bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building capacity for integrated knowledge translation: a description of what we can learn from trainees’ experiences during the COVID-19 pandemic
Authors: Medeiros Priscilla , Laur Celia , Nguyen Tram , Gilfoyle Meghan , Conway Aislinn , Giroux Emily , Hoekstra Femke , Legasto Jean Michelle , Ramage Emily , Tittlemier Brenda , Wood Brianne , Steinwender Sandy ,   IKT Research Network Trainee Group, Moser Cheryl , MacKenzie Nicole , Ormel Ilja , Degen Charly 
Published: September 2022

AbstractThe use of collaborative health research approaches, such as integrated knowledge translation (IKT), was challenged during the COVID-19 pandemic due to physical distancing measures and transition to virtual platforms. As IKT trainees (i.e. graduate students, postdoctoral scholars) within the Integrated Knowledge Translation Research Network (IKTRN), we experienced several changes and adaptations to our daily routine, work and research environments due to the rapid transition to virtual platforms. While there was an increased capacity to communicate at local, national and international levels, gaps in equitable access to training and partnership opportunities at universities and organizations have emerged. This essay explores the experiences and reflections of 16 IKTRN trainees during the first 2 years of the COVID-19 pandemic at the micro (individual), meso (organizational) and macro (system) levels. The micro level, or individual experiences, focuses on topics of self-care (taking care of oneself for physical and mental well-being), maintaining research activities and productivity, and leisure (social engagement and taking time for oneself), while conducting IKT research during the pandemic. At the meso level, the role of programmes and organizations explores whether and how institutions were able to adapt and continue research and/or partnerships during the pandemic. At the macro level, we discuss implications for policies to support IKT trainees and research, during and beyond emergency situations. Themes were identified that intersected across all levels, which included (i) equitable access to training and partnerships; (ii) capacity for reflexivity; (iii) embracing changing opportunities; and (iv) strengthening collaborative relationships. These intersecting themes represent ways of encouraging sustainable and equitable improvements towards establishing and maintaining collaborative health research approaches. This essay is a summary of our collective experiences and aims to provide suggestions on how organizations and universities can support future trainees conducting collaborative research. Thus, we hope to inform more equitable and sustainable collaborative health research approaches and training in the post-pandemic era.
Changes in the 24-h movement behaviors during the transition to retirement: compositional data analysis
Authors: Suorsa Kristin , Leskinen Tuija , Pasanen Jesse , Pulakka Anna , Myllyntausta Saana , Pentti Jaana , Chastin Sebastien , Vahtera Jussi , Stenholm Sari 
Published: September 2022

AbstractBackgroundTransition to retirement is shown to affect sleep, sedentary time and physical activity, but no previous studies have examined how retirement changes the distribution of time spent daily in these movement behaviors. The aim of this study was to examine longitudinally how the composition of 24-h movement behaviors changes during the transition to retirement using compositional data analysis (CoDA).MethodsWe included 551 retiring public sector workers (mean age 63.2 years, standard deviation 1.1) from the Finnish Retirement and Aging study. The study participants wore a wrist-worn ActiGraph accelerometer for one week 24 h per day before and after retirement, with one year between the measurements. The daily proportions to time spent sleeping, in sedentary behavior (SED), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were estimated using the GGIR package. Changes in the daily proportions of movement behaviors were examined using Compositional Data Analysis version of linear mixed models.ResultsIn general, the proportion of time spent in active behaviors decreased relative to time spent in passive behaviors after retirement (p < .001). This change depended on occupation (occupation*time interactionp < .001). After retirement manual workers increased the proportions of both sleep and SED in relation to active behaviors, whereas non-manual workers increased the proportion of sleep in relation to active behaviors and SED. The proportion of MVPA decreased relatively more than the proportion of LPA (p = 0.01), independently of gender and occupation.ConclusionsRetirement induced a decrease in the proportion of time spent in active behaviors, especially time spent in MVPA. Future studies are needed to find ways to maintain or increase daily physical activity levels at the cost of sedentary behaviors among retirees.
A novel in-situ method to determine the respiratory tract deposition of carbonaceous particles reveals dangers of public commuting in highly polluted megacity
Authors: Madueño Leizel , Kecorius Simonas , Löndahl Jakob , Schnelle-Kreis Jürgen , Wiedensohler Alfred , Pöhlker Mira 
Published: September 2022

Abstract
Background
Exposure to air pollutants is one of the major environmental health risks faced by populations globally. Information about inhaled particle deposition dose is crucial in establishing the dose–response function for assessing health-related effects due to exposure to air pollution.

