bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for #iBeatCRC: a community-based intervention to increase early-onset colorectal cancer awareness using a sequential explanatory mixed-methods approach
Authors: Rogers Charles R , Brooks Ellen , Curtin Karen , De Vera Mary A , Qeadan Fares , Rogers Tiana N , Petersen Ethan , Gallagher Phuong , Pesmen Curt , Johnson Wenora , Henley Candace , Hickman Walter , Newcomb Elaine , Korous Kevin M , Handley Margaret A 
Published: December 2021

IntroductionThe last two decades have seen a twofold increase in colorectal cancer (CRC) incidence among individuals under the recommended screening age of 50 years. Although the origin of this early-onset CRC (EOCRC) spike remains unknown, prior studies have reported that EOCRC harbours a distinct molecular and clinical phenotype in younger individuals. The sharp increase in EOCRC incidence rates may be attributable to a complex interplay of factors, including race; lifestyle; and ecological, sociodemographic and geographical factors. However, more research that address psychosocial experiences and accounts for lifestyle-related behaviours before, during and after an EOCRC diagnosis are warranted. This study aims to develop and pilot test a theory-driven, community-based intervention to increase awareness of EOCRC, reduce its associated risk factors and improve early detection among adults aged 18–49 years.Methods and analysisGuided by the Behaviour Change Wheel, we will use a multistage mixed-methods study design. We will pilot a sequential mixed-methods intervention study as follows: (1) First, we will analyse linked quantitative data from the Utah Cancer Registry and National Cancer Institute Surveillance, Epidemiology and End Results registry, linked to state-wide demographic and vital records in the Utah Population Database to identify EOCRC hotspots in Utah by examining the EOCRC incidence and survival variance explained by personal and county-level factors. (2) Next, we will conduct one-on-one interviews with 20 EOCRC survivors residing in EOCRC hotspots to ascertain psychosocial and lifestyle challenges that accompany an EOCRC diagnosis. (3) Finally, we will consider existing evidence-based approaches, our integrated results (quantitative +qualitative) and community action board input to design a community-based intervention to increase EOCRC awareness that can feasibly be delivered by means of outdoor mass media, and via social media. We will pilot the multicomponent media campaign with a quasiexperimental design among 17 EOCRC hotspot residents and 17 EOCRC ‘coldspot’ residents.Ethics and disseminationEthics approval was obtained from the University of Utah Institutional Review Board (IRB_00138357). Signed informed consent will be obtained from all participants prior to any data collection. Study results will be disseminated through CRC community blogs, targeted infographics, conference presentations at national and international professional conferences and publications in peer-reviewed journals. Final intervention-specific data will be available on reasonable request from the corresponding author.Trial registration numberNCT04715074.
Liothyronine for hypothyroidism: a candidate for disinvestment or in need of further research? A value of information analysis
Authors: Hughes Dyfrig A , Skiadas Konstantinos , Fitzsimmons Deborah , Anderson Pippa , Heald Adrian 
Published: December 2021

ObjectiveMedicines with limited evidence of effectiveness are prime candidates for disinvestment. However, investment in further research may be preferable to deimplementation, given that the absence of evidence is not evidence of absence, and research can inform formulary decisions. A case in point is liothyronine, which is sometimes prescribed to levothyroxine-treated patients who continue to experience hypothyroid symptoms. It is a putative low value medicine, associated with uncertainties in both clinical and cost-effectiveness. The aim was to assess the cost-effectiveness of liothyronine in this context, and estimate the value of conducting further research.DesignCost utility and value of information analyses.SettingPrimary care within the National Health Service in the UK.ParticipantsFifty-four levothyroxine-treated patients with persistent symptoms of hypothyroidism.InterventionsLiothyronine plus levothyroxine versus levothyroxine alone.Primary and secondary outcome measuresIncremental cost per quality-adjusted life year (QALY) gained, and the expected monetary value of sample information.Results20/54 (37%) of patients who responded to the survey reported severe problems in carrying out usual activities of everyday living and 12/54 (22%) reported severe anxiety or depression symptoms. Mean (SD) utility was 0.53 (0.23). The differences in expected total, 10-year costs and QALYs between a treatment strategy of liothyronine/levothyroxine combination therapy, and levothyroxine alone, was £12 053 and 1.014, respectively. The incremental cost-effectiveness ratio of £11 881 per QALY gained was sensitive to the price of liothyronine. The probability of liothyronine/levothyroxine combination therapy being cost effective at a threshold of £20 000 per QALY was 0.56. The value of reducing uncertainty in the efficacy of treatment was £3.64 m per year in the UK.ConclusionsA definitive clinical trial to confirm clinical effectiveness may be preferable to immediate disinvestment, and would be justified given the value of the information gained far exceeds the cost.
Sedentary behaviour in non-ambulant children and young people with physical disabilities: a systematic search and review protocol
Authors: Bradbury Marilyn , O"Brien Ciara , Giles Nathan , Fenton Sally , Neilson Sue , Duda Joan L 
Published: December 2021

