bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Exploratory Study of Respiratory Quotient Calibration and Association with Postmenopausal Breast Cancer
Authors: Prentice Ross L. , Neuhouser Marian L. , Tinker Lesley F. , Pettinger Mary , Thomson Cynthia A. , Mossavar-Rahmani Yasmin , Thomas Fridtjof , Qi Lihong , Huang Ying 
Published: October 2013

AbstractBackground: The respiratory quotient (RQ), defined as the ratio of carbon dioxide exhaled to oxygen uptake, reflects substrate utilization when energy is expended. Fat and alcohol have RQ values of approximately 0.7, compared with 1.0 for carbohydrate, and approximately 0.8 for protein. Here, the association between RQ and postmenopausal breast cancer risk is studied.Methods: Paired RQ measurements were obtained, separated by approximately 6 months, for women in the reliability subset of a Women's Health Initiative (WHI) Nutrition and Physical Activity Assessment Study. Linear regression of the average of the paired log RQ assessments on a corresponding log food quotient (FQ) average and other study subject characteristics, including age, body mass index, race, and education, yielded calibration equations for predicting RQ.Results: Calibration equations, using any of food frequency, food record, or dietary recall data, explained an appreciable fraction of measured log RQ variation, and these were used to compute calibrated RQ estimates throughout WHI cohorts. Calibrated RQ estimates using 4-day food record (4DFR) data related inversely (P = 0.004) to (invasive) breast cancer risk in the WHI Dietary Modification trial comparison group, and corresponding RQ estimates using food-frequency data related inversely (P = 0.002) to breast cancer incidence in this cohort combined with the larger WHI observational study.Conclusion: Although preliminary, these analyses suggest a substantially higher postmenopausal breast cancer risk among women having relatively low RQ.Impact: RQ elevation could provide a novel target for breast cancer risk reduction. Cancer Epidemiol Biomarkers Prev; 22(12); 2374–83. ©2013 AACR.
Circulating Soluble CD27 and CD30 in Workers Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
Authors: Saberi Hosnijeh Fatemeh , Portengen Lützen , Bueno-de-Mesquita H. Bas , Heederik Dick , Vermeulen Roel 
Published: October 2013

Abstract
Previous studies suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings remain inconclusive. There is a need for mechanistic studies to evaluate the biologic plausibility of this association. In this cross-sectional study, we investigated changes in plasma levels of interleukin 1 receptor antagonist (IL1RA) and soluble (s)CD27 and sCD30 which have been found to be predictive of lymphoma, among workers of a cohort occupationally exposed to TCDD. Eighty-five workers who had been exposed to TCDD more than 30 years before blood collection were included in the current investigation. Plasma level of the markers was measured by ELISA. Current plasma levels of TCDD were determined by high-resolution gas chromatography/isotope dilution high-resolution mass spectrometry. TCDD blood levels at time of last exposure were estimated using a one-compartment first order kinetic model. Exposure-response analyses showed no significant association between blood levels of sCD27, and sCD30 and current and estimated TCDD levels at time of last exposure. IL1RA showed a borderline significant decrease with increasing plasma TCDD levels (P = 0.07), which reached formal statistical significance when excluding subjects with chronic diseases. In conclusion, no clear dose–response relationship was observed between the measured markers and TCDD level. However, there was a suggestion that markers in particular IL1RA tended to decrease with increasing TCDD levels. This observation is consistent with our earlier observation on decreasing cytokine levels, suggesting immunosuppression, with increasing exposures. These findings possibly provide new insights in the etiology of NHL and the mechanisms through which TCDD can increase lymphoma risk. Cancer Epidemiol Biomarkers Prev; 22(12); 2420–4. ©2013 AACR.
Parity and Kidney Cancer Risk: Evidence from Epidemiologic Studies
Authors: Guan Hong-Bo , Wu Qi-Jun , Gong Ting-Ting 
Published: October 2013