Objective
This study aims to quantify the respiratory tract deposition (RTD) of equivalent black carbon (BC) particles in healthy young adults during a real-world commuting scenario, analyze factors affecting RTD of BC, and provide key parameters for the assessment of RTD.

Methods
A novel in situ method was applied to experimentally determine the RTD of BC particles among subjects in the highly polluted megacity of Metro Manila, Philippines. Exposure measurements were made for 40 volunteers during public transport and walking.

Results
The observed BC exposure concentration was up to 17-times higher than in developed regions. The deposition dose rate (DDR) of BC was up to 3 times higher during commute inside a public transport compared to walking (11.6 versus 4.4 μg hr−1, respectively). This is twice higher than reported in similar studies. The average BC mass deposition fraction (DF) was found to be 43 ± 16%, which can in large be described by individual factors and does not depend on gender.

Conclusions
Commuting by open-sided public transport, commonly used in developing regions, poses a significant health risk due to acquiring extremely high doses of carcinogenic traffic-related pollutants. There is an urgent need to drastically update air pollution mitigation strategies for reduction of dangerously high emissions of BC in urban setting in developing regions. The presented mobile measurement set-up to determine respiratory tract deposition dose is a practical and cost-effective tool that can be used to investigate respiratory deposition in challenging environments.
A fast method to evaluate in a combinatorial manner the synergistic effect of different biostimulants for promoting growth or tolerance against abiotic stress
Authors: Benito Patricia , Ligorio Daniele , Bellón Javier , Yenush Lynne , Mulet José M. 
Published: September 2022

Abstract
Background
According to the most popular definition, a biostimulant is any substance or microorganism applied to plants with the aim to enhance nutrition efficiency, abiotic stress tolerance and/or crop quality traits, regardless of its nutrient content. Therefore, a biostimulant can help crops to withstand abiotic stress, while maintaining or even increasing productivity. We have previously designed a sequential system, based on two different model organisms, the baker’s yeast Saccharomyces cerevisiae and the plant Arabidopsis thaliana, to evaluate the potential of different natural extracts as biostimulants employing a blind-test strategy.

Results
In this report, we further expand this concept to evaluate different biostimulants in a combinatorial approach to reveal the potential additive, synergistic or antagonistic effects of different combinations of biostimulants in order to design new formulations with enhanced effects on plant growth or tolerance to abiotic stress. The method is based on yeast assays (growth tests in solid medium, and continuous growth in liquid cultures) and plant assays (mass accumulation in hydroponic culture) to assess effects on early growth.

Conclusions
With this novel approach, we have designed new formulations and quantified the ability to enhance growth and promote biomass accumulation under normal conditions and in the presence of abiotic stresses, such as drought, salinity or cold. This method enables a fast screen of many different products in a combinatorial manner, in order to design novel formulations of natural extracts with biostimulant potential.
Potential role of tea drinking in preventing hyperuricaemia in rats: biochemical and molecular evidence
Authors: Sang Siyao , Wang Lufei , Liang Taotao , Su Mingjie , Li Hui 
Published: September 2022

Abstract
Background
Lifestyle and diet play a significant role in hyperuricaemia. Accumulating evidence indicates that tea consumption is associated with hyperuricaemia and gout. However, diverse compounds in different types of tea make it quite difficult to determine the relevant molecular mechanism. Here, we compared the effects of six types of tea on hyperuricaemia induced by potassium oxonate (PO) and hypoxanthine in rats and investigated the possible underlying mechanisms.

