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ObjectiveTo determine if methotrexate or folic acid prescription was associated with differential risk for COVID-19 diagnosis or mortality.DesignCase–control analysis.SettingThe population-based UK Biobank (UKBB) cohort.ParticipantsData from 380 380 UKBB participants with general practice prescription data for 2019–2021. Updated medical information was retrieved on 13 December 2021.Primary and secondary outcome measuresThe outcomes of COVID-19 diagnosis and COVID-19-related mortality were analysed by multivariable logistic regression. Exposures evaluated were prescription of folic acid and/or methotrexate. Criteria for COVID-19 diagnosis were (1) a positive SARS-CoV-2 test or (2) ICD-10 code for confirmed COVID-19 (U07.1) or probable COVID-19 (U07.2) in hospital records, or death records. By these criteria, 26 003 individuals were identified with COVID-19 of whom 820 were known to have died from COVID-19. Logistic regression statistical models were adjusted for age sex, ethnicity, Townsend deprivation index, body mass index, smoking status, presence of rheumatoid arthritis, sickle cell disease, use of anticonvulsants, statins and iron supplements.ResultsCompared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had increased risk of diagnosis of COVID-19 (OR 1.51 (1.42–1.61)). The prescription of methotrexate with or without folic acid was not associated with COVID-19 diagnosis (p≥0.18). People prescribed folic acid supplementation had positive association with death after a diagnosis of COVID-19 (OR 2.64 (2.15–3.24)) in a fully adjusted model. The prescription of methotrexate in combination with folic acid was not associated with an increased risk for COVID-19-related death (1.07 (0.57–1.98)).ConclusionsWe report an association of increased risk for COVID-19 diagnosis and COVID-19-related death in people prescribed folic acid supplementation. Our results also suggest that methotrexate might attenuate these associations.

Charting microRNA (miRNA) regulation across pathways is central to characterizing their role in disease. Yet, current methods reveal only individual miRNA-pathway interactions. We have developed a systems biology approach,Pathway networks of miRNA Regulation(PanomiR), that overcomes these limitations to identify miRNA targeting of groups of interacting pathways using gene expression. The approach does not depend on statistically significant enrichment of miRNA target genes in individual pathways or significant differentially expressed genes. Rather, it directly captures differential activity of pathways between states, determining their up-or-down regulation while sensitively detecting biologically-meaningful signals. PanomiR analyzes the co-activity of differentially regulated pathways to determine coordinate functional groups and uses these co-activated grouped pathways to uncover miRNAs that target them. Incorporating both experimentally-supported or predicted miRNA-mRNA interactions, PanomiR robustly identifies miRNAs central to the regulation of disease functions. We applied PanomiR to a liver cancer dataset and showed that it can organize liver cancer pathways and their regulating miRNAs into coordinated transcriptional programs, reflecting the pathogenic mechanisms of hepatocellular carcinoma. PanomiR recapitulated known central miRNAs in liver cancer with a biologically meaningful assignment of pathways under their regulation, unbiased by the number of genes targeted by each miRNA. PanomiR is a granular framework for detecting broad-scale multi-pathway programs under miRNA regulation. It is accessible as an open-source R/Bioconductor package: .

INTRODUCTIONGenome-wide association studies have led to numerous genetic loci associated with Alzheimer’s disease (AD). Whole-genome sequencing (WGS) now permit genome-wide analyses to identify rare variants contributing to AD risk.METHODSWe performed single-variant and spatial clustering-based testing on rare variants (minor allele frequency ≤1%) in a family-based WGS-based association study of 2,247 subjects from 605 multiplex AD families, followed by replication in 1,669 unrelated individuals.RESULTSWe identified 13 new AD candidate loci that yielded consistent rare-variant signals in discovery and replication cohorts (4 from single-variant, 9 from spatial-clustering), implicating these genes: FNBP1L, SEL1L, LINC00298, PRKCH, C15ORF41, C2CD3, KIF2A, APC, LHX9, NALCN, CTNNA2, SYTL3, CLSTN2.DISCUSSIONDownstream analyses of these novel loci highlight synaptic function, in contrast to common AD-associated variants, which implicate innate immunity. These loci have not been previously associated with AD, emphasizing the ability of WGS to identify AD-associated rare variants, particularly outside of coding regions.

