bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer Incidence in Appalachia, 2004–2011
Authors: Wilson Reda J. , Ryerson A. Blythe , Singh Simple D. , King Jessica B. 
Published: January 2016

Abstract
Background: Limited literature is available about cancer in the Appalachian Region. This is the only known analysis of all cancers for Appalachia and non-Appalachia covering 100% of the US population. Appalachian cancer incidence and trends were evaluated by state, sex, and race and compared with those found in non-Appalachian regions.
Methods: US counties were identified as Appalachian or non-Appalachian. Age-adjusted cancer incidence rates, standard errors, and confidence intervals were calculated using the most recent data from the United States Cancer Statistics for 2004 to 2011.
Results: Generally, Appalachia carries a higher cancer burden compared with non-Appalachia, particularly for tobacco-related cancers. For all cancer sites combined, Appalachia has higher rates regardless of sex, race, or region. The Appalachia and non-Appalachia cancer incidence gap has narrowed, with the exception of oral cavity and pharynx, larynx, lung and bronchus, and thyroid cancers.
Conclusions: Higher cancer incidence continues in Appalachia and appears at least in part to reflect high tobacco use and potential differences in socioeconomic status, other risk factors, patient health care utilization, or provider practices. It is important to continue to evaluate this population to monitor results from screening and early detection programs, understand behavioral risk factors related to cancer incidence, increase efforts to reduce tobacco use and increase cancer screening, and identify other areas where effective interventions may mediate disparities.
Impact: Surveillance and evaluation of special populations provide means to monitor screening and early detection programs, understand behavioral risk factors, and increase efforts to reduce tobacco use to mediate disparities. Cancer Epidemiol Biomarkers Prev; 25(2); 250–8. ©2016 AACR.
Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration
Authors: Ock Chan-Young , Keam Bhumsuk , Kim Sehui , Lee Ju-Seog , Kim Miso , Kim Tae Min , Jeon Yoon Kyung , Kim Dong-Wan , Chung Doo Hyun , Heo Dae Seog 
Published: January 2016

Abstract
Purpose: There is currently no reliable biomarker to predict who would benefit from anti-PD-1/PD-L1 inhibitors. We comprehensively analyzed the immunogenomic properties in The Cancer Genome Atlas (TCGA) according to the classification of tumor into four groups based on PD-L1 status and tumor-infiltrating lymphocyte recruitment (TIL), a combination that has been suggested to be a theoretically reliable biomarker of anti-PD-1/PD-L1 inhibitors.
Experimental Design: The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (N = 9,677) were analyzed. Based on their median values, the samples were classified into four tumor microenvironment immune types (TMIT). The mutational profiles, PD-L1 amplification, and viral association of the samples were compared according to the four TMITs.
Results: The proportions of TMIT I, defined by high PD-L1 and CD8A expression, were high in lung adenocarcinoma (67.1%) and kidney clear cell carcinoma (64.8%) among solid cancers. The number of somatic mutations and the proportion of microsatellite instable-high tumor in TMIT I were significantly higher than those in other TMITs, respectively (P &lt; 0.001). PD-L1 amplification and oncogenic virus infection were significantly associated with TMIT I, respectively (P &lt; 0.001). A multivariate analysis confirmed that the number of somatic mutations, PD-L1 amplification, and Epstein–Barr virus/human papillomavirus infection were independently associated with TMIT I.
Conclusions: TMIT I is associated with a high mutational burden, PD-L1 amplification, and oncogenic viral infection. This integrative analysis highlights the importance of the assessment of both PD-L1 expression and TIL recruitment to predict responders to immune checkpoint inhibitors. Clin Cancer Res; 22(9); 2261–70. ©2016 AACR.
See related commentary by Schalper et al., p. 2102
Synergistic COX2 Induction by IFNγ and TNFα Self-Limits Type-1 Immunity in the Human Tumor Microenvironment
Authors: Wong Jeffrey L. , Obermajer Nataša , Odunsi Kunle , Edwards Robert P. , Kalinski Pawel 
Published: January 2016

