bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substrate Specificity for Bacterial RNases HII and HIII Is Influenced by Metal Availability
Authors: Randall Justin R. , Hirst William G. , Simmons Lyle A. 
Published: October 2017

ABSTRACT

We tested the activities of four predicated RNase H enzymes, including two RNase HI-type enzymes, in addition to RNase HII (RnhB) and RNase HIII (RnhC), on several RNA-DNA hybrid substrates with different divalent metal cations. We found that the two RNase HI-type enzymes, YpdQ and YpeP, failed to show activity on the three substrates tested. RNase HII and RNase HIII cleaved all the substrates tested, although the activity was dependent on the metal made available. We show that
Bacillus subtilis
RNase HII and RNase HIII are both able to incise 5′ to a single ribonucleoside monophosphate (rNMP). We show that RNase HIII incision at a single rNMP occurs most efficiently with Mn
2+
, an activity we found to be conserved among other Gram-positive RNase HIII enzymes. Characterization of RNases HII and HIII with metal concentrations in the physiological range showed that RNase HII can cleave at single rNMPs embedded in DNA while RNase HIII is far less effective. Further, using metal concentrations within the physiological range, RNase HIII efficiently cleaved longer RNA-DNA hybrids lacking an RNA-DNA junction, while RNase HII was much less effective. Phenotypic analysis showed that cells with an
rnhC
deletion were sensitive to hydroxyurea (HU). In contrast, cells with an
rnhB
deletion showed wild-type growth in the presence of HU, supporting the hypothesis that RNases HII and HIII have distinct substrate specificities
in vivo
. This work demonstrates how metal availability influences the substrate recognition and activity of RNases HII and HIII, providing insight into their functions
in vivo
.

IMPORTANCE
RNase H represents a class of proteins that cleave RNA-DNA hybrids, helping resolve R-loops and Okazaki fragments, as well as initiating the process of ribonucleotide excision repair (RER). We investigated the activities of four
Bacillus subtilis
RNase H enzymes and found that only RNases HII and HIII have activity and that their substrate preference is dependent on metal availability. To understand the factors that contribute to RNase HII and RNase HIII substrate preference, we show that in the presence of metal concentrations within the physiological range, RNases HII and HIII have distinct activities on different RNA-DNA hybrids. This work provides insight into how RNases HII and HIII repair the broad range of RNA-DNA hybrids that form in Gram-positive bacteria.
How can we implement exercise therapy for patellofemoral pain if we don’t know what was prescribed? A systematic review
Authors: Holden Sinead , Rathleff Michael Skovdal , Jensen Martin Bach , Barton Christian J 
Published: October 2017

ObjectiveTo evaluate the completeness of exercise prescription in randomised controlled trials (RCTs) for patellofemoral pain (PFP), identify which elements are most frequently missing and supplement recommendations based on additional data from authors.DesignSystematic review.Data sourcesAll studies included in the most recent Cochrane review were evaluated. Additionally, the Cochrane search was updated in June 2016 in Cochrane, MEDLINE, EMBASE, PEDro, CINAHL and AMED databases. Two raters independently assessed completeness of reporting using the Toigo and Boutellier mechanobiological exercise descriptors, and Template for Intervention Description and Replication (TIDieR) checklist. Authors were also contacted to provide additional information.Eligibility criteria for selecting studiesRCTs of exercise interventions for PFP.ResultsWe included 38 RCTs. The level of exercise prescription detail was low, with no study providing complete information. The most commonly reported exercise descriptors were the ’duration of the experimental period' (n=38/38) and ’number of exercise interventions' (n=35). From TIDieR, the most commonly reported items were the ’intervention name' (n=38) and ’rationale' (n=36).The least reported items from the exercise descriptors were ’volitional muscular failure', ’temporal distribution of contraction modes', ’time under tension' and ’recovery between exercise sessions' (all n=2/38). From TIDieR, the least reported item was ‘How well (fidelity and adherence)’ (n=3/38).36 authors were contacted, with 22 replies and 13 providing additional exercise prescription details .ConclusionExercise prescriptions in RCTs with proven efficacy for PFP are poorly reported, impairing their implementation in clinical practice.PROSPERO registration numberCRD42016039138.
Direct medical costs of hospitalisations for mental disorders in Shanghai, China: a time series study
Authors: Chen Wenming , Wang Shengnan , Wang Qi , Wang Weibing 
Published: October 2017

