Core Set Research Articles

A DIGITAL LIFE STORY BOOK ACTIVITY FOR OLDER ADULTS WITH MEMORY DIFFICULTIES: PROGRAM EVALUATION

Abstract Reminiscence activities are based on maintaining a core set of personal memories to aid self-continuity (Woods, 2012). Some interventions find limited effects (Charlesworth et al, 2016) but with participants reporting high satisfaction with the program. The aims of the current study were to: (i) demonstrate feasibility of intervention delivery to older individuals with memory difficulties, and (ii) provide analyses of program efficacy using a pre-posttest, control group design. Participants (N = 45; Mage = 76.12) were randomized to the Life Story Book intervention or Waitlist Control. A Life Story Book Interview was developed, using five evidence-based principles of autobiographical memory. Personalized multimedia books were created and reviewed by participants for fourteen days. To assess feasibility, participants in the intervention completed a memory quality questionnaire and feedback survey. Those who reviewed Life Story Books reported improved memory quality pre-post intervention, t(22) = -2.39, p = .026. Participants also positively rated their intervention experience at post-test, (M = 4.46/5). All participants completed self-related questionnaires (e.g., self-continuity, self-esteem) at pretest-posttest. No measure showed significant effects. Our results represent a conundrum for researchers. We provide evidence of feasibility of, and participant enthusiasm for, this reminiscence-based intervention. As seen in the literature, however, (Elfrink et al., 2021), sensitivity to detect pretest-postest change remains a challenge. The current study highlights participants positive reactions to reminiscence-based Life Story Books. Findings are discussed in terms of methods for assessing intervention efficacy in individuals with memory decline.

Sequencing-based protein–protein interaction analysis provides a core set of immune gene for understanding white body immune response mechanisms against Poly I:C stimulation in Amphioctopus fangsiao

Pathogenic infections significantly limit the culture of marine organisms, such as cephalopods. However, there is a lack of immune information regarding cephalopods to address pathogen problems. Polyriboinosinic polyribocytidylic acid (Poly I:C), a synthetic virus-like molecule, can be recognized by the immune cells as pathogen-associated molecular patterns (PAMPs), and this process is often used to simulate the invasion of viruses. The white body is an immune and hematopoietic organ, and its RNA-seq information obtained from Amphioctopus fangsiao stimulated by Poly I:C is essential for understanding the antiviral immune response in this species. In this research, we performed transcriptome sequencing and bioinformatics analysis of A. fangsiao white body tissue within 24 h stimulated by Poly I:C. A large number of differentially expressed genes (DEGs) were detected in this study, including 2,613 and 8 DEGs at 6 h and 24 h, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used for searching immune-related terms and genes. A protein–protein interaction (PPI) network was constructed to identify the relationship between immune genes. Finally, the 20 hub genes including RAC1, MAPK14, PIK3CA and other seventeen hub genes were identified based on the network and pathway analyses, and we validated the accuracy of 20 hub genes using qRT-PCR. These hub genes mainly participated in PI3K-Akt signaling pathway, Chemokine signaling pathway and other signaling pathways, in addition to the ubiquitin family. These research results provided a valuable theoretical basis for researching A. fangsiao white body immunity and significantly improved our cognition about innate immunity of cephalopods.

Automating methods for estimating metabolite volatility.

The volatility of metabolites can influence their biological roles and inform optimal methods for their detection. Yet, volatility information is not readily available for the large number of described metabolites, limiting the exploration of volatility as a fundamental trait of metabolites. Here, we adapted methods to estimate vapor pressure from the functional group composition of individual molecules (SIMPOL.1) to predict the gas-phase partitioning of compounds in different environments. We implemented these methods in a new open pipeline called volcalc that uses chemoinformatic tools to automate these volatility estimates for all metabolites in an extensive and continuously updated pathway database: the Kyoto Encyclopedia of Genes and Genomes (KEGG) that connects metabolites, organisms, and reactions. We first benchmark the automated pipeline against a manually curated data set and show that the same category of volatility (e.g., nonvolatile, low, moderate, high) is predicted for 93% of compounds. We then demonstrate how volcalc might be used to generate and test hypotheses about the role of volatility in biological systems and organisms. Specifically, we estimate that 3.4 and 26.6% of compounds in KEGG have high volatility depending on the environment (soil vs. clean atmosphere, respectively) and that a core set of volatiles is shared among all domains of life (30%) with the largest proportion of kingdom-specific volatiles identified in bacteria. With volcalc, we lay a foundation for uncovering the role of the volatilome using an approach that is easily integrated with other bioinformatic pipelines and can be continually refined to consider additional dimensions to volatility. The volcalc package is an accessible tool to help design and test hypotheses on volatile metabolites and their unique roles in biological systems.

