A Family of Cyclic Lipopeptides Found in Human Isolates of Bacillus Ameliorates Acute Colitis via Direct Agonism of Toll-Like Receptor 2 in a Murine Model of Inflammatory Bowel Disease.

BACKGROUND: The Bacillus-derived cyclic lipopeptides (surfactin, iturin, and fengycin) form potent Heterogeneous Lipopeptide Micelle (HeLM) complexes. HeLM is a small molecule that has been shown to have immunomodulatory effects. However, how HeLM regulates inflammation is not clear, moreover its application to Inflammatory Bowel Disease (IBD), specifically Ulcerative Colitis (UC), has not been tested before. AIMS: To use a murine model of IBD and determine the effects of HeLM and related molecular mechanisms of action. METHODS: Colitis was induced in mice by administration of 4% Dextran Sodium Sulfate. Three preparations were tested against negative and positive controls: Purified HeLM, the wild-type strain that produces it, and an isogenic mutant that does not produce HeLM. Clinical, biochemical, and histological scoring systems were used to assess the severity of colitis. RT-qPCR and cell cultures were used to determine the levels of molecular signaling. Fecal samples were processed for metagenomic analysis. RESULTS: Purified HeLM, and the wild-type strain, significantly decreased the severity of colitis as determined by the disease activity index (DAI), mouse colitis histology index (MCHI), fecal calprotectin, and colonic length. This effect was not seen in the mutant. HeLM was found to be an agonist to TLR-2, seemingly activating the Toll-Like Receptor 2/IL-10 pathway, with subsequent downregulation of inflammatory cytokines (TNF-α, IL-1ß, and IL-6). At higher concentrations HeLM inhibited lipopolysaccharide ligands from activating TLR-4. The reduction in colitis was not due to microbiome modulation, as had previously been hypothesized. CONCLUSION: Our results indicate that HeLM ameliorates colitis by TLR-2-induced IL-10 production and possibly via the inhibition of lipopolysaccharide.

Age, gender and household infrastructural inequality in COVID-19: Contextual analysis of Mamelodi.

BACKGROUND:  Age, gender and household infrastructure are important social determinants affecting health inequalities. This study aims to assess the ways that age and gender of the household head and household infrastructure intersect to create relative advantage and disadvantage in COVID-19 vulnerability. METHODS:  Using household primary care survey data from Mamelodi, Gauteng, headed households were sorted into three risk categories for each of the relevant infrastructural determinants of COVID-19. Bivariate ordinal logistic regression was used to determine the odds of households falling into each risk category. The proportion of high-risk (HR) categories and dwelling types was also calculated. RESULTS:  Households headed by someone ≥ 65 years were less likely to be in all HR categories and more frequently had formal houses. Male-head households were more likely to be HR for water, sanitation and hygiene infrastructure and indoor pollution; however, female-headed households (FHHs) were at higher risk for crowding. In Mamelodi, households headed by ≥ 65 years olds were relatively infrastructurally protected, likely because of pro-equity housing policy, as were FHHs, except for crowding. The care load on FHHs results in their infrastructural protection benefiting more community members, while simultaneously incurring risk. CONCLUSION:  Infrastructural support based on the household head's age and gender could improve targeting and the effectiveness of health interventions. These results demonstrate the importance of a contextual understanding of gender and age inequalities and tailoring public health support based on this understanding.Contribution: This research describes patterns of health-related infrastructural inequality, identifies ways to improve health interventions, and demonstrates the importance of equity-focused policy in an African context.

Functional trait mismatch between native and introduced bee pollinators servicing a global fruit crop.