ObjectivesTo provide cost burden estimates and long-term trend forecast of mental disorders that need hospitalisations in Shanghai, China.DesignDaily hospital admissions and medical expenditures for mental disorder hospitalisations between 1 January 2011 and 31 December 2015 were used for analysis. Yearly total health expenditures and expenditures per hospital admission for different populations, as well as per-admission-per-year medical costs of each service for mental disorder hospitalisations, were estimated through data from 2015. We also established time series analyses to determine the long-time trend of total direct medical expenditures for mental disorders and forecasted expenditures until 31 December 2030.SettingShanghai, China.ParticipantsDaily hospital admissions for mental disorders of registered residents living in all 16 districts of Shanghai, who participated in workers’ basic medical insurance or the urban residents’ basic medical insurance (n=60 306).ResultsFrom 2011 to 2015, there were increased yearly trends for both hospitalisations (from 10 919 to 14 054) and total costs (from US$23.56 to 42.13 million per year in 2015 currency) in Shanghai. Cost per mental disorder hospitalisation in 2015 averaged US$2998.01. Most direct medical costs were spent on medical supplies. By the end of 2030, the average cost per admission per month for mental disorders was estimated to be US$7394.17 (95% CI US$6782.24 to 8006.10) for mental disorders, and the total health expenditure for mental disorders would reach over US$100.52 million (95% CI US$92.20 to 108.83 million) without additional government interventions.ConclusionsThese findings suggest total health expenditures for mental disorders in Shanghai will be higher in the future. Effective measures should be taken to reduce the rapid growth of the economic burden of mental disorders.
How to measure experiences of healthcare quality in Denmark among patients with heart disease? The development and psychometric evaluation of a patient-reported instrument
Authors: Zinckernagel Line , Schneekloth Nanna , Zwisler Ann-Dorthe Olsen , Ersbøll Annette Kjær , Rod Morten Hulvej , Jensen Poul Dengsøe , Timm Helle , Holmberg Teresa 
Published: October 2017

ObjectiveMeasuring the quality of care as experienced by patients is increasingly recognised as a way of improving healthcare services. However, disease-specific measures that take the patient journey into account are needed. This paper presents the development of such a measure for patients with heart disease and details the psychometric evaluation.DesignThe questionnaire was developed based on a literature review, qualitative interviews and a pilot-test. The psychometric evaluation of the measure was assessed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), Cronbach’s alpha coefficient and differential item functioning analysis with data from a population-based survey.SettingDenmark in 2013–2014.Study participantsNineteen heart patients, four relatives and eight health professionals participated in qualitative interviews in the development phase, and 15 patients participated in the pilot-test. The questionnaire was subsequently sent to a random sample of 5000 heart patients who were diagnosed in 2013.ResultsThe comprehensive development phase and pilot-testing contributed to high content validity of the questionnaire. Eligible questionnaire responses were received from 2496 patients. EFA indicated a nine-factor model: communication at the hospital, communication with the general practitioner, information on disease and treatment, information on psychosocial aspects, rehabilitation/support, organisation, medication, involvement of relatives and consideration of comorbidity. CFA confirmed the proposed factor structure (eg, goodness-of-fit index=0.88, adjusted goodness-of-fit index=0.86, root mean square error of approximation=0.05), and Cronbach’s alpha coefficient revealed good internal consistency of the factors (range: 0.69–0.93).ConclusionsThe results suggest that this disease-specific patient-reported experience measure is of good quality when measuring the quality of care among heart patients. The inclusion of patients in the development phase contributed to high content validity, and subsequent psychometric evaluation found high construct validity and internal consistency. This measure may be especially relevant when seeking information about which aspects of care require improvement and the impact on health outcomes.
Safety of thrombolysis in stroke mimics: an observational cohort study from an urban teaching hospital in Sweden
Authors: Kostulas Nikolaos , Larsson Martin , Kall Tor-Bjorn , von Euler Mia , Nathanson David 
Published: October 2017

