Independent control of neurogenesis and dorsoventral patterning by NKX2-2.

Human neurogenesis is disproportionately protracted, lasting >10 times longer than in mouse, allowing neural progenitors to undergo more rounds of self-renewing cell divisions and generate larger neuronal populations. In the human spinal cord, expansion of the motor neuron lineage is achieved through a newly evolved progenitor domain called vpMN (ventral motor neuron progenitor) that uniquely extends and expands motor neurogenesis. This behavior of vpMNs is controlled by transcription factor NKX2-2, which in vpMNs is co-expressed with classical motor neuron progenitor (pMN) marker OLIG2.

A Clinical Prediction Model to Assess Risk for Pancreatic Cancer Among Patients With Acute Pancreatitis.

Objectives: We aimed to develop and validate a prediction model as the first step in a sequential screening strategy to identify acute pancreatitis (AP) individuals at risk for pancreatic cancer (PC).

Materials And Methods: We performed a population-based retrospective cohort study among individuals 40 years or older with a hospitalization for AP in the US Veterans Health Administration. For variable selection, we used least absolute shrinkage and selection operator regression with 10-fold cross-validation to identify a parsimonious logistic regression model for predicting the outcome, PC diagnosed within 2 years after AP.

A SARS-CoV-2 Vaccine Designed for Manufacturability Results in Unexpected Potency and Non-Waning Humoral Response.

The rapid development of several highly efficacious SARS-CoV-2 vaccines was an unprecedented scientific achievement that saved millions of lives. However, now that SARS-CoV-2 is transitioning to the endemic stage, there exists an unmet need for new vaccines that provide durable immunity and protection against variants and can be more easily manufactured and distributed. Here, we describe a novel protein component vaccine candidate, MT-001, based on a fragment of the SARS-CoV-2 spike protein that encompasses the receptor binding domain (RBD).

Photoselective sequencing: microscopically guided genomic measurements with subcellular resolution.

In biological systems, spatial organization and function are interconnected. Here we present photoselective sequencing, a new method for genomic and epigenomic profiling within morphologically distinct regions. Starting with an intact biological specimen, photoselective sequencing uses targeted illumination to selectively unblock a photocaged fragment library, restricting the sequencing-based readout to microscopically identified spatial regions.

The ultimate tradeoff: how red cell adaptations to malaria alter the host response during critical illness.

The human immune system evolved in response to pathogens. Among these pathogens, malaria has proven to be one of the deadliest and has exerted the most potent selective pressures on its target cell, the red blood cell. Red blood cells have recently gained recognition for their immunomodulatory properties, yet how red cell adaptations contribute to the host response during critical illness remains understudied.

Development and validation of case-finding algorithms to identify acute pancreatitis in the Veterans Health Administration.

Purpose: Acute pancreatitis (AP) is a frequently encountered adverse drug reaction. However, the validity of diagnostic codes for AP is unknown. We aimed to determine the positive predictive value (PPV) of a diagnostic code-based algorithm for identifying patients with AP within the US Veterans Health Administration and evaluate the value of adding readily available structured laboratory information.

Immunomodulatory roles of red blood cells.

Purpose Of The Review: To discuss recent advances supporting the role of red blood cells (RBCs) in the host immune response.

Recent Findings: Over the last century, research has demonstrated that red blood cells exhibit functions beyond oxygen transport, including immune function. Recent work indicates that the nucleic acid sensing receptor, toll-like receptor 9 (TLR9), is expressed on the RBC surface and implicated in innate immune activation and red cell clearance during inflammatory states.

Bat Red Blood Cells Express Nucleic Acid-Sensing Receptors and Bind RNA and DNA.

RBCs demonstrate immunomodulatory capabilities through the expression of nucleic acid sensors. However, little is known about bat RBCs, and no studies have examined the immune function of bat erythrocytes. In this study, we show that bat RBCs express the nucleic acid-sensing TLRs TLR7 and TLR9 and bind the nucleic acid ligands, ssRNA, and CpG DNA.

Anemia in a young Guinean male.

The etiology of anemia in adults is often multifactorial. This case highlights an uncommon combination of causes of anemia and the importance of a diagnostic workup guided by a patient's unique history, risk factors, and laboratory findings.

Passive Coping Strategies During Repeated Social Defeat Are Associated With Long-Lasting Changes in Sleep in Rats.

Exposure to severe stress has immediate and prolonged neuropsychiatric consequences and increases the risk of developing Posttraumatic Stress Disorder (PTSD). Importantly, PTSD develops in only a subset of individuals after exposure to a traumatic event, with the understanding of this selective vulnerability being very limited. Individuals who go on to develop PTSD after a traumatic experience typically demonstrate sleep disturbances including persistent insomnia and recurrent trauma-related nightmares.

Orexin signaling during social defeat stress influences subsequent social interaction behaviour and recognition memory.

Orexins are neuropeptides synthesized in the lateral hypothalamus that influence arousal, feeding, reward pathways, and the response to stress. However, the role of orexins in repeated stress is not fully characterized. Here, we examined how orexins and their receptors contribute to the coping response during repeated social defeat and subsequent anxiety-like and memory-related behaviors.

Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade.

Background: TGFβ signaling plays a pleotropic role in tumor biology, promoting tumor proliferation, invasion and metastasis, and escape from immune surveillance. Inhibiting TGFβ's immune suppressive effects has become of particular interest as a way to increase the benefit of cancer immunotherapy. Here we utilized preclinical models to explore the impact of the clinical stage TGFβ pathway inhibitor, galunisertib, on anti-tumor immunity at clinically relevant doses.

Reduced Orexin System Function Contributes to Resilience to Repeated Social Stress.

Exposure to stress increases the risk of developing affective disorders such as depression and post-traumatic stress disorder (PTSD). However, these disorders occur in only a subset of individuals, those that are more vulnerable to the effects of stress, whereas others remain resilient. The coping style adopted to deal with the stressor, either passive or active coping, is related to vulnerability or resilience, respectively.

Intracardiac migration of operatively placed epicardial pacing leads.

This study describes intracardiac migration of epicardial pacemaker leads after open heart surgery in 2 patients. Discovery of these pacemaker leads or remnants led to diagnostic confusion until an appropriate diagnosis was established by both invasive and noninvasive means. Intracardiac migration of epicardial pacemaker leads has only rarely been reported.

Characterizing medical providers for jail inmates in New York State.

Objectives: People who are incarcerated exhibit high rates of disease, but data evaluating the delivery of medical services to inmates are sparse, particularly for jail settings. We sought to characterize the primary medical care providers for county jail inmates in New York State.

Methods: From 2007 through 2009, we collected data on types of medical care providers for jail inmates in all New York State counties.

Vitamin D deficiency in HIV-infected postmenopausal Hispanic and African-American women.

Unlabelled: We evaluated vitamin D status in HIV+ and HIV- postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation.

Low bone mass and high bone turnover in postmenopausal human immunodeficiency virus-infected women.

Context: Low bone mineral density (BMD) is commonly reported in young men and women with HIV infection, and fracture rates may be higher. With effective antiretroviral therapy (ART), the HIV population is aging. However, little is known about the skeletal status of postmenopausal women.

A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.

Background: Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease.

Methods: Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects.

Bone mass and mineral metabolism in HIV+ postmenopausal women.

The objective of this cross-sectional study was to estimate the prevalence of and risk factors for osteoporosis in HIV+ postmenopausal women. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) and biochemical indices of mineral metabolism were measured in 31 Hispanic and African American HIV+ postmenopausal women. BMD was compared with 186 historical controls, matched for age, ethnicity and postmenopausal status.