bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Two-Step Hierarchical Screening of Mutant Pools Reveals Mutants under Selection in Chicks
Authors: Yang Hee-Jeong , Bogomolnaya Lydia M. , Elfenbein Johanna R. , Endicott-Yazdani Tiana , Reynolds M. Megan , Porwollik Steffen , Cheng Pui , Xia Xiao-Qin , McClelland Michael , Andrews-Polymenis Helene 
Published: February 2016

ABSTRACT

Contaminated chicken/egg products are major sources of human salmonellosis, yet the strategies used by
Salmonella
to colonize chickens are poorly understood. We applied a novel two-step hierarchical procedure to identify new genes important for colonization and persistence of
Salmonella enterica
serotype Typhimurium in chickens. A library of 182
S.
Typhimurium mutants each containing a targeted deletion of a group of contiguous genes (for a total of 2,069 genes deleted) was used to identify regions under selection at 1, 3, and 9 days postinfection in chicks. Mutants in 11 regions were under selection at all assayed times (colonization mutants), and mutants in 15 regions were under selection only at day 9 (persistence mutants). We assembled a pool of 92 mutants, each deleted for a single gene, representing nearly all genes in nine regions under selection. Twelve single gene deletion mutants were under selection in this assay, and we confirmed 6 of 9 of these candidate mutants via competitive infections and complementation analysis in chicks.
STM0580
,
STM1295
,
STM1297
,
STM3612
,
STM3615
, and
STM3734
are needed for
Salmonella
to colonize and persist in chicks and were not previously associated with this ability. One of these key genes,
STM1297
(
selD
), is required for anaerobic growth and supports the ability to utilize formate under these conditions, suggesting that metabolism of formate is important during infection. We report a hierarchical screening strategy to interrogate large portions of the genome during infection of animals using pools of mutants of low complexity. Using this strategy, we identified six genes not previously known to be needed during infection in chicks, and one of these (
STM1297
) suggests an important role for formate metabolism during infection.
Expectations and patients’ experiences of obesity prior to bariatric surgery: a qualitative study
Authors: Homer Catherine Verity , Tod Angela Mary , Thompson Andrew R , Allmark Peter , Goyder Elizabeth 
Published: February 2016

ObjectivesThis study aimed to understand the experiences and expectations of people seeking bariatric surgery in England and identify implications for behavioural and self-management interventions.DesignA qualitative study using modified photovoice methods, triangulating photography with semistructured indepth interviews analysed using framework techniques.SettingAreas served by two bariatric surgery multidisciplinary teams in the north of England.Participants18 adults (14 women and 4 men) who accepted for bariatric surgery, and were aged between 30 and 61 years. Participants were recruited through hospital-based tier 4 bariatric surgery multidisciplinary teams.ResultsThe experiences of participants indicates the nature and extent of the burden of obesity. Problems included stigmatisation, shame, poor health, physical function and reliance on medications. Participants expected surgery to result in major physical and psychological improvement. They described how this expectation was rooted in their experiences of stigma and shame. These feelings were reinforced by previous unsuccessful weight loss attempts. Participants expected extreme and sometimes unrealistic levels of sustained weight loss, as well as improvements to physical and mental health. The overall desire and expectation of bariatric surgery was of ‘normality’. Participants had received previous support from clinicians and in weight management services. However, they reported that their expectations of surgery had not been reviewed by services, and expectations appeared to be unrealistic. Likewise, their experience of stigmatisation had not been addressed.ConclusionsThe unrealistic expectations identified here may negatively affect postoperative outcomes. The findings indicate the importance of services addressing feelings of shame and stigmatisation, and modifying patient's expectations and goals for the postoperative period.
Randomised controlled pilot study to assess the feasibility of a Mediterranean Portfolio dietary intervention for cardiovascular risk reduction in HIV dyslipidaemia: a study protocol
Authors: Stradling Clare , Thomas G Neil , Hemming Karla , Frost Gary , Garcia-Perez Isabel , Redwood Sabi , Taheri Shahrad 
Published: February 2016

