Contributions of connectional pathways to shaping Alzheimer's disease pathologies.

Four important imaging biomarkers of Alzheimer's disease, namely grey matter atrophy, glucose hypometabolism and amyloid-β and tau deposition, follow stereotypical spatial distributions shaped by the brain network of structural and functional connections. In this case-control study, we combined several predictors reflecting various possible mechanisms of spreading through structural and functional pathways to predict the topography of the four biomarkers in amyloid-positive patients while controlling for the effect of spatial distance along the cortex. For each biomarker, we quantified the relative contribution of each predictor to the variance explained by the model.

The HIP mouse and all of its organs are completely invisible to allogeneic immune cells.

Hypoimmune (HIP) allogeneic cell therapeutics hold the promise to allow off-the-shelf treatments for a broad patient population. Our HIP approach includes the depletion of major histocompatibility complex (MHC) class I and II molecules and the overexpression of Cd47. Here, we report the engineering of HIP mice that stably exhibit the HIP phenotype in all cell types.

Dual α-globin-truncated erythropoietin receptor knockin restores hemoglobin production in α-thalassemia-derived erythroid cells.

The most severe form of α-thalassemia results from loss of all four copies of α-globin. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to the imbalance of β-globin and α-globin chains. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for α-thalassemia.

Molecular basis of proton sensing by G protein-coupled receptors.

Three proton-sensing G protein-coupled receptors (GPCRs)-GPR4, GPR65, and GPR68-respond to extracellular pH to regulate diverse physiology. How protons activate these receptors is poorly understood. We determined cryogenic-electron microscopy (cryo-EM) structures of each receptor to understand the spatial arrangement of proton-sensing residues.

Transcriptional coupling of telomeric retrotransposons with the cell cycle.

Unlike most species that use telomerase for telomere maintenance, many dipterans, including , rely on three telomere-specific retrotransposons (TRs)-, , and -to form tandem repeats at chromosome ends. Although TR transcription is crucial in their life cycle, its regulation remains poorly understood. This study identifies the Mediator complex, E2F1-Dp, and Scalloped/dTEAD as key regulators of TR transcription.

Effect of FLASH dose-rate and oxygen concentration in the production of HOin cellular-like media versus water: a Monte Carlo track-structure study.

To study the effect of dose-rate in the time evolution of chemical yields produced in pure water versus a cellular-like environment for FLASH radiotherapy research. A version of TOPAS-nBio with Tau-Leaping algorithm was used to simulate the homogenous chemistry stage of water radiolysis using three chemical models: 1) liquid water model that considered scavenging of eaq-, H● by dissolved oxygen; 2) Michaels & Hunt model that considered scavenging of ●OH, eaq-, and H● by biomolecules existing in cellular environment; 3) Wardman model that considered model 2) and the chemical repair enzyme glutathione (GHS). H2O2 concentrations at conventional and FLASH dose-rates were compared with published measurements.

Association of binge alcohol use with functional outcomes among individuals with COVID-19 infection.

Aims: Alcohol consumption along with negative sequelae from excess alcohol intake increased during the COVID-19 pandemic. We evaluated the association between binge alcohol use and long-term functional outcomes among COVID-19-positive individuals.

Methods: Using a prospective, longitudinal, multisite cohort study design, we evaluated the association between binge alcohol use and mental and physical functional outcomes using Patient-Reported Outcomes Measurement Information System (PROMIS)-29 scores three and six months postinfection.

The association between posttraumatic stress symptoms and hope following intensive care unit discharge: Findings from a longitudinal cohort study.

Background: Hope is essential for mental health in general and for recovery following severe illness. However, the associations between posttraumatic stress symptoms (PTSS) and hope among intensive care unit (ICU) survivors has not been investigated.

Objectives: To assess hope at 3, 6 and 12 months after ICU admission and examine possible associations between hope and selected demographic data, clinical characteristics, and 3-month PTSS-levels among ICU patients.

Reconciling heterogeneous dengue virus infection risk estimates from different study designs.

Uncovering rates at which susceptible individuals become infected with a pathogen, i.e., the force of infection (FOI), is essential for assessing transmission risk and reconstructing distribution of immunity in a population.

Adolescents' perceptions, experiences, and reactions to "fake" vaping devices.

Unlabelled: Use of electronic cigarette (vaping) devices, whether to inhale nicotine, cannabis, or other substances, may pose health risks to adolescents. Those risks could be heightened when a vaping device is "fake," a term we use to include inauthentic, knockoff, counterfeit, and/or adulterated devices, an issue exemplified by the Electronic Cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) outbreak of 2019-2020.

Methods: Investigators completed in-depth, semi-structured interviews in 2020-2021 with 47 California adolescents (ages 13-17) who used nicotine products.

New indices to track interoperability among US hospitals.

