The Minnesota Critical Care Working Group 2: Crisis Conditions During the COVID-19 Pandemic, July 2021 through March 2022.

Background: The Minnesota Statewide Healthcare Coordination Center requested that the Minnesota Critical Care Working Group (CCWG) and Ethics Working Group (EWG), comprising interprofessional leaders from Minnesota's 9 largest health systems, plan and coordinate critical care operations during the COVID-19 pandemic, including the fall 2021 surge.

Research Question: Can a statewide working group collaboratively analyze real-time evidence to identify crisis conditions and to engage state leadership to implement care processes?

Study Design And Methods: The CCWG and EWG met via videoconferencing during the severe surge of fall 2021 to analyze evidence and plan for potential crisis care conditions. Five sources of evidence informed their actions: group consensus on operating conditions, federal teletracking data, the Medical Operations Coordination Center (MOCC) patient placement data, and 2 surveys created and distributed to hospitals and health care professionals.

The small molecule inhibitor of SARS-CoV-2 3CLpro EDP-235 prevents viral replication and transmission in vivo.

The COVID-19 pandemic has led to the deaths of millions of people and severe global economic impacts. Small molecule therapeutics have played an important role in the fight against SARS-CoV-2, the virus responsible for COVID-19, but their efficacy has been limited in scope and availability, with many people unable to access their benefits, and better options are needed. EDP-235 is specifically designed to inhibit the SARS-CoV-2 3CLpro, with potent nanomolar activity against all SARS-CoV-2 variants to date, as well as clinically relevant human and zoonotic coronaviruses.

Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts.

TREX1 Inactivation Unleashes Cancer Cell STING-Interferon Signaling and Promotes Antitumor Immunity.

Unlabelled: A substantial fraction of cancers evade immune detection by silencing Stimulator of Interferon Genes (STING)-Interferon (IFN) signaling. Therapeutic reactivation of this program via STING agonists, epigenetic, or DNA-damaging therapies can restore antitumor immunity in multiple preclinical models. Here we show that adaptive induction of three prime exonuclease 1 (TREX1) restrains STING-dependent nucleic acid sensing in cancer cells via its catalytic function in degrading cytosolic DNA.

CHEX-seq detects single-cell genomic single-stranded DNA with catalytical potential.

Genomic DNA (gDNA) undergoes structural interconversion between single- and double-stranded states during transcription, DNA repair and replication, which is critical for cellular homeostasis. We describe "CHEX-seq" which identifies the single-stranded DNA (ssDNA) in situ in individual cells. CHEX-seq uses 3'-terminal blocked, light-activatable probes to prime the copying of ssDNA into complementary DNA that is sequenced, thereby reporting the genome-wide single-stranded chromatin landscape.

Single-Nucleus Transcriptome Profiling of Dorsolateral Prefrontal Cortex: Mechanistic Roles for Neuronal Gene Expression, Including the 17q21.31 Locus, in PTSD Stress Response.

Objective: Multidisciplinary studies of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) implicate the dorsolateral prefrontal cortex (DLPFC) in disease risk and pathophysiology. Postmortem brain studies have relied on bulk-tissue RNA sequencing (RNA-seq), but single-cell RNA-seq is needed to dissect cell-type-specific mechanisms. The authors conducted the first single-nucleus RNA-seq postmortem brain study in PTSD to elucidate disease transcriptomic pathology with cell-type-specific resolution.

A microneedle vaccine printer for thermostable COVID-19 mRNA vaccines.

Decentralized manufacture of thermostable mRNA vaccines in a microneedle patch (MNP) format could enhance vaccine access in low-resource communities by eliminating the need for a cold chain and trained healthcare personnel. Here we describe an automated process for printing MNP Coronavirus Disease 2019 (COVID-19) mRNA vaccines in a standalone device. The vaccine ink is composed of lipid nanoparticles loaded with mRNA and a dissolvable polymer blend that was optimized for high bioactivity by screening formulations in vitro.

Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors.

Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host-graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair.

The proteogenomic subtypes of acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. We report a comprehensive proteogenomic analysis of bone marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative proteomics, our analysis includes cytogenetic profiling and DNA/RNA sequencing.

Discovery and population genomics of structural variation in a songbird genus.

Structural variation (SV) constitutes an important type of genetic mutations providing the raw material for evolution. Here, we uncover the genome-wide spectrum of intra- and interspecific SV segregating in natural populations of seven songbird species in the genus Corvus. Combining short-read (N = 127) and long-read re-sequencing (N = 31), as well as optical mapping (N = 16), we apply both assembly- and read mapping approaches to detect SV and characterize a total of 220,452 insertions, deletions and inversions.

Bleeding to death in a big city: An analysis of all trauma deaths from hemorrhage in a metropolitan area during 1 year.

Background: Hemorrhage is the most common cause of potentially preventable trauma deaths, but no studies have focused on all civilian traumatic deaths from hemorrhage, so we describe a year of these deaths from a large county to identify opportunities for preventing hemorrhagic deaths.

Methods: All trauma-related deaths in Harris County, Texas, in 2014 underwent examination by the medical examiner; patients were excluded if hemorrhage was not their primary reason for death. Deaths were then categorized as preventable/potentially preventable hemorrhage (PPH) or nonpreventable hemorrhage.

