bluuebunny/crossref_metadata_2025_split huggingface dataset:
Young adolescent girls are at high risk for adverse pregnancy outcomes in sub-Saharan Africa: an observational multicountry study
Authors: Mombo-Ngoma Ghyslain , Mackanga Jean Rodolphe , González Raquel , Ouedraogo Smaila , Kakolwa Mwaka A , Manego Rella Zoleko , Basra Arti , Rupérez María , Cot Michel , Kabanywany Abdunoor M , Matsiegui Pierre-Blaise , Agnandji Seldiji T , Vala Anifa , Massougbodji Achille , Abdulla Salim , Adegnika Ayôla A , Sevene Esperança , Macete Eusebio , Yazdanbakhsh Maria , Kremsner Peter G , Aponte John J , Menéndez Clara , Ramharter Michael 
Published: June 2016

ObjectivesOne of Africa's most important challenges is to improve maternal and neonatal health. The identification of groups at highest risk for adverse pregnancy outcomes is important for developing and implementing targeted prevention programmes. This study assessed whether young adolescent girls constitute a group at increased risk for adverse birth outcomes among pregnant women in sub-Saharan Africa.SettingData were collected prospectively as part of a large randomised controlled clinical trial evaluating intermittent preventive treatment of malaria in pregnancy (NCT00811421—Clinical Trials.gov), conducted between September 2009 and December 2013 in Benin, Gabon, Mozambique and Tanzania.ParticipantsOf 4749 participants, pregnancy outcomes were collected for 4388 deliveries with 4183 live births including 83 multiple gestations. Of 4100 mothers with a singleton live birth delivery, 24% (975/4100) were adolescents (≤19 years of age) and 6% (248/4100) were aged ≤16 years.Primary and secondary outcome measuresPrimary outcomes of this predefined analysis were preterm delivery and low birth weight.ResultsThe overall prevalence of low birthweight infants and preterm delivery was 10% (371/3851) and 4% (159/3862), respectively. Mothers aged ≤16 years showed higher risk for the delivery of a low birthweight infant (OR: 1.96; 95% CI 1.35 to 2.83). Similarly, preterm delivery was associated with young maternal age (≤16 years; OR: 2.62; 95% CI 1.59 to 4.30). In a subanalysis restricted to primiparous women: preterm delivery, OR 4.28; 95% CI 2.05 to 8.93; low birth weight, OR: 1.29; 95% CI 0.82 to 2.01.ConclusionsYoung maternal age increases the risk for adverse pregnancy outcomes and it is a stronger predictor for low birth weight and preterm delivery than other established risk factors in sub-Saharan Africa. This finding highlights the need to improve adolescent reproductive health in sub-Saharan Africa.Trial registration numberNCT00811421; Post-results.
Changes in movement symmetry over the stages of the shoeing process in military working horses
Authors: Pfau T. , Daly K. , Davison J. , Bould A. , Housby N. , Weller R. 
Published: June 2016

Military working horses perform a high proportion of work on road surfaces and are shod frequently to deal with high attrition rates. The authors investigate the influence of shoeing on movement symmetry as an indirect indicator of mechanical differences affecting force production between contralateral limbs. In this quantitative observational study, inertial sensor gait analysis was performed in 23 Irish sport type horses (4–21 years, 1.58–1.85 m) in full ceremonial work at the King's Troop, Royal Horse Artillery. Changes in two movement symmetry measures (SI: symmetry index; MinDiff: difference between displacement minima) for head and pelvic movement were assessed at four stages of routine shoeing: ‘old shoes’, ‘shoes removed’, ‘trimmed’, ‘reshod’. Horses were assessed applying shoes to the front limbs (N=10), to the hindlimbs (N=10) or both (N=3). Changes in head movement symmetry between conditions were small and inconsistent. Changes in pelvic movement symmetry were small and showed significant differences between shoeing stages (SI: P=0.013, MinDiff: P=0.04) with most symmetrical pelvic movement after trimming. In military working horses with high frequency shoeing small changes in movement symmetry were measured. All significant changes involved trimming, which indicates that future studies should in particular assess changes before/after trimming and investigate longer shoeing intervals.
CLIMATE CHANGE AND LAND USE IN SOUTHEASTERN U.S.: DID THE “DUMB FARMER” GET IT WRONG?
Authors: TSVETANOV TSVETAN , QI LINGQIAO , MUKHERJEE DEEP , SHAH FARHED , BRAVO-URETA BORIS 
Published: June 2016