Objectives: To develop indices of US hospital interoperability to capture the current state and assess progress over time.

Materials And Methods: A Technical Expert Panel (TEP) informed selection of items from the American Hospital Association Health IT Supplement survey, which were aggregated into interoperability concepts (components) and then further combined into indices. Indices were refined through psychometric analysis and additional TEP input.

Robust interpolation of EEG/MEG sensor time-series via electromagnetic source imaging.

Objective: Electroencephalography (EEG) and Magnetoencephalography (MEG) are widely used non-invasive techniques in clinical and cognitive neuroscience. However, low spatial resolution measurements, partial brain coverage by some sensor arrays, as well as noisy sensors could result in distorted sensor topographies resulting in inaccurate reconstructions of underlying brain dynamics. Solving these problems has been a challenging task, This paper proposes a robust framework based on electromagnetic source imaging for interpolation of unknown or poor quality EEG/MEG measurements.

Conventional radiography for the assessment of focal bone lesions of the appendicular skeleton: fundamental concepts in the modern imaging era.

Bone lesions of the appendicular skeleton can be caused by primary benign or malignant tumors, metastases, osteomyelitis, or pseudotumors. Conventional radiography plays a crucial role in the initial assessment of osseous lesions and should not be underestimated even in this era of modern complex and advanced imaging technologies. Combined with patient age, clinical symptoms and biology, and lesion features including location, solitary versus multiplicity, density, margin (transitional zone evaluated with Lodwick-Madewell grading score), and, if present, the type of periosteal reaction and matrix mineralization can narrow the differential diagnosis or offer a likely diagnosis.

How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.

Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE).

Framework for developing self-actualization skills in young adults with autism.

Purpose: Young adults with autism spectrum disorder (YAASD) often lack the skills needed for successful adult living and subsequently develop lower quality of life and health in adulthood. Therefore, we developed a framework to support resilience and improve quality of life in YAASD, which will be used to develop a life-skills curriculum for YAASD.

Methods: We conducted a qualitative study of YAASD, parents of YAASD and service providers recruited from agencies that serve YAASD using Grounded Theory.

Contextual modulation emerges by integrating feedforward and feedback processing in mouse visual cortex.

Sensory systems use context to infer meaning. Accordingly, context profoundly influences neural responses to sensory stimuli. However, a cohesive understanding of the circuit mechanisms governing contextual effects across different stimulus conditions is still lacking.

Inflammation switches the chemoattractant requirements for naive lymphocyte entry into lymph nodes.

Sustained lymphocyte migration from blood into lymph nodes (LNs) is important for immune responses. The CC-chemokine receptor-7 (CCR7) ligand CCL21 is required for LN entry but is downregulated during inflammation, and it has been unclear how recruitment is maintained. Here, we show that the oxysterol biosynthetic enzyme cholesterol-25-hydroxylase (Ch25h) is upregulated in LN high endothelial venules during viral infection.

Synthetic organizer cells guide development via spatial and biochemical instructions.

In vitro development relies primarily on treating progenitor cells with media-borne morphogens and thus lacks native-like spatial information. Here, we engineer morphogen-secreting organizer cells programmed to self-assemble, via cell adhesion, around mouse embryonic stem (ES) cells in defined architectures. By inducing the morphogen WNT3A and its antagonist DKK1 from organizer cells, we generated diverse morphogen gradients, varying in range and steepness.

Healthcare provider communication and current contraceptive use among transgender men and gender-diverse people: results from an online, cross-sectional survey in the United States.

Objectives: To explore whether discussing contraceptive use with a healthcare provider is associated with current contraceptive use among transgender men and gender-diverse (TMGD) individuals.

Study Design: In 2019, we conducted a cross-sectional survey among transgender men and gender-diverse adults in the United States who were assigned female or intersex at birth. We measured whether respondents had ever discussed contraception with a healthcare provider as well as current use of contraception, reasons for use, and barriers to use.

A hybrid epithelial-mesenchymal transition program enables basal epithelial cells to bypass stress-induced stasis and contributes to a metaplastic breast cancer progenitor state.

Background: Human mammary epithelial cell (HMEC) cultures encounter a stress-associated barrier termed stasis, during which most cells adopt a senescence-like phenotype. From these cultures, rare variants emerge from the basal epithelial population, re-initiating growth. Variants exhibit pre-malignant properties, including an aberrant epigenetic program that enables continued proliferation and acquisition of genetic changes.

Gene Signatures and Oncology Treatment Implications.

Gene expression signatures (GES) are a powerful tool in oncology used for classification, prognostication, and therapeutic response prediction of malignancies. In this article, we review the disease site guidelines by the National Comprehensive Cancer Network that use GES for treatment planning and clinical use. We identified 4 cancer types for which treatment decisions are frequently influenced by GES.