Automated infection risks assessments (AIRa) for decision-making using a blockchain-based alert system: A case study in a representative building.

Indoor air quality (IAQ) is an important parameter in protecting the occupants of an indoor environment. Previous studies have shown that an indoor environment with poor ventilation increases airborne virus transmission. Existing research has concluded that high ventilation rates can reduce the risk of individuals in indoor environments being infected.

Human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) structure and biochemistry reveals remarkable similarities to HIV-1 RT and opportunities for HERV-K-specific inhibition.

Human endogenous retroviruses (HERVs) comprise nearly 8% of the human genome and are derived from ancient integrations of retroviruses into the germline. The biology of HERVs is poorly defined, but there is accumulating evidence supporting pathological roles in diverse diseases, such as cancer, autoimmune, and neurodegenerative diseases. Functional proteins are produced by HERV-encoded genes, including reverse transcriptases (RTs), which could be a contributor to the pathology attributed to aberrant HERV-K expression.

Reducing Alert Fatigue by Sharing Low-Level Alerts With Patients and Enhancing Collaborative Decision Making Using Blockchain Technology: Scoping Review and Proposed Framework (MedAlert).

Background: Clinical decision support (CDS) is a tool that helps clinicians in decision making by generating clinical alerts to supplement their previous knowledge and experience. However, CDS generates a high volume of irrelevant alerts, resulting in alert fatigue among clinicians. Alert fatigue is the mental state of alerts consuming too much time and mental energy, which often results in relevant alerts being overridden unjustifiably, along with clinically irrelevant ones.

Give Intravenous Bolus Overdose a Brake: User Experience and Perception of Safety Device.

Objectives: Drugs can come in concentrated solutions that require dilution before intravenous bolus administration. Upon dilution, the syringe can contain more than the required amount of drug. The user may mistakenly administer the full contents of the syringe, resulting in an overdose.

Structural analysis of the LDL receptor-interacting FERM domain in the E3 ubiquitin ligase IDOL reveals an obscured substrate-binding site.

Hepatic abundance of the low-density lipoprotein receptor (LDLR) is a critical determinant of circulating plasma LDL cholesterol levels and hence development of coronary artery disease. The sterol-responsive E3 ubiquitin ligase inducible degrader of the LDLR (IDOL) specifically promotes ubiquitination and subsequent lysosomal degradation of the LDLR and thus controls cellular LDL uptake. IDOL contains an extended N-terminal FERM (4.

Reorganising the emergency department to manage the COVID-19 outbreak.

Background: The COVID-19 disease outbreak that first surfaced in Wuhan, China, in December 2019, has taken the world by storm and ravaged almost every country in the world. Emergency departments (ED) in hospitals are on the frontlines, serving an essential function in identifying these patients, isolating them early whilst providing urgent medical care. This outbreak has reinforced the role of Emergency Medicine in public health.

Emergency department 'outbreak rostering' to meet challenges of COVID-19.

The COVID-19 outbreak has posed unique challenges to the emergency department rostering. Additional infection control, the possibility of quarantine of staff and minimising contact among staff have significant impact on the work of doctors in the emergency department. Infection of a single healthcare worker may require quarantine of close contacts at work.

Structural insights into the critical DNA damage sensors DNA-PKcs, ATM and ATR.

ATM, ATR and DNA-PKCs are key effectors of DNA Damage response and have been extensively linked to tumourigenesis and survival of cancer cells after radio/chemotherapy. Despite numerous efforts, the structures of these proteins remained elusive until very recently. The resolution revolution in Cryo-EM allowed for molecular details of these proteins to be seen for the first time.

Inhibition of low-density lipoprotein receptor degradation with a cyclic peptide that disrupts the homodimerization of IDOL E3 ubiquitin ligase.

Cellular uptake of circulating cholesterol occurs the low density lipoprotein receptor (LDLR). The E3 ubiquitin ligase IDOL is a mediator of LDLR degradation, with IDOL homodimerization thought to be required for its activity. To probe the possibility of modulating LDLR levels with an inhibitor of IDOL homodimerization, we screened a SICLOPPS library of 3.

Role of peak current in conversