Bdelloid rotifers deploy horizontally acquired biosynthetic genes against a fungal pathogen.

Coevolutionary antagonism generates relentless selection that can favour genetic exchange, including transfer of antibiotic synthesis and resistance genes among bacteria, and sexual recombination of disease resistance alleles in eukaryotes. We report an unusual link between biological conflict and DNA transfer in bdelloid rotifers, microscopic animals whose genomes show elevated levels of horizontal gene transfer from non-metazoan taxa. When rotifers were challenged with a fungal pathogen, horizontally acquired genes were over twice as likely to be upregulated as other genes - a stronger enrichment than observed for abiotic stressors. Among hundreds of upregulated genes, the most markedly overrepresented were clusters resembling bacterial polyketide and nonribosomal peptide synthetases that produce antibiotics. Upregulation of these clusters in a pathogen-resistant rotifer species was nearly ten times stronger than in a susceptible species. By acquiring, domesticating, and expressing non-metazoan biosynthetic pathways, bdelloids may have evolved to resist natural enemies using antimicrobial mechanisms absent from other animals.

Speech-language within and between network disruptions in primary progressive aphasia variants.

Primary progressive aphasia (PPA) variants present with distinct disruptions in speech-language functions with little known about the interplay between affected and spared regions within the speech-language network and their interaction with other functional networks. The Neurodegenerative Research Group, Mayo Clinic, recruited 123 patients with PPA (55 logopenic (lvPPA), 44 non-fluent (nfvPPA) and 24 semantic (svPPA)) who were matched to 60 healthy controls. We investigated functional connectivity disruptions between regions within the left-speech-language network (Broca, Wernicke, anterior middle temporal gyrus (aMTG), supplementary motor area (SMA), planum temporale (PT) and parietal operculum (PO)), and disruptions to other networks (visual association, dorsal-attention, frontoparietal and default mode networks (DMN)). Within the speech-language network, multivariate linear regression models showed reduced aMTG-Broca connectivity in all variants, with lvPPA and nfvPPA findings remaining significant after Bonferroni correction. Additional loss in Wernicke-Broca connectivity in nfvPPA, Wernicke-PT connectivity in lvPPA and greater aMTG-PT connectivity in svPPA were also noted. Between-network connectivity findings in all variants showed reduced aMTG-DMN and increased aMTG-dorsal-attention connectivity, with additional disruptions between aMTG-visual association in both lvPPA and svPPA, aMTG-frontoparietal in lvPPA, and Wernicke-DMN breakdown in svPPA. These findings suggest that aMTG connectivity breakdown is a shared feature in all PPA variants, with lvPPA showing more extensive connectivity disruptions with other networks.

Muscle mitochondrial function is impaired in adults with type 1 diabetes.

AIMS: Type 1 diabetes has been associated with mitochondrial dysfunction. However, the mechanism of this dysfunction in adults remains unclear. METHODS: A secondary analysis was conducted using data from several clinical trials measuring in-vivo and ex-vivo mitochondrial function in adults with type 1 diabetes (n = 34, age 38.8 ± 14.6 years) and similarly aged controls (n = 59, age 44.6 ± 13.9 years). In-vivo mitochondrial function was assessed before, during, and after isometric exercise with 31phosphorous magnetic resonance spectroscopy. High resolution respirometry of vastus lateralis muscle tissue was used to assess ex-vivo measures. RESULTS: In-vivo data showed higher rates of anaerobic glycolysis (p = 0.013), and a lower maximal mitochondrial oxidative capacity (p = 0.012) and mitochondrial efficiency (p = 0.024) in adults with type 1 diabetes. After adjustment for age and percent body fat maximal mitochondrial capacity (p = 0.014) continued to be lower and anaerobic glycolysis higher (p = 0.040) in adults with type 1 diabetes. Ex-vivo data did not demonstrate significant differences between the two groups. CONCLUSIONS: The in-vivo analysis demonstrates that adults with type 1 diabetes have mitochondrial dysfunction. This builds on previous research showing in-vivo mitochondrial dysfunction in youths with type 1 diabetes and suggests that defects in substrate or oxygen delivery may play a role in in-vivo dysfunction.

