bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between women's smoking and laryngeal disorders based on the urine cotinine test: results of a national population-based survey
Authors: Byeon Haewon , Lee Dongwoo , Cho Sunghyoun 
Published: November 2016

ObjectivesThere is a possibility of underestimation in the smoking rate surveyed by self-reported questionnaires. This study investigated the difference between the Korean female smoking rate as determined by self-reports and that determined by a biochemical test and elucidated the relationship between women's smoking and laryngeal disorders.DesignNationwide cross-sectional survey.Setting2008 Korea National Health and Nutrition Examination Survey.Participants1849 women who completed the health survey, urinary cotinine test and laryngoscope examinations.Main outcome measureThis study defined smokers as those with urine cotinine contents of 50 ng/mL and over. Confounding factors included age, level of education, household income, occupation and problem drinking in the past year. For statistical tests, OR and 95% CI were presented by using complex samples logistic regression.ResultsWhile there was no relationship between smoking as determined by a self-reported questionnaire and laryngeal disorders, smoking as determined by the urine cotinine test had a significant relationship with laryngeal disorders (p<0.05). After all the confounding factors were adjusted, those with urine cotinine concentrations of over 50 ng/mL had a 2.1 times higher risk of laryngeal disorders than those with urine cotinine concentrations of <50 ng/mL (OR=2.05, 95% CI 1.11 to 3.78) (p<0.05).ConclusionsThis national cross-sectional study verified that smoking is a significant risk factor for laryngeal disorders. Longitudinal studies are required to identify the causal relationship between smoking and laryngeal disorders.
Early Diagnosis of Gestational Diabetes Mellitus (EDoGDM) study: a protocol for a prospective, longitudinal cohort study
Authors: Liu Bin , Xu Yun , Zhang Ying , Cai Jian , Deng Langhui , Yang Jianbo , Zhou Yi , Long Yuhang , Zhang Jinxin , Wang Zilian 
Published: November 2016

IntroductionA diagnosis of gestational diabetes mellitus (GDM) in low-risk pregnant women is based on an oral glucose tolerance test (OGTT) between 24 and 28 gestational weeks. However, there is insufficient evidence for why the test is performed in this time period. Moreover, the fetus may be exposed to hyperglycaemia prior to the current testing time frame, making earlier administration potentially advantageous. The main purpose of the present study is to investigate the GDM diagnostic value of an OGTT performed at 18–20 gestational weeks. The results of the study may provide scientific insight into the most beneficial time of OGTT for pregnant women.Methods and analysisAs a prospective, longitudinal cohort study, the Early Diagnosis of Gestational Diabetes Mellitus (EDoGDM) study will recruit 570 pregnant women who meet the inclusion and exclusion criteria outlined below. OGTTs will be performed between 18 and 20 gestational weeks (early OGTT) and 24–28 gestational weeks (regular OGTT). Clinical and laboratory information of the mother and their offspring will be collected for analysis. The prevalence of GDM at 18–20 gestational weeks will be described, and the sensitivity, specificity, positive predictive value and negative predictive value of early OGTT on diagnosis of GDM will be studied. Clinical outcomes associated with hyperglycaemia will be compared between groups diagnosed by early or regular OGTT.Ethics and disseminationThe study was approved by The Ethical Committees of The First Affiliated Hospital of Sun Yat-sen University (number 2016-042). Signed informed consent will be obtained from all participants. The results of this study will be disseminated in peer-reviewed journals.Trial registration numberNCT02740283.
Protocol for a multicentre randomised feasibility trial evaluating early Surgery Alone In LOw Rectal cancer (SAILOR)
Authors: Harris Dean A , Thorne Kymberley , Hutchings Hayley , Islam Saiful , Holland Gail , Hatcher Olivia , Gwynne Sarah , Jenkins Ian , Coyne Peter , Duff Michael , Feldman Melanie , Winter Des C , Gollins Simon , Quirke Phil , West Nick , Brown Gina , Fitzsimmons Deborah , Brown Alan , Beynon John 
Published: November 2016