Abstract
Maintenance of CTL-, Th1-, and NK cell–mediated type-1 immunity is essential for effective antitumor responses. Unexpectedly, we observed that the critical soluble mediators of type-1 immune effector cells, IFNγ and TNFα, synergize in the induction of cyclooxygenase 2 (COX2), the key enzyme in prostaglandin (PG)E2 synthesis, and the subsequent hyperactivation of myeloid-derived suppressor cells (MDSC) within the tumor microenvironment (TME) of ovarian cancer patients. MDSC hyperactivation by type-1 immunity and the resultant overexpression of indoleamine 2,3-dioxygenase (IDO), inducible nitric oxide synthase (iNOS/NOS2), IL10, and additional COX2 result in strong feedback suppression of type-1 immune responses. This paradoxical immune suppression driven by type-1 immune cell activation was found to depend on the synergistic action of IFNγ and TNFα, and could not be reproduced by either of these factors alone. Importantly, from a therapeutic standpoint, these negative feedback limiting type-1 responses could be eliminated by COX2 blockade, allowing amplification of type-1 immunity in the ovarian cancer TME. Our data demonstrate a new mechanism underlying the self-limiting nature of type-1 immunity in the human TME, driven by the synergistic induction of COX2 by IFNγ and TNFα, and provide a rationale for targeting the COX2–PGE2 axis to enhance the effectiveness of cancer immunotherapies. Cancer Immunol Res; 4(4); 303–11. ©2016 AACR.
The class I phosphoinositide 3-kinases α and β control antiphospholipid antibodies-induced platelet activation
Authors: Laurent Pierre-Alexandre , Garcia Cédric , Gratacap Marie-Pierre , Vanhaesebroeck Bart , Sié Pierre , Payrastre Bernard , Terrisse Anne-Dominique 
Published: January 2016

SummaryAntiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL) associated with increased thrombotic risk and pregnancy morbidity. Although aPL are heterogeneous auto-antibodies, the major pathogenic target is the plasma protein β2-glycoprotein 1. The molecular mechanisms of platelet activation by aPL remain poorly understood. Here, we explored the role of the class IA phosphoinositide 3-kinase (PI3K) α and β isoforms in platelet activation by aPL. Compared to control IgG from healthy individuals, the IgG fraction isolated from patients with APS potentiates platelet aggregation induced by low dose of thrombin in vitro and increases platelet adhesion and thrombus growth on a collagen matrix under arterial shear rate through a mechanism involving glycoprotein Ib (GPIb) and Toll Like Receptor 2 (TLR-2). Using isoforms-selective pharmacological PI3K inhibitors and mice with megakaryocyte/platelet lineage-specific inactivation of class IA PI3K isoforms, we demonstrate a critical role of the PI3Kβ and PI3Kα isoforms in platelet activation induced by aPL. Our data show that aPL potentiate platelet activation through GPIbα and TLR-2 via a mechanism involving the class IA PI3Kα and β isoforms, which represent new potential therapeutic targets in the prevention or treatment of thrombotic events in patients with APS.
Gêneros orais, argumentação e ensino de língua portuguesa
Authors: Aquino Zilda G. O. 
Published: January 2016

A proposta deste trabalho é tratar de questões relacionadas à língua falada em sala de aula, centralizando-se nas práticas discursivas em que se destaque a argumentação. Entende-se que discussões que se fizeram em torno dos gêneros discursivos, especialmente orientados pelos estudos de Bakhtin e da Linguística de texto, vêm propiciando um avanço em torno da necessidade que tem a escola de promover o ensino da língua a partir da abordagem de gêneros discursivos. Nesta acepção, tanto a modalidade escrita quanto a falada merecem espaço no aprendizado, como se espera que venha ocorrendo; entretanto, acreditamos que os gêneros orais, por demandarem do professor conhecimentos específicos das características da língua falada e da interação que advém de seu uso em situações concretas, e em razão de esses estudos serem recentes entre nossos pesquisadores (não passam de três décadas), ainda devam estar muito presentes em nossas discussões. No caso deste trabalho, o recorte recai sobre um gênero da oralidade específico – o debate, tendo em vista o fato de se constituir em um espaço privilegiado de construção de conhecimento, de posicionamento frente a questões que se apresentam na vida em sociedade – pontos de interesse da escola. Além de contribuir para o desenvolvimento de habilidades necessárias às práticas sociodiscursivas determinadas, propõe-se que o ensino da argumentação nos gêneros orais se atenha à observação de estratégias selecionadas em interações na quais se destaque o jogo interacional que se delineia quando se busca persuadir o(s) interlocutor(es). O corpus constitui-se de transcrições de debates, tanto a partir de sua ocorrência em sala de aula, quanto em outros contextos, como o da mídia. O tratamento metodológico faz-se a partir da identificação dos argumentos e de seu uso estratégico em situações específicas. A discussão teórica recai sobre os trabalhos de Orecchioni (2010), Marcuschi (2004), Dolz e Schneuwly (2004), Perelman e Olbrechts-Tyteca (1996[1958]), entre outros.
Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor
Authors: Howangyin Kiave-Yune , Zlatanova Ivana , Pinto Cristina , Ngkelo Anta , Cochain Clément , Rouanet Marie , Vilar José , Lemitre Mathilde , Stockmann Christian , Fleischmann Bernd K. , Mallat Ziad , Silvestre Jean-Sébastien 
Published: January 2016