ImportanceFolate metabolism is implicated in SARS-CoV-2 infectivity. Medication affecting folate metabolism may influence the risk of COVID-19 diagnosis and outcomes.Objectiveto determine if methotrexate (an antifolate) or folic acid prescription were associated with differential risk, for COVID-19 diagnosis or mortality.Design, Setting, and ParticipantsCase-control analysis of COVID-19 from the population-based UK Biobank (UKBB) cohort. Updated medical information was retrieved on the 13th December 2021. Data from 380,380 UKBB participants with general practice prescription data for 2019 to 2021 were used. Criteria for COVID-19 diagnosis were 1) a positive SARS-CoV-2 test or 2) ICD-10 code for confirmed COVID-19 (U07.1) or probable COVID-19 (U07.2) in hospital records, or death records. By these criteria 26,003 individuals were identified with COVID-19 of whom 820 were known to have died from COVID-19. Logistic regression statistical models were adjusted for age sex, ethnicity, Townsend deprivation index, BMI, smoking status, presence of rheumatoid arthritis, sickle cell disease, use of anticonvulsants, statins and iron supplements.ExposuresPrescription of folic acid and/or methotrexate.Main outcomes and measuresThe outcomes of COVID-19 diagnosis and COVID-19 related mortality were analyzed by multivariable logistic regression. The odds ratios from different exposures were compared.ResultsCompared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had increased risk of diagnosis of COVID-19 (OR 1.51 [1.42 ; 1.61]). The prescription of methotrexate with or without folic acid was not associated with COVID-19 diagnosis (P≥0.18). People prescribed folic acid supplementation had positive association with death after a diagnosis of COVID-19 (OR 2.64 [2.15 ; 3.24]) in a fully adjusted model. The prescription of methotrexate in combination with folic acid was not associated with an increased risk for COVID-19 related death (1.07 [0.57 ; 1.98]).Conclusions and RelevanceWe report increased risk for COVID-19 diagnosis and COVID-19-related death for people prescribed folic acid supplementation. Prescription and use of supplemental folic acid may confer increased risk of infection with SARS-CoV-2 and increased risk of death resulting from COVID-19. Our results indicate that methotrexate attenuates an increased risk for COVID-19 diagnosis and death conferred by folic acid.Key PointsQuestionDoes folate supplementation and/or methotrexate use affect the risk COVID-19 diagnosis and COVID-19 associated mortality?FindingsIn this epidemiological analysis from the UK Biobank, folic acid supplementation was associated with a 1.5-fold increased risk of COVID-19 diagnosis and a 2.6-fold increased risk of COVID-19 associated mortality. Methotrexate use might attenuate an increased risk for COVID-19 diagnosis and death conferred by folic acid.MeaningFolic acid supplementation appears to be associated with increased risk for COVID-19 diagnosis and associated mortality while methotrexate use attenuated this risk

Dual-energy X-ray absorptiometry (DXA) is the method of choice for assessing bone mineral density (BMD). Unfortunately, the performance and interpretation of DXA can be challenging and errors are common. In fact, it has been reported that up to 90% of BMD reports contain at least 1 error. Errors can be the result of technique or interpretative in nature or both and can result in inappropriate diagnosis and management. In this article, we review the various types of pitfalls frequently encountered by physicians interpreting DXA studies. Being aware of these pitfalls will help readers recognize and avoid them when encountered in clinical practice.

INTRODUCTION AND HYPOTHESIS: The current study aims to characterize the association between pelvic floor disorder symptoms and bone strength reflecting a potential connective tissue pathophysiology in postmenopausal women. METHODS: A cross-sectional study was conducted in postmenopausal women undergoing osteoporosis evaluation from 2007 to 2010. Urinary incontinence (UI) was defined as urinary leakage ≥2–3 times/week. UI types were defined using the 3 Incontinence Questionnaire. Fecal incontinence was defined as stool leakage ≥1/month, and pelvic organ prolapse as a positive response to “Do you have a bulge or something falling out that you can see or feel in your vaginal area?” Bone quality and quantity were assessed by trabecular bone score (TBS) and bone mineral density, respectively; i) bone strength was defined by combined quality/quantity index, low strength being equivalent to moderate-severe fracture risk ii) low quality as TBS≤1.31; iii) low quantity by T-score