BACKGROUND: Understanding connections between biodiversity and ecosystem services can be enhanced by shifting focus from species richness to functional trait-based approaches, that when paired with comparative phylogenetic methods can provide even deeper insights. We investigated the functional ecology and phylogenetic diversity of pollination services provided by hymenopteran insects visiting apple flowers in orchards surrounded by either 'natural' or 'disturbed' landscapes in New South Wales, Australia. We assessed whether morphological and behavioural traits (hairiness, body size, glossa length, pollen load purity, and probability of loose pollen) exhibited non-random phylogenetic patterns. Then, explored whether bees, the primary pollinators in this system, filled unique or overlapping functional entities (FEs). For each landscape, we calculated phylogenetic diversity and used FEs to assess functional richness, evenness, and diversion. RESULTS: A phylogenomic matrix based on ultraconserved elements (UCEs; 1,382,620 bp from 1,969 loci) was used to infer a fully-resolved and well-supported maximum likelihood phylogeny for 48 hymenopteran morphospecies. There was no significant difference in species richness between landscape categories. Pollinator communities at natural sites had higher phylogenetic complexity (X = 2.37) and functional divergence (x̄ = 0.74 ± 0.02 s.e.) than disturbed sites (X = 1.65 and x̄ = 0.6 ± 0.01 s.e.). Hairiness showed significant phylogenetic clustering (K = 0.94), whereas body size, glossa length, and loose pollen showed weaker non-random phylogenetic patterns (K between 0.3-0.5). Pollen load purity showed no association with phylogeny. The assemblage of 17 bee morphospecies comprised nine FEs: eight FEs consisted of native bees with three containing 65% of all native bee taxa. The introduced honey bee (Apis mellifera) occupied a unique FE, likely due to its different evolutionary history. Both landscape types supported six FEs each with three overlapping: two native bee FEs and the honey bee FE. CONCLUSIONS: Bee hairiness was the only functional trait to exhibit demonstrable phylogenetic signal. Despite differences in species richness, and functional and phylogenetic diversity between orchard landscape types, both maintained equal bee FE numbers. While no native bee taxon was analogous to the honey bee FE, four native bee FEs shared the same hairiness level as honey bees. Health threats to honey bee populations in Australia will likely disrupt pollination services to apple, and other pollination-dependent food crops, given the low level of functional redundancy within the investigated pollinator assemblages.

Genome-wide association studies for citric and lactic acids in dairy sheep milk in a New Zealand flock.

The objectives of this study were to estimate genetic parameters for citric acid content (CA) and lactic acid content (LA) in sheep milk and to identify the associated candidate genes in a New Zealand dairy sheep flock. Records from 165 ewes were used. Heritability estimates based on pedigree records for CA and LA were 0.65 and 0.33, respectively. The genetic and phenotypic correlations between CA and LA were strong-moderate and negative. Estimates of genomic heritability for CA and LA were also high (0.85, 0.51) and the genomic correlation between CA and LA was strongly negative (-0.96 ± 0.11). No significant associations were found at the Bonferroni level. However, one intragenic SNP in C1QTNF1 (chromosome 11) was associated with CA, at the chromosomal significance threshold. Another SNP associated with CA was intergenic (chromosome 15). For LA, the most notable SNP was intragenic in CYTH1 (chromosome 11), the other two SNPs were intragenic in MGAT5B and TIMP2 (chromosome 11), and four SNPs were intergenic (chromosomes 1 and 24). The functions of candidate genes indicate that CA and LA could potentially be used as biomarkers for energy balance and clinical mastitis. Further research is recommended to validate the present results.

Mental health and well-being of elite youth athletes: a scoping review.

BACKGROUND: There is increasing recognition of the prevalence and risk factors for mental health symptoms and disorders among adult elite athletes, with less research involving elite youth athletes. This scoping review aimed to characterise the mental health and well-being of elite youth athletes who travel internationally and compete for their sport. METHOD: Four databases were searched in March 2023. Inclusion criteria were studies with elite youth athlete populations (mean age 12-17 years) reporting mental health and well-being outcomes. Data from included studies were charted by outcome, and risk/protective factors identified. RESULTS: Searches retrieved 3088 records, of which 33 studies met inclusion criteria, encapsulating data from 5826 athletes (2538 males, 3288 females). The most frequently studied issue was disordered eating (k=16), followed by anxiety (k=7), depression (k=5) and mixed anxiety/depression (k=2). Caseness estimates (a symptom level where mental health treatment is typically indicated) for disordered eating were wide ranging (0%-14% for males; 11%-41% for females), whereas only two studies estimated caseness for depression (7% in a mixed-sex sample; 14% for males, 40% for females) and one for anxiety (8% for males, 28% for females). Common risk factors for mental ill-health included sex, athlete status (compared with non-athletes) and social/relationship factors (with coaches/parents/peers). Contradictory evidence was observed for elite/competition level, which was associated with higher and lower rates of disordered eating. CONCLUSION: Further representative research into the mental health and well-being of elite youth athletes is needed to enhance understanding and guide prevention and intervention measures.

Exploration of Alzheimer's disease-related gene expression following high-intensity and moderate-intensity exercise interventions.

