bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dairy Consumption in Adolescence and Early Adulthood and Risk of Breast Cancer
Authors: Farvid Maryam S. , Eliassen A. Heather , Cho Eunyoung , Chen Wendy Y. , Willett Walter C. 
Published: May 2018

Abstract
Background: Carcinogenic exposure in early life may be critical for subsequent breast cancer risk. Dairy consumption was examined during adolescence and early adulthood in relation to incident breast cancer in the Nurses' Health Study II cohort.
Methods: For the analyses of early adulthood dairy consumption, we included 90,503 premenopausal women ages 27 to 44 years in 1991 who reported dairy consumption using a validated food-frequency questionnaire. From 1991 to 2013, 3,191 invasive breast cancer cases were identified. In 1998, 44,264 women recalled adolescent dairy consumption. This subgroup of women was followed up from 1998 to 2013; 1,318 invasive breast cancer cases were identified. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard regression.
Results: Adolescent and early adulthood total dairy consumption was not associated with overall breast cancer risk (each serving/day during adolescence, total dairy HR = 1.02, 95% CI, 0.97–1.07; for early adulthood total dairy HR = 1.01, 95% CI, 0.97–1.04), as were intakes of calcium, vitamin D, and lactose. Adolescent consumption of total and high-fat dairy was associated with higher risk of estrogen and progesterone receptor negative (each serving/day: total dairy HR = 1.11, 95% CI, 1.00–1.24; high-fat dairy HR = 1.17, 95% CI, 1.04–1.31). However, higher adolescent high-fat dairy consumption was associated with lower risk of estrogen and progesterone receptor positive tumors (each serving/day HR = 0.91, 95% CI, 0.86–0.97).
Conclusions: Our results suggest no overall association between dairy consumption during adolescence or early adulthood and breast cancer risk, but the findings may differ by hormone receptor status of tumors.
Impact: Dairy consumption in adolescence or early adulthood may not be a significant predictor of breast cancer incidence. Cancer Epidemiol Biomarkers Prev; 27(5); 575–84. ©2018 AACR.
MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease
Authors: Bhanvadia Raj R. , VanOpstall Calvin , Brechka Hannah , Barashi Nimrod S. , Gillard Marc , McAuley Erin M. , Vasquez Juan Manuel , Paner Gladell , Chan Wen-Ching , Andrade Jorge , De Marzo Angelo M. , Han Misop , Szmulewitz Russell Z. , Vander Griend Donald J. 
Published: May 2018

Abstract
Purpose: Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS–HOX interactions in prostate cancer etiology and progression. The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored.
Experimental Design: Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression.
Results: These analyses demonstrate a stepwise decrease in the expression of both MEIS1 and MEIS2 from benign epithelia, to primary tumor, to metastatic tissues. Positive expression of MEIS proteins in primary tumors, however, is associated with a lower hazard of clinical metastasis (HR = 0.28) after multivariable analysis. Pathway and gene set enrichment analyses identified MEIS-associated networks involved in cMYC signaling, cellular proliferation, motility, and local tumor environment. Depletion of MEIS1 and MEIS2 resulted in increased tumor growth over time in vivo, and decreased MEIS expression in both patient-derived tumors and MEIS-depleted cell lines was associated with increased expression of the protumorigenic genes cMYC and CD142, and decreased expression of AXIN2, FN1, ROCK1, SERPINE2, SNAI2, and TGFβ2.
Conclusions: These data implicate a functional role for MEIS proteins in regulating cancer progression, and support a hypothesis whereby tumor expression of MEIS1 and MEIS2 expression confers a more indolent prostate cancer phenotype, with a decreased propensity for metastatic progression. Clin Cancer Res; 24(15); 3668–80. ©2018 AACR.
The IGF2/IR/IGF1R Pathway in Tumor Cells and Myofibroblasts Mediates Resistance to EGFR Inhibition in Cholangiocarcinoma
Authors: Vaquero Javier , Lobe Cindy , Tahraoui Sylvana , Clapéron Audrey , Mergey Martine , Merabtene Fatiha , Wendum Dominique , Coulouarn Cédric , Housset Chantal , Desbois-Mouthon Christèle , Praz Françoise , Fouassier Laura 
Published: May 2018