© 2021 Moore et al., Bioinformatics training is required at every stage of a scientist’s research career. Continual bioinformatics training allows exposure to an ever-changing and growing repertoire of techniques and databases, and so biologists, computational scientists, and healthcare practitioners are all seeking learning opportunities in the use of computational resources and tools designed for data storage, retrieval, and analysis. There are abundant opportunities for accessing bioinformatics training for scientists in high-income countries (HICs), with well-equipped facilities and participants and trainers requiring minimal travel and financial costs alongside a range of general advice for developing short bioinformatics training courses [1–3]. However, regionally targeted bioinformatics training in low- and middle-income countries (LMICs) often requires more extensive local and external support, organization, and travel. Due to the limited expertise in bioinformatics in LMICs in general, most bioinformatics training requires a fair amount of collaboration with experts beyond the local community, country, or region. A common model of training, used as the basis of this article, includes a local host collaborating with local, regional, and international experts gathering to train local or regional participants. Recently, there has been a growth of capacity strengthening initiatives in LMICs, such as the Pan African Bioinformatics Network for Human Heredity and Health in Africa (H3ABioNet) Initiative [4–6], the Capacity Building for Bioinformatics in Latin America (CABANA) Project [7], the Asia Pacific BioInformatics Network (APBioNet) [8], and the Wellcome Connecting Science Courses and Conferences program [9]. One of the important strands of these initiatives is a drive to organize and deliver valuable bioinformatics training, but organizing and delivering short bioinformatics training workshops in an LMIC present a unique set of challenges. This paper attempts to build upon the sage advice for organizing bioinformatics workshops with specific guidance for organizing and delivering them in LMICs. It describes the processes to follow in organizing courses taking into consideration the low-resource setting. We should also note that LMICs are not a monolithic group and that setting, context, temporality, and specific location matters. LMICs are a complex regional grouping [10] and should be treated as such; however, we will present some common lessons that we hope will help organizers and trainers of bioinformatics training events in LMICs to navigate the often different, challenging, and rewarding experience., The authors who contributed to this manuscript are funded as follows: BM receives salary support from Wellcome Trust grants [WT108749/Z/15/Z, WT108749/Z/15/A], PC, VR, NM, AG’s salaries are funded in whole, or in part, by the NIH Common Fund H3ABioNet grant [U24HG006941], MC, SLFV, AR, PG, PCL’s salaries were partly funded by the UKRI-BBSRC ‘Capacity building for bioinformatics in Latin America’ (CABANA) grant, on behalf of the Global Challenges Research Fund [BB/P027849/1], JDLR is funded by ISCiii AES [ref. PI18/00591] at the CSIC/USAL (Spain) and by CYTED, RIABIO (Red Iberoamericana 521RT0118), AM’s salary is funded by [WT206194/Z/17/Z], GO is funded by the CABANA grant and SM is funded by the EMBL-EBI.

Alzheimer’s disease (AD) is a genetically complex disease for which roughly 30 genes have been identified via genome-wide association studies. We attempted to identify rare variants (minor allele frequency −6, using the burden test or the SKAT statistic. The genomic region around the dystobrevin beta (DTNB) gene was identified with the burden test and replicated in case/control samples from the ADSP study (pmeta = 4.74×10−8). SKAT analysis revealed region-based association around the discs large homolog 2 (DLG2) gene and replicated in case/control samples from the ADSP study (pmeta =1×10−6). Here, in a region-based GSAS of AD we identified two novel AD genes, DLG2 and DTNB, based on association with rare variants.

Osteoporosis is the most prevalent bone disease worldwide and predisposes affected individuals to fragility fractures. Exercise has been shown to have multiple health benefits in post-menopausal osteoporotic women, but often recommendations regarding the benefits of specific exercise types are vague. Improving bone mineral density (BMD) is an essential component in any program to prevent osteoporotic vertebral fractures. The objective of this report is to briefly review the current understanding on the impact of exercise on BMD in postmenopausal women as it pertains to fragility fractures. Broad categories of exercises include aerobic, resistance, stretching, and balance. Tai Chi, Yoga, and Pilates are a heterogeneous group of specific exercise modalities that can span multiple categories. Current literature suggests that only resistance type exercises have a convincing impact on BMD. Core-strengthening exercises and attention to posture/balance can help mitigate falls. A number of barriers affect patient compliance and accessibility to exercise. In summary, exercise should be included in any multi-modality osteoporosis treatment plan with the goal of sustained exercise throughout life. If possible, osteoporotic women should be on a resistance-based regimen incorporating weight-bearing exercises, and also target posture and balance. Healthcare providers and educators should have resources readily available for patients.