IntroductionHIV drug treatment has greatly improved life expectancy, but increased risk of cardiovascular disease remains, potentially due to the additional burdens of infection, inflammation and antiretroviral treatment. The Mediterranean Diet has been shown to reduce cardiovascular risk and mortality in the general population, but no evidence exists for this effect in the HIV population. This study will explore the feasibility of a randomised controlled trial (RCT) to examine whether a Mediterranean-style diet that incorporates a portfolio of cholesterol-lowering foods, reduces cardiovascular risk in people with HIV dyslipidaemia.Methods and analysis60 adults with stable HIV infection on antiretroviral treatment and low-density lipoprotein cholesterol >3 mmol/L will be recruited from 3 West Midlands HIV services. Participants will be randomised 1:1 to 1 of 2 dietary interventions, with stratification by gender and smoking status. Participants allocated to Diet1 will receive advice to reduce saturated fat intake, and those to Diet2 on how to adopt the Mediterranean Portfolio Diet with additional cholesterol-lowering foods (nuts, stanols, soya, oats, pulses). Measurements of fasting blood lipids, body composition and arterial stiffness will be conducted at baseline, and month 6 and 12 of the intervention. Food intake will be assessed using the Mediterranean Diet Score, 3-day food diaries and metabolomic biomarkers. Questionnaires will be used to assess quality of life and process evaluation. Qualitative interviews will explore barriers and facilitators to making dietary changes, and participant views on the intervention. Qualitative data will be analysed using the Framework Method. Feasibility will be assessed in terms of trial recruitment, retention, compliance to study visits and the intervention. SD of outcomes will inform the power calculation of the definitive RCT.EthicsThe West Midlands Ethics Committee has approved this study and informed consent forms. This trial is the first to test cholesterol-lowering foods in adults with HIV.Trial registration numberISRCTN32090191; Pre-results.
Residential segregation, dividing walls and mental health: a population-based record linkage study
Authors: Maguire Aideen , French Declan , O'Reilly Dermot 
Published: February 2016

BackgroundNeighbourhood segregation has been described as a fundamental determinant of physical health, but literature on its effect on mental health is less clear. While most previous research has relied on conceptualised measures of segregation, Northern Ireland is unique as it contains physical manifestations of segregation in the form of segregation barriers (or ‘peacelines’) which can be used to accurately identify residential segregation.MethodsWe used population-wide health record data on over 1.3 million individuals, to analyse the effect of residential segregation, measured by both the formal Dissimilarity Index and by proximity to a segregation barrier, on the likelihood of poor mental health.ResultsUsing multilevel logistic regression models, we found residential segregation measured by the Dissimilarity Index poses no additional risk to the likelihood of poor mental health after adjustment for area-level deprivation. However, residence in an area segregated by a ‘peaceline’ increases the likelihood of antidepressant medication by 19% (OR=1.19, 95% CI 1.14 to 1.23) and anxiolytic medication by 39% (OR=1.39, 95% CI 1.32 to 1.48), even after adjustment for gender, age, conurbation, deprivation and crime.ConclusionsLiving in an area segregated by a ‘peaceline’ is detrimental to mental health suggesting segregated areas characterised by a heightened sense of ‘other’ pose a greater risk to mental health. The difference in results based on segregation measure highlights the importance of choice of measure when studying segregation.
Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer
Authors: Morris Michael J. , Rathkopf Dana E. , Novotny William , Gibbons Jacqueline A. , Peterson Amy C. , Khondker Zakaria , Ouatas Taoufik , Scher Howard I. , Fleming Mark T. 
Published: February 2016

