Hyperinsulinemic Hypoglycemia Due to an Insulinoma in a 2-Year-Old Child.

Insulinomas are rare insulin-secreting tumors that most commonly affect adults. A 26-month-old child presented to her local emergency department with severe hypoglycemia. Initial workup was consistent with hyperinsulinemic hypoglycemia.

SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC).

Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection.

BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8 T cells.

During chronic infection and cancer, a self-renewing CD8 T cell subset maintains long-term immunity and is critical to the effectiveness of immunotherapy. These stem-like CD8 T cells diverge from other CD8 subsets early after chronic viral infection. However, pathways guarding stem-like CD8 T cells against terminal exhaustion remain unclear.

Patients with ACVR1 mutations have an increased prevalence of cardiac conduction abnormalities on electrocardiogram in a natural history study of Fibrodysplasia Ossificans Progressiva.

Background: Genetic contributors to cardiac arrhythmias are often found in cardiovascular conduction pathways and ion channel proteins. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disease of massive heterotopic ossification caused by a highly recurrent R206H mutation in ACVR1/ALK2. This mutation causes abnormal activation of the bone morphogenetic protein (BMP) pathway in response to Activin A.

Single-cell RNA-seq reveals TOX as a key regulator of CD8 T cell persistence in chronic infection.

Progenitor-like CD8 T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct programs to adapt to the immunosuppressive environment. By comparing the single-cell transcriptomes and epigenetic profiles of CD8 T cells responding to acute and chronic viral infections, we found that progenitor-like CD8 T cells became distinct from memory precursor cells before the peak of the T cell response.

Arterial spin labeling provides a reliable neurobiological marker of autism spectrum disorder.

Background: Research on neurobiological markers of autism spectrum disorder (ASD) has been elusive. However, radionuclide studies of cerebral blood flow (CBF) have shown decreased blood flow (hypoperfusion) in the temporal lobes of individuals with ASD across ages and intelligence. This observation fits with current neuroscientific models that implicate temporal regions in social perception and social cognition.

Long-Term Persistence of Exhausted CD8 T Cells in Chronic Infection Is Regulated by MicroRNA-155.

Persistent viral infections and tumors drive development of exhausted T (T) cells. In these settings, T cells establish an important host-pathogen or host-tumor stalemate. However, T cells erode over time, leading to loss of pathogen or cancer containment.

Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells.

Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns.

Optimal Sampling Duration for Continuous Glucose Monitoring to Determine Long-Term Glycemic Control.

Objective: To determine the minimum sample of continuous glucose monitoring (CGM) data needed to accurately reflect 3 months of glycemic control.

Research Design And Methods: Three months of CGM data were collected on 257 individuals (age 10-78 years) with type 1 diabetes in two studies (one using the Abbott FreeStyle Libre Pro™ and the other using the Dexcom™ G4). Correlations were calculated between the full 3 months and incremental sampling periods of CGM data.

Challenges in the development of dopamine D2- and D3-selective radiotracers for PET imaging studies.

The dopamine D2-like receptors (ie, D2/3 receptors) have been the most extensively studied CNS receptor with Positron Emission Tomography (PET). The 3 different radiotracers that have been used in these studies are [ C]raclopride, [ F]fallypride, and [ C]PHNO. Because these radiotracers have a high affinity for both dopamine D2 and D3 receptors, the density of dopamine receptors in the CNS is reported as the D2/3 binding potential, which reflects a measure of the density of both receptor subtypes.

Transient expression of ZBTB32 in anti-viral CD8+ T cells limits the magnitude of the effector response and the generation of memory.

Virus infections induce CD8+ T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8+ T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8+ T cells.

Small Molecule Receptor Ligands for PET Studies of the Central Nervous System-Focus on G Protein Coupled Receptors.

G protein-coupled receptors (GPRCs) are a class of proteins that are expressed in high abundance and are responsible for numerous signal transduction pathways in the central nervous system. Consequently, alterations in GPRC function have been associated with a wide variety of neurologic and neuropsychiatric disorders. The development of PET probes for imaging GPRCs has served as a major emphasis of PET radiotracer development and PET imaging studies over the past 30 years.

Ulnar Artery Aneurysm in a 6-Month-Old: A Case Report.

Background: Pediatric ulnar aneurysms are rare and, unlike their adult counterparts, cannot be explained by repetitive trauma to the palm. A small number of case reports describe diagnostic difficulty with these lesions and different treatments.

Methods: We present the case of a 6-month-old with an ulnar artery aneurysm of unknown cause.

Sigma-2 ligands and PARP inhibitors synergistically trigger cell death in breast cancer cells.

The sigma-2 receptor is overexpressed in proliferating cells compared to quiescent cells and has been used as a target for imaging solid tumors by positron emission tomography. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target for cancer therapy. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage response.

Deep immune profiling by mass cytometry links human T and NK cell differentiation and cytotoxic molecule expression patterns.

The elimination of infected or tumor cells by direct lysis is a key T and NK cell effector function. T and NK cells can kill target cells by coordinated secretion of cytotoxic granules containing one or both pore-forming proteins, perforin and granulysin and combinations of granzyme (Gzm) family effector proteases (in humans: Gzm A, B, K, M and H). Understanding the pattern of expression of cytotoxic molecules and the relationship to different states of T and NK cells may have direct relevance for immune responses in autoimmunity, infectious disease and cancer.

Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8(+) T Cell Exhaustion.

Dynamic reprogramming of metabolism is essential for T cell effector function and memory formation. However, the regulation of metabolism in exhausted CD8(+) T (Tex) cells is poorly understood. We found that during the first week of chronic lymphocytic choriomeningitis virus (LCMV) infection, before severe dysfunction develops, virus-specific CD8(+) T cells were already unable to match the bioenergetics of effector T cells generated during acute infection.

CD39 Expression Identifies Terminally Exhausted CD8+ T Cells.

Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells.

Molecular and cellular insights into T cell exhaustion.

In chronic infections and cancer, T cells are exposed to persistent antigen and/or inflammatory signals. This scenario is often associated with the deterioration of T cell function: a state called 'exhaustion'. Exhausted T cells lose robust effector functions, express multiple inhibitory receptors and are defined by an altered transcriptional programme.

Bystander chronic infection negatively impacts development of CD8(+) T cell memory.

Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8(+) T cells, the hallmark of protective immunity against intracellular pathogens.

What is the cost associated with the implementation and maintenance of an ACS/APDS-based surgical skills curriculum?

Purpose: The purpose of this study was to evaluate the cost associated with the American College of Surgery (ACS)/Association of Program Directors in Surgery (APDS)-based surgical skills curriculum (SSC) within a general surgery residency program.

Methods: The Penn Surgical Simulation Center (PSSC) of the University of Pennsylvania was established by the Department of Surgery during the 2006-2007 academic year and became a Level-I ACS Accredited Education Institute in 2008. Each academic year, 38 junior residents are assigned to a 4-week dedicated simulation rotation based on the ACS/APDS-based SSC.