bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated systematic review of Australian school-based prevention programmes for alcohol and other drugs: a review protocol
Authors: Devine Emma Krogh , Teesson Maree , Debenham Jennifer , Guckel Tara , Stapinski Lexine Ann , Barrett Emma , Champion Katrina Elizabeth , Chapman Cath , Newton Nicola Clare 
Published: November 2022

IntroductionAdolescent onset substance use is associated with neurodevelopmental, social and psychological harms. Thus, alcohol and other drug prevention programmes are essential to promote health and well-being during this period. Schools are uniquely positioned to deliver such prevention programmes. The last decade has seen a large expansion of school-based alcohol and drug prevention programmes in Australia, warranting an update of the comprehensive review conducted by Teessonet alin 2012. This proposed review aims to (1) identify school-based substance use prevention programmes that have been trialled in Australia since 2011, (2) evaluate their efficacy and (3) identify intervention components associated with effectiveness. This will assist schools in identifying and adopting effective evidence-based programmes and inform future programme development, evaluation and policy.Methods and analysisStudies published from 2011 will be identified by searching the electronic databases PubMed, PsycINFO, Medline, Embase, ProQuest and Cochrane Library in addition to grey literature searches. Eligible studies will be controlled trials (including randomised controlled trials, cluster randomised controlled trials and quasi-experimental trials) of programmes measuring drug and alcohol related outcomes that are conducted in a school setting and have been trialled within Australia. Records will be independently screened for eligibility by two review authors, with disagreements being resolved by consensus or a third review author where necessary. Data extraction, risk of bias and study quality will also be completed independently by two review authors. A qualitative synthesis of all eligible studies will be presented. In addition, if there are sufficient data to combine studies, a random-effects meta-analysis will be conducted.Ethics and disseminationThis research is exempt from ethics approval as no primary data are collected, with work instead being carried out on published documents. The findings of this proposed review will be disseminated in a peer-reviewed journal and at conferences.PROSPERO registration numberCRD42021272959.
Effects of insoles adapted in flip-flop sandals for persistent heel pain: a protocol for a sham-controlled randomised trial
Authors: Fagundes Marina Gomes , Teixeira Mendes André Augusto Martines , Barbosa Germanna Medeiros , de Souza Marcelo Cardoso 
Published: November 2022

IntroductionPersistent heel pain is a prevalent complaint affecting up to 10% of the population. Insoles adapted in flip-flop sandals are an alternative treatment for pain and function of individuals with persistent heel pain, showing improvement within 12 weeks of treatment. Most studies considered foot posture and biomechanics to prescribe insoles for persistent heel pain, but few verified the effects of a 12-week treatment on pain catastrophising. This study will investigate the effects of insoles adapted in flip-flop sandals on pain intensity, function, functional walking capacity and pain catastrophising of individuals with persistent heel pain.Methods and analysisThis is a protocol for a sham-controlled randomised trial. Eighty individuals with persistent heel pain will be assessed and randomised into two intervention groups: insoles adapted in flip-flop sandals and flip-flop sandals with sham (ie, flat) insoles. Assessments will be conducted at baseline (T0), after 6 weeks (T6), 12 weeks postintervention (T12) and after a 4-week follow-up (T16). The primary outcome will be the pain intensity, and secondary outcomes will be foot function, functional walking capacity and pain catastrophising. Analysis of variance with mixed design (if normal distribution) or Friedman’s test (if not normal distribution) will verify intergroup and intragroup differences. Bonferroni post hoc tests will be performed in case of significant group or time interaction. Intent-to-treat analysis will be used, and a significance level of 5% and 95% CIs will be considered.Ethics and disseminationThis study was approved by the research ethics committee of the Federal University of Rio Grande do Norte (registry no. 4,018,821). Results will be disseminated to individuals, submitted to a peer-reviewed journal and disclosed in scientific meetings.Trial registration numberNCT04784598.
Development of the SPREAD framework to support the scaling of de-implementation strategies: a mixed-methods study
Authors: Kroon Daniëlle , van Dulmen Simone A , Westert Gert P , Jeurissen Patrick P T , Kool Rudolf B 
Published: November 2022