IntroductionThere are 11 500 rectal cancers diagnosed annually in the UK. Although surgery remains the primary treatment, there is evidence that preoperative radiotherapy (RT) improves local recurrence rates. High-quality surgery in rectal cancer is equally important in minimising local recurrence. Advances in MRI-guided prediction of resection margin status and improvements in abdominoperineal excision of the rectum (APER) technique supports a reassessment of the contribution of preoperative RT. A more selective approach to RT may be appropriate given the associated toxicity.Methods and analysisThis trial will explore the feasibility of a definitive trial evaluating the omission of RT in resectable low rectal cancer requiring APER. It will test the feasibility of randomising patients to (1) standard care (neoadjuvant long course RT±chemotherapy and APER, or (2) APER surgery alone for cT2/T3ab N0/1 low rectal cancer with clear predicted resection margins on MRI. RT schedule will be 45 Gy over 5 weeks as current standard, with restaging and surgery after 8–12 weeks. Recruitment will be for 24 months with a minimum 12-month follow-up.ObjectivesObjectives include testing the ability to recruit, consent and retain patients, to quantify the number of patients eligible for a definitive trial and to test feasibility of outcomes measures. These include locoregional recurrence rates, distance to circumferential resection margin, toxicity and surgical complications including perineal wound healing, quality of life and economic analysis. The quality of MRI staging, RT delivery and surgical specimen quality will be closely monitored.Ethics and disseminationThe trial is approved by the Regional Ethics Committee and Health Research Authority (HRA) or equivalent. Written informed consent will be obtained. Serious adverse events will be reported to Swansea Trials Unit (STU), the ethics committee and trial sites. Trial results will be submitted for peer review publication and to trial participants.Trial registration numberISRCTN02406823.
Cost burden of type 2 diabetes in Germany: results from the population-based KORA studies
Authors: Ulrich Susanne , Holle Rolf , Wacker Margarethe , Stark Renee , Icks Andrea , Thorand Barbara , Peters Annette , Laxy Michael 
Published: November 2016

ObjectiveTo examine the impact of type 2 diabetes on direct and indirect costs and to describe the effect of relevant diabetes-related factors, such as type of treatment or glycaemic control on direct costs.DesignBottom-up excess cost analysis from a societal perspective based on population-based survey data.Participants9160 observations from 6803 individuals aged 31–96 years (9.6% with type 2 diabetes) from the population-based KORA (Cooperative Health Research in the Region of Augsburg) studies in Southern Germany.Outcome measuresHealthcare usage, productivity losses, and resulting direct and indirect costs.MethodsInformation on diabetes status, biomedical/sociodemographic variables, medical history and on healthcare usage and productivity losses was assessed in standardised interviews and examinations. Healthcare usage and productivity losses were costed with reference to unit prices and excess costs of type 2 diabetes were calculated using generalised linear models.ResultsIndividuals with type 2 diabetes had 1.81 (95% CI 1.56 to 2.11) times higher direct (€3352 vs €1849) and 2.07 (1.51 to 2.84) times higher indirect (€4103 vs €1981) annual costs than those without diabetes. Cardiovascular complications, a long diabetes duration and treatment with insulin were significantly associated with increased direct costs; however, glycaemic control was only weakly insignificantly associated with costs.ConclusionsThis study illustrates the substantial direct and indirect societal cost burden of type 2 diabetes in Germany. Strong effort is needed to optimise care to avoid progression of the disease and costly complications.
The Challenge of Universal Eye Health in Latin America: distributive inequality of ophthalmologists in 14 countries
Authors: Hong Hannah , Mújica Oscar J , Anaya José , Lansingh Van C , López Ellery , Silva Juan Carlos 
Published: November 2016