This position development conference (PDC) Task Force examined the assessment of bone status in orthopedic surgery patients. Key questions included which orthopedic surgery patients should be evaluated for poor bone health prior to surgery and which subsets of patients are at high risk for poor bone health and adverse outcomes. Second, the reliability and validity of using bone densitometry techniques and measurement of specific geometries around the hip and knee before and after arthroplasty was determined. Finally, the use of computed tomography (CT) attenuation coefficients (Hounsfield units) to estimate bone quality at anatomic locations where orthopedic surgery is performed including femur, tibia, shoulder, wrist, and ankle were reviewed. The literature review identified 665 articles of which 198 met inclusion exclusion criteria and were selected based on reporting of methodology, reliability, or validity results. We recommend that the orthopedic surgeon be aware of established ISCD guidelines for determining who should have additional screening for osteoporosis. Patients with inflammatory arthritis, chronic corticosteroid use, chronic renal disease, and those with history of fracture after age 50 are at high risk of osteoporosis and adverse events from surgery and should have dual energy X-ray absorptiometry (DXA) screening before surgery. In addition to standard DXA, bone mineral density (BMD) measurement along the femur and proximal tibia is reliable and valid around implants and can provide valuable information regarding bone remodeling and identification of loosening. Attention to positioning, selection of regions of interest, and use of special techniques and software is required. Plain radiographs and CT provide simple, reliable methods to classify the shape of the proximal femur and to predict osteoporosis; these include the Dorr Classification, Cortical Index, and critical thickness. Correlation of these indices to central BMD is moderate to good. Many patients undergoing orthopedic surgery have had preoperative CT which can be utilized to assess regional quality of bone. The simplest method available on most picture archiving and communications systems is to simply measure a regions of interest and determine the mean Hounsfield units. This method has excellent reliability throughout the skeleton and has moderate correlation to DXA based on BMD. The prediction of outcome and correlation to mechanical strength of fixation of a screw or implant is unknown.

Objective.Essential tremor (ET) is associated with psychological difficulties, including anxiety and depression. Demoralization (feelings of helplessness, hopelessness, inability to cope), another manifestation of psychological distress, has yet to be investigated in ET. Our objectives are to (1) estimate the prevalence of demoralization in ET, (2) assess its clinical correlates, and (3) determine whether demoralization correlates with tremor severity.Methods.We administered the Kissane Demoralization Scale (KDS-II) and several psychosocial evaluations (ie, scales assessing subjective incompetence, resilience, and depression [eg, Geriatric Depression Scale]) to 60 ET subjects. Tremor was assessed with a disability score and total tremor score. KDS-II >8 indicated demoralization.Results.Among 60 ET subjects (mean age = 70.2 ± 6.8 years), the prevalence of demoralization was 13.3%, 95% confidence interval = 6.9–24.2%. Although there was overlap between demoralization and depression (10% of the sample meeting criteria for both), 54% of depressed subjects were not demoralized, and 25% of demoralized subjects were not depressed. Demoralization correlated with psychological factors, but demoralized subjects did not have significantly higher total tremor scores, tremor disability scores, or years with tremor.Conclusions.Demoralization has a prevalence of 13.3% in ET, similar to that in other chronic or terminal illnesses (eg, cancer 13–18%, Parkinson’s disease 18.1%, coronary heart disease 20%). Demoralization was not a function of increased tremor severity, suggesting that it is a separable construct, which could dictate how a patient copes with his/her disease. These data further our understanding of the psychological and psychosocial correlates of ET.

OBJECTIVE The aim of this study was to conduct a 9-month pilot Internet randomized controlled trial (RCT) of cherry extract and diet modification in gout to assess the feasibility of an Internet study and obtain effect estimates. METHODS After providing online informed consent in response to Internet advertisements and social media or clinic flyers, 84 people with physician-confirmed gout were randomized to either cherry extract 3,600 mg/d (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via Internet and phone calls. The primary objective was the feasibility of an Internet study, and secondary objectives were to obtain effect estimates for gout flares, functional ability assessed with the Health Assessment Questionnaire (HAQ), and adverse events (AEs) for future trials. RESULTS Of the 84 people randomized, overall completion rates were more than 80% for most study procedures up to 6 months and similar for the 2 active comparators. Improvements were seen in gout flares and HAQ scores in cherry extract and diet modification groups at 9 months compared with baseline: gout flares per month, 0.22 versus 0.36 (p = 0.049) and 0.28 versus 0.31 (p = 0.76); proportion with any gout flare, 56% versus 98% (p < 0.0001) and 65% versus 98% (p = 0.0002); and mean ± standard deviation HAQ score, 0.28 ± 0.54 versus 0.55 ± 0.68 (p = 0.001) and 0.23 ± 0.40 versus 0.48 ± 0.61 (p = 0.06), respectively. Any AEs and gastrointestinal symptoms/AEs at 9 months in cherry extract and diet modification groups were 3% versus 0% and 28% versus 27%, respectively. CONCLUSIONS An Internet gout RCT is feasible for nonpharmacological gout treatments. A hypothesis-testing, large Internet RCT of cherry extract versus placebo is needed.