Radiographic Findings Associated With Mild Hip Dysplasia in 3869 Patients Using a Deep Learning Measurement Tool.

Background: Hip dysplasia is considered one of the leading etiologies contributing to hip degeneration and the eventual need for total hip arthroplasty (THA). We validated a deep learning (DL) algorithm to measure angles relevant to hip dysplasia and applied this algorithm to determine the prevalence of dysplasia in a large population based on incremental radiographic cutoffs. Methods: Patients from the Osteoarthritis Initiative with anteroposterior pelvis radiographs and without previous THAs were included. A DL algorithm automated 3 angles associated with hip dysplasia: modified lateral center-edge angle (LCEA), Tönnis angle, and modified Sharp angle. The algorithm was validated against manual measurements, and all angles were measured in a cohort of 3869 patients (61.2 ± 9.2 years, 57.1% female). The percentile distributions and prevalence of dysplastic hips were analyzed using each angle. Results: The algorithm had no significant difference (P > .05) in measurements (paired difference: 0.3°-0.7°) against readers and had excellent agreement for dysplasia classification (kappa = 0.78-0.88). In 140 minutes, 23,214 measurements were automated for 3869 patients. LCEA and Sharp angles were higher and the Tönnis angle was lower (P < .01) in females. The dysplastic hip prevalence varied from 2.5% to 20% utilizing the following cutoffs: 17.3°-25.5° (LCEA), 9.4°-15.6° (Tönnis), and 41.3°-45.9° (Sharp). Conclusions: A DL algorithm was developed to measure and classify hips with mild hip dysplasia. The reported prevalence of dysplasia in a large patient cohort was dependent on both the measurement and threshold, with 12.4% of patients having dysplasia radiographic indices indicative of higher THA risk.

F@#$ pain! A mini-review of the hypoalgesic effects of swearing.

Swearing, or the use of taboo language, has been repeatedly shown to induce hypoalgesia. While reliable hypoalgesic effects have been observed across studies, the mechanisms by which swearing influences pain and the optimal dosage of swearing remain poorly understood. Plausible mechanistic rationale for swearing's impact on pain include sympathetic response, emotion, humor, distraction, aggression, state disinhibition, psychological flow, risky behavior, and self-confidence. It remains unknown how the intensity of the swear word, speech volume, frequency, or timing influences pain modulation. While the majority of evidence demonstrates the efficacy of swearing at attenuating acute pain responses, these studies have utilized healthy populations with controlled experiments in laboratory settings. Comparatively, less is known about how laboratory findings translate practically/clinically to diverse populations, various dosages, and different pain chronicities. A greater understanding of mechanistic underpinnings and practical implications are necessary to feasibly implement swearing as a therapeutic modality to combat pain. The purpose of the following mini-review is to provide an overview of the current evidence on swearing for the reduction of pain, speculate on plausible underlying mechanisms, and discuss the potential for optimization of swearing for real-world translation. Lastly, identifying knowledge gaps to aid in directing future research will be discussed.

Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Staging Extramitral Cardiac Damage in Mitral Annular Calcification With Mitral Valve Dysfunction.

BACKGROUND: Mitral annular calcification (MAC) is a progressive degenerative process associated with comorbidities and increased mortality. A staging system that considers extramitral cardiac damage in MAC may help improve patient selection for mitral valve interventions. OBJECTIVES: This study sought to develop a transthoracic echocardiogram (TTE)-based cardiac staging system in patients with MAC and significant mitral valve dysfunction and assess its prognostic utility. METHODS: We retrospectively evaluated all adults who underwent TTE over 1 year at Mayo Clinic with MAC and significant mitral valve dysfunction defined as mitral stenosis and/or at least moderate mitral regurgitation. Patients were categorized into 5 stages according to extramitral cardiac damage by TTE. All-cause mortality and heart failure hospitalization were assessed. RESULTS: For the 953 included patients, the mean age was 76.2 ± 10.7 years, and 54.0% were women. Twenty-eight (2.9%) patients were classified in stages 0 to 1, 499 (52.4%) in stage 2, 115 (12.1%) in stage 3, and 311 (32.6%) in stage 4. At the 3.8-year follow-up, mortality was significantly higher in patients in stages 2 to 4 compared to stages 0 to 1 and increased with each stage. Survival differences were maintained after adjustment for age, diabetes mellitus, and glomerular filtration rate. The rate of heart failure hospitalization was significantly higher in stages 3 and 4 compared to stages 0 to 1. Similar results were observed in subgroup analysis in patients with moderate or severe MAC, predominant mitral stenosis, or predominant mitral regurgitation. CONCLUSIONS: Using the proposed extramitral cardiac damage staging system in patients with MAC and significant mitral valve dysfunction, more advanced stages are associated with higher mortality.

