bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A12: The immune composition of a spontaneous mouse breast cancer
Authors: Velica Pedro , Rundqvist Helene , Gojkovic Milos , Johnson Randall S.
Published: October 2016

The MMTV-PyMT mouse strain is a widely used model for the study of breast cancer. In this strain, the mouse mammary tumor virus (MMTV) promoter drives expression of the polyoma middle T (PyMT) oncogene in breast epithelium resulting in widespread transformation of the tissue and formation of progressive tumors that eventually metastasize to the lungs and lymph nodes, closely recapitulating the human disease.

It is know that MMTV-PyMT tumors are infiltrated by large numbers of immune cells and the role of some immune populations in cancer progression and metastasis has been described. However a detailed characterization of the myeloid and lymphoid populations infiltrating MMTV-PyMT during tumor progression is yet to be performed.

In this study we used comprehensive flow cytometry panels to enumerate and quantify B cells, αβ T cells (CD4 and CD8), γδ T cells, NK T cells, NK cells, neutrophils, monocytes, dendritic cells and macrophages within MMTV-PyMT tumors in different stages of progression. Given that hypoxia is a prominent aspect of breast cancer we extended this characterization to strains with targeted deletion of hypoxia-inducible factor (HIF) 1α and HIF2α in myeloid cells.

We found lymphoid cells to be the predominant immune populations within PyMT tumors particularly B cells and αβ T cells (CD4+ and CD8+) but their frequencies did not markedly change with progression or tumor mass. Surprisingly the majority of CD8 T cells expressed the NK cell marker NK1.1 (>80%).

In addition we found dendritic cells (CD11chigh, MHC IIhigh) to be the prevalent myeloid population and that the frequency of this population had a strong positive correlation with tumor mass.

Myeloid deletion of HIF1a, but not HIF2a, resulted in increased tumor mass and dendritic cell infiltration while other immune population frequencies remained unchanged.

Whether dendritic cells directly affect tumor growth and to what extent HIF1α is involved in this process remains to be elucidated. We expect that this immune characterization of PyMT tumors will serve as a reference for future breast cancer immunology studies and possibly assist in the development of new immunotherapies.

Citation Format: Pedro Velica, Helene Rundqvist, Milos Gojkovic, Randall S. Johnson. The immune composition of a spontaneous mouse breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A12.
Abstract B05: N-Myc downstream regulated gene 2 is a novel regulator of lipid metabolism and ubiquitin-proteasome system in cancer
Authors: Yao Libo , Li Xia , Liu Xiping , Ru Yi , Zhang Mei
Published: October 2016

Background and Aims: Oncogene activation and tumor suppressor gene inactivation alter multiple intracellular signaling pathways that affect metabolism of cancer cells. NDRG2 (N-Myc downstream regulated gene 2) is a newly identified tumor suppressor gene in our lab and others. We reported previously that NDRG2 functions as an essential regulator in glycolysis and glutaminolysis via repression of c-MYC, and acts as a suppressor of carcinogenesis through coordinately targeting glucose and glutamine transporter, multiple catalytic enzymes involved in glycolysis and glutaminolysis, which fuels the bioenergy and biomaterials needed for cancer proliferation and progress. Our recent studies showed that NDRG2 is involved in cell apoptosis or survival when the cells are challenged by various stress factors such as hypoxia and lipotoxicity. However, whether NDRG2 is implicated in lipid metabolism and other cellular process is unknown.

Methods: We explored the role of NDRG2 in lipid metabolism by using Oil red staining of the liver tissues from Ndrg2 mouse v.s. wild-type counterpart. We also examined the effect of Ndrg2 on the transcription of the proteasome subunits by RT-PCR, its effect on the proteasome activity by protease activity assay, as well as Nrf1 relevance in such regulation, through using the liver tissues of mouse and NDRG2-overxepressing HepG2 cells.

Results: Ndrg2 mice exhibited lipid accumulation in liver compared with the wild-type counterpart. Besides, the proteasome genes transcription were upregulated in Ndrg2 liver tissue but downregulated in NDRG2-overexpressing HepG2 cells. Moreover, NDRG2-overexpression suppressed the proteasome activity in HepG2 cells. Such effect is comparable to, but not additive with, siRNA-mediated silence of Nrf1, a well-known proteasome regulator that coordinately induces proteasome gene transcription. This implies that NDRG2 exerts its role by inhibiting Nrf1. Finally, we demonstrated that NDRG2 interacts with Nrf1 and promotes its downregulation.

Conclusion: We demonstrated for the first time that NDRG2 is a critical regulator of lipid metabolism and proteasome activity. NDRG2 inhibits the proteasome activity probably by interacting with Nrf1 and promoting its downregulation.

Note: This abstract was not presented at the conference.

Citation Format: Libo Yao, Xia Li, Xiping Liu, Yi Ru, Mei Zhang. N-Myc downstream regulated gene 2 is a novel regulator of lipid metabolism and ubiquitin-proteasome system in cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B05.
Abstract B14: Discoidin domain receptor 1 activity drives an aggressive phenotype in gastric adenocarcinoma
Authors: Hur Hoon , Ham In-hye , Lee Da Keun , Jin Hye-Jin , Y Aguilera Kristina , Oh Hae Jeong , Han Sang-Uk , Kwon Ji-Eun , Kim Young Bae , Ding Ke , Brekken Rolf
Published: October 2016

Purpose: Stromal content in gastric cancer patients inversely correlates with outcome. However, underlying molecular mechanisms for these clinical observations have not been determined. Here, we investigated the contribution of the collagen receptor, discoidin domain receptor-1 (DDR1), in the aggressive phenotype of gastric cancer induced by tumor stroma.

