bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver‐specific Sirtuin6 ablation impairs liver regeneration after 2/3 partial hepatectomy
Authors: Liu Qinhui , Pu Shiyun , Chen Lei , Shen Jing , Cheng Shihai , Kuang Jiangying , Li Hong , Wu Tong , Li Rui , Jiang Wei , Zou Min , Zhang Zhiyong , Li Yanping , Li Jian , He Jinhan 
Published: February 2019

ABSTRACTSirtuin 6 (Sirt6) is an NAD+‐dependent deacetylase that regulates central metabolic functions such as glucose homeostasis, fat metabolism, and cell apoptosis. However, the tissue‐specific function of Sirt6 in liver regeneration remains unknown. Here, we show that liver‐specific Sirt6 knockout (Sirt6LKO) impaired liver reconstitution after 2/3 partial hepatectomy, which was attributed to an alteration of cell cycle progression. Sirt6 LKO delayed hepatocyte transition into S phase during liver regeneration, as shown by the analysis of cell cycle‐related proteins and the immuno staining of Ki‐67 and 5‐bromo‐2‐deoxyuridine (BrdU). The delayed cell cycle in Sirt6 LKO mice was attributed to the disruption of m‐TOR and Akt activity, which is an important pro‐proliferation pathway in liver regeneration. Sirt6 LKO also reduced carbon tetrachloride (CCl4)‐induced liver damage. Our results suggest that Sirt6 LKO impaired liver regeneration via delayed cell cycle and impaired m‐TOR and Akt activity.
Referendum opposition to fluoridation and health literacy: a cross-sectional analysis conducted in three large US cities
Authors: Curiel John A , Slade Gary D , Christian Thu-Mai L , Lafferty-Hess Sophia , Carsey Thomas M , Sanders Anne E 
Published: February 2019

ObjectiveTo explore health literacy as a marker of voter confusion in order to understand the basis for public opposition to community water fluoridation.DesignA cross-sectional study.SettingConducted in three large US cities of San Antonio, Texas (602 voting precincts); Wichita, Kansas (171 voting precincts); and Portland, Oregon (132 voting precincts). Precinct-level voting data were compiled from community water fluoridation referendums conducted in San Antonio in 2002, Wichita in 2012 and Portland in 2013.ParticipantsVoter turnout expressed as a percentage of registered voters was 38% in San Antonio (n=2 92 811), 47% in Wichita (n=129 199) and 38% in Portland (n=164 301).Main outcome measuresThe dependent variable was the percentage of votes in favour of fluoridating drinking water. Precinct-level voting data were mapped to precinct scores of health literacy, and to US Census and American Community Survey characteristics of race/ethnicity, age, income and educational attainment. Multilevel regression with post-stratification predicted the precinct mean health literacy scores, with weights generated from the National Association of Adult Literacy health literacy survey, with item response theory computed scoring for health literacy. Predictive models on voter support of community water fluoridation were compared using robust linear regression to determine how precinct-level characteristics influenced voter support in order to determine whether health literacy explained more variance in voting preference than sociodemographic characteristics.ResultsPrecinct-level health literacy was positively associated with voter turnout, although sociodemographic characteristics were better predictors of turnout. Approximately 60% of voters opposed community water fluoridation in Wichita and Portland, whereas in San Antonio, a small majority (53%) voted in favour of it. Models suggest that a one SD increase in health literacy scores predicted a 12 percentage point increase support for community water fluoridation.ConclusionEducational attainment and health literacy are modifiable characteristics associated with voting precincts' support for community water fluoridation.
Metastatic breast cancer incidence, site and survival in Australia, 2001–2016: a population-based health record linkage study protocol
Authors: Lord Sarah J , Kiely Belinda E , Pearson Sallie-Anne , Daniels Benjamin , O’Connell Dianne L , Beith Jane , Bulsara Max K , Houssami Nehmat 
Published: February 2019

