Combining GWAS and comparative genomics to fine map candidate genes for days to flowering in mung bean.

BACKGROUND: Mung bean (Vigna radiata (L.) Wilczek), is an important pulse crop in the global south. Early flowering and maturation are advantageous traits for adaptation to northern and southern latitudes. This study investigates the genetic basis of the Days-to-Flowering trait (DTF) in mung bean, combining genome-wide association studies (GWAS) in mung bean and comparisons with orthologous genes involved with control of DTF responses in soybean (Glycine max (L) Merr) and Arabidopsis (Arabidopsis thaliana). RESULTS: The most significant associations for DTF were on mung bean chromosomes 1, 2, and 4. Only the SNPs on chromosomes 1 and 4 were heavily investigated using downstream analysis. The chromosome 1 DTF association is tightly linked with a cluster of locally duplicated FERONIA (FER) receptor-like protein kinase genes, and the SNP occurs within one of the FERONIA genes. In Arabidopsis, an orthologous FERONIA gene (AT3G51550), has been reported to regulate the expression of the FLOWERING LOCUS C (FLC). For the chromosome 4 DTF locus, the strongest candidates are Vradi04g00002773 and Vradi04g00002778, orthologous to the Arabidopsis PhyA and PIF3 genes, encoding phytochrome A (a photoreceptor protein sensitive to red to far-red light) and phytochrome-interacting factor 3, respectively. The soybean PhyA orthologs include the classical loci E3 and E4 (genes GmPhyA3, Glyma.19G224200, and GmPhyA2, Glyma.20G090000). The mung bean PhyA ortholog has been previously reported as a candidate for DTF in studies conducted in South Korea. CONCLUSION: The top two identified SNPs accounted for a significant proportion (~ 65%) of the phenotypic variability in mung bean DTF by the six significant SNPs (39.61%), with a broad-sense heritability of 0.93. The strong associations of DTF with genes that have orthologs with analogous functions in soybean and Arabidopsis provide strong circumstantial evidence that these genes are causal for this trait. The three reported loci and candidate genes provide useful targets for marker-assisted breeding in mung beans.

Perceptions and experiences of living with and providing care for multimorbidity: A qualitative interview study.

Background: Experiences of living with and seeking care for multimorbidity is a relatively under-researched field. By analysing experiences of people with multimorbidity, caregivers and care professionals, we can better understand the complex care needs of those with multimorbidity and identify improvements to care management. This paper reports findings from research that elicited the views of key stakeholders to inform future care practice and policy. Aim: To elicit care recipient and care provider views to understand the care needs of those living with and seeking care for multimorbidity. Method: A qualitative interview study using purposive sampling of those living with and providing care in multimorbidity. Results: Increased support to those with multimorbidity and caregivers to navigate care systems was advocated. Establishing trusting care relationships featured prominently in participants accounts. Fragmented care, inadequate coordination and poor communication between care providers, were identified as system-wide challenges. There was agreement that integrated care models were needed, which delivered personalised care, such as shared decision-making, choice in care options and accessing services, and individualised care plans. Conclusion: We found significant agreement among stakeholders on care need and management in multimorbidity. Understanding the experiences of those with multimorbidity, caregivers and care professionals, can inform future improvements in care management.

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection.

Virus-neutralizing antibodies are often accepted as a correlate of protection against infection, though questions remain about which components of the immune response protect against SARS-CoV-2 infection. In this small observational study, we longitudinally measured spike receptor binding domain (RBD)-specific and nucleocapsid (NP)-specific serum IgG in a human cohort immunized with the Pfizer BNT162b2 vaccine. NP is not encoded in the vaccine, so an NP-specific response is serological evidence of natural infection. A greater than fourfold increase in NP-specific antibodies was used as the serological marker of infection. Using the RBD-specific IgG titers prior to seroconversion for NP, we calculated a protective threshold for RBD-specific IgG. On average, the RBD-specific IgG response wanes below the protective threshold 169 days following vaccination. Many participants without a history of a positive test result for SARS-CoV-2 infection seroconverted for NP-specific IgG. As a group, participants who seroconverted for NP-specific IgG had significantly higher levels of RBD-specific IgG following NP-seroconversion. RBD-specific IgG titers may serve as one correlate of protection against SARS-CoV-2 infection. These titers wane below the proposed protective threshold approximately six months following immunization. Based on serological evidence of infection, the frequency of breakthrough infections and consequently the level of SARS-CoV-2-specific immunity in the population may be higher than what is predicted based on the frequency of documented infections.