Experimental Design: We conducted immunohistochemical analyses with a tissue microarray of 217 gastric cancer specimens. We examined the effect of collagen-induced activation of DDR1 on cell signaling, tumorigenesis and cell migration in gastric cancer, and evaluated the effects of DDR1 inhibition in organotypic culture and xenograft animal models of gastric cancer.

Results: High DDR1 expression in gastric cancer tissue significantly correlated with poor prognosis. Gastric cancer patients were classified into two groups based on the stromal collagen and the expression of DDR1 was significantly associated with cancer invasion and lymph node metastasis in the collagen-positive group. Decreased expression of E-cadherin was associated with cancer progression in the collagen and DDR1 positive groups. We also demonstrated that collagen activated DDR1 and increased clonogenicity and cell migration. Importantly, we demonstrated that a DDR1 inhibitor, 7rh benzamide, reduced the invasiveness of gastric cancer in organotypic culture system and suppressed tumor growth in gastric cancer xenografts.

Conclusions: Taken together, these findings suggest that collagen enhances the aggressive phenotype of gastric cancer through the DDR1 signaling pathway and that inhibition of DDR1 is an attractive candidate for the therapy of aggressive gastric cancer.

Citation Format: Hoon Hur, In-hye Ham, Da Keun Lee, Hye-Jin Jin, Aguilera Kristina Y., Hae Jeong Oh, Sang-Uk Han, Ji-Eun Kwon, Young Bae Kim, Ke Ding, Rolf Brekken. Discoidin domain receptor 1 activity drives an aggressive phenotype in gastric adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B14.
Abstract B30: Discovery and functional characterization of novel anti-PD-1 antibodies using ex vivo cell-based assays, single-cell immunoprofiling, and in vivo studies in humanized mice
Authors: Scheuplein Felix , Ranganath Sheila , McQuade Thomas , Wang Lei , Spaulding Vikki , Vadde Sri , Watkins-Yoon Jennifer , Feng Bin , Mehta Shanu , Chiu Maria Isabel , Nguyen Cokey
Published: October 2016

Given recent approvals of anti-PD-1 inhibitors Keytruda (pembrolizumab) and Opdivo (nivolumab) for treatment of metastatic melanoma and non-small cell lung cancer NSCLC, we asked whether additional anti-PD-1 inhibitors with different epitopes or potentially differentiated mechanisms of action can provide clinical benefit beyond the two marketed therapies.

Using Enumeral's proprietary single cell technology, we generated more than 300 anti-PD-1 monoclonal antibodies from primary B cells. Bioinformatics analysis of sequences show these antibodies comprise 26 distinct clades, or families, that bind to PD-1. Results from binding studies further indicate we have discovered a family of novel antibodies that do not appear to compete with currently marketed antibodies for binding to PD-1, nor do they appear to compete with PD-L1, suggesting a differentiated mechanism of action. We have humanized two lead antibodies for preclinical testing and in preparation for clinical studies.

Here we describe functional characterization of the two lead antibodies using cell-based ex vivo assays, patient-derived tumor profiling assays using our single-cell platform, and in vivo studies in humanized NSG mice. Results show that the two lead anti-PD-1 antibodies exhibit a higher level of T cell activation in mixed lymphocyte reaction (MLR) assays using primary human immune cells. Second, these antibodies also demonstrated dose-dependent increases in T cell CD25 expression. Next, to test the effect of the two lead anti-PD-1 antibodies on tumor growth, we are conducting a study using a patient-derived tumor (PDX) model on humanized NSG mice. NSG mice reconstitute a full human immune system including a functional T, B cell repertoire, enabling the direct, in vivo evaluation of our human anti-PD-1 antibodies. Effects of drug treatment on tumor growth, transcriptome (RNA seq) and protein expression (IHC) will be described. Finally, results from ex vivo tumor profiling comparing the immmunomodulatory effects of our anti-PD-1 antibodies on tumor-infiltrating lymphocyte function will also be presented.

Citation Format: Felix Scheuplein, Sheila Ranganath, Thomas McQuade, Lei Wang, Vikki Spaulding, Sri Vadde, Jennifer Watkins-Yoon, Bin Feng, Shanu Mehta, Maria Isabel Chiu, Cokey Nguyen. Discovery and functional characterization of novel anti-PD-1 antibodies using ex vivo cell-based assays, single-cell immunoprofiling, and in vivo studies in humanized mice. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B30.
Abstract C10: The role of FIH in macrophage function
Authors: Gojkovic Milos , Rundqvist Helene , Veliça Pedro , Johnson Randall S.
Published: October 2016

The cells of the immune system have to be able to exert its functions in areas of low oxygen tension. In macrophages, functions such as phagocytosis, migration and antigen presentation has been shown to be partly dependent on the hypoxia sensitive transcription factor HIF-1 activation. Previous studies on tissue specific deletion of HIF-1 in macrophages showed decreased infiltration, activation and bacterial killing, as well as decreased cancer progression and growth in the MMTV-PyMT mouse model of breast cancer. However, the effects of increased HIF-1 expression and activity in macrophages are not fully understood. In light of the current literature, we hypothesize that increased activity of HIF-1 may lead to enhanced immunological activity in macrophages. When we knock down FIH (a hydroxylase that inhibits HIF-1 activity) in Raw cells, migration towards a PyMT derived tumor cell line increases. FIH knock down macrophages was characterized by increased MHC Class II surface expression and improved phagocytosis under normoxic conditions, however the difference between knock down FIH and wild type macrophages are less in hypoxic conditions, indicating that the enhanced immunological function may depend on increased HIF-1 activity.