OBJECTIVES: There are currently 29 genome regions that demonstrate associations with Alzheimer's disease (AD) risk. Regular physical exercise can promote systemic change in gene expression and may modify the risk of cognitive decline and AD. This study is a secondary analysis of a randomised controlled trial and examines the effect of a six-month exercise intervention versus control on AD-related gene expression. DESIGN: Single-site parallel pilot randomised controlled trial. METHODS: 91 cognitively unimpaired older adults were enrolled in the Intense Physical Activity and Cognition (IPAC) study. Participants were randomised into one of three groups: high-intensity exercise, moderate-intensity exercise, or inactive control for six months. Blood samples were collected prior to, and within two weeks of intervention completion, for later expression analysis of 96 genes. To explore the relationship between changes in gene expression and the intervention groups, an interaction term ("time point × intervention group") was subsequently used. RESULTS: There were no significant differences in gene expression between the three intervention groups at baseline, nor after the intervention. Within groups, five genes were upregulated, seven were downregulated and the remainder remained unchanged. None of the examined genes showed significant change from pre- to post-intervention in the exercise groups compared to the control. CONCLUSIONS: Exercise does not change AD-related gene expression in cognitively unimpaired older adults. Several gene expression targets have been identified for further study.

Interface Engineering of Water-Dispersible Near-Infrared-Emitting CuInZnS/ZnSe/ZnS Quantum Dots.

We report the synthesis of near-infrared (IR)-emitting core/shell/shell quantum dots of CuInZnS/ZnSe/ZnS and their phase transfer to water. The intermediate ZnSe shell was added to inhibit the migration of ions from the standard ZnS shell into the emitting core, which often leads to a blue shift in the emission profile. By engineering the interface between the core and terminal shell layer, the optical properties can be controlled, and emission was maintained in the near-IR region, making the materials attractive for biological applications. In addition, the hydrodynamic diameter of the particle was controlled using amphiphilic polymers.

Measuring personal characteristics in applicants to German medical schools: Piloting an online Situational Judgement Test with an open-ended response format.

Objectives: Situational Judgement Tests (SJT) are a cost-efficient method for the assessment of personal characteristics (e.g., empathy, professionalism, ethical thinking) in medical school admission. Recently, complex open-ended response format SJTs have become more feasible to conduct. However, research on their applicability to a German context is missing. This pilot study tests the acceptability, reliability, subgroup differences, and validity of an online SJT with open-ended response format developed in Canada ("Casper"). Methods: German medical school applicants and students from Hamburg were invited to take Casper in 2020 and 2021. The test consisted of 12 video- and text-based scenarios, each followed by three open-ended questions. Participants subsequently evaluated their test experience in an online survey. Data on sociodemographic characteristics, other admission criteria (Abitur, TMS, HAM-Nat, HAM-SJT) and study success (OSCE) was available in a central research database (stav). Results: The full sample consisted of 582 participants. Test-takers' global perception of Casper was positive. Internal consistency was satisfactory in both years (α=0.73; 0.82) while interrater agreement was moderate (ICC(1,2)=0.54). Participants who were female (d=0.37) or did not have a migration background (d=0.40) received higher scores. Casper scores correlated with HAM-SJT (r=.18) but not with OSCE communication stations performance. The test was also related to Abitur grades (r=-.15), the TMS (r=.18), and HAM-Nat logical reasoning scores (r=.23). Conclusion: This study provides positive evidence for the acceptability, internal consistency, and convergent validity of Casper. The selection and training of raters as well as the scenario content require further observation and adjustments to a German context to improve interrater reliability and predictive validity.

Progress and future directions for seaweed holobiont research.

In the marine environment, seaweeds (i.e. marine macroalgae) provide a wide range of ecological services and economic benefits. Like land plants, seaweeds do not provide these services in isolation, rather they rely on their associated microbial communities, which together with the host form the seaweed holobiont. However, there is a poor understanding of the mechanisms shaping these complex seaweed-microbe interactions, and of the evolutionary processes underlying these interactions. Here, we identify the current research challenges and opportunities in the field of seaweed holobiont biology. We argue that identifying the key microbial partners, knowing how they are recruited, and understanding their specific function and their relevance across all seaweed life history stages are among the knowledge gaps that are particularly important to address, especially in the context of the environmental challenges threatening seaweeds. We further discuss future approaches to study seaweed holobionts, and how we can apply the holobiont concept to natural or engineered seaweed ecosystems.

Syndemic Theory and Its Use in Developing Health Interventions and Programming: A Scoping Review.