Background—
In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction.

Methods and Results—

We generated double-deficient mice for Mertk and Mfge8 (Mertk
−/−
/Mfge8
−/−
) and challenged them with acute coronary ligature. Compared with wild-type, Mertk-deficient (Mertk
−/−
), or Mfge8-deficient (Mfge8
−/−
) animals, Mertk
−/−
/Mfge8
−/−
mice displayed greater alteration in cardiac function and remodeling. Mertk and Mfge8 were expressed mainly by cardiac Ly6C
High and Low
monocytes and macrophages. In parallel, Mertk
−/−
/Mfge8
−/−
bone marrow chimeras manifested increased accumulation of apoptotic cells, enhanced fibrotic area, and larger infarct size, as well as reduced angiogenesis. We found that the abrogation of efferocytosis affected neither the ability of circulating monocytes to infiltrate cardiac tissue nor the number of resident Ly6C
High
and Ly6C
How
monocytes/macrophages populating the infarcted milieu. In contrast, combined Mertk and Mfge8 deficiency in Ly6C
High
/Ly6C
Low
monocytes/macrophages either obtained from in vitro differentiation of bone marrow cells or isolated from infarcted hearts altered their capacity of efferocytosis and subsequently blunted vascular endothelial growth factor A (VEGFA) release. Using LysMCre
+
/VEGFA
fl/fl
mice, we further identified an important role for myeloid-derived VEGFA in improving cardiac function and angiogenesis.

Conclusions—
After myocardial infarction, Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of VEGFA to locally repair the dysfunctional heart.
Life history traits, liquid culture production and storage temperatures of Steinernema yirgalemense
Authors: Addis Temesgen , Mijušković Nevena , Strauch Olaf , Ehlers Ralf-Udo 
Published: January 2016

Using the hanging drop technique with nematode growth gelrite medium, life history traits of Steinernema yirgalemense (strain Sy 157-C) were investigated at a bacterial density of 10 × 109 cells ml−1 of Xenorhabdus indica at 25°C. With the same technique, the exit of dauer juveniles (DJ) from the arrested stage (recovery) was assessed at 5 × 109, 10 × 109 and 20 × 109 cells ml−1 of X. indica. Additionally, S. yirgalemense was incubated in nematode liquid medium at 25, 27 and 30°C. At each culture temperature, DJ recovery, sex ratio at 3 days post DJ inoculation and DJ yield and DJ as a percentage of non-DJ stages at 15 days post DJ inoculation were assessed. DJ survival in Ringer’s solution stored at 4, 15 and 25°C was assessed for 66 days. Steinernema yirgalemense has a total fertility rate and net reproductive rate of 487 and 314 offspring per female, respectively. The intrinsic rate of natural increase was 0.98 day−1, population doubling time PDT = 0.71 days and mean generation time days. The average lifespan of S. yirgalemense females starting from first-stage juveniles was 6.55 days. In liquid culture, DJ recovery ranged from 63-75% at 72 h post DJ inoculation and was not significantly different between the incubation temperatures. Parental male to female ratio was not influenced by incubation temperature and usually was at a ratio of 1:2. The percentage of females that entered into endotokia matricida at 72 h post DJ inoculation was 61% at 25°C, whereas at 27 and 30°C it was 24% and 0.5%, respectively. The highest DJ yield was recorded at 25°C (284 114 DJ ml−1) followed by 27°C (176 932 DJ ml−1) and the lowest at 30°C with 26 298 DJ ml−1. At a storage temperature of 4°C, DJ survival did not exceed 42 days, whereas at 15 and 25°C more than 95% of the DJ survived 66 days. Although S. yirgalemense DJ survived for long periods at both 15 and 25°C in liquid storage, their survival in formulated product and virulence after storage needs further investigation.
Localized Ensemble-Based Tangent Linear Models and Their Use in Propagating Hybrid Error Covariance Models
Authors: Frolov Sergey , Bishop Craig H. 
Published: January 2016

