SMORE: spatial motifs reveal patterns in cellular architecture of complex tissues.

Deciphering the link between tissue architecture and function requires methods to identify and interpret patterns in spatial arrangement of cells. We present SMORE, an approach to detect patterns in sequential arrangements of cells and examine their associated gene expression specializations. Applied to retina, brain, and embryonic tissue maps, SMORE identifies novel spatial motifs, including one that offers a new mechanism of action for type 1b bipolar cells.

Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.

Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.

Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.

KDM6A facilitates Xist upregulation at the onset of X inactivation.

Background: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions.

Pica practices, anemia, and oral health outcomes: a systemic review.

Objectives: Pica is a non-nutritive eating behavior. The potential impact of pica on oral health and the association between pica and anemia are understudied. We examined the current evidence on the relationship between pica practices, anemia, and oral health outcomes.

Predictors of self-reported hypertension among women of reproductive age in North Dakota.

Background: Understanding the risk factors of hypertension among women of reproductive age (18-44 years) is important for guiding health programs aimed at reducing the burden of hypertensive disorders in this population. Therefore, the objective of this study was to investigate predictors of self-reported hypertension among women of reproductive age in North Dakota.

Methods: Behavioral Risk Factor Surveillance System data for the years 2017, 2019, and 2021 were obtained from North Dakota Department of Health and Human Services.

Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases.

Aging remains the foremost risk factor for cardiovascular and cerebrovascular diseases, surpassing traditional factors in epidemiological significance. This review elucidates the cellular and molecular mechanisms underlying vascular aging, with an emphasis on sex differences that influence disease progression and clinical outcomes in older adults. We discuss the convergence of aging processes at the macro- and microvascular levels and their contributions to the pathogenesis of vascular diseases.

Moderate and Vigorous Physical Activity Intensity Cut-Points for Hip-, Wrist-, Thigh-, and Lower Back Worn Accelerometer in Very Old Adults.

Physical activity (PA) reduces the risk of negative mental and physical health outcomes in older adults. Traditionally, PA intensity is classified using METs, with 1 MET equal to 3.5 mL O·min·kg.

Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.

Large floods drive changes in cause-specific mortality in the United States.

Flooding greatly endangers public health and is an urgent concern as rapid population growth in flood-prone regions and more extreme weather events will increase the number of people at risk. However, an exhaustive analysis of mortality following floods has not been conducted. Here we used 35.

A bipartite bacterial virulence factor targets the complement system and neutrophil activation.

The complement system and neutrophils constitute the two main pillars of the host innate immune defense against infection by bacterial pathogens. Here, we identify T-Mac, a novel virulence factor of the periodontal pathogen Treponema denticola that allows bacteria to evade both defense systems. We show that T-Mac is expressed as a pre-protein that is cleaved into two functional units.

Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation.

Hypoxia is a common feature of solid tumors that has previously been linked to resistance to radiotherapy and chemotherapy, and more recently to immunotherapy. In particular, hypoxic tumors exclude T cells and inhibit their activity, suggesting that tumor cells acquire a mechanism to evade T-cell recognition and killing. Our analysis of hypoxic tumors indicates that hypoxia downregulates the expression of MHC class I and its bound peptides (i.

Adaptive average arterial pressure control by multi-agent on-policy reinforcement learning.

The current research introduces a model-free ultra-local model (MFULM) controller that utilizes the multi-agent on-policy reinforcement learning (MAOPRL) technique for remotely regulating blood pressure through precise drug dosing in a closed-loop system. Within the closed-loop system, there exists a MFULM controller, an observer, and an intelligent MAOPRL algorithm. Initially, a flexible MFULM controller is created to make adjustments to blood pressure and medication dosages.

The State of Psychosocial Oncology Research on Black Canadian Affected by Cancer: A Scoping Review.

Purpose Of Review: This study aims to examine the current state of psychosocial oncology (PSO) research concerning Black Canadian communities, focusing on their experiences, psychological states, and non-biological aspects of their cancer journey.

Recent Findings: Although there has been increased attention to PSO in the past two decades, there remains a lack of studies specifically addressing the experiences of Black Canadians affected by cancer. This is especially concerning considering the disparities identified by PSO researchers among Black individuals in the United States and the acknowledged health inequities affecting Black individuals in Canada.