Abstract
Background: Observational studies have reported conflicting results between parity and kidney cancer risk. To our knowledge, a comprehensive and quantitative assessment of the association between parity and kidney cancer has not been reported. Thus, we conducted a systematic review and dose–response meta-analysis of published epidemiologic studies to summarize the evidence of this association.
Methods: Relevant published studies of parity and kidney cancer were identified using MEDLINE (PubMed) database through end of June 2013. Two authors independently assessed eligibility and extracted data. Six prospective and eight case–control studies reported relative risk (RR) estimates and 95% confidence intervals (CI) of kidney cancer associated with parity or parity number. Fixed- or random-effects models were used to estimate summary relative risk.
Results: The summary relative risk of kidney cancer for the parity versus nulliparous was 1.23 (95% CI, 1.10–1.36; Q = 12.41; P = 0.413; I2 = 3.3%). In addition, significant association was also found for the highest versus lowest parity number, with summary RR = 1.36 (95% CI, 1.19–1.56; Q = 8.24; P = 0.766; I2 = 0%). In the dose–response analysis, the summary per one live birth relative risk was 1.08 (95% CI: 1.05–1.10; Q = 9.34; P = 0.500; I2 = 0%), also indicating the positive effect of parity on kidney cancer risk. No evidence of publication bias and significant heterogeneity between subgroups was detected by meta-regression analyses.
Conclusions: In summary, findings from this meta-analysis suggest that ever parity and higher parity number is significantly associated with increased risk of kidney cancer.
Impact: The present results suggest a positive association between parity and kidney cancer risk. Cancer Epidemiol Biomarkers Prev; 22(12); 2345–53. ©2013 AACR.
Small Molecule Inhibition of PAX3-FOXO1 through AKT Activation Suppresses Malignant Phenotypes of Alveolar Rhabdomyosarcoma
Authors: Jothi Mathivanan , Mal Munmun , Keller Charles , Mal Asoke K. 
Published: October 2013

Abstract
Alveolar rhabdomyosarcoma comprises a rare highly malignant tumor presumed to be associated with skeletal muscle lineage in children. The hallmark of the majority of alveolar rhabdomyosarcoma is a chromosomal translocation that generates the PAX3-FOXO1 fusion protein, which is an oncogenic transcription factor responsible for the development of the malignant phenotype of this tumor. Alveolar rhabdomyosarcoma cells are dependent on the oncogenic activity of PAX3-FOXO1, and its expression status in alveolar rhabdomyosarcoma tumors correlates with worst patient outcome, suggesting that blocking this activity of PAX3-FOXO1 may be an attractive therapeutic strategy against this fusion-positive disease. In this study, we screened small molecule chemical libraries for inhibitors of PAX3-FOXO1 transcriptional activity using a cell-based readout system. We identified the Sarco/endoplasmic reticulum Ca2+-ATPases (SERCA) inhibitor thapsigargin as an effective inhibitor of PAX3-FOXO1. Subsequent experiments in alveolar rhabdomyosarcoma cells showed that activation of AKT by thapsigargin inhibited PAX3-FOXO1 activity via phosphorylation. Moreover, this AKT activation appears to be associated with the effects of thapsigargin on intracellular calcium levels. Furthermore, thapsigargin inhibited the binding of PAX3-FOXO1 to target genes and subsequently promoted its proteasomal degradation. In addition, thapsigargin treatment decreases the growth and invasive capacity of alveolar rhabdomyosarcoma cells while inducing apoptosis in vitro. Finally, thapsigargin can suppress the growth of an alveolar rhabdomyosarcoma xenograft tumor in vivo. These data reveal that thapsigargin-induced activation of AKT is an effective mechanism to inhibit PAX3-FOXO1 and a potential agent for targeted therapy against alveolar rhabdomyosarcoma. Mol Cancer Ther; 12(12); 2663–74. ©2013 AACR.
SIRT1 Is Downregulated in Gastric Cancer and Leads to G1-phase Arrest via NF-κB/Cyclin D1 Signaling
Authors: Yang Qing , Wang Bo , Gao Wei , Huang Shanying , Liu Zhifang , Li Wenjuan , Jia Jihui 
Published: October 2013