The assumption of a fixed amount of land remaining in agriculture regardless of changing climate conditions — one of the features of the “dumb farmer scenario” — is likely to bias the estimated social welfare impacts of climate change. In order to quantify this bias, we employ a demand-supply framework to determine both the amount of land allocated to agricultural and nonagricultural uses as well as the social welfare associated with this allocation choice when no market distortions exist. We present an application of our model to the Southeastern United States and simulate the effects of changing climate conditions on land allocation in the region between 2007 and 2040. We find a very modest welfare bias when maintaining current farmland preservation policies and a more substantial bias if we assume that additional land policies are instituted which have spillover welfare effects in other land-using sectors.
Time–space variability of paralic strata deposited in a high accommodation, high sediment supply setting: example from the Cretaceous of Utah
Authors: Mulhern Julia S. , Johnson Cari L. 
Published: June 2016

Abstract

A previously unstudied section of the John Henry Member (Upper Cretaceous, Straight Cliffs Formation) preserves four stacked regressive–transgressive cycles of paralic strata from the Kaiparowits Plateau in south-central Utah. Meso-scale (10–100 s m thick) shoreface, wave-dominated delta and estuarine depositional environments stack vertically and show the complexity of paralic facies in a single location through time. Correlations with nearby exposures show the palaeogeographical variability updip and along-strike over
c.
6.5 myr. Such variability highlights the importance of high accommodation settings in preserving transgressive deposits, including landwards-stepping barrier island and lagoon systems. The Buck Hollow section is expanded two to three times compared with correlative successions only 15–40 km away. Tectonics, eustasy and climate contributed to relative shifts in base level, but these regional controls do not explain the dramatic local thickening observed. Local controls on accommodation were quantified through decompaction analysis. The results showed that the expanded thickness of the John Henry Member in Buck Hollow can be explained by differences in decompaction (
c.
9%), local erosion by fluvial incision (
c.
5%), early compaction (
c.
30%) and local structures such as faults (
c.
100–150%). This outcrop-based study illustrates facies variability within a thick paralic succession and investigates accommodation controls on the preservation of these strata with the goal of improving predictive models for analogous deposits.

Supplementary material:
40
Ar/
39
Ar age data methods and sample location available at
https://doi.org/10.6084/m9.figshare.c.3277436.v1
Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas
Authors: Kim Jennifer E. , Patel Mira A. , Mangraviti Antonella , Kim Eileen S. , Theodros Debebe , Velarde Esteban , Liu Ann , Sankey Eric W. , Tam Ada , Xu Haiying , Mathios Dimitrios , Jackson Christopher M. , Harris-Bookman Sarah , Garzon-Muvdi Tomas , Sheu Mary , Martin Allison M. , Tyler Betty M. , Tran Phuoc T. , Ye Xiaobu , Olivi Alessandro , Taube Janis M. , Burger Peter C. , Drake Charles G. , Brem Henry , Pardoll Drew M. , Lim Michael 
Published: June 2016

AbstractPurpose: Checkpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme. Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produce long-term survivors in a murine glioma model. However, tumor-infiltrating lymphocytes (TIL) can express multiple checkpoints, and expression of ≥2 checkpoints corresponds to a more exhausted T-cell phenotype. We investigate TIM-3 expression in a glioma model and the antitumor efficacy of TIM-3 blockade alone and in combination with anti-PD-1 and SRS.Experimental Design: C57BL/6 mice were implanted with murine glioma cell line GL261-luc2 and randomized into 8 treatment arms: (i) control, (ii) SRS, (iii) anti-PD-1 antibody, (iv) anti-TIM-3 antibody, (v) anti-PD-1 + SRS, (vi) anti-TIM-3 + SRS, (vii) anti-PD-1 + anti-TIM-3, and (viii) anti-PD-1 + anti-TIM-3 + SRS. Survival and immune activation were assessed.Results: Dual therapy with anti-TIM-3 antibody + SRS or anti-TIM-3 + anti-PD-1 improved survival compared with anti-TIM-3 antibody alone. Triple therapy resulted in 100% overall survival (P &lt; 0.05), a significant improvement compared with other arms. Long-term survivors demonstrated increased immune cell infiltration and activity and immune memory. Finally, positive staining for TIM-3 was detected in 7 of 8 human GBM samples.Conclusions: This is the first preclinical investigation on the effects of dual PD-1 and TIM-3 blockade with radiation. We also demonstrate the presence of TIM-3 in human glioblastoma multiforme and provide preclinical evidence for a novel treatment combination that can potentially result in long-term glioma survival and constitutes a novel immunotherapeutic strategy for the treatment of glioblastoma multiforme. Clin Cancer Res; 23(1); 124–36. ©2016 AACR.
Immunomodulatory Effect of Vitamin D after Allogeneic Stem Cell Transplantation: Results of a Prospective Multicenter Clinical Trial
Authors: Caballero-Velázquez Teresa , Montero Isabel , Sánchez-Guijo Fermín , Parody Rocío , Saldaña Raquel , Valcarcel David , López-Godino Oriana , Ferra i Coll Christelle , Cuesta Marian , Carrillo-Vico Antonio , Sánchez-Abarca Luis I. , López-Corral Lucía , Márquez-Malaver Francisco J. , Pérez-Simón José A. 
Published: June 2016

