bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between breastfeeding support and breastfeeding rates in the UK: a comparison of late preterm and term infants
Authors: Rayfield Sarah , Oakley Laura , Quigley Maria A 
Published: November 2015

ObjectiveTo explore the association between breastfeeding support and breastfeeding among late preterm (gestation 34–36 weeks) and term (gestation ≥37 weeks) infants.MethodsSecondary analysis of the UK 2010 Infant Feeding Survey. Logistic regression was used to determine the association of breastfeeding support with breastfeeding at 10 days and 6 weeks in late preterm and term infants.ResultsThe study included 14 525 term and 579 late preterm infants. A total of 11 729 infants initiated breastfeeding (11 292 (81.1%) term, 437 (79.4%) late preterm infants, p=0.425). Of these, 9230 (84.3%) term and 365 (85.6%) late preterm infants were breastfeeding at 10 days (p=0.586); of these 7547 (82.0%) term and 281 (75.4%) late preterm infants were still breastfeeding at 6 weeks (p=0.012). Mothers who reported receiving contact details for breastfeeding support groups had a higher likelihood of breastfeeding late preterm (adjusted ORs, aOR 3.14, 95% CI 1.40 to 7.04) and term infants (aOR 2.24, 95% CI 1.86 to 2.68) at 10 days and term infants at 6 weeks (aOR 1.83, 95% CI 1.51 to 2.22). Those who reported that they did not receive enough help with breastfeeding in hospital had a lower likelihood of breastfeeding late preterm at 10 days and term infants at 10 days and 6 weeks, compared to those who reported having enough help.ConclusionsReceiving sufficient help with breastfeeding in hospital and the contact details for breastfeeding support groups is associated with breastfeeding term infants up to 6 weeks and late preterm infants at 10 days.
Waist circumference values equivalent to body mass index points for predicting absolute cardiovascular disease risks among adults in an Aboriginal community: a prospective cohort study
Authors: Adegbija Odewumi , Hoy Wendy E , Wang Zhiqiang 
Published: November 2015

ObjectiveThere have been suggestions that currently recommended waist circumference (WC) cut-off points for Australians of European origin may not be applicable to Aboriginal people who have different body habitus profiles. We aimed to generate equivalent WC values that correspond to body mass index (BMI) points for identifying absolute cardiovascular disease (CVD) risks.DesignProspective cohort study.SettingAn Aboriginal community in Australia's Northern Territory.ParticipantsFrom 1992 to 1998, 920 adults without CVD, with age, WC and BMI measurements were followed-up for up to 20 years.Outcome measuresIncident CVD, coronary artery disease (CAD) and heart failure (HF) events during the follow-up period ascertained from hospitalisation data. We generated WC values with 10-year absolute risks equivalent for the development of CVD as BMI values (20–34 kg/m2) using the Weibull accelerated time-failure model.ResultsThere were 211 incident cases of CVD over 13 669 person-years of follow-up. At the average age of 35 years, WC values with absolute CVD, CAD and HF risks equivalent to BMI of 25 kg/m2were 91.5, 91.8 and 91.7 cm, respectively, for males, and corresponding WC values were 92.5, 92.7 and 93 cm for females. WC values with equal absolute CVD, CAD and HF risks to BMI of 30 kg/m2were 101.7, 103.1 and 102.6 cm, respectively, for males, and corresponding values were 99.2, 101.6 and 101.5 cm for females. Association between WC and CVD did not depend on gender (p=0.54).ConclusionsWC ranging from 91 to 93 cm was equivalent to BMI 25 kg/m2for overweight, and 99 to 103 cm was equivalent to BMI of 30 kg/m2for obesity in terms of predicting 10-year absolute CVD risk. Replicating the absolute risk method in other Aboriginal communities will further validate the WC values generated for future development of WC cut-off points for Aboriginal people.
Decreased argyrophilic nucleolar organiser region (AgNOR) expression in Purkinje cells: first signal of neuronal damage in sudden fetal and infant death
Authors: Lavezzi Anna M , Alfonsi Graziella , Pusiol Teresa , Matturri Luigi 
Published: November 2015