Methotrexate (MTX), an antifolate, is the anchor drug for the treatment of rheumatoid arthritis (RA). It is inexpensive, effective, and generally safe. When clinical response is inadequate, biological therapies are commonly used in combination with MTX. However, biological agents have safety concerns (i.e. infections, malignancy) and the addition of a biologic agent is expensive, making strategies to improve MTX efficacy important. Inhibition of pathways of folate metabolism involving purine metabolism by MTX, have been traditionally emphasized as important in MTX efficacy. However, inhibition MTX catabolism may also be important. MTX is irreversibly hydroxylated to form 7-hydroxy methotrexate (7-OH-MTX) by aldehyde oxidase (EC 1.2.3.1) (AOX). Catabolism of MTX to 7-OH-MTX is the first metabolic process imposed on an oral dose of MTX and will alter subsequent interactions of MTX with other enzymes. 7-OH-MTX is less potent than MTX in the treatment of rat adjuvant arthritis. RA patients with a low capacity to catabolize MTX to 7-OH-MTX do better clinically than individuals who are rapid formers of 7-OH-MTX. Therefore, altering the catabolism of MTX may be an innovative way to improve MTX efficacy. Raloxifene is a FDA-approved therapy for postmenopausal osteoporosis and for the reduction of invasive breast cancers but has no known activity in RA. Raloxifene is a potent inhibitor of human liver AOX. Postmenopausal women with RA frequently have low bone mineral density and would be candidates for raloxifene and MTX combination therapy. The effect of raloxifene on MTX metabolism has never been studied. Our hypothesis is that in postmenopausal women with RA and osteoporosis treated with MTX and raloxifene, the inhibition of AOX with resultant decreased formation of 7-OH MTX; will increase MTX levels and improve MTX efficacy. This hypothesis could be studied in an open-label, proof of concept clinical study in individuals before and after the addition of raloxifene. Red blood cell MTX and 7-OH-MTX levels and RA disease activity (DAS28) would be measured. In possible future studies, there are dietary substances, as supplements, (e.g. epigallocatechin gallate in green tea and resveratrol) which inhibit human liver AOX which could be evaluated.

The ‘WWI and WWII Symposium: Legislation, Recovery, Identification and Burial of Human Remains’, took place on 13th March 2020 (Márquez-Grant and Errickson, 2021). The event was in the form of a round table discussion with participating specialists who focus on the forensic recovery and identification of war casualties, particularly with a focus on Europe. Although the event saw a large amount of knowledge exchange, the discussion went far beyond those who attended the session. As a result, this Special Issue in ‘Forensic Science International’ is aimed at disseminating the discussion to a wider number of individuals while incorporating further views and input from specialists who could not be in attendance on the day.

OBJECTIVE: To determine whether the Dietary Approaches to Stop Hypertension (DASH) diet or an alternative, simplified diet, emphasizing high fiber fruit and vegetables, lowers serum urate (SU). METHODS: We conducted a secondary study of the DASH feeding study, a 3-arm, parallel-design, randomized trial of 459 adults with systolic blood pressure (SBP)

Background: Biocuration involves a variety of teams and individuals across the globe. However, they may not self-identify as biocurators, as they may be unaware of biocuration as a career path or because biocuration is only part of their role. The lack of a clear, up-to-date profile of biocuration creates challenges for organisations like ELIXIR, the ISB and GOBLET to systematically support biocurators and for biocurators themselves to develop their own careers. Therefore, the ELIXIR Training Platform launched an Implementation Study in order to i) identify communities of biocurators, ii) map the type of curation work being done, iii) assess biocuration training, and iv) draw a picture of biocuration career development. Methods: To achieve the goals of the study, we carried out a global survey on the nature of biocuration work, the tools and resources that are used, training that has been received and additional training needs. To examine these topics in more detail we ran workshop-based discussions at ISB Biocuration Conference 2019 and the ELIXIR All Hands Meeting 2019. We also had guided conversations with selected people from the EMBL-European Bioinformatics Institute. Results: The study illustrates that biocurators have diverse job titles, are highly skilled, perform a variety of activities and use a wide range of tools and resources. The study emphasises the need for training in programming and coding skills, but also highlights the difficulties curators face in terms of career development and community building. Conclusion: Biocurators themselves, as well as organisations like ELIXIR, GOBLET and ISB must work together towards structural change to overcome these difficulties. In this article we discuss recommendations to ensure that biocuration as a role is visible and valued, thereby helping biocurators to proceed with their career.

