Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence.

Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry.

Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics.

The diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility.

Genetic associations between orexin genes and phenotypes related to behavioral regulation in humans, including substance use.

The hypothalamic neuropeptide system of orexin (hypocretin) neurons provides projections throughout the neuraxis and has been linked to sleep regulation, feeding and motivation for salient rewards including drugs of abuse. However, relatively little has been done to examine genes associated with orexin signaling and specific behavioral phenotypes in humans. Here, we tested for association of twenty-seven genes involved in orexin signaling with behavioral phenotypes in humans.

Neural signatures of risk-taking adaptions across health, bipolar disorder, and lithium treatment.

Cognitive and neural mechanisms underlying bipolar disorder (BD) and its treatment are still poorly understood. Here we examined the role of adaptations in risk-taking using a reward-guided decision-making task. We recruited volunteers with high (n = 40) scores on the Mood Disorder Questionnaire, MDQ, suspected of high risk for bipolar disorder and those with low-risk scores (n = 37).

Oxidation state of bioavailable dissolved organic matter influences bacterioplankton respiration and growth efficiency.

Oxygen consumption by oceanic microbes can predict respiration (CO production) but requires an assumed respiratory quotient (RQ; ΔO/ΔCO). Measured apparent RQs (ARQs) can be impacted by various processes, including nitrification and changes in dissolved organic matter (DOM) composition, leading to discrepancies between ARQ and actual RQ. In DOM remineralization experiments conducted in the eastern North Atlantic Ocean, ARQs averaged 1.

Understanding and promoting equitable post-discharge care in firearm injury survivors: a retrospective chart review.

Patients that survive firearm injuries frequently require follow-up care. This study aims to explore demographic characteristics of patients presenting to the emergency department for post-firearm injury care and to understand the reasons for their return visits. This was a retrospective chart review of all emergency department and readmission patient encounters for post-firearm injury care during the study period, January 1, 2019 to December 31, 2022, at an urban safety net hospital.

Fluo-Cast-Bright: a deep learning pipeline for the non-invasive prediction of chromatin structure and developmental potential in live oocytes.

In mammalian oocytes, large-scale chromatin organization regulates transcription, nuclear architecture, and maintenance of chromosome stability in preparation for meiosis onset. Pre-ovulatory oocytes with distinct chromatin configurations exhibit profound differences in metabolic and transcriptional profiles that ultimately determine meiotic competence and developmental potential. Here, we developed a deep learning pipeline for the non-invasive prediction of chromatin structure and developmental potential in live mouse oocytes.

Progress in personalized immunotherapy for patients with brain metastasis.

Brain metastasis leads to poor outcomes and CNS injury, significantly reducing quality of life and survival rates. Advances in understanding the tumor immune microenvironment have revealed the promise of immunotherapies, which, alongside surgery, chemotherapy, and radiation, offer improved survival for some patients. However, resistance to immunotherapy remains a critical challenge.

Examining the physical and psychological effects of combining multimodal feedback with continuous control in prosthetic hands.

Myoelectric prosthetic hands are typically controlled to move between discrete positions and do not provide sensory feedback to the user. In this work, we present and evaluate a closed-loop, continuous myoelectric prosthetic hand controller, that can continuously control the position of multiple degrees of freedom of a prosthesis while rendering proprioceptive feedback to the user via a haptic feedback armband. Twenty-eight participants without and ten participants with upper limb difference (ULD) were recruited to holistically evaluate the physical and psychological effects of the controller via isolated control and sensory tasks, dexterity assessments, embodiment and task load questionnaires, and post-study interviews.

Engineering synthetic signaling receptors to enable erythropoietin-free erythropoiesis.

Blood transfusion plays a vital role in modern medicine, but frequent shortages occur. Ex vivo manufacturing of red blood cells (RBCs) from universal donor cells offers a potential solution, yet the high cost of recombinant cytokines remains a barrier. Erythropoietin (EPO) signaling is crucial for RBC development, and EPO is among the most expensive media components.

scRNA seq of an F1 cross of Marek's disease resistant and susceptible chickens identifies allele specific expression signatures enriched in transcription modulators.

Marek's disease (MD), a T cell lymphoma disease in chickens, is caused by the Marek's disease virus (MDV) found ubiquitously in the poultry industry. Genetically resistant Line 6 (L6) and susceptible Line 7 (L7) chickens have been instrumental to research on avian immune system response to MDV infection. In this study we characterized molecular signatures unique to splenic immune cell types across different genetic backgrounds 6 days after infection.

A reagent to access methyl sulfones.

