bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects ofLactobacillus rhamnosusGG andBifidobacterium lactisBb12 on beta-cell function in children with newly diagnosed type 1 diabetes: protocol of a randomised controlled trial
Authors: Groele Lidia , Szajewska Hania , Szypowska Agnieszka 
Published: October 2017

IntroductionRecent evidence has demonstrated that, among other factors, dysbiosis (imbalances in the composition and function of the gut microbiota) may be relevant in the development of type 1 diabetes (T1D). Thus, gut microbiota may be a target for improving outcomes in subjects with T1D. The aim of the study is to examine the effects ofLactobacillus rhamnosusGG andBifidobacterium lactisBb12 on beta-cell function in children with newly diagnosed T1D.Methods and analysisA total of 96 children aged 8 to 17 years with newly diagnosed T1D, confirmed by clinical history and the presence of at least one positive autoantibody, will be enrolled in a double-blind, randomised, placebo-controlled trial in which they will receiveL. rhamnosusGG andB. lactisBb12 at a dose of 109colony-forming units or an identically appearing placebo, orally, once daily, for 6 months. The follow-up will be for 12 months. The primary outcome measures will be the area under the curve of the C-peptide level during 2-hour responses to a mixed meal.Ethics and disseminationThe Bioethics Committee approved the study protocol. The findings of this trial will be submitted to a peer-reviewed paediatric journal. Abstracts will be submitted to relevant national and international conferences.Trial registration numberNCT03032354; Pre-results.
Association between childhood allergic diseases, educational attainment and occupational status in later life: systematic review protocol
Authors: von Kobyletzki Laura Beate , Beckman Linda , Smeeth Liam , McKee Martin , Quint Jennifer K , Abuabara Katrina , Langan Sinead 
Published: October 2017

IntroductionChildhood allergic diseases may prevent affected children from achieving their academic potential. Potential mechanisms include absence from school due to illness and medical appointments. Experience of symptoms in classes or leisure time, and stigma associated with visible signs and symptoms, including skin disease, requirements for medication during school time or the need for specific diets, may also contribute to reduced educational attainment. Studies have investigated the association between specific allergic diseases and educational attainment. The aim of this study is to systematically review the literature on allergic diseases, educational attainment and occupational status, and if possible, calculate meta-analytic summary estimates for the associations.MethodsSystematic electronic searches in Medline, EMBASE, Cochrane, Cumulative Index to Nursing & Allied Health Literature (CINAHL), PsycINFO and education Resources Information Center (ERIC); hand search in reference lists of included papers and conference reports; search for unpublished studies in clinical trial registers and the New York Academy of Medicine Grey Literature Report; data extraction; and study quality assessment (Newcastle-Ottawa Scale) will be performed.AnalysisData will be summarised descriptively, and meta-analysis including meta-regression to explore sources of heterogeneities will be performed if possible.Ethics and disseminationDissemination in a peer-reviewed, open-access, international scientific journal is planned.PROSPERO registration numberCRD42017058036.
Family attitudes, actions, decisions and experiences following implementation of deemed consent and the Human Transplantation (Wales) Act 2013: mixed-method study protocol
Authors: Noyes Jane , Morgan Karen , Walton Phillip , Roberts Abigail , Mclaughlin Leah , Stephens Michael 
Published: October 2017

IntroductionThe Human Transplantation (Wales) Act 2013 (the Act) introduced a ‘soft opt-out’ system of organ donation on 1 December 2015. Citizens are encouraged to make their organ donation decision known during their lifetime. In order to work, the Act and media campaign need to create a context, whereby organ donation becomes the norm, and create a mechanism for people to behave as intended (formally register their decision; consider appointing a representative; convey their donation decision to their families and friends or do nothing—deemed consent). In addition, family members/appointed representatives need to be able to put their own views aside to support the decision of their loved one. The aim of this study is to evaluate initial implementation, outcomes and impact on families and appointed representatives who were approached about organ donation during the first 18 months.Methods and analysisProspective mixed-method coproductive study undertaken with National Health Service Blood and Transplant (NHSBT), and multiple patient/public representatives. The study is designed to collect information on all cases who meet specified criteria (≥18 years, deceased person voluntarily resident in Wales and died in Wales or England) whose family were approached between 1 December 2015 and 31 June 2017). Data for analysis include: NHSBT routinely collected anonymised audit data on all cases; Specialist Nurse in Organ Donation (SNOD) completed anonymised form for all cases documenting their perception of the families’ understanding of the Act, media campaign and outcome of the donation approach; questionnaires and depth interviews with any family member or appointed representative (minimum 50 cases). Additional focus groups and interviews with SNODs. Anonymised donation outcomes and registration activity reports for Wales provide additional context.Ethics and disseminationApproved by NHSBT Research, Innovation and Technology Advisory Group on 23 October 2015; Wales Research Ethics Committee 5 (IRAS190066; Rec Reference 15/WA/0414) on 25 November 2015 and NHSBT R&D Committee (NHSBT ID: AP-15–02) on 24 November 2015.RegistrationThe protocol is registered on the Health and Care Research Wales Clinical Research Portfolio. Study ID number 34396, www.ukctg.nihr.ac.uk
Investigating Canadian parents' HPV vaccine knowledge, attitudes and behaviour: a study protocol for a longitudinal national online survey
Authors: Shapiro Gilla K , Perez Samara , Naz Anila , Tatar Ovidiu , Guichon Juliet R , Amsel Rhonda , Zimet Gregory D , Rosberger Zeev 
Published: October 2017