AbstractHybrid error covariance models that blend climatological estimates of forecast error covariances with ensemble-based, flow-dependent forecast error covariances have led to significant reductions in forecast error when employed in 4DVAR data assimilation schemes. Tangent linear models (TLMs) designed to predict the differences between perturbed and unperturbed simulations of the weather forecast are a key component of such 4DVAR schemes. However, many forecasting centers have found that TLMs and their adjoints do not scale well computationally and are difficult to create and maintain—particularly for coupled ocean–wave–ice–atmosphere models. In this paper, the authors create ensemble-based TLMs (ETLMs) and test their ability to propagate both climatological and flow-dependent parts of hybrid error covariance models. These tests demonstrate that rank deficiency limits the utility of unlocalized ETLMs. High-rank, time-evolving, flow-adaptive localization functions are constructed and tested using recursive application of short-duration ETLMs, each of which is localized using a static localization. Since TLM operators do not need to be semipositive definite, the authors experiment with a variety of localization approaches including step function localization. The step function localization leads to a local formulation that was found to be highly effective. In tests using simple one-dimensional models with both dispersive and nondispersive dynamics, it is shown that practical ETLM configurations were effective at propagating covariances as far as four error correlation scales.
On the Impact of the Choice of Global Ensemble in Forcing a Regional Ensemble System
Authors: Weidle Florian , Wang Yong , Smet Geert 
Published: January 2016

Abstract
It is quite common that in a regional ensemble system the large-scale initial condition (IC) perturbations and the lateral boundary condition (LBC) perturbations are taken from a global ensemble prediction system (EPS). The choice of global EPS as a driving model can have a significant impact on the performance of the regional EPS. This study investigates the impact of large-scale IC/LBC perturbations obtained from different global EPSs on the forecast quality of a regional EPS. For this purpose several experiments are conducted where the Aire Limitée Adaption dynamique Développement International–Limited Area Ensemble Forecasting (ALADIN-LAEF) regional ensemble is forced by two of the world’s leading global ensembles, the European Centre for Medium-Range Weather Forecasts’ Ensemble Prediction System (ECMWF-EPS) and the Global Ensemble Forecasting System (GEFS) from the National Centers for Environmental Prediction (NCEP), which provide the IC and LBC perturbations. The investigation is carried out for a 51-day period during summer 2010 over central Europe. The results indicate that forcing of the regional ensemble with GEFS performs better for surface parameters, whereas at upper levels forcing with ECMWF-EPS is superior. Using perturbations from GEFS lead to a considerably higher spread in ALADIN-LAEF, which is beneficial near the surface where regional EPSs are usually underdispersive. At upper levels, forcing with GEFS leads to an overdispersion of ALADIN-LAEF as a result of the large spread of some parameters, where forcing ALADIN-LAEF with ECMWF-EPS provides statistically more reliable forecasts. The results indicate that the best global EPS might not always provide the best ICs and LBCs for a regional ensemble.
Oral Health in Primary Care
Authors: Phillips K.E. , Hummel J. 
Published: January 2016

Knowledge Transfer Statement: This special communication presents the Oral Health Delivery Framework, a conceptual model for incorporating preventive oral health care in routine medical care and improving referrals from primary care to dentistry. The framework, along with supporting case examples and stakeholder actions, was published in Oral Health: An Essential Component of Primary Care in June 2015. To access the full white paper and supporting resources, visit www.QualisHealth.org/white-paper .
Decidual macrophages: key regulators of vascular remodeling in human pregnancy
Authors: Lash Gendie E , Pitman Hedele , Morgan Hannah L , Innes Barbara A , Agwu Chinedu N , Bulmer Judith N 
Published: January 2016