Multiple long-term conditions, loneliness and social isolation: A scoping review of recent quantitative studies.

BACKGROUND: Multiple long-term conditions (MLTC), loneliness and social isolation are common in older adults. Recent studies have explored the association of MLTC with loneliness and social isolation. This scoping review aimed to map this current evidence and identify gaps in the literature. METHODS: A scoping review was conducted following the PRISMA guidelines for scoping reviews. Ovid Medline, Embase, CINAHL, The Cochrane Library, PsycInfo, and Bielefeld Academic Search Engine were searched for studies published between January 2020-April 2023. Quantitative studies, published in any language, that assessed the association of MLTC with loneliness and/or social isolation were included. RESULTS: 1827 records were identified and screened. Of these, 17 met inclusion criteria. Most studies were cross-sectional and based on older adults. Studies were conducted in Europe, the US, Canada, and low- and middle-income countries. Ten studies focused on the association between MLTC and loneliness, six assessed the association between MLTC and social isolation and one examined associations with both loneliness and social isolation. Most studies reported a significant cross-sectional association of MLTC with loneliness, but there was weaker evidence for a longitudinal association between MLTC and loneliness and an association between MLTC and social isolation. Studies were heterogenous in terms of measures and definitions of loneliness/social isolation and MLTC, confounders adjusted for, and analytical models used, making comparisons difficult. CONCLUSIONS: Further population-based longitudinal studies using consistent measures and methodological approaches are needed to improve understanding of the association of MLTC with both loneliness and social isolation.

Genome assembly of Medicago truncatula accession SA27063 provides insight into spring black stem and leaf spot disease resistance.

Medicago truncatula, model legume and alfalfa relative, has served as an essential resource for advancing our understanding of legume physiology, functional genetics, and crop improvement traits. Necrotrophic fungus, Ascochyta medicaginicola, the causal agent of spring black stem (SBS) and leaf spot is a devasting foliar disease of alfalfa affecting stand survival, yield, and forage quality. Host resistance to SBS disease is poorly understood, and control methods rely on cultural practices. Resistance has been observed in M. truncatula accession SA27063 (HM078) with two recessively inherited quantitative-trait loci (QTL), rnpm1 and rnpm2, previously reported. To shed light on host resistance, we carried out a de novo genome assembly of HM078. The genome, referred to as MtHM078 v1.0, is comprised of 23 contigs totaling 481.19 Mbp. Notably, this assembly contains a substantial amount of novel centromere-related repeat sequences due to deep long-read sequencing. Genome annotation resulted in 98.4% of BUSCO fabales proteins being complete. The assembly enabled sequence-level analysis of rnpm1 and rnpm2 for gene content, synteny, and structural variation between SBS-resistant accession SA27063 (HM078) and SBS-susceptible accession A17 (HM101). Fourteen candidate genes were identified, and some have been implicated in resistance to necrotrophic fungi. Especially interesting candidates include loss-of-function events in HM078 because they fit the inverse gene-for-gene model, where resistance is recessively inherited. In rnpm1, these include a loss-of-function in a disease resistance gene due to a premature stop codon, and a 10.85 kbp retrotransposon-like insertion disrupting a ubiquitin conjugating E2. In rnpm2, we identified a frameshift mutation causing a loss-of-function in a glycosidase, as well as a missense and frameshift mutation altering an F-box family protein. This study generated a high-quality genome of HM078 and has identified promising candidates, that once validated, could be further studied in alfalfa to enhance disease resistance.

Supporting people with type 2 diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D pilot): results of a feasibility randomised trial.