IntroductionHuman papillomavirus (HPV), a sexually transmitted infection, can cause anogenital warts and a number of cancers. To prevent morbidity and mortality, three vaccines have been licensed and are recommended by Canada’s National Advisory Committee on Immunisation (for girls since 2007 and boys since 2012). Nevertheless, HPV vaccine coverage in Canada remains suboptimal in many regions. This study will be the first to concurrently examine the correlates of HPV vaccine decision-making in parents of school-aged girls and boys and evaluate changes in parental knowledge, attitudes and behaviours over time.Methods and analysisUsing a national, online survey utilising theoretically driven constructs and validated measures, this study will identify HPV vaccine coverage rates and correlates of vaccine decision-making in Canada at two time points (August–September 2016 and June–July 2017). 4606 participants will be recruited to participate in an online survey through a market research and polling firm using email invitations. Data cleaning methods will identify inattentive or unmotivated participants.Ethics and disseminationThe study received research ethics board approval from the Research Review Office, Integrated Health and Social Services University Network for West-Central Montreal (CODIM-FLP-16–219). The study will adopt a multimodal approach to disseminate the study’s findings to researchers, clinicians, cancer and immunisation organisations and the public in Canada and internationally.
A multicentre randomised controlled trial assessing whether MRI-targeted biopsy is non-inferior to standard transrectal ultrasound guided biopsy for the diagnosis of clinically significant prostate cancer in men without prior biopsy: a study protocol
Authors: Kasivisvanathan Veeru , Jichi Fatima , Klotz Laurence , Villers Arnauld , Taneja Samir S , Punwani Shonit , Freeman Alex , Emberton Mark , Moore Caroline M 
Published: October 2017

IntroductionThe classical pathway for the diagnosis of prostate cancer is transrectal ultrasound-guided (TRUS) biopsy of the prostate initiated on the basis of a raised prostate-specific antigen (PSA). An alternative pathway is to perform multi-parametricMRI (MPMRI) to localise cancer and to use this information to influence the decision for, and conduct of, a subsequent biopsy, known as an MPMRI-targeted biopsy. An MPMRI pathway has been shown to detect a similar or greater amount of clinically significant cancer as TRUS biopsy but has several advantages, including the potential to biopsy fewer men with fewer cores.MethodsThis is a pragmatic, international, multicentre, parallel group randomised study in which men are allocated in a 1:1 ratio to an MPMRI or TRUS biopsy pathway. This study will assess whether an MPMRI-targeted biopsy approach is non-inferior to a standard TRUS biopsy approach in the diagnosis of clinically significant cancer.Men in the MRI arm will undergo targeted biopsy of suspicious areas only and no biopsy will be carried out if the MRI is non-suspicious. Men in the TRUS biopsy will undergo a standard 10–12-core TRUS biopsy. The main inclusion criteria are a serum PSA ≤20 ng/mL, a digital rectal examination finding of T2 or less and no prior prostate biopsy.The primary outcome is the proportion of men with clinically significant cancer detected. A sample size of at least 470 patients is required. Key secondary outcomes include the proportion of clinically insignificant cancer detected.Ethics and disseminationEthical approval was obtained from the National Research Ethics Committee East Midlands, Leicester (15/EM/0188). Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study.Registration detailsNCT02380027; Pre-results
Validity and reliability of the Fitbit Zip as a measure of preschool children’s step count
Authors: Sharp Catherine A , Mackintosh Kelly A , Erjavec Mihela , Pascoe Duncan M , Horne Pauline J 
Published: October 2017

