Radiosynthesis of [F]brequinar for PET imaging of hDHODH for potential studies of acute myeloid leukemia and cancers.

Dihydroorotate dehydrogenase (DHODH), an enzyme that plays a critical role in the pyrimidine biosynthesis, has been recognized as a promising target for the treatment of diseases that involve cellular proliferation, such as autoimmune diseases and cancers. Pharmacological inhibition of human DHODH (hDHODH) that offers a potential therapeutic strategy for the treatment in adult subjects with acute myeloid leukemia (AML) has recently been supported by phase I/II clinical trials for the treatment of patients with relapsed/refractory AML. To facilitate the development of optimized hDHODH inhibitors, the presence of an imaging probe that is able to demonstrate target engagement is critical and desirable.

Heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases and has a prevalence that is expected to rise with the growing ageing population. HFpEF is associated with significant morbidity and mortality. Specific HFpEF risk factors include age, diabetes, hypertension, obesity and atrial fibrillation.

Evaluation of a Slim Modiolar Electrode Array: A Temporal Bone Study.

Hypothesis: Evaluation of the Slim Modiolar (SM) electrode in temporal bones (TB) will elucidate the electrode's insertion outcomes.

Background: The SM electrode was designed for atraumatic insertion into the scala tympani, for ideal perimodiolar positioning and with a smaller caliber to minimize interference with cochlear biological processes.

Methods: The SM electrode was inserted into TBs via a cochleostomy.

Maternal heart rate variability at 3-months postpartum is associated with maternal mental health and infant neurophysiology.

Previous research has demonstrated a critical link between maternal mental health and infant development. However, there is limited understanding of the role of autonomic regulation in postpartum maternal mental health and infant outcomes. In the current study, we tested 76 mother-infant dyads from diverse socioeconomic backgrounds when infants were 3-months of age.

, the Gene Mutated in Familial Dysautonomia, Is Required for Normal Enteric Nervous System Development and Maintenance and for Gut Epithelium Homeostasis.

Familial dysautonomia (FD) is a rare sensory and autonomic neuropathy that results from a mutation in the gene. Virtually all patients report gastrointestinal (GI) dysfunction and we have recently shown that FD patients have a dysbiotic gut microbiome and altered metabolome. These findings were recapitulated in an FD mouse model and moreover, the FD mice had reduced intestinal motility, as did patients.

Naturalistic patterns of sustained attention across early childhood: Developmental profiles and longitudinal associations with executive functions.

The capacity to sustain attention over time develops rapidly over early childhood and is associated with socioemotional and cognitive outcomes. However, sustained attention has largely been studied in either shared or independent contexts, leading to gaps in our understanding of how trade-offs between sustained attention to shared versus individual targets may predict later outcomes. We examined this question in a longitudinal sample of 1,290 children (49% female, 43% Black), living in predominately rural, low-income regions, using a naturalistic shared picture book reading task.

Laminar pattern of sensory-evoked dynamic high-frequency oscillatory activity in the macaque auditory cortex.

High-frequency (>60 Hz) neuroelectric signals likely have functional roles distinct from low-frequency (<30 Hz) signals. While high-gamma activity (>60 Hz) does not simply equate to neuronal spiking, they are highly correlated, having similar information encoding. High-gamma activity is typically considered broadband and poorly phase-locked to sensory stimuli and thus is typically analyzed after transformations into absolute amplitude or spectral power.

Sample preparation and data collection for serial block face scanning electron microscopy of mammalian cell monolayers.

Volume electron microscopy encompasses a set of electron microscopy techniques that can be used to examine the ultrastructure of biological tissues and cells in three dimensions. Two block face techniques, focused ion beam scanning electron microscopy (FIB-SEM) and serial block face scanning electron microscopy (SBF-SEM) have often been used to study biological tissue samples. More recently, these techniques have been adapted to in vitro tissue culture samples.

Prenatal organophosphate pesticide exposure and sex-specific estimated Fetal size.

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at three time points.

Associations of bisphenol and phthalate exposure and anti-Müllerian hormone levels in women of reproductive age.

Background: In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations.

Methods: Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study.

Demographic and geographic distribution of diabetes and pre-diabetes risk in rural settings: results from a cross-sectional, countywide rural health survey in Sullivan County, New York.

Objective: To perform a detailed characterisation of diabetes burden and pre-diabetes risk in a rural county with previously documented poor health outcomes in order to understand the local within-county distribution of diabetes in rural areas of America.

Design, Setting, And Participants: In 2021, we prospectively mailed health surveys to all households in Sullivan County, a rural county with the second-worst health outcomes of all counties in New York State. Our survey included questions on demographics, medical history and the American Diabetes Association's Pre-diabetes Risk Test.

RORγt-dependent antigen-presenting cells direct regulatory T cell-mediated tolerance to food antigen.

The gastrointestinal tract is continuously exposed to foreign antigens in food and commensal microbes with potential to induce adaptive immune responses. Peripherally induced T regulatory (pTreg) cells are essential for mitigating inflammatory responses to these agents. While RORγt antigen-presenting cells (RORγt-APCs) were shown to program gut microbiota-specific pTregs, understanding of their characteristics remains incomplete, and the APC subset responsible for food tolerance has remained elusive.

Novel Inhibition of Central Carbon Metabolism Pathways by Rac and CDC42 inhibitor MBQ167 and Paclitaxel.

Triple negative breast cancer (TNBC) represents a therapeutic challenge in which standard chemotherapy is limited to paclitaxel. MBQ167, a clinical stage small molecule inhibitor that targets Rac and Cdc42, inhibits tumor growth and metastasis in mouse models of TNBC. Herein, we investigated the efficacy of MBQ167 in combination with paclitaxel in TNBC preclinical models, as a prelude to safety trials of this combination in patients with advanced breast cancer.

Chronic viral infection alters PD-1 locus subnuclear localization in cytotoxic CD8 T cells.

During chronic infection, virus-specific CD8 cytotoxic T lymphocytes (CTLs) progressively lose their ability to mount effective antiviral responses. This "exhaustion" is coupled to persistent upregulation of inhibitory receptor programmed death-1 (PD-1) (Pdcd1)-key in suppressing antiviral CTL responses. Here, we investigate allelic Pdcd1 subnuclear localization and transcription during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection in mice.

Catheter ablation compared to medical therapy for ventricular tachycardia in sarcoidosis: nationwide outcomes and hospital readmissions.

Background: Catheter ablation (CA) for ventricular tachycardia (VT) can be a useful treatment strategy, however, few studies have compared CA to medical therapy (MT) in the sarcoidosis population.

Objective: To assess in-hospital outcomes and unplanned readmissions following CA for VT compared to MT in patients with sarcoidosis.

Methods: Data was obtained from the Nationwide Readmissions Database between 2010 and 2019 to identify patients with sarcoidosis admitted for VT either undergoing CA or MT during elective and non-elective admission.

Inclusion of Trainee Stakeholders Is Necessary for Effective Change in Health-Service-Psychology Internship Training.

In a recent call to action, we described pressing issues in the health-service-psychology (HSP) internship from the perspective of interns. In our article, we sought to initiate a dialogue that would include trainees and bring about concrete changes. The commentaries on our article are a testament to the readiness of the field to engage in such a dialogue, and we applaud the actionable recommendations that they make.