ObjectivesAcute stroke management has changed dramatically over the recent years, where a timely assessment is driven by the expanding treatment options of acute ischaemic stroke. This increases the risk in treating non-stroke patients (stroke mimics) with a possibly hazardous intravenous thrombolysis treatment (IVT).SettingPatients of the thrombolysis registry of Södersjukhuset AB, a secondary health centre in Stockholm, were retrospectively studied to determine complications and outcome after IVT in strokes and stroke mimics.ParticipantsConsecutively, 674 recruited patients from 1 January 2008 to 1 December 2013 were analysed regarding demographics and outcome at 3 months after onset of symptoms.ResultsIschaemic stroke was confirmed in 625 patients (93%), and 48 patients (7%) were stroke mimics. Patients with strokes were older than stroke mimics 72 (IQR: 64–81) vs 54 years (IQR 40–67), p<0.0001. Antihypertensive and antithrombotic treatment were more common in patients with stroke (p<0.0001 and p=0.006, respectively). National Institute of Health Stroke Scale did not differ at time of presentation. Excellent outcome defined as modified Rankin Scale score 0–1, at 3 months, was less common in stroke than in stroke mimics (50% vs 87.5%, p<0.0001). No stroke mimic had a symptomatic intracerebral haemorrhage. Age of less than 40 years may be a predictor for a patient to be a stroke mimic (OR: 8.7, 95% CI: 3.2 to 24.0, p<0.0001).ConclusionsStroke mimics receiving IVT had a more favourable outcome compared with patients with stroke, and showed no haemorrhagic complications. Age below 40 years may be a predictor for stroke mimics.
Dietary intake and sources of sodium and potassium among Australian schoolchildren: results from the cross-sectional Salt and Other Nutrients in Children (SONIC) study
Authors: Grimes Carley A , Riddell Lynn J , Campbell Karen J , Beckford Kelsey , Baxter Janet R , He Feng J , Nowson Caryl A 
Published: October 2017

ObjectivesTo examine sodium and potassium urinary excretion by socioeconomic status (SES), discretionary salt use habits and dietary sources of sodium and potassium in a sample of Australian schoolchildren.DesignCross-sectional study.SettingPrimary schools located in Victoria, Australia.Participants666 of 780 children aged 4–12 years who participated in the Salt and Other Nutrients in Children study returned a complete 24-hour urine collection.Primary and secondary outcome measures24-hour urine collection for the measurement of sodium and potassium excretion and 24-hour dietary recall for the assessment of food sources. Parent and child reported use of discretionary salt. SES defined by parental highest level of education.ResultsParticipants were 9.3 years (95% CI 9.0 to 9.6) of age and 55% were boys. Mean urinary sodium and potassium excretion was 103 (95% CI 99 to 108) mmol/day (salt equivalent 6.1 g/day) and 47 (95% CI 45 to 49) mmol/day, respectively. Mean molar Na:K ratio was 2.4 (95% CI 2.3 to 2.5). 72% of children exceeded the age-specific upper level for sodium intake. After adjustment for age, sex and day of urine collection, children from a low socioeconomic background excreted 10.0 (95% CI 17.8 to 2.1) mmol/day more sodium than those of high socioeconomic background (p=0.04). The major sources of sodium were bread (14.8%), mixed cereal-based dishes (9.9%) and processed meat (8.5%). The major sources of potassium were dairy milk (11.5%), potatoes (7.1%) and fruit/vegetable juice (5.4%). Core foods provided 55.3% of dietary sodium and 75.5% of potassium while discretionary foods provided 44.7% and 24.5%, respectively.ConclusionsFor most children, sodium intake exceeds dietary recommendations and there is some indication that children of lower socioeconomic background have the highest intakes. Children are consuming about two times more sodium than potassium. To improve sodium and potassium intakes in schoolchildren, product reformulation of lower salt core foods combined with strategies that seek to reduce the consumption of discretionary foods are required.
Comparing safety climate for nurses working in operating theatres, critical care and ward areas in the UK: a mixed methods study
Authors: Tarling Maggie , Jones Anne , Murrells Trevor , McCutcheon Helen 
Published: October 2017