Abstract
Sirtuin 1 (SIRT1) is a class III histone/protein deacetylase, and its activation status has been well documented to have physiologic benefits in human health. However, the function of SIRT1 in cancer remains controversial. Here, the expression and role of SIRT1 in gastric cancer is delineated. SIRT1 was present in all normal gastric mucosa specimens; however, it was only present in a portion of the matched gastric cancer tumor specimens. In SIRT1-positive tumors, both mRNA and protein levels were downregulated as compared with the corresponding nonneoplastic tissue. Ectopic expression of SIRT1 inhibited cell proliferation, diminished clonogenic potential, and induced a G1-phase cell-cycle arrest, the effects of which were not apparent when a catalytic-domain mutant form of SIRT1 was introduced, suggesting that SIRT1 functions in gastric cancer are dependent on its deacetylase activity. Further evidence was obtained from depletion of SIRT1. At the molecular level, SIRT1 inhibited the transcription of Cyclin D1 (CCND1), and inhibition of NF-κB in SIRT1-depleted cells rescued Cyclin D1 expression. Furthermore, inhibition of either NF-κB or Cyclin D1 in SIRT1-depleted cells reversed the inhibitory effects of SIRT1. The inhibitory role of SIRT1 was also verified in vivo using xenografts. This work characterizes SIRT1 status and demonstrates its inhibitory function in gastric cancer development, which involves NF-κB/Cyclin D1 signaling, offering a therapeutic role for SIRT1 activators.
Implications: The inhibitory functions of SIRT1, which involve NF-κB/Cyclin D1 signaling, suggest the utility of SIRT1 activators in the prevention and therapy of gastric cancer. Mol Cancer Res; 11(12); 1497–507. ©2013 AACR.
An Abscopal Response to Radiation and Ipilimumab in a Patient with Metastatic Non–Small Cell Lung Cancer
Authors: Golden Encouse B. , Demaria Sandra , Schiff Peter B. , Chachoua Abraham , Formenti Silvia C. 
Published: October 2013

AbstractA posteriori evidence suggests that radiotherapy to a targeted tumor can elicit an immune-mediated abscopal (ab-scopus, away from the target) effect in nontargeted tumors, when combined with an anti-CTL antigen-4 (CTLA-4) monoclonal antibody. Concurrent radiotherapy and CTLA-4 blockade induced immune-mediated abscopal effects in poorly immunogenic preclinical tumor models and patients with metastatic melanoma. However, no such reports exist for patients with metastatic lung adenocarcinoma. We report the first abscopal response in a treatment-refractory lung cancer patient treated with radiotherapy and ipilimumab (a human anti-CTLA-4 monoclonal antibody). A posttreatment increase in tumor-infiltrating cytotoxic lymphocytes, tumor regression, and normalization of tumor markers was observed. One year after treatment with concurrent radiotherapy and ipilimumab, the patient is without evidence of disease. Cancer Immunol Res; 1(6); 365–72. ©2013 AACR.
CCR6 selectively promotes monocyte mediated inflammation and atherogenesis in mice
Authors: Manthey Helga D. , Cochain Clément , Barnsteiner Stefanie , Karshovska Ela , Pelisek Jaroslav , Koch Miriam , Chaudhari Sweena M. , Busch Martin , Eckstein Hans-Henning , Weber Christian , Koenen Rory R. , Zernecke Alma 
Published: October 2013

SummaryThe chemokine receptor CCR6 is expressed by various cell subsets implicated in atherogenesis, such as monocytes, Th17 and regulatory T cells. In order to further define the role of CCR6 in atherosclerosis, CCR6-deficient (Ccr6
-/-) mice were crossed with low-density lipoprotein receptor-deficient (Ldlr
-/-) mice to generate atherosclerosis-prone mice deficient in CCR6. Compared to Ldlr
-/- controls, atherosclerotic burden in the aortic sinus and aorta were reduced in Ccr6
-/-
Ldlr
-/- mice fed a high fat diet, associated with a profound depression in lesional macrophage accumulation. Local and systemic distributions of T cells, including frequencies of Th1, Th17 and regulatory T cells were unaltered. In contrast, circulating counts of both Gr-1high and Gr1low monocytes were reduced in Ccr6
-/-
Ldlr
-/- mice. Moreover, CCR6 was revealed to promote monocyte adhesion to inflamed endothelium in vitro and leukocyte adhesion to carotid arteries in vivo. Finally, CCR6 selectively recruited monocytes but not T cells in an acute inflammatory air pouch model. We here show that CCR6 functions on multiple levels and regulates the mobilisation, adhesion and recruitment of monocytes/macrophages to the inflamed vessel, thereby promoting atherosclerosis, but is dispensable for hypercholesterolaemia-associated adaptive immune priming. Targeting CCR6 or its ligand CCL20 may therefore be a promising therapeutic strategy to alleviate atherosclerosis.Note: The review process for this manuscript was fully handled by G. Y. H. Lip, Editor in Chief.
Extracellular haemoglobin upregulates and binds to tissue factor on macrophages: Implications for coagulation and oxidative stress
Authors: Bahl Neha , Winarsih Imelda , Tucker-Kellogg Lisa , Ding Jeak Ling 
Published: October 2013