BackgroundNo comprehensive study currently exists on the supply of ophthalmologists across Latin America. We explored sociogeographic inequalities in the availability and distribution of ophthalmologists across 14 Latin American countries.MethodsThe National Ophthalmologic Societies of Argentina, Bolivia, Brazil, Colombia, Costa Rica, Chile, the Dominican Republic, Ecuador, Guatemala, Mexico, Paraguay, Peru, Uruguay and Venezuela provided data on affiliated ophthalmologists by first-order subnational divisions in 2013. Human Development Index (HDI) estimates at the corresponding subnational division were used as equity stratifiers. Distributional inequality of ophthalmologists within each country was assessed by the health concentration index (HCI) and the index of dissimilarity (ID), along with the mean level of ophthalmologists per population.ResultsAcross all countries studied, there were 5.2 ophthalmologists per 100 000 population on average (95% CI 5.0 to 5.4) in 2013, with a mean HCI of 0.26 (0.16 to 0.37) and a mean relative ID of 22.7% (20.9% to 24.7%). There was wide inequality in ophthalmologist availability between countries, ranging from 1.2 (1.1 to 1.4) in Ecuador to 8.6 (8.5 to 8.8) in Brazil. All countries had positive (ie, pro-rich) HCI values ranging from 0.68 (0.66 to 0.71) in Guatemala to 0.02 (−0.11 to 0.14) in Venezuela. Correspondingly, redistributive potential to achieve equity was closest in Venezuela (ID: 1.5%) and farthest in Guatemala (ID: 60.3%). Benchmarked against regional averages, most countries had a lower availability of ophthalmologists and higher relative inequality.ConclusionsThere is high inequality in the level and distribution of ophthalmologists between and within countries in Latin America, with a disproportionate number concentrated in more developed, socially advantaged areas. More equitable access to ophthalmologists could be achieved by implementing incentivised human resources redistribution programmes and by improving the social determinants of health in underserved areas.
Polymyxin B-immobilised haemoperfusion and mortality in critically ill patients with sepsis/septic shock: a protocol for a systematic review and meta-analysis
Authors: Fujii Tomoko , Ganeko Riki , Kataoka Yuki , Featherstone Robin , Bagshaw Sean M , Furukawa Toshi A 
Published: November 2016

IntroductionPolymyxin-B immobilised haemoperfusion (PMX-HP) is a promising adjuvant strategy for the treatment of sepsis and septic shock. PMX-HP therapy works by clearing circulating endotoxin through binding to polymyxin-immobilised fibres during haemoperfusion. Small clinical trials have shown that PMX-HP therapy is associated with improved haemodynamic profile, oxygenation and survival. However, clear inferences have been largely inconclusive due to limitations in study design (eg, small, unblinded) and generalisability. We therefore propose to perform an up-to-date systematic review and evidence synthesis to describe the efficacy, safety and effectiveness of PMX-HP for adult patients with sepsis or septic shock.Methods and analysisWe will search the following databases from 1946 to 2016 MEDLINE (Ovid), EMBASE (Ovid), Cochrane Library, Health Technology Assessment Database (HTA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and ‘Igaku Chuo Zasshi’ (ICHUSHI) for randomised controlled trials of PMX-HP in critically ill patients with sepsis or septic shock. There will be no language restrictions in the electronic search for studies. Two reviewers will extract data and appraise the quality of each study independently. The primary outcome will be the pooled risk ratio of 28-day all-cause mortality. Serious adverse events and changes in organ dysfunction scores will also be evaluated. The secondary outcomes will be 90-day all-cause mortality, changes in haemodynamic profile and endotoxin levels, and health services use.Ethics and disseminationOur systematic review will synthesise the evidence on use of the PMX-HP as an adjuvant therapy in sepsis/septic shock to improve patient-centred, physiological and health services outcomes. Research ethics is not required for this review. The study will be disseminated by peer-reviewed publication and conference presentation.Trial registration numberCRD42016038356.
Railway suicide clusters: how common are they and what predicts them?
Authors: Too Lay San , Pirkis Jane , Milner Allison , Bugeja Lyndal , Spittal Matthew J 
Published: November 2016

BackgroundA growing number of studies have sought to detect clusters of all suicides, but few have sought to identify clusters of method-specific suicides.MethodsData on railway suicides occurring in Victoria, Australia, between 2001 and 2012 were obtained from the National Coronial Information System. We used the Poisson discrete scan statistic to identify railway suicides that occurred close together in space and/or time. We then used a case–control design to compare clustered railway suicides with non-clustered railway suicides on a range of individual and neighbourhood factors.ResultsWe detected four spatial clusters that accounted for 35% of all railway suicides. Railway suicides by individuals who were hospitalised for mental illness had nearly double the odds of being in a cluster compared with those individuals who had never been hospitalised (OR 1.80, 95% CI 1.02 to 3.18). Higher frequency train services were associated with increased odds of being in a cluster (OR 1.11, 95% CI 1.03 to 1.19). No other predictors were associated with being in a cluster.ConclusionsRailway suicides that occur in clusters warrant particular attention because of the ripple effect they can have for communities and the risk that they may lead to copycat acts. Railway suicide prevention strategies should consider the fact that these suicides can occur in clusters, particularly among individuals who had previous hospitalisations for mental illness or live in areas with high-frequency train services.
Preliminary conceptual design about the CEPC calorimeters
Authors: Yang Haijun 
Published: November 2016