IntroductionNon-ambulant children and young people with physical disabilities are at high risk of experiencing negative health outcomes associated with sedentary time. A previous scoping review summarising evidence relating to sedentary behaviours of children with physical disabilities identified the need for validated methods of measuring physical activity of children who use wheelchairs and evaluation of interventions to reduce sedentary time. The scoping review did not assess the quality of evidence relating to this topic, therefore its validity remains unclear. No reviews focussing on non-ambulant children and young people up to the age of 25 years have been undertaken.The objectives of this systematic search and review are to:Identify all peer-reviewed articles relating to sedentary behaviour of non-ambulant children and young people.Categorise the articles according to study design and four subquestions relating to (i) measurement, (ii) patterns, (iii) associated risks and (iv) interventions to reduce sedentary time or behaviour.Critically appraise quality of the articles using established critical appraisal tools.Summarise the evidence for each subquestion. Describe its cumulative strength and identify knowledge gaps.Methods and analysisThis protocol was developed using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. The research questions, inclusion/exclusion criteria and search terms have been developed a priori using the ‘Population, Concept and Context’ framework. Online databases will be systematically searched to identify peer-reviewed articles published between 1996 and 2021. Two reviewers will screen, categorise and critically appraise the articles. Data extraction and analysis will be verified by the second reviewer.Results will be reported as a best evidence synthesis, with reference to the PRISMA checklist.Ethics and disseminationEthical approval is not required. The review will be submitted to an appropriate peer-reviewed journal.RegistrationThe review is registered on the Open Science Framework database. DOI:https://doi.org/10.17605/OSF.IO/SQXJB. Any protocol amendments will be recorded in the Open Science Framework database.
Exploring key stakeholders’ attitudes and opinions on medical assistance in dying and palliative care in Canada: a qualitative study protocol
Authors: Shapiro Gilla K , Tong Eryn , Nissim Rinat , Zimmermann Camilla , Allin Sara , Gibson Jennifer , Li Madeline , Rodin Gary 
Published: December 2021

IntroductionCanadians have had legal access to medical assistance in dying (MAiD) since 2016. However, despite substantial overlap in populations who request MAiD and who require palliative care (PC) services, policies and recommended practices regarding the optimal relationship between MAiD and PC services are not well developed. Multiple models are possible, including autonomous delivery of these services and formal or informal coordination, collaboration or integration. However, it is not clear which of these approaches are most appropriate, feasible or acceptable in different Canadian health settings in the context of the COVID-19 pandemic and in the post-pandemic period. The aim of this qualitative study is to understand the attitudes and opinions of key stakeholders from the government, health system, patient groups and academia in Canada regarding the optimal relationship between MAiD and PC services.Methods and analysisA qualitative, purposeful sampling approach will elicit stakeholder feedback of 25–30 participants using semistructured interviews. Stakeholders with expertise and engagement in MAiD or PC who hold leadership positions in their respective organisations across Canada will be invited to provide their perspectives on the relationship between MAiD and PC; capacity-building needs; policy development opportunities; and the impact of the COVID-19 pandemic on the relationship between MAiD and PC services. Transcripts will be analysed using content analysis. A framework for integrated health services will be used to assess the impact of integrating services on multiple levels.Ethics and disseminationThis study has received ethical approval from the University Health Network Research Ethics Board (No 19-5518; Toronto, Canada). All participants will be required to provide informed electronic consent before a qualitative interview is scheduled, and to provide verbal consent prior to the start of the qualitative interview. Findings from this study could inform healthcare policy, the delivery of MAiD and PC, and enhance the understanding of the multilevel factors relevant for the delivery of these services. Findings will be disseminated in conferences and peer-reviewed publications.
Pulmonary referrals to specialist palliative medicine: a survey
Authors: Bonares Michael , Mah Kenneth , Christiansen David , Granton John , Weiss Andrea , Lau Christine , Rodin Gary , Zimmermann Camilla , Wentlandt Kirsten 
Published: December 2021

ObjectivesPatients with chronic respiratory disease have significant palliative care needs, but low utilisation of specialist palliative care (SPC) services. Decreased access to SPC results in unmet palliative care needs among this patient population. We sought to determine the referral practices to SPC among respirologists in Canada.MethodsRespirologists across Canada were invited to participate in a survey about their referral practices to SPC. Associations between referral practices and demographic, professional and attitudinal factors were analysed using regression analyses.ResultsThe response rate was 64.7% (438/677). Fifty-nine per cent of respondents believed that their patients have negative perceptions of palliative care and 39% were more likely to refer to SPC earlier if it was renamed supportive care. While only 2.7% never referred to SPC, referral was late in 52.6% of referring physicians. Lower frequency of referral was associated with equating palliative care to end-of-life care (p<0.001), male sex of respirologist (p=0.019), not knowing referral criteria of SPC services (p=0.015) and agreement that SPC services prioritise patients with cancer (p=0.025); higher referral frequency was associated with satisfaction with SPC services (p=0.001). Late referral was associated with equating palliative care to end-of-life care (p<0.001) and agreement that SPC services prioritise patients with cancer (p=0.013).ConclusionsPossible barriers to respirologists’ timely SPC referral include misperceptions about palliative care, lack of awareness of referral criteria and the belief that SPC services prioritise patients with cancer. Future studies should confirm these barriers and evaluate the effectiveness of strategies to overcome them.
Immunization with short peptide particles reveals a functional CD8+T-cell neoepitope in a murine renal carcinoma model
Authors: He Xuedan , Zhou Shiqi , Dolan Melissa , Shi Yuhao , Wang Jianxin , Quinn Breandan , Jahagirdar Dushyant , Huang Wei-Chiao , Tsuji Moriya , Pili Roberto , Ito Fumito , Ortega Joaquin , Abrams Scott I , Ebos John M L , Lovell Jonathan F 
Published: December 2021

BackgroundInduction of CD8+T cells that recognize immunogenic, mutated protein fragments in the context of major histocompatibility class I (MHC-I) is a pressing challenge for cancer vaccine development.MethodsUsing the commonly used murine renal adenocarcinoma RENCA cancer model, MHC-I restricted neoepitopes are predicted following next-generation sequencing. Candidate neoepitopes are screened in mice using a potent cancer vaccine adjuvant system that converts short peptides into immunogenic nanoparticles. An identified functional neoepitope vaccine is then tested in various therapeutic experimental tumor settings.ResultsConversion of 20 short MHC-I restricted neoepitope candidates into immunogenic nanoparticles results in antitumor responses with multivalent vaccination. Only a single neoepitope candidate, Nesprin-2 L4492R (Nes2LR), induced functional responses but still did so when included within 20-plex or 60-plex particles. Immunization with the short Nes2LR neoepitope with the immunogenic particle-inducing vaccine adjuvant prevented tumor growth at doses multiple orders of magnitude less than with other vaccine adjuvants, which were ineffective. Nes2LR vaccination inhibited or eradicated disease in subcutaneous, experimental lung metastasis and orthotopic tumor models, synergizing with immune checkpoint blockade.ConclusionThese findings establish the feasibility of using short, MHC-I-restricted neoepitopes for straightforward immunization with multivalent or validated neoepitopes to induce cytotoxic CD8+T cells. Furthermore, the Nes2LR neoepitope could be useful for preclinical studies involving renal cell carcinoma immunotherapy.
Incidence of COVID-19 in patients treated with infliximab compared with patients treated with rituximab
Authors: Melong Pianta Taleng Cathy Mireille , Lauper Kim , Gilbert Benoit , Cunningham Tim , Guemara Romain , Brulhart Laure , Dan Diana , Courvoisier Delphine , Finckh Axel 
Published: December 2021