Methods
Rats were randomly assigned to ten groups: the control, hyperuricaemia model, benzbromarone positive control, traditional Chinese medicine Simiao San positive control, green tea, yellow tea, black tea, white tea, red tea, and cyan tea treatment groups. After 21 days, uric acid (UA), xanthine oxidase (XOD), alanine aminotransferase (ALT),blood urea nitrogen (BUN), and creatinine (CRE) were assessed. Serum levels of interleukin-1β (IL-1β) were measured with an enzyme-linked immunosorbent assay. Haematoxylin–eosin staining and immunohistochemistry were used to assess liver and kidney injury.

Results
The levels of UA, CRE, and BUN in the treatment group were decreased to varying degrees. There was a significant reduction in UA, CRE, and BUN levels for yellow tea compared to the positive control drugs. Yellow tea suppressed XOD activity and alleviated hepatic and kidney injury. Network pharmacology and untargeted metabolomics indicated that ten yellow tea bioactive ingredients and 35 targets were responsible for preventing hyperuricaemia, which was mediated by 94 signalling pathways, including IL-1β and TNF.

Conclusion
These findings indicate that green tea cannot reduce the serum uric acid level of hyperuricaemic rats. Yellow tea can significantly improve hyperuricaemia by regulating the inflammatory response, autophagy, and apoptosis. This study provides a potential candidate for the treatment of hyperuricaemia and a basis for selecting therapeutic tea for patients with hyperuricaemia.
Outcomes of mitochondrial long chain fatty acid oxidation and carnitine defects from a single center metabolic genetics clinic
Authors: Ambrose Anastasia , Sheehan Melissa , Bahl Shalini , Athey Taryn , Ghai-Jain Shailly , Chan Alicia , Mercimek-Andrews Saadet 
Published: September 2022

AbstractBackgroundMitochondrial long-chain fatty acid oxidation and carnitine metabolism defects are a group of inherited metabolic diseases. We performed a retrospective cohort study to report on the phenotypic and genotypic spectrum of mitochondrial long-chain fatty acid oxidation and carnitine metabolism defects as well as their treatment outcomes.MethodsAll patients with mitochondrial long-chain fatty acid oxidation and carnitine metabolism defects were included. We divided patients into two groups to compare outcomes of those treated symptomatically (SymX) and asymptomatically (AsymX). We reviewed patient charts for clinical features, biochemical investigations, molecular genetic investigations, cardiac assessments, neuroimaging, treatments, and outcomes.ResultsThere were 38 patients including VLCAD (n = 5), LCHAD (n = 4), CACT (n = 3), MAD (n = 1), CPT-I (n = 13), CPT-II (n = 3) deficiencies and CTD (n = 9). Fourteen patients were diagnosed symptomatically (SymX), and 24 patients were diagnosed asymptomatically (AsymX). Twenty-eight variants in seven genes were identified in 36 patients (pathogenic/likely pathogenicn = 25; variant of unknown significancen = 3). Four of those variants were novel. All patients with LCHAD deficiency had the common variant (p.Glu474Gln) inHADHAand their phenotype was similar to the patients reported in the literature for this genotype. Only one patient with VLCAD deficiency had the common p.Val283Ala inACADVL.The different genotypes in the SymX and AsymX groups for VLCAD deficiency presented with similar phenotypes. Eight patients were treated with carnitine supplementation [CTD (n = 6), CPT-II (n = 1), and MAD (n = 1) deficiencies]. Thirteen patients were treated with a long-chain fat restricted diet and MCT supplementation. A statistically significant association was found between rhabdomyolysis, and hypoglycemia in the SymX group compared to the AsymX group. A higher number of hospital admissions, longer duration of hospital admissions and higher CK levels were observed in the SymX group, even though the symptomatic group was only 37% of the study cohort.ConclusionSeven different mitochondrial long-chain fatty acid oxidation and carnitine metabolism defects were present in our study cohort. In our clinic, the prevalence of mitochondrial long-chain fatty acid oxidation and carnitine defects was 4.75%.
Anthelmintic resistance of horse strongyle nematodes to fenbendazole in Lithuania
Authors: Dauparaitė Evelina , Kupčinskas Tomas , Varady Marian , Petkevičius Saulius 
Published: September 2022

Abstract
Background
Control of strongyle infections presents a global challenge for horse practitioners due to the development of anthelmintic resistance (AR), however comprehensive information on AR in Lithuania is still lacking. The aim of this study was to assess the current situation of fenbendazole (FBZ) AR in horses at stable level in Lithuania.

