Resolving tissue complexity by multimodal spatial omics modeling with MISO.

Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets.

The Relationships between Subjective Wellbeing and Frailty: Staying with a Positive Mind, Stepping away from Accelerated Aging.

Background: Subjective wellbeing (SWB) is a crucial measure of life quality in older adults. Understanding its relationship with frailty may inform strategies to promote healthy aging.

Methods: We analyzed data for older adults aged ≥ 60 years old from Waves 3 and 4 of the China Health and Retirement Longitudinal Study.

Factors associated with tuberculosis treatment initiation among bacteriologically negative individuals evaluated for tuberculosis: An individual patient data meta-analysis.

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.

Methods And Findings: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613).

Disparities in cervical cancer elimination timeframes in the United States: a comparative modeling study.

Population-level estimates in timeframes for reaching cervical cancer (CC) elimination (ie, <4 cases per 100,000 women) in the United States may mask potential disparities in achieving elimination among sub-populations. We used three independent Cancer Intervention and Surveillance Modeling Network (CISNET) models to estimate differences in the time to CC elimination across seven strata of correlated screening and human papillomavirus vaccination uptake, based on national survey data. Compared to the average population, elimination was achieved ≥22 years earlier for the high-uptake strata and ≥27 years later for the most extreme low-uptake strata.

Development and Evaluation of Five-in-One Vaccine Microneedle Array Patch for Diphtheria, Tetanus, Pertussis, Hepatitis B, and Type b: Immunological Efficacy and Long-Term Stability.

: The development of a five-in-one vaccine microneedle patch (five-in-one MN patch) aims to address challenges in administering vaccines against Diphtheria (DT), Tetanus (TT), Pertussis (wP), Hepatitis B (HBsAg), and type b (Hib). Combining multiple vaccines into a single patch offers a novel solution to improve vaccine accessibility, stability, and delivery efficiency, particularly in resource-limited settings. : The five-in-one MN patch consists of four distinct microneedle arrays: DT and TT vaccines are coated together on one array, while wP, HepB, and Hib vaccines are coated separately on individual arrays.

FAF2 is a bifunctional regulator of peroxisomal homeostasis and saturated lipid responses.

Exposure to saturated fatty acids (SFAs), such as palmitic acid, can lead to cellular metabolic dysfunction known as lipotoxicity. Although canonical adaptive metabolic processes like lipid storage or desaturation are known cellular responses to saturated fat exposure, the link between SFA metabolism and organellar biology remains an area of active inquiry. We performed a genome-wide CRISPR knockout screen in human epithelial cells to identify modulators of SFA toxicity.

Depth-corrected multi-factor dissection of chromatin accessibility for scATAC-seq data with PACS.

Single cell ATAC-seq (scATAC-seq) experimental designs have become increasingly complex, with multiple factors that might affect chromatin accessibility, including genotype, cell type, tissue of origin, sample location, batch, etc., whose compound effects are difficult to test by existing methods. In addition, current scATAC-seq data present statistical difficulties due to their sparsity and variations in individual sequence capture.

Exploring novel determinants of exercise behavior: a lagged exposure-wide approach.

Unlabelled: Many middle-aged to older adults do not engage in regular exercise at all, despite its importance for healthy aging. Extensive research grounded in behavioral and social science theories has identified numerous determinants of exercise. However, few studies used an exposure-wide approach, a data-driven exploratory method particularly useful for identifying novel determinants.

Genetic factors shaping the plasma lipidome and the relations to cardiometabolic risk in children and adolescents.

Background: Lipid species are emerging as biomarkers for cardiometabolic risk in both adults and children. The genetic regulation of lipid species and their impact on cardiometabolic risk during early life remain unexplored.

Methods: Using mass spectrometry-based lipidomics, we measured 227 plasma lipid species in 1149 children and adolescents (44.

Changes in optimism and subsequent health and wellbeing outcomes in older adults: an outcome-wide analysis.

Objectives: This study examined whether changes in optimism in older adulthood are associated with subsequent health and wellbeing outcomes.

Method: Longitudinal data are from the Health and Retirement Study, a nationally representative sample of U.S.

Enhancing toxicity prediction for natural products in herbal medicine and dietary supplements: Integrating (Q)STR models and in vitro assays.

New approach methods (NAMs) are required to predict human toxicity effectively, particularly due to limitations in conducting in vivo studies. While NAMs have been established for various industries, such as cosmetics, pesticides, and drugs, their applications in natural products (NPs) are lacking. NPs' complexity (multiple ingredients and structural differences from synthetic compounds) complicates NAM development.

Efficient gene deletion of Integrin alpha 4 in primary mouse CD4 T cells using CRISPR RNA pair-mediated fragmentation.

The functional specialization of CD4 T lymphocytes into various subtypes, including T1 and T cells, is crucial for effective immune responses. T cells facilitate B cell differentiation within germinal centers, while T1 cells are vital for cell-mediated immunity against intracellular pathogens. Integrin α4, a cell surface adhesion molecule, plays significant roles in cell migration and co-stimulatory signaling.