PURPOSE OF REVIEW: The central tenet of syndemics theory is that disease interactions are driven by social factors, and that these factors have to be understood in order to reduce the health burdens of local populations. Without an understanding of the theory and how it is being put into practice, there is a strong possibility of losing the potential for syndemic theory to positively impact change at community and individual level. METHODS: Following an initial database search that produced 921 articles, we developed a multi-stage scoping review process identifying invention studies that employ syndemic theory. Inclusion was defined as the presence of healthcare interventions examining multiple social-biological outcomes, refering to a specific (local) at risk population, developing or attempting to develop interventions impacting upon multiple health and/or social targets, and explicit employment of syndemic theory in developing the intervention. RESULTS: A total of 45 articles contained a substantial engagement with syndemic theory and an original healthcare intervention. However, only eleven studies out of all 921 articles met the inclusion criteria. DISCUSSION/CONCLUSION: It is strongly suggested that when employing syndemic theory researchers focus close attention to demonstrating disease interactions, providing evidence of the social drivers of these disease interactions, and constructing interventions grounded in these analytical findings. We conclude that although frequently referred to, syndemic theory is rarely employed in its entirety and recommend that interventions be developed using a more thorough grounding in this important and powerful theory.

Stereodivergency in Copper-Catalyzed Borylative Difunctionalizations: The Impact of Boron Coordination.

A reagent-controlled diastereodivergent copper-catalyzed borylative difunctionalization is reported. The formation of Lewis adducts that guide selectivity is commonly invoked in organic reaction mechanisms. Using density functional theory calculations, we identified BpinBdan as a sterically similar and less Lewis acidic alternative to B-2pin2. Using a newly developed borylative aldol domino reaction as the proof-of-concept, we demonstrate a change in stereochemical outcome by a simple change of borylating reagent - B2pin2 affords the diastereomer associated with coordination control while BpinBdan overturns this mode of binding. We show that this strategy can be generalized to other scaffolds and, more importantly, that BpinBdan does not alter the diastereomeric outcome of the reaction when coordination is not involved. BpinBdan can be viewed as a mechanistic probe for coordination in future copper-catalyzed borylation reactions.

Mouse adaptation of human inflammatory bowel diseases microbiota enhances colonization efficiency and alters microbiome aggressiveness depending on the recipient colonic inflammatory environment.

BACKGROUND: Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis. RESULTS: Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota-associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10-/- mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10-/- mice. Engraftment of human-to-mouse FMT stochastically varied with individual transplantation events more than mouse-adapted FMT. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10-/- host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10-/- mice than the distinct microbiota reassembled in non-inflamed WT hosts. CONCLUSIONS: Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated by gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer. Video Abstract.

The Relationship Between Autistic Traits and Quality of Life: Investigation of Indirect Effects Through Self-Determination.

Background: Self-determination, described broadly as experiencing causal agency, is positively associated with quality of life (QoL) and increases through satisfaction of three basic psychological needs: autonomy (feeling able to make choices free from pressure), competence (perceived self-efficacy), and relatedness (social connection). Both unsupportive environments and challenges with social interaction can interfere with satisfaction of psychological needs. Social challenges are a key trait for autism diagnosis, and unsupportive environments are also known to adversely affect QoL for autistic people. Autistic people report, on average, lower self-determination than non-autistic people. Therefore, it is hypothesized that higher levels of autistic traits may reduce opportunities to develop self-determination, affecting QoL. Methods: We tested a parallel indirect effects model where we hypothesized that the relationships between autistic traits and four domains of QoL (psychological, social, physical, and environmental) would be indirectly influenced through self-determination (represented through satisfaction of the basic psychological needs for autonomy, competence, and relatedness). This study drew participants from the general population (N = 262; M AGE = 37.6, standard deviation = 11.92; 1.9% reported an autism diagnosis and 2.7% identified as autistic without a diagnosis). Participants completed an online survey. Results: Higher levels of autistic traits were associated with lower levels of self-determination and lower levels of QoL, and there was a significant indirect effect between autistic traits and QoL via self-determination. More specifically, we found a significant indirect effect between autistic traits and all QoL domains via competence; between autistic traits and the environmental, social, and psychological QoL domains via relatedness; and between autistic traits and the physical and environmental QoL domains through autonomy. Conclusions: Our results suggest that supporting satisfaction of the needs for autonomy, competence, and relatedness may represent an important element in designing effective programs to support the development of self-determination in people with higher levels of autistic traits (potentially including autistic individuals) and also to support these people to improve their QoL.