Abstract
Purpose: Preclinical evidence suggests that both docetaxel and enzalutamide target androgen receptor translocation and signaling. This phase Ib study assessed the safety, tolerability, and pharmacokinetics of docetaxel when administered with enzalutamide as first-line systemic chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC).
Experimental Methods: Docetaxel-naïve patients received 21-day cycles of docetaxel (75 mg/m2). Enzalutamide (160 mg/day) was administered daily starting on day 2 of cycle 1. Patients were allowed to stop and restart docetaxel at any time following cycle 2. Treatment continued indefinitely until unacceptable toxicity or discontinuation due to investigator or patient preference.
Results: A total of 22 patients received docetaxel, of whom 21 also received enzalutamide. Docetaxel was administered for a median of 5.0 cycles and enzalutamide for a median of 12.0 months. With concomitant treatment, geometric mean docetaxel exposure decreased by 11.8%, whereas peak concentrations decreased by 3.7% relative to docetaxel alone. The most common toxicities observed during the period of concomitant therapy were neutropenia (86.4%) and fatigue (77.3%). Common toxicities observed with post-docetaxel enzalutamide were constipation (23.8%), decreased appetite (19.0%), fatigue (19.0%), and musculoskeletal pain (19.0%). Treatment with enzalutamide and docetaxel resulted in prostate-specific antigen decreases in almost all patients based on exploratory analysis of available baseline and on-study prostate-specific antigen data.
Conclusions: The combination of docetaxel and enzalutamide is feasible, although higher rates of neutropenia and neutropenic fever than anticipated were observed. Reductions in docetaxel exposure with enzalutamide coadministration were not considered clinically meaningful. This combination warrants further study in a larger mCRPC population. Clin Cancer Res; 22(15); 3774–81. ©2016 AACR.
Twenty-Seven Years Experience With Transvenous Pacemaker Implantation in Children Weighing <10 kg
Authors: Konta Laura , Chubb Mark Henry , Bostock Julian , Rogers Jan , Rosenthal Eric 
Published: February 2016

Background—
Epicardial pacemaker implantation is the favored approach in children weighing <10 kg in many units. The high incidence of premature failure and fractures with earlier epicardial leads led our unit to undertake transvenous pacemaker implantation in neonates and infants from 1987. To date there have been no long-term follow-up reports of what is for many a controversial strategy.

Methods and Results—
Between 1987 and 2003, 37 neonates and infants—median age 6.7 months (1 day to 3 years) and median weight 4.6 kg (2.7–10 kg)—had a permanent transvenous pacing system implanted. Pacing leads were placed into the right ventricular apex/outflow tract through a subclavian vein puncture with a redundant loop in the atrium. Three patients were lost to follow-up, 4 patients died from complications of cardiac surgery, and 2 patients had their system removed. At long-term follow-up in 28 patients at a median of 17.2 (range, 11.2–27.4) years, 10 patients have a single chamber ventricular pacemaker, 14 a dual chamber pacemaker, 3 a biventricular pacemaker, and 1 has a single chamber implantable cardioverter defibrillator. Subclavian vein patency was assessed in 26 patients. The overall subclavian vein occlusion rate was 10 of 13 (77%) <5 kg and 2 of 13 (15%) >5 kg during long-term follow-up. After a median of 14.3 (range, 13.4–17.6) years of pacing, 7 patients continue with their original lead.

Conclusions—
Transvenous pacing in infants <10 kg results in encouraging short- and long-term clinical outcomes. Subclavian vein occlusion remains an important complication, occurring predominantly in those weighing <5 kg.
Six Versus 12 Months of Dual Antiplatelet Therapy After Implantation of Biodegradable Polymer Sirolimus-Eluting Stent
Authors: Han Yaling , Xu Bo , Xu Kai , Guan Changdong , Jing Quanmin , Zheng Qiangsun , Li Xueqi , Zhao Xianxian , Wang Haichang , Zhao Xuezhong , Li Xiaoyan , Yu Pengfei , Zang Hongyun , Wang Zhifang , Cao Xuebin , Zhang Jun , Pang Wenyue , Li Jing , Yang Yuejin , Dangas George D. 
Published: February 2016

Background—
There are no reports on a large-scale randomized trial exploring optimal dual antiplatelet therapy (DAPT) duration after biodegradable polymer sirolimus-eluting stent implantation. We sought to report the outcomes of a randomized substudy of the prospective Evaluate Safety and Effectiveness of the Tivoli DES and the Firebird DES for Treatment of Coronary Revascularization (I-LOVE-IT 2) trial.