ObjectiveWe aimed to increase the understanding of the scaling of de-implementation strategies by identifying the determinants of the process and developing a determinant framework.Design and methodsThis study has a mixed-methods design. First, we performed an integrative review to build a literature-based framework describing the determinants of the scaling of healthcare innovations and interventions. PubMed and EMBASE were searched for relevant studies from 1995 to December 2020. We systematically extracted the determinants of the scaling of interventions and developed a literature-based framework. Subsequently, this framework was discussed in four focus groups with national and international de-implementation experts. The literature-based framework was complemented by the findings of the focus group meetings and adapted for the scaling of de-implementation strategies.ResultsThe literature search resulted in 42 articles that discussed the determinants of the scaling of innovations and interventions. No articles described determinants specifically for de-implementation strategies. During the focus groups, all participants agreed on the relevance of the extracted determinants for the scaling of de-implementation strategies. The experts emphasised that while the determinants are relevant for various countries, the implications differ due to different contexts, cultures and histories. The analyses of the focus groups resulted in additional topics and determinants, namely, medical training, professional networks, interests of stakeholders, clinical guidelines and patients’ perspectives. The results of the focus group meetings were combined with the literature framework, which together formed the supporting the scaling of de-implementation strategies (SPREAD) framework. The SPREAD framework includes determinants from four domains: (1) scaling plan, (2) external context, (3) de-implementation strategy and (4) adopters.ConclusionsThe SPREAD framework describes the determinants of the scaling of de-implementation strategies. These determinants are potential targets for various parties to facilitate the scaling of de-implementation strategies. Future research should validate these determinants of the scaling of de-implementation strategies.
Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study: idarubicin dose selection, tissue response and survival
Authors: Nyman Sofi Sennefelt , Ahlström Håkan , Creusen Angeliki Dimopoulou , Dahlgren David , Hedeland Mikael , Heindryckx Femke , Johnson Ulf , Khaled Jaafar , Kullenberg Fredrik , Nyman Rickard , Rorsman Fredrik , Sheikhi Reza , Simonsson Ulrika S H , Sjögren Erik , Wanders Alkwin , Lennernäs Hans , Ebeling Barbier Charlotte 
Published: November 2022

IntroductionHepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance.Methods and analysisThe study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient’s first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival.Ethics and disseminationParticipants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden.Trial registration numberEudraCT number: 2021-001257-31.
Cohort profile: Risk and risk factors for female breast cancer after treatment for childhood and adolescent cancer: an internationally pooled cohort
Authors: Wang Yuehan , Kremer Leontien C M , van Leeuwen Flora E , Armstrong Gregory T , Leisenring Wendy , de Vathaire Florent , Hudson Melissa M , Kuehni Claudia E , Arnold Michael A , Haddy Nadia , Demoor-Goldschmidt Charlotte , Diallo Ibrahima , Howell Rebecca M , Ehrhardt Matthew J , Moskowitz Chaya S , Neglia Joseph P , van der Pal Helena J H , Robison Leslie L , Schaapveld Michael , Turcotte Lucie M , Waespe Nicolas , Ronckers Cécile M , Teepen Jop C 
Published: November 2022

PurposeThe International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer was established in 2018 to address gaps in knowledge of risk and risk factors for breast cancer subsequent to childhood/adolescent cancer by pooling individual patient data from seven cohorts. Initially, the pooled cohort will focus on three clinically relevant questions regarding treatment-related subsequent breast cancer risk in female survivors, which are the risk related to low-dose radiotherapy exposure to the chest, specific chemotherapy agents and attained age.ParticipantsThe consortium database includes pooled data on 21 892 female survivors from seven cohorts in North America and Europe with a primary cancer diagnosis at <21 years of age, and survival ≥5 years from diagnosis.Findings to dateThis is a newly established pooled study. The cohort profile summarised the data collected from each included cohort, including childhood cancer diagnosis information and treatment details (ie, radiotherapy fields and cumulative doses, and chemotherapy agents and cumulative doses for each agent). Included cohorts’ follow-up started 1951–1981 and ended 2013–2021, respectively, for a median follow-up duration of 24.3 (IQR 18.0–32.8) years since primary cancer diagnosis. The median age at primary cancer diagnosis was 5.4 (IQR 2.5–11.9) years. And the median attained age at last follow-up was 32.2 (IQR 24.0–40.4) years. In all, 4240 (19.4%) survivors were treated with radiotherapy to the chest and 9308 (42.5%) with anthracyclines. At the end of the follow-up, 835 females developed a first subsequent breast cancer, including 635 invasive breast cancer only, 184 carcinomas in situ only (172 ductal carcinomas in situ and 12 lobular carcinomas in situ), and 16 with both an invasive and in situ diagnosis at the same moment. The cumulative incidences of subsequent breast cancer (both invasive and in situ) 25 and 35 years after primary cancer diagnosis were 2.2% and 6.2%, respectively.Future plansThe consortium is intended to serve as a model and robust source of childhood/adolescent cancer survivor data for elucidating other knowledge gaps on subsequent breast cancer risk, and risk of other subsequent malignancies (including data on males) in the future.
Review of the utility of routine mortality reviews among deaths on General Internal Medicine wards in a Canadian tertiary care hospital
Authors: Tran Kelvin , Padwal Raj , Hamilton Peter , Ngo Jennifer 
Published: November 2022