Future work includes the use of a conditional cre-loxP knockout mouse, with cre expression driven by the myeloid specific promoter for LysM, knocking out either VHL (a negative regulator of HIF stability) or FIH. These mice will also be used to investigate the role of constitutively active myeloid HIF-1 in tumor progression.

Citation Format: Milos Gojkovic, Helene Rundqvist, Pedro Veliça, Randall S. Johnson. The role of FIH in macrophage function. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C10.
Abstract C28: Platelet-derived growth factor receptor-β (PDGFRβ) in the breast metastatic tumor microenvironment
Authors: Sizemore Gina , Mathur Anisha , Thies Katie , Bolyard Chelsea , Sizemore Steven , Kladney Raleigh , Trimboli Anthony , Kaur Balveen , Leone Gustavo , Ostrowski Michael
Published: October 2016

A role for the tumor microenvironment (TME) in cancer progression is irrefutable and our laboratory has been at the forefront of this field providing evidence for both tumor suppressive and oncogenic roles of the TME. The PDGF pathway is an exemplar for the study of tumor-stroma interaction as PDGF receptors (PDGFR) are frequently expressed in the fibroblasts and pericytes within the tumor-associated stroma of epithelial tumors including breast cancer. In contrast, PDGF ligands are expressed by the epithelial tumor cells themselves. However, beyond a few descriptive studies, the role of interactive PDGFRβ signaling in the TME during breast cancer initiation, progression and metastases is not understood. This can be attributed in part to limited in vivo models to study the complex TME, especially for breast cancer associated metastases. To overcome this limitation, we have established a transgenic knock-in mouse model that expresses constitutively active PDGFRβ in the stroma of the mammary gland as well in the lung and the brain, two common sites of metastatic breast cancer dissemination. We have found that these mice develop mammary gland hyperplasia highlighting the importance of PDGFRβ in the TME in driving mammary epithelial cell growth. To test whether activation of mutant PDGFRβ in either the lung or the brain increases metastatic growth at either site, two experimental metastases assays were performed: (1) tail vein and (2) intracranial injections to test for lung and brain metastatic outgrowth, respectively. Tail vein injection of the non-metastatic murine mammary cancer cell line DB7 cells led to pronounced lung metastases in PDGFRβ knock-in mice in less than 4 weeks. No macrometastases were seen in the control at this same time point. Similar to the surge in lung metastasis, intracranial injection of DB7 cells led to an increase in tumor growth in brains of the mutant versus wild type controls, revealing an important role for PDGFRβ signaling in the breast cancer metastatic microenvironment. In addition, knockdown of PDGF-B in mammary cancer cells represses intracranial growth in wild type animals. Combined these data support a role for PDGFRβ signaling in the breast cancer metastatic microenvironment. Ongoing investigation is aimed to delineate how activated PDGF-B to PDGFRβ signaling primes the metastatic niche.

Citation Format: Gina Sizemore, Anisha Mathur, Katie Thies, Chelsea Bolyard, Steven Sizemore, Raleigh Kladney, Anthony Trimboli, Balveen Kaur, Gustavo Leone, Michael Ostrowski. Platelet-derived growth factor receptor-β (PDGFRβ) in the breast metastatic tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C28.
Abstract IA03: Fibroblast heterogeneity in skin tumour stroma
Authors: Watt Fiona M.
Published: October 2016

The fibroblasts of mouse skin connective tissue arise from two distinct lineages during embryonic development. One forms the upper dermis, including the dermal papilla, dermal sheath and arrector pili muscle, and is required for hair follicle formation. The other forms the lower dermis, including the reticular fibroblasts that synthesize the bulk of the fibrillar ECM, and the skin adipocyte layer. The lower dermal lineage is responsible for the first phase wound repair. We have been investigating the changes in the composition of adult mouse dermis when epidermal tumors arise through oncogenic beta-catenin activation. Our studies highlight the contribution of different fibroblast subpopulations to the stroma of skin tumors.

