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Core-Substituted Pyromellitic Diimides: A Versatile Molecular Scaffold for Tunable Triplet Emission

Cardiac electrical abnormalities in a mouse model of left ventricular non-compaction cardiomyopathy

Mutations in MINDBOMB 1 ( MIB1 ), encoding an E3 ubiquitin ligase of the NOTCH signaling pathway, cause left ventricular noncompaction cardiomyopathy (LVNC) in mice and humans, increasing the risk of arrhythmia and left ventricular dysfunction. This study aimed to investigate the effect of MIB1 mutations on cardiac electrical activity. We examined male Mib1 flox ;Tnnt2 Cre mice, a disease model of LVNC, and wildtype littermates on the C57BL/6J genetic background. Our results demonstrate that the gap-junction protein connexin43 was delocalized from the intercalated disks to the lateral long axis of Mib1 flox ;Tnnt2 Cre cardiomyocytes. Cardiomyocyte electrophysiology revealed an increase in the Na (I Na ) peak density at potentials between -50 and -30 mV in Mib1 flox ;Tnnt2 Cre mice, with no changes in I Na activation or inactivation kinetics. Mib1 flox ;Tnnt2 Cre cardiomyocytes also showed decreases in outward K + peak currents and currents at the end of depolarizing pulses at potentials ≥−10 mV and ≥−20 mV, respectively, and this was accompanied by a lower charge density at ≥−20 mV. Action potential duration was increased in Mib1 flox ;Tnnt2 Cre cardiomyocytes. The cardiac stress, induced by swimming endurance training or β-adrenergic stimulation with isoproterenol, increases QTc duration in Mib1 flox ;Tnnt2 Cre mice, accompanied by a decrease in T-wave amplitude and area. Swimming endurance training decreased heart rate in wildtype and Mib1 flox ;Tnnt2 Cre mice but was unaffected by long-term isoproterenol treatment. These mouse findings are in agreement with an increased QTc duration found in LVNC patients carrying MIB1 mutations. These results provide insight into the outcomes of LVNC and relate its pathogenicity to impaired ventricular repolarization.

Permanent Efferocytosis Prevention by Terminating MerTK Recycle on Tumor-Associated Macrophages for Cancer Immunotherapy

Food, Pregnancy & Me: Exploring food insecurity in pregnancy in the UK to inform future public health intervention needs–A mixed-methods study protocol

Introduction There are several known risks relating to poor nutrition during pregnancy, including the development of complications and poor birth outcomes. While food insecurity is associated with poorer nutrition, data on the prevalence and severity of food insecurity in pregnancy in the UK is lacking. This study aims to explore the prevalence, experiences and health impact of food insecurity in pregnancy in England to develop strategic recommendations for intervention strategies. Methods and analysis Food, Pregnancy & Me is an observational, multi-method study. Questionnaires exploring diet quality, food security, mental health, and other health behaviours will be distributed to all women and pregnant people in their third trimester in two NHS Trusts in England (North East and West Midlands). Returned questionnaires (n=605) will be linked to routine maternal and birth outcome data and pseudo-anonymised. We will estimate the prevalence of food insecurity in pregnancy in these locations, associations with diet quality, maternal mental health, and pregnancy outcomes (e.g., pre-term birth, pre-eclampsia, gestational diabetes). Qualitative interviews (n=40) with participants identified as having experienced food insecurity will explore their lived experience, support received, and recommendations for additional support needs. Through a series of co-production workshops with local and national system shapers and experts by lived experience, we will use the data gathered to produce strategic recommendations for intervention with pregnant women and people facing food insecurity. We will then explore the potential costs and benefits of implementing the proposed recommendations. Ethics and dissemination Ethical approval was obtained from Newcastle and North Tyneside 1 NHS Research Ethics Committee (24/NE/0027). Findings will be disseminated to key national and local system shapers and policy makers, advocacy groups, and the public through reports, presentations, the media and open access publications. Study registration number ISRCTN16655955

The Heat-Shock Metabolite Streptolactam D, Produced by High-Temperature Culture of <i>Streptomyces</i> sp. JA74, Promotes Thermotolerance via Self-Membrane Stabilization

Do young and older adult populations perform equivalently across different automatic face-trait judgements? Evidence for differential impacts of ageing