IntroductionAdvances in systemic therapy for early and metastatic breast cancer (BC) over the last two decades have improved patients’ survival, but their impact on metastatic disease outcomes at a population level is not well described. The aim of this study is to investigate changes in the incidence, site and survival of metastatic disease for women with a first diagnosis of BC in 2001–2002 vs 2006–2007.Methods and analysisPopulation-based retrospective cohort study of women with first primary invasive BC registered in the New South Wales (NSW) Cancer Registry in 2001–2002 and 2006–2007. We will use linked records from NSW hospitals, dispensed medicines, outpatient services and death registrations to determine: women’s demographic and tumour characteristics; treatments received; time to first distant metastasis; site of first metastasis and survival. We will use the Kaplan-Meier method to estimate cumulative incidence of distant metastasis, distant recurrence-free interval and postmetastasis survival by extent of disease at initial diagnosis, site of metastasis and treatment-defined tumour receptor type (hormone receptor-positive, human epidermal growth factor receptor-2-positive, triple negative). We will use Cox proportional hazards regression to estimate the relative effects of prognostic factors, and we will compare systemic therapy patterns by area-of-residence and area-level socioeconomic status to examine equity of access to healthcare.Ethics and disseminationResearch ethics committee approval was granted by the Australian Institute of Health and Welfare (#EO2017/2/255), NSW Population and Health Services (#HREC/17/CIPHS/19) and University of Notre Dame Australia (#0 17 144S). We will disseminate research findings to oncology, BC consumer and epidemiology audiences through national and international conference presentations, lay summaries to BC consumer groups and publications in international peer-reviewed oncology and cancer epidemiology journals.
Pharmacotherapeutic management of paediatric heart failure and ACE-I use patterns: a European survey
Authors: Castro Díez Cristina , Khalil Feras , Schwender Holger , Dalinghaus Michiel , Jovanovic Ida , Makowski Nina , Male Christoph , Bajcetic Milica , van der Meulen Marijke , de Wildt Saskia N , Ablonczy László , Szatmári András , Klingmann Ingrid , Walsh Jennifer , Läer Stephanie 
Published: February 2019

ObjectiveTo characterise heart failure (HF) maintenance pharmacotherapy for children across Europe and investigate how angiotensin-converting enzyme inhibitors (ACE-I) are used in this setting.MethodsA Europe-wide web-based survey was conducted between January and May 2015 among European paediatricians dedicated to cardiology.ResultsOut of 200-eligible, 100 physicians representing 100 hospitals in 27 European countries participated. All participants reported prescribing ACE-I to treat dilated cardiomyopathy-related HF and 97% in the context of congenital heart defects; 87% for single ventricle physiology. Twenty-six per cent avoid ACE-I in newborns. Captopril was most frequently selected as first-choice for newborns (73%) and infants and toddlers (66%) and enalapril for children (56%) and adolescents (58%). Reported starting and maintenance doses varied widely. Up to 72% of participants follow formal creatinine increase limits for decision-making when up-titrating; however, heterogeneity in the cut-off points selected existed. ACE-I formulations prescribed by 47% of participants are obtained from more than a single source. Regarding symptomatic HF maintenance therapy, 25 different initial drug combinations were reported, although 79% select a regimen that includes ACE-I and diuretic (thiazide and/or loop), 61% ACE-I and aldosterone antagonist; 44% start with beta-blocker, 52% use beta-blockers as an add-on drug. Of the 89 participants that prescribe pharmacotherapy to asymptomatic patients, 40% do not use ACE-I monotherapy or ACE-I-beta-blocker two-drug only combination.ConclusionsDespite some reluctance to use them in newborns, ACE-I seem key in paediatric HF treatment strategies. Use in single ventricle patients seems frequent, in apparent contradiction with current paediatric evidence. Disparate dosage criteria and potential formulation-induced variability suggest significant differences may exist in the risk-benefit profile children are exposed to. No uniformity seems to exist in the drug regimens in use. The information collected provides relevant insight into real-life clinical practice and may facilitate research to identify the best therapeutic options for HF children.
Family talk intervention in paediatric oncology: a pilot study protocol
Authors: Lövgren Malin , Kreicbergs Ulrika , Udo Camilla 
Published: February 2019