Results
Faecal samples from 121 horses from six stables were examined using the Mini-FLOTAC method. Of these, 89 horses met the inclusion criteria that included strongyle faecal egg counts (FEC) exceeding 200 eggs per gram (EPG). Faecal egg count reduction tests (FECRTs) were performed in these. AR was evaluated at horse stable level based on faecal egg count reduction (FECR) and the lower limit of the 95% credible interval (LLCI) using the Bayesian hierarchical model. This study confirmed that strongylids (Cyathostominae (CYA)) resistant to FBZ are pervasive in Lithuania. FBZ was ineffective in three of the six stables (FECR 77.1–79.0%; 49.8–99.8 LLCI), was suspected to be ineffective in one stable (FECR 93.6%; 85.4–100 LLCI) and was effective (FECR 99.8–100%; 99.8–100 LLCI) in two stables. FEC showed a significant (P < 0.01) difference between the treatment and control groups. Only CYA larvae were detected in larval cultures derived from strongyle-positive faecal samples collected 14 days after treatment of a test group with FBZ.

Conclusion
This in vivo study showed that resistance to FBZ in the treatment of strongyle nematodes is prevalent in horse stables in Lithuania. These findings should guide the implementation of more sustainable management of strongyle infections in horses in Lithuania.
Rapamycin and inulin for booster vaccine response stimulation (RIVASTIM)—rapamycin: study protocol for a randomised, controlled trial of immunosuppression modification with rapamycin to improve SARS-CoV-2 vaccine response in kidney transplant recipients
Authors: Tunbridge Matthew , Perkins Griffith B. , Singer Julian , Salehi Tania , Ying Tracey , Grubor-Bauk Branka , Barry Simon , Sim Beatrice , Hissaria Pravin , Chadban Steven J. , Coates P. Toby 
Published: September 2022

AbstractKidney transplant recipients are at an increased risk of severe COVID-19-associated hospitalisation and death. Vaccination has been a key public health strategy to reduce disease severity and infectivity, but the effectiveness of COVID vaccines is markedly reduced in kidney transplant recipients. Urgent strategies to enhance vaccine efficacy are needed.Methods:RIVASTIM-rapamycin is a multicentre, randomised, controlled trial examining the effect of immunosuppression modification prior to a third dose of COVID-19 vaccine in kidney transplant recipients who have failed to develop protective immunity to a 2-dose COVID-19 vaccine schedule. Participants will be randomised 1:1 to either remain on standard of care immunosuppression with tacrolimus, mycophenolate, and prednisolone (control) or cease mycophenolate and commence sirolimus (intervention) for 4 weeks prior to and following vaccination. The primary outcome is the proportion of participants in each trial arm who develop protective serological neutralisation of live SARS-CoV-2 virus at 4–6 weeks following a third COVID-19 vaccination. Secondary outcomes include SARS-CoV-receptor binding domain IgG, vaccine-specific immune cell populations and responses, and the safety and tolerability of sirolimus switch.Discussion:Immunosuppression modification strategies may improve immunological vaccine response. We hypothesise that substituting the mTOR inhibitor sirolimus for mycophenolate in a triple drug regimen will enhance humoral and cell-mediated responses to COVID vaccination for kidney transplant recipients.Trial registration:Australia New Zealand Clinical Trials Registry ACTRN12621001412820. Registered on 20 October 2021;https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382891&isReview=true
Identifying obstacles hindering the conduct of academic-sponsored trials for drug repurposing on rare-diseases: an analysis of six use cases
Authors: del Álamo Marta , Bührer Christoph , Fisher Dirk , Griese Matthias , Lingor Paul , Palladini Giovanni , Sireau Nicolas , Hivert Virginie , Sangiorgi Luca , Guillot Florence , Halftermeyer Juliane , Soucková Lenka , Nosková Kristýna , Demlová Regina 
Published: September 2022

Abstract
Background
Academic-sponsored trials for rare diseases face many challenges; the present paper identifies hurdles in the set-up of six multinational clinical trials for drug repurposing, as use cases.

