bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant‐produced Zika virus envelope protein elicits neutralizing immune responses that correlate with protective immunity against Zika virus in mice
Authors: Yang Ming , Sun Haiyan , Lai Huafang , Hurtado Jonathan , Chen Qiang 
Published: July 2017

SummaryThe global Zika virus (ZIKV) outbreak and its link to foetal and newborn microcephaly and severe neurological complications in adults call for the urgent development of ZIKV vaccines. In response, we developed a subunit vaccine based on the ZIKV envelope (E) protein and investigated its immunogenicity in mice. Transient expression of ZIKV E (zE) resulted in its rapid accumulation in leaves of Nicotiana benthamiana plants. Biochemical analysis revealed that plant‐produced ZIKV E (PzE) exhibited specific binding to a panel of monoclonal antibodies that recognize various zE conformational epitopes. Furthermore, PzE can be purified to >90% homogeneity with a one‐step Ni2+ affinity chromatography process. PzE are found to be highly immunogenic, as two doses of PzE elicited both potent zE‐specific antibody and cellular immune responses in mice. The delivery of PzE with alum induced a mixed Th1/Th2 immune response, as the antigen‐specific IgG isotypes were a mixture of high levels of IgG1/IgG2c and splenocyte cultures from immunized mice secreted significant levels of IFN‐gamma, IL‐4 and IL‐6. Most importantly, the titres of zE‐specific and neutralizing antibodies exceeded the threshold that correlates with protective immunity against multiple strains of ZIKV. Thus, our results demonstrated the feasibility of plant‐produced ZIKV protein antigen as effective, safe and affordable vaccines against ZIKV.
Early Life UV and Risk of Basal and Squamous Cell Carcinoma in New South Wales, Australia
Authors: Kricker Anne , Weber Marianne , Sitas Freddy , Banks Emily , Rahman Bayzidur , Goumas Chris , Kabir Ahsanul , Hodgkinson Verity S. , van Kemenade Cathelijne H. , Waterboer Tim , Armstrong Bruce K. 
Published: July 2017

AbstractSun exposure is the main cause of squamous (SCC) and basal cell carcinoma (BCC) although pattern and amount differ by cancer type, and sun sensitivity is the major host risk factor. Our study investigated risk factors and residential ambient UV in a population‐based sample of Australian 45 and Up Study participants: 916 BCC cases, 433 SCC cases, 1224 controls. Unconditional logistic regression models adjusting for key covariates demonstrated 60% increased BCC risk and two‐fold increased SCC risk with sun sensitivity, and three‐ and four‐fold increased risk, respectively, with solar keratoses. BCC but not SCC risk increased with higher early‐life residential UV in all participants (odds ratio (OR) = 1.54; 95% CI 1.22–1.96 for intermediate; OR = 1.31; 95% CI 1.03–1.68 for high UV at birthplace) and similarly in Australian‐born participants (P‐values < 0.05). Risk of SCC but not BCC increased with long‐term cumulative sun exposure assessed by self‐reported outdoor work (OR 1.74, 95% CI 1.21–2.49). In conclusion, sun sensitivity is important for both cancers, early‐life UV but not cumulative UV appears to increase BCC risk, the former an apparently novel finding, and SCC risk appears only to be related to long‐term cumulative sun exposure.
Increased Processivity, Misincorporation, and Nucleotide Incorporation Efficiency in Sulfolobus solfataricus Dpo4 Thumb Domain Mutants
Authors: Wang Li , Liang Chenchen , Wu Jing , Liu Liming , Tyo Keith E. J. 
Published: July 2017

ABSTRACT

The present study aimed to increase the processivity of
Sulfolobus solfataricus
DNA polymerase Dpo4. Protein engineering and bioinformatics were used to compile a library of potential Dpo4 mutation sites. Ten potential mutants were identified and constructed. A primer extension assay was used to evaluate the processivity of Dpo4 mutants. Thumb (A181D) and finger (E63K) domain mutants showed a processivity of 20 and 19 nucleotides (nt), respectively. A little finger domain mutant (I248Y) exhibited a processivity of 17 nt, only 1 nt more than wild-type Dpo4. Furthermore, the A181D mutant showed lower fidelity and higher nucleotide incorporation efficiency (4.74 × 10
−4
s
−1
μM
−1
) than E63K and I248Y mutants. When tasked with bypassing damage, the A181D mutant exhibited a 3.81-fold and 2.62-fold higher catalytic efficiency (
k
cat
/