BACKGROUND: The purpose of this 6-month intervention pilot feasibility randomised trial was to test sending brief messages using mobile phones to promote self-management through taking medication as prescribed to people with type 2 diabetes. This was to inform the design and conduct of a future large-scale United Kingdom-based clinical trial and establish the feasibility of recruitment, the technology used, follow-up, and data collection. METHODS: A multicentre individually randomised, controlled parallel group trial in primary care, recruiting adults (≥ 35 years) with type 2 diabetes in England. Consenting participants were randomly allocated to receive short message system text messages up to four times a week, or usual care, for a period of 6 months; messages contained behavioural change techniques targeting medication use. The primary outcome was the rate of recruitment to randomisation of participants to the trial with a planned rate of 22 participants randomised per month. The study also aimed to establish the feasibility of follow-up at 6 months, with an aim of retaining more than 80% of participants. Data, including patient-reported measures, were collected at baseline and the end of the 6-month follow-up period, and a notes review was completed at 24 months. RESULTS: The trial took place between 26 November 2018 and 30 September 2019. In total 209 participants were randomly allocated to intervention (n = 103) or usual care (n = 106). The maximum rate of monthly recruitment to the trial was 60-80 participants per month. In total, 12,734 messages were sent to participants. Of these messages, 47 were identified as having failed to be sent by the service provider. Participants sent 2,864 messages to the automated messaging system. Baseline data from medical records were available for > 90% of participants with the exception of cholesterol (78.9%). At 6 months, a further HbA1c measurement was reported for 67% of participants. In total medical record data were available at 6 months for 207 (99.0%) of participants and completed self-report data were available for 177 (84.7%) of participants. CONCLUSION: The feasibility of a large-scale randomised evaluation of brief message intervention for people with type 2 diabetes appears to be high using this efficient design. Failure rate of sending messages is low, rapid recruitment was achieved among people with type 2 diabetes, clinical data is available on participants from routine medical records and self-report of economic measures was acceptable. TRIAL REGISTRATION: ISCTRN ISRCTN13404264. Registered on 10 October 2018.

A view of the pan-genome of domesticated Cowpea (Vigna unguiculata [L.] Walp.).

Cowpea, Vigna unguiculata L. Walp., is a diploid warm-season legume of critical importance as both food and fodder in sub-Saharan Africa. This species is also grown in Northern Africa, Europe, Latin America, North America, and East to Southeast Asia. To capture the genomic diversity of domesticates of this important legume, de novo genome assemblies were produced for representatives of six subpopulations of cultivated cowpea identified previously from genotyping of several hundred diverse accessions. In the most complete assembly (IT97K-499-35), 26,026 core and 4963 noncore genes were identified, with 35,436 pan genes when considering all seven accessions. GO terms associated with response to stress and defense response were highly enriched among the noncore genes, while core genes were enriched in terms related to transcription factor activity, and transport and metabolic processes. Over 5 million single nucleotide polymorphisms (SNPs) relative to each assembly and over 40 structural variants >1 Mb in size were identified by comparing genomes. Vu10 was the chromosome with the highest frequency of SNPs, and Vu04 had the most structural variants. Noncore genes harbor a larger proportion of potentially disruptive variants than core genes, including missense, stop gain, and frameshift mutations; this suggests that noncore genes substantially contribute to diversity within domesticated cowpea.

The association between stress and multiple long-term conditions: A cohort study.

BACKGROUND: Stress is an important predictor of long-term conditions. We examine whether hair cortisol (a biomarker of stress) is associated with incidence and accumulation of multiple long-term conditions (MLTC). METHODS: We included data from 4295 individuals aged ≥50 years within the English Longitudinal Study of Ageing dataset with data on hair cortisol, sociodemographic and health behaviour variables. Cox proportional hazards models were used to quantify the association between hair cortisol at baseline and accumulation of MLTC between 2012/2013 and 2018/2019, both for individuals with and without MLTC at baseline. RESULTS: Our cohort included 1458 (34.0%) individuals who accumulated MLTC between 2012/2013 and 2018/2019. The proportion of individuals with zero, 1, and ≥ 2 conditions at baseline who accumulated MLTC were 12.0% (n = 127), 40.4% (n = 520), and 41.7% (n = 811), respectively. Higher cortisol levels were associated with higher risk of accumulation of MLTC in both unadjusted [HR:1.15(1.05-1.25)] and models adjusted for sociodemographic and health behaviours [HR:1.12(1.02-1.22)]. For individuals without MLTC at baseline, higher cortisol levels were significantly associated with higher risk of developing MLTC in unadjusted [HR: 1.20(1.05-1.36)] and adjusted models [HR: 1.16(1.02-1.32)]. CONCLUSION: The study provides the first evidence of the role of stress in the development and accumulation of MLTC. This modifiable risk factor could be targeted to reduce the risk of MLTC. However, further work is needed to better understand the mechanisms and pathways that link stress and accumulation of MLTC.

