Volume electron microscopy reveals unique laminar synaptic characteristics in the human entorhinal cortex.

The entorhinal cortex (EC) plays a pivotal role in memory function and spatial navigation, connecting the hippocampus with the neocortex. The EC integrates a wide range of cortical and subcortical inputs, but its synaptic organization in the human brain is largely unknown. We used volume electron microscopy to perform a 3D analysis of the microanatomical features of synapses in all layers of the medial EC (MEC) from the human brain.

Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions.

The network of proteins at the interface between cell-cell adherens junctions and the actomyosin cytoskeleton provides robust yet dynamic connections that facilitate cell shape change and motility. While this was initially thought to be a simple linear connection via classic cadherins and their associated catenins, we now have come to appreciate that many more proteins are involved, providing robustness and mechanosensitivity. Defining the full set of proteins in this network remains a key objective in our field.

Construction of functional tissue-engineered microvasculatures using circulating fibrocytes as mural cells.

Mural cells are essential for maintaining the proper functions of microvasculatures. However, a key challenge of microvascular tissue engineering is identifying a cellular source for mural cells. We showed that , circulating fibrocytes (CFs) can (1) shear and stabilize the microvasculatures formed by vascular endothelial cells (VECs) in a collagen gel, (2) form gap junctions with VECs and (3) induce basement membrane formation.

Alloreactive-free CAR-VST therapy: a step forward in long-term tumor control in viral context.

CAR-T cell therapy has revolutionized immunotherapy but its allogeneic application, using various strategies, faces significant challenges including graft-versus-host disease and graft rejection. Recent advances using Virus Specific T cells to generate CAR-VST have demonstrated potential for enhanced persistence and antitumor efficacy, positioning CAR-VSTs as a promising alternative to conventional CAR-T cells in an allogeneic setting. This review provides a comprehensive overview of CAR-VST development, emphasizing strategies to mitigate immunogenicity, such as using a specialized TCR, and approaches to improve therapeutic persistence against host immune responses.

Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients.

Rationale: COVID-19-associated acute-respiratory distress syndrome (C-ARDS) results from a direct viral injury associated with host excessive innate immune response mainly affecting the lungs. However, cytokine profile in the lung compartment of C-ARDS patients has not been widely studied, nor compared to non-COVID related ARDS (NC-ARDS).

Objectives: To evaluate caspase-1 activation, IL-1 signature, and other inflammatory cytokine pathways associated with tissue damage using post-mortem lung tissues, bronchoalveolar lavage fluids (BALF), and serum across the spectrum of COVID-19 severity.

A conserved element in the first intron of has a lineage specific, TCR signal-responsive, canonical enhancer function that matches the timing of cell surface CD4 upregulation required to prevent lineage choice error.

Introduction: The regulation of expression during T-cell development and immune responses is essential for proper lineage commitment and function in the periphery. However, the mechanisms of genetic and epigenetic regulation are complex, and their interplay not entirely understood. Previously, we demonstrated the need for CD4 upregulation during positive selection to ensure faithful commitment of MHC-II-restricted T cells to the CD4 lineage.

Predicting conversion to psychosis using machine learning: response to Cannon.

Background: We previously reported that machine learning could be used to predict conversion to psychosis in individuals at clinical high risk (CHR) for psychosis with up to 90% accuracy using the North American Prodrome Longitudinal Study-3 (NAPLS-3) dataset. A definitive test of our predictive model that was trained on the NAPLS-3 data, however, requires further support through implementation in an independent dataset. In this report we tested for model generalization using the previous iteration of NAPLS-3, the NAPLS-2, using the identical machine learning algorithms employed in our previous study.

Preparation and Biodistribution Assessment of Lu-curcumin as a Possible Therapeutic Agent.

Purpose: Curcumin as a potent anti-inflammatory and cancer-prevention molecule was labeled with n.c.a Lu.

LASF: a local adaptive segmentation framework for coronary angiogram segments.

Coronary artery disease (CAD) remains the leading cause of death globally, highlighting the critical need for accurate diagnostic tools in medical imaging. Traditional segmentation methods for coronary angiograms often struggle with vessel discontinuity and inaccuracies, impeding effective diagnosis and treatment planning. To address these challenges, we developed the Local Adaptive Segmentation Framework (LASF), enhancing the YOLOv8 architecture with dilation and erosion algorithms to improve the continuity and precision of vascular image segmentation.

Explorative Study of Modulatory Effects of Notochordal Cell-Derived Extracellular Vesicles on the IL-1β-Induced Catabolic Cascade in Nucleus Pulposus Cell Pellets and Explants.

Background: Cell-free regenerative strategies, such as notochordal cell (NC)-derived extracellular vesicles (EVs), are an attractive alternative in developing new therapies for intervertebral disc (IVD) degeneration. NC-EVs have been reported to elicit matrix anabolic effects on nucleus pulposus cells from degenerated IVDs cultured under basal conditions. However, the degenerative process is exacerbated by pro-inflammatory cytokines contributing to the vicious degenerative cycle.

Assessing ChatGPT's Capability in Addressing Thyroid Cancer Patient Queries: A Comprehensive Mixed-Methods Evaluation.