Mental Health Treatment among U.S. Military Veterans: Insights from the National Health Interview Survey.

Background: In the United States (U.S.), the prevalence of anxiety and depression is increasing, yet significant barriers to mental health treatment remain.

Vessel strike encounter risk model informs mortality risk for endangered North Atlantic right whales along the United States east coast.

Vessel strikes are a critical threat to endangered North Atlantic right whales (Eubalaena glacialis), significantly contributing to their elevated mortality. Accurate estimates of these mortality rates are essential for developing effective management strategies to aid in the species' recovery. This study enhances existing vessel strike models by incorporating detailed regional data on vessel traffic characteristics as well as whale distribution and behavior.

Differential gray matter correlates and machine learning prediction of abuse and internalizing psychopathology in adolescent females.

Childhood abuse represents one of the most potent risk factors for the development of psychopathology during childhood, accounting for 30-60% of the risk for onset. While previous studies have separately associated reductions in gray matter volume (GMV) with childhood abuse and internalizing psychopathology (IP), it is unclear whether abuse and IP differ in their structural abnormalities, and which GMV features are related to abuse and IP at the individual level. In a pooled multisite, multi-investigator sample, 246 child and adolescent females between the ages of 8-18 were recruited into studies of interpersonal violence (IPV) and/or IP (i.

Application of a targeted amplicon sequencing panel to screen for insecticide resistance mutations in Anopheles darlingi populations from Brazil.

Large-scale surveillance and informed vector control approaches are urgently needed to ensure that national malaria programs remain effective in reducing transmission and, ultimately, achieving malaria elimination targets. In South America, Anopheles darlingi is the primary malaria vector and is responsible for the majority of Plasmodium species transmission. However, little is known about the molecular markers associated with insecticide resistance in this species.

Two decades of bacterial ecology and evolution in a freshwater lake.

Ecology and evolution are considered distinct processes that interact on contemporary time scales in microbiomes. Here, to observe these processes in a natural system, we collected a two-decade, 471-metagenome time series from Lake Mendota (Wisconsin, USA). We assembled 2,855 species-representative genomes and found that genomic change was common and frequent.

High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons.

Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia, and primary lateral sclerosis. Cortical hyperexcitation followed by in-excitability suggests the early involvement of cortical dysfunction in ALS pathology.

Discovery of potent anti-toxoplasmosis drugs from secondary metabolites in Citrus limon (lemon) leaves, supported in-silico study.

Toxoplasmosis induced by Toxoplasma gondii is a well-known health threat, that prompts fatal encephalitis increased with immunocompromised patients, in addition, it can cause chorioretinitis, microcephaly, stillbirth in the fetus and even led to death. Standard therapy uses sulfadiazine and pyrimethamine drugs revealed beneficial results during the acute stage, however, it has severe side effects. UPLC-ESI-MS/MS used to explore C.

Heterodyne analysis of high-order partial waves in attosecond photoionization of helium.

Partial wave analysis is key to interpretation of the photoionization of atoms and molecules on the attosecond timescale. Here we propose a heterodyne analysis approach, based on the delay-resolved anisotropy parameters to reveal the role played by high-order partial waves during photoionization. This extends the Reconstruction of Attosecond Beating By Interference of Two-photon Transitions technique into the few-photon regime.

Exploring transition states of protein conformational changes via out-of-distribution detection in the hyperspherical latent space.

Identifying transitional states is crucial for understanding protein conformational changes that underlie numerous biological processes. Markov state models (MSMs), built from Molecular Dynamics (MD) simulations, capture these dynamics through transitions among metastable conformational states, and have demonstrated success in studying protein conformational changes. However, MSMs face challenges in identifying transition states, as they partition MD conformations into discrete metastable states (or free energy minima), lacking description of transition states located at the free energy barriers.

Isolated Neutral Organic Radical Unveiled Solvent-Radical Interaction in Highly Reducing Photocatalysis.

Diffusion-limited kinetics is a key mechanistic debate when consecutive photoelectron transfer (conPET) is discussed in photoredox catalysis. In-situ generated organic photoactive radicals can access catalytic systems as reducing as alkaline metals that can activate remarkably stable bonds. However, in many cases, the extremely short-lived transient nature of these doublet state open-shell species has led to debatable mechanistic studies, hindering adoption and development.