AimsThe nucleolus is an important cellular component involved in the biogenesis of the ribosome. This study was performed in order to validate the introduction of the argyrophilic nucleolar organiser region (AgNOR) stain technique, specific for the nucleoli detection, in neuropathological studies on sudden fetal and infant death.MethodsIn a wide set of fetuses and infants, aged from 27 gestational weeks to eight postnatal months and dead from both known and unknown causes, an in-depth neuropathological study usually applied at the Lino Rossi Research Center of the Milan University was implemented by the AgNOR method.ResultsPeculiar abnormalities of the nucleoli, as partial or total disruption above all in Purkinje cells (PCs), were exclusively found in victims of sudden fetal and infant death, and not in controls. The observed nucleolar alterations were frequently related to nicotine absorption in pregnancy.ConclusionsWe conclude that these findings represent early hallmarks of PC degeneration, contributing to the pathophysiology of sudden perinatal death.
Contribution of health behaviours and clinical factors to socioeconomic differences in frailty among older adults
Authors: Soler-Vila Hosanna , García-Esquinas Esther , León-Muñoz Luz Mª , López-García Esther , Banegas José R , Rodríguez-Artalejo Fernando 
Published: November 2015

BackgroundTo examine the association between socioeconomic status (SES) and risk of frailty, and to assess whether behavioural and clinical factors (BCF) mediate this association.MethodsCohort of 1857 non-institutionalised individuals aged ≥60 years recruited in 2008–2010 and followed through 2012. Education, occupation, and BCF were ascertained at baseline, and incident frailty was assessed at follow-up with the Fried frailty criteria.ResultsMen showed no differences in frailty risk by education or occupation. Compared with women with university education, the adjusted OR (aOR) adjusted for age and the number of frailty criteria at baseline for incident frailty in women with primary or lower education was 3.02 (95% CI 1.25 to 7.30); once fully adjusted for BCF, the OR was 2.00 (95% CI 0.76 to 5.23). No alcohol intake (vs light–moderate), longer time spent watching TV, less time spent reading, and a higher frequency of obesity, depression and musculoskeletal disease in those with primary or lower education accounted for most of the decline in OR. BCF explained 50.5% of the excess frailty risk associated with lower education. The aOR of frailty incidence for manual versus non-manual occupation was 2.24 (95% CI 1.41 to 3.56) versus a fully aOR of 2.05 (95% CI 1.24 to 3.37). BCF explained 15.3% of the association, with individual mediators being similar to those for education-related differences.ConclusionsA lower education or a manual occupation was associated with higher frailty risk in older women. These associations were partly explained by lower alcohol consumption, higher sedentariness, and higher obesity and chronic disease rates in women with lower SES.
A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from theMAINTAIN Nephritis Trial
Authors: Tamirou Farah , Lauwerys Bernard R , Dall'Era Maria , Mackay Meggan , Rovin Brad , Cervera Ricard , Houssiau Frédéric A 
Published: November 2015

BackgroundAlthough an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely theMAINTAIN Nephritis Trial(MNT).MethodsLong-term (at least 7 years) renal function data were available for 90 patients randomised in theMNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV).ResultsAfter 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells ≤5/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%.ConclusionsIn this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts.Trial registration number:NCT00204022.
First-principles study of oxygen and hydrogen adsorption on Pt(111) and PtML/Pd(111) surfaces
Authors: Nie J. L. , Ao L. , Zu X. T. 
Published: November 2015