Methods and Results—

In the prospective noninferiority randomized I-LOVE-IT 2 trial, 1829 patients allocated to the biodegradable polymer sirolimus-eluting stent group were also randomized to receive either 6-month (n=909) or 12-month DAPT (n=920). The primary end points of this noninferiority substudy were 12-month target lesion failure (composite of cardiac death, target vessel myocardial infarction or clinically indicated target lesion revascularization), and the major secondary end points were 12-month net adverse clinical and cerebral events (composite of all-cause death, all myocardial infarction, stroke, or major bleeding [Bleeding Academic Research Consortium type ≥3]). The 12-month target lesion failure in 6-month DAPT group was comparable with the 12-month DAPT group (6.8% versus 5.9%; difference and 95% confidence interval, 0.87% [−1.37% to 3.11%],
P
for noninferiority=0.0065). Further follow-up at 18 months showed that incidence of target lesion failure and net adverse clinical and cerebral events were similar between the 2 groups (7.5% versus 6.3%, log-rank
P
=0.32; 7.8% versus 7.3%, log-rank
P
=0.60; respectively), as well as their individual end point components.

Conclusions—
This study indicated noninferiority in safety and efficacy of 6-month versus 12-month DAPT after implantation of a novel biodegradable polymer sirolimus-eluting stent.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01681381.
Intraseasonal Variation of the Strength of the East Asian Trough and Its Climatic Impacts in Boreal Winter
Authors: Song Lei , Wang Lin , Chen Wen , Zhang Yang 
Published: February 2016

Abstract
The East Asian trough (EAT) is a distinct component of the boreal winter circulation whose strength corresponds to the amplitude of the Northern Hemispheric stationary waves. In this study, the mechanism and climatic impacts of the intraseasonal variations of the EAT’s strength are investigated through composite analysis and dynamical diagnostics. The significant roles played by the low-frequency Rossby wave (RW) and synoptic transient eddy (TE) are revealed. Before the peaks of strong EAT events, an upper-tropospheric RW train propagates across northern Eurasia and interacts with preexisting surface cold anomalies over central Siberia. This pattern intensifies the Siberian high and causes RW convergence toward the EAT, leading to 30% of the EAT’s amplification directly via the RW-induced feedback forcing. Meanwhile, RW weakens the background baroclinicity and reduces TE activities near the entrance region of the North Pacific storm track. The TE-induced feedback forcing leads to another 30% of the EAT’s amplification. The evolution and dynamical processes of the weak EAT events generally resemble those of the strong events with opposite signs. These results are consistent with the knowledge on the mechanism of the strong and weak EAT events regarding the role of RWs with additional quantitative description and provide new insights regarding the role of TEs. Variations of the EAT’s strength exert significant climatic impacts on East Asia and its downstream region. Near-surface air temperature is below (above) normal over East Asia during the growth and peak stages of the strong (weak) EAT events and above (below) normal over North America afterward.
Effects of Roughness Length Parameterizations on Regional-Scale Land Surface Modeling of Alpine Grasslands in the Yangtze River Basin
Authors: Huang Ying , Salama M. Suhyb , Su Zhongbo , van der Velde Rogier , Zheng Donghai , Krol Maarten S. , Hoekstra Arjen Y. , Zhou Yunxuan 
Published: February 2016

AbstractCurrent land surface models (LSMs) tend to largely underestimate the daytime land surface temperature for high-altitude regions. This is partly because of underestimation of heat transfer resistance, which may be resolved through adequate parameterization of roughness lengths for momentum and heat transfer. In this paper, the regional-scale effects of the roughness length parameterizations for alpine grasslands are addressed and the performance of the Noah LSM using the updated roughness lengths compared to the original ones is assessed. The simulations were verified with various satellite products and validated with ground-based observations. More specifically, four experimental setups were designed using two roughness length schemes with two different parameterizations of (original and updated). These experiments were conducted in the source region of the Yangtze River during the period 2005–10 using the Noah LSM. The results show that the updated parameterizations of roughness lengths reduce the mean biases of the simulated daytime in spring, autumn, and winter by up to 2.7 K, whereas larger warm biases are produced in summer. Moreover, model efficiency coefficients (Nash–Sutcliffe) of the monthly runoff results are improved by up to 26.3% when using the updated roughness parameterizations. In addition, the spatial effects of the roughness length parameterizations on the simulations are discussed. This study stresses the importance of proper parameterizations of and for LSMs and highlights the need for regional adaptation of the and values.
Predictors of place of death in South West Scotland 2000–2010: Retrospective cohort study
Authors: Black Heather , Waugh Craig , Munoz-Arroyo Rosalia , Carnon Andrew , Allan Ananda , Clark David , Graham Fiona , Isles Christopher 
Published: February 2016