K
m

) at incorporating dCTP and dATP, respectively, than wild-type Dpo4. It also showed a 55% and 91.5% higher catalytic efficiency when moving beyond the damaged 8-oxoG:C and 8-oxoG:A base pairs, respectively, compared to wild-type Dpo4. Protein engineering and bioinformatics methods can effectively increase the processivity and translesion synthesis ability of Dpo4.

IMPORTANCE
DNA polymerases with poor fidelity can be exploited to store data and record changes in response to the intracellular environment.
Sulfolobus solfataricus
Dpo4 is such an enzyme, although its use is hindered by its low processivity. In this work, we used a bioinformatics and protein engineering approach to generate Dpo4 mutants with improved processivity. We identified the Dpo4 thumb domain as the most relevant in controlling processivity.
Effect of interdisciplinary care on weight loss: a randomised controlled trial
Authors: Tapsell Linda C , Lonergan Maureen , Batterham Marijka J , Neale Elizabeth P , Martin Allison , Thorne Rebecca , Deane Frank , Peoples Gregory 
Published: July 2017

ObjectiveTo determine the effectiveness of a novel interdisciplinary treatment compared with usual care on weight loss in overweight and obese adult volunteers.DesignSingle blinded controlled trial. Participants randomly assigned to usual care (C, general guideline-based diet and exercise advice), intervention (I, interdisciplinary protocol) or intervention + a healthy food supplement (30 g walnuts/day) (IW).SettingCommunity based study, Illawarra region, south of Sydney, Australia.ParticipantsGenerally well volunteer adult residents, 25-54 years, body mass index (BMI) 25-40kg/m2were eligible. At baseline 439 were assessed, 377 were randomised, 298 completed the 3-month intensive phase and 178 completed the 12-month follow-up.InterventionsTreatment was provided at clinic visits intensively (0 months, 1 month, 2 months, 3 months) then quarterly to 12 months. Support phone calls were quarterly. All participants underwent blinded assessments for diet, exercise and psychological status.Primary and secondary measuresThe primary outcome was difference in weight loss between baseline and 12 months (clinically relevant target 5% loss). Secondary outcomes were changes in blood pressure, fasting blood glucose and lipids, and changes in diet, exercise and psychological parameters.ResultsAt 12 months, differences in weight loss were identified (p<0.001). The I group lost more than controls at 3 months (91.11 (92.23,90.00), p<0.05) and the IW more than controls at 3 months (91.25 (92.35,90.15), p<0.05) and 6 months (92.20 (93.90,90.49), p<0.01). The proportion achieving 5% weight loss was significantly different at 3 months, 6 months and 9 months (p=0.04, p=0.03, p=0.03), due to fewer controls on target at 3 months, 6 months and 9 months and more IW participants at 6 months. Reductions in secondary outcomes (systolic blood pressure, blood glucose/lipid parameters and lifestyle measures) followed the pattern of weight loss.ConclusionsAn interdisciplinary intervention produced greater and more clinically significant and sustained weight loss compared with usual care. The intensive phase was sufficient to reach clinically relevant targets, but long-term management plans may be required.Trial registration numberANZCTRN 12614000581662; Post-results.
Comorbidities, complications and mortality in people of South Asian ethnicity with type 1 diabetes compared with other ethnic groups: a systematic review
Authors: Sarwar Komil N , Cliff Phoebe , Saravanan Ponnusamy , Khunti Kamlesh , Nirantharakumar Krishnarajah , Narendran Parth 
Published: July 2017