Context: Literature suggests patients with thyroid cancer have unmet informational needs in many aspects of care. Patients often turn to online resources for their health-related information, and generative artificial intelligence programs such as ChatGPT are an emerging and attractive resource for patients.

Objective: To assess the quality of ChatGPT's responses to thyroid cancer-related questions.

Performance of algorithms using wrist temperature for retrospective ovulation day estimate and next menses start day prediction: a prospective cohort study.

Study Question: Can algorithms using wrist temperature, available on compatible models of iPhone and Apple Watch, retrospectively estimate the day of ovulation and predict the next menses start day?

Summary Answer: Algorithms using wrist temperature can provide retrospective ovulation estimates and next menses start day predictions for individuals with typical or atypical cycle lengths.

What Is Known Already: Wrist skin temperature is affected by hormonal changes associated with the menstrual cycle and can be used to estimate the timing of cycle events.

Study Design, Size, Duration: We conducted a prospective cohort study of 262 menstruating females (899 menstrual cycles) aged 14 and older who logged their menses, performed urine LH testing to define day of ovulation, recorded daily basal body temperature (BBT), and collected overnight wrist temperature.

Multidisciplinary perspectives on cumulative impact assessment for vulnerable communities: expert elicitation using a Delphi method.

Prompted by a series of executive orders, the U.S. Environmental Protection Agency (USEPA) is promoting cumulative impact assessment (CIA) to integrate numerous factors that have the potential to impact community health, which include nonchemical stressors such as socioeconomic conditions, pre-existing health conditions, and many others that historically have not been addressed by USEPA's chemical risk assessment paradigm.

Long-term effects of adolescent versus adult nicotine self-administration on cholinergic modulation of dopamine in the nucleus accumbens core.

Adolescence is a developmental period marked by significant alterations to brain neurobiology and behavior. Adolescent nicotine use disrupts developmental trajectories and increases vulnerability to maladaptive drug-taking in adulthood. The mesolimbic dopamine (DA) system, including the nucleus accumbens core (NAc), mediates the reinforcing effects of nicotine.

Comparison of transcriptomic profiles between intracellular and extracellular Bartonella henselae.

The Bartonella genus of bacteria encompasses ubiquitous species, some of which are pathogenic in humans and animals. Bartonella henselae, the causative agent of Cat Scratch disease, is responsible for a large portion of human Bartonella infections. These bacteria can grow outside of cells, replicate in erythrocytes and invade endothelial and monocytic cells.

Strength and durability of indirect protection against SARS-CoV-2 infection through vaccine and infection-acquired immunity.

Early investigation revealed a reduced risk of SARS-CoV-2 infection among social contacts of COVID-19 vaccinated individuals, referred to as indirect protection. However, indirect protection from SARS-CoV-2 infection-acquired immunity and its comparative strength and durability to vaccine-derived indirect protection in the current epidemiologic context of high levels of vaccination, prior infection, and novel variants are not well characterized. Here, we show that both vaccine-derived and infection-acquired immunity independently yield indirect protection to close social contacts with key differences in their strength and waning.

Comparison of Pharmacokinetics of Long-Acting Local Analgesics: CPL-01, a Novel Extended-Release Ropivacaine, Demonstrates Consistent and Predictable Exposure Compared with Liposomal Bupivacaine.

Background And Objective: There is a significant medical need for improved long-acting local anesthetics to decrease postsurgical pain and reduce postoperative opioid use. While ropivacaine is considered a safer local anesthetic than bupivacaine, no long-acting ropivacaine formulation is currently marketed. Available formulations of bupivacaine show inconsistent pharmacokinetics (PK) among different surgical models, and inconsistency in PK may lead to a reluctance to use the medication owing to fear of local anesthetic systemic toxicity (LAST) or unreliable efficacy.

A Retrospective Study of Pediatric Allergic Contact Dermatitis from 2017-2022.

Objectives: Allergic contact dermatitis occurs frequently in children. The proportion of children of color in the US is increasing, and racial and ethnic minority representation is important in pediatric allergic contact dermatitis research. The objectives of our study were to identify differences in age, sex, race and ethnicity among pediatric patch tests obtained from 2017 to 2022.

Evaluation of the Digital Ventilated Cage® system for circadian phenotyping.

The study of circadian rhythms has been critically dependent upon analysing mouse home cage activity, typically employing wheel running activity under different lighting conditions. Here we assess a novel method, the Digital Ventilated Cage (DVC, Tecniplast SpA, Italy), for circadian phenotyping. Based upon capacitive sensors mounted under black individually ventilated cages with inbuilt LED lighting, each cage becomes an independent light-controlled chamber.

Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase.

γ-Glutamyl carboxylase (GGCX) is the sole identified enzyme that uses vitamin K (VK) as a cofactor in humans. This protein catalyses the oxidation of VK hydroquinone to convert specific glutamate residues to γ-carboxyglutamate residues in VK-dependent proteins (VDPs), which are involved in various essential biological processes and diseases. However, the working mechanism of GGCX remains unclear.

Copper-dependent halogenase catalyses unactivated C-H bond functionalization.

Carbon-hydrogen (C-H) bonds are the foundation of essentially every organic molecule, making them an ideal place to do chemical synthesis. The key challenge is achieving selectivity for one particular C(sp)-H bond. In recent years, metalloenzymes have been found to perform C(sp)-H bond functionalization.

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.