Summary of the National Cancer Institute 2023 Virtual Workshop on Medical Image De-identification-Part 2: Pathology Whole Slide Image De-identification, De-facing, the Role of AI in Image De-identification, and the NCI MIDI Datasets and Pipeline.

De-identification of medical images intended for research is a core requirement for data sharing initiatives, particularly as the demand for data for artificial intelligence (AI) applications grows. The Center for Biomedical Informatics and Information Technology (CBIIT) of the United States National Cancer Institute (NCI) convened a two half-day virtual workshop with the intent of summarizing the state of the art in de-identification technology and processes and exploring interesting aspects of the subject. This paper summarizes the highlights of the second day of the workshop, the recordings and presentations of which are publicly available for review. The topics covered included pathology whole slide image de-identification, de-facing, the role of AI in image de-identification, and the NCI Medical Image De-Identification Initiative (MIDI) datasets and pipeline.

Implementation strategies to improve HIV care cascade outcomes in low- and middle-income countries: a systematic review from 2014 to 2021.

INTRODUCTION: In low- and middle-income countries (LMICs), which are disproportionately affected by the HIV epidemic and manage limited resources, optimized implementation strategies are needed to enhance the efficiency of the HIV response. Assessing strategy usage to date could identify research gaps and inform future implementation efforts. We conducted a systematic review to describe the features and distributions of published implementation strategies attempting to improve HIV treatment service delivery and outcomes. METHODS: We searched PubMed, Embase, and CINAHL and screened abstracts and full texts published between 1 January 2014 and 27 August 2021, for English-language studies conducted in LMICs that described the implementation of HIV intervention and reported at least one HIV care cascade outcome, ranging from HIV testing to viral suppression. Implementation strategies were inductively specified, characterized by unique combinations of actor, action and action target, and summarized based on existing implementation strategy taxonomies. All strategies included in this study were independently reviewed to ensure accuracy and consistency. RESULTS: We identified 44,126 abstracts and reviewed 1504 full-text manuscripts. Among 485 included studies, 83% were conducted in sub-Saharan Africa; the rest were conducted in South-East Asia and Western Pacific (12%), and the Americas (8%). A total of 7253 unique implementation strategies were identified, including changing health service delivery (48%) and providing capacity building and support strategies (34%). Healthcare providers and researchers led 59% and 28% of the strategies, respectively. People living with HIV and their communities (62%) and healthcare providers (38%) were common strategy targets. Strategies attempting to change governance, financial arrangements and implementation processes were rarely reported. DISCUSSION: We identified a range of published implementation strategies that addressed HIV cascade outcomes, though some key gaps exist. We may need to expand the application of implementation strategies to ensure that all stakeholders are meaningfully involved to support equitable implementation efforts across the geographic regions and target populations, and to optimize implementation outcomes. CONCLUSIONS: Some health service delivery and capacity building and support strategies have been most commonly used to date. Future research and implementation may incorporate a more diverse range of strategies and detailed reporting on their usage to inform improved HIV responses globally.

Advanced chronic kidney disease increases complications in anterior cervical discectomies with fusions: An analysis of 75,508 patients.