ObjectiveThe aim of this systematic review is to explore the association of South Asian (SA) ethnicity on comorbidities, microvascular and macrovascular complications and mortality compared with other ethnic groups in people with type 1 diabetes mellitus (T1DM).DesignSystematic review.MethodA systematic literature search strategy was designed and carried out using Medline and Embase for full-text and abstract studies published in English from 1946 to February 2016. The initial search identified 4722 papers. We assessed 305 full-text articles in detail for potential inclusion. Ten papers met the inclusion criteria for review and an additional one paper was included from our secondary search strategy using the bibliography of included studies. In total, 11 studies were included.Eligibility criteria for selecting studiesStudies were included if they were published in English, involved SA participants with T1DM and compared them with non-SA participants and assessed one of the outcomes of comorbidities, microvascular complications, macrovascular complications and mortality.ResultsSA with T1DM have higher mortality compared with white Europeans (WE), mainly contributed to by excess cardiovascular disease. SA have significantly higher glycated haemoglobin (HbA1c), lower high-density lipoprotein (HDL) and lower rates of neuropathy compared with WE. There were no differences in rates of retinopathy and nephropathy. Compared with Africans, SA had lower levels of microalbuminuria, HbA1c and systolic blood pressure and higher HDL levels. There were no significant differences in the remaining outcomes: cardiovascular disease, retinopathy, neuropathy and body mass index. Furthermore, SA have higher HbA1c levels than Malay and Chinese and higher waistâ€“hip ratio and lower HDL levels compared with Chinese only.ConclusionOur analysis highlights ethnic disparity in macrovascular outcomes that is so evident for type 2 diabetes mellitus may also be present for SA patients with T1DM. We highlight the need for a large, prospective, cohort study exploring the effect of ethnicity in a uniform healthcare setting.
Occupational risk forLegionellainfection among dental healthcare workers: meta-analysis in occupational epidemiology
Authors: Petti Stefano , Vitali Matteo 
Published: July 2017

ObjectiveThe occupational risk forLegionellainfection among dental healthcare workers (DHCWs) is conjectured because of the risk of routine inhalation of potentially contaminated aerosols produced by the dental instruments. Nevertheless, occupational epidemiology studies are contrasting. This meta-analysis assessed the level of scientific evidence regarding the relative occupational risk forLegionellainfection among DHCWs.MethodsLiterature search was performed without time and language restrictions, using broad data banks (PubMed, Scopus, Web of Science, GOOGLE Scholar) and generic keywords (‘legionella’ AND ‘dent*’). Analytical cross-sectional studies comparing prevalence of high serumLegionellaantibody levels in DHCWs and occupationally unexposed individuals were considered. The relative occupational risk was assessed through prevalence ratio (PR) with 95% CI. Between-study heterogeneity was assessed (Cochran’s Q test) and was used to choose the meta-analytic method. Study quality (modified Newcastle-Ottawa Scale) and publication bias (Begg and Mazumdar’s test, Egger and colleagues’ test, trim and fill R0method) were assessed formally and considered for the sensitivity analysis. Sensitivity analysis to study inclusion, subgroup analyses (dental staff categories; publication year, before vs after 1998, ie, 5 years after the release by the Centers for Disease Control and Prevention of the infection control guidelines in dental healthcare setting) were performed.ResultsSeven studies were included (2232 DHCWs, 1172 occupationally unexposed individuals). No evidence of publication bias was detected. The pooled PR estimate was statistically non-significant at 95% level (1.7; 95% CI 0.8 to 3.2), study-quality adjustment did not change the PR considerably (PR, 1.5; 95% CI 0.5 to 4.1). PR was statistically significant before 1998 and no longer significant after 1998. Subgroup analysis according to DHCW categories was inconclusive.ConclusionsThere is no scientific evidence that DHCWs are at high occupational risk. The differences between former and recent studies could be due to different characteristics of municipal water systems and the infection control guideline dissemination.
A study protocol for an observational cohort investigating COGnitive outcomes and WELLness in survivors of critical illness: the COGWELL study
Authors: Wilcox M Elizabeth , Lim Andrew S , McAndrews Mary P , Wennberg Richard A , Pinto Ruxandra L , Black Sandra E , Walczak Karolina D , Friedrich Jan O , Taglione Michael S , Rubenfeld Gordon D 
Published: July 2017

