Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy.

Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and limited existing therapeutic interventions, in part due to a lack of actionable targets and translational animal models for preclinical trials. Comprehensive data on this tumour type are scarce, and existing data often overlooks the importance of the anatomical site of origin. We evaluated human and canine oronasal mucosal melanoma (OMM) to determine whether the common canine disease could inform the rare human equivalent.

Evaluation of the diagnostic accuracy of Xpert® Mpox and STANDARD™ M10 MPX/OPX for the detection of monkeypox virus.

Objectives: Evaluation of diagnostic accuracy of two point-of-care (POC) molecular diagnostic tests for the detection of monkeypox virus (MPXV): Xpert® Mpox (Cepheid, Inc., USA) and STANDARD™ M10 MPX/OPX (SD Biosensor, Inc., Korea).

Enhanced kinase translocation reporters for simultaneous real-time measurement of PKA, ERK, and calcium.

Kinase translocation reporters (KTRs) are powerful tools for single-cell measurement of time-integrated kinase activity but suffer from restricted dynamic range and limited sensitivity, particularly in neurons. To address these limitations, we developed enhanced KTRs (eKTRs) for protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) by (i) increasing KTR size, which reduces the confounding effect of KTR diffusion through the nuclear pore, and (ii) modulating the strength of the bipartite nuclear localization signal (bNLS) in their kinase sensor domains, to ensures that the relative distribution of the KTR between the nucleus and cytoplasmic is determined by active nuclear import, active nuclear export, and relative activity of their cognate kinase. The resultant sets of ePKA-KTRs and eERK-KTRs display high sensitivity, broad dynamic range, and cell type-specific tuning.

Equestrian Sports Safety: An Update on Safety Equipment and Event Medical Coverage.

Equestrian sports are associated with high rates of major injury compared to collision and powered two-wheel sports. Advancements in rider and horse safety equipment and the implementation of comprehensive emergency action planning standards may help mitigate injuries, particularly in regard to the Olympic disciplines of dressage, show jumping, and three-day eventing covered in this review. Personal safety equipment to consider includes helmets, safety and air vests, and horse tack including safety stirrups, acoustic dampeners, and breakaway reins.

Common Benign Bone Lesions and Return to Sports: A Case Report and Scoping Review.

Background: Benign bone lesions are a common incidental finding in athletes during workup for musculoskeletal complaints, and athletes are frequently advised to halt participation in contact sports. There are no current guidelines to assist clinicians in referring patients with these lesions to a subspecialist or in advising athletes on the safety of returning to sport.

Purpose: To assist sports medicine physicians in appropriate referral for patients with benign bone lesions through presentation of a literature review and the case of an adolescent athlete with a benign bone lesion in a location with a significant fracture risk.

Pan-cancer analysis of biallelic inactivation in tumor suppressor genes identifies KEAP1 zygosity as a predictive biomarker in lung cancer.

The canonical model of tumor suppressor gene (TSG)-mediated oncogenesis posits that loss of both alleles is necessary for inactivation. Here, through allele-specific analysis of sequencing data from 48,179 cancer patients, we define the prevalence, selective pressure for, and functional consequences of biallelic inactivation across TSGs. TSGs largely assort into distinct classes associated with either pan-cancer (Class 1) or lineage-specific (Class 2) patterns of selection for biallelic loss, although some TSGs are predominantly monoallelically inactivated (Class 3/4).

The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.

Severity of COVID-19 is affected by multiple factors; however, it is not understood how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure affects the control of viral replication. Here, we demonstrate that immune events in the mouse lung closely preceding SARS-CoV-2 infection affect viral control and identify innate immune pathways that limit viral replication. Pulmonary inflammatory stimuli including resolved, antecedent respiratory infections with or influenza, ongoing pulmonary infection, ovalbumin/alum-induced asthma, or airway administration of TLR ligands and recombinant cytokines all establish an antiviral state in the lung that restricts SARS-CoV-2 replication.

Application of machine learning algorithms to identify serological predictors of COVID-19 severity and outcomes.

Background: Critically ill hospitalized patients with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized.

Methods: In a cohort study of 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and more than 20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms.

Reliability of plastid and mitochondrial localisation prediction declines rapidly with the evolutionary distance to the training set increasing.

Mitochondria and plastids import thousands of proteins. Their experimental localisation remains a frequent task, but can be resource-intensive and sometimes impossible. Hence, hundreds of studies make use of algorithms that predict a localisation based on a protein's sequence.

Are Repeat-Dose Toxicity Studies Informative for Safety Assessment of Vaccine Candidates? A Survey of Vaccine Developers.

A BioSafe-sponsored survey investigated how vaccine companies (n = 12) perceive the value of the repeat-dose toxicity studies for safety assessment of vaccine candidates. As all major vaccine developers were part of the survey, it was considered representative for the industry practices up to 2022. Vaccine developers indicated that they see scientific value in performing repeat-dose toxicity studies with vaccines, especially when novel components (e.

Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells.