AbstractPurpose: We describe the results of a prospective multicenter phase I/II trial evaluating the impact of the use of vitamin D (VitD) from day −5 to +100 on the outcome of patients undergoing allogeneic transplantation (EudraCT: 2010-023279-25; ClinicalTrials.gov: NCT02600988).Experimental Design: A total of 150 patients were included in three consecutive cohorts of 50 patients each group: control group (CG, not receive VitD); low-dose group (LdD, received 1,000 IU VitD daily); and high-dose group (HdD, 5,000 IU VitD daily). We measured levels of VitD, cytokines, and immune subpopulations after transplantation.Results: No significant differences were observed in terms of cumulative incidence of overall and grades 2–4 acute GVHD in terms of relapse, nonrelapse mortality, and overall survival. However, a significantly lower cumulative incidence of both overall and moderate plus severe chronic GVHD (cGVHD) at 1 year was observed in LdD (37.5% and 19.5%, respectively) and HdD (42.4% and 27%, respectively) as compared with CG (67.5% and 44.7%, respectively; P &lt; 0.05). In multivariable analysis, treatment with VitD significantly decreased the risk of both overall (for LdD: HR = 0.31, P = 0.002; for HdD: HR = 0.36, P = 0.006) and moderate plus severe cGVHD (for LdD: HR = 0.22, P = 0.001; for HdD: HR = 0.33, P = 0.01). VitD modified the immune response, decreasing the number of B cells and naïve CD8 T cells, with a lower expression of CD40L.Conclusions: This is the first prospective trial that analyzes the effect of VitD postransplant. We observed a significantly lower incidence of cGVHD among patients receiving VitD. Interestingly, VitD modified the immune response after allo-SCT. Clin Cancer Res; 22(23); 5673–81. ©2016 AACR.
HER3 Targeting Sensitizes HNSCC to Cetuximab by Reducing HER3 Activity and HER2/HER3 Dimerization: Evidence from Cell Line and Patient-Derived Xenograft Models
Authors: Wang Dongsheng , Qian Guoqing , Zhang Hongzheng , Magliocca Kelly R. , Nannapaneni Sreenivas , Amin A.R.M. Ruhul , Rossi Michael , Patel Mihir , El-Deiry Mark , Wadsworth J. Trad , Chen Zhengjia , Khuri Fadlo R. , Shin Dong M. , Saba Nabil F. , Chen Zhuo G. 
Published: June 2016

AbstractPurpose: Our previous work suggested that HER3 inhibition sensitizes head and neck squamous cell carcinoma (HNSCC) to EGFR inhibition with cetuximab. This study aimed to define the role of HER3 in cetuximab resistance and the antitumor mechanisms of EGFR/HER3 dual targeting in HNSCC.Experimental Design: We treated cetuximab-resistant HNSCC UMSCC1-C and parental UMSCC1-P cell lines with anti-EGFR antibody cetuximab, anti-HER3 antibody MM-121, and their combination. We assessed activities of HER2, HER3, and downstream signaling pathways by Western blotting and cell growth by sulforhodamine B (SRB) and colony formation assays. HER3-specific shRNA was used to confirm the role of HER3 in cetuximab response. The combined efficacy and alterations in biomarkers were evaluated in UMSCC1-C xenograft and patient-derived xenograft (PDX) models.Results: Cetuximab treatment induced HER3 activation and HER2/HER3 dimerization in HNSCC cell lines. Combined treatment with cetuximab and MM-121 blocked EGFR and HER3 activities and inhibited the PI3K/AKT and ERK signaling pathways and HNSCC cell growth more effectively than each antibody alone. HER3 knockdown reduced HER2 activation and resensitized cells to cetuximab. Cetuximab-resistant xenografts and PDX models revealed greater efficacy of dual EGFR and HER3 inhibition compared with single antibodies. In PDX tissue samples, cetuximab induced HER3 expression and MM-121 reduced AKT activity.Conclusions: Clinically relevant PDX models demonstrate that dual targeting of EGFR and HER3 is superior to EGFR targeting alone in HNSCC. Our study illustrates the upregulation of HER3 by cetuximab as one mechanism underlying resistance to EGFR inhibition in HNSCC, supporting further clinical investigations using multiple targeting strategies in patients who have failed cetuximab-based therapy. Clin Cancer Res; 23(3); 677–86. ©2016 AACR.
Bone Marrow Microenvironment Niche Regulates miR-221/222 in Acute Lymphoblastic Leukemia
Authors: Moses Blake S. , Evans Rebecca , Slone William L. , Piktel Debbie , Martinez Ivan , Craig Michael D. , Gibson Laura F. 
Published: June 2016