The Circular Electron Positron Collider (CEPC) as a Higgs factory was proposed in September 2013. The preliminary conceptual design report was completed in 2015.1 The CEPC detector design was using International Linear Collider Detector — ILD2 as an initial baseline. The CEPC calorimeters, including the high granularity electromagnetic calorimeter (ECAL) and the hadron calorimeter (HCAL), are designed for precise energy measurements of electrons, photons, taus and hadronic jets. The basic resolution requirements for the ECAL and HCAL are about 16%[Formula: see text][Formula: see text] (GeV) and 50%[Formula: see text][Formula: see text] (GeV), respectively. To fully exploit the physics potential of the Higgs, [Formula: see text], [Formula: see text] and related Standard Model processes, the jet energy resolution is required to reach 3%–4%, or 30%/[Formula: see text] (GeV) at energies below about 100 GeV. To achieve the required performance, a Particle Flow Algorithm (PFA) — oriented calorimetry system is being considered as the baseline design. The CEPC ECAL detector options include silicon–tungsten or scintillator–tungsten structures with analog readout, while the HCAL detector options have scintillator or gaseous detector as the active sensor and iron as the absorber. Some latest R&D studies about ECAL and HCAL within the CEPC working group is also presented.
Targeting Tumor-Associated Fibroblasts for Therapeutic Delivery in Desmoplastic Tumors
Authors: Miao Lei , Liu Qi , Lin C. Michael , Luo Cong , Wang Yuhua , Liu Lina , Yin Weiyan , Hu Shihao , Kim William Y. , Huang Leaf 
Published: November 2016

Abstract
The off-target distribution of anticancer nanoparticles to fibroblasts creates a barrier to the effective treatment of desmoplastic tumors. However, we hypothesized that this nanoparticle detriment might be exploited to target the expression of secreted cytotoxic proteins from tumor-associated fibroblasts (TAF) as an anticancer strategy. In addressing this hypothesis, plasmids encoding the secretable TNF-related factor sTRAIL were loaded into lipid-coated protamine DNA complexes and administered by infusion in a murine xenograft model of human desmoplastic bladder carcinoma. Three doses were sufficient to generate approximately 70% of TAFs as sTRAIL-producing cells. sTRAIL triggered apoptosis in tumor cell nests adjacent to TAFs. Furthermore, it reverted residual fibroblasts to a quiescent state due to insufficient activation, further compromising tumor growth and remodeling the microenvironment to favor second-wave nanotherapy. We confirmed the efficacy of this strategy in an orthotopic xenograft model of human pancreatic cancer, where the desmoplastic stroma is well known to be a major barrier to the delivery of therapeutic nanoparticles. Collectively, our results offer a proof of concept for the use of nanoparticles to modify TAFs as an effective strategy to treat desmoplastic cancers. Cancer Res; 77(3); 719–31. ©2016 AACR.
Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer
Authors: Wali Vikram B. , Langdon Casey G. , Held Matthew A. , Platt James T. , Patwardhan Gauri A. , Safonov Anton , Aktas Bilge , Pusztai Lajos , Stern David F. , Hatzis Christos 
Published: November 2016

Abstract
Triple-negative breast cancer (TNBC) remains an aggressive disease without effective targeted therapies. In this study, we addressed this challenge by testing 128 FDA-approved or investigational drugs as either single agents or in 768 pairwise drug combinations in TNBC cell lines to identify synergistic combinations tractable to clinical translation. Medium-throughput results were scrutinized and extensively analyzed for sensitivity patterns, synergy, anticancer activity, and were validated in low-throughput experiments. Principal component analysis revealed that a fraction of all upregulated or downregulated genes of a particular targeted pathway could partly explain cell sensitivity toward agents targeting that pathway. Combination therapies deemed immediately tractable to translation included ABT-263/crizotinib, ABT-263/paclitaxel, paclitaxel/JQ1, ABT-263/XL-184, and paclitaxel/nutlin-3, all of which exhibited synergistic antiproliferative and apoptotic activity in multiple TNBC backgrounds. Mechanistic investigations of the ABT-263/crizotinib combination offering a potentially rapid path to clinic demonstrated RTK blockade, inhibition of mitogenic signaling, and proapoptotic signal induction in basal and mesenchymal stem–like TNBC. Our findings provide preclinical proof of concept for several combination treatments of TNBC, which offer near-term prospects for clinical translation. Cancer Res; 77(2); 566–78. ©2016 AACR.
E6 and E7 Antibody Levels Are Potential Biomarkers of Recurrence in Patients with Advanced-Stage Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma
Authors: Spector Matthew E. , Sacco Assuntina G. , Bellile Emily , Taylor Jeremy M.G. , Jones Tamara , Sun Kan , Brown William C. , Birkeland Andrew C. , Bradford Carol R. , Wolf Gregory T. , Prince Mark E. , Moyer Jeffrey S. , Malloy Kelly , Swiecicki Paul , Eisbruch Avraham , McHugh Jonathan B. , Chepeha Douglas B. , Rozek Laura , Worden Francis P. 
Published: November 2016