ObjectivesValidation of physical activity measurement tools is essential to determine the relationship between physical activity and health in preschool children, but research to date has not focused on this priority. The aims of this study were to ascertain inter-rater reliability of observer step count, and interdevice reliability and validity of Fitbit Zip accelerometer step counts in preschool children.MethodsFifty-six children aged 3–4 years (29 girls) recruited from 10 nurseries in North Wales, UK, wore two Fitbit Zip accelerometers while performing a timed walking task in their childcare settings. Accelerometers were worn in secure pockets inside a custom-made tabard. Video recordings enabled two observers to independently code the number of steps performed in 3 min by each child during the walking task. Intraclass correlations (ICCs), concordance correlation coefficients, Bland-Altman plots and absolute per cent error were calculated to assess the reliability and validity of the consumer-grade device.ResultsAn excellent ICC was found between the two observer codings (ICC=1.00) and the two Fitbit Zips (ICC=0.91). Concordance between the Fitbit Zips and observer counts was also high (r=0.77), with an acceptable absolute per cent error (6%–7%). Bland-Altman analyses identified a bias for Fitbit 1 of 22.8±19.1 steps with limits of agreement between −14.7 and 60.2 steps, and a bias for Fitbit 2 of 25.2±23.2 steps with limits of agreement between −20.2 and 70.5 steps.ConclusionsFitbit Zip accelerometers are a reliable and valid method of recording preschool children’s step count in a childcare setting.
Golimumab: early experience and medium-term outcomes from two UK tertiary IBD centres
Authors: Samaan Mark A , Pavlidis Polychronis , Digby-Bell Jonathan , Johnston Emma L , Dhillon Angad , Paramsothy Ramesh , Akintimehin Abisoye O , Medcalf Lucy , Chung-Faye Guy , DuBois Patrick , Koumoutsos Ioannis , Powell Nick , Anderson Simon H C , Sanderson Jeremy , Hayee Bu’ Hussain , Irving Peter M 
Published: October 2017

ObjectiveTo gain an understanding of the effectiveness of golimumab in a ‘real-world’ setting.DesignRetrospective cohort study using prospectively maintained clinical records.SettingTwo UK tertiary IBD centres.PatientsPatients with ulcerative colitis (UC) were given golimumab at Guy’s & St Thomas and King’s College Hospitals between September 2014 and December 2016.InterventionGolimumab, a subcutaneously administered antitumour necrosis factor agent.Main outcome measuresClinical disease activity was assessed at baseline and at the first clinical review following induction therapy using the Simple Clinical Colitis Activity Index (SCCAI). Response was defined as an SCCAI reduction of 3 points or more. Remission was defined as an SCCAI of less than 3.ResultsFifty-seven patients with UC completed golimumab induction therapy. Paired preinduction and postinduction SCCAI values were available for 31 patients and fell significantly from 7 (2–19) to 3 (0–11) (p<0.001). To these 31, an additional 13 patients who did not have paired SCCAI data but stopped treatment due to documented ‘non-response’ in the opinion of their supervising clinician, were added. Among this combined cohort, 23/44 (52%) had a clinical response, 15/44 (34%) achieved remission and 13/44 (30%) achieved corticosteroid-free remission.Faecal calprotectin and CRP fell (FC: pre-induction: 1096 (15-4800) μg/g, post-induction: 114 (11-4800) μg/g, p = 0.011; n = 20; CRP: pre-induction: 4 (1-59) mg/L, post-induction: 2 (1-34) mg/L, p = 0.01 for n = 43). Post-induction endoscopy was carried out in 23 patients and a mucosal healing (Mayo 0 or 1) rate of 35% was observed.ConclusionsOur experience mirrors previously reported real-world cohorts and demonstrates similar outcomes to those observed in randomised controlled trials. These data demonstrate a meaningful reduction in clinical, biochemical and endoscopic disease activity as well as a steroid-sparing effect in patients with previously refractory disease.
Incompletely obliterated cranial arteriovenous fistulae are safely and effectively treated with adjuvant ε-aminocaproic acid
Authors: Howard Brian M , Grossberg Jonathan A , Prater Adam , Cawley C Michael , Dion Jacques E , Tong Frank C 
Published: October 2017

