bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering Streptomyces coelicolor Carbonyl Reductase for Efficient Atorvastatin Precursor Synthesis
Authors: Li Min , Zhang Zhi-Jun , Kong Xu-Dong , Yu Hui-Lei , Zhou Jiahai , Xu Jian-He 
Published: April 2017

ABSTRACTStreptomyces coelicolorCR1 (ScCR1) has been shown to be a promising biocatalyst for the synthesis of an atorvastatin precursor, ethyl-(S)-4-chloro-3-hydroxybutyrate [(S)-CHBE]. However, limitations ofScCR1 observed for practical application include low activity and poor stability. In this work, protein engineering was employed to improve the catalytic efficiency and stability ofScCR1. First, the crystal structure ofScCR1 complexed with NADH and cosubstrate 2-propanol was solved, and the specific activity ofScCR1 was increased from 38.8 U/mg to 168 U/mg (ScCR1I158V/P168S) by structure-guided engineering. Second, directed evolution was performed to improve the stability usingScCR1I158V/P168Sas a template, affording a triple mutant,ScCR1A60T/I158V/P168S, whose thermostability (T5015, defined as the temperature at which 50% of initial enzyme activity is lost following a heat treatment for 15 min) and substrate tolerance (C5015, defined as the concentration at which 50% of initial enzyme activity is lost following incubation for 15 min) were 6.2°C and 4.7-fold higher than those of the wild-type enzyme. Interestingly, the specific activity of the triple mutant was further increased to 260 U/mg. Protein modeling and docking analysis shed light on the origin of the improved activity and stability. In the asymmetric reduction of ethyl-4-chloro-3-oxobutyrate (COBE) on a 300-ml scale, 100 g/liter COBE could be completely converted by only 2 g/liter of lyophilizedScCR1A60T/I158V/P168Swithin 9 h, affording an excellent enantiomeric excess (ee) of >99% and a space-time yield of 255 g liter−1day−1. These results suggest high efficiency of the protein engineering strategy and good potential of the resulting variant for efficient synthesis of the atorvastatin precursor.IMPORTANCEApplication of the carbonyl reductaseScCR1 in asymmetrically synthesizing (S)-CHBE, a key precursor for the blockbuster drug Lipitor, from COBE has been hindered by its low catalytic activity and poor thermostability and substrate tolerance. In this work, protein engineering was employed to improve the catalytic efficiency and stability ofScCR1. The catalytic efficiency, thermostability, and substrate tolerance ofScCR1 were significantly improved by structure-guided engineering and directed evolution. The engineeredScCR1 may serve as a promising biocatalyst for the biosynthesis of (S)-CHBE, and the protein engineering strategy adopted in this work would serve as a useful approach for future engineering of other reductases toward potential application in organic synthesis.
Earned print media in advancing tobacco control in Himachal Pradesh, India: a descriptive study
Authors: Sharma Renu , Shewade Hemant Deepak , Gopalan Balasubramaniam , Badrel Ramesh Kumar , Rana Jugdeep Singh 
Published: April 2017

BackgroundThe Union-Bloomberg Initiative tobacco control projects were implemented in Himachal Pradesh (a hilly state in North India) from 2007 to 2014. The project focused on the establishment of an administrative framework; increasing the capacity of stakeholders; enforcement of legislation; coalition and networking with multiple stakeholders; awareness generation with focus on earned media and monitoring and evaluation with policy-focussed research. This study aimed to systematically analyse all earned print news items related to the projects.MethodsIn this cross-sectional descriptive study, quantitative content analysis of earned print news items was carried out using predetermined codes related to areas of tobacco control policies. We also carried out a cost description of the hypothetical value of this earned media. The area of the news item in cm2was multiplied by the average rate of space for the paid news item in that particular newspaper.ResultsThere were 6348 news items: the numbers steadily increased with time. Focus on Monitoring tobacco use, Protecting people from tobacco smoke, Offering help to quit, Warning about dangers of tobacco, Enforcing a ban on tobacco advertising and promotion, Raising tax on tobacco products was seen in 24, 17, 9, 23, 22 and 3% of news items, respectively. Press releases were highest at 44% and report by correspondents at 24%. Further, 55, 23 and 21% news items focused on smoking, smokeless and both forms of tobacco use, respectively. Sixty-six per cent and 34% news items, respectively, were focused on youth and women. The news items had a hypothetical value of US$1503 628.3, which was three times more than the funds spent on all project activities.ConclusionsIn the absence of funding for paid media, the project strategically used earned media to promote tobacco control policies in the state.
Relationship between uric acid and technique failure in patients on continuous ambulatory peritoneal dialysis: a long-term observational cohort study
Authors: Hsieh Yao-Peng , Chang Chia-Chu , Kor Chew-Teng , Yang Yu , Wen Yao-Ko , Chiu Ping-Fang , Lin Chi-Chen 
Published: April 2017