A chemical reagent to access methyl sulfones has been developed. Its reaction with various bis-nucleophiles leads to the rapid formation of previously unknown heteroaromatic methyl sulfones. Analogous strategy can also be used to construct alkyl-, CHF-, CF- and even bicyclo[1.

Three-dimensional diffractive acoustic tomography.

Acoustically probing biological tissues with light or sound, photoacoustic and ultrasound imaging can provide anatomical, functional, and/or molecular information at depths far beyond the optical diffusion limit. However, most photoacoustic and ultrasound imaging systems rely on linear-array transducers with elevational focusing and are limited to two-dimensional imaging with anisotropic resolutions. Here, we present three-dimensional diffractive acoustic tomography (3D-DAT), which uses an off-the-shelf linear-array transducer with single-slit acoustic diffraction.

Assessment of Hsp90β-selective inhibitor safety and on-target effects.

The heat shock protein 90 (Hsp90) family of molecular chaperones mediates the folding and activation of ~ 400 client proteins, many of which contribute to oncogenesis. As a result, Hsp90 pan-inhibitors, which inhibit all four Hsp90 isoforms, have been investigated in the clinic for the treatment of cancer. Unfortunately, detrimental side effects were observed and hindered the clinical development of pan-Hsp90 inhibitors.

Salicylic acid confers cadmium tolerance in wheat by regulating photosynthesis, yield and ionic homeostasis.

Wheat (Triticum aestivum L.) productivity and quality can be threatened by soil cadmium (Cd) contamination, posing a concern to food security. Salicylic acid (SA) is an endogenously produced signaling molecule that activates the defense system imparting abiotic stress tolerance in plants.

Convergent evidence for the temperature-dependent emergence of silicification in terrestrial plants.

Research on silicon (Si) biogeochemistry and its beneficial effects for plants has received significant attention over several decades, but the reasons for the emergence of high-Si plants remain unclear. Here, we combine experimentation, field studies and analysis of existing databases to test the role of temperature on the expression and emergence of silicification in terrestrial plants. We first show that Si is beneficial for rice under high temperature (40 °C), but harmful under low temperature (0 °C), whilst a 2 °C increase results in a 37% increase in leaf Si concentrations.

Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL) associated with favorable prognosis, but the optimal therapy for this subtype remains unclear. Profiling the genomic and pharmacological landscape of 194 pediatric ETV6::RUNX1 ALL cases, we uncover two transcriptomic clusters, C1 (61%) and C2 (39%). Compared to C1, the C2 subtype features higher white blood cell counts and younger age at diagnosis, as well as better early treatment responses.

Large exciton binding energy in a bulk van der Waals magnet from quasi-1D electronic localization.

Excitons, bound electron-hole pairs, influence the optical properties in strongly interacting solid-state systems and are typically most stable and pronounced in monolayer materials. Bulk systems with large exciton binding energies, on the other hand, are rare and the mechanisms driving their stability are still relatively unexplored. Here, we report an exceptionally large exciton binding energy in single crystals of the bulk van der Waals antiferromagnet CrSBr.

Is there a mental health diagnostic crisis in primary care? Current research practices in global mental health cannot answer that question.

In low- and middle-income countries, fewer than 1 in 10 people with mental health conditions are estimated to be accurately diagnosed in primary care. This is despite more than 90 countries providing mental health training for primary healthcare workers in the past two decades. The lack of accurate diagnoses is a major bottleneck to reducing the global mental health treatment gap.

Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting.

Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments.

Time-resolved Brownian tomography of single nanocrystals in liquid during oxidative etching.

Colloidal nanocrystals inherently undergo structural changes during chemical reactions. The robust structure-property relationships, originating from their nanoscale dimensions, underscore the significance of comprehending the dynamic structural behavior of nanocrystals in reactive chemical media. Moreover, the complexity and heterogeneity inherent in their atomic structures require tracking of structural transitions in individual nanocrystals at three-dimensional (3D) atomic resolution.

Categorization of 34 computational methods to detect spatially variable genes from spatially resolved transcriptomics data.

In the analysis of spatially resolved transcriptomics data, detecting spatially variable genes (SVGs) is crucial. Numerous computational methods exist, but varying SVG definitions and methodologies lead to incomparable results. We review 34 state-of-the-art methods, classifying SVGs into three categories: overall, cell-type-specific, and spatial-domain-marker SVGs.

Adaptation of the Florida Cognitive Activities Scale for Latinx adults with chronic diseases.

Background: Latinx adults experience disparately high rates of chronic diseases and cognitive dysfunction. Participating in cognitive-stimulating activities, such as reading, is thought to improve and preserve cognitive function. However, little is known about cognitively stimulating activities preferred by Latinx adults.