Background: Although anterior cervical discectomy and fusion (ACDF) procedures for cervical spine disease have been increasing amid a growing population of patients with kidney dysfunction, there is a scarcity of literature focusing on kidney dysfunction as a risk-factor for post-operative ACDF complications. The purpose is to evaluate the differential impact of kidney dysfunction on perioperative outcomes including surgical and medical complications, extended length of hospital stay (LOS), and death within 30 days following ACDF. Patient Sample: This was a retrospective cohort study of prospectively collected data using the American College of Surgeons National Surgical Quality Improvement Program database to identify patients who had undergone an elective ACDF procedure between 2011-2021 using Current Procedural Terminology code 22551. Patients were categorized into five cohorts based on eGFR according to the "Kidney Disease: Improving Global Outcomes" Classification: values of: ≥ 90(reference cohort), 60-89 (G2), 30-59 (G3), 15-29 (G4), and <15 (G5). One-way ANOVA for continuous variables and chi-square tests for categorical variables were used to identify differences in perioperative variables between the five groups. Multivariable logistic regression analysis assessed the effect of kidney dysfunction on post-operative surgical outcomes. Significance was defined as p<.05. Results: About 75,508 ACDF patients were included, of who 57,480 were G1, 15,186 were G2, 2,192 were G3, 312 were G4, and 338 were G5. G4 and G5 independently increased the risk of medical complications (OR: 1.893, 95% CI [1.296-2.705]; OR: 2.241, 95% CI [1.222-3.964]) and blood transfusion. Only G5 independently increased the risk for extended LOS (OR: 2.410, 95% CI [1.281-4.371], p=.005). Conclusion: High grade CKD is an independent risk factor for medical complications, extended hospital LOS, and blood transfusions following ACDF, underscoring the importance of risk stratification to optimize perioperative management and reduce the burden of complications and healthcare costs. Conversely, low grade CKD does not increase the risk of complications in ACDF.

Collective peroxide detoxification determines microbial mutation rate plasticity in E. coli.

Mutagenesis is responsive to many environmental factors. Evolution therefore depends on the environment not only for selection but also in determining the variation available in a population. One such environmental dependency is the inverse relationship between mutation rates and population density in many microbial species. Here, we determine the mechanism responsible for this mutation rate plasticity. Using dynamical computational modelling and in culture mutation rate estimation, we show that the negative relationship between mutation rate and population density arises from the collective ability of microbial populations to control concentrations of hydrogen peroxide. We demonstrate a loss of this density-associated mutation rate plasticity (DAMP) when Escherichia coli populations are deficient in the degradation of hydrogen peroxide. We further show that the reduction in mutation rate in denser populations is restored in peroxide degradation-deficient cells by the presence of wild-type cells in a mixed population. Together, these model-guided experiments provide a mechanistic explanation for DAMP, applicable across all domains of life, and frames mutation rate as a dynamic trait shaped by microbial community composition.

A Single-Shot Technique for Measuring Broadband Two-Photon Absorption Spectra in Solution.

Applications involving two-photon activation, including two-photon fluorescence imaging, photodynamic therapy, and 3D data storage, require precise knowledge of the two-photon absorption (2PA) spectra of target chromophores. Broadband pump-probe spectroscopy using femtosecond laser pulses provides wavelength-dependent 2PA spectra with absolute cross sections, but the measurements are sometimes complicated by cross-phase modulation effects and dispersion of the broadband probe. Here, we introduce a single-shot approach that eliminates artifacts from cross-phase modulation and enables more rapid measurements by avoiding the need to scan the time delay between the pump and the probe pulses. The approach uses counterpropagating beams to automatically integrate over the full interaction between the two pulses as they cross. We demonstrate this single-shot approach for a common 2PA reference, coumarin 153 (C153), in three different solvents using the output from a Yb:KGW laser. This approach provides accurate 2PA cross sections that are more reliable and easier to obtain compared with scanning pump-probe methods using copropagating laser beams. The single-shot method for broadband two-photon absorption (BB-2PA) spectroscopy also has significant advantages compared with single-wavelength measurements, such as z-scan and two-photon fluorescence.

Can white matter hyperintensities based Fazekas visual assessment scales inform about Alzheimer's disease pathology in the population?