Abstract
Acute lymphoblastic leukemia (ALL) has many features in common with normal B-cell progenitors, including their ability to respond to diverse signals from the bone marrow microenvironment (BMM) resulting in regulation of cell-cycle progression and survival. Bone marrow–derived cues influence many elements of both steady state hematopoiesis and hematopoietic tumor cell phenotypes through modulation of gene expression. miRNAs are one regulatory class of small noncoding RNAs that have been shown to be increasingly important in diverse settings of malignancy. In the current study, miRNA profiles were globally altered in ALL cells following exposure to primary human bone marrow niche cells, including bone marrow stromal cells (BMSC) and primary human osteoblasts (HOB). Specifically, mature miR-221 and miR-222 transcripts were decreased in ALL cells cocultured with BMSC or HOB, coincident with increased p27 (CDKN1B), a previously validated target. Increased p27 protein in ALL cells exposed to BMSC or HOB is consistent with accumulation of tumor cells in the G0 phase of the cell cycle and resistance to chemotherapy-induced death. Overexpression of miR-221 in ALL cells during BMSC or HOB coculture prompted cell-cycle progression and sensitization of ALL cells to cytotoxic agents, blunting the protective influence of the BMM. These novel observations indicate that BMM regulation of miR-221/222 contributes to marrow niche-supported tumor cell quiescence and survival of residual cells.
Implications: Niche-influenced miR-221/222 may define a novel therapeutic target in ALL to be combined with existing cytotoxic agents to more effectively eradicate refractory disease that contributes to relapse. Mol Cancer Res; 14(10); 909–19. ©2016 AACR.
HDAC6 Deacetylates HMGN2 to Regulate Stat5a Activity and Breast Cancer Growth
Authors: Medler Terry R. , Craig Justin M. , Fiorillo Alyson A. , Feeney Yvonne B. , Harrell J. Chuck , Clevenger Charles V. 
Published: June 2016

AbstractStat5a is a transcription factor utilized by several cytokine/hormone receptor signaling pathways that promotes transcription of genes associated with proliferation, differentiation, and survival of cancer cells. However, there are currently no clinically approved therapies that directly target Stat5a, despite ample evidence that it contributes to breast cancer pathogenesis. Here, deacetylation of the Stat5a coactivator and chromatin-remodeling protein HMGN2 on lysine residue K2 by HDAC6 promotes Stat5a-mediated transcription and breast cancer growth. HDAC6 inhibition both in vitro and in vivo enhances HMGN2 acetylation with a concomitant reduction in Stat5a-mediated signaling, resulting in an inhibition of breast cancer growth. Furthermore, HMGN2 is highly acetylated at K2 in normal human breast tissue, but is deacetylated in primary breast tumors and lymph node metastases, suggesting that targeting HMGN2 deacetylation is a viable treatment for breast cancer. Together, these results reveal a novel mechanism by which HDAC6 activity promotes the transcription of Stat5a target genes and demonstrate utility of HDAC6 inhibition for breast cancer therapy.Implications: HMGN2 deacetylation enhances Stat5a transcriptional activity, thereby regulating prolactin-induced gene transcription and breast cancer growth. Mol Cancer Res; 14(10); 994–1008. ©2016 AACR.
Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma
Authors: Gil del Alcazar Carlos Rodrigo , Todorova Pavlina Krasimirova , Habib Amyn A. , Mukherjee Bipasha , Burma Sandeep 
Published: June 2016