Why is this an important issue? In this study, we looked at how autistic traits might affect self-determination and quality of life. Quality of life is the way that you feel about your own life circumstances. In this study, we looked at four aspects of quality of life­psychological (e.g., mental health), social (how you interact with other people), physical (e.g., disability or sickness), and environmental (e.g., where you live). Self-determination is the ability to choose based on your own wants, needs, and interests, without feeling pressured. To be self-determined, you need to meet your needs for autonomy (experiencing free choice), competence (feeling able to do things effectively), and relatedness (feeling connected with others). Meeting these needs is affected by the world around you (e.g., where you live, if you have a job, whether you are disabled) and by the actions and beliefs of the people around you. People with higher autistic traits report, on average, lower quality of life and self-determination than people with lower autistic traits. Because other researchers have found that self-determination influences quality of life, lower levels of self-determination might partly explain lower quality of life. Programs that promote self-determination may reduce the gap in quality of life between autistic and non-autistic people. What was the purpose of this study? We thought that self-determination might partly explain why people with higher autistic traits report lower quality of life than people with lower autistic traits, so we wanted to test this idea. What did the researchers do? We asked people to answer questions about autistic traits, self-determination, and quality of life in an online survey. We statistically analyzed their answers to find out whether autistic traits influenced the levels of self-determination (feelings of autonomy, competence, and relatedness) or quality of life (psychological, social, physical and environmental quality of life). What were the results of this study? Autistic traits did not directly influence psychological, physical, or environmental quality of life but did directly influence social quality of life. In our study, people with higher autistic traits reported less satisfaction of their psychological needs than people with lower autistic traits. People with lower satisfaction of psychological needs also reported lower quality of life. Autistic traits influenced self-determination, which in turn influenced quality of life. What do these findings add to what was already known? To the best of our knowledge, this was the first study to explore relationships between autistic traits, self-determination, and quality of life. Our results showed that people with higher levels of autistic traits may report lower quality of life partly because autistic traits might make it difficult to become self-determined. What are the potential weaknesses in the study? We investigated self-determination and quality of life among one group of people from the general population. We did not compare autistic and non-autistic people. While some studies have shown that people with high levels of autistic traits may be similar to autistic people in some ways, this is not necessarily the case all the time. We cannot assume that results will be the same in other groups, that autistic traits cause lower self-determination, or that lower self-determination causes lower quality of life. We also did not consider all the things that might have influenced self-determination or quality of life (e.g., where people lived, how much money they had, or what their health was like). How will these findings help autistic adults now or in the future? People with higher autistic traits (including autistic adults) may find it harder to be self-determined both because of their autistic traits (e.g., difficulty in social interaction, sensory sensitivities) and also because school, work, and community systems may not be designed to support acceptance of differences. The results from this study suggest that higher autistic traits might make it difficult to meet the psychological needs for autonomy, competence, and relatedness. Research that compares autistic and non-autistic people is needed to determine both personal and environmental factors which may support the development of self-determination in autistic people and empower them to achieve higher quality of life.

Centering cognitive neuroscience on task demands and generalization.

Cognitive neuroscience seeks generalizable theories explaining the relationship between behavioral, physiological and mental states. In pursuit of such theories, we propose a theoretical and empirical framework that centers on understanding task demands and the mutual constraints they impose on behavior and neural activity. Task demands emerge from the interaction between an agent's sensory impressions, goals and behavior, which jointly shape the activity and structure of the nervous system on multiple spatiotemporal scales. Understanding this interaction requires multitask studies that vary more than one experimental component (for example, stimuli and instructions) combined with dense behavioral and neural sampling and explicit testing for generalization across tasks and data modalities. By centering task demands rather than mental processes that tasks are assumed to engage, this framework paves the way for the discovery of new generalizable concepts unconstrained by existing taxonomies, and moves cognitive neuroscience toward an action-oriented, dynamic and integrated view of the brain.

Monkeypox and chickenpox co-infection in a person living with Human Immunodeficiency Virus.