SummaryThe mechanisms of crosstalk between haemolysis, coagulation and innate immunity are evolutionarily conserved from the invertebrate haemocyanin to the vertebrate haemoglobin (Hb). In vertebrates, extracellular Hb resulting from haemolytic infections binds bacterial lipopolysaccharide (LPS) to unleash the antimicrobial redox activity of Hb. Because bacterial invasion also upregulates tissue factor (TF), the vertebrate coagulation initiator, we asked whether there may be functional interplay between the redox activity of Hb and the procoagulant activity of TF. Using real-time PCR, TF-specific ELISA, flow cytometry and TF activity assay, we found that Hb upregulated the expression of functional TF in macrophages. ELISA, flow cytometry and immunofluorescence microscopy showed binding between Hb and TF, in isolation and in situ. Bioinformatic analysis of Hb and TF protein sequences showed co-evolution across species, suggesting that Hbβ binds TF. Empirically, TF suppressed the LPS-induced activation of Hb redox activity. Furthermore, Hb desensitised TF to the effects of antioxidants like glutathione or serum. This bi-directional regulation between Hb and TF constitutes a novel link between coagulation and innate immunity. In addition, induction of TF by Hb is a potentially central mechanism for haemolysis to trigger coagulation.
Nitroxyl (HNO)
Authors: Sabbah Hani N. , Tocchetti Carlo Gabriele , Wang Mengjun , Daya Samantapudi , Gupta Ramesh C. , Tunin Richard S. , Mazhari Reza , Takimoto Eiki , Paolocci Nazareno , Cowart Douglas , Colucci Wilson S. , Kass David A. 
Published: October 2013

Background—
The nitroxyl (HNO) donor, Angeli’s salt, exerts positive inotropic, lusitropic, and vasodilator effects in vivo that are cAMP independent. Its clinical usefulness is limited by chemical instability and cogeneration of nitrite which itself has vascular effects. Here, we report on effects of a novel, stable, pure HNO donor (CXL-1020) in isolated myoctyes and intact hearts in experimental models and in patients with heart failure (HF).

Methods and Results—

CXL-1020 converts solely to HNO and inactive CXL-1051 with a t
1/2
of 2 minutes. In adult mouse ventricular myocytes, it dose dependently increased sarcomere shortening by 75% to 210% (50–500 μmol/L), with a ≈30% rise in the peak Ca
2+
transient only at higher doses. Neither inhibition of protein kinase A nor soluble guanylate cyclase altered this contractile response. Unlike isoproterenol, CXL-1020 was equally effective in myocytes from normal or failing hearts. In anesthetized dogs with coronary microembolization-induced HF, CXL-1020 reduced left ventricular end-diastolic pressure and myocardial oxygen consumption while increasing ejection fraction from 27% to 40% and maximal ventricular power index by 42% (both
P
<0.05). In conscious dogs with tachypacing-induced HF, CXL-1020 increased contractility assessed by end-systolic elastance and provided venoarterial dilation. Heart rate was minimally altered. In patients with systolic HF, CXL-1020 reduced both left and right heart filling pressures and systemic vascular resistance, while increasing cardiac and stroke volume index. Heart rate was unchanged, and arterial pressure declined modestly.

Conclusions—
These data show the functional efficacy of a novel pure HNO donor to enhance myocardial function and present first-in-man evidence for its potential usefulness in HF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT01096043, NCT01092325.
Writing about the “Other”: Israel in Recent Iraqi Novels
Authors: Zeidel Ronen 
Published: October 2013

Abstract
Writing about Israel is extremely rare in the Arab world. For many in the Arab World, Israel is the ultimate “Other”. This article will discuss several recent Iraqi novels in which part or the entire plot takes place in Israel. The books were written by leading Arab Iraqi novelists and were published by publishers in Iraq and the Arab world. Despite their small number, the books originate from a significant change in Iraqi intellectual life, especially after 2003: the emergence of a new literary generation “The Generation of the 1990s” (ğīl al-tisʿīnāt), challenging the basics of Iraqi national culture. The article will explore this development from the point of view of the “Other”: an Israeli scholar.
Dysfunctional family environment in affected versus unaffected offspring of parents with bipolar disorder
Authors: Ferreira Guilherme S , Moreira Carolina RL , Kleinman Ana , Nader Edmir CGP , Gomes Bernardo Carramão , Teixeira Ana Maria A , Rocca Cristiana C Almeida , Nicoletti Mark , Soares Jair C , Busatto Geraldo F , Lafer Beny , Caetano Sheila C 
Published: October 2013