Factors associated with multimorbidity in England: an analysis of the English Longitudinal Study of Ageing.

BACKGROUND: Multimorbidity, defined as the presence of two or more long-term conditions, is a growing public health challenge, especially in terms of prevention and accumulation of long-term conditions among particular population cohorts. To date, efforts to understand multimorbidity has focused mainly on specific disease combinations, with little known about the sociodemographic factors associated with it. The study aimed to assess the factors associated with multimorbidity in England. METHODS: A cross-sectional study was conducted using the English Longitudinal Study of Ageing (ELSA), a dataset of people aged 50 years and older. The study identified ten long-term conditions from waves 2 to 9. Wave 2 to 9 were conducted between June 2004 to July 2005, May 2006 to August 2007, May 2008 to July 2009, June 2010 to July 2011, May 2012 to June 2013, June 2014 to May 2015, May 2016 to June 2017 and June 2018 to July 2019, respectively. The study included people with two or more long-term conditions. We identified the number of long-term conditions and multimorbidity, and we examined their association with age, gender, ethnicity, marital status, employment status, education, weekly contact with relative, and feeling lonely, sad or depressed using multinomial logistic regression. FINDINGS: Of 16 731 people recruited from wave 2 to wave 9, we identified 10 026 people with multimorbidity aged 50 years and older. The majority had two conditions (39%) and were female (55%), aged 50-69 years (32%), of white ethnicity (96%), married (69%) and unemployed (65·3%). The adjusted odds ratio (aOR) of having more than two long-term conditions increased with age, after adjusting for sex and ethnicity (≥5 conditions: aOR 12·89, 95% CI 2·23-3·76). Being female was associated with an increased risk of having more than two long-term conditions (≥5 conditions: aOR 1·21, 1·04-1·42). Similarly, being separated, divorced, or widowed were associated with having more than two long-term conditions (≥5 conditions: aOR 1·45, 1·21-1·74). Not owning a home was independently associated with more than two long-term conditions (≥5 conditions: aOR 1·59, 1·35-1·88). INTERPRETATION: The current analysis used only ten long-term conditions that were available in the ELSA data, so a different association might have arisen if other conditions had been considered. Our findings provide insights into which particular groups of the multimorbid population could be the target of preventive public health strategies and wider clinical and social care interventions in England to reduce the burden of multimorbidity. FUNDING: National Institute for Health and Care Research (NIHR).

Data sharing and ontology use among agricultural genetics, genomics, and breeding databases and resources of the Agbiodata Consortium.

Over the last couple of decades, there has been a rapid growth in the number and scope of agricultural genetics, genomics and breeding databases and resources. The AgBioData Consortium (https://www.agbiodata.org/) currently represents 44 databases and resources (https://www.agbiodata.org/databases) covering model or crop plant and animal GGB data, ontologies, pathways, genetic variation and breeding platforms (referred to as 'databases' throughout). One of the goals of the Consortium is to facilitate FAIR (Findable, Accessible, Interoperable, and Reusable) data management and the integration of datasets which requires data sharing, along with structured vocabularies and/or ontologies. Two AgBioData working groups, focused on Data Sharing and Ontologies, respectively, conducted a Consortium-wide survey to assess the current status and future needs of the members in those areas. A total of 33 researchers responded to the survey, representing 37 databases. Results suggest that data-sharing practices by AgBioData databases are in a fairly healthy state, but it is not clear whether this is true for all metadata and data types across all databases; and that, ontology use has not substantially changed since a similar survey was conducted in 2017. Based on our evaluation of the survey results, we recommend (i) providing training for database personnel in a specific data-sharing techniques, as well as in ontology use; (ii) further study on what metadata is shared, and how well it is shared among databases; (iii) promoting an understanding of data sharing and ontologies in the stakeholder community; (iv) improving data sharing and ontologies for specific phenotypic data types and formats; and (v) lowering specific barriers to data sharing and ontology use, by identifying sustainability solutions, and the identification, promotion, or development of data standards. Combined, these improvements are likely to help AgBioData databases increase development efforts towards improved ontology use, and data sharing via programmatic means. Database URL  https://www.agbiodata.org/databases.

