Seed color patterns in domesticated common bean are regulated by MYB-bHLH-WD40 transcription factors and temperature.

Seed colors and color patterns are critical for the survival of wild plants and the consumer appeal of crops. In common bean, a major global staple, these patterns are also essential in determining market classes, yet the genetic and environmental control of many pigmentation patterns remains unresolved. In this study, we genetically mapped variation for several important seed pattern loci, including T, Bip, phbw, and Z, which co-segregated with candidate genes PvTTG1, PvMYC1, PvTT8, and PvTT2, respectively. Proteins encoded by these genes are predicted to work together in MYB-bHLH-WD40 (MBW) complexes, propagating flavonoid biosynthesis across the seed coat as observed in Arabidopsis. Whole-genome sequencing of 37 accessions identified mutations, including seven unique parallel mutations in T (PvTTG1) and non-synonymous SNPs in highly conserved residues in bipana (PvMYC1) and z (PvTT2). A 612 bp intron deletion in phbw (PvTT8) eliminated motifs conserved since the Papilionoideae origin and corresponded to a 20-fold reduction in transcript abundance. In multi-location field trials of seven varieties with partial seed coat pigmentation patterning, the pigmented seed coat area correlated positively with ambient temperature, with up to 11-fold increases in the pigmented area from the coolest to the warmest environments. In controlled growth chamber conditions, an increase of 4°C was sufficient to cause pigmentation on an average additional 21% of the seed coat area. Our results shed light on key steps of flavonoid biosynthesis in common bean. They will inform breeding efforts for seed coat color/patterning to improve consumer appeal in this nutritious staple crop.

Trajectories in long-term condition accumulation and mortality in older adults: a group-based trajectory modelling approach using the English Longitudinal Study of Ageing.

OBJECTIVES: To classify older adults into clusters based on accumulating long-term conditions (LTC) as trajectories, characterise clusters and quantify their associations with all-cause mortality. DESIGN: We conducted a longitudinal study using the English Longitudinal Study of Ageing over 9 years (n=15 091 aged 50 years and older). Group-based trajectory modelling was used to classify people into clusters based on accumulating LTC over time. Derived clusters were used to quantify the associations between trajectory memberships, sociodemographic characteristics and all-cause mortality by conducting regression models. RESULTS: Five distinct clusters of accumulating LTC trajectories were identified and characterised as: 'no LTC' (18.57%), 'single LTC' (31.21%), 'evolving multimorbidity' (25.82%), 'moderate multimorbidity' (17.12%) and 'high multimorbidity' (7.27%). Increasing age was consistently associated with a larger number of LTCs. Ethnic minorities (adjusted OR=2.04; 95% CI 1.40 to 3.00) were associated with the 'high multimorbidity' cluster. Higher education and paid employment were associated with a lower likelihood of progression over time towards an increased number of LTCs. All the clusters had higher all-cause mortality than the 'no LTC' cluster. CONCLUSIONS: The development of multimorbidity in the number of conditions over time follows distinct trajectories. These are determined by non-modifiable (age, ethnicity) and modifiable factors (education and employment). Stratifying risk through clustering will enable practitioners to identify older adults with a higher likelihood of worsening LTC over time to tailor effective interventions to prevent mortality.

Clustering by health and social care need in multple long-term conditions (MLTC): an exploratory qualitative study to understand the views of professionals and people living with MLTC about future interventions.

BACKGROUND: Around one in four people are living with multiple long-term conditions (MLTC). Integrated care to holistically manage both health and social needs could improve outcomes for people living with MLTC, including lower rates of hospitalisation and mortality. However, given the number of people with MLTC and increasing strain on health and social care, stratified approaches to identifying and addressing social care needs may be more efficient and cost-effective. We have developed data driven clusters that group people with similar health and social care needs, which could identify patients at the highest risk of poor outcomes related to social care need. AIM: To explore views about a future intervention based on these clusters. METHOD: We aim to plan a cluster-based intervention that engages people living with MLTC and health and social care professionals to consider social care needs (SCNs) when consulting in primary care. We have conducted 14 interviews with professionals to explore their priorities and concerns about care delivery by MLTC clusters and 19 remote interviews with people living with MLTC to find out how well they identify with the MLTC clusters we have defined. Data were analysed using reflexive thematic analysis. RESULTS: GPs are the 'starting point' for conversations about SCNs but need an efficient system to enable effective conversations. The cluster-based intervention could fill this gap. CONCLUSION: This research identifies key considerations needed for an intervention to engage people with MLTC and health and social care professionals to consider SCNs in primary care.