ObjectiveTo determine whether patients with inflammatory autoimmune diseases treated with rituximab (RTX) have more severe forms of COVID-19 compared with patients treated with anticytokine therapies, such as Tumour Necrosis Factor (TNF) inhibitors.MethodsWe included all patients who were on either RTX or infliximab (IFX) in two Swiss cantons during the first wave of the COVID-19 pandemic. We collected self-reported symptoms compatible with COVID-19, PCR-confirmed diagnoses of COVID-19 and the evolution of COVID-19 infections. We computed the raw and propensity score-adjusted incidence of COVID-19 by treatment group.Results190 patients were enrolled, of whom 121 (64%) were in the RTX group and 69 (36%) were in the IFX group. Twenty-one patients (11%) reported symptoms compatible with COVID-19 (RTX: 10, IFX: 11, p=0.14). Among patients with COVID-19 symptoms, four developed severe forms of the disease, with life-threatening pulmonary manifestations requiring intensive mechanical ventilation (RTX: 4 of 10, IFX: 0 of 11, Fisher’s exact test p=0.04). The incidence rate of COVID-19 symptoms was 0.73 (95% CI 0.39 to 1.37) cases per 1000 patient-days on RTX vs 1.52 (95% CI 0.82 to 2.85) cases per 1000 patient-days on IFX (crude p=0.10, adjusted p=0.07). The incidence rate of severe COVID-19 was 0.28 (95% CI 0.08 to 0.7.2) cases per 1000 patient-days on RTX compared with null on IFX (95% CI 0.0 to 0.44) (p=0.13). A replication in an independent validation cohort confirmed these findings, with consistent results in the Swiss Clinical Quality Management registry.ConclusionWhile the incidence of symptoms compatible with COVID-19 was overall similar in patients receiving RTX or IFX, the incidence of severe COVID-19 tended to be higher in the RTX group.
Risk factors for progression of juvenile-onset non-radiographic axial spondyloarthritis to juvenile-onset ankylosing spondylitis: a nested case–control study
Authors: Li Hao-Guang , Wang Dan-Min , Shen Feng-Cai , Huang Shu-Xin , Hou Zhi-Duo , Lin Ling , Xiao Zheng-Yu 
Published: December 2021

ObjectiveTo evaluate the clinical characteristics of juvenile-onset non-radiographic axial spondyloarthritis (nr-axSpA) and to investigate risk factors associated with progression to juvenile-onset ankylosing spondylitis (JoAS).MethodsA nested case–control study was conducted using the retrospectively collected data of 106 patients with juvenile-onset nr-axSpA (age at disease onset, <16 years) in the Clinical characteristic and Outcome in Chinese Axial Spondyloarthritis study cohort. Baseline demographic and clinical characteristics and prognosis were reviewed. Logistic regression analyses were performed to investigate risk factors associated with progression to JoAS.ResultsOverall, 58.5% of patients with juvenile-onset nr-axSpA presented with peripheral symptoms at disease onset. In 82.1% of these patients, axial with peripheral involvement occurred during the disease course. The rate of disease onset at >12 years and disease duration of ≤10 years were significantly higher in those with progression to JoAS than in those without progression to JoAS (83.0% vs 52.8%, p=0.001; 92.5% vs 56.6%, p<0.001, respectively). Multivariable logistic regression analysis revealed that inflammatory back pain (IBP) (OR 13.359 (95% CI 2.549 to 70.013)), buttock pain (OR 10.171 (95% CI 2.197 to 47.085)), enthesitis (OR 7.113 (95% CI 1.670 to 30.305)), elevated baseline C reactive protein (CRP) levels (OR 7.295 (95% CI 1.984 to 26.820)) and sacroiliac joint-MRI (SIJ-MRI) positivity (OR 53.821 (95% CI 9.705 to 298.475)) were significantly associated with progression to JoAS.ConclusionPeripheral involvement was prevalent in juvenile-onset nr-axSpA. IBP, buttock pain, enthesitis, elevated baseline CRP levels and SIJ-MRI positivity in patients with the disease are associated with higher risk of progression to JoAS.
Risk of psoriatic arthritis depending on age: analysis of data from 65 million people on statutory insurance in Germany
Authors: Deike Madeline , Brinks Ralph , Meller Stephan , Schneider Matthias , Sewerin Philipp 
Published: December 2021