BACKGROUND: White matter hyperintensities (WMH) are considered hallmark features of cerebral small vessel disease and have recently been linked to Alzheimer's disease (AD) pathology. Their distinct spatial distributions, namely periventricular versus deep WMH, may differ by underlying age-related and pathobiological processes contributing to cognitive decline. We aimed to identify the spatial patterns of WMH using the 4-scale Fazekas visual assessment and explore their differential association with age, vascular health, AD imaging markers, namely amyloid and tau burden, and cognition. Because our study consisted of scans from GE and Siemens scanners with different resolutions, we also investigated inter-scanner reproducibility and combinability of WMH measurements on imaging. METHODS: We identified 1144 participants from the Mayo Clinic Study of Aging consisting of a population-based sample from Olmsted County, Minnesota with available structural magnetic resonance imaging (MRI), amyloid, and tau positron emission tomography (PET). WMH distribution patterns were assessed on FLAIR-MRI, both 2D axial and 3D, using Fazekas ratings of periventricular and deep WMH severity. We compared the association of periventricular and deep WMH scales with vascular risk factors, amyloid-PET, and tau-PET standardized uptake value ratio, automated WMH volume, and cognition using Pearson partial correlation after adjusting for age. We also evaluated vendor compatibility and reproducibility of the Fazekas scales using intraclass correlations (ICC). RESULTS: Periventricular and deep WMH measurements showed similar correlations with age, cardiometabolic conditions score (vascular risk), and cognition, (p < 0.001). Both periventricular WMH and deep WMH showed weak associations with amyloidosis (R = 0.07, p = < 0.001), and none with tau burden. We found substantial agreement between data from the two scanners for Fazekas measurements (ICC = 0.82 and 0.74). The automated WMH volume had high discriminating power for identifying participants with Fazekas ≥ 2 (area under curve = 0.97) and showed poor correlation with amyloid and tau PET markers similar to the visual grading. CONCLUSION: Our study investigated risk factors underlying WMH spatial patterns and their impact on global cognition, with no discernible differences between periventricular and deep WMH. We observed minimal impact of amyloidosis on WMH severity. These findings, coupled with enhanced inter-scanner reproducibility of WMH data, suggest the combinability of inter-scanner data assessed by harmonized protocols in the context of vascular contributions to cognitive impairment and dementia biomarker research.

Insights from an N3C RECOVER EHR-based cohort study characterizing SARS-CoV-2 reinfections and Long COVID.

BACKGROUND: Although the COVID-19 pandemic has persisted for over 3 years, reinfections with SARS-CoV-2 are not well understood. We aim to characterize reinfection, understand development of Long COVID after reinfection, and compare severity of reinfection with initial infection. METHODS: We use an electronic health record study cohort of over 3 million patients from the National COVID Cohort Collaborative as part of the NIH Researching COVID to Enhance Recovery Initiative. We calculate summary statistics, effect sizes, and Kaplan-Meier curves to better understand COVID-19 reinfections. RESULTS: Here we validate previous findings of reinfection incidence (6.9%), the occurrence of most reinfections during the Omicron epoch, and evidence of multiple reinfections. We present findings that the proportion of Long COVID diagnoses is higher following initial infection than reinfection for infections in the same epoch. We report lower albumin levels leading up to reinfection and a statistically significant association of severity between initial infection and reinfection (chi-squared value: 25,697, p-value: <0.0001) with a medium effect size (Cramer's V: 0.20, DoF = 3). Individuals who experienced severe initial and first reinfection were older in age and at a higher mortality risk than those who had mild initial infection and reinfection. CONCLUSIONS: In a large patient cohort, we find that the severity of reinfection appears to be associated with the severity of initial infection and that Long COVID diagnoses appear to occur more often following initial infection than reinfection in the same epoch. Future research may build on these findings to better understand COVID-19 reinfections.

More than three years after the start of the COVID-19 pandemic, individuals are frequently reporting multiple COVID-19 infections. However, these reinfections remain poorly understood. Here, we investigate COVID-19 reinfections in a large electronic health record cohort of over 3 million patients. We use data summary techniques and statistical tests to characterize reinfections and their relationships with disease severity, biomarkers, and Long COVID. We find that individuals with severe initial infection are more likely to experience severe reinfection, that some protein levels are lower, leading to reinfection, and that a lower proportion of individuals are diagnosed with Long COVID following reinfection than initial infection. Our work highlights the prevalence and impact of reinfections and suggests the need for further research.