BackgroundAdministration of ε-aminocaproic acid (εACA), as adjuvant therapy following incompletely embolized cranial dural arteriovenous (dAVFs) and direct carotid artery to cavernous sinus fistulae (CCFs), is a strategy to promote post-procedural thrombosis. However, the efficacy of εACA to treat incompletely obliterated dAVFs and CCFs has not been published. The purpose of this study was to determine if administration of εACA following incomplete embolization of cranial dAVFs or CCFs was associated with an increased likelihood of cure on follow-up imaging compared with patients not given adjuvant εACA.MethodsA retrospective cohort study was performed. All patients who underwent treatment of a dAVF or CCF at our institution between 1998 and 2016 were reviewed (n=262). Patients with residual shunting following the first attempted endovascular embolization were included in the analysis (n=52). The study groups were those treated with εACA following incomplete obliteration of the fistula and those who were not. The primary outcome was obliteration of the fistula on initial follow-up imaging. Complication rates between cohorts were compared.Results20 (38%) patients with incompletely obliterated fistulae were treated with adjuvant εACA. A trend towards an improved rate of complete obliteration on initial follow-up imaging was observed in the group treated with εACA (55% vs 34% in the group not treated with εACA, p=0.14). No difference in clinical outcomes or thromboembolic complications was observed between the groups.ConclusionsIn summary, these data suggest that administration of εACA is a safe adjuvant therapy in the management of cranial dAVFs and CCFs that are incompletely treated endovascularly.
Histone Acetyltransferase KAT6A Upregulates PI3K/AKT Signaling through TRIM24 Binding
Authors: Lv Deguan , Jia Feng , Hou Yanli , Sang Youzhou , Alvarez Angel A. , Zhang Weiwei , Gao Wei-Qiang , Hu Bo , Cheng Shi-Yuan , Ge Jianwei , Li Yanxin , Feng Haizhong 
Published: October 2017

Abstract
Lysine acetyltransferase KAT6A is a chromatin regulator that contributes to histone modification and cancer, but the basis of its actions are not well understood. Here, we identify a KAT6A signaling pathway that facilitates glioblastoma (GBM), where it is upregulated. KAT6A expression was associated with GBM patient survival. KAT6A silencing suppressed cell proliferation, cell migration, colony formation, and tumor development in an orthotopic mouse xenograft model system. Mechanistic investigations demonstrated that KAT6A acetylates lysine 23 of histone H3 (H3K23), which recruits the nuclear receptor binding protein TRIM24 to activate PIK3CA transcription, thereby enhancing PI3K/AKT signaling and tumorigenesis. Overexpressing activated AKT or PIK3CA rescued the growth inhibition due to KAT6A silencing. Conversely, the pan-PI3K inhibitor LY294002 abrogated the growth-promoting effect of KAT6A. Overexpression of KAT6A or TRIM24, but not KAT6A acetyltransferase activity–deficient mutants or TRIM24 mutants lacking H3K23ac-binding sites, promoted PIK3CA expression, AKT phosphorylation, and cell proliferation. Taken together, our results define an essential role of KAT6A in glioma formation, rationalizing its candidacy as a therapeutic target for GBM treatment. Cancer Res; 77(22); 6190–201. ©2017 AACR.
PKCϵ Controls Mitotic Progression by Regulating Centrosome Migration and Mitotic Spindle Assembly
Authors: Martini Silvia , Soliman Tanya , Gobbi Giuliana , Mirandola Prisco , Carubbi Cecilia , Masselli Elena , Pozzi Giulia , Parker Peter J. , Vitale Marco 
Published: October 2017

Abstract
To form a proper mitotic spindle, centrosomes must be duplicated and driven poleward in a timely and controlled fashion. Improper timing of centrosome separation and errors in mitotic spindle assembly may lead to chromosome instability, a hallmark of cancer. Protein kinase C epsilon (PKCϵ) has recently emerged as a regulator of several cell-cycle processes associated with the resolution of mitotic catenation during the metaphase–anaphase transition and in regulating the abscission checkpoint. However, an engagement of PKCϵ in earlier (pre)mitotic events has not been addressed. Here, we now establish that PKCϵ controls prophase-to-metaphase progression by coordinating centrosome migration and mitotic spindle assembly in transformed cells. This control is exerted through cytoplasmic dynein function. Importantly, it is also demonstrated that the PKCϵ dependency of mitotic spindle organization is correlated with the nonfunctionality of the TOPO2A-dependent G2 checkpoint, a characteristic of many transformed cells. Thus, PKCϵ appears to become specifically engaged in a programme of controls that are required to support cell-cycle progression in transformed cells, advocating for PKCϵ as a potential cancer therapeutic target.
Implications: The close relationship between PKCϵ dependency for mitotic spindle organization and the nonfunctionality of the TOPO2A-dependent G2 checkpoint, a hallmark of transformed cells, strongly suggests PKCϵ as a therapeutic target in cancer. Mol Cancer Res; 16(1); 3–15. ©2017 AACR.
Effectiveness of IHD with Adsorptive PMMA Membrane in Myeloma Cast Nephropathy: A Cohort Study
Authors: Sens Florence , Chaintreuil Déborah , Jolivot Anne , Guebre-Egziabher Fitsum , Robinson Philip , Karlin Lionel , Bridoux Frank , Juillard Laurent 
Published: October 2017