Purpose Of Review: Sepsis-induced inflammatory lung injury includes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). There are currently no effective treatments for ALI/ARDS, but clinical outcomes could be improved by inhibiting lung injury and/or promoting post-sepsis vascular repair. In this review, we describe studies of endothelial cell metabolic pathways in sepsis-induced ALI/ARDS and vascular repair and identify areas of research that deserve attention in future studies.

Optimization of SARS-CoV-2 culture from clinical samples for clinical trial applications.

Unlabelled: Clinical trials of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics often include virological secondary endpoints to compare viral clearance and viral load reduction between treatment and placebo arms. This is typically achieved using quantitative reverse-transcriptase PCR (RT-qPCR), which cannot differentiate replicant competent virus from non-viable virus or free RNA, limiting its utility as an endpoint. Culture-based methods for SARS-CoV-2 exist; however, these are often insensitive and poorly standardized for use as clinical trial endpoints.

Enhanced kinase translocation reporters for simultaneous real-time measurement of PKA, ERK, and Ca.

Kinase translocation reporters (KTRs) are powerful tools for single-cell measurement of time-integrated kinase activity but suffer from restricted dynamic range and limited sensitivity, particularly in neurons. To address these limitations, we developed enhanced KTRs (eKTRs) for protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) that display high sensitivity, rapid response kinetics, broad dynamic range, cell type-specific tuning, and an ability to detect PKA and ERK activity in primary sensory neurons. Moreover, co-expression of optically separable eKTRs for PKA and ERK revealed the kinetics of expected and unexpected crosstalk between PKA, ERK, protein kinase C, and calcium signaling pathways, demonstrating the utility of eKTRs for live cell monitoring of diverse and interacting signaling pathways.

Detection of γ-OHPdG in Circulating Tumor Cells of Patients With Hepatocellular Carcinoma as a Potential Prognostic Biomarker of Recurrence.

Background And Aims: Blood-based biomarkers for hepatocellular carcinoma (HCC) and its recurrence are lacking. We previously showed that hepatic γ-hydroxy-1, -propano-2'-deoxyguanosine (γ-OHPdG), an endogenous DNA adduct derived from acrolein by lipid peroxidation, increased during hepatocarcinogenesis. Additionally, higher hepatic γ-OHPdG from HCC patients after surgery were strongly associated with poor survival ( < .

CNS and Thorax Injury and Associated Risks Factors in Equestrian Sports.

Context: Equestrian sports continue to gain popularity in the United States and are associated with a high injury rate, especially involving the central nervous system and thorax. Due to this high rate of injury and the potential for long-term consequences associated with participation, an understanding of the unique risks of this sport is needed.

Objective: To describe severe injury in equestrian sports and review the role that protective gear plays in injury mitigation.

Pediatric forensic postmortem computed tomography: basics to advanced.

The approach to postmortem computed tomography (CT) differs significantly from that of diagnostic CT in living patients. Elimination of artifacts such as noise and beam hardening as well as optimization of tissue contrast requires alteration of exposure parameters from protocols designed to limit radiation dose in children. Multiple scans may be performed, and detailed post-processing can be used to enhance subtle findings such as small intracranial extra axial collections and non-displaced fractures.

An Evaluation of the Replacement of Animal-derived Biomaterials in Human Primary Cell Culture.

The likelihood that potential new drugs will successfully navigate the current translational pipeline is poor, with fewer than 10% of drug candidates making this transition successfully, even after their entry into clinical trials. Prior to this stage, candidate drugs are typically evaluated by using models of increasing complexity, beginning with basic cell culture studies and progressing through to animal studies, where many of these candidates are lost due to lack of efficacy or toxicology concerns. There are many reasons for this poor translation, but interspecies differences in functional and physiological parameters undoubtedly contribute to the problem.

Identification of a lumped-parameter model of the intervertebral joint from experimental data.

Through predictive simulations, multibody models can aid the treatment of spinal pathologies by identifying optimal surgical procedures. Critical to achieving accurate predictions is the definition of the intervertebral joint. The joint pose is often defined by virtual palpation.

COVID-19 Diarrhea Is Inflammatory, Caused by Direct Viral Effects Plus Major Role of Virus-induced Cytokines.

Background & Aims: Diarrhea occurs in up to 50% of cases of COVID-19. Nonetheless, the pathophysiologic mechanism(s) have not been determined.

Methods: This was examined using normal human enteroid monolayers exposed apically to live SARS-CoV-2 or non-replicating virus-like particles (VLPs) bearing the 4 SARS-CoV-2 structural proteins or irradiated virus, all of which bound and entered enterocytes.

Scalable Deep Color Quantization: A Cluster Imitation Approach.

Color quantization reduces the number of colors used in an image while preserving its content, which is essential in pixel art and knitting art creation. Traditional methods primarily focus on visual fidelity and treat it as a clustering problem in the RGB space. While effective in large (5-6 bits) color spaces, these approaches cannot guarantee semantics in small (1-2 bits) color spaces.

Airbag Vests in Equestrian Sports: Is Use Associated with Harm?

Airbag vests (AV) are increasingly popular in equestrian sports. The efficacy of AV in protecting against serious injury has not been adequately analyzed, nor have product testing standards been established. This study provides an overview of current research to understand AV efficacy and future areas of improvement.