Eliciting and prioritising determinants of improved care in multimorbidity: A modified online Delphi study.

Background: Multimorbidity is a major challenge to health and social care systems around the world. There is limited research exploring the wider contextual determinants that are important to improving care for this cohort. In this study, we aimed to elicit and prioritise determinants of improved care in people with multiple conditions. Methods: A three-round online Delphi study was conducted in England with health and social care professionals, data scientists, researchers, people living with multimorbidity and their carers. Results: Our findings suggest a care system which is still predominantly single condition focused. 'Person-centred and holistic care' and 'coordinated and joined up care', were highly rated determinants in relation to improved care for multimorbidity. We further identified a range of non-medical determinants that are important to providing holistic care for this cohort. Conclusions: Further progress towards a holistic and patient-centred model is needed to ensure that care more effectively addresses the complex range of medical and non-medical needs of people living with multimorbidity. This requires a move from a single condition focused biomedical model to a person-based biopsychosocial approach, which has yet to be achieved.

Assay-agnostic spatial profiling detects tumor microenvironment signatures: new diagnostic insights for triple-negative breast cancer.

The role of the tumor microenvironment (TME) in immuno-oncology has driven demand for technologies that deliver in situ, or spatial, molecular information. Compartmentalized heterogeneity that traditional methods miss is becoming key to predicting both acquired drug resistance to targeted therapies and patient response to immunotherapy. Here, we describe a novel method for assay-agnostic spatial profiling and demonstrate its ability to detect immune microenvironment signatures in breast cancer patients that are unresolved by the immunohistochemical (IHC) assessment of programmed cell death ligand-1 (PD-L1) on immune cells, which represents the only FDA microenvironment-based companion diagnostic test that has been approved for triple-negative breast cancer (TNBC). Two distinct physiological states were found that are uncorrelated to tumor mutational burden (TMB), microsatellite instability (MSI), PD-L1 expression, and intrinsic cancer subtypes.

Clustering by multiple long-term conditions and social care needs: a cross-sectional study among 10 026 older adults in England.

BACKGROUND   : People with multiple long-term conditions (MLTC) face health and social care challenges. This study aimed to classify people by MLTC and social care needs (SCN) into distinct clusters and quantify the association between derived clusters and care outcomes. METHODS : A cross-sectional study was conducted using the English Longitudinal Study of Ageing, including people with up to 10 MLTC. Self-reported SCN was assessed through 13 measures of difficulty with activities of daily living, 10 measures of mobility difficulties and whether health status was limiting earning capability. Latent class analysis was performed to identify clusters. Multivariable logistic regression quantified associations between derived MLTC/SCN clusters, all-cause mortality and nursing home admission. RESULTS: Our study included 9171 people at baseline with a mean age of 66.3 years; 44.5% were men. Nearly 70.8% had two or more MLTC, the most frequent being hypertension, arthritis and cardiovascular disease. We identified five distinct clusters classified as high SCN/MLTC through to low SCN/MLTC clusters. The high SCN/MLTC included mainly women aged 70-79 years who were white and educated to the upper secondary level. This cluster was significantly associated with higher nursing home admission (OR=8.71; 95% CI: 4.22 to 18). We found no association between clusters and all-cause mortality. CONCLUSIONS: We have highlighted those at risk of worse care outcomes, including nursing home admission. Distinct clusters of individuals with shared sociodemographic characteristics can help identify at-risk individuals with MLTC and SCN at primary care level.

Type 2 diabetes remission trajectories and variation in risk of diabetes complications: A population-based cohort study.