Abstract
Successful remodeling of the uterine spiral arteries is essential for a complication-free pregnancy and is best described in terms of its morphologic features. The molecular mediators and cellular sources of spiral artery remodeling are not known, although a role for uterine leukocytes has been proposed. Immunohistochemical assessment of placental bed biopsies demonstrated uterine NK cells, macrophages, and T lymphocytes in the wall and adventitia of spiral arteries at different stages of remodeling, regardless of the presence of extravillous trophoblast cells. Leukocytes were more prevalent in vessel adventitia than wall, and macrophages were the most abundant leukocyte population. Macrophages, separated from early pregnancy decidua, did not alter extravillous trophoblast cells invasion or vascular smooth muscle cell organization or differentiation status but did induce extracellular matrix breakdown (reduced immunostaining of laminin, P = 0.05; fibronectin, P = 0.02) and were able to phagocytose apoptotic vascular smooth muscle cells. Decidual macrophages were shown to secrete a wide range of cytokines (IL-1β, -2, -4, -5, -6, -8, -10, and -13 and TNF-α), proteases (matrix metalloproteinase-1, -2, -7, -9, and -10), and angiogenic growth factors (angiogenin, keratinocyte growth factor, fibroblast growth factor B, vascular endothelial growth factor A, and angiopoietin-1 and -2). We conclude that spiral artery remodeling involves the coordinated activity of a range of cell types, including extravillous trophoblast cells, decidual uterine NK cells, and macrophages in a carefully, spatiotemporally regulated manner.
Screening by Clinical Breast Examination in Western Kenya: Who Comes?
Authors: Busakhala Naftali Wisindi , Chite Fredrick Asirwa , Wachira Juddy , Naanyu Violet , Kisuya Job Wapangana , Keter Alfred , Mwangi Ann , Njiru Evanjeline , Chumba David , Lumarai Lugaria , Biwott Penina , Kiplimo Ivan , Otieno Grieven , Kigen Gabriel , Loehrer Patrick , Inui Thomus 
Published: January 2016

PurposeMore than 80% of women with breast cancer in Kenya present to medical care with established late-stage disease. We sought to understand why women might not participate in breast cancer screening when it is offered by comparing the views of a cohort of those who attended a screening special event with those of community controls who did not attend.MethodsAll residents living close to three health centers in western Kenya were invited to participate in screening. Participants (attendees) underwent clinical breast examination by trained physician oncologists. In addition, women who consented were interviewed by using a modified Breast Cancer Awareness Module questionnaire. Nonattendees were interviewed in their homes the following day.ResultsA total of 1,511 attendees (1,238 women and 273 men) and 467 nonattendee women participated in the study. Compared with nonattendees, the women attendees were older, more often employed, knew that breast cancer presented as a lump, and were more likely to have previously felt a lump in a breast. In addition, they were more likely to report previously participating in screening activities, were more likely to have performed breast self-examination, and were less concerned about wasting a doctor’s time. Almost all those surveyed (attendees and nonattendees) expressed interest in future breast cancer screening opportunities.ConclusionThe women who volunteer for breast cancer screening in western Kenya are more aware of breast cancer than those who do not volunteer. Screening recruitment should seek to close these knowledge gaps to increase participation.
“Corrupted by Ambition”: Justice and Patronage in Imperial New Spain and Spain, 1650–1755
Authors: Rosenmüller Christoph 
Published: January 2016

Abstract
Renewed interest in the linkage between finance and the state has led historians to reexamine corruption. While there is scholarly consensus that the royal sale of appointments (beneficio) corrupted governance and weakened royal authority in a stagnant Spanish empire, the historical record suggests otherwise. Beneficio allowed social newcomers to buy their way into the judiciary. Traditional elites thought that these newcomers were innately corrupt and that making them judges violated distributive justice, or the fair awarding of entitlements by traditional notions of merit. Between 1650 and 1755, enlightened thinking challenged these precepts. The idea that corruption entailed violating royal laws in office gained strength. Performance mattered more, and accepting money for appointments instead of considering traditional merit was part of a utilitarian approach. Thus in 1675 absolutist governments in Madrid began selling appointments to alcaldes mayores in New Spain to gain oversight, appropriate resources, and weaken the viceroys, who lost half, if not more, of their patronage power. Beneficio therefore strengthened the monarchy and should be seen as part of yet another cycle of royal reforms beginning in the late seventeenth century.