Traits associated with intermittent drought tolerance in sesameIndian core set genotypes

A field experiment was conducted to investigate the effect of deficit moisture stress on eleven sesame genotypes IC-132171, IC-132186, IC-204445, IC-131500, IC-132207, IC-205471, IC-203962, IC-205353, IC96229, IC-204966 included with a national check (GT-10). The precise deficit moisture stress (WS) was imposed from flowering to the physiological maturity stage (50-55 days). Results indicated that the morphological, physiological, and yield traits were significantly decreased under WS in comparison to irrigated conditions (WW). Based on the mean performance the genotype IC-204966 was found most superior for capsules number/plant, seed weight, total dry matter, leaf area, and reduced canopy temperature under WS conditions. The correlation analysis of different traits with seed yield indicated that the plant height and number of capsules/plant were highly and positively correlated with seed yield under both WW and WS conditions. The principal component analysis (PCA) revealed that among the traits studied, number of capsules/plant, total dry matter, stomatal conductance, transpiration rate and fatty acid i.e., palmitic acid were the most important traits that accounted for more than half of the totalvariation among the sesame genotypes studied. Furthermore, the scatter plot revealed that two genotypes, IC 132207 and IC 205471 were stable performers under both stress and irrigated conditions, whereas the performance of check GT-10 varied depending upon conditions.

Immunorecognition of Streptococcus mutans secreted proteins protects against caries by limiting tooth adhesion

IntroductionChildhood caries, a prevalent chronic disease, affects 60–90 % of children in industrialized regions, leading to lesions in both primary and permanent teeth. This condition precipitates hospital admissions, emergency room visits, elevated treatment costs, and missed school days, thereby impeding the child's academic engagement and increasing the likelihood of caries into adulthood. Despite multiple identified risk factors, significant interpersonal variability remains unexplained. The immune system generates a unique antibody repertoire, essential for maintaining a balanced and healthy oral microbiome. Streptococcus mutans is a primary contributor to the development of caries. MethodsEmploying mass spectrometry, we investigated the S. mutans proteins targeted by antibodies in children both with and without caries, delineating a fundamental suite of proteins discernible by the immune systems of a majority of individuals. Notably, this suite was enriched with proteins pivotal for bacterial adhesion. To ascertain the physiological implications of these discoveries, we evaluated the efficacy of saliva in thwarting S. mutans adherence to dental surfaces. ResultsAntibodies in most children recognized a core set of ten S. mutans proteins, with additional proteins identified in some individuals. There was no significant difference in the proteins identified by children with or without caries, but there was variation in antibody binding intensity to some proteins. Functionally, saliva from caries-free individuals, but not children with caries, was found to hinder the binding of S. mutans to teeth. These findings delineate the S. mutans proteome targeted by the immune system and suggest that the inhibition of bacterial adherence to teeth is a primary mechanism employed by the immune system to maintain oral balance and prevent caries formation. ConclusionsThese findings enhance our knowledge of the immune system's function in oral health maintenance and caries prevention, shedding light on how immunoglobulins interact with S. mutans proteins. Clinical SignificanceTargeting S. mutans proteins implicated in bacterial adhesion could be a promising strategy for preventing childhood caries.