Citation Format: Fiona M. Watt. Fibroblast heterogeneity in skin tumour stroma. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA03.
Abstract IA12: Stromal cells in the targeting and transport of tumor-penetrating peptides
Authors: Ruoslahti Erkki , Ruoslahti Erkki
Published: October 2016

This laboratory studies tissue-specific vascular markers, “vascular zip codes”, and their use in selective targeting of drugs to diseased tissues. Screening of phage libraries in live mice identifies peptides that direct phage homing to a specific target in the body. When the libraries are injected into the circulation, tissue-specific or tumor-specific differences in endothelial cells are primarily targeted. The endothelial target molecules are frequently also expressed by other tumor stromal cells and tumor cells, but not cells in normal tissues. Recently discovered tumor-penetrating peptides, through a complex mechanism that involves a proteolytic cleavage and binding to a second receptor, activate an endocytic transport pathway related to but distinct from macropinocytosis. This trans-tissue pathway, dubbed the CendR pathway, mediates the exit of payloads ranging from small molecule drugs to nanoparticles from the blood vessels and transport through extravascular tumor tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a drug, antibody, or nanoparticle payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Remarkably the payload does not have to be coupled to the peptide; the peptide activates a bulk transport system that sweeps along any compound that is present in the blood. Treatment studies in mice show improved anti-tumor efficacy and less damage to normal tissues.

Citation Format: Erkki Ruoslahti, Erkki Ruoslahti. Stromal cells in the targeting and transport of tumor-penetrating peptides. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA12.
Abstract IA19: Microenvironmental regulation of breast cancer invasion, dissemination, and lung colonization
Authors: Ewald Andrew J.
Published: October 2016

The majority of cancer deaths are associated with the metastasis of epithelial tumors. This clinical reality presents an interesting conceptual puzzle: homeostatic epithelial cells are tightly adherent to each other and exhibit comparatively modest levels of proliferation and motility. Conversely, metastatic cancer cells must escape from the primary tumor, navigate the local stroma, access the systemic circulation, evade the immune system, and survive in distant sites with molecularly distinct microenvironments. We seek to understand the molecular changes that underlie this large change in epithelial cell behavior.

To accomplish this goal, we first developed a series of 3D organotypic assays to elucidate the specific molecular changes downstream of expression of genes associated with metastatic cell behaviors, such as Twist1. We found that Twist1 expression is sufficient to induce mammary cells to disseminate but, surprisingly, its major effectors are proteins that constitute, interpret, or modify the extracellular compartment. We further demonstrated that Twist1 induced dissemination occurs in the presence of membrane localized adherens junction components and requires E-cadherin (Shamir et al, JCB, 2014). We are currently leveraging our bioinformatic analyses to identify molecular targets that can be inhibited to block invasion and dissemination.

In addition to candidate gene approaches, we sought to identify invasion and metastasis associated genes in an unbiased fashion. We therefore developed 3D organotypic culture assays using primary and metastatic tumor tissue from mouse models and clinical breast cancer samples (n>150). We discovered a conserved molecular program expressed in the most invasive breast cancer cells across molecular subtypes (Cheung et al, Cell, 2013). We next used lineage analysis in vivo to demonstrate that the majority of metastases in the MMTV-PyMT mouse model are founded by multicellular groups of cancer cells. Importantly, the keratin-14+ (K14+) invasive molecular phenotype is common in invasion strands, locally disseminated cancer cells, CTC clusters, and micrometastases but rare in the macrometastases. We are now focused on understanding how the microenvironment determines the likelihood of dissemination from the primary tumor and metastatic outgrowth in distant organs.

Citation Format: Andrew J. Ewald. Microenvironmental regulation of breast cancer invasion, dissemination, and lung colonization. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA19.
Abstract IA25: Hallmark capabilities modulated by the tumor microenvironment during tumor progression and adaptive resistance to therapy
Authors: Hanahan Douglas , Hanahan Douglas
Published: October 2016

The hallmarks of cancer constitute an organizing concept that may provide a rational basis for distilling the diversity and complexity of human cancers so as to better understand mechanisms of the disease and its manifestations. The integration of these hallmark capabilities in symptomatic disease involves multiple cell types populating the tumor microenvironment, including heterogeneous populations of cancer cells, and three prominent classes of stromal support cells - angiogenic vascular cells, cancer associated fibroblasts, and infiltrating immune cells. Dynamic interactions amongst these cell types convey hallmark capabilities whose roles and functional importance vary during multi-step tumorigenesis and tumor progression, and in the context of adaptive responses to hallmark-targeting therapies, suggesting potential benefits in multi-targeting the TME. A few examples from our research program will seek to be illustrative.

Citation Format: Douglas Hanahan, Douglas Hanahan. Hallmark capabilities modulated by the tumor microenvironment during tumor progression and adaptive resistance to therapy. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA25.
Abstract PR14: Epidermal neoplasms bypass immune evasion requirements via niche occupancy
Authors: Kubick Brad , Roop Dennis
Published: October 2016

Anti-tumor immune effectors exert selective pressure against transformed clones, ultimately permitting only mutation cascades that are either non-immunogenic or include immune-evasive adaptations. This evolutionary process often includes an equilibrium phase during which immunogenic transformed cells are prevented from outgrowth by the immune system without being eliminated. In most cases, escape from this state requires loss of antigen presentation and consequent loss of immunogenicity. To characterize this pre-outgrowth phase of cancer-immune interaction and test the efficacy of interventions during dormancy, we assembled a genetically-engineered mouse model (GEMM) of inducible, Kras-driven carcinogenesis coupled to a fluorescent reporter. Early characterization of this model revealed a confounding artificial tolerance mechanism that renders inducible alleles automatically non-immunogenic in autochthonous settings. To circumvent this tolerance, we transplant dissociated epidermal keratinocytes from the GEMM onto recipient animals that do not carry the inducible mutant Kras allele. This transplant step also enables the use recipient animals carrying various immune deficiencies. After graft healing, transformation is induced and the grafts are imaged repeatedly over time via intravital confocal microscopy. In immunocompromised recipients, transformation initiates the rapid growth of labeled cells and subsequent tumor formation. In immunocompetent cohorts, tumor formation does not occur. Instead, we observe establishment of a long-term equilibrium phase characterized by cyclic growth and regression of labeled clones originating exclusively from hair follicles, suggesting that the immune privilege of this stem cell niche provides a safe harbor for transformed cells. Surprisingly, the architecture of the normal tissue defines a protected reservoir for the survival of transformed cells, a fate that usually requires cell-intrinsic immune-evasive adaptations. This provides a mechanism by which a single source of anti-tumor activity could produce the observed biphasic nature of cancer-immune interaction, including both elimination of some clones and immune-mediated dormancy of others. Most importantly, we have identified a novel pre-malignant, immune-controlled state that may represent a vulnerable target population for rational cancer prevention strategies.

Citation Format: Brad Kubick, Dennis Roop. Epidermal neoplasms bypass immune evasion requirements via niche occupancy. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr PR14.
Telenovelas e a questão da feminilidade de classe
Authors: Ronsini Veneza Mayora
Published: October 2016

This article theoretically discusses the concept of social class to understand the construction of heteronormative femininity in studies on the social uses of telenovelas. Inspired by the work of Pierre Bordieu, Latin American cultural studies, and feminist theory, I argue for the centrality of the bodily hexis in conforming a classed femininity based on the incorporation of media capital by working-class women. The analysis reveals that the automatisms of schemes of classification are powerful mechanisms of reproduction of both gender and social injustice.
A ética da mediação: aspectos da crítica da mídia em Roger Silverstone
Authors: Serelle Marcio
Published: October 2016

This is a theoretical article that aims to contribute to a debate on the concept of mediation in Roger Silverstone’s work. According to Silverstone, mediation is a multiple, transformative and asymmetrical process, which involves technological and social dimensions. Mediation is fundamental for the ways we relate to the other in everyday life and it has ethical implications. In this paper, I review some notions of authors as Raymond Williams, Martín-Barbero and Nick Couldry, which inform and/or dialogue with Silverstone’s ideas. Some key points in this discussion highlight the need for criticism based on the challenging of mediation, what demands a reflection on our relations with the media and their representational modes.
Laura Robinson: uma comunicóloga “brasileira” no exterior
Authors: Martinez Monica
Published: October 2016

Interview with the American researcher Laura Robinson, who talks about his research interests and partnerships that have established with Brazilian researchers.
Impact of Left Ventricular to Mitral Valve Ring Mismatch on Recurrent Ischemic Mitral Regurgitation After Ring Annuloplasty
Authors: Capoulade Romain , Zeng Xin , Overbey Jessica R. , Ailawadi Gorav , Alexander John H. , Ascheim Deborah , Bowdish Michael , Gelijns Annetine C. , Grayburn Paul , Kron Irving L. , Levine Robert A. , Mack Michael J. , Melnitchouk Serguei , Michler Robert E. , Mullen John C. , O’Gara Patrick , Parides Michael K. , Smith Peter , Voisine Pierre , Hung Judy
Published: October 2016

Background:

In ischemic mitral regurgitation (IMR), ring annuloplasty is associated with a significant rate of recurrent MR. Ring size is based on intertrigonal distance without consideration of left ventricular (LV) size. However, LV size is an important determinant of mitral valve (MV) leaflet tethering before and after repair. We aimed to determine whether LV-MV ring mismatch (mismatch of LV size relative to ring size) is associated with recurrent MR in patients with IMR after restrictive ring annuloplasty.

Methods:

Patients with moderate or severe IMR from the 2 Cardiothoracic Surgical Trials Network IMR trials who received MV repair were examined at 1 year after surgery. Baseline LV size was assessed by LV end-diastolic dimension and LV end-systolic dimension (LVESd). LV-MV ring mismatch was calculated as the ratio of LV to ring size (LV end-diastolic dimension/ring size and LVESd/ring size).

Results:

At 1 year after ring annuloplasty, 45 of 214 patients with MV repair (21%) had moderate or greater MR. In univariable logistic regression analysis, larger LVESd (
P
=0.02) and LVESd/ring size (
P
=0.007) were associated with recurrent MR. In multivariable models adjusted for age, sex, baseline LV ejection fraction, and severe IMR, only LVESd/ring size (odd ratio per 0.5 increase, 2.20; 95% confidence interval, 1.05–4.62;
P
=0.038) remained significantly associated with 1-year MR recurrence.

Conclusions:

LV-MV ring size mismatch is associated with increased risk of MR recurrence. This finding may be helpful in guiding choice of ring size to prevent recurrent MR in patients undergoing MV repair and in identifying patients who may benefit from MV repair with additional subvalvular intervention or MV replacement rather than repair alone.