IntroductionUp to 9 out of 10 intensive care unit (ICU) survivors will suffer some degree of cognitive impairment at hospital discharge and approximately half will have decrements that persist for years. The mechanisms for this newly acquired brain injury are poorly understood. The purpose of this study is to describe the prevalence of sleep abnormalities and their association with cognitive impairment, examine a well-known genetic risk factor for dementia (Apolipoprotein E ε4) that may allow for genetic risk stratification of ICU survivors at greatest risk of cognitive impairment and determine if electroencephalography (EEG) is an independent predictor of long-term cognitive impairment and possibly a candidate intermediate end point for future clinical trials.Methods and analysisThis is a multisite, prospective, observational cohort study. The setting for this trial will be medical and surgical ICUs of five large tertiary care referral centres. The participants will be adult patients admitted to a study ICU and invasively ventilated for ≥3 days . Participants will undergo follow-up within 7 days of ICU discharge, 6 months and 1 year. At each time point, patients will have an EEG, blood work (biomarkers; gene studies), sleep study (actigraphy), complete a number of questionnaires as well as undergo neuropsychological testing. The primary outcome of this study will be long-term cognitive function at 12 months follow-up as measured by the Repeatable Battery for the Assessment of Neuropsychological Status and Trails Making Test B.Ethics and disseminationThe study has received the following approvals: University Health Network Research Ethics Committee (13–6425-BE), Sunnybrook Health Centre Research Ethics Committee (365–2013), Mount Sinai Research Ethics Committee (14–0194-E) and St. Michael’s Hospital Research Ethics Committee (14-295). Results will be made available to critical care survivors, their caregivers, the funders, the critical care societies and other researchers.Trial registration numberNCT02086877; Pre-results.
Trends in readmission rates for safety net hospitals and non-safety net hospitals in the era of the US Hospital Readmission Reduction Program: a retrospective time series analysis using Medicare administrative claims data from 2008 to 2015
Authors: Salerno Amy M , Horwitz Leora I , Kwon Ji Young , Herrin Jeph , Grady Jacqueline N , Lin Zhenqiu , Ross Joseph S , Bernheim Susannah M 
Published: July 2017

ObjectiveTo compare trends in readmission rates among safety net and non-safety net hospitals under the US Hospital Readmission Reduction Program (HRRP).DesignA retrospective time series analysis using Medicare administrative claims data from January 2008 to June 2015.SettingWe examined 3254 US hospitals eligible for penalties under the HRRP, categorised as safety net or non-safety net hospitals based on the hospital’s proportion of patients with low socioeconomic status.ParticipantsAdmissions for Medicare fee-for-service patients, age ≥65 years, discharged alive, who had a valid five-digit zip code and did not have a principal discharge diagnosis of cancer or psychiatric illness were included, for a total of 52 516 213 index admissions.Primary and secondary outcome measuresMean hospital-level, all-condition, 30-day risk-adjusted standardised unplanned readmission rate, measured quarterly, along with quarterly rate of change, and an interrupted time series examining: April–June 2010, after HRRP was passed, and October–December 2012, after HRRP penalties were implemented.Results58.0% (SD 15.3) of safety net hospitals and 17.1% (SD 10.4) of non-safety net hospitals’ patients were in the lowest quartile of socioeconomic status. The mean safety net hospital standardised readmission rate declined from 17.0% (SD 3.7) to 13.6% (SD 3.6), whereas the mean non-safety net hospital declined from 15.4% (SD 3.0) to 12.7% (SD 2.5). The absolute difference in rates between safety net and non-safety net hospitals declined from 1.6% (95% CI 1.3 to 1.9) to 0.9% (0.7 to 1.2). The quarterly decline in standardised readmission rates was 0.03 percentage points (95% CI 0.03 to 0.02, p<0.001) greater among safety net hospitals over the entire study period, and no differential change among safety net and non-safety net hospitals was found after either HRRP was passed or penalties enacted.ConclusionsSince HRRP was passed and penalties implemented, readmission rates for safety net hospitals have decreased more rapidly than those for non-safety net hospitals.
A developmental evaluation to enhance stakeholder engagement in a wide-scale interactive project disseminating quality improvement data: study protocol for a mixed-methods study
Authors: Laycock Alison , Bailie Jodie , Matthews Veronica , Cunningham Frances , Harvey Gillian , Percival Nikki , Bailie Ross 
Published: July 2017