Abstract
Purpose: Cholangiocarcinoma (CCA) is a desmoplastic tumor of the biliary tree in which epidermal growth factor receptor (EGFR) is overexpressed and contributes to cancer progression. Although EGFR has been envisaged as a target for therapy, treatment with tyrosine kinase inhibitors (TKI) such as erlotinib did not provide therapeutic benefit in patients with CCA, emphasizing the need to investigate resistance mechanisms against EGFR inhibition.
Experimental Design: Resistant CCA cells to EGFR inhibition were obtained upon long-time exposure of cells with erlotinib. Cell signaling, viability, migration, and spheroid growth were determined in vitro, and tumor growth was evaluated in CCA xenograft models.
Results: Erlotinib-resistant CCA cells displayed metastasis-associated signatures that correlated with a marked change in cell plasticity associated with an epithelial–mesenchymal transition (EMT) and a cancer stem cell (CSC)–like phenotype. Resistant cells exhibited an upregulation of insulin receptor (IR) and insulin-like growth factor (IGF) 1 receptor (IGF1R), along with an increase in IGF2 expression. IR/IGF1R inhibition reduced EMT and CSC-like traits in resistant cells. In vivo, tumors developed from resistant CCA cells were larger and exhibited a more prominent stromal compartment, enriched in cancer-associated fibroblasts (CAF). Pharmacological coinhibition of EGFR and IR/IGF1R reduced tumor growth and stromal compartment in resistant tumors. Modeling of CCA-CAF crosstalk showed that IGF2 expressed by fibroblasts boosted IR/IGF1R signaling in resistant cells. Furthermore, IR/IGF1R signaling positively regulated fibroblast proliferation and activation.
Conclusions: To escape EGFR-TKI treatment, CCA tumor cells develop an adaptive mechanism by undergoing an IR/IGF1R-dependent phenotypic switch, involving a contribution of stromal cells. Clin Cancer Res; 24(17); 4282–96. ©2018 AACR.
A Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure
Authors: Zeidan Amer M. , Knaus Hanna A. , Robinson Tara M. , Towlerton Andrea M.H. , Warren Edus H. , Zeidner Joshua F. , Blackford Amanda L. , Duffield Amy S. , Rizzieri David , Frattini Mark G. , Levy Yair M. , Schroeder Mark A. , Ferguson Anna , Sheldon Katherine E. , DeZern Amy E. , Gojo Ivana , Gore Steven D. , Streicher Howard , Luznik Leo , Smith B. Douglas 
Published: May 2018

Abstract
Purpose: After failure of hypomethylating agents (HMA), patients with myelodysplastic syndromes (MDS) have dismal survival and no approved treatment options.
Patients and Methods: We conducted a phase 1b investigator-initiated trial of ipilimumab in patients with higher risk MDS who have failed HMAs. Patients received monotherapy at two dose levels (DL; 3 and 10 mg/kg) with an induction followed by a maintenance phase. Toxicities and responses were evaluated with CTCAE.4 and IWG-2006 criteria, respectively. We also performed immunologic assays and T-cell receptor sequencing on serial samples.
Results: Twenty-nine patients from 7 centers were enrolled. In the initial DL1 (3 mg), 3 of 6 patients experienced grade 2–4 immune-related adverse events (IRAE) that were reversible with drug discontinuation and/or systemic steroids. In DL2, 4 of 5 patients experienced grade 2 or higher IRAE; thus, DL1 (3 mg/kg) was expanded with no grade 2–4 IRAEs reported in 18 additional patients. Best responses included marrow complete response (mCR) in one patient (3.4%). Prolonged stable disease (PSD) for ≥46 weeks occurred in 7 patients (24% of entire cohort and 29% of those treated with 3 mg/kg dose), including 3 patients with more than a year of SD. Five patients underwent allografting without excessive toxicity. Median survival for the group was 294 days (95% CI, 240–671+). Patients who achieved PSD or mCR had significantly higher frequency of T cells expressing ICOS (inducible T-cell co-stimulator).
Conclusions: Our findings suggest that ipilimumab dosed at 3 mg/kg in patients with MDS after HMA failure is safe but has limited efficacy as a monotherapy. Increased frequency of ICOS-expressing T cells might predict clinical benefit. Clin Cancer Res; 24(15); 3519–27. ©2018 AACR.
Plk1 Inhibition Enhances the Efficacy of BET Epigenetic Reader Blockade in Castration-Resistant Prostate Cancer
Authors: Mao Fengyi , Li Jie , Luo Qian , Wang Ruixin , Kong Yifan , Carlock Colin , Liu Zian , Elzey Bennet D. , Liu Xiaoqi 
Published: May 2018

