Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight.

Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station.

A second space age spanning omics, platforms and medicine across orbits.

The recent acceleration of commercial, private and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit, concomitant with the largest-ever number of crewed missions entering space and preparations for exploration-class (lasting longer than one year) missions. Such rapid advancement into space from many new companies, countries and space-related entities has enabled a 'second space age'. This era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews.

Chronic inflammation and the hallmarks of aging.

Background: Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, the low-grade chronic inflammation during aging, without overt infection, is defined as "inflammaging," which is associated with increased morbidity and mortality in the aging population. Emerging evidence suggests a bidirectional and cyclical relationship between chronic inflammation and the development of age-related conditions, such as cardiovascular diseases, neurodegeneration, cancer, and frailty.

Glutathione peroxidase 4 inhibition induces ferroptosis and mTOR pathway suppression in thyroid cancer.

Papillary thyroid carcinoma (PTC) demonstrates significantly reduced patient survival with metastatic progression. Tumor progression can be influenced by metabolism, including antioxidant glutathione (GSH). Glutathione peroxidase 4 (GPX4) is a selenoenzyme that uses GSH as a co-factor to regulate lipid peroxidation of cell membranes during increased oxidative stress.

Clinical Predictors of Pseudohypoxia-Type Pheochromocytomas.

Introduction: Pheochromocytomas (PCCs) are rare tumors of neural crest origin with divergent transcriptional and metabolic profiles associated with mutational cluster types. Pseudohypoxia-type (PHT) PCCs have a poor prognosis; however diagnostic genetic testing is not always available. We aimed to investigate clinical parameters predictive of PHT PCCs.

Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy. Nearly half of ACC tumours overproduce and secrete adrenal steroids. Excess cortisol secretion, in particular, has been associated with poor prognosis among ACC patients.

Insurance-based Disparities in Gastro-Entero-Pancreatic Neuroendocrine Tumor Patients.

In the United States, uninsurance remains a major barrier in accessing health care for many citizens and residents. Studies have shown that uninsured patients with many cancers and chronic diseases have worse survival than insured patients. A recent study similarly showed that uninsured patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) have significantly shortened survival.

Cumulative GRAS Score as a Predictor of Survival After Resection for Adrenocortical Carcinoma: Analysis From the U.S. Adrenocortical Carcinoma Database.

Background: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection.

Modeling the impact of delaying surgery for early esophageal cancer in the era of COVID-19.

Background: Surgical society guidelines have recommended changing the treatment strategy for early esophageal cancer during the novel coronavirus (COVID-19) pandemic. Delaying resection can allow for interim disease progression, but the impact of this delay on mortality is unknown. The COVID-19 infection rate at which immediate operative risk exceeds benefit is unknown.

Specific Growth Rate as a Predictor of Survival in Pancreatic Neuroendocrine Tumors: A Multi-institutional Study from the United States Neuroendocrine Study Group.

Background: Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs.

Methods: A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database.

Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

Background: Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear.

An endocannabinoid-regulated basolateral amygdala-nucleus accumbens circuit modulates sociability.

Deficits in social interaction (SI) are a core symptom of autism spectrum disorders (ASDs); however, treatments for social deficits are notably lacking. Elucidating brain circuits and neuromodulatory signaling systems that regulate sociability could facilitate a deeper understanding of ASD pathophysiology and reveal novel treatments for ASDs. Here we found that in vivo optogenetic activation of the basolateral amygdala-nucleus accumbens (BLA-NAc) glutamatergic circuit reduced SI and increased social avoidance in mice.

Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group.

Background: Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection.

Methods: A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database.

Endocannabinoid signalling modulates susceptibility to traumatic stress exposure.

Stress is a ubiquitous risk factor for the exacerbation and development of affective disorders including major depression and posttraumatic stress disorder. Understanding the neurobiological mechanisms conferring resilience to the adverse consequences of stress could have broad implications for the treatment and prevention of mood and anxiety disorders. We utilize laboratory mice and their innate inter-individual differences in stress-susceptibility to demonstrate a critical role for the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) in stress-resilience.

C1q nephropathy and minimal change nephrotic syndrome.

C1q nephropathy (C1qN) is an uncommon disorder seen in children and adults with nephrotic syndrome and non-specific urinary findings. It has been described with minimal change nephrotic syndrome (MCNS), focal segmental glomerulonephritis and isolated mesangial proliferative glomerulonephritis. We describe nine children with MCNS and mesangial C1q deposition.

A randomized, double-blind comparison between parecoxib sodium and propacetamol for parenteral postoperative analgesia after inguinal hernia repair in adult patients.

The newly injectable cyclooxygenase-2 selective nonsteroidal antiinflammatory drug, parecoxib, has never been compared with propacetamol, a parenteral formulation of acetaminophen. In this prospective, randomized, double-blind, double-dummy study, we randomly assigned 182 patients scheduled for initial inguinal hernia repair under general anesthesia to receive a single injection of 40 mg parecoxib or 2 injections of 2 g propacetamol within the first 12 h after surgery. The study variables were morphine consumption, pain at rest and while coughing, and patient satisfaction throughout the first 12 h postoperatively.