ELIXIR is a pan-European intergovernmental organisation for life science that aims to coordinate bioinformatics resources in a single infrastructure across Europe; bioinformatics training is central to its strategy, which aims to develop a training community that spans all ELIXIR member states. In an evidence-based approach for strengthening bioinformatics training programmes across Europe, the ELIXIR Training Platform, led by the ELIXIR EXCELERATE Quality and Impact Assessment Subtask in collaboration with the ELIXIR Training Coordinators Group, has implemented an assessment strategy to measure quality and impact of its entire training portfolio. Here, we present ELIXIR’s framework for assessing training quality and impact, which includes the following: specifying assessment aims, determining what data to collect in order to address these aims, and our strategy for centralised data collection to allow for ELIXIR-wide analyses. In addition, we present an overview of the ELIXIR training data collected over the past 4 years. We highlight the importance of a coordinated and consistent data collection approach and the relevance of defining specific metrics and answer scales for consortium-wide analyses as well as for comparison of data across iterations of the same course. ELIXIR-EXCELERATE is funded by the European Commission within the Research Infrastructures programme of Horizon 2020, grant agreement number 676559 (https://ec.europa.eu/programmes/horizon2020/en/area/researchinfrastructures). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Very dense artifacts confound bone density measurement. Hologic and GE densitometers exclude artifact density and GE also excludes associated area. Consequently, BMD is decreased with Hologic software. Despite different manufacturers’ approaches, when dense artifacts overlay the spine, the affected vertebral body should be excluded from the reported BMD. Very dense objects, such as lead bullets are described as “black hole” artifacts on Hologic densitometers. Whether similar results occur on GE scanners is not reported. We hypothesized that dense artifacts confound both brands of densitometers. Three lead bullets of varying size were placed overlying or adjacent to L3 on anthropomorphic and encapsulated aluminum spine phantoms. Three scans were acquired with and without projectiles on a Hologic Discovery W, GE iDXA, and Prodigy densitometer. Lead bullets are measured as having high bone mineral content (BMC); they appear black in dual-energy mode on Hologic scanners and are colored blue on GE scanners. On Hologic scanners, BMC of a dense artifact over bone is excluded, but the bone area is not altered. Consequently, bone mineral density (BMD) of the affected vertebra, and of L1–4, is decreased. For example, a .45 caliber bullet over L3 decreased BMD (p

Sharing, reusing and reproducing data, software and other digital objects forms the cornerstone of open science practices. Such practices are guided by the Findable, Accessible, Interoperable and Reusable (FAIR) principles. Implementing FAIR principles is not always straightforward, especially in the context of Bioinformatics training. If we are to meet worldwide demand for such training, adhering to the FAIR principles is vital not only for data and software, but also for training materials (any digital object used in a training context, such as slide presentations, exercises, datasets). To facilitate this process, and break the principles down into practical steps, the ELIXIR Training Platform community has put together ten simple rules for making training materials FAIR. Above all is the need to plan to share your training materials online from the outset. Amongst the remaining rules is the importance of describing materials properly, assigning unique identifiers, registering them online, defining access criteria, and using interoperable formats. The full set of ten rules is presented here.

Objectives:Essential tremor (ET) confers an increased risk for developing both amnestic and non-amnestic mild cognitive impairment (MCI). Yet, the optimal measures for detecting mild cognitive changes in individuals with this movement disorder have not been established. We sought to identify the cognitive domains and specific motor-free neuropsychological tests that are most sensitive to mild deficits in cognition as defined by a Clinical Dementia Rating (CDR) of 0.5, which is generally associated with a clinical diagnosis of MCI.Methods:A total of 196 ET subjects enrolled in a prospective, longitudinal, clinical-pathological study underwent an extensive motor-free neuropsychological test battery and were assigned a CDR score. Logistic regression analyses were performed to identify the neuropsychological tests which best identified individuals with CDR of 0.5 (mild deficits in cognition)versus0 (normal cognition).Results:In regression models, we identified five tests in the domains of Memory and Executive Function which best discriminated subjects with CDR of 0.5versus0 (86.9% model classification accuracy). These tests were the California Verbal Learning Test II Total Recall, Logical Memory II, Verbal-Paired Associates I, Category Switching Fluency, and Color-Word Inhibition.Conclusions:Mild cognitive difficulty among ET subjects is best predicted by combined performance on five measures of memory and executive function. These results inform the nature of cognitive dysfunction in ET and the creation of a brief cognitive battery to assess patients with ET for cognitively driven dysfunction in life that could indicate the presence of MCI. (JINS, 2018,24, 1084–1098)