Accurate implicit personality trait judgements can be made from faces, but as yet the focus has been on young participants making judgements of young faces. The current study sought to explore if similar patterns of performance are seen across the age range, with both young and older adult groups. In addition, we investigated whether implicit trait judgements are associated with cognitive, and trait factors including face recognition, emotional expression perception, autism traits, and alexithymia traits. Across two experiments we explored the extent to which young and older adult populations were able to make accurate implicit associations from faces signalling two different traits – extraversion (positive) and neuroticism (negative). Interestingly, we find that young participants were accurate at making both kinds of automatic trait judgments, and older adults were equivalent to younger controls for the neuroticism personality trait but impaired with automatic extraversion judgements. In both studies, implicit associations were unrelated to any of the other cognitive and trait factors we measured. Based on this pattern of findings, we conclude that face-based implicit trait judgements utilise some independent processes to other face processing abilities, and that the interpretation of particular personality traits is differentially impacted by the ageing process.

Exploring the accuracy of the Xpert MTB/RIF assay in detecting lymph node tuberculosis: A systematic review and meta-analysis

Background The Xpert MTB/RIF assay has exhibited high diagnostic efficiency in detecting lymph node tuberculosis (LNTB). However, different gold standards and types of LNTB specimens may impact Xpert’s diagnostic accuracy. This meta-analysis compared the performance of Xpert MTB/RIF on fine needle aspiration (FNA) and tissue samples against that of culture and composite reference standards (CRS) for LNTB diagnosis. In addition, we further reported the diagnostic accuracy of the Xpert MTB/RIF assay in identifying LNTB in different age groups and rifampicin resistance in LNTB patients. Methods A systematic search of Embase, Cochrane Library, PubMed, Web of Science, and Scopus up to October 26, 2023, was conducted. Studies comparing Xpert MTB/RIF with culture and CRS were selected. Meta-analyses and meta-regression were performed using Stata and Meta Disc software. Results In 9 studies, Xpert MTB/RIF was compared with CRS, while in 24 studies, it was compared with culture. The sensitivity and specificity of the Xpert MTB/RIF test were 85% and 97%, respectively, against CRS and 85% and 78%, respectively, against culture. FNA sensitivity and specificity were 93% and 88% respectively against CRS and 87% and 77% respectively against culture. For tissue samples, the sensitivity and specificity were 74% and 100%, respectively, against CRS and 74% and 77%, respectively, against culture. For the adult cohort (&gt;14 years), the sensitivity and specificity of FNA samples were 80% and 75% against culture and 85% and 88% respectively against CRS. The pooled sensitivity and specificity of Xpert for detecting rifampicin resistance were 90% and 99% respectively. Conclusion Xpert MTB/RIF demonstrated excellent accuracy for diagnosing LNTB and rifampicin resistance, with FNA samples outperforming tissue samples acquired through biopsy and CRS as superior to culture standards.

Developments of the mDZ-RhoBAST Probe for Super-Resolution Imaging of FTO Demethylation in Live Cells

Seasonal and spatial variations in eutrophication and water quality of Lake Aha, Guiyang city, China

This study aimed to analyze the spatial and temporal variations in water quality status and eutrophication level of Lake Aha, influenced by human activities and seasonal changes. Ten indicators were sampled and analyzed at seven sampling points in Lake Aha in different seasons and vertical layers. The eutrophication level and water quality status were evaluated using the Trophic Level Index (TLI) and Water Quality Index (WQI). Results showed that the average TLI and WQI values during the wet season (July) were 31.06 and 92.14, respectively, compared to 28.64 and 109.14 during the dry season (April). Eutrophication was more severe in the wet season than in the dry season, whereas water quality was poorer in the dry season than in the wet season. The main factors driving these patters were temperature and precipitation, respectively. Spatially, the northern part of Lake Aha exhibited higher eutrophication levels than the southern part, while water quality was better in the south than in the north, largely due to the impact of human activities. Significant differences in eutrophication levels and water quality were observed among the seven sampling points, though variations across vertical layers were minimal. Strong positive correlations between key indicators—such as CODMn, TP, and Chl-a—highlighted interdependencies affecting overall water quality, with these factors identified as critical drivers of TLI and WQI. These findings indicate the important impacts of seasonal changes and human activities on the water quality of Lake Aha and suggest the need for targeted water pollution management strategies.

Isoleucine Side Chains as Reporters of Conformational Freedom in Protein Folding Studied by DNP-Enhanced NMR

Interventions to improve awareness and reduce the stigma associated with neurodegenerative conditions in minority ethnic communities: A scoping review protocol

Objective This scoping review aims to identify interventions aiming to improve awareness of and reduce stigma related to neurodegenerative conditions within South Asian and Black (African-Caribbean, African, African American, Black British) communities with a focus on synthesising the methods employed for culturally tailoring interventions. Introduction Minority ethnic communities affected by neurodegenerative conditions often face health and social care disparities. This can lead to delayed diagnosis and poor health outcomes. Interventions that provide relevant, accessible information about neurodegenerative conditions may help reduce disparities in care access. There is limited knowledge about the methods used to culturally tailor interventions for minority ethnic communities and their efficacy. Inclusion criteria Eligible sources will include interventions specifically tailored for South Asian and Black communities, living with dementia, Parkinson’s disease, Huntington’s disease, or motor neurone disease. Interventions must be conducted in countries that are member states of the Organisation for Economic Co-operation and Development where these two groups constitute minority populations and are likely to face inequalities in care access. Methods A scoping review guided by the Joanna Briggs Institute Manual for Evidence Synthesis will be conducted. Searches of Medline (EBSCO), APA PsycInfo (EBSCO), and EMBASE (Elsevier) will be conducted. Study selection will be based on 100% agreement between two reviewers. Data will be extracted, charted, and summarised narratively followed by consultation with stakeholders. Implications This review will identify culturally sensitive strategies for raising awareness and reducing the stigma associated with neurodegenerative conditions among South Asian and Black communities within the Organisation for Economic Co-operation and Development countries. By utilising these inclusive approaches, communities may feel more empowered to seek a diagnosis for symptoms and live better with the condition. The findings of this review will be shared with the public and policymakers to promote awareness and evidence-based policy making.

Molecular Dynamics Simulations of Native Protein Charging in Electrosprayed Droplets with Experimentally Relevant Compositions

Global trends and patterns in cardiovascular disease burden attributable to low physical activity: A systematic analysis for Global Burden of Disease Study from 1990 to 2021

Background This study analyzes the global burden of cardiovascular diseases (CVD) related to low physical activity from 1990 to 2021, focusing on spatiotemporal changes. Method Using data from the GBD study, we examined trends in CVD burden linked to low physical activity, including mortality counts, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and age-standardized disability rates (ASDR). Decomposition analysis was used to identify key drivers of these changes, and frontier analysis visualized each country's potential to reduce the burden. An autoregressive integrated moving average model was used to forecast the burden from 2022 to 2036. Results In 2021, approximately 370,000 deaths globally were attributed to CVD due to low physical activity. The ASMR and ASDR for CVD were 4.53 per 100,000 (95% uncertainty interval: 1.52 to 8.05) and 85.95 (95% UI: 35.25 to 140.65), respectively. From 1990 to 2021, the global burden increased, particularly in regions with a middle socio-demographic index, driven by aging populations and population growth. The ASMR is projected to decrease to 3.49 per 100,000 by 2036. Conclusions Low physical activity is a major contributor to CVD-related mortality and disability worldwide. Public health interventions aimed at increasing physical activity, especially in regions with rising burdens, are essential to reduce the global CVD burden.

Uncovering the Molecular Landscape of Tetracycline Family Natural Products through Bacterial Genome Mining

Mapping Important Shark and Ray Areas (ISRAs) in the Central and South American Pacific: Existing knowledge and data needs

Identifying critical habitats is key to the conservation and recovery of threatened species. A third of chondrichthyans (sharks, rays, and chimaeras) are threatened with extinction but robust biological and ecological information to delineate critical habitats for many species remains limited. Here, we investigated (1) research outputs and trends across the Central and South American Pacific region to determine whether sufficient information was available to identify critical habitats; (2) whether regional Important Shark and Ray Areas (ISRAs) were spatially representative; (3) what species and which ecological traits were most commonly used in the delineation of critical habitats; and (4) discuss how ISRAs can inform research priorities and area-based management in support of chondrichthyan conservation. Sixty-five ISRAs were identified for 97 of 190 chondrichthyan species occurring in the region (51%). Across key life-history processes, reproductive areas were most identified (n = 50). Of 821 published studies (2,160 entries), 31.48% (28% entries) primarily focused on fisheries and 48.51% included enough information to inform the ISRA process. Most (58.98%) of these studies originated from Mexico (n = 342, 744 entries) and Ecuador (n = 147, 276 entries). France and Honduras had the least regional research outputs relevant to apply the ISRA Criteria. Significant ecological data gaps were identified in oceanic (including areas beyond national jurisdiction), deepwater (&gt;200 m), and along the southern part of the region (i.e., southern Chile). Deepwater species, chimaeras, and 21% of threatened species had knowledge gaps that did not allow the identification of ISRAs. If area-based management decisions in this region were based on ISRAs, and effectively implemented and enforced, diversity hotspots and at least 97 species could receive protection, including 79% of threatened species and 54% of those considered range-restricted. Increased monitoring and research efforts, with a corresponding increase in funding to fill existing gaps is key to support the identification of important habitats across this region.