In this paper, first-principles calculations based on density functional theory (DFT) have been performed to investigate the adsorption of oxygen and hydrogen on [Formula: see text] and [Formula: see text] surfaces covered by monolayer (ML) of [Formula: see text]. The results have shown that the oxygen molecule tends to adsorb on fcc site on both surfaces at the coverage of 0.25 ML, which becomes degeneration with hcp site when the coverage increases to 1 ML. For both oxygen and hydrogen, the adsorption on [Formula: see text] surface are stronger than those on [Formula: see text] surface. The adsorption energy difference for oxygen on the two surfaces is [Formula: see text][Formula: see text]0.2 eV at the coverage of 1 ML, which increases to [Formula: see text][Formula: see text]0.6 eV with the coverage decreasing to 0.25 ML. The similar energy difference was also found for hydrogen adsorption. The density of states analysis have demonstrated the chemical interaction of adsorbed oxygen with both pure [Formula: see text] and [Formula: see text] surfaces with certain shift of [Formula: see text] states to lower level compared to isolated oxygen. For hydrogen adsorption, the hybridization of [Formula: see text] with [Formula: see text] states were observed for both surfaces, indicating the covalent bonding component of H–Pt bond.
Radiotherapy Combined with Novel STING-Targeting Oligonucleotides Results in Regression of Established Tumors
Authors: Baird Jason R. , Friedman David , Cottam Benjamin , Dubensky Thomas W. , Kanne David B. , Bambina Shelly , Bahjat Keith , Crittenden Marka R. , Gough Michael J. 
Published: November 2015

Abstract
Cytotoxic therapies prime adaptive immune responses to cancer by stimulating the release of tumor-associated antigens. However, the tumor microenvironment into which these antigens are released is typically immunosuppressed, blunting the ability to initiate immune responses. Recently, activation of the DNA sensor molecule STING by cyclic dinucleotides was shown to stimulate infection-related inflammatory pathways in tumors. In this study, we report that the inflammatory pathways activated by STING ligands generate a powerful adjuvant activity for enhancing adaptive immune responses to tumor antigens released by radiotherapy. In a murine model of pancreatic cancer, we showed that combining CT-guided radiotherapy with a novel ligand of murine and human STING could synergize to control local and distant tumors. Mechanistic investigations revealed T-cell–independent and TNFα-dependent hemorrhagic necrosis at early times, followed by later CD8 T-cell–dependent control of residual disease. Clinically, STING was found to be expressed extensively in human pancreatic tumor and stromal cells. Our findings suggest that this novel STING ligand could offer a potent adjuvant for leveraging radiotherapeutic management of pancreatic cancer. Cancer Res; 76(1); 50–61. ©2015 AACR.
PD-1 Blunts the Function of Ovarian Tumor–Infiltrating Dendritic Cells by Inactivating NF-κB
Authors: Karyampudi Lavakumar , Lamichhane Purushottam , Krempski James , Kalli Kimberly R. , Behrens Marshall D. , Vargas Doris M. , Hartmann Lynn C. , Janco Jo Marie T. , Dong Haidong , Hedin Karen E. , Dietz Allan B. , Goode Ellen L. , Knutson Keith L. 
Published: November 2015

Abstract
The PD-1:PD-L1 immune signaling axis mediates suppression of T-cell–dependent tumor immunity. PD-1 expression was recently found to be upregulated on tumor-infiltrating murine (CD11c+CD11b+CD8−CD209a+) and human (CD1c+CD19−) myeloid dendritic cells (TIDC), an innate immune cell type also implicated in immune escape. However, there is little knowledge concerning how PD-1 regulates innate immune cells. In this study, we examined the role of PD-1 in TIDCs derived from mice bearing ovarian tumors. Similar to lymphocytes, TIDC expression of PD-1 was associated with expression of the adapter protein SHP-2, which signals to NF-κB; however, in contrast to its role in lymphocytes, we found that expression of PD-1 in TIDC tonically paralyzed NF-κB activation. Further mechanistic investigations showed that PD-1 blocked NF-κB–dependent cytokine release in a SHP-2–dependent manner. Conversely, inhibition of NF-κB–mediated antigen presentation by PD-1 occurred independently of SHP-2. Collectively, our findings revealed that PD-1 acts in a distinct manner in innate immune cells compared with adaptive immune cells, prompting further investigations of the signaling pathways controlled by this central mediator of immune escape in cancer. Cancer Res; 76(2); 239–50. ©2015 AACR.
PRC2 Epigenetically Silences Th1-Type Chemokines to Suppress Effector T-Cell Trafficking in Colon Cancer
Authors: Nagarsheth Nisha , Peng Dongjun , Kryczek Ilona , Wu Ke , Li Wei , Zhao Ende , Zhao Lili , Wei Shuang , Frankel Timothy , Vatan Linda , Szeliga Wojciech , Dou Yali , Owens Scott , Marquez Victor , Tao Kaixiong , Huang Emina , Wang Guobin , Zou Weiping 
Published: November 2015