Pathways of Self-Determination: A Constructivist Grounded Theory Study of Slut-shaming Vulnerability in a Group of Young Adults

AbstractSlut-shaming is a sexual stigmatization that consists in a form of discrimination against those who do not respect gender stereotypes of external appearance and/or sexual behaviors and attitudes. Individuals may also be exposed to slut-shaming merely due to fortuitous elements unrelated to the sexual dimension. Slut-shaming is perpetrated through ostracism, rejection and sexual stigmatization and may have negative effects on psychophysical well-being. The primary aim of the present study is to explore the victimization of young adults through slut-shaming. A sample of thirty-six participants (aged 19–28) was recruited and focus groups and interviews were conducted to explore participants’ slut-shaming experiences. Constructivist grounded theory was employed to understand how young adults deal with slut-shaming and analyze sociocultural factors involved in slut-shaming dynamics. Several individual, social and cultural factors are involved in sexual stigmatization processes. A core set of 6 categories related to slut-shaming exposure was identified: exposure to slut-shaming, antecedents of slut-shaming, socio-cultural context facilitating slut-shaming, LGBTQIA + and slut-shaming, negative effects of slut-shaming, and reactions to slut-shaming. Results emphasized that, even if young adults showed a generally high level of awareness of sexual discrimination and stigmatization processes, slut-shaming victimization is not uniformly experienced by them. Young adults’ narratives seem to show conflicting feelings and thoughts regarding the possible strategies that could be employed to deal with slut-shaming exposure and pervasive internal and external forms of oppression.

Developing a taxonomy of hazards and hazard mitigation strategies for Motorised mobility scooter users

The increased use of motorised mobility scooters (MMSs) presents a road safety challenge as using a MMS has risks for the user, pedestrians, and other road users. In relation to enhancing MMS driving safety, much of the training and available literature focuses on training vehicular control. Equally important is the need to investigate higher-order cognitive skills involved in driving MMSs, particularly hazard perception. Through a large questionnaire study with MMS users, we develop a taxonomy of the types of hazard MMS users encounter when crossing roads and strategies that are used to negotiate these hazards. Whilst MMS experience modulated hazard perception and strategy use, a core set of hazards and strategies were identified that have policy and practice implications for training interventions and the built environment. Exploration of the advantages and disadvantages of MMS use indicated its impact on various wellbeing outcomes as well as some potential barriers to use.

Identifying core measures to be used in mental health research with care experienced young people: A Delphi study

BackgroundCare experienced young people, including those who are neurodivergent, experience worse mental health outcomes than their non-care counterparts. Understanding the mental health of this population, including how it changes over time, is critically important to the development of more effective, supportive services. However, one of the challenges to this is the lack of consensus around a set of suitable mental health measures that can be used with care experienced young people, including those who are neurodivergent. AimThe primary aim of this study was to develop consensus around a core set of measures that can be used by researchers when investigating the mental health of care experienced young people, including with those who are neurodivergent. Additional research questions included: (1) what are the strengths and limitations of these measures?; (2) what is the value and drawbacks of attempting to develop a set of core measures?; (3) what do young people with care experience think about the measures? MethodsThis study used a mixed methods approach. The primary method was a classical Delphi design where consensus from a panel of experts (n = 18) was sought in relation to the recommendation of 7 mental health measures. These measures covered 4 domains: general mental health, quality of life/related quality of life, anxiety and depression, suicide and self-harm. Alongside the Delphi, an advisory group of care experienced young people (n = 6) was asked to examine the suitability/ appropriateness of the collection of measures. FindingsThere were a number of strengths and limitations of the measures highlighted by the panel of experts. Given these, only the SDQ and the RCADS-25 were recommended for routine use with care experienced young people. Moreover, the panel recommended the use of the SDQ for care experienced young people who are neurodivergent. In addition, the advisory group suggested that there would need to be significant changes to the wording and content of all measures to improve their suitability. Lastly, a tension exists relating to the utility of recommending a core set and the potential restrictions this may impose.

Yeast diversity in open agave fermentations across Mexico.

Yeasts are a diverse group of fungal microorganisms that are widely used to produce fermented foods and beverages. In Mexico, open fermentations are used to obtain spirits from agave plants. Despite the prevalence of this traditional practice throughout the country, yeasts have only been isolated and studied from a limited number of distilleries. To systematically describe the diversity of yeast species from open agave fermentations, here we generate the YMX-1.0 culture collection by isolating 4524 strains from 68 sites with diverse climatic, geographical, and biological contexts. We used MALDI-TOF mass spectrometry for taxonomic classification and validated a subset of the strains by ITS and D1/D2 sequencing, which also revealed two potential novel species of Saccharomycetales. Overall, the composition of yeast communities was weakly associated with local variables and types of climate, yet a core set of six species was consistently isolated from most producing regions. To explore the intraspecific variation of the yeasts from agave fermentations, we sequenced the genomes of four isolates of the nonconventional yeast Kazachstania humilis. The genomes of these four strains were substantially distinct from a European isolate of the same species, suggesting that they may belong to different populations. Our work contributes to the understanding and conservation of an open fermentation system of great cultural and economic importance, providing a valuable resource to study the biology and genetic diversity of microorganisms living at the interface of natural and human-associated environments.