Abstract
Polo-like kinase 1 (Plk1), a crucial regulator of cell-cycle progression, is overexpressed in multiple types of cancers and has been proven to be a potent and promising target for cancer treatment. In case of prostate cancer, we once showed that antineoplastic activity of Plk1 inhibitor is largely due to inhibition of androgen receptor (AR) signaling. However, we also discovered that Plk1 inhibition causes activation of the β-catenin pathway and increased expression of c-MYC, eventually resulting in resistance to Plk1 inhibition. JQ1, a selective small-molecule inhibitor targeting the amino-terminal bromodomains of BRD4, has been shown to dramatically inhibit c-MYC expression and AR signaling, exhibiting antiproliferative effects in a range of cancers. Because c-MYC and AR signaling are essential for prostate cancer initiation and progression, we aim to test whether targeting Plk1 and BRD4 at the same time is an effective approach to treat prostate cancer. Herein, we show that a combination of Plk1 inhibitor GSK461364A and BRD4 inhibitor JQ1 had a strong synergistic effect on castration-resistant prostate cancer (CRPC) cell lines, as well as in CRPC xenograft tumors. Mechanistically, the synergistic effect is likely due to two reasons: (i) Plk1 inhibition results in the accumulation of β-catenin in the nucleus, thus elevation of c-MYC expression, whereas JQ1 treatment directly suppresses c-MYC transcription; (ii) Plk1 and BRD4 dual inhibition acts synergistically in inhibition of AR signaling. Mol Cancer Ther; 17(7); 1554–65. ©2018 AACR.
Nuclear Receptor CAR Suppresses GADD45B-p38 MAPK Signaling to Promote Phenobarbital-induced Proliferation in Mouse Liver
Authors: Hori Takeshi , Saito Kosuke , Moore Rick , Flake Gordon P. , Negishi Masahiko 
Published: May 2018

Abstract
Phenobarbital, a nongenotoxic hepatocarcinogen, induces hepatic proliferation and promotes development of hepatocellular carcinoma (HCC) in rodents. Nuclear receptor constitutive active/androstane receptor (NR1I3/CAR) regulates the induction and promotion activities of phenobarbital. Here, it is demonstrated that phenobarbital treatment results in dephosphorylation of a tumor suppressor p38 MAPK in the liver of C57BL/6 and C3H/HeNCrlBR mice. The molecular mechanism entails CAR binding and inhibition of the growth arrest and DNA-damage-inducible 45 beta (GADD45B)-MAPK kinase 6 (MKK6) scaffold to repress phosphorylation of p38 MAPK. Phenobarbital-induced hepatocyte proliferation, as determined by BrdUrd incorporation, was significantly reduced in both male and female livers of GADD45B knockout (KO) mice compared with the wild-type mice. The phenobarbital-induced proliferation continued until 48 hours after phenobarbital injection in only the C57BL/6 males, but neither in males of GADD45B KO mice nor in females of C57BL/6 and GADD45B KO mice. Thus, these data reveal nuclear receptor CAR interacts with GADD45B to repress p38 MAPK signaling and elicit hepatocyte proliferation in male mice.
Implications: This GADD45B-regulated male-predominant proliferation can be expanded as a phenobarbital promotion signal of HCC development in future studies.
Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/8/1309/F1.large.jpg. Mol Cancer Res; 16(8); 1309–18. ©2018 AACR.
Risk Factor Burden, Heart Failure, and Survival in Women of Different Ethnic Groups
Authors: Breathett Khadijah , Leng Iris , Foraker Randi E. , Abraham William T. , Coker Laura , Whitfield Keith E. , Shumaker Sally , Manson JoAnn E. , Eaton Charles B. , Howard Barbara V. , Ijioma Nkechinyere , Cené Crystal W. , Martin Lisa W. , Johnson Karen C. , Klein Liviu , Rossouw Jacques , Ludlam Shari , Burwen Dale , McGowan Joan , Ford Leslie , Geller Nancy , Anderson Garnet , Prentice Ross , LaCroix Andrea , Kooperberg Charles , Stefanick Marcia L. , Jackson Rebecca , Thomson Cynthia A. , Wactawski-Wende Jean , Limacher Marian , Wallace Robert , Kuller Lewis 
Published: May 2018

Background:
The higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups.

Methods and Results:

In the WHI (Women’s Health Initiative; 1993–2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased (
P
<0.0001, interaction of race/ethnicity and RF number
P
=0.18)—African-Americans 1 RF: 1.80 (1.01–3.20), 2 RFs: 3.19 (1.84–5.54), 3+ RFs: 7.31 (4.26–12.56); Whites 1 RF: 1.27 (1.04–1.54), 2 RFs: 1.95 (1.60–2.36), 3+ RFs: 4.07 (3.36–4.93); Hispanics 1 RF: 1.72 (0.68–4.34), 2 RFs: 3.87 (1.60–9.37), 3+ RFs: 8.80 (3.62–21.42). Risk of death before developing HF increased with subsequent RFs (
P
<0.0001) but differed by racial/ethnic group (interaction
P
=0.001). The number of RFs was not associated with the risk of death after developing HF in any group (
P
=0.25; interaction
P
=0.48).

Conclusions:
Among diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups.
Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy
Authors: Pradhan Aruna D. , Aday Aaron W. , Rose Lynda M. , Ridker Paul M 
Published: May 2018

Background:
The combination of statin therapy and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition markedly lowers low-density lipoprotein cholesterol (LDL-C) and reduces cardiovascular event rates. Whether residual inflammatory risk as measured by on-treatment high sensitivity C-reactive protein (hsCRP) remains an important clinical issue in such patients is uncertain.

Methods:

We evaluated residual inflammatory risk among 9738 patients participating in the SPIRE-1 and SPIRE-2 cardiovascular outcomes trials (Studies of PCSK9 Inhibition and the Reduction in Vascular Events), who were receiving both statin therapy and bococizumab, according to on-treatment levels of hsCRP (hsCRP
OT
) and LDL-C
OT
measured 14 weeks after drug initiation. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death.

Results:

At 14 weeks, the mean percentage change in LDL-C among statin-treated patients who additionally received bococizumab was −60.5% (95% confidence interval [CI], −61.2 to −59.8;
P
<0.001; median change, −65.4%) as compared to 6.6% (95% CI, −1.0 to 14.1;
P
=0.09; median change, 0.0%) for hsCRP. Incidence rates for future cardiovascular events for patients treated with both statin therapy and bococizumab according to hsCRP
OT
<1, 1 to 3, and >3 mg/L were 1.96, 2.50, and 3.59 events per 100 person-years, respectively, corresponding to multivariable adjusted hazard ratios of 1.0, 1.16 (95% CI, 0.81–1.66), and 1.62 (95% CI, 1.14–2.30) (
P
-trend=0.001) after adjustment for traditional cardiovascular risk factors and LDL-C
OT
. Comparable adjusted hazard ratios for LDL-C
OT
(<30, 30–50, >50 mg/dL) were 1.0, 0.87, and 1.21, respectively (
P
-trend=0.16). Relative risk reductions with bococizumab were similar across hsCRP
OT
groups (
P
-interaction=0.87).

Conclusions:
In this post hoc analysis of the SPIRE trials of bococizumab in a stable outpatient population, evidence of residual inflammatory risk persisted among patients treated with both statin therapy and proprotein convertase subtilisin-kexin type 9 inhibition.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifiers: NCT01975376, NCT01975389.
Description of Tripylella jianjuni sp. n. (Nematoda: Tripylidae) from New Zealand
Authors: Xu Yumei , Leduc Daniel , Ye Weimin , Zhao Zengqi 
Published: May 2018

SummaryTripylella jianjunisp. n. (Tripylidae) is described from New Zealand. Females are characterised by a relatively long body (1743 (1675-1860)μm in the female and 1747 (1576-1979)μm in the male), outer labial setae (8-9μm long) and cephalic setae (4-5 μm long) in a single circle, two large subventral teeth in two adjacent stomatal chambers, relatively short pharynx (b = 5.5 (5.4-5.6) in the female and 5.7 (5.3-6.1) in the male), vulva located slightly anterior to mid-body (V = 44 (43-46)), protuberant lips, and long filiform tail (461 (398-531) μm, c = 3.8 (3.3-4.2) and c′ = 23.2 (18-29) in the female, and 450 (362-511)μm, c = 3.9 (3.6-4.4) and c′ = 19.0 (16.0-20.8) in the male), tail with three ventromedian caudal setae. Males have arcuate spicules 37 (35-41) μm long, gubernaculum straight, 14 (12-16) μm long, three ventromedian supplementary papillae located anterior to the cloacal aperture, and a single plus four pairs of subventral caudal setae located posterior to the cloacal aperture on the tail. Preliminary analyses of phylogenetic relationships within the Triplonchida were done using the SSU and D2-D3 region of LSU DNA sequences.
Lethal Violence, the Lack of Resonance and the Challenge of Forgiveness in Brazil
Authors: von Sinner Rudolf , Westphal Euler Renato 
Published: May 2018

