Geo-Spatial Analysis of Acute Ischemic Stroke Reperfusion Treatment in India: An Assessment of Distribution and Access to Centers.

Background: Stroke is a leading cause of global mortality and disability, with a disproportionately high burden in low- and middle-income countries. Access to intravenous thrombolysis (IVT) and endovascular treatment (EVT) remains extremely limited.

Aims: We evaluated the spatial distribution and geographic accessibility of stroke centers in India.

A function of TPL/TBL1-type corepressors is to nucleate the assembly of the preinitiation complex.

The plant corepressor TPL is recruited to diverse chromatin contexts, yet its mechanism of repression remains unclear. Previously, we leveraged the fact that TPL retains its function in a synthetic transcriptional circuit in the yeast model Saccharomyces cerevisiae to localize repressive function to two distinct domains. Here, we employed two unbiased whole-genome approaches to map the physical and genetic interactions of TPL at a repressed locus.

Structural and political determinants of health among Syrian refugee young adults in the Bekaa, Lebanon: a prospective cohort study of the impact of security raids on perceived discrimination and well-being.

Objectives: In this work, which forms part of a larger study of a longitudinal intervention focused on empowering Community Mental Health Workers in a humanitarian context, we examine changes in and correlates of well-being of refugees as a result of discriminatory practices by the State, with comparisons motivated by a mechanistic model of well-being.

Design: This cohort study examines well-being at a single follow-up time as predicted by baseline characteristics in response to a changing social conditions including security raids on our participants; the parent interventional randomised trial focuses on a population of youth in a refugee context, but the present work precedes the main intervention period.

Setting: Refugee populations are among the most vulnerable globally, and the total refugee population is growing dramatically.

Evaluating Usability and Feasibility of Implementing a Novel Cancer Mapping Tool.

Purpose: Cancer registries are often asked to present cancer data for small geographic areas to inform and facilitate targeted interventions and prevention programs. However, it is challenging to compute and visualize reliable cancer estimates for areas with small case counts and populations to support cancer control planning.

Methods: We used a Bayesian hierarchical model that borrows strength from neighboring areas and over time to produce cancer estimates for small areas.

pSPObooster: A Plasmid System to Improve Sporulation Efficiency of Saccharomyces cerevisiae Lab Strains.

Common Saccharomyces cerevisiae lab yeast strains derived from S288C have meiotic defects and therefore are poor sporulators. Here, we developed a plasmid system containing corrected alleles of the MKT1 and RME1 genes to rescue the meiotic defects and show that standard BY4741 and BY4742 strains containing the plasmid display faster and more efficient sporulation. The plasmid, pSPObooster, can be maintained as an episome and easily cured or stably integrated into the genome at a single locus.

The power and pitfalls of underpowered studies.

This article reflects on the potential value and many pitfalls of underpowered studies to help authors and readers consider whether and how they contribute meaningfully to the published literature. A basic introduction to power and sample size calculations is provided. Several problems that can arise in analysis and publication of underpowered studies are described.

A TNIP1-driven systemic autoimmune disorder with elevated IgG4.

Whole-exome sequencing of two unrelated kindreds with systemic autoimmune disease featuring antinuclear antibodies with IgG4 elevation uncovered an identical ultrarare heterozygous TNIP1 variant segregating with disease. Mice with the orthologous Q346P variant developed antinuclear autoantibodies, salivary gland inflammation, elevated IgG2c, spontaneous germinal centers and expansion of age-associated B cells, plasma cells and follicular and extrafollicular helper T cells. B cell phenotypes were cell-autonomous and rescued by ablation of Toll-like receptor 7 (TLR7) or MyD88.

Syrian refugee young adults as community mental health workers implementing problem management plus: Protocol for a pilot randomized controlled trial to measure the mechanisms of effect on their own wellbeing, stress and coping.

Unlabelled: This pilot randomized controlled trial protocol aims to (1) assess the impact on the wellbeing of Syrian refugee young adults (18-24 years) of being a community mental health worker (CMHW) implementing WHO's evidence-based psychosocial intervention - Problem Management Plus (PM+) - with adults in their community, and (2) identify the mechanisms associated with the outcomes of enhanced wellbeing and coping, and reduced stress among these CMHWs. Over 108 million people have been forcibly displaced as of the end of 2022. Mental health consequences of these displacements are significant, yet human resources for health are not sufficient to meet the needs.

The cytidine deaminase APOBEC3C has unique sequence and genome feature preferences.

APOBEC proteins are cytidine deaminases that restrict the replication of viruses and transposable elements. Several members of the APOBEC3 family, APOBEC3A, APOBEC3B, and APOBEC3H-I, can access the nucleus and cause what is thought to be indiscriminate deamination of the genome, resulting in mutagenesis and genome instability. Although APOBEC3C is also present in the nucleus, the full scope of its deamination target preferences is unknown.

Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics.

New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, the sublineage-defining mutations vary between the VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for mutations at each spike position or the stochastic nature of their appearance.

Predictive Modeling for One-Year Lower Extremity Endovascular Revascularization Failure in Black Persons.