Abstract
Purpose: There is a paucity of biomarkers to predict failure in human papillomavirus–positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) following curative therapy. E6/E7 viral oncoproteins are constitutively expressed in HPV+ tumors and highly immunogenic, resulting in readily detected serum antibodies. The purpose of this study is to determine whether serum E6 and E7 antibody levels can potentially serve as a biomarker of recurrence in patients with HPV+OPSCC.
Experimental Design: We evaluated E6/E7 antibody levels in patients with previously untreated, advanced stage (III, IVa-b), HPV+OPSCC receiving definitive chemoradiation under a uniform protocol from 2003 to 2010. Baseline and longitudinal serum samples were obtained from our archived repository. E6/E7 serum levels were measured using a glutathione-S-transferase capture ELISA and quantified by approximating the area under the dilution curve, and were analyzed using ANOVA and linear mixed model for longitudinal analysis.
Results: We compared 22 HPV+OPSCC patients who developed recurrence with 30 patients who remained disease-free. There were no differences in T classification, N classification, disease subsite, or smoking status between the groups. In a longitudinal analysis, recurrent patients had significantly higher E6 and E7 serum antibody levels than the nonrecurrent patients over the follow-up period (P = 0.02 and P = 0.002, respectively). Patients who recurred had a lower clearance of E7 antibody than patients who remained disease-free (P = 0.0016).
Conclusions: Patients with HPV+OPSCC whose disease recurs have a lower clearance of E6 and E7 antibodies than patients who do not have recurrence. The ratio of E7 antibody at disease recurrence compared with baseline is potentially a clinically significant measurement of disease status in HPV+OPSCC. Clin Cancer Res; 23(11); 2723–9. ©2016 AACR.
A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors
Authors: Saura Cristina , Roda Desamparados , Roselló Susana , Oliveira Mafalda , Macarulla Teresa , Pérez-Fidalgo José Alejandro , Morales-Barrera Rafael , Sanchis-García Juan Manuel , Musib Luna , Budha Nageshwar , Zhu Jin , Nannini Michelle , Chan Wai Y. , Sanabria Bohórquez Sandra M. , Meng Raymond D. , Lin Kui , Yan Yibing , Patel Premal , Baselga José , Tabernero Josep , Cervantes Andrés 
Published: November 2016

Abstract
Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of AKT that preferentially targets active phosphorylated AKT (pAKT) and is potent in cell lines with evidence of AKT activation. In this phase I study, ipatasertib was well tolerated; most adverse events were gastrointestinal and grade 1–2 in severity. The exposures of ipatasertib ≥200 mg daily in patients correlated with preclinical TGI90, and pharmacodynamic studies confirmed that multiple targets (i.e., PRAS40, GSK3β, and mTOR) were inhibited in paired on-treatment biopsies. Preliminary antitumor activity was observed; 16 of 52 patients (30%), with diverse solid tumors and who progressed on prior therapies, had radiographic stable disease, and many of their tumors had activation of AKT.
Significance: Potent inhibition of AKT signaling with ipatasertib was associated with a tolerable safety profile and meaningful disease control in a subgroup of patients. Targeting pAKT with an ATP-competitive inhibitor provides a greater therapeutic window than allosteric inhibitors. Further investigation with ipatasertib is ongoing in phase II studies. Cancer Discov; 7(1); 102–13. ©2016 AACR.
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