The potential of genomic medicine in improving the quality of healthcare both at population and individual-level is well-recognized globally. However, successful adoption of genetic and genomic evidence into clinical practice depends on training the healthcare workforce and clinical researchers in genomic medicine. Due to limited expertise in the medical genetics and genomics field, widespread uptake largely depends on task-shifting for the implementation of genomic medicine implementation to key healthcare professionals such as nurses. Their knowledge would be developed through courses aimed at professional development. Globally, trainers, and training initiatives in genomic medicine are in early stages of development, but resource limited settings such as the African continent face additional logistical and institutional challenges. The African Genomic Medicine Training (AGMT) Initiative was conceived during a combined conference of the African Society of Human Genetics (AfSHG) and the Human Heredity and Health in Africa Consortium (H3Africa) in 2016, Senegal, in response to the needs for developing knowledge and skills in genomic medicine. AGMT was established to implement a sustainable genomic medicine training initiative primarily for healthcare professionals who are not geneticists but are nurses, doctors, and pharmacists in Africa. This paper reports on the establishment of the AGMT initiative and the strategies developed and piloted by this initiative in designing and implementing an accredited frame-work and community-based blended learning course for nurses across 11 African countries. The global implementation experiences, outcomes and lessons learnt are highlighted. The AGMT initiative strategy takes advantage of existing research consortia and networks to train and create a pool of trainers and has adopted evidence-based approaches to guide curriculum and content development/adaptation. This initiative established the first Africa-wide online blended learning genomic medicine course which forms the basis from which to develop courses for other healthcare professionals and the wider public.

Osteoporosis is the most commonly encountered metabolic bone disease, and metabolic bone-disease clinics have been established to assist in the diagnosis and treatment of uncommon causes of low bone-mineral density. Hypophosphatemia leading to metabolic bone disease may be encountered, and an understanding of phosphate homeostasis can aid in the diagnosis. Two cases of hypophosphatemia leading to low bone-mineral densities were seen at the University of Alabama at Birmingham Osteoporosis Clinic. We developed a diagnostic algorithm, and the laboratory values of each patient were tested with the algorithm. The algorithm, incorporating the use of a spot urine phosphate and spot urine creatinine level at the time of initial serum metabolic profile evaluation, accurately determined the cause of hypophosphatemia in each case.

In a large, pragmatic clinical trial, we calculated the costs of achieving four successful patient-centered outcomes using a tailored patient activation DXA result letter accompanied by a bone health brochure. The cost to achieve one successful outcome (e.g., a 0.5 standard deviation improvement in care satisfaction) ranged from $127.41 to $222.75. Pragmatic randomized controlled trials (RCTs) should focus on patient-centered outcomes and report the costs for achieving those outcomes. We calculated per person incremental intervention costs, the number-needed-to-treat (NNT), and incremental per patient costs (cost per NNT) for four patient-centered outcomes in a direct-to-patient bone healthcare intervention. The Patient Activation after DXA Result Notification (PAADRN) pragmatic RCT enrolled 7749 patients presenting for DXA at three health centers between February 2012 and August 2014. Interviews occurred at baseline and 52 weeks post-DXA. Intervention subjects received an individually tailored DXA result letter accompanied by an educational bone health brochure 4 weeks post-DXA, while the usual care subjects did not. Outcomes focused on patients (a) correctly identifying their results, (b) contacting their providers, (c) discussing their results with their providers, and (d) satisfaction with their bone healthcare. NNTs were determined using intention-to-treat linear probability models, per person incremental intervention costs were calculated, and costs per NNT were computed. Mean age was 66.6 years old, 83.8% were women, and 75.3% were non-Hispanic whites. The incremental per patient cost (costs per NNT) to increase the ability of a patient to (a) correctly identify their DXA result was $171.07; (b) contact their provider about their DXA result was $222.75; (c) discuss their DXA result with their provider was $193.55; and (d) achieve a 0.5 SD improvement in satisfaction with their bone healthcare was $127.41. An individually tailored DXA result letter accompanied by an educational brochure can improve four patient-centered outcomes at a modest cost. clinicaltrials.gov identifier NCT01507662

The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide “drug holiday” clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a comprehensive recruitment approach will be needed to effectively achieve the scientific goals of the EDGE study.