Clinical Trial Registration:

URL:
http://clinicaltrials.gov
. Unique identifiers: NCT00806988 and NCT00807040.
Temporal Trends in Predictors of Early and Late Mortality After Emergency Coronary Artery Bypass Grafting for Cardiogenic Shock Complicating Acute Myocardial Infarction
Authors: Davierwala Piroze M. , Leontyev Sergey , Verevkin Alexander , Rastan Ardawan J. , Mohr Matthias , Bakhtiary Farhad , Misfeld Martin , Mohr Friedrich W.
Published: October 2016

Background:

Cardiogenic shock after acute myocardial infarction is an indication for emergent coronary artery bypass grafting in patients not amenable to percutaneous coronary intervention. Our study aimed to evaluate and identify risk factors for early and long-term outcomes in such patients.

Methods:

A total of 508 patients who underwent coronary artery bypass grafting for cardiogenic shock complicating acute myocardial infarction between January 2000 and June 2014 were divided into 3 time cohorts: 2000 to 2004 (n=204), 2005 to 2009 (n=166), and 2010 to 2014 (n=138). Predictors of in-hospital mortality for each time cohort and long-term mortality for all patients were identified by logistic and Cox regression analyses, respectively.

Results:

Mean age was 68.3±9.8 years. Of the 508 patients, 78.5% had 3-vessel and 47.1% had left main disease. Left ventricular function <30% was observed in 44.1% of patients, with 30.4%, 37.9%, 52.9%, and 3.1% requiring preoperative resuscitation, ventilation, intra-aortic balloon pump, and extracorporeal membrane oxygenation support, respectively. Overall in-hospital mortality was 33.7%; declined from 42.2% to 30.7% to 24.6%, respectively, for the 3 time cohorts (
P
=0.02); and was independently predicted by serum lactate >4 mmol/L (odds ratio [OR], 4.78; 95% confidence interval, 2.88–7.95;
P
<0.0001), ST-segment–elevation myocardial infarction (OR, 2.10; 95% confidence interval, 1.36–3.26;
P
=0.001), age >75 years (OR, 2.01; 95% confidence interval, 1.06–3.85;
P
=0.03), and left ventricular ejection fraction <30% (OR, 1.83; 95% confidence interval, 1.15–2.91;
P
=0.01). Cumulative survival was 42.6±2.0% and 33.4±2.0% at 5 and 10 years, respectively, and correspondingly improved to 64.3±3.0% and 49.8±3.0% in hospital survivors. Serum lactate >4 mmol/L (OR, 2.2;
P
<0.0001), incremental age (OR, 1.05;
P
<0.0001), New York Heart Association class IV (OR, 1.33;
P
=0.02), diabetes mellitus (OR, 1.39;
P
=0.005), and preoperative inotropic (OR, 2.61;
P
=0.001) and extracorporeal membrane oxygenation (OR, 1.68;
P
=0.05) support predicted late mortality.

Conclusions:

Emergency coronary artery bypass grafting in patients with acute myocardial infarction complicated by cardiogenic shock is associated with a high in-hospital mortality, which showed a significant decline with time. Hospital survivors have good long-term outcomes, which demonstrate the beneficial effect of surgical revascularization. Preoperative serum lactate >4 mmol/L is a strong predictor of both early and late mortality.
Single-Ventricle Outcomes After Neonatal Palliation of Severe Ebstein Anomaly With Modified Starnes Procedure
Authors: Kumar S. Ram , Kung Grace , Noh Nathan , Castillo Novel , Fagan Brian , Wells Winfield J. , Starnes Vaughn A.
Published: October 2016

Background:

We have previously shown that neonates in profound cardiogenic shock caused by a severe Ebstein anomaly can be successfully salvaged with fenestrated right ventricular exclusion and systemic to pulmonary shunt (modified Starnes procedure). The long-term outcome of single-ventricle management in these patients is not known.

Methods:

We retrospectively reviewed the records of patients who underwent neonatal Starnes procedure between 1989 and 2015. Patient demographics, clinical variables, and outcome data were collected.

Results:

Twenty-seven patients (13, 48% boys) underwent the Starnes procedure at 7 (5–9) days of life. All were intubated and on prostaglandin, 24 (89%) were inotrope dependent, and 22 (81%) had no antegrade flow from the right ventricle. Three patients underwent nonfenestrated right ventricular exclusion, 2 (67%) of whom died. Of the remaining 24, 3 (13%) died during the same hospitalization. The 22 neonatal survivors have been followed for 7 (6–8) years: 1 patient is awaiting a Glenn procedure; 1 died after undergoing a Glenn procedure; and the remaining 20 patients have successfully undergone Fontan completion. Their indexed pulmonary vascular resistance was 1.8 (1.2–2.3) W/m
2
, and mean pulmonary pressure was 12 (9–18) mm Hg. At last follow-up, 1 patient had died, and the remaining patients had normal left ventricular function, and all but 1 have New York Heart Association class I symptoms. Two patients have required pacemaker implantation, whereas the rest are in sinus rhythm. Survival for the entire cohort at 1, 5, and 10 years is 81±4%, 81±5%, and 76±3%, respectively, whereas for those with fenestrated right ventricular exclusion, survival at 1, 5, and 10 years is 87±2%, 87±2%, and 81±4%, respectively.