Biochemical remission of type 2 diabetes is achievable through dietary changes, physical activity and subsequent weight loss. We aim to identify distinct diabetes remission trajectories in a large population-based cohort over seven-years follow-up and to examine associations between remission trajectories and diabetes complications. Group-based trajectory modelling examined longitudinal patterns of HbA1c level (adjusting for remission status) over time. Multivariable Cox models quantified the association between each remission trajectory and microvascular complications, macrovascular complications, cardiovascular (CVD) events and all-cause mortality. Four groups were assigned. Group 1 (8,112 [13.5%]; achieving HbA1c <48 mmol/mol (6.5%) followed by increasing HbA1c levels); Group 2 (6,369 [10.6%]; decreasing HbA1c levels >48 mmol/mol (6.5%)); Group 3 (36,557 [60.6%]; stable high HbA1c levels); Group 4 (9,249 [15.3%]; stable low HbA1c levels (<48mmol/mol or <6.5%)). Compared to Group 3, Groups 1 and 4 had lower risk of microvascular complications (aHRs (95% CI): 0.65 (0.61-0.70), p-value <0.001;0.59 (0.55-0.64) p-value<0.001, respectively)), macrovascular complications (aHRs (95% CI): 0.83 (0.75-0.92), p-value<0.001; 0.66 (0.61-0.71), p-value<0.001) and CVD events (aHRs (95% CI): 0.74(0.67-0.83), p-value<0.001; 0.67(0.61-0.73), p-vlaue<0.001). Risk of CVD outcomes were similar for Groups 2 and 3. Compared to Group 3, Group 1 (aHR: 0.82(95% CI: 0.76-0.89)) had lower risk of mortality, but Group 4 had higher risk of mortality (aHR: 1.11(95% CI: 1.03-1.19)). Risk of CVD outcomes vary by pattern of remission over time, with lowest risk for those in remission longer. People who achieve remission, even for shorter periods of time, continue to benefit from this lower exposure to hyperglycaemia, which may, in turn, lower the risk of CVD outcomes including mortality.

Trajectories of multiple long-term conditions and mortality in older adults: A retrospective cohort study using English Longitudinal Study of Ageing (ELSA).

Objectives: To classify older adults with MLTC into clusters based on accumulating conditions as trajectories over time, characterise clusters and quantify associations between derived clusters and all-cause mortality. Design: We conducted a retrospective cohort study using the English Longitudinal Study of Ageing (ELSA) over nine years (n=15,091 aged 50 years and older). Group-based trajectory modelling was used to classify people into MLTC clusters based on accumulating conditions over time. Derived clusters were used to quantify the associations between MLTC trajectory memberships, sociodemographic characteristics, and all-cause mortality. Results: Five distinct clusters of MLTC trajectories were identified and characterised as: "no-LTC" (18.57%), "single-LTC" (31.21%), "evolving MLTC" (25.82%), "moderate MLTC" (17.12%), and "high MLTC" (7.27%). Increasing age was consistently associated with an increased number of MLTC. Female sex (aOR = 1.13; 95%CI 1.01 to 1.27) and ethnic minority (aOR = 2.04; 95%CI 1.40 to 3.00) were associated with the "moderate MLTC" and "high MLTC" clusters, respectively. Higher education and paid employment were associated with a lower likelihood of progression over time towards an increased number of MLTC. All the clusters had higher all-cause mortality than the "no-LTC" cluster. Conclusions: The development of MLTC and the increase in the number of conditions over time follow distinct trajectories. These are determined by non-modifiable (age, sex, ethnicity) and modifiable factors (education and employment). Stratifying risk through clustering will enable practitioners to identify older adults with a higher likelihood of worsening MLTC over time to tailor effective interventions.

Implementing a text message-based intervention to support type 2 diabetes medication adherence in primary care: a qualitative study with general practice staff.