Infarct density defined by ADC threshold is associated with long-term functional outcome after endovascular thrombectomy.

OBJECTIVES: Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the reduction in final infarct volume only accounts for 10-15% of the treatment benefit. We aimed to develop a novel MRI-ADC-based metric that quantify the degree of tissue injury to test the hypothesis that it outperforms infarct volume in predicting long-term outcome. MATERIALS AND METHODS: A single-center cohort consisted of consecutive acute stroke patients with anterior circulation large vessel occlusion, successful recanalization via EVT (mTICI ≥2b), and MRI of the brain between 12 hours and 7 days post-EVT. Imaging was processed via RAPID software. Final infarct volume was based on the traditional ADC <620 threshold. Logistic regression quantified the association of lesion volumes and good outcome (90-day modified Rankin Scale ≤2) at a range of lower ADC thresholds (<570, <520, and <470). Infarct density was calculated as the percentage of the final infarct volume below the ADC threshold with the greatest effect size. Univariate and multivariate logistic regression quantified the association between imaging/clinical metrics and functional outcome. RESULTS: 120 patients underwent MRI after successful EVT. Lesion volume based on the ADC threshold <470 had the strongest association with good outcome (OR: 0.81 per 10mL; 95% CI: 0.66-0.99). In a multivariate model, infarct density (<470/<620 * 100) was independently associated with good outcome (aOR 0.68 per 10%; 95% CI: 0.49-0.95), but final infarct volume was not (aOR 0.98 per 10mL; 95% CI: 0.85-1.14). CONCLUSIONS: Infarct density after EVT is more strongly associated with long-term clinical outcome than infarct volume.

Nourishing Physical Productivity and Performance On a Warming Planet - Challenges and Nutritional Strategies to Mitigate Exertional Heat Stress.

PURPOSE OF REVIEW: Climate change is predicted to increase the frequency and severity of exposure to hot environments. This can impair health, physical performance, and productivity for active individuals in occupational and athletic settings. This review summarizes current knowledge and recent advancements in nutritional strategies to minimize the impact of exertional-heat stress (EHS). RECENT FINDINGS: Hydration strategies limiting body mass loss to < 3% during EHS are performance-beneficial in weight-supported activities, although evidence regarding smaller fluid deficits (< 2% body mass loss) and weight-dependent activities is less clear due to a lack of well-designed studies with adequate blinding. Sodium replacement requirements during EHS depends on both sweat losses and the extent of fluid replacement, with quantified sodium replacement only necessary once fluid replacement > 60-80% of losses. Ice ingestion lowers core temperature and may improve thermal comfort and performance outcomes when consumed before, but less so during activity. Prevention and management of gastrointestinal disturbances during EHS should focus on high carbohydrate but low FODMAP availability before and during exercise, frequent provision of carbohydrate and/or protein during exercise, adequate hydration, and body temperature regulation. Evidence for these approaches is lacking in occupational settings. Acute kidney injury is a potential concern resulting from inadequate fluid replacement during and post-EHS, and emerging evidence suggests that repeated exposures may increase the risk of developing chronic kidney disease. Nutritional strategies can help regulate hydration, body temperature, and gastrointestinal status during EHS. Doing so minimizes the impact of EHS on health and safety and optimizes productivity and performance outcomes on a warming planet.

ViViEchoformer: Deep Video Regressor Predicting Ejection Fraction.

