Novel broadly reactive monoclonal antibody protects against infection.

The incidence of infections attributed to antimicrobial-resistant (AMR) pathogens has increased exponentially over the recent decades reaching 1.27 million deaths worldwide in 2019. Without intervention, these infections are predicted to cause up to 10 million deaths a year and incur costs of up to 100 trillion US dollars globally by 2050.

VAERS Vasculitis Adverse Events Retrospective Study: Etiology Model of Immune Complexes Activating Fc Receptors in Kawasaki Disease and Multisystem Inflammatory Syndromes.

Background: Vasculitis diseases include Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), Multisystem Inflammatory Syndrome (MIS), Henoch-Schönlein purpura (HS), or IgA vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than in adults.

Omics Analysis and Quality Control Pipelines in a High-Performance Computing Environment.

Data quality is often an overlooked feature in the analysis of omics data. This is particularly relevant in studies of chemical and pathogen exposures that can modify an individual's epigenome and transcriptome with persistence over time. Portable, quality control (QC) pipelines for multiple different omics datasets are therefore needed.

Using FastID to analyze complex SNP mixtures from indoor dust.

Forensically relevant single nucleotide polymorphisms (SNPs) can provide valuable supplemental information to short tandem repeats (STRs) for investigative leads, and genotyping can now be streamlined using massively parallel sequencing (MPS). Dust is an attractive evidence source, as it accumulates on undisturbed surfaces, often is overlooked by perpetrators, and contains sufficient human DNA for analysis. To assess whether SNPs genotyped from indoor dust using MPS could be used to detect known household occupants, 13 households were recruited and provided buccal samples from each occupant and dust from five predefined indoor locations.

Elevated Histamine Etiology Model for Most Major Vaccine Associated Adverse Events including SARS-CoV-2 Spike Vaccines.

Vaccinees experience no adverse events, mild adverse events, multiple adverse events, or serious adverse events post vaccination. Many of these vaccine adverse events occur with different vaccines with different occurrence frequencies. Many of these adverse events are generally considered as associated with immune responses to the active vaccine components (antigens) and/or to possibly one or more of the vaccine excipients.

Models for SARS-CoV-2 associated thrombocytopenia associated with hemophagocytic histiocytes.

A subset of COVID-19 patients is experiencing secondary immune thrombocytopenia, also called immune thrombocytopenic purpura (ITP) or secondary hemophagocytic lymphohistiocytosis (HLH). The pathogenesis of SARS-CoV-2 associated thrombocytopenia is unknown. Very rare cases of vaccine induced prothrombotic immune thrombocytopenia (VIPIT) are occurring associated with COVID-19 vaccines.

Models for COVID-19 Early Cardiac Pathology Following SARS-CoV-2 Infection.

Objectives: The clinical manifestations of COVID-19 associated cardiac complications are heterogeneous, ranging from asymptomatic to severe symptoms, including arrhythmias and cardiogenic shock. For COVID-19 patients with cardiac sequela, only a small subset of patients have myocarditis; the pathogenesis of cardiac sequela caused by SARS-CoV-2 other than microthrombi associated sequela remains to be determined.

Methods: Retrospective analysis of 71 heart autopsy specimens from COVID-19 and putative COVID-19 in the NIH COVID Digital Pathology Repository.

COVID-19 Disease, Women's Predominant Non-Heparin Vaccine-Induced Thrombotic Thrombocytopenia and Kounis Syndrome: A Passepartout Cytokine Storm Interplay.

Unlabelled: Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitute one of the deadliest pandemics in modern history demonstrating cardiovascular, gastrointestinal, hematologic, mucocutaneous, respiratory, neurological, renal and testicular manifestations and further complications. COVID-19-induced excessive immune response accompanied with uncontrolled release of cytokines culminating in cytokine storm seem to be the common pathogenetic mechanism of these complications. The aim of this narrative review is to elucidate the relation between anaphylaxis associated with profound hypotension or hypoxemia with pro-inflammatory cytokine release.

COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms.

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. SARS-CoV-2 infection is necessary but not sufficient for development of clinical COVID-19 disease. Currently, there are no approved pre- or post-exposure prophylactic COVID-19 medical countermeasures.

Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies.

COVID-19 (SARS-CoV-2) disease severity and stages varies from asymptomatic, mild flu-like symptoms, moderate, severe, critical, and chronic disease. COVID-19 disease progression include lymphopenia, elevated proinflammatory cytokines and chemokines, accumulation of macrophages and neutrophils in lungs, immune dysregulation, cytokine storms, acute respiratory distress syndrome (ARDS), etc. Development of vaccines to severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and other coronavirus has been difficult to create due to vaccine induced enhanced disease responses in animal models.

COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms.