INTRODUCTION: The 2022 mpox global outbreak underscores the need for an improved understanding of mpox epidemiology, co-morbidities, and clinical management/outcome. We report a case of a 30-year-old Nigerian antiretroviral treatment-experienced person living with human immunodeficiency virus (PLHIV) who had PCR-confirmed mpox and chickenpox co-infection. CASE PRESENTATION: The patient presented with a generalized itchy rash of three weeks and antecedent low-grade fever. He had no recent travel, animal exposure, or same-sex relationship. Examination revealed generalized pustular and nodular eruptions without peripheral lymphadenopathy. RESULTS: CD4 count was 78 cells/mm3, wound swab microscopy revealed Gram-positive cocci in clusters and Gram-negative bacilli while culture yielded Pseudomonas aeruginosa. Despite supportive care and definitive antimicrobial therapy, his clinical condition deteriorated with sepsis-related multi-organ dysfunction and ultimately death. CONCLUSIONS: Mpox and chickenpox co-infection may occur, with potentially fatal complications in the setting of advanced HIV disease. Increased surveillance for co-viral infections in PLHIV with febrile exanthema and aggressive management to improve outcome are recommended.

Alternative Venous Pathways: A Potential Key Imaging Feature for Early Diagnosis of Sturge-Weber Syndrome Type 1.

BACKGROUND AND PURPOSE: Sturge-Weber syndrome is a rare congenital disorder characterized by cortical atrophy and calcifications on late-stage imaging. Understanding the evolution of brain lesions is crucial for effective early interventions, yet the timeline remains unclear. We aimed to evaluate early brain MRI findings and their progression longitudinally on follow up MRI in children diagnosed with Sturge-Weber syndrome. MATERIALS AND METHODS: We retrospectively included all children with a confirmed diagnosis of Sturge-Weber syndrome between 2009 and 2023 that had at least 2 available MRIs performed before the age of 2 years. A pediatric radiologist and a pediatric neuroradiologist evaluated all the MRI scans for pial enhancement, choroid plexus enlargement, atrophy, calcifications, a prominent subarachnoid varicose network, trans medullary veins, subependymal veins, and deep extra ventricular veins. Descriptive analysis was used for demographic data and brain lesion prevalence. Cumulative incidence curves were used to show the timeline of emerging lesions. K-means clustering was used to categorize the lesions based on their prevalence at 1, 2, 3, 6, 12, 18, and 24 months after birth. RESULTS: Nine patients met the inclusion criteria. Median ages at the first and last MRIs were 35 days (IQR: 11-123) and 294 days (IQR: 208-465), respectively. The most prevalent lesions at the first MRI were subarachnoid varicose network (88.9%) and trans medullary veins (77.8%), while prevalence of atrophy and calcifications differed most between the first and last MRIs. The results of the elbow method and K-means clustering showed that we can divide Sturge-Weber syndrome lesions into 3 groups based on their timeline of emergence. The first cluster contained subarachnoid varicose network, trans medullary veins, subependymal veins, and choroid plexus enlargement. The second cluster contained deep extra ventricular veins, pial enhancement, accelerated myelination, and atrophy. The last cluster contained calcifications. CONCLUSIONS: Our findings suggest that dilated venous channels emerge early as a compensatory mechanism, preceding atrophy and calcification. Additionally, these dilated channels precede the appearance of abnormal contrast enhancement of the pia, often termed leptomeningeal angioma. This underscores the importance of early recognition and monitoring of these initial imaging indicators in clinical practice. ABBREVIATIONS: ASL = Arterial Spin Labelled; MinIP = Minimum intensity projection; SWS = Sturge-Weber Syndrome.

Synthesis and Development of Inverse-Type Nucleoside Diarylethene Photoswitches.

Nucleosidic diarylethenes (DAEs) have evolved from an emerging class of photochromes into a well-established option for integrating photochromic functionalities into biological systems. However, a comprehensive understanding of how chemical structure influences their photochromic properties remains essential. While structural features, such as an inverse connection between the aryl residues and the ethene bridge, are well-documented for classical DAEs, their application to nucleosidic DAEs has been underexplored. In this study, we address this gap by developing three distinct types of inverse nucleosidic DAEs - semi-inverse thiophenes, semi-inverse uridines and inverse uridines. We successfully synthesized these compounds and conducted comprehensive analyses of their photostationary states, thermal stability, reversibility, and reaction quantum yields. Additionally, we conducted an in-depth comparison of their photochromic properties with those of their normal-type counterparts. Among the synthesized compounds, seven semi-inverse thiophenes exhibited the most promising characteristics. Notably, these compounds demonstrated excellent fatigue resistance, with up to 96% retention of photochromic activity over 40 switching cycles, surpassing the performance of all comparable nucleosidic DAEs reported to date. These findings hold significant promise for future applications in various fields.