ObjectivesUric acid (UA) is the product of purine or nucleotide metabolism via the pathway of xanthine oxidase or xanthine dehydrogenase. Although epidemiological studies assessing the role of UA in cardiovascular disease or mortality have produced inconsistent results, the correlation between UA and technique failure in patients on continuous ambulatory peritoneal dialysis (CAPD) remains to be assessed.DesignA retrospective cohort study.SettingPatients starting CAPD between 2001 and 2009 in a single centre in Taiwan.ParticipantsA total of 371 patients on CAPD.Primary outcome measuresAll-cause and peritonitis-related technique failure.ResultsA cohort of 371 participants (43.9% male) was enrolled in the study with a mean age of 55.7±15.9 years at the start of CAPD. During the study period, technique failure occurred in 41 (34.4%) patients in the hyperuricaemia group compared with 49 (19.4%) in the normouricaemia group (p=0.003). In the multivariate Cox regression models, hyperuricaemia at baseline was significantly associated with both a higher risk of technique failure (HR 1.24; 95% CI 1.09 to 1.42, p=0.001) and peritonitis-related technique failure (HR 1.29; 95% CI 1.07 to 1.57, p=0.008).ConclusionsUA was shown to be associated with all-cause and peritonitis-related technique failure in our study. Patients on CAPD with hyperuricaemia should be closely monitored and strategies of increasing survival on CAPD should be taken.
What are the risks and benefits of temporarily discontinuing medications to prevent acute kidney injury? A systematic review and meta-analysis
Authors: Whiting Penny , Morden Andrew , Tomlinson Laurie A , Caskey Fergus , Blakeman Thomas , Tomson Charles , Stone Tracey , Richards Alison , Savović Jelena , Horwood Jeremy 
Published: April 2017

ObjectivesTo summarise evidence on temporary discontinuation of medications to prevent acute kidney injury (AKI).DesignSystematic review and meta-analysis of randomised and non-randomised studies.ParticipantsAdults taking diuretics, ACE inhibitors (ACEI), angiotensin receptor blockers (ARB), direct renin inhibitors, non-steroidal anti-inflammatories, metformin or sulfonylureas, experiencing intercurrent illnesses, radiological or surgical procedures.InterventionsTemporary discontinuation of any of the medications of interest.Primary and secondary outcome measuresRisk of AKI. Secondary outcome measures were estimated glomerular filtration rate and creatinine post-AKI, urea, systolic and diastolic blood pressure, death, clinical outcomes and biomarkers.Results6 studies were included (1663 participants), 3 randomised controlled trials (RCTs) and 3 prospective cohort studies. The mean age ranged from 65 to 73 years, and the proportion of women ranged from 31% to 52%. All studies were in hospital settings; 5 evaluated discontinuation of medication prior to coronary angiography and 1 prior to cardiac surgery. 5 studies evaluated discontinuation of ACEI and ARBs and 1 small cohort study looked at discontinuation of non-steroidal anti-inflammatory drugs. No studies evaluated discontinuation of medication in the community following an acute intercurrent illness. There was an increased risk of AKI of around 15% in those in whom medication was continued compared with those in whom it was discontinued (relative risk (RR) 1.17, 95% CI 0.99 to 1.38; 5 studies). When only results from RCTs were pooled, the increase in risk was almost 50% (RR 1.48, 95% CI 0.84 to 2.60; 3 RCTs), but the CI was wider. There was no difference between groups for any secondary outcomes.ConclusionsThere is low-quality evidence that withdrawal of ACEI/ARBs prior to coronary angiography and cardiac surgery may reduce the incidence of AKI. There is no evidence of the impact of drug cessation interventions on AKI incidence during intercurrent illness in primary or secondary care.Trial registration numberPROSPERO CRD42015023210.
Epidemiology of rubella infection in Cameroon: a 7-year experience of measles and rubella case-based surveillance, 2008–2014
Authors: Nimpa Mengouo Marcellin , Ndze Valantine Ngum , Baonga Frangy , Kobela Marie , Wiysonge Charles Shey 
Published: April 2017