ObjectivesThe main aim of the study was to explore the potential sources of variation and understand the meaning of safety climate for nursing practice in acute hospital settings in the UK.DesignA sequential mixed methods design included a cross-sectional survey using the Safety Climate Questionnaire (SCQ) and thematic analysis of focus group discussions. Confirmatory factor analysis (CFA) was used to validate the factor structure of the SCQ. Factor scores were compared between nurses working in operating theatres, critical care and ward areas. Results from the survey and the thematic analysis were then compared and synthesised.SettingA London University.Participants319 registered nurses working in acute hospital settings completed the SCQ and a further 23 nurses participated in focus groups.ResultsCFA indicated that there was a good model fit on some criteria (χ2=1683.699, df=824, p<0.001; χ2/df=2.04; root mean square error of approximation=0.058) but a less acceptable fit on comparative fit index which is 0.804. There was a statistically significant difference between clinical specialisms in management commitment (F (4,266)=4.66, p=0.001). Nurses working in operating theatres had lower scores compared with ward areas and they also reported negative perceptions about management in their focus group. There was significant variation in scores for communication across clinical specialism (F (4,266)=2.62, p=0.035) but none of the pairwise comparisons achieved statistical significance. Thematic analysis identified themes of human factors, clinical management and protecting patients. The system and the human side of caring was identified as a meta-theme.ConclusionsThe results suggest that the SCQ has some utility but requires further exploration. The findings indicate that safety in nursing practice is a complex interaction between safety systems and the social and interpersonal aspects of clinical practice.
NAITRE study on the impact of conditional cash transfer on poor pregnancy outcomes in underprivileged women: protocol for a nationwide pragmatic cluster-randomised superiority clinical trial in France
Authors: Bardou Marc , Crépon Bruno , Bertaux Anne-Claire , Godard-Marceaux Aurélie , Eckman-Lacroix Astrid , Thellier Elise , Falchier Frédérique , Deruelle Philippe , Doret Muriel , Carcopino-Tusoli Xavier , Schmitz Thomas , Barjat Thiphaine , Morin Mathieu , Perrotin Franck , Hatem Ghada , Deneux-Tharaux Catherine , Fournel Isabelle , Laforet Laurent , Meunier-Beillard Nicolas , Duflo Esther , Le Ray Isabelle 
Published: October 2017

IntroductionPrenatal care is recommended during pregnancy to improve neonatal and maternal outcomes. Women of lower socioeconomic status (SES) are less compliant to recommended prenatal care and suffer a higher risk of adverse perinatal outcomes. Several attempts to encourage optimal pregnancy follow-up have shown controversial results, particularly in high-income countries. Few studies have assessed financial incentives to encourage prenatal care, and none reported materno-fetal events as the primary outcome. Our study aims to determine whether financial incentives could improve pregnancy outcomes in women with low SES in a high-income country.Methods and analysisThis pragmatic cluster-randomised clinical trial includes pregnant women with the following criteria: (1) age above 18 years, (2) first pregnancy visit before 26 weeks of gestation and (3) belonging to a socioeconomically disadvantaged group. The intervention consists in offering financial incentives conditional on attending scheduled pregnancy follow-up consultations. Clusters are 2-month periods with random turnover across centres. A composite outcome of maternal and neonatal morbidity and mortality is the primary endpoint. Secondary endpoints include maternal or neonatal outcomes assessed separately, qualitative assessment of the perception of the intervention and cost-effectiveness analysis for which children will be followed to the end of their first year through the French health insurance database. The study started in June 2016, and based on an expected decrease in the primary endpoint from 18% to 14% in the intervention group, we plan to include 2000 women in each group.Ethics and disseminationEthics approval was first gained on 28 September 2014. An independent data security and monitoring committee has been established. Results of the main trial and each of the secondary analyses will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT02402855; pre-results.
Inhibition of REDD1 Sensitizes Bladder Urothelial Carcinoma to Paclitaxel by Inhibiting Autophagy
Authors: Zeng Qinghai , Liu Jianye , Cao Peiguo , Li Jingjing , Liu Xiaoming , Fan Xiaojun , Liu Ling , Cheng Yan , Xiong Wei , Li Jigang , Bo Hao , Zhu Yuxing , Yang Fei , Hu Jun , Zhou Ming , Zhou Yanhong , Zou Qiong , Zhou Jianda , Cao Ke 
Published: October 2017