Background: Surveys suggest most people would prefer to die in their own home. Aim: To examine predictors of place of death over an 11-year period between 2000 and 2010 in Dumfries and Galloway, south west Scotland. Design: Retrospective cohort study. Setting/Participants: 19,697 Dumfries and Galloway residents who died in the region or elsewhere in Scotland. We explored the relation between age, gender, cause of death (cancer, respiratory, ischaemic heart disease, stroke and dementia) and place of death (acute hospital, cottage hospital, residential care and home) using regression models to show differences and trends. The main acute hospital in the region had a specialist palliative care unit. Results: Fewer people died in their own homes (23.2% vs 29.6%) in 2010 than in 2000. Between 2007 and 2010, men were more likely to die at home than women ( p < 0.001), while both sexes were less likely to die at home as they became older ( p < 0.001) and in successive calendar years ( p < 0.003). Older people with dementia as the cause of death were particularly unlikely to die in an acute hospital and very likely to die in a residential home ( p < 0.001). Between 2007 and 2010, an increasing proportion of acute hospital deaths occurred in the specialist palliative care unit (6% vs 11% of all deaths in the study). Conclusion: The proportion of people dying at home fell during our survey. Place of death was strongly associated with age, calendar year and cause of death. A mismatch remains between stated preference for place of death and where death occurs.
Serum cross-linked N-telopeptide of type I collagen for the diagnosis of bone metastases from solid tumours in the Chinese population: Meta-analysis
Authors: Zhang Yudong , Yi Minhan , Cao Jie , Hou Can , Zhou Yanyan , Zhong Yanjun 
Published: February 2016

Objective A meta-analysis to determine the diagnostic value of serum cross-linked N-telopeptide of type I collagen (NTx) for bone metastasis from solid tumours in the Chinese population. Methods Eligible case–control studies published up until 22 September 2014 were identified by searching the electronic literature databases PubMed®, Web of Science, China National Knowledge Infrastructure and Wanfang using the keyword ‘NTx’ in combination with ‘cancer’. A meta-analysis of the diagnostic value of serum NTx for bone metastasis from solid tumours was undertaken. Results The meta-analysis included 14 studies (1279 patients: 668 with bone metastasis; 611 controls without bone metastasis). There was a significant relationship between serum NTx concentration and bone metastasis from solid tumours in the Chinese population (odds ratio 1.39, 95% confidence intervals 1.26, 1.51). Significant heterogeneity was found in this study, but no publication bias was observed. Conclusion Serum NTx concentration may play an important role in the diagnosis of bone metastasis from solid tumours in the Chinese population.
Adipokine zinc-alpha-2-glycoprotein as a novel urinary biomarker presents earlier than microalbuminuria in diabetic nephropathy
Authors: Wang Yuan , Li Yan-Mei , Zhang Shu , Zhao Jiu-Yang , Liu Chun-Yan 
Published: February 2016

Objective To investigate the role of zinc-alpha-2-glycoprotein (ZAG) in the early stage of diabetic nephropathy, in patients with type 2 diabetes mellitus (T2DM). Methods This cross-sectional observational study recruited patients with longstanding T2DM and healthy control subjects. Patients with T2DM were further stratified based on their urine albumin–creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Serum and urine concentrations of ZAG were determined using an enzyme-linked immunosorbent assay. Results Eighty patients with T2DM and 20 healthy control subjects were enrolled in the study. Mean ± SD concentrations of ZAG in serum and urine were both significantly higher in patients with T2DM (serum: 38.29 ± 22.72 mg/l; urine: 53.64 ± 29.48 mg/g) compared with concentrations in healthy control subjects (serum: 21.61 ± 8.83 mg/l; urine: 28.17 ± 10.64 mg/g). Serum ZAG concentration was positively correlated with serum creatinine and eGFR. Urine ZAG concentration was positively correlated with UACR. Urine concentration of ZAG in the higher eGFR group was higher than that in the normal eGFR group (41.26 ± 13.67 versus 32.05 ± 8.55 mg/g, respectively). Conclusion These preliminary findings suggest that ZAG might be a potentially useful biomarker for early diagnosis of diabetic nephropathy in patients with T2DM.