosis infection screening in north-west England: a retrospective cohort study of reactivation
Authors: Zenner Dominik , Loutet Miranda G. , Harris Ross , Wilson Stephen , Ormerod L. Peter 
Published: July 2017

Approximately 72% of tuberculosis (TB) cases in England occur among non-UK born individuals, mostly as a result of reactivation of latent TB infection (LTBI). Programmatic LTBI screening is a key intervention of the TB strategy for England. This article reviews the results of a long-standing LTBI screening initiative in England.A retrospective cohort was created through probabilistic linkage between LTBI screening data and national TB case notifications. Screened persons were followed until they died, became a case, emigrated or until cohort-end. TB incidence rates and rate ratios (IRR) were calculated.97 out of 1820 individuals screened for LTBI were reported to have active TB. Crude incidence rates among LTBI-positive, treatment-naïve individuals were 4.1 and 2.3 per 100 person-years in the QuantiFERON and tuberculin skin test cohorts, respectively. Among the QuantiFERON cohort, Poisson regression showed that LTBI positivity (IRR 22.6, 95% CI 6.8–74.6) and no chemoprophylaxis increased the probability of becoming a TB case (IRR 0.17, 95% CI 0.05–0.6).We found high TB rates in LTBI-positive, treatment-naïve individuals and a strong association between no treatment and becoming a TB case, demonstrating feasibility and effectiveness of LTBI screening and providing important policy lessons for LTBI screening in England and beyond.