ObjectiveThe aim of this study was to estimate the proportion of rubella disease in a measles case-based surveillance in Cameroon prior to rubella vaccine introduction into the national immunisation programme.DesignThis was a cross-sectional study for rubella infection in Cameroon for the period 2008 to 2014.SettingPatients suspected with measles from the 10 regions of Cameroon were recruited according to the WHO measles case definition and were tested for rubella IgM antibodies accompanied with the case report/investigation forms.ParticipantsAll persons with rash and fever within 14 days of onset of rash according to the standard WHO African Regional Office (WHO/AFRO) case definition for a suspected measles case.Outcome measuresDescriptive analyses and simple logistic regressions were performed. OR were estimated.ResultsA total of 9907 serum samples from people with fever and rash were received in the laboratory from 2008 to 2014. A total of 7489 (75.59%) measles-negative samples were tested for rubella; 699 (9.3%) were positive for rubella IgM antibodies. Logistic regression analysis was done using IgM antibodies detection as the outcome variable. Age, sex and setting were explanatory variables. Logistic regression analysis revealed that, comparing the proportion of rubella IgM seropositivity status by age, the association to a positive rubella IgM increased with age from 1 to 4 years (OR 7.11; 95% CI 4.35 to 12.41; p<0.0001), through 5 to 9 years (OR 13.07; 95% CI 7.93 to 22.93; p<0.001), to 10 to 14 years of age (OR 13.86; 95% CI 8.06 to 25.12; p<0.001). Persons aged ≥15 years were also more likely to have rubella infection than children under one (OR 3.69; 95% CI 1.85 to 7.48; p=0.0001). There were also significant associations with sex, with males being less associated to a positive rubella serology than females (OR 1.33; 95% CI 1.14 to 1.56; p=0.0001). No statistically significant difference in proportion of rubella cases was observed between urban and rural populations (OR 1.11; 95% CI 0.94 to 1.31; p=0.208).ConclusionsThis study reveals that rubella virus circulates in Cameroon, with important number of cases in children under 15 years. This finding supports the planned introduction of rubella-containing vaccines into the Expanded Program on Immunization.
Long-term use benefits of personal frequency-modulated systems for speech in noise perception in patients with stroke with auditory processing deficits: a non-randomised controlled trial study
Authors: Koohi Nehzat , Vickers Deborah , Warren Jason , Werring David , Bamiou Doris-Eva 
Published: April 2017

ObjectivesApproximately one in five stroke survivors suffer from difficulties with speech reception in noise, despite normal audiometry. These deficits are treatable with personal frequency-modulated systems (FMs). This study aimed to evaluate long-term benefits in speech reception in noise, after daily 10-week use of personal FMs, in non-aphasic patients with stroke with auditory processing deficits.DesignThis was a prospective non-randomised controlled trial study. Patients were allocated to an intervention care group or standard care subjects group according to their willingness to use the intervention or not.SettingTertiary care setting.ParticipantsNine non-aphasic subjects with ischaemic stroke, normal/near-normal audiometry and auditory processing deficits and with reported difficulties understanding speech in background noise were recruited in the subacute stroke stage (3–12 months after stroke).InterventionsFour patients (intervention care subjects) used the FMs in their daily life over 10 weeks. Five patients (standard care subjects) received standard care.Primary outcome measuresAll subjects were tested at baseline (visit 1) and 10 weeks later (visit 2) on a sentences in noise test with the FMs (aided) and without the FMs (unaided).ResultsSpeech reception thresholds showed clinically and statistically significant improvements in intervention but not in standard care subjects at 10 weeks in aided and unaided conditions.Conclusions10-week use of FMs by adult patients with stroke may lead to benefits in unaided speech in noise perception. Our findings may indicate auditory plasticity type changes and require further investigation.Trial registration numberPre-results;NCT02889107.
Social prescribing: less rhetoric and more reality. A systematic review of the evidence
Authors: Bickerdike Liz , Booth Alison , Wilson Paul M , Farley Kate , Wright Kath 
Published: April 2017