IntroductionBringing together continuous quality improvement (CQI) data from multiple health services offers opportunities to identify common improvement priorities and to develop interventions at various system levels to achieve large-scale improvement in care. An important principle of CQI is practitioner participation in interpreting data and planning evidence-based change. This study will contribute knowledge about engaging diverse stakeholders in collaborative and theoretically informed processes to identify and address priority evidence-practice gaps in care delivery. This paper describes a developmental evaluation to support and refine a novel interactive dissemination project using aggregated CQI data from Aboriginal and Torres Strait Islander primary healthcare centres in Australia. The project aims to effect multilevel system improvement in Aboriginal and Torres Strait Islander primary healthcare.Methods and analysisData will be gathered using document analysis, online surveys, interviews with participants and iterative analytical processes with the research team. These methods will enable real-time feedback to guide refinements to the design, reports, tools and processes as the interactive dissemination project is implemented. Qualitative data from interviews and surveys will be analysed and interpreted to provide in-depth understanding of factors that influence engagement and stakeholder perspectives about use of the aggregated data and generated improvement strategies. Sources of data will be triangulated to build up a comprehensive, contextualised perspective and integrated understanding of the project's development, implementation and findings.Ethics and disseminationThe Human Research Ethics Committee (HREC) of the Northern Territory Department of Health and Menzies School of Health Research (Project 2015-2329), the Central Australian HREC (Project 15-288) and the Charles Darwin University HREC (Project H15030) approved the study. Dissemination will include articles in peer-reviewed journals, policy and research briefs. Results will be presented at conferences and quality improvement network meetings. Researchers, clinicians, policymakers and managers developing evidence-based system and policy interventions should benefit from this research.
Assessing the effectiveness of a 3-month day-and-night home closed-loop control combined with pump suspend feature compared with sensor-augmented pump therapy in youths and adults with suboptimally controlled type 1 diabetes: a randomised parallel study protocol
Authors: Bally Lia , Thabit Hood , Tauschmann Martin , Allen Janet M , Hartnell Sara , Wilinska Malgorzata E , Exall Jane , Huegel Viki , Sibayan Judy , Borgman Sarah , Cheng Peiyao , Blackburn Maxine , Lawton Julia , Elleri Daniela , Leelarathna Lalantha , Acerini Carlo L , Campbell Fiona , Shah Viral N , Criego Amy , Evans Mark L , Dunger David B , Kollman Craig , Bergenstal Richard M , Hovorka Roman 
Published: July 2017

IntroductionDespite therapeutic advances, many individuals with type 1 diabetes are unable to achieve tight glycaemic target without increasing the risk of hypoglycaemia. The objective of this study is to determine the effectiveness of a 3-month day-and-night home closed-loop glucose control combined with a pump suspend feature, compared with sensor-augmented insulin pump therapy in youths and adults with suboptimally controlled type 1 diabetes.Methods and analysisThe study adopts an open-label, multi-centre, multi-national (UK and USA), randomised, single-period, parallel design and aims for 84 randomised patients. Participants are youths (6–21 years) or adults (>21 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c) ≥7.5% (58 mmol/mol) and ≤10% (86 mmol/mol)). Following a 4-week run-in period, eligible participants will be randomised to a 3-month use of automated closed-loop insulin delivery combined with pump suspend feature or to sensor-augmented insulin pump therapy. Analyses will be conducted on an intention-to-treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3-month free-living phase. Secondary outcomes include HbA1c at 3 months, mean glucose, time spent below and above target; time with glucose levels <3.5 and <2.8 mmol/L; area under the curve when sensor glucose is <3.5 mmol/L, time with glucose levels >16.7 mmol/L, glucose variability; total, basal and bolus insulin dose and change in body weight. Participants’ and their families’ perception in terms of lifestyle change, daily diabetes management and fear of hypoglycaemia will be evaluated.Ethics and disseminationEthics/institutional review board approval has been obtained. Before screening, all participants/guardians will be provided with oral and written information about the trial. The study will be disseminated by peer-reviewed publications and conference presentations.Trial registration numberNCT02523131; Pre-results.