Abstract
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults and is universally fatal. The DNA alkylating agent temozolomide is part of the standard-of-care for GBM. However, these tumors eventually develop therapy-driven resistance and inevitably recur. While loss of mismatch repair (MMR) and re-expression of MGMT have been shown to underlie chemoresistance in a fraction of GBMs, resistance mechanisms operating in the remaining GBMs are not well understood. To better understand the molecular basis for therapy-driven temozolomide resistance, mice bearing orthotopic GBM xenografts were subjected to protracted temozolomide treatment, and cell lines were generated from the primary (untreated) and recurrent (temozolomide-treated) tumors. As expected, the cells derived from primary tumors were sensitive to temozolomide, whereas the cells from the recurrent tumors were significantly resistant to the drug. Importantly, the acquired resistance to temozolomide in the recurrent lines was not driven by re-expression of MGMT or loss of MMR but was due to accelerated repair of temozolomide-induced DNA double-strand breaks (DSB). Temozolomide induces DNA replication–associated DSBs that are primarily repaired by the homologous recombination (HR) pathway. Augmented HR appears to underpin temozolomide resistance in the recurrent lines, as these cells were cross-resistant to other agents that induced replication-associated DSBs, exhibited faster resolution of damage-induced Rad51 foci, and displayed higher levels of sister chromatid exchanges (SCE). Furthermore, in light of recent studies demonstrating that CDK1 and CDK2 promote HR, it was found that CDK1/2 inhibitors countered the heightened HR in recurrent tumors and sensitized these therapy-resistant tumor cells to temozolomide.
Implications: Augmented HR repair is a novel mechanism underlying acquired temozolomide resistance in GBM, and this raises the possibility of improving the therapeutic response to temozolomide by targeting HR with small-molecule inhibitors of CDK1/2. Mol Cancer Res; 14(10); 928–40. ©2016 AACR.
No balé e no teatro: a família como mediação na formação do professor-espectador
Authors: Ferreira Taís 
Published: June 2016

Esse artigo apresenta, a partir de exemplos localizados de experiências de dois professores de teatro e dança brasileiros, considerações sobre a relação entre a formação de uma identidade de espectador e a mediação da família nesse processo constitutivo, a partir das primeiras memórias dos professores como espectadores. Alicerçando a discussão, são evocados conceitos seminais da obra bourdiana como de capital cultural e simbólico e habitus, além da concepção da memória trazida pelo neurocientista Iván Izquierdo. A partir das pistas apresentadas, concluo com uma sugestão para a formação docente em artes cênicas.
A pulsão de teatralidade e a sobrevivência do teatro na atualidade
Authors: Medeiros Elen de , Santos Matheus Borelli dos 
Published: June 2016

Este artigo busca, por meio de uma leitura de O teatro é necessário?, de Denis Guénoun, aproximar as ideias abordadas pelo autor ao conceito de “pulsão de ficção”, forjado por Suzi Frankl Sperper, em uma tentativa de refletir acerca das motivações do espectador contemporâneo ao buscar uma obra teatral. Esse pensamento, apoiado na noção da tríplice mimese, de Paul Ricoeur, irá levantar possibilidades que investigam como um espaço institucionalizado pode proporcionar terreno fértil para o cultivo dessa necessidade humana pela ficcionalização.
Lugares da experiência na cena performativa recente: uma problematização acerca do espectador e seu exercício crítico de leitura/produção
Authors: Campos Cecília Lauritzen Jácome 
Published: June 2016

Este artigo problematiza o conceito de experiência e suas aproximações com a cena teatral performativa recente. Ao abordar a dinâmica da cena contemporânea, é exposto um relato da autora como espectadora do evento cênico performativo A última palavra é a penúltima – 2.0 do grupo Teatro da Vertigem (SP), em que os lugares do público são revisitados sob a ótica do ato de leitura enquanto ato produtivo. A discussão traça relações entre a experiência como conceito e vivência, a estética relacional de Nicolas Bourriaud e os estudos da recepção de Flávio Desgranges, Paul Zumthor, John Dewey e Hans Ulrich Gumbrecht. A partir da noção da arte como expressão potente na alteração da percepção, questiona-se a possibilidade de falar em um ‘exercício crítico da experiência’.
Aos nossos inimigos. Reflexões sobre o público
Authors: Cornago Óscar 
Published: June 2016

Este trabalho tem o objetivo de estudar a construção do público, entendido como os interlocutores em ação, a partir de duas histórias diferentes. A primeira consiste em uma conversação improvisada da dupla de performers Los Torreznos, em La caverna (2012), que tinha o público como seu objeto de observação; e a outra é extraída da análise que o Comité Invisible fez sobre o movimento de ocupação das praças, ocorrido em diferentes cidades do mundo desde 2008. O objetivo é confrontar duas abordagens diferentes do público – cênica e estética, por um lado, e social e política, por outro – e traçar um caminho de ida e volta entre a cena e a rua, considerando ambos os espaços como dispositivos de ação e de representação procurando operar de outras maneiras ante a ordem política e econômica, reforçada desde a década de 1990.