Heterometallic Aluminum Metal–Organic Frameworks

Timing and predictors of disease incidence among named contacts of reported tuberculosis patients in a low incidence setting

Contact investigations are crucial for tuberculosis (TB) control, yet the temporal dynamics of disease progression among exposed contacts remain poorly understood. We conducted a retrospective cohort study of 44,106 contacts linked to 6,243 index TB cases diagnosed between 2009 and 2023. During the 15-year follow-up, 454 contacts developed TB disease, with 43.4% being incident cases. Using time-to-event analysis with left truncation to account for varying follow-up times, and mixed effect Cox models to account for index case and county-level variability, we estimated the median time to TB incidence at 11 (IQR 4–48) months after initiating contact investigation. The risk of TB disease varied markedly by age and immune status. Children aged 0–15 showed over nine times higher risk compared to adults aged 25–44 (aHR = 9.59; 95% CI: 3.17–29.02; p &lt; 0.001). Contacts co-infected with HIV demonstrated a three-fold increased risk of TB (aHR = 2.35; 95% CI: 1.08–5.10; p = 0.031) relative to those without HIV. A history of a previous TB diagnosis conferred a protective effect on the risk of TB incident (aHR = 0.40; 95% CI: 0.20–0.80; p = 0.009). Additionally, individuals who had incomplete therapy for latent TB infection (LTBI) also experienced a protective effect (aHR = 0.32; 95% CI: 0.15–0.71; p = 0.005). These findings highlight a critical window for intervention with follow-up needed for at least 1–4 years after initial contact investigations. The results also emphasize the need for targeted, risk-stratified surveillance and LTBI treatment for children and individuals with HIV who are contacts of confirmed TB cases.

Correction to “In-Situ Identification of Zinc Sites as Potential-Dependent Selectivity Switch over Dual-Atom Catalysts for H₂O₂ Electrosynthesis”

Retrospective radiographic myelogram measurements and long-term outcomes in horses undergoing cervical interbody fusion surgery: 22 cases

Site selection for cervical stabilization surgery in horses with spinal ataxia frequently relies on measurements derived from radiographic myelography. A variety of measurement criteria exist and can provide conflicting results. The main objectives of this study were to assess the correlation between two commonly used myelographic measures, dorsal contrast column reduction (DCCR) and dural diameter reduction (DDR), and their association with previously selected operative sites in a population of horses operated at a tertiary clinic. Secondary objectives were to determine if articular process joint (APJ) atrophy occurred in a subset of operated horses with radiographic follow-up, and to describe complications of cervical stabilization surgery and long term outcomes. The study was primarily cross-sectional using previously recorded medical information and images from horses operated between 2008 and 2022: three masked raters assessed previously acquired pre-operative myelograms obtained in neutral, flexed and extended neck positions from horses that had subsequently undergone stabilization surgery consisting of cervical interbody fusion via a Kerf-cut cylinder technique at one or two sites. A veterinary radiologist evaluated changes in APJ in radiographs obtained in a subset of horses re-evaluated &gt;18 months after surgery. DCCR was unremarkable at nearly all articulations in all horses, while DDR met reduction criteria at over 50% of articulations in flexed position. Neither DCCR nor DDR distinguished operated from non-operated sites at most intervertebral junctions, except at the C6-7 articulation in neutral and extended position. The two measures were also poorly correlated at most sites and in most positions. Surgical complications included a high incidence of laryngeal hemiplegia. Comparison of operated to non-operated sites within individuals radiographed years later showed consistent, mildly reduced APJ opacity at most operated sites without a consistent decrease in APJ height or area ratios. Our results suggest that DCCR and DDR measures did not reliably predict surgical site selection in this surgical cohort except at C6-7, and that the two measures yielded conflicting diagnostic classification at many sites and positions. Complication rates from stabilization surgery were high; and predictable reduction in APJ height or area after surgery was not demonstrated by radiography in this study.

Quantitative Skeletal-Charge Engineering of Anion-Selective COF Membrane for Ultrahigh Osmotic Power Output