IntroductionThere is evidence that families with a child diagnosed with cancer need psychosocial support throughout the illness trajectory. Unfortunately, there is little research into psychosocial interventions for such families, especially interventions where the entire family is involved. The aim of this pilot study is therefore to evaluate a psychosocial intervention, the family talk intervention (FTI), in paediatric oncology in terms of study feasibility and potential effects.Methods and analysisThis pretest/post-test intervention pilot study is based on families with a child diagnosed with cancer. All families that include at least one child aged 6–19 years (ill child and/or sibling) at one of the six paediatric oncology centres in Sweden between September 2018 and September 2019 will be asked about participation. The intervention consists of six meetings with the family (part of the family or the entire family), led by two interventionists. The core elements in the intervention are to support the families in talking about the illness and related subjects, support the parents in understanding the needs of their children and how to support them and support the families in identifying their strengths and how to use them best. Mixed methods are used to evaluate the intervention (web-based questionnaires, interviews, field notes and observations). Self-reported data from all family members are collected at baseline, directly after the intervention and 6 months later. Study outcomes are family communication, knowledge about the illness, resilience, quality of life and grief.Ethics and disseminationThe study has been approved by the Regional Ethical Review Board in Stockholm (Dnr 2018/250-31/2 and 2018/1852–32). Data are processed in coded form, accessible only to the research team and stored at Ersta Sköndal Bräcke University College in a secure server.Trial registrationClinicalTrials.gov IdentifierNCT03650530, registered in August 2018.
Hierarchical process using Brier Score Metrics for lower leg injury risk curves in vertical impact
Authors: DeVogel Nicholas , Yoganandan N , Banerjee A , Pintar F A 
Published: February 2019

IntroductionParametric survival models are used to develop injury risk curves (IRCs) from impact tests using postmortem human surrogates (PMHS). Through the consideration of different output variables, input parameters and censoring, different IRCs could be created. The purpose of this study was to demonstrate the feasibility of the Brier Score Metric (BSM) to determine the optimal IRCs and derive them from lower leg impact tests.MethodsTwo series of tests of axial impacts to PMHS foot–ankle complex were used in the study. The first series used the metrics of force, time and rate, and covariates of age, posture, stature, device and presence of a boot. Also demonstrated were different censoring schemes: right and exact/uncensored (RC-UC) or right and uncensored/left (RC-UC-LC). The second series involved only one metric, force, and covariates age, sex and weight. It contained interval censored (IC) data demonstrating different censoring schemes: RC-IC-UC, RC-IC-LC and RC-IC-UC-LC.ResultsFor each test set combination, optimal IRCs were chosen based on metric–covariate combination that had the lowest BSM value. These optimal IRCs are shown along with 95% CIs and other measures of interval quality. Forces were greater for UC than LC data sets, at the same risk levels (10% used in North Atlantic Treaty Organisation (NATO)). All data and IRCs are presented.ConclusionsThis study demonstrates a novel approach to examining which metrics and covariates create the best parametric survival analysis-based IRCs to describe human tolerance, the first step in describing lower leg injury criteria under axial loading to the plantar surface of the foot.
Relationship between obesity and health problems in help-seeking military veterans
Authors: Williamson Victoria , Rossetto A , Murphy D 
Published: February 2019