ObjectivesSocial prescribing is a way of linking patients in primary care with sources of support within the community to help improve their health and well-being. Social prescribing programmes are being widely promoted and adopted in the UK National Health Service and so we conducted a systematic review to assess the evidence for their effectiveness.Setting/data sourcesNine databases were searched from 2000 to January 2016 for studies conducted in the UK. Relevant reports and guidelines, websites and reference lists of retrieved articles were scanned to identify additional studies. All the searches were restricted to English language only.ParticipantsSystematic reviews and any published evaluation of programmes where patient referral was made from a primary care setting to a link worker or facilitator of social prescribing were eligible for inclusion. Risk of bias for included studies was undertaken independently by two reviewers and a narrative synthesis was performed.Primary and secondary outcome measuresPrimary outcomes of interest were any measures of health and well-being and/or usage of health services.ResultsWe included a total of 15 evaluations of social prescribing programmes. Most were small scale and limited by poor design and reporting. All were rated as a having a high risk of bias. Common design issues included a lack of comparative controls, short follow-up durations, a lack of standardised and validated measuring tools, missing data and a failure to consider potential confounding factors. Despite clear methodological shortcomings, most evaluations presented positive conclusions.ConclusionsSocial prescribing is being widely advocated and implemented but current evidence fails to provide sufficient detail to judge either success or value for money. If social prescribing is to realise its potential, future evaluations must be comparative by design and consider when, by whom, for whom, how well and at what cost.Trial registration numberPROSPERO Registration: CRD42015023501.
What is the care pathway of patients who undergo thyroid surgery in France and its potential pitfalls? A national cohort
Authors: Mathonnet Muriel , Cuerq Anne , Tresallet Christophe , Thalabard Jean-Christophe , Fery-Lemonnier Elisabeth , Russ Gilles , Leenhardt Laurence , Bigorgne Claude , Tuppin Philippe , Millat Bertrand , Fagot-Campagna Anne 
Published: April 2017

ContextThe rate of thyroid cancer is increasing in France, as well as concerns about overdiagnosis and treatment.ObjectivesTo examine the care pathway of patients who undergo thyroid surgery in France and detect potential pitfalls.DesignA large observational study based on medical reimbursements, 2009–2011.SettingData from the Sniiram (National Health Insurance Information System).PatientsPatients with thyroid surgery in 2010, classified into 4 groups: thyroid cancer, benign nodule, goitre or multiple nodules, other (hyperthyroidism, head–neck cancer).Main outcome measuresMedical investigations during, prior and after thyroidectomy.ResultsA total of 35 367 patients underwent surgery (mean age 51 years, 80% women): 17% had a reported diagnosis of thyroid cancer, 20% benign nodule, 38% goitre or multiple nodules and 25% another diagnosis. The ratio of thyroidectomies with cancer over thyroidectomies with benign nodule was 0.8 and varied across regions. In the year preceding surgery, 82% of patients had an investigation by thyroid ultrasonography, 21% thyroid scintigraphy, 34% fine-needle aspiration cytology, 40% serum calcitonin assay and 54% serum calcium assay. In the following year, all patients with total thyroidectomy and 44% of patients with partial thyroidectomy and a diagnosis of benign nodule were taking thyroid hormone therapy. 100 patients had been reoperated for a compressive haematoma and 63 died during the first month, half of whom had been operated for cancer. Mean rates of recurrent laryngeal nerve injury and hypocalcaemia (requiring blood tests plus treatments within 4–12 months) were estimated at 1.5% and 3.4%, respectively, and were higher in the cancer group (2.3% and 5.7%).ConclusionsThis almost nationwide study demonstrates the suboptimal management of patients prior to thyroidectomy in France. It suggests overdiagnosis and potential harms to patients, and calls for a review of the relevance of thyroidectomy, particularly with regard to microcancers.
Secular trends in the incidence of dementia in high-income countries: a protocol of a systematic review and a planned meta-analysis
Authors: Roehr Susanne , Pabst Alexander , Luck Tobias , Riedel-Heller Steffi G 
Published: April 2017