Conclusions:

Long-term single-ventricle outcomes among neonatal survivors of the modified Starnes procedure are excellent. There is reliable remodeling of the excluded right ventricle and good function of the left ventricle.
Surgical Management of Infective Endocarditis Complicated by Embolic Stroke
Authors: Yanagawa Bobby , Pettersson Gosta B. , Habib Gilbert , Ruel Marc , Saposnik Gustavo , Latter David A. , Verma Subodh
Published: October 2016

There has been an overall improvement in surgical mortality for patients with infective endocarditis (IE), presumably because of improved diagnosis and management, centered around a more aggressive early surgical approach. Surgery is currently performed in approximately half of all cases of IE. Improved survival in surgery-treated patients is correlated with a reduction in heart failure and the prevention of embolic sequelae. It is reported that between 20% and 40% of patients with IE present with stroke or other neurological conditions. It is for these IE patients that the timing of surgical intervention remains a point of considerable discussion and debate. Despite evidence of improved survival in IE patients with earlier surgical treatment, a significant proportion of patients with IE and preexisting neurological complications either undergo delayed surgery or do not have surgery at all, even when surgery is indicated and guideline endorsed. Physicians and surgeons are caught in a common conundrum where the urgency of the heart operation must be balanced against the real or perceived risks of neurological exacerbation. Recent data suggest that the risk of neurological exacerbation may be lower than previously believed. Current guidelines reflect a shift toward early surgery for such patients, but there continue to be important areas of clinical equipoise. Individualized clinical assessment is of major importance for decision making, and, as such, we emphasize the need for the functioning of an endocarditis team, including cardiac surgeons, cardiologists, infectious diseases specialists, neurologists, neurosurgeons, and interventional neuroradiologists. Here, we present 2 illustrative cases, critically review contemporary data, and offer conceptual and practical suggestions for clinicians to address this important, common, and often fatal cardiac condition.
Systematics and host plant associations of the Australian lace bug genus Nethersia (Insecta: Heteroptera: Tingidae), including the description of eighteen new species
Authors: Cassis Gerasimos , Koenig Philippe , Symonds Celia , Shofner Ryan
Published: October 2016

A systematic revision of the lace bug genusNethersiaHorváth 1925 is given including a redescription of the genus. Previously described speciesN.absimilisDrake 1944,N.haplotesDrake and Ruhoff 1962,N.maculosaHorváth 1925 andN.setosa(Hacker 1927) are redescribed. The New Caledonian speciesTingis chazeauiGuilbert (1997) is transferred toNethersia. Eighteen new species are described:N.acaciaphilasp.n.,N.apphasp.n.,N.bipannanotasp.n.,N.boorabbinensissp.n.,N.costatasp.n.,N.finlayaesp.n.,N.kimberleyensissp.n.,N.magnasp.n.,N.mareebasp.n.,N.mcquillanisp.n.,N.nigrasp.n.,N.pilbarasp.n.,N.silveiraesp.n.,N.stipulasp.n.,N.tatarnicisp.n.,N.tanamisp.n.,N.tomentosasp.n. andN.westralensissp.n.Nethersia pugnaDrake 1944 is removed from synonymy withN.maculosaHorváth and treated as a valid species. An identification key species is given which relies on colour patterning, vestiture and texture of the dorsum.Nethersia nigritarsis(Horváth, 1925) is transferred fromNethersiatoTingisand designated asincertae sedis. Phylogenetic analysis ofNethersiawas undertaken resulting in fully resolved topologies for a range of concavity constant settings (K= 2–6) under implied weights. The plant associations ofNethersiaare documented, with most species recorded from phyllodinousAcaciaspecies, with twenty designated as host plants.
Spatiotemporal Temperature Variability over the Tibetan Plateau: Altitudinal Dependence Associated with the Global Warming Hiatus
Authors: Cai Danlu , You Qinglong , Fraedrich Klaus , Guan Yanning
Published: October 2016

The recent slowdown in global warming has initiated a reanalysis of temperature data in some mountainous regions for understanding the consequences and impact that a hiatus has on the climate system. Spatiotemporal temperature variability is analyzed over the Tibetan Plateau because of its sensitivity to climate change with a station network updated to 2014, and its linkages to remote sensing–based variability of MODIS daytime and nighttime temperature are investigated. Results indicate the following: 1) Almost all stations have experienced a notable warming in the time interval 1961–2014, with most obvious warming in winter, which depends on the selected time intervals. 2) There is no clear shift from a predominant warming to a near stagnation during the most recent period (2001–present). 3) Uniform altitudinal dependence of temperature change trends could not be confirmed for all regions, time intervals, and seasons, but sometimes an altitude threshold around 3 km is apparent. 4) Most of the meteorological stations are associated with MODIS temperature warming pixels, and thus regional cooling is missing when considering only the locations of meteorological stations. In summarizing, previous studies based on station observations do not provide a complete picture for the temperature change over the Tibetan Plateau. Remote sensing–based analyses have the potential to find early signals of regional climate changes and assess the impact of global climate changes in complex regional, seasonal, and altitudinal environments.
CMIP5 Projections of Two Types of El Niño and Their Related Tropical Precipitation in the Twenty-First Century
Authors: Xu Kang , Tam Chi-Yung , Zhu Congwen , Liu Boqi , Wang Weiqiang
Published: October 2016