Life course social mobility and cognitive function among middle-aged and older adults in India: Exploring heterogeneity by gender.

This study investigates the link between life course social mobility and cognitive function among middle-aged and older adults in India, specifically emphasizing whether upward and downward mobility exerts symmetric associations and potential gender heterogeneity within these associations. Leveraging data from the Longitudinal Aging Study in India 2017-2018, encompassing 64,710 individuals aged 45 years or above, we classified social mobility as 'consistently high,' 'upward mobility,' 'downward mobility,' and 'consistently low,' based on socioeconomic position during childhood and late adulthood. Multivariable regression and gender-interaction analyses were employed to assess associations.

Early versus late infectious complications following chimeric antigen receptor-modified T-cell therapy.

Despite increasing utilization of CAR T-cell therapy, data are lacking regarding long term follow up and risk of infectious complications after the early period following CAR T-cell infusion. In this study, we sought to compare epidemiology and risk factors for early (≤ 3 months) and late (3 months to 1 year) infections. Data were retrospectively collected at six time points: pre-CAR T, day of infusion, and at 3, 6, 9, and 12 months post CAR-T infusion for all consecutive adult patients treated at our institution.

Cryoballoon Pulmonary Vein Isolation With Versus Without Additional Right Atrial Linear Ablation for Persistent Atrial Fibrillation: The CRALAL Randomized Clinical Trial.

Background: Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with those with paroxysmal AF. We investigate whether additional linear ablation from the superior vena cava to the right atrial septum and cavotricuspid isthmus ablation improves the rhythm outcome of patients with persistent AF undergoing cryoballoon PVI (Cryo-PVI).

Methods: In this investigator-initiated, multicenter, randomized clinical trial, 289 patients with persistent AF refractory to antiarrhythmic drug therapy were randomized 1:1 to either Cryo-PVI with additional right atrium (RA) linear ablation or Cryo-PVI alone.

Overcoming the streetlight effect: Qualitative examination of community experts' perceptions of foundations of learning and development (FOLD) skills.

Developmental science has a long history of studying skills that children need to thrive. However, there has been a primary focus on academic skills, with little attention to the breadth and diversity of other skills that young children need to thrive. Furthermore, little is known about the extent to which community experts involved in early childhood care and education (ECCE) value different early developmental skills.

Mastering the canvas of life: Identifying the antecedents of sense of control using a lagged exposure-wide approach.

Accumulating studies have documented strong associations between a higher sense of control and improved health and well-being outcomes. However, less is known about the determinants of increased sense of control. Our analysis used data from 13,771 older adults in the Health and Retirement Study (HRS)-a diverse, longitudinal, and national study of adults aged >50 in the United States.

Building Social Capital in University Students: A Physical Education Intervention Program.

Background: This study examines the effects of physical education on the social capital of university students, focusing on improving family, neighborhood, and academic relationships through group exercise.

Methods: In Zagreb, Croatia, 976 participants aged 19-20 years participated in a randomized controlled trial. The intervention group (n = 472) engaged in teamwork exercises, and the control group (n = 504) completed individual exercises.

HPV genotype-specific prevalence and infection risks: A 10-year population-based study from the United States.

Background: Various studies have reported on the impact of human papillomavirus (HPV) vaccines. Here we present the largest population-based investigation of genotype-specific distributions over the decade following implementation of the 4-valent HPV vaccine (HPV6/11/16/18) in the United States.

Methods: Liquid-based cervical cytology samples from individuals aged 15-30 years undergoing cervical screening throughout New Mexico were tested by broad-spectrum HPV genotyping.

The 'T paradox' in inflammatory arthritis.

Classic regulatory T (T) cells expressing CD4 and the hallmark transcription factor FOXP3 are integral to the prevention of multi-system autoimmunity. However, immune-mediated arthritis is often associated with increased numbers of T cells in the inflamed joints. To understand these seemingly conflicting observations, which we collectively describe as 'the T paradox', we provide an overview of T cell biology with a focus on T cell heterogeneity, function and dysfunction in arthritis.

Exploring the Trajectories of Depressive Symptoms Associated With Bullying Victimization: The Intersection of Gender and Family Support.

Introduction: Children from multicultural families in South Korea are at high risk of bullying victimization, highlighting the need for a deeper understanding of the challenges they face. This study explores the gendered dynamics of depressive symptoms associated with persistent exposure to bullying victimization among these youths, as well as the role of family support.

Methods: This study utilizes data from nine waves of the Multicultural Adolescents Panel Study (MAPS), spanning from 2011 (Wave 1) to 2019 (Wave 9).

Prevalence of severe and moderate anthropometric failure among children in India, 1993-2021.

Though child anthropometric failure (CAF) is a persistent problem in India, previous studies have often neglected state-level variance and aggregated moderate and severe CAF categories. This study addresses this gap by examining moderate and severe malnutrition across India's states and union territories (UTs) from 1993 to 2021. Data of children under 2 years old from five waves of National Family Health Surveys, a representative cross-sectional survey of Indian households, were analysed.