<b><i>Background:</i></b> In patients with cast nephropathy and acute kidney injury (AKI) requiring dialysis, the reduction of serum free light chains (FLC) using chemotherapy and intensive hemodialysis (IHD) with a high cut-off filter may improve renal and patient outcomes. We evaluated the effectiveness of a combination of chemotherapy and IHD with an adsorbent polymethylmethacrylate membrane (IHD-PMMA) on renal recovery and survival. <b><i>Methods:</i></b> A single-center retrospective cohort-study was conducted. Between 2007 and 2014, patients with dialysis-dependent acute cast nephropathy treated with chemotherapy and IHD-PMMA were included. Patients had six 6-h hemodialysis sessions a week, until predialysis serum FLC fell below 200 mg/L, for a maximum of 3 weeks. Primary outcomes were renal recovery, defined as dialysis independence, and survival. <b><i>Results:</i></b> Seventeen patients were included, all with stage 3 AKI. All received chemotherapy, mostly based on bortezomib and steroids (88%). Twelve patients (71%) achieved renal recovery, usually within 60 days (92%). At 3 months, the overall hematological response rate was 57%; hematological response was maintained for at least 2 years in 86% of responders. At 6, 12, and 24 months, 76, 75, and 62% of patients were alive, respectively. Higher reduction in involved FLC by day 12 (<i>p</i> = 0.022) and day 21 (<i>p</i> = 0.003) was associated with renal recovery. Patients with FLC reduction rate &#x3e;50% by day 21 experienced a lower mortality (hazard ratio 0.10, 95% CI 0.02–0.63). <b><i>Conclusion:</i></b> In patients with dialysis-dependent myeloma cast nephropathy, early FLC removal by IHD-PMMA combined with chemotherapy was associated with high rates of renal recovery and survival.
Early Right Ventricular Assist Device Use in Patients Undergoing Continuous-Flow Left Ventricular Assist Device Implantation
Authors: Kiernan Michael S. , Grandin E. Wilson , Brinkley Marshall , Kapur Navin K. , Pham Duc Thinh , Ruthazer Robin , Rame J. Eduardo , Atluri Pavan , Birati Edo Y. , Oliveira Guilherme H. , Pagani Francis D. , Kirklin James K. , Naftel David , Kormos Robert L. , Teuteberg Jeffrey J. , DeNofrio David 
Published: October 2017

Background:
To investigate preimplant risk factors associated with early right ventricular assist device (RVAD) use in patients undergoing continuous-flow left ventricular assist device (LVAD) surgery.

Methods and Results:

Patients in the Interagency Registry for Mechanically Assisted Circulatory Support who underwent primary continuous-flow–LVAD surgery were examined for concurrent or subsequent RVAD implantation within 14 days of LVAD. Risk factors for RVAD implantation and the combined end point of RVAD or death within 14 days of LVAD were assessed with stepwise logistic regression. We compared survival between patients with and without RVAD using Kaplan–Meier method and Cox proportional hazards modeling. Of 9976 patients undergoing continuous-flow–LVAD implantation, 386 patients (3.9%) required an RVAD within 14 days of LVAD surgery. Preimplant characteristics associated with RVAD use included interagency registry for mechanically assisted circulatory support patient profiles 1 and 2, the need for preoperative extracorporeal membrane oxygenation or renal replacement therapy, severe preimplant tricuspid regurgitation, history of cardiac surgery, and concomitant procedures other than tricuspid valve repair at the time of LVAD. Hemodynamic determinants included elevated right atrial pressure, reduced pulmonary artery pulse pressure, and reduced stroke volume. The final model demonstrated good performance for both RVAD implant (area under the curve, 0.78) and the combined end point of RVAD or death within 14 days (area under the curve, 0.73). Compared with patients receiving an isolated LVAD, patients requiring RVAD had decreased 1- and 6-month survival: 78.1% versus 95.8% and 63.6% versus 87.9%, respectively (
P
<0.0001 for both).

Conclusions:
The need for RVAD implantation after LVAD is associated with indices of global illness severity, markers of end-organ dysfunction, and profiles of hemodynamic instability.