Protocol for the development of a core outcome set for neonatal sepsis (NESCOS).

Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for studies evaluating the effectiveness of treatments for neonatal sepsis. Since a systematic review of key outcomes from randomised trials of therapeutic interventions in neonatal sepsis was published recently, we will complement this with a qualitative systematic review of the key outcomes of neonatal sepsis identified by parents, other family members, parent representatives, healthcare providers, policymakers, and researchers. We will interpret the outcomes of both studies using a previously established framework. Stakeholders across three different groups i.e., (1) researchers, (2) healthcare providers, and (3) patients' parents/family members and parent representatives will rate the importance of the outcomes in an online Real-Time Delphi Survey. Afterwards, consensus meetings will be held to agree on the final COS through online discussions with key stakeholders. This COS is expected to minimize outcome heterogeneity in measurements and publications, improve comparability and synthesis, and decrease research waste.

Measuring health equity in the ASEAN region: conceptual framework and assessment of data availability

BackgroundExisting research on health equity falls short of identifying a comprehensive set of indicators for measurement across health systems. Health systems in the ASEAN region, in particular, lack a standardised framework to assess health equity. This paper proposes a comprehensive framework to measure health equity in the ASEAN region and highlights current gaps in data availability according to its indicator components.MethodsA comprehensive literature review was undertaken to map out a core set of indicators to evaluate health equity at the health system level. Secondary data collection was subsequently conducted to assess current data availability for ASEAN states in key global health databases, national health accounts, and policy documents.ResultsA robust framework to measure health equity was developed comprising 195 indicators across Health System Inputs and Processes, Outputs, Outcomes, and Contextual Factors. Total indicator data availability equated to 72.9% (1423/1950). Across the ASEAN region, the Inputs and Processes sub-component of Health Financing had complete data availability for all indicators (160/160, 100%), while Access to Essential Medicine had the least data available (6/30, 20%). Under Outputs and Outcomes, Coverage of Selected Interventions (161/270, 59.63%) and Population Health (350/350, 100%) respectively had the most data available, while other indicator sub-components had little to none (≤ 38%). 72.145% (384/530) of data is available for all Contextual Factors. Out of the 10 ASEAN countries, the Philippines had the highest data availability overall at 77.44% (151/195), while Brunei Darussalam and Vietnam had the lowest data availability at 67.18% (131/195).ConclusionsThe data availability gaps highlighted in this study underscore the need for a standardised framework to guide data collection and benchmarking of health equity in ASEAN. There is a need to prioritise regular data collection for overlooked indicator areas and in countries with low levels of data availability. The application of this indicator framework and resulting data availability analysis could be conducted beyond ASEAN to enable cross-regional benchmarking of health equity.

A core outcome set (COS) for dementia with Lewy bodies

AbstractBackgroundMethodological heterogeneity in the outcome measurements adopted in DLB trials impedes effective evidence synthesis, rigorous meta‐analysis, and clinical translation. We aimed to develop a Core Outcome Set (COS), an agreed standardised set of outcomes that should be measured and reported, as a minimum, in all clinical DLB trials.MethodWe adopted a multi‐faceted approach to COS development, adopting the principles of the Core Outcome Measures in Effectiveness Trials (COMET) initiative. We conducted systematic reviews of outcomes used in intervention trials, qualitative studies, and health economic studies in DLB. A resulting shortlist of outcome measures formed the basis of an e‐Delphi consensus process, piloted among members of the study group, before it was administered in two rounds to clinicians, scientists, policy and third sector leads. Lay stakeholders, including people with DLB and their caregivers, also contributed to the e‐Delphi process. Consensus on inclusion was determined by at least 70% of respondents grading an outcome measure as “critical for inclusion” and less than 15% grading as “not important”. After appraisal of each outcome using Consensus‐based Standards for the selection of health Measurement Instruments (COSMIN) guidelines, a consensus meeting was conducted, in which all participants were invited to agree on final outcomes and rate each outcome on impact, relevance and clinical feasibility.ResultsThrough validated mechanisms we constructed a COS including measurements of motor, cognitive, neuropsychiatric, autonomic, health economic, health provision, and quality of life. A diverse group of international and intersectional stakeholders have lent approval to its use.ConclusionWe propose a COS; a benchmark which all DLB trials should meet. This standardised approach will could optimise research resources, facilitate multicentre collaboration, and minimize methodological bias.