Sensory and working memory in a spatial change-detection task by pigeons and humans.

Judgements of items viewed less than 100 ms prior are predominantly supported by a sensory, or iconic, memory system. Iconic memory is of high-capacity, but is also volatile and limited in duration. Judgements after longer delays increasingly rely on a working memory system, which is lower in capacity and volatility than sensory memory, but is longer in duration.

Regulatory CD4 T Cells Recognize Major Histocompatibility Complex Class II Molecule-Restricted Peptide Epitopes of Apolipoprotein B.

Background: CD4 T cells play an important role in atherosclerosis, but their antigen specificity is poorly understood. Immunization with apolipoprotein B (ApoB, core protein of low density lipoprotein) is known to be atheroprotective in animal models. Here, we report on a human APOB peptide, p18, that is sequence-identical in mouse ApoB and binds to both mouse and human major histocompatibility complex class II molecules.

Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure.

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP.

Interaction between the gene, body mass index and depression: meta-analysis of 13701 individuals.

Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the gene, suggesting its implication in the association between depression and obesity.To confirm these findings by investigating the polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.

A comparison of prognosis calculators for geriatric trauma: A Prognostic Assessment of Life and Limitations After Trauma in the Elderly consortium study.

Background: The nine-center Prognostic Assessment of Life and Limitations After Trauma in the Elderly consortium has validated the Geriatric Trauma Outcome Score (GTOS) as a prognosis calculator for injured elders. We compared GTOS' performance to that of the Trauma Injury Severity Score (TRISS) in a multicenter sample.

Methods: Three Prognostic Assessment of Life and Limitations After Trauma in the Elderly centers not submitting subjects to the GTOS validation study identified subjects aged 65 years to 102 years admitted from 2000 to 2013.

7-T (35)Cl and (23)Na MR Imaging for Detection of Mutation-dependent Alterations in Muscular Edema and Fat Fraction with Sodium and Chloride Concentrations in Muscular Periodic Paralyses.

Purpose To determine whether altered sodium (Na(+)) and chloride (Cl(-)) homeostasis can be visualized in periodic paralyses by using 7-T sodium 23 ((23)Na) and chlorine 35 ((35)Cl) magnetic resonance (MR) imaging. Materials and Methods Institutional review board approval and informed consent of all participants were obtained. (23)Na (repetition time msec/echo time msec, 160/0.

Posttranslational Control of ALA Synthesis Includes GluTR Degradation by Clp Protease and Stabilization by GluTR-Binding Protein.

5-Aminolevulinic acid (ALA) is the first committed substrate of tetrapyrrole biosynthesis and is formed from glutamyl-tRNA by two enzymatic steps. Glutamyl-tRNA reductase (GluTR) as the first enzyme of ALA synthesis is encoded by HEMA genes and tightly regulated at the transcriptional and posttranslational levels. Here, we show that the caseinolytic protease (Clp) substrate adaptor ClpS1 and the ClpC1 chaperone as well as the GluTR-binding protein (GBP) interact with the N terminus of GluTR Loss-of function mutants of ClpR2 and ClpC1 proteins show increased GluTR stability, whereas absence of GBP results in decreased GluTR stability.

Multicenter external validation of the Geriatric Trauma Outcome Score: A study by the Prognostic Assessment of Life and Limitations After Trauma in the Elderly (PALLIATE) consortium.

Background: A prognostic tool for geriatric mortality after injury called the Geriatric Trauma Outcome Score (GTOS), where GTOS = [age] + [ISS × 2.5] + [22 if transfused any PRBCs by 24 hours after admission], was previously developed based on 13 years of data from geriatric trauma patients admitted to Parkland Hospital. We sought to validate this model.

In vivo 35Cl MR imaging in humans: a feasibility study.

Purpose: To implement chlorine 35 ((35)Cl) magnetic resonance (MR) at a 7-T whole-body MR system and evaluate its feasibility for imaging humans.

Materials And Methods: All examinations were performed with ethical review board approval; written informed consent was obtained from all volunteers. Seven examinations each of brain and muscle in healthy volunteers and four examinations of patients were performed.

Visual discrimination learning with an iPad-equipped apparatus.

Visual discrimination tasks are commonly used to assess visual learning and memory in non-human animals. The current experiments explored the suitability of an iPad (Apple, Cupertino, California), as a low-cost alternative touchscreen for visual discrimination tasks. In Experiment 1, rats were trained with patterned black-and-white stimuli in a successive non-match to sample procedure.

Neurovascular Contact of Cranial Nerve IX and X Root-Entry Zone in Hypertensive Patients.

-Neurovascular contact of the left rostral ventrolateral medulla has been implicated in the pathogenesis of "essential" hypertension, and recent intervention studies suggest that surgical decompression of the ventrolateral medulla lowers blood pressure in these patients. We assessed the prevalence of this vascular anomaly in patients with essential hypertension by using an advanced MRI technique. We performed MRI of the brain stem in 125 hypertensive patients and in 105 age-matched, sex-matched, and body mass index-matched normotensive control subjects.