BackgroundHospital morbidity and mortality reviews are common quality assurance activities, intended to uncover latent or unrecognised systemic issues that contribute to preventable adverse events and patient harm. Mortality reviews may be routinely mandated by hospital policy or for accreditation purposes. However, patients under the care of certain specialties, such as general internal medicine (GIM), are affected by a substantial burden of chronic disease, advanced age, frailty or limited life expectancy. Many of their deaths could be viewed as reasonably foreseeable, and unrelated to poor-quality care.MethodsWe sought to determine how frequently postmortem chart reviews for hospitalised GIM patients at our tertiary care centre in Canada would uncover patient safety or quality of care issues that directly led to these patients’ deaths. We reviewed the charts of all patients who died while admitted to the GIM admitting service over a 12-month time period between 1 July 2020 and 30 June 2021.ResultsWe found that in only 2% of cases was a clinical adverse event detected that directly contributed to a poor or unexpected outcome for the patient, and of those cases, more than half were related to unfortunate nosocomial transmission of COVID-19 infection.ConclusionDue to an overall low yield, we discourage routine mortality chart reviews for general medical patients, and instead suggest that organisations focus on strategies to recognise and capture safety incidents that may not necessarily result in death.
Inhibiting DNA methylation and RNA editing upregulates immunogenic RNA to transform the tumor microenvironment and prolong survival in ovarian cancer
Authors: Gomez Stephanie , Cox Olivia L , Walker Reddick R , Rentia Uzma , Hadley Melissa , Arthofer Elisa , Diab Noor , Grundy Erin E , Kanholm Tomas , McDonald James I , Kobyra Julie , Palmer Erica , Noonepalle Satish , Villagra Alejandro , Leitenberg David , Bollard Catherine M , Saunthararajah Yogen , Chiappinelli Katherine B 
Published: November 2022

BackgroundNovel therapies are urgently needed for ovarian cancer (OC), the fifth deadliest cancer in women. Preclinical work has shown that DNA methyltransferase inhibitors (DNMTis) can reverse the immunosuppressive tumor microenvironment in OC. Inhibiting DNA methyltransferases activate transcription of double-stranded (ds)RNA, including transposable elements. These dsRNAs activate sensors in the cytoplasm and trigger type I interferon (IFN) signaling, recruiting host immune cells to kill the tumor cells. Adenosine deaminase 1 (ADAR1) is induced by IFN signaling and edits mammalian dsRNA with an A-to-I nucleotide change, which is read as an A-to-G change in sequencing data. These edited dsRNAs cannot be sensed by dsRNA sensors, and thus ADAR1 inhibits the type I IFN response in a negative feedback loop. We hypothesized that decreasing ADAR1 editing would enhance the DNMTi-induced immune response.MethodsHuman OC cell lines were treated in vitro with DNMTi and then RNA-sequenced to measure RNA editing. Adar1 was stably knocked down in ID8Trp53-/-mouse OC cells. Control cells (shGFP) or shAdar1 cells were tested with mock or DNMTi treatment. Tumor-infiltrating immune cells were immunophenotyped using flow cytometry and cell culture supernatants were analyzed for secreted chemokines/cytokines. Mice were injected with syngeneic shAdar1 ID8Trp53-/-cells and treated with tetrahydrouridine/DNMTi while given anti-interferon alpha and beta receptor 1, anti-CD8, or anti-NK1.1 antibodies every 3 days.ResultsWe show that ADAR1 edits transposable elements in human OC cell lines after DNMTi treatment in vitro. Combining ADAR1 knockdown with DNMTi significantly increases pro-inflammatory cytokine/chemokine production and sensitivity to IFN-β compared with either perturbation alone. Furthermore, DNMTi treatment and Adar1 loss reduces tumor burden and prolongs survival in an immunocompetent mouse model of OC. Combining Adar1 loss and DNMTi elicited the most robust antitumor response and transformed the immune microenvironment with increased recruitment and activation of CD8+ T cells.ConclusionIn summary, we showed that the survival benefit from DNMTi plus ADAR1 inhibition is dependent on type I IFN signaling. Thus, epigenetically inducing transposable element transcription combined with inhibition of RNA editing is a novel therapeutic strategy to reverse immune evasion in OC, a disease that does not respond to current immunotherapies.
Perception of heated tobacco products and support for regulations: a cross-sectional study in Hong Kong
Authors: Wu Yongda Socrates , Cheung Yee Tak Derek , Ho Sai Yin , Tong Henry Sau Chai , Lai Vienna Wai Yin , Lam Tai Hing , Wang Man Ping 
Published: November 2022

BackgroundHong Kong has proposed banning the sale of heated tobacco products (HTPs). Perceptions of reduced harms and effectiveness for quitting combustible cigarettes (CCs) of HTPs due to their promotions may erode public support for regulations. We assessed the associations between perceptions of HTPs and support for regulations in Hong Kong.MethodsIn two population-based landline surveys conducted in 2018–2019, 1985 respondents (51.4% male; 22.7% aged 60+ years) reported perceived relative harm of HTPs to CCs and effectiveness for quitting CCs, and support for five HTP regulations (ban on promotion and advertisements, use in smoke-free areas, sales to minors, registration before sale, sale licence) and a total ban on sale. Current and former smokers were oversampled due to low prevalence. Descriptive statistics were weighted to the general population. Associations were analysed, adjusting for sociodemographic characteristics, smoking status and ever HTP use.Results27.4% (N=515) of respondents perceived HTPs as less harmful, and 18.8% (N=1299) perceived them as effective for quitting CCs. Support was generally high (at least one regulation, 99.1%, N=1959; all five regulations, 66.8%, N=1114; total ban, 63.5%, N=946). Perceptions of reduced harm were associated with lower support for all five regulations (adjusted risk ratio 0.85, 0.75 to 0.96) and a total ban on sale (0.58, 0.51 to 0.66). Results were similar for perceptions of effectiveness for quitting.ConclusionsLower support for HTP regulations and a total ban on sale were associated with perceptions of reduced harm and effectiveness for quitting CCs of HTPs in Hong Kong.
Macrophage migration inhibitory factor promotes glucocorticoid resistance of neutrophilic inflammation in a murine model of severe asthma
Authors: Allam Venkata Sita Rama Raju , Pavlidis Stelios , Liu Gang , Kermani Nazanin Zounemat , Simpson Jennifer , To Joyce , Donnelly Sheila , Guo Yi-Ke , Hansbro Philip M , Phipps Simon , Morand Eric F , Djukanovic Ratko , Sterk Peter , Chung Kian Fan , Adcock Ian , Harris James , Sukkar Maria B 
Published: November 2022

BackgroundSevere neutrophilic asthma is resistant to treatment with glucocorticoids. The immunomodulatory protein macrophage migration inhibitory factor (MIF) promotes neutrophil recruitment to the lung and antagonises responses to glucocorticoids. We hypothesised that MIF promotes glucocorticoid resistance of neutrophilic inflammation in severe asthma.MethodsWe examined whether sputum MIF protein correlated with clinical and molecular characteristics of severe neutrophilic asthma in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. We also investigated whether MIF regulates neutrophilic inflammation and glucocorticoid responsiveness in a murine model of severe asthma in vivo.ResultsMIF protein levels positively correlated with the number of exacerbations in the previous year, sputum neutrophils and oral corticosteroid use across all U-BIOPRED subjects. Further analysis of MIF protein expression according to U-BIOPRED-defined transcriptomic-associated clusters (TACs) revealed increased MIF protein and a corresponding decrease in annexin-A1 protein in TAC2, which is most closely associated with airway neutrophilia and NLRP3 inflammasome activation. In a murine model of severe asthma, treatment with the MIF antagonist ISO-1 significantly inhibited neutrophilic inflammation and increased glucocorticoid responsiveness. Coimmunoprecipitation studies using lung tissue lysates demonstrated that MIF directly interacts with and cleaves annexin-A1, potentially reducing its biological activity.ConclusionOur data suggest that MIF promotes glucocorticoid-resistance of neutrophilic inflammation by reducing the biological activity of annexin-A1, a potent glucocorticoid-regulated protein that inhibits neutrophil accumulation at sites of inflammation. This represents a previously unrecognised role for MIF in the regulation of inflammation and points to MIF as a potential therapeutic target for the management of severe neutrophilic asthma.
Formula for two-loop divergent part of 4-D Yang–Mills effective action
Authors: Ivanov A. V. , Kharuk N. V. 
Published: November 2022

AbstractIn the paper, we study the two-loop contribution to the effective action of the four-dimensional quantum Yang–Mills theory. We derive a new formula for the contribution in terms of three functions, formed from the Green’s function expansion near the diagonal. This result can be applied to different types of regularization. Therefore, we test it by using the dimensional regularization and cutoff ones and show the consistence with the results, obtained in other works.