Objective: Children of parents with bipolar disorder (BD) are at heightened risk for developing mood and other psychiatric disorders. We proposed to evaluate the environment of families with at least one parent with BD type I (BDF) with affected offspring (aBDF) and unaffected offspring (uBDF) compared with control families without a history of DSM-IV Axis I disorder (CF). Method: We used the Family Environment Scale (FES) to evaluate 47 BDF (aBDF + uBDF) and 30 CF. Parents were assessed through the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Diagnosis of the offspring was determined through the Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Version (K-SADS-PL) interview. Results: There were statistically significant differences between aBDF, uBDF and CF in cohesion ( p = 0.003), intellectual-cultural orientation ( p = 0.01), active-recreational orientation ( p = 0.007), conflict ( p = 0.001), control ( p = 0.01), moral-religious emphasis ( p = 0.01) and organization ( p = 0.001). The aBDF showed higher levels of control ( p = 0.02) when compared to the uBDF. Conclusions: Families with a BD parent presented more dysfunctional interactions among members. Moreover, the presence of BD or other psychiatric disorders in the offspring of parents with BD is associated with higher levels of control. These results highlight the relevance of psychosocial interventions to improve resilience and family interactions.
Gender, ethnicity and graduate status, and junior doctors’ self-reported preparedness for clinical practice: national questionnaire surveys
Authors: Svirko Elena , Lambert Trevor , Goldacre Michael J 
Published: October 2013

Objectives Medical schools need to ensure that graduates feel well prepared for their first medical job. Our objective was to report on differences in junior doctors’ self-reported preparedness for work according to gender, ethnicity and graduate status. Design Postal and electronic questionnaires. Setting UK. Participants Medical graduates of 2008 and 2009, from all UK medical schools, one year after graduation. Main outcome measures The main outcome measure was the doctors’ level of agreement with the statement that ‘ My experience at medical school prepared me well for the jobs I have undertaken so far’, to which respondents were asked to reply on a scale from ‘ strongly agree’ to ‘ strongly disagree’. Results Women were slightly less likely than men to agree that they felt well prepared for work (50% of women agreed or strongly agreed vs. 54% of men), independently of medical school, ethnicity, graduate entry status and intercalated degree status, although they were no more likely than men to regard lack of preparedness as having been a problem for them. Adjusting for the other subgroup differences, non-white respondents were less likely to report feeling well prepared than white (44% vs. 54%), and were more likely to indicate that lack of preparedness was a problem (30% non-white vs. 24% white). There were also some gender and ethnic differences in preparedness for specific areas of work. Conclusions The identified gender and ethnic differences need to be further explored to determine whether they are due to differences in self-confidence or in actual preparedness.
Compassion in healthcare – lessons from a qualitative study of the end of life care of people with dementia
Authors: Crowther Jacqueline , Wilson Kenneth CM , Horton Siobhan , Lloyd-Williams Mari 
Published: October 2013

Objectives A lack of compassion in UK healthcare settings has received much recent attention. This study explores the experiences of people with dementia in the last year of life and time surrounding death and how the presence and lack of compassion, kindness and humanity influenced the experience of care. Design Qualitative in-depth interviews with bereaved informal carers of people with dementia. Setting United Kingdom. Participants Forty bereaved carers – 31 women and nine men – with an age range of 18–86 years and from wide socioeconomic backgrounds participated. Main outcome measures Experiences of carers of care for person with dementia during last year of life. Results The interviews highlighted differences and challenges in care settings in providing compassionate, humanistic care and the impact of the care experienced by the person with dementia during the last year of life on informal carers during the bereavement period and beyond. Excellent examples of compassionate care were experienced alongside very poor and inhumane practices. Conclusion The concepts of compassion, kindness and humanity in dementia care are discussed within the paper. The ability to deliver care that is compassionate, kind and humanistic exists along a continuum across care settings – examples of excellent care sit alongside examples of very poor care and the reasons for this are explored together with discussion as to how health and social care staff can be trained and supported to deliver compassionate care.