Abstract
Purpose: Regulated in development and DNA damage response-1 (REDD1) is a stress-related protein and is involved in the progression of cancer. The role and regulatory mechanism of REDD1 in bladder urothelial carcinoma (BUC), however, is yet unidentified.
Experimental Design: The expression of REDD1 in BUC was detected by Western blot analysis and immunohistochemistry (IHC). The correlation between REDD1 expression and clinical features in patients with BUC were assessed. The effects of REDD1 on cellular proliferation, apoptosis, autophagy, and paclitaxel sensitivity were determined both in vitro and in vivo. Then the targeted-regulating mechanism of REDD1 by miRNAs was explored.
Results: Here the significant increase of REDD1 expression is detected in BUC tissue, and REDD1 is first reported as an independent prognostic factor in patients with BUC. Silencing REDD1 expression in T24 and EJ cells decreased cell proliferation, increased apoptosis, and decreased autophagy, whereas the ectopic expression of REDD1 in RT4 and BIU87 cells had the opposite effect. In addition, the REDD1-mediated proliferation, apoptosis, and autophagy are found to be negatively regulated by miR-22 in vitro, which intensify the paclitaxel sensitivity via inhibition of the well-acknowledged REDD1–EEF2K–autophagy axis. AKT/mTOR signaling initially activated or inhibited in response to silencing or enhancing REDD1 expression and then recovered rapidly. Finally, the inhibited REDD1 expression by either RNAi or miR-22 sensitizes BUC tumor cells to paclitaxel in a subcutaneous transplant carcinoma model in vivo.
Conclusions: REDD1 is confirmed as an oncogene in BUC, and antagonizing REDD1 could be a potential therapeutic strategy to sensitize BUC cells to paclitaxel. Clin Cancer Res; 24(2); 445–59. ©2017 AACR.
CD31 Expression Determines Redox Status and Chemoresistance in Human Angiosarcomas
Authors: Venkataramani Vivek , Küffer Stefan , Cheung Kenneth C.P. , Jiang Xuejun , Trümper Lorenz , Wulf Gerald G. , Ströbel Philipp 
Published: October 2017

Abstract
Purpose: Angiosarcomas are soft tissue sarcomas with endothelial differentiation and vasoformative capacity. Most angiosarcomas show strong constitutive expression of the endothelial adhesion receptor CD31/PECAM-1 pointing to an important role of this molecule. However, the biological function of CD31 in angiosarcomas is unknown.
Experimental Design: The expression levels of CD31 in angiosarcoma cells and its effects on cell viability, colony formation, and chemoresistance were evaluated in human angiosarcoma clinical samples and in cell lines through isolation of CD31high and CD31low cell subsets. The redox-regulatory CD31 function linked to YAP signaling was determined using a CD31-blocking antibody and siRNA approach and was further validated in CD31-knockout endothelial cells.
Results: We found that most angiosarcomas contain a small CD31low cell population. CD31low cells had lost part of their endothelial properties and were more tumorigenic and chemoresistant than CD31high cells due to more efficient reactive oxygen species (ROS) detoxification. Active downregulation of CD31 resulted in loss of endothelial tube formation, nuclear accumulation of YAP, and YAP-dependent induction of antioxidative enzymes. Addition of pazopanib, a known enhancer of proteasomal YAP degradation resensitized CD31low cells for doxorubicin resulting in growth suppression and induction of apoptosis.
Conclusions: Human angiosarcomas contain a small aggressive CD31low population that have lost part of their endothelial differentiation programs and are more resistant against oxidative stress and DNA damage due to intensified YAP signaling. Our finding that the addition of YAP inhibitors can resensitize CD31low cells toward doxorubicin may aid in the rational development of novel combination therapies to treat angiosarcomas. Clin Cancer Res; 24(2); 460–73. ©2017 AACR.
Targeting CDH17 in Cancer: When Blocking the Ligand Beats Blocking the Receptor?
Authors: Marshall John F. 
Published: October 2017

Abstract
Cadherin-17 (CDH17) has been implicated as protumorigenic for many years, but mechanisms have been unclear. A Spanish team has generated antibodies to an RGD motif in CDH17 that inhibits integrin α2β1 binding to CDH17 and thereby inhibits integrin activation, tumorigenesis, and metastasis. These reagents may have therapeutic potential. Clin Cancer Res; 24(2); 253–5. ©2017 AACR.
See related article by Bartolomé et al., p. 433