Abstract
Infiltration of tumors with effector T cells is positively associated with therapeutic efficacy and patient survival. However, the mechanisms underlying effector T-cell trafficking to the tumor microenvironment remain poorly understood in patients with colon cancer. The polycomb repressive complex 2 (PRC2) is involved in cancer progression, but the regulation of tumor immunity by epigenetic mechanisms has yet to be investigated. In this study, we examined the relationship between the repressive PRC2 machinery and effector T-cell trafficking. We found that PRC2 components and demethylase JMJD3-mediated histone H3 lysine 27 trimethylation (H3K27me3) repress the expression and subsequent production of Th1-type chemokines CXCL9 and CXCL10, mediators of effector T-cell trafficking. Moreover, the expression levels of PRC2 components, including EZH2, SUZ12, and EED, were inversely associated with those of CD4, CD8, and Th1-type chemokines in human colon cancer tissue, and this expression pattern was significantly associated with patient survival. Collectively, our findings reveal that PRC2-mediated epigenetic silencing is not only a crucial oncogenic mechanism, but also a key circuit controlling tumor immunosuppression. Therefore, targeting epigenetic programs may have significant implications for improving the efficacy of current cancer immunotherapies relying on effective T-cell–mediated immunity at the tumor site. Cancer Res; 76(2); 275–82. ©2015 AACR.
Promises and Challenges of Smac Mimetics as Cancer Therapeutics
Authors: Fulda Simone 
Published: November 2015

Abstract
Inhibitor of Apoptosis (IAP) proteins block programmed cell death and are expressed at high levels in various human cancers, thus making them attractive targets for cancer drug development. Second mitochondrial activator of caspases (Smac) mimetics are small-molecule inhibitors that mimic Smac, an endogenous antagonist of IAP proteins. Preclinical studies have shown that Smac mimetics can directly trigger cancer cell death or, even more importantly, sensitize tumor cells for various cytotoxic therapies, including conventional chemotherapy, radiotherapy, or novel agents. Currently, several Smac mimetics are under evaluation in early clinical trials as monotherapy or in rational combinations (i.e., GDC-0917/CUDC-427, LCL161, AT-406/Debio1143, HGS1029, and TL32711/birinapant). This review discusses the promise as well as some challenges at the translational interface of exploiting Smac mimetics as cancer therapeutics. Clin Cancer Res; 21(22); 5030–6. ©2015 AACR.
See all articles in this CCR Focus section, “Cell Death and Cancer Therapy.”
Autophagy, Metabolism, and Cancer
Authors: White Eileen , Mehnert Janice M. , Chan Chang S. 
Published: November 2015

Abstract
Macroautophagy (autophagy hereafter) captures intracellular proteins and organelles and degrades them in lysosomes. The degradation breakdown products are released from lysosomes and recycled into metabolic and biosynthetic pathways. Basal autophagy provides protein and organelle quality control by eliminating damaged cellular components. Starvation-induced autophagy recycles intracellular components into metabolic pathways to sustain mitochondrial metabolic function and energy homeostasis. Recycling by autophagy is essential for yeast and mammals to survive starvation through intracellular nutrient scavenging. Autophagy suppresses degenerative diseases and has a context-dependent role in cancer. In some models, cancer initiation is suppressed by autophagy. By preventing the toxic accumulation of damaged protein and organelles, particularly mitochondria, autophagy limits oxidative stress, chronic tissue damage, and oncogenic signaling, which suppresses cancer initiation. This suggests a role for autophagy stimulation in cancer prevention, although the role of autophagy in the suppression of human cancer is unclear. In contrast, some cancers induce autophagy and are dependent on autophagy for survival. Much in the way that autophagy promotes survival in starvation, cancers can use autophagy-mediated recycling to maintain mitochondrial function and energy homeostasis to meet the elevated metabolic demand of growth and proliferation. Thus, autophagy inhibition may be beneficial for cancer therapy. Moreover, tumors are more autophagy-dependent than normal tissues, suggesting that there is a therapeutic window. Despite these insights, many important unanswered questions remain about the exact mechanisms of autophagy-mediated cancer suppression and promotion, how relevant these observations are to humans, and whether the autophagy pathway can be modulated therapeutically in cancer. Clin Cancer Res; 21(22); 5037–46. ©2015 AACR.
See all articles in this CCR Focus section, “Cell Death and Cancer Therapy.”
Cell Death and Cancer Therapy: Don't Forget to Kill the Cancer Cell!
Authors: Letai Anthony 
Published: November 2015