BACKGROUND: The Support through Mobile Messaging and digital health Technology for Diabetes (SuMMiT-D) project has developed, and is evaluating, a mobile phone-based intervention delivering brief messages targeting identified behaviour change techniques promoting medication use to people with type 2 diabetes in general practice. The present study aimed to inform refinement and future implementation of the SuMMiT-D intervention by investigating general practice staff perceptions of how a text message-based intervention to support medication adherence should be implemented within current and future diabetes care. METHODS: Seven focus groups and five interviews were conducted with 46 general practice staff (including GPs, nurses, healthcare assistants, receptionists and linked pharmacists) with a potential role in the implementation of a text message-based intervention for people with type 2 diabetes. Interviews and focus groups were audio-recorded, transcribed and analysed using an inductive thematic analysis approach. RESULTS: Five themes were developed. One theme 'The potential of technology as a patient ally' described a need for diabetes support and the potential of technology to support medication use. Two themes outlined challenges to implementation, 'Limited resources and assigning responsibility' and 'Treating the patient; more than diabetes medication adherence'. The final two themes described recommendations to support implementation, 'Selling the intervention: what do general practice staff need to see?' and 'Fitting the mould; complementing current service delivery'. CONCLUSIONS: Staff see the potential for a text message-based support intervention to address unmet needs and to enhance care for people with diabetes. Digital interventions, such as SuMMiT-D, need to be compatible with existing systems, demonstrate measurable benefits, be incentivised and be quick and easy for staff to engage with. Interventions also need to be perceived to address general practice priorities, such as taking a holistic approach to care and having multi-cultural reach and relevance. Findings from this study are being combined with parallel work with people with type 2 diabetes to ensure stakeholder views inform further refinement and implementation of the SuMMiT-D intervention.

Hiding in plain sight: Genome-wide recombination and a dynamic accessory genome drive diversity in Fusarium oxysporum f.sp. ciceris.

Understanding the origins of variation in agricultural pathogens is of fundamental interest and practical importance, especially for diseases that threaten food security. Fusarium oxysporum is among the most important of soil-borne pathogens, with a global distribution and an extensive host range. The pathogen is considered to be asexual, with horizontal transfer of chromosomes providing an analog of assortment by meiotic recombination. Here, we challenge those assumptions based on the results of population genomic analyses, describing the pathogen's diversity and inferring its origins and functional consequences in the context of a single, long-standing agricultural system. We identify simultaneously low nucleotide distance among strains, and unexpectedly high levels of genetic and genomic variability. We determine that these features arise from a combination of genome-scale recombination, best explained by widespread sexual reproduction, and presence-absence variation consistent with chromosomal rearrangement. Pangenome analyses document an accessory genome more than twice the size of the core genome, with contrasting evolutionary dynamics. The core genome is stable, with low diversity and high genetic differentiation across geographic space, while the accessory genome is paradoxically more diverse and unstable but with lower genetic differentiation and hallmarks of contemporary gene flow at local scales. We suggest a model in which episodic sexual reproduction generates haplotypes that are selected and then maintained through clone-like dynamics, followed by contemporary genomic rearrangements that reassort the accessory genome among sympatric strains. Taken together, these processes contribute unique genome content, including reassortment of virulence determinants that may explain observed variation in pathogenic potential.

Genome Context Viewer (GCV) version 2: enhanced visual exploration of multiple annotated genomes.

The Genome Context Viewer is a web application for identifying, aligning, and visualizing genomic regions based on their micro and macrosyntenic structures. By using functional elements such as gene annotations as the unit of search and comparison, the Genome Context Viewer can compute and display relationships between regions across many assemblies from federated data sources in real-time, enabling users to rapidly explore multiple annotated genomes and identify divergence and structural events that can help provide insight into evolutionary mechanisms associated with functional consequences. In this work, we introduce version 2 of the Genome Context Viewer and highlight new features that enhance usability, performance, and ease of deployment.

Major proliferation of transposable elements shaped the genome of the soybean rust pathogen Phakopsora pachyrhizi.

With >7000 species the order of rust fungi has a disproportionately large impact on agriculture, horticulture, forestry and foreign ecosystems. The infectious spores are typically dikaryotic, a feature unique to fungi in which two haploid nuclei reside in the same cell. A key example is Phakopsora pachyrhizi, the causal agent of Asian soybean rust disease, one of the world's most economically damaging agricultural diseases. Despite P. pachyrhizi's impact, the exceptional size and complexity of its genome prevented generation of an accurate genome assembly. Here, we sequence three independent P. pachyrhizi genomes and uncover a genome up to 1.25 Gb comprising two haplotypes with a transposable element (TE) content of ~93%. We study the incursion and dominant impact of these TEs on the genome and show how they have a key impact on various processes such as host range adaptation, stress responses and genetic plasticity.