Introduction: Black persons bear a disproportionate burden of peripheral artery disease (PAD) and experience higher rates of endovascular revascularization failure (ERF) when compared with non-Hispanic White persons. We aimed to identify predictors of ERF in Black persons using predictive modeling.

Methods: This retrospective study included all persons identifying as Black who underwent an initial endovascular revascularization procedure for PAD between 2011 and 2018 at a midwestern tertiary care center.

Predicting dental caries outcomes in young adults using machine learning approach.

Objectives: To predict the dental caries outcomes in young adults from a set of longitudinally-obtained predictor variables and identify the most important predictors using machine learning techniques.

Methods: This study was conducted using the Iowa Fluoride Study dataset. The predictor variables - sex, mother's education, family income, composite socio-economic status (SES), caries experience at ages 9, 13, and 17, and the cumulative estimates of risk and protective factors, including fluoride, dietary, and behavioral variables from ages 5-9, 9-13, 13-17, and 17-23 were used to predict the age 23 DMFS count.

A conserved function of corepressors is to nucleate assembly of the transcriptional preinitiation complex.

The plant corepressor TPL is recruited to diverse chromatin contexts, yet its mechanism of repression remains unclear. Previously, we have leveraged the fact that TPL retains its function in a synthetic transcriptional circuit in the yeast model to localize repressive function to two distinct domains. Here, we employed two unbiased whole genome approaches to map the physical and genetic interactions of TPL at a repressed locus.

Cytidine deaminases APOBEC3C and APOBEC3D promote DNA replication stress resistance in pancreatic cancer cells.

Gemcitabine is a potent inhibitor of DNA replication and is a mainstay therapeutic for diverse cancers, particularly pancreatic ductal adenocarcinoma (PDAC). However, most tumors remain refractory to gemcitabine therapies. Here, to define the cancer cell response to gemcitabine, we performed genome-scale CRISPR-Cas9 chemical-genetic screens in PDAC cells and found selective loss of cell fitness upon disruption of the cytidine deaminases APOBEC3C and APOBEC3D.

Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about their contribution to disease pathogenesis. Amongst them, SH2B3-a negative regulator of cytokine and growth factor receptor signaling-harbors rare coding variants in over 5% of SLE patients.

Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection.

The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of Leishmania infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease.

Joint Bayesian longitudinal models for mixed outcome types and associated model selection techniques.

Motivated by data measuring progression of leishmaniosis in a cohort of US dogs, we develop a Bayesian longitudinal model with autoregressive errors to jointly analyze ordinal and continuous outcomes. Multivariate methods can borrow strength across responses and may produce improved longitudinal forecasts of disease progression over univariate methods. We explore the performance of our proposed model under simulation, and demonstrate that it has improved prediction accuracy over traditional Bayesian hierarchical models.

Genetic screens in Saccharomyces cerevisiae identify a role for 40S ribosome recycling factors Tma20 and Tma22 in nonsense-mediated decay.

The decay of messenger RNA with a premature termination codon by nonsense-mediated decay (NMD) is an important regulatory pathway for eukaryotes and an essential pathway in mammals. NMD is typically triggered by the ribosome terminating at a stop codon that is aberrantly distant from the poly-A tail. Here, we use a fluorescence screen to identify factors involved in NMD in Saccharomyces cerevisiae.

FBXW7-loss Sensitizes Cells to ATR Inhibition Through Induced Mitotic Catastrophe.

Unlabelled: FBXW7 is a commonly mutated tumor suppressor gene that functions to regulate numerous oncogenes involved in cell-cycle regulation. Genome-wide CRISPR fitness screens identified a signature of DNA repair and DNA damage response genes as required for the growth of FBXW7-knockout cells. Guided by these findings, we show that FBXW7-mutant cells have high levels of replication stress, which results in a genotype-specific vulnerability to inhibition of the ATR signaling pathway, as these mutant cells become heavily reliant on a robust S-G2 checkpoint.

Predicting Dental Caries Outcomes in Young Adults Using Machine Learning Approach.

Objectives: To predict the dental caries outcomes in young adults from a set of longitudinally-obtained predictor variables and identify the most important predictors using machine learning techniques.

Methods: This study was conducted using the Iowa Fluoride Study dataset. The predictor variables - sex, mother's education, family income, composite socio-economic status (SES), caries experience at ages 9, 13, and 17, and the cumulative estimates of risk and protective factors, including fluoride, dietary, and behavioral variables from ages 5-9, 9-13, 13-17, and 17-23 were used to predict the age 23 DMFS count.

Olfaction and reaction: The role of olfactory and hypothalamic investment in the antipredator responses to chemical alarm cues by northern redbelly dace.

Neuroplasticity enables teleosts to promote or downregulate the growth of their brains regionally. To compensate for the effects of predation pressure, teleosts may alter their brain morphology and behavioral responses to mitigate its impact on individual fitness. High-predation environments often promote specific patterns of brain growth and produce bolder and more proactive populations.

Uncertainty about predation risk: a conceptual review.

Uncertainty has long been of interest to economists and psychologists and has more recently gained attention among ecologists. In the ecological world, animals must regularly make decisions related to finding resources and avoiding threats. Here, we describe uncertainty as a perceptual phenomenon of decision-makers, and we focus specifically on the functional ecology of such uncertainty regarding predation risk.