BackgroundUK Armed Forces (UK AF) veterans may be particularly vulnerable to obesity and its comorbid physical and mental health problems.AimTo examine the relationship between body mass index (BMI), physical health problems, mental health disorders and sociodemographic characteristics in UK AF veterans engaged in psychological treatment.MethodsInformation regarding veteran BMI, demographic characteristics, physical health conditions and mental health problems was collected and analysed using univariate and multivariate regression analyses. Rates of veteran obesity were also compared with the UK general population.ResultsOf the 384 help-seeking veterans, 37.5% (n=151) were overweight (BMI 26–30) and 35.5% (n=143) were obese. Obesity in help-seeking male veterans was two to four times higher than that of the general population of UK. Higher scores on measures of anger and common mental health problems were significantly associated with greater BMI. Problems with physical systemic functioning and mobility were also significantly associated with greater BMI.ConclusionsThe results indicate that treatment-seeking UK AF veterans exhibit higher levels of obesity compared with the general population, and clinically significant physical and mental comorbidities. The findings highlight a need for mental health services to offer treatments that effectively integrate physical and mental healthcare in the treatment of people with mental health problems.
Modulating cardiac conduction during metabolic ischemia with perfusate sodium and calcium in guinea pig hearts
Authors: George Sharon A. , Hoeker Gregory , Calhoun Patrick J. , Entz Michael , Raisch Tristan B. , King D. Ryan , Khan Momina , Baker Chandra , Gourdie Robert G. , Smyth James W. , Nielsen Morten S. , Poelzing Steven 
Published: February 2019

We previously demonstrated that altering extracellular sodium (Nao) and calcium (Cao) can modulate a form of electrical communication between cardiomyocytes termed “ephaptic coupling” (EpC), especially during loss of gap junction coupling. We hypothesized that altering Nao and Cao modulates conduction velocity (CV) and arrhythmic burden during ischemia. Electrophysiology was quantified by optically mapping Langendorff-perfused guinea pig ventricles with modified Nao (147 or 155 mM) and Cao (1.25 or 2.0 mM) during 30 min of simulated metabolic ischemia (pH 6.5, anoxia, aglycemia). Gap junction-adjacent perinexal width ( WP), a candidate cardiac ephapse, and connexin (Cx)43 protein expression and Cx43 phosphorylation at S368 were quantified by transmission electron microscopy and Western immunoblot analysis, respectively. Metabolic ischemia slowed CV in hearts perfused with 147 mM Nao and 2.0 mM Cao; however, theoretically increasing EpC with 155 mM Nao was arrhythmogenic, and CV could not be measured. Reducing Cao to 1.25 mM expanded WP, as expected during ischemia, consistent with reduced EpC, but attenuated CV slowing while delaying arrhythmia onset. These results were further supported by osmotically reducing WP with albumin, which exacerbated CV slowing and increased early arrhythmias during ischemia, whereas mannitol expanded WP, permitted conduction, and delayed the onset of arrhythmias. Cx43 expression patterns during the various interventions insufficiently correlated with observed CV changes and arrhythmic burden. In conclusion, decreasing perfusate calcium during metabolic ischemia enhances perinexal expansion, attenuates conduction slowing, and delays arrhythmias. Thus, perinexal expansion may be cardioprotective during metabolic ischemia. NEW & NOTEWORTHY This study demonstrates, for the first time, that modulating perfusate ion composition can alter cardiac electrophysiology during simulated metabolic ischemia.
Modulations of the Diurnal Cycle of Coastal Rainfall over South China Caused by the Boreal Summer Intraseasonal Oscillation
Authors: Chen Xingchao , Zhang Fuqing , Ruppert James H. 
Published: February 2019