Methods
Six academic-sponsored multinational trials aiming to generate knowledge on rare diseases drug repurposing were used as examples to identify problems in their set-up. Coordinating investigators leading these trials provided feedback on hurdles linked to study, country, and site set up, on the basis of pre-identified categories established through the analysis of previous peer-reviewed publications.

Results
Administrative burden and lack of harmonization for trial-site agreements were deemed as a major hurdle. Other main identified obstacles included the following: (1) complexity and restriction on the use of public funding, especially in a multinational set up, (2) drug supply, including procurement tendering rules and country-specific requirements for drug stability, and (3) lack of harmonization on regulatory requirements to get trial approvals.

Conclusion
A better knowledge of the non-commercial clinical research landscape and its challenges and requirements is needed to make drugs—especially those with less commercial gain—accessible to rare diseases patients. Better information about existing resources like research infrastructures, clinical research programs, and counseling mechanisms is needed to support and guide clinicians through the many challenges associated to the set-up of academic-sponsored multinational trials.
Development and evaluation of an electronic algorithm using a combination of a two-step malaria RDT and other rapid diagnostic tools for the management of febrile illness in children under 5 attending outpatient facilities in Burkina Faso
Authors: Kiemde Francois , Compaore Adelaide , Koueta Fla , Some Athanase M. , Kabore Berenger , Valia Daniel , Rouamba Toussaint , Bocoum Fadima Yaya , Sawadogo Seydou , Nana Macaire , Some Diane Y. , Kone Nadine A. , Pagbeleguem Valentin , Sangare Inoussa , Bere Antonia W. , Bonko Massa dit Achille , Tougri Gautier , Youl Sylvie Yeri , Schallig Henk , Tinto Halidou 
Published: September 2022

Abstract
Background
In Sub-Saharan Africa (SSA), febrile illnesses remain a major public health problem in children. However, the persistence of hrp2 antigen and the low sensitivity of pLDH RDT negatively affect antimalarials and antibiotics prescription practices. These limitations lead to poor management of febrile diseases and antimicrobial resistance (AMR). To improve the diagnosis of these febrile diseases and subsequent prescription of antimicrobials, it is hypothesized that the implementation of an algorithm including a two-step malaria RDT PfHRP2/pLDH supported by point-of-care (PoC) tests for bacterial infections could significantly improve the management of febrile diseases and thereby tackling AMR.

Methods
To assess the value of the proposed algorithm, an open-label randomized controlled trial with three arms, enrolling febrile children from 6 to 59 months is proposed.
In the control arm, febrile children will be managed according to the Integrated Management of Childhood Illnesses (IMCI), which is part of the standard of care in Burkina Faso. Treatment will be done according to national guidelines.
In the RDT decisional algorithm (RDT-DA) arm (intervention), the clinical examination based on IMIC will be supported by a two-step malaria RDT and bacterial infections RDTs. Prescription will be left to the discretion of the healthcare workers based on clinical examination and PoC test results.
In the e-algorithm arm (intervention), artificial intelligence integrating multiple layers of clinical information such as clinical examination, signs/symptoms and medical history, and biological information such as biomarkers (CRP and WBC) and pathogen-specific PoC tests, and oximetry will be developed. The e-algorithm will serve to guide the diagnostic and management of febrile infections in children.
In the 3 arms, the case report forms will be digitalized. A final follow-up visit (day 7) will be scheduled for all participants. Patients will be asked to come back to the health facilities before the scheduled visit if the symptoms persist or in case of health condition worsening.

Discussion
If successful, this study could contribute to improve the management of febrile diseases and reduce inappropriate use of antimicrobials.

Trial registration
The trial is registered at ClinicalTrial.gov, NCT05285657. Enrolment started on 4 March 2022 with long-term outcome being assessed completely by 2023.