IntroductionA global dementia epidemic is projected for the year 2050 with an ever-rising number of individuals living with the syndrome worldwide. However, increasingly, studies are emerging from high-income countries (HIC) that show a positive trend towards a possible decrease in dementia occurrence. Therefore, we aim to systematically summarise evidence regarding secular trends in the incidence of dementia in HIC.Methods and analysisWe will conduct a systematic review of the literature on secular trends in dementia incidence in HIC according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statements. To do so, we will search the databases MEDLINE (PubMed interface), EMBASE (Ovid interface) and Web of Science (Web of Science interface), as well as the grey literature on unpublished studies. To be eligible, studies must have been published in English or German since 1990 and provide sufficient information on prespecified eligibility criteria regarding outcome measurement and methodological approach. Study selection, data extraction and risk of bias assessment will be performed independently by 2 reviewers. Disagreement will be resolved by discussion and/or the involvement of a third researcher. Data abstraction will include study and participant characteristics, outcomes and methodological aspects. Results will be described and discussed regarding methodology. Depending on the number of studies found and the heterogeneity between the studies, we plan to combine outcome data through meta-analysis in order to get pooled incidence measures.Ethics and disseminationNo primary data will be collected; thus, ethical approval is not required. The results will be disseminated through a peer-reviewed publication and conference presentations.PROSPERO registration numberCRD42016043232.
Long-term effect of smartphone-delivered Interval Walking Training on physical activity in patients with type 2 diabetes: protocol for a parallel group single-blinded randomised controlled trial
Authors: Valentiner Laura Staun , Ried-Larsen Mathias , Karstoft Kristian , Brinkløv Cecilie Fau , Brøns Charlotte , Nielsen Rasmus Oestergaard , Christensen Robin , Nielsen Jens Steen , Vaag Allan Arthur , Pedersen Bente Klarlund , Langberg Henning 
Published: April 2017

IntroductionPhysical activity is a cornerstone in type 2 diabetes (T2D) rehabilitation. Effective long-term and low-cost strategies to keep these patients' physically active are needed. However, maintaining physical activity behaviour is difficult once formalised interventions end. Structured exercise training supported by mobile technology and remote feedback is potentially an effective strategy. The objective of the trial is to investigate whether mobile health support using the InterWalk application for smartphones is effective in increasing physical activity levels in persons with T2D over time compared with standard care. We investigate whether Interval Walking Training using the InterWalk application is superior to Danish municipality-based rehabilitation in increasing moderate-and-vigorous physical activity levels in patients with T2D across 52 weeks. Secondary, we hypothesise that a motivational programme added from end of intervention to 52 weeks further increases level of physical activity in everyday life in patients with T2D.Methods and analysisThe trial is a parallel-group, open-labelled, randomised controlled trial with long-term follow-up at 52 week including patients with T2D. The primary outcome is change in moderate-and-vigorous physical activity. The key secondary outcome includes motivation for physical activity behaviour change. Other secondary outcomes are VO2-peak, strength in the lower extremities. Exclusion criterion is medical contraindication to exercise. We include up to 246 patients and randomly allocate them into a control (standard group) or an experimental group (8–12 weeks of IWT supported by the smartphone-based InterWalk application) in a 1:2 fashion. After intervention, the experimental group is randomly allocated into two follow-up conditions with unsupervised IWT with or without motivational support until 52-week follow-up. The intention-to-treat principle is applied.Ethics and disseminationThe local regional Research Ethics Committee in Denmark (H-1-2014-074) and the Danish Data Protection Agency (j.nr. 2014-54-0897) have approved the trial. Positive, negative or inconclusive results will be disseminated in scientific journals and conferences.Trial registration numberNCT02341690.