Core outcome set for economic evaluation of dementia interventions: A consensus exercise with health economists who incorporate economic evaluations into dementia trial

AbstractBackgroundHealthcare decision‐makers worldwide are increasingly seeking to optimise allocation of resources to dementia and the incorporation of economic evaluations into randomised control trials provide definitive information for such decisions. Economic evaluations are rapidly increasing in number in dementia and standardisation of methods ensure comparability of economic evidence.MethodCore outcomes sets (COS) aim to provide international recommendations on outcome measurement in trials and currently there exists no COS for economic evaluations of dementia interventions. Our systematic searches identified over 100 economic evaluations of dementia interventions, and critical appraisal demonstrates opportunities for greater standardisation of applied economic methods. This study aims to agree standardised methods for economic measures of a) health outcomes and b) resource use that should be measured and reported in future trial‐based economic evaluation in dementia.ResultThe COS for the economic evaluation of dementia interventions will be developed from two main steps:First, a systematic review (currently being finalised) extracts information on how costs and benefits are estimated, analysed and reported. All studies published before December 2022, and confirmed as trial‐based economic evaluation, are included. Included studies all contain economic measures and we will report participant characteristics (type of dementia, severity), study design and evaluation types, type of interventions, mode of data collection and instrument(s) used to derive the health outcomes and resource uses.Second, which speaks specifically to action research at AAIC 2023, we will conduct a Delphi consensus focus groups with economists who have collaborated with dementia‐trial teams. Data extracted during the systematic review will be presented to provide a basis for the consensus recommendations on measures commonly required for economic evaluation in dementia. In the case where consensus was not reached, we may conduct additional consensus exercises. We will also consider country contexts (high versus low‐middle income, or country‐level financing and reimbursement mechanisms) in finalising recommended COS of health and resource use measures.ConclusionFindings from COS for economic evaluations of dementia intervention will be published in a dementia‐focused journal and more broadly communicated to a broad range of stakeholders.

Multimodal and multiregional atlas of Alzheimer’s disease changes

AbstractBackgroundAlzheimer’s disease (AD) is the most common form of dementia. The progression of AD throughout the brain follows a stereotypical pattern that can be described by the quantification of histopathological changes in several brain regions. As part of The Seattle Alzheimer’s Disease Cell Atlas (SEA‐AD, https://sea-ad.org), we previously quantified pathological proteins in the middle temporal gyrus (MTG) and used them to describe disease progression, vulnerable cell types, and the MTG molecular changes related to diseaseMethodIn this work, we expanded our results and undertook a comparative approach. We measured a battery of neuropathological proteins (staining NeuN, AT8, IBA1, GFAP, 6e10, pTDP43, and a‐Syn immunoreactivity, and analyzing them with machine learning) in the middle temporal gyrus, the middle frontal gyrus, and medial entorhinal cortex in 84 donors. In addition, we undertook a multimodal single‐cell analysis of such regions, profiling cells using single‐cell RNA‐seq, ATAC‐seq, Multiome, and spatial transcriptomic.Borrowing from our hierarchically resolved cell types in MTG, based on the BRAIN initiative cell type reference, we used machine learning algorithms to create multimodal cell type maps across regions. We used Bayesian statistics to identify differentially accessible regulatory elements, link them to the affected genes and the regulatory transcriptional machinery binding in such elements.ResultWe identified regional vulnerable neuronal populations and a core set of transcriptionally similar cell types susceptible to disease across the cortex. We created a cortex‐wide disease progression map combining neuropathological data from our three profiled regions with latent Bayesian statistical algorithms. In each area, we developed an AD pseudo‐progression timescale that describes the burden of disease in the area and, next, combined all areas to create a cortex‐wide holistic pseudo‐progression. We used the mapped cell types and our developed scale to synchronize changes occurring in each patient, describing abundances, gene expression, and chromatin accessibility modifications.ConclusionThe progression scale developed in this study serves as a reference to align changes across brain regions and, in the future, to reconcile differences across cohorts.