AbstractThe influence of the boreal summer intraseasonal oscillation (BSISO) on the diurnal cycle of coastal rainfall over south China during the mei-yu (heavy rainfall) season is investigated using the OLR-based Madden–Julian oscillation index (OMI), satellite rainfall data, and atmospheric reanalysis. Results show that the mei-yu season coastal rainfall is enhanced during the BSISO phase 1 (convectively active phase over the western Indian Ocean), with 25% greater rainfall than the climatological regional mean. Rainfall is suppressed during the BSISO phases 4 and 5 (convectively active phase in the Bay of Bengal and South China Sea), with negative rainfall anomalies of 39% and 46%, respectively. During phase 1, the rainfall enhancement is mostly over the inland region during the afternoon, while there is little diurnal variability of the rainfall anomaly offshore. During phases 4 and 5, the rainfall suppression is considerably stronger over the offshore region in the morning, whereas stronger rainfall suppression occurs inland during the afternoon. In phase 8, positive rainfall anomalies are found over the offshore region with a peak from the morning to the early afternoon, whereas negative rainfall anomalies are found over the inland region with the strongest suppression in the late afternoon. Analysis of phase composites and horizontal moisture advection shows that the diurnal variation of rainfall anomalies over the south China coastal area during different BSISO phases can be interpreted as the interaction between the large-scale anomalous moisture advection and the local land and sea breeze circulations.
On Producing Reliable and Affordable Numerical Weather Forecasts on Public Cloud-Computing Infrastructure
Authors: Chui Timothy C. Y. , Siuta David , West Gregory , Modzelewski Henryk , Schigas Roland , Stull Roland 
Published: February 2019

AbstractCloud-computing resources are increasingly used in atmospheric research and real-time weather forecasting. The aim of this study is to explore new ways to reduce cloud-computing costs for real-time numerical weather prediction (NWP). One way is to compress output files to reduce data egress costs. File compression techniques can reduce data egress costs by over 50%. Data egress costs can be further minimized by postprocessing in the cloud and then exporting the smaller resulting files while discarding the bulk of the raw NWP output. Another way to reduce costs is to use preemptible resources, which are virtual machines (VMs) on the Google Cloud Platform (GCP) that clients can use at an 80% discount (compared to nonpreemptible VMs), but which can be turned off by the GCP without warning. By leveraging the restart functionality in the Weather Research and Forecasting (WRF) Model, preemptible resources can be used to save 60%–70% in weather simulation costs without compromising output reliability. The potential cost savings are demonstrated in forecasts over the Canadian Arctic and in a case study of NWP runs for the West African monsoon (WAM) of 2017. The choice in model physics, VM specification, and use of the aforementioned cost-saving measures enable simulation costs to be low enough such that the cloud can be a viable platform for running short-range ensemble forecasts when compared to the cost of purchasing new computer hardware.
Increased interleukin-6 and C-reactive protein levels after instrumented lumbar spine fusion in older patients
Authors: Repo Jussi P , Häkkinen Arja H , Porkka Tuukka , Häkkinen Keijo , Kautiainen Hannu , Kyrölä Kati , Neva Marko H 
Published: February 2019

Purpose: Interleukin 6 (IL-6) and the acute phase C-reactive protein (CRP) blood concentrations after lumbar spine fusion may be affected by age. The purpose of this prospective observational study was to assess postoperative serum levels of pro-inflammatory IL-6 and CRP after instrumented lumbar spine fusion surgery. We hypothesized that older patients would have increased levels of IL-6 and CRP after surgery. Methods: IL-6 and high-sensitive CRP biochemical marker levels were measured before instrumented spinal fusion, and postoperatively at 1 and 3 days, 6 weeks, and 3 months. The 49 patients in this sample were divided into two groups: age ≤ 60 years ( n = 23) and age > 60 years ( n = 26). Results: Acute changes in IL-6 high-sensitivity and CRP from preoperative levels to postoperative day (POD) 1 increased with age. Mean (95% CI) difference between the age-groups in changes of IL-6 at PODs 1 and 3 was 45 pg/ml (10–83, p = 0.014) and 20 pg/ml (5–36, p = 0.021), respectively. Mean (95% CI) difference between groups in changes of CRP at PODs 1 and 3 was 9.6 mg/l (−3.5 to 22.7, p = 0.47) and 24.8 mg/l (−17 to 67, p = 0.33), respectively. Both groups had decreased IL-6 and CRP levels at 6 weeks after surgery compared to the preoperative level. Conclusions: Elevation of IL-6 and CRP is stronger in patients over 60 years old after instrumented lumbar spinal fusion. The CRP and IL-6 are sensitive markers for acute postoperative inflammation. Even high acute CRP values do not necessarily indicate postoperative infection.