Abstract
According to recent data there has been a considerable increase in lethal violence in Brazil as well as evidence of a growing brutality. Such data bears witness to the wide perception of impunity and the apparent commonality, even an acceptance of killing. The general political and economic insecurity reinforces a sense of abandonment among the population. The affluent hire private security services. The poor, with no alternative option, become victims of crime and drug trafficking wars. The police are often a part of organized crime rather than combatting such. They are understaffed and underequipped. The prison system is unfit to promote resocialization. What can the churches, theology and the state do to establish and foster justice worthy of the name? The purpose of this article is to analyse the situation in Brazil, referring to acclaimed interpreters as historian Sérgio Buarque de Holanda, to ponder possible reasons for violence using the sociological theory of resonance by Hartmut Rosa, and to reflect on a theology of justice that, rather than revenge, emphasises transformation, forgiveness and reconciliation. Through reference to Jürgen Moltmann, it seeks to show how a public theology can contribute to such transformation.
Democracy and Climate Justice: Public Theology in the Anthropocene
Authors: Fretheim Kjetil 
Published: May 2018

Abstract
Although controversial, the concept of the Anthropocene has gained prominence in the scholarly and political discourse on climate change, its effects and implications. This article presents key characteristics and dimensions of the Anthropocene with an emphasis on Bruno Latour’s interpretation and analysis of the term. This provides the background for a discussion of how religious actors and Christian theology have conceptualized climate change and the implications of the Anthropocene for public theology. I focus in particular on the interdisciplinary and normative dimensions of the field. The main argument is that public theology should acknowledge the conflicting interests and agendas in the climate change debate and promote democratic participation. I also highlight some of the implications of the Anthropocene to public theology in terms of the social analysis, politics and ethics, as well as language and voice used when participating in such debates. I conclude by arguing that public theology can give a unique contribution to climate justice by offering perspectives and insights from Christian narratives and imaginaries.
Race Rescue
Authors: Eves Richard 
Published: May 2018

Abstract
This paper examines Methodist missionary discourse in Papua at the turn of the nineteenth century, locating two themes: what I call a pathology of desire, to be found in the polemical missionary discourses directed at sexuality, immorality and licentiousness, and a pathology of culture, to be found in their polemical discourses against abortion, infanticide and child-rearing practices. Together, these pathologies were seen as the main causes of population decline. The two discourses, constantly at play, produce a doubled image of Papuan women – the fallen woman and the bad mother – which, it was considered, necessitated the intervention of “a civilising mission.” This involved race rescue – the isolation of those thought vulnerable (children and young women) on the mission station, away from the dangers of the villages, at the same time instilling in them their own notions of sexual morality, and above all the training of Papuan women in European models of motherhood and domesticity, so they would become good wives and mothers.
The Deflection of the China Coastal Current over the Taiwan Bank in Winter
Authors: Liao Enhui , Oey Lie Yauw , Yan Xiao-Hai , Li Li , Jiang Yuwu 
Published: May 2018

AbstractIn winter, an offshore flow of the coastal current can be inferred from satellite and in situ data over the western Taiwan Bank. The dynamics related to this offshore flow are examined here using observations as well as analytical and numerical models. The currents can be classified into three regimes. The downwind (i.e., southward) cold coastal current remains attached to the coast when the northeasterly wind stress is stronger than a critical value depending on the upwind (i.e., northward) large-scale pressure gradient force. By contrast, an upwind warm current appears over the Taiwan Bank when the wind stress is less than the critical pressure gradient force. The downwind coastal current and upwind current converge and the coastal current deflects offshore onto the bank during a moderate wind. Analysis of the vorticity balance shows that the offshore transport is a result of negative bottom stress curl that is triggered by the positive vorticity of the two opposite flows. The negative bottom stress curl is reinforced by the gentle slope over the bank, which enhances the offshore current. Composite analyses using satellite observations show cool waters with high chlorophyll in the offshore current under moderate wind. The results of composite analyses support the model findings and may explain the high productivity over the western bank in winter.