Demand for training life scientists in bioinformatics skills led to the development of a train-the-trainer collaboration between the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI) and 2 Australian organisations, Bioplatforms Australia and Commonwealth Scientific and Industrial Research Organisation (CSIRO) in 2012. The goal of the collaboration was to establish a group of trained instructors who could develop and deliver short bioinformatics courses nationally. A train-the-trainer course introduces instructors to aspects of andragogy and evidence-based learning principles to help them better design, develop, and deliver high-quality training. Since then, both the number of trainers in the network and the course portfolio have grown. Best practises have been developed and shared between the Australian cohort and EMBL-EBI to address common challenges in bioinformatics training. The Australian trainer cohort undertook a train-the-trainer instructor course, again with EMBL-EBI, and subsequently successfully delivered train-the-trainer courses to interested bioinformatics trainers within Australia. We conclude that a train-the-trainer approach can help build national capacity and maintain a critical mass of trained instructors.

Objective The aim of this study was to report patient-centered outcomes and finalization of key study procedures from a 9-month pilot internet randomized controlled trial of cherry extract versus diet modification. Methods We randomized 84 people with physician-confirmed gout in an internet study to cherry extract (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via internet and phone calls. We finalized key study procedures. We assessed acceptability and feasibility of the intervention and satisfaction with study website. Results Study participant satisfaction with the intervention was high. The intervention was perceived as easy, enjoyable, understandable, and helpful (scores 65-88 for all; higher = better). The amount of time spent for the study was acceptable. Participant satisfaction with website interaction and content was very high; 85% or more were moderately to extremely satisfied. Significantly lower total calories, total carbohydrate, and saturated fat intake were noted at 6 months in the diet modification versus cherry extract group; differences were insignificant at 9 months. Six of the 8 Health Assessment Questionnaire sections/domains improved significantly from baseline to 9 months in cherry extract versus 2 Health Assessment Questionnaire sections/domains in the diet modification group. Key study procedures were finalized for a future trial, including an internet diet assessment tool, gout flare assessment, provider confirmation of gout diagnosis, patient reporting of classification criteria, and centralized laboratory-assisted serum urate testing. Conclusions High patient acceptability and feasibility of study/intervention and finalization of key study procedures indicate that hypothesis-testing internet gout trials of cherry extract and/or diet modification can be conducted in the future.

Physical inactivity may be the result of medical comorbidities. Inactivity itself may also lead to important health consequences, especially in older patients. Essential tremor (ET) patients may have a variety of physical and cognitive problems that could detrimentally impact on level of physical activity. Yet, to our knowledge, there have been no studies of physical activity in these patients.Self-reported physical activity was assessed using the Physical Activity Scale for the Elderly (PASE) in 100 ET cases (mean age 80.5years) enrolled in a clinical study. Additional clinical measures were the total tremor score, Montreal Cognitive Assessment (MOCA) score and number of steps taken off of the straight line during tandem gait (a measure of balance).Lower PASE score was associated with older age, more tandem gait difficulty, higher total tremor score and lower MOCA score (all p0.05). In a linear regression model that included total tremor score, MOCA score, number of steps off of the straight line during tandem gait, and age, higher total tremor score (p=0.046) and more steps off of the straight line during tandem gait (p=0.014) were independently associated with reductions in physical activity.Several of the motor features of ET (tremor and imbalance) are independently associated with reductions in level of physical activity.

This retrospective chart review (N = 150) examined weight, height, urinary urea nitrogen, and feeding method in acutely ill adults. Using 2 evidence-based approaches, estimated protein needs were compared with laboratory-measured protein requirements. Comparisons were significantly associated for normal weight patients ( r = 0.21, P = .03) but not for patients who were obese ( r = 0.10, P = .49), showing that the use of body weight and standard formulas to calculate protein needs may not be appropriate for individuals who are obese. Considerations for individual patients should be considered. More research is needed to determine how to accurately estimate protein during acute illness in patients who are obese.

The incidence of osteoporosis and osteoporotic-related fractures continues to increase with the aging population. Early diagnosis of low bone mineral density with dual-energy absorptiometry (DXA) and appropriate treatment can prevent fractures. Accurate DXA imaging and patient education regarding the importance of DXA screening play a critical role in patient management. Recognition of osteoporotic fractures on X-ray at the time of an injury or incidentally during imaging for other indications can lead to early treatment and prevention of future fractures. Radiology nurses and other providers are strategically positioned to impact patient outcomes. An overview of osteoporosis, diagnosis, screening guidelines, and nuances of DXA imaging are provided. Case studies provide the clinician with a summary and application of content.