ObjectivesThis study aims to provide a comprehensive analysis of the age-dependent risk of psoriatic arthritis (PsA). For this purpose, it focuses on the varying incidences within the different age groups.MethodsThe data were collected as part of the morbidity-based risk adjustment of the statutory health insurance companies in Germany. This survey recorded the International Statistical Classification of Diseases and Related Health Problems (ICD)-coded diagnoses of 65 million German citizens. Our population-based study used these raw data to calculate the prevalence of PsA in the first step. Subsequently, we employed a new approach for the estimation of the age-specific and sex-specific incidence of PsA.ResultsThe age-specific and sex-specific incidence of PsA showed a continuous increase with rising age until it peaked slightly before the age of 60 and declined thereafter. The maximum value was higher in women (40 per 100 000 py) than in men (30 per 100 000 py). Furthermore, the incidence rate tends to climb over the survey period.ConclusionsThe data sets identified an unexpected high incidence. A meta-analysis by Scotti et al and other recent population-based studies served as a reference for the comparison. The pattern of the age-specific incidence illustrated that the risk for PsA disease shows considerable variations depending on age.
Extended Green’s relations on Mn(D), a characterization
Authors: Narasimha Shenoi Prakash G. , Rajan A. R. 
Published: December 2021

In this paper, we consider the semiring [Formula: see text] of all [Formula: see text] matrices over a distributive lattice [Formula: see text] and extended Green’s relations [Formula: see text] and [Formula: see text] using [Formula: see text]-ideals. A (left, right) ideal [Formula: see text] of a semiring [Formula: see text] is called a (left, right) [Formula: see text]-ideal if [Formula: see text], where [Formula: see text]. We define [Formula: see text] and [Formula: see text] on a [Formula: see text]-regular semiring [Formula: see text], in which [Formula: see text] is a semilattice, as follows: [Formula: see text] if [Formula: see text] and [Formula: see text] if [Formula: see text], where [Formula: see text] is the left [Formula: see text]-ideal generated by [Formula: see text] and [Formula: see text] is the right [Formula: see text]-ideal generated by [Formula: see text]. Here we characterize [Formula: see text] and [Formula: see text] in [Formula: see text] in terms of rows and columns of the matrices.
Large scale services for connecting and integrating hundreds of linked datasets
Authors: Mountantonakis Michalis 
Published: December 2021

Michalis Mountantonakis is a Postdoctoral Researcher of the Information Systems Laboratory at FORTH-ICS (Greece) and a Visiting Lecturer in the Computer Science Department at University of Crete (CSD-UoC), Greece. He obtained his PhD degree from the CSD-UoC in 2020. His research interests fall in the areas of large-scale semantic data integration, linked data and semantic data management. The results of his research have been published in more than 20 research papers. For his dissertation, he awarded a) the prestigious SWSA Distinguished Dissertation Award 2020, which is given to the PhD dissertation from the previous year with the highest originality, significance, and impact in the area of semantic web, and b) the Maria Michael Manasaki Legacy's fellowship, which is awarded to the best graduate student of CSD-UoC, once a year.
In his dissertation, supervised by Associate Professor Yannis Tzitzikas (Computer Science Department at University of Crete), Michalis Mountantonakis dealt with the problem of Linked Data Integration at large scale, which is a very big challenging problem. He factorized the integration process according to various dimensions, for better understanding the overall problem and for identifying the open challenges, and proposed novel indexes and algorithms for providing core services, which can be exploited for several tasks related to Data Integration, such as: for finding all the URIs and all the available information for an entity, for producing connectivity analytics, for discovering the most relevant datasets for a given task, for dataset enrichment, and many others.