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure.

Analysis of complex DNA mixtures using massively parallel sequencing of SNPs with low minor allele frequencies.

DNA mixtures from 3 or more contributors have proven difficult to analyze using the current state-of-the-art method of short-tandem repeat (STR) amplification followed by capillary electrophoresis (CE). Here we analyze samples from both laboratory-defined mixtures and complex multi-contributor touch samples using a single nucleotide polymorphism (SNP) panel comprised of 2311 low-minor-allele-frequency loci, combined with massively parallel sequencing (MPS). This approach demonstrates that as many as 10 people can be identified in touch samples using a threshold of -Log P(RMNE) of 6, and a detection rate of 18-94 % across 10 different materials using a threshold of -Log P(RMNE) of 2.

Predicting Influenza A Tropism with End-to-End Learning of Deep Networks.

The type of host that a virus can infect, referred to as host specificity or tropism, influences infectivity and thus is important for disease diagnosis, epidemic response, and prevention. Advances in DNA sequencing technology have enabled rapid metagenomic analyses of viruses, but the prediction of virus phenotype from genome sequences is an active area of research. As such, automatic prediction of host tropism from analysis of genomic information is of considerable utility.

Estimating Individual Contributions to Complex DNA SNP Mixtures.

High-throughput sequencing (HTS) of large panels of single nucleotide polymorphisms (SNPs) provides an alternative or complimentary approach to short tandem repeats (STRs) panels for the analysis of complex DNA mixture forensic samples. For STRs, methods to estimate individual contribution concentrations compare capillary electrophoresis peak heights, peak areas, or HTS allele read counts within a mixture. This article introduces three approaches (mean, median, and slope methods) for estimating individual DNA contributions to forensic mixtures for HTS/massively parallel sequencing (MPS) SNP panels.

GrigoraSNPs: Optimized Analysis of SNPs for DNA Forensics.

High-throughput sequencing (HTS) of single nucleotide polymorphisms (SNPs) enables additional DNA forensic capabilities not attainable using traditional STR panels. However, the inclusion of sets of loci selected for mixture analysis, extended kinship, phenotype, biogeographic ancestry prediction, etc., can result in large panel sizes that are difficult to analyze in a rapid fashion.

Association Between Single Gene Polymorphisms and Bone Biomarkers and Response to Calcium and Vitamin D Supplementation in Young Adults Undergoing Military Training.

Initial military training (IMT) is associated with increased stress fracture risk. In prior studies, supplemental calcium (Ca) and vitamin D provided daily throughout IMT reduced stress fracture incidence, suppressed parathyroid hormone (PTH), and improved measures of bone health compared with placebo. Data were analyzed from a randomized, double-blind, placebo-controlled trial to determine whether single-nucleotide polymorphisms (SNPs) in Ca and vitamin D-related genes were associated with circulating biomarkers of bone metabolism in young adults entering IMT, and whether responses to Ca and vitamin D supplementation were modulated by genotype.

In vivo Monitoring of Transcriptional Dynamics After Lower-Limb Muscle Injury Enables Quantitative Classification of Healing.

Traumatic lower-limb musculoskeletal injuries are pervasive amongst athletes and the military and typically an individual returns to activity prior to fully healing, increasing a predisposition for additional injuries and chronic pain. Monitoring healing progression after a musculoskeletal injury typically involves different types of imaging but these approaches suffer from several disadvantages. Isolating and profiling transcripts from the injured site would abrogate these shortcomings and provide enumerative insights into the regenerative potential of an individual's muscle after injury.

Absolute quantification of monoclonal antibodies in biofluids by liquid chromatography-tandem mass spectrometry.

The development of a quantification method for monoclonal antibodies in serum has been accomplished by high-performance liquid chromatography multiple reactions monitoring mass spectrometry. A human monoclonal antibody (HmAb) was used as the model protein for method development and validation. A peptide from the CDR3-region of its heavy chain was selected and used for quantifying the entire mAb.

Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.

New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study.

Genomic approaches to drug discovery.

Considerable progress has been made in exploiting the enormous amount of genomic and genetic information for the identification of potential targets for drug discovery and development. New tools that incorporate pathway information have been developed for gene expression data mining to reflect differences in pathways in normal and disease states. In addition, forward and reverse genetics used in a high-throughput mode with full-length cDNA and RNAi libraries enable the direct identification of components of signaling pathways.

A draft sequence of the rice genome (Oryza sativa L. ssp. japonica).

The genome of the japonica subspecies of rice, an important cereal and model monocot, was sequenced and assembled by whole-genome shotgun sequencing. The assembled sequence covers 93% of the 420-megabase genome. Gene predictions on the assembled sequence suggest that the genome contains 32,000 to 50,000 genes.