Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein.
View Article and Find Full Text PDFFibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies.
View Article and Find Full Text PDFOrgan donation after brain death has been practiced in China since 2003 in the absence of brain death legislation. Similar to international standards, China's brain death diagnostic criteria include coma, absence of brainstem reflexes, and the lack of spontaneous respiration. The Chinese criteria require that the lack of spontaneous respiration must be verified with an apnea test by disconnecting the ventilator for 8 min to provoke spontaneous respiration.
View Article and Find Full Text PDFAlthough mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection.
View Article and Find Full Text PDFSARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4 T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4 T (T) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node T.
View Article and Find Full Text PDFAlthough mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 memory T cells is poorly understood. Here, we utilize DNA-barcoded MHC-multimers combined with scRNAseq and scTCRseq to capture the profile of SARS-CoV-2-responsive T cells within a cohort of individuals with one, two, or three antigen exposures, including vaccination, primary infection, and breakthrough infection.
View Article and Find Full Text PDFSince 1997, execution in China has been increasingly performed by lethal injection. The current criteria for determination of death for execution by lethal injection (cessation of heartbeat, cessation of respiration, and dilated pupils) neither conform to current medical science nor to any standard of medical ethics. In practice, death is pronounced in China within tens of seconds after starting the lethal injection.
View Article and Find Full Text PDFThis report investigates the excited-state properties of a series of N-aryl-2,3-naphthalimides along with their fabrication into OLEDs and electroluminescence measurements. The N-aryl-2,3-NIs substituted specifically with chloro, fluoro, and methoxy substituents were chosen because of their unique propensity to display two emission bands or panchromatic fluorescence. Using the Lippert-Mataga analysis along with TD-DFT calculations, the excited states were determined to be n,π* and π,π*.
View Article and Find Full Text PDFBackground: Over 90% of the organs transplanted in China before 2010 were procured from prisoners. Although Chinese officials announced in December 2014 that the country would completely cease using organs harvested from prisoners, no regulatory adjustments or changes in China's organ donation laws followed. As a result, the use of prisoner organs remains legal in China if consent is obtained.
View Article and Find Full Text PDFBackground: In December 2014, China announced that only voluntarily donated organs from citizens would be used for transplantation after January 1, 2015. Many medical professionals worldwide believe that China has stopped using organs from death-row prisoners.
Discussion: In the present article, we briefly review the historical development of organ procurement from death-row prisoners in China and comprehensively analyze the social-political background and the legal basis of the announcement.
The effect of hospital organizational affiliation on perinatal outcomes is unknown. Using the 2004 American Hospital Association Annual Survey and Healthcare Cost and Utilization Project State Inpatient Databases, the authors examined relationships among organizational affiliation, equipment and service availability and provision, and in-hospital mortality for 5,133 infants across five states born with very low and extremely low birth weight and congenital anomalies. In adjusted bivariate probit selection models, the authors found that government hospitals had significantly higher mortality rates than not-for-profit nonreligious hospitals.
View Article and Find Full Text PDFThe United States is facing a health care crisis with the number of uninsured Americans exceeding 46 million and health care premiums and overall costs increasing at 3 to 4 times the rate of inflation. Proposed solutions include continuing managed care, moving to a single-payer financing system with universal coverage, and replacing traditional health plans with high-deductible policies that allow patients to draw from health savings accounts (HSAs) to pay out-of-pocket costs. Despite physicians' vital role in health care, few studies have assessed their preferences regarding health care financing systems.
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