Future projections of the eastern-Pacific (EP) and central-Pacific (CP) types of El Niño in the twenty-first century, as well as their associated tropical circulation and precipitation variability, are investigated using historical runs and representative concentration pathway 8.5 (RCP8.5) simulations from 31 coupled models in phase 5 of the Coupled Model Intercomparison Project (CMIP5). As inferred from CMIP5 models that best capture both El Niño flavors, EP El Niño sea surface temperature (SST) variability will become weaker in the future climate, while no robust change of CP El Niño SST is found. Models also reach no consensus on the future change of relative frequency from CP to EP El Niño. However, there are robust changes in the tropical overturning circulation and precipitation associated with both types of El Niño. Under a warmer climate, magnitudes of precipitation anomalies during EP El Niño are projected to increase, presenting significant enhancement of the dry (wet) signal over the western (central–eastern) Pacific. This is consistent with an accelerated hydrological cycle in the deep tropics; hence, a “wet get wetter” picture appears under global warming, accompanied by a weakened anomalous Walker circulation. For CP El Niño, drier-than-normal conditions will be intensified over the tropical central–eastern Pacific in the future climate, with stronger anomalous sinking related to the strengthened North Pacific local Hadley cell. These results suggest that, besides the enhanced basic-state hydrological cycle over the tropics, other elements, such as the anomalous overturning circulation, might also play a role in determining the ENSO precipitation response to a warmer background climate.
Tropical Cyclones in the 7-km NASA Global Nature Run for Use in Observing System Simulation Experiments
Authors: Reale Oreste , Achuthavarier Deepthi , Fuentes Marangelly , Putman William M. , Partyka Gary
Published: October 2016

The National Aeronautics and Space Administration (NASA) nature run (NR), released for use in observing system simulation experiments (OSSEs), is a 2-yr-long global nonhydrostatic free-running simulation at a horizontal resolution of 7 km, forced by observed sea surface temperatures (SSTs) and sea ice, and inclusive of interactive aerosols and trace gases. This article evaluates the NR with respect to tropical cyclone (TC) activity. It is emphasized that to serve as an NR, a long-term simulation must be able to produce realistic TCs, which arise out of realistic large-scale forcings. The presence in the NR of the relevant dynamical features over the African monsoon region and the tropical Atlantic is confirmed, along with realistic African easterly wave activity. The NR Atlantic TC seasons, produced with 2005 and 2006 SSTs, show interannual variability consistent with observations, with much stronger activity in 2005. An investigation of TC activity over all the other basins (eastern and western North Pacific Ocean, north and south Indian Ocean, and Australian region), together with important elements of the atmospheric circulation, such as the Somali jet and westerly bursts, reveals that the model captures the fundamental aspects of TC seasons in every basin, producing a realistic number of TCs with realistic tracks, life spans, and structures. This confirms that the NASA NR is a very suitable tool for OSSEs targeting TCs and represents an improvement with respect to previous long simulations that have served the global atmospheric OSSE community.
A Multiscale Reexamination of the Pacific–South American Pattern
Authors: O’Kane Terence J. , Monselesan Didier P. , Risbey James S.
Published: October 2016

The authors undertake a multiscale spectral reexamination of the variability of the Pacific–South American (PSA) pattern and the mechanisms by which this variability occurs. Time scales from synoptic to interannual are investigated, focusing on the means by which tropical variability is communicated to the midlatitudes and on in situ forcing within the midlatitude waveguides. Particular interest is paid to what fraction of the total variability associated with the PSA, occurring on interannual time scales, is attributable to tropical forcing relative to that occurring on synoptic and intraseasonal time scales via internal waveguide dynamics. In general, it is found that the eastward-propagating wave train pattern typically associated with the PSA manifests across time scales from synoptic to interannual, with the majority of the variability occurring on synoptic-to-intraseasonal time scales largely independent of tropical convection. It is found that the small fraction of the total variance with a tropical signal occurs via the zonal component of the thermal wind modulating both the subtropical and polar jets. The respective roles of the Hadley circulation and stationary Rossby wave sources are also examined. Further, a PSA-like mode is identified in terms of the slow components of higher-order modes of tropospheric geopotential height. This study reestablishes the multiscale nonlinear nature of the PSA modes arising largely as a manifestation of internal midlatitude waveguide dynamics and local disturbances.
Introduction to the Special Issue on Urban Teacher Residencies
Authors: Hammerness Karen , Williamson Peter , Kosnick Clare
Published: October 2016

Despite the rapid expansion of and investment in urban residency programs, a key tenet of the residency model—that they prepare teachers for targeted urban settings—remains largely unexamined. Although some might argue that a “good teacher” can transcend contexts—we ask in this issue whether there may be particular features of the setting or context that are important for new teachers to learn about. In the papers in our special issue, the authors examine more closely what kind of preparation may be necessary for specific contexts. This themed issue features scholarship that examines efforts to prepare teachers for clinical practice in particular contexts. The articles share evidence from three residency programs (each engaged in systematic data collection) on opposite sides of the US to point to features of the context that may matter for teaching; the design of opportunities to learn in these programs; and data that sheds light upon these questions. Given recent findings about the strong retention of graduates of ‘context-specific programs’ these examinations not only provide insight into the promise of urban residency programs but also serve as a call for programs to be epecially clear about the specific features of the setting that may matter for teaching.