Abstract
In our current age of targeted therapies, there is understandably considerable attention paid to the specific molecular targets of pharmaceutical intervention. For a targeted drug to work, it must bind to a target selectively and impair its function. Monitoring biomarkers of the impaired target function can provide vital in vivo pharmacodynamic information. Moreover, genetic changes to the target are often the source of resistance to targeted agents. However, for the treatment of cancer, it is necessary that the therapy not only provide efficient binding and inhibition of the target, but also that this intervention reliably kills the cancer cell. In this CCR Focus section, four articles make the connection between therapies that target T-cell activation, autophagy, IAP proteins, and BCL-2 and the commitment of cancer cells to cell death. Before addressing those exciting classes of targeted therapies, however, an overview is provided to discuss cell death induced by what is arguably still the most successful set of drugs in the history of medical oncology, conventional chemotherapy. Clin Cancer Res; 21(22); 5015–20. ©2015 AACR.
See all articles in this CCR Focus section, "Cell Death and Cancer Therapy."
Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms
Authors: Diamond Eli L. , Durham Benjamin H. , Haroche Julien , Yao Zhan , Ma Jing , Parikh Sameer A. , Wang Zhaoming , Choi John , Kim Eunhee , Cohen-Aubart Fleur , Lee Stanley Chun-Wei , Gao Yijun , Micol Jean-Baptiste , Campbell Patrick , Walsh Michael P. , Sylvester Brooke , Dolgalev Igor , Aminova Olga , Heguy Adriana , Zappile Paul , Nakitandwe Joy , Ganzel Chezi , Dalton James D. , Ellison David W. , Estrada-Veras Juvianee , Lacouture Mario , Gahl William A. , Stephens Philip J. , Miller Vincent A. , Ross Jeffrey S. , Ali Siraj M. , Briggs Samuel R. , Fasan Omotayo , Block Jared , Héritier Sebastien , Donadieu Jean , Solit David B. , Hyman David M. , Baselga José , Janku Filip , Taylor Barry S. , Park Christopher Y. , Amoura Zahir , Dogan Ahmet , Emile Jean-Francois , Rosen Neal , Gruber Tanja A. , Abdel-Wahab Omar 
Published: November 2015

Abstract
Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (non-LCH), respectively. The discovery of BRAFV600E mutations in approximately 50% of these patients provided the first molecular therapeutic target in histiocytosis. However, recurrent driving mutations in the majority of patients with BRAFV600E–wild-type non-LCH are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole-exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in patients with BRAFV600E–wild-type non-LCH. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of patients with MAP2K1- and ARAF-mutated non-LCH using MEK and RAF inhibitors, respectively, resulted in clinical efficacy, demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders.
Significance: We provide the first description of kinase fusions in systemic histiocytic neoplasms and activating ARAF and MAP2K1 mutations in non-Langerhans histiocytic neoplasms. Refractory patients with MAP2K1- and ARAF-mutant histiocytoses had clinical responses to MEK inhibition and sorafenib, respectively, highlighting the importance of comprehensive genomic analysis of these disorders. Cancer Discov; 6(2); 154–65. ©2015 AACR.
This article is highlighted in the In This Issue feature, p. 109