Does the brief ICF core set for multiple sclerosis needs to be modified?

Does the brief ICF core set for multiple sclerosis needs to be modified?

Sex‐specific transcriptome alterations in the cingulate cortex of Lewy body dementia cases

AbstractBackgroundLewy body dementia (LBD) is one of the most common causes of dementia and is characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of alpha‐synuclein in the form of Lewy bodies and neurites. Many of these individuals also have concomitant neuropathological changes such as vascular disease, tangles, and TDP‐43. Like in Alzheimer’s disease, APOE4 is the most significant genetic risk factor for the development of LBD. We sought to survey the landscape of transcriptional changes in the cingulate cortex from a large cohort of LBD cases (>400) compared to normal controls of both sexes.MethodWe performed bulk tissue RNAseq and aligned reads to a human reference genome that is informed on the sex chromosome complement of the sample. Differentially expressed genes were determined after genome‐wide correction.ResultWe found a core set of transcriptional changes that were shared between both sexes in pathways related to neuronal functions and inflammation. However, we also identified numerous changes in genetic female samples that were not significantly altered in genetic males, or that were significantly altered but in the opposite direction. Similar male‐specific changes were also found. These alterations were present for genes on both sex chromosomes as well as autosomes. Though cohort sizes were smaller, we also compared this dataset to Alzheimer’s disease and found shared but unique transcriptional alterations.ConclusionOverall, genetic males and females exhibit sex‐shared and sex‐specific gene expression patterns in dementia with Lewy bodies. We are currently assessing splice alterations, running causal gene network analysis, and performing histological validation.

Russian-language translation and cultural adaptation of the Norwegian ‘Patient Experience Questionnaire’

The availability of patient-reported experience measures (PREM) is an unmet need in Russian healthcare. To translate, adapt culturally, and validate PREM for outpatients. A core set of questions from the Patient Experience Questionnaire (PEQ, in Norwegian, available in English) was translated to Russian (forward-backward translation). Acceptability, construct validity, and reliability were assessed. Patients aged ≥18 y.o. were invited to complete the questionnaire via QR-code within 24 h after a medical encounter. A questionnaire with adequate conceptual and linguistic equivalence was obtained. For four questions, a rating scale was replaced by Likert-type. A total of 308 responses were received (median age 55 y.o., 52% females). The correlation matrix was factorable. Four factors were extracted using varimax rotation: 1) outcome of this specific visit; 2) communication experiences; 3) communication competency; 4) emotions after this visit. These explained 65.4% of the total variance. Three items were excluded. The model was confirmed to be adequate. The Cronbach alpha was >0.9. Item-total correlation confirmed discriminative validity. These preliminary results show that the Russian version of PEQ, adapted to national features, shows good psychometric properties. External validation is needed for the broad implementation of this PREM. This research is first attempt to use PREM in the Russian Federation. The use of quick response codes is feasible and eases survey conduction. The more PREMs are used the higher the quality of healthcare.

Coronatine-Induced Maize Defense against Gibberella Stalk Rot by Activating Antioxidants and Phytohormone Signaling.