Remote Vital Sign Monitoring in Admission Avoidance Hospital at Home: A Systematic Review.

OBJECTIVES: To examine randomized controlled trials (RCTs) of "hospital at home" (HAH) for admission avoidance in adults presenting with acute physical illness to identify the use of vital sign monitoring approaches and evidence for their effectiveness. DESIGN: Systematic review. SETTING AND PARTICIPANTS: This review compared strategies for vital sign monitoring in admission avoidance HAH for adults presenting with acute physical illness. Vital sign monitoring can support HAH acute multidisciplinary care by contributing to safety, determining requirement of further assessment, and guiding clinical decisions. There are a wide range of systems currently available, including reliable and automated continuous remote monitoring using wearable devices. METHODS: Eligible studies were identified through updated database and trial registries searches (March 2, 2016, to February 15, 2023), and existing systematic reviews. Risk of bias was assessed using the Cochrane risk of bias 2 tool. Random effects meta-analyses were performed, and narrative summaries provided stratified by vital sign monitoring approach. RESULTS: Twenty-one eligible RCTs (3459 participants) were identified. Two approaches to vital sign monitoring were characterized: manual and automated. Reporting was insufficient in the majority of studies for classification. For HAH compared to hospital care, 6-monthly mortality risk ratio (RR) was 0.94 (95% CI 0.78-1.12), 3-monthly readmission to hospital RR 1.02 (0.77-1.35), and length of stay mean difference 1.91 days (0.71-3.12). Readmission to hospital was reduced in the automated monitoring subgroup (RR 0.30 95% CI 0.11-0.86). CONCLUSIONS AND IMPLICATIONS: This review highlights gaps in the reporting and evidence base informing remote vital sign monitoring in alternatives to admission for acute illness, despite expanding implementation in clinical practice. Although continuous vital sign monitoring using wearable devices may offer added benefit, its use in existing RCTs is limited. Recommendations for the implementation and evaluation of remote monitoring in future clinical trials are proposed.

Single-cell transcriptome atlases of soybean root and mature nodule reveal new regulatory programs that control the nodulation process.

The soybean root system is complex. In addition to being composed of various cell types, the soybean root system includes the primary root, the lateral roots, and the nodule, an organ in which mutualistic symbiosis with N-fixing rhizobia occurs. A mature soybean root nodule is characterized by a central infection zone where atmospheric nitrogen is fixed and assimilated by the symbiont, resulting from the close cooperation between the plant cell and the bacteria. To date, the transcriptome of individual cells isolated from developing soybean nodules has been established, but the transcriptomic signatures of cells from the mature soybean nodule have not yet been characterized. Using single-nucleus RNA-seq and Molecular Cartography technologies, we precisely characterized the transcriptomic signature of soybean root and mature nodule cell types and revealed the co-existence of different sub-populations of B. diazoefficiens-infected cells in the mature soybean nodule, including those actively involved in nitrogen fixation and those engaged in senescence. Mining of the single-cell-resolution nodule transcriptome atlas and the associated gene co-expression network confirmed the role of known nodulation-related genes and identified new genes that control the nodulation process. For instance, we functionally characterized the role of GmFWL3, a plasma membrane microdomain-associated protein that controls rhizobial infection. Our study reveals the unique cellular complexity of the mature soybean nodule and helps redefine the concept of cell types when considering the infection zone of the soybean nodule.

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.

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.

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.

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.

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.

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.