Heart disease is the leading cause of death worldwide, and cardiac function as measured by ejection fraction (EF) is an important determinant of outcomes, making accurate measurement a critical parameter in PT evaluation. Echocardiograms are commonly used for measuring EF, but human interpretation has limitations in terms of intra- and inter-observer (or reader) variance. Deep learning (DL) has driven a resurgence in machine learning, leading to advancements in medical applications. We introduce the ViViEchoformer DL approach, which uses a video vision transformer to directly regress the left ventricular function (LVEF) from echocardiogram videos. The study used a dataset of 10,030 apical-4-chamber echocardiography videos from patients at Stanford University Hospital. The model accurately captures spatial information and preserves inter-frame relationships by extracting spatiotemporal tokens from video input, allowing for accurate, fully automatic EF predictions that aid human assessment and analysis. The ViViEchoformer's prediction of ejection fraction has a mean absolute error of 6.14%, a root mean squared error of 8.4%, a mean squared log error of 0.04, and an R 2 of 0.55. ViViEchoformer predicted heart failure with reduced ejection fraction (HFrEF) with an area under the curve of 0.83 and a classification accuracy of 87 using a standard threshold of less than 50% ejection fraction. Our video-based method provides precise left ventricular function quantification, offering a reliable alternative to human evaluation and establishing a fundamental basis for echocardiogram interpretation.

The impact of regional disparities on the availability of meningococcal vaccines in the US.

BACKGROUND: In the United States (US), three types of vaccines are available to prevent invasive meningococcal disease (IMD), a severe and potentially fatal infection: quadrivalent conjugate vaccines against serogroups A, C, W, Y (MenACWY), and monovalent vaccines against serogroup B (MenB) as well as a newly licensed pentavalent vaccine (MenABCWY) protecting against serogroup A, B, C, W, and Y. The CDC's Advisory Committee on Immunization Practices (ACIP) routinely recommends MenACWY vaccine for all 11- to 12-year-olds with a booster dose at 16 years. MenB vaccination is recommended based on shared clinical decision-making (SCDM) for 16- to 23-year-olds. Recently, the pentavalent meningococcal vaccine (MenABCWY) was recommended by the ACIP. Meningococcal vaccine uptake is suboptimal across the country, particularly among individuals with lower socioeconomic status (SES), despite these recommendations. The objective of the spatial analyses was to assess the relationship between stocking of MenACWY and MenB vaccines, area-level SES, and state-level policies. METHODS: The number of MenACWY and MenB doses stocked by vaccinators was obtained from IQVIA and the CDC's Vaccine for Children (VFC) program and compiled into a county-level dataset from 2016 to 2019. SES, as measured using the CDC's Social Vulnerability Index (SVI), state-level school recommendations, and universal purchasing programs were among the main county-level covariates included to control for factors likely influencing stocking. Data were stratified by public and private market. Bayesian spatial regression models were developed to quantify the variations in rates of stocking and the relative rates of stocking of both vaccines. RESULTS: After accounting for county-level characteristics, lower SES counties tended to have fewer doses of MenB relative to MenACWY on both public and private markets. Lower SES counties tended to have more supply of public vs. private doses. Universal purchasing programs had a strong effect on the markets for both vaccines shifting nearly all doses to the public market. School vaccination strategy was key for improving stocking rates. CONCLUSIONS: Overall, the results show that MenACWY has greater stock relative to MenB across the US. This difference is exacerbated in vulnerable areas without school entry requirements for vaccination and results in inequity of vaccine availability. Beyond state-level policy and SES differences, SCDM recommendations may be a contributing factor, although this was not directly assessed by our model.

Epigenetic signals associated with delirium replicated across four independent cohorts.

Delirium is risky and indicates poor outcomes for patients. Therefore, it is crucial to create an effective delirium detection method. However, the epigenetic pathophysiology of delirium remains largely unknown. We aimed to discover reliable and replicable epigenetic (DNA methylation: DNAm) markers that are associated with delirium including post-operative delirium (POD) in blood obtained from patients among four independent cohorts. Blood DNA from four independent cohorts (two inpatient cohorts and two surgery cohorts; 16 to 88 patients each) were analyzed using the Illumina EPIC array platform for genome-wide DNAm analysis. We examined DNAm differences in blood between patients with and without delirium including POD. When we compared top CpG sites previously identified from the initial inpatient cohort with three additional cohorts (one inpatient and two surgery cohorts), 11 of the top 13 CpG sites showed statistically significant differences in DNAm values between the delirium group and non-delirium group in the same directions as found in the initial cohort. This study demonstrated the potential value of epigenetic biomarkers as future diagnostic tools. Furthermore, our findings provide additional evidence of the potential role of epigenetics in the pathophysiology of delirium including POD.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.