One of the most destructive diseases, Gibberella stalk rot (GSR), caused by Fusarium graminearum, reduces maize yields significantly. An induced resistance response is a potent and cost-effective plant defense against pathogen attack. The functional counterpart of JAs, coronatine (COR), has attracted a lot of interest recently due to its ability to control plant growth and stimulate secondary metabolism. Although several studies have focused on COR as a plant immune elicitor to improve plant resistance to pathogens, the effectiveness and underlying mechanisms of the suppressive ability against COR to F. graminearum in maize have been limited. We investigated the potential physiological and molecular mechanisms of COR in modulating maize resistance to F. graminearum. COR treatment strongly enhanced disease resistance and promoted stomatal closure with H2O2 accumulation, and 10 μg/mL was confirmed as the best concentration. COR treatment increased defense-related enzyme activity and decreased the malondialdehyde content with enhanced antioxidant enzyme activity. To identify candidate resistance genes and gain insight into the molecular mechanism of GSR resistance associated with COR, we integrated transcriptomic and metabolomic data to systemically explore the defense mechanisms of COR, and multiple hub genes were pinpointed using weighted gene correlation network analysis (WGCNA). We discovered 6 significant modules containing 10 candidate genes: WRKY transcription factor (LOC100279570), calcium-binding protein (LOC100382070), NBR1-like protein (LOC100275089), amino acid permease (LOC100382244), glutathione S-transferase (LOC541830), HXXXD-type acyl-transferase (LOC100191608), prolin-rich extensin-like receptor protein kinase (LOC100501564), AP2-like ethylene-responsive transcription factor (LOC100384380), basic leucine zipper (LOC100275351), and glycosyltransferase (LOC606486), which are highly correlated with the jasmonic acid-ethylene signaling pathway and antioxidants. In addition, a core set of metabolites, including alpha-linolenic acid metabolism and flavonoids biosynthesis linked to the hub genes, were identified. Taken together, our research revealed differentially expressed key genes and metabolites, as well as co-expression networks, associated with COR treatment of maize stems after F. graminearum infection. In addition, COR-treated maize had higher JA (JA-Ile and Me-JA) levels. We postulated that COR plays a positive role in maize resistance to F. graminearum by regulating antioxidant levels and the JA signaling pathway, and the flavonoid biosynthesis pathway is also involved in the resistance response against GSR.

Structure of methyltransferase RedM that forms the dimethylpyrrolinium of the bisindole reductasporine

Bisindoles are biologically active natural products that arise from the oxidative dimerization of two molecules of l-tryptophan. In bacterial bisindole pathways, a core set of transformations is followed by the action of diverse tailoring enzymes that catalyze reactions that lead to diverse bisindole products. Among bisindoles, reductasporine is distinct due to its dimethylpyrrolinium structure. Its previously reported biosynthetic gene cluster encodes two unique tailoring enzymes, the imine reductase RedE and the dimethyltransferase RedM, which were shown to produce reductasporine from a common bisindole intermediate in recombinant E. coli. To gain more insight into the unique tailoring enzymes in reductasporine assembly, we reconstituted the biosynthetic pathway to reductasporine in vitro and then solved the 1.7 Å resolution structure of RedM. Our work reveals RedM adopts a variety of conformational changes with distinct open and closed conformations, and site-directed mutagenesis alongside sequence analysis identifies important active site residues. Finally, our work sets the stage for understanding how RedM evolved to react with a pyrrolinium scaffold and may enable development of new dimethyltransferase catalysts.

A Core Outcome Set for inflammatory bowel diseases: development and recommendations for implementation in clinical practice through an international multi-stakeholder consensus process.

Standardising health outcome measurements supports delivery of care, enables data-driven learning systems, and secondary data use for research. As part of the Health Outcomes Observatory initiative and building on existing knowledge, a core outcome set (COS) for inflammatory bowel diseases (IBD) was defined through an international modified Delphi method. Stakeholders rated 90 variables on a 9-point importance scale twice, allowing score modification based on feedback displayed per stakeholder group. Two consecutive consensus meetings were held to discuss results and formulate recommendations for measurement in clinical practice. Variables scoring 7 or higher by ≥80% of the participants, or based on consensus meeting agreement, were included in the final set. In total, 136 stakeholders (45 IBD patients (advocates), 74 healthcare professionals/researchers, 13 industry representatives and 4 regulators), from 20 different countries participated. The final set includes 18 case-mix variables, 3 biomarkers (haemoglobin to detect anaemia, C-reactive protein and faecal calprotectin to detect inflammation) for completeness and 28 outcomes (including 16 patient-reported outcomes (PROs) and 1 patient-reported experience). The PRO-2 and IBD-Control questionnaires were recommended to collect disease-specific PROs at every contact with an IBD practitioner, and the Subjective Health Experience model questionnaire, PROMIS Global Health and Self-Efficacy short form to collect generic PROs annually. A COS for IBD, including a recommendation for use in clinical practice, was defined. Implementation of this set will start in Vienna, Berlin, Barcelona, Leuven and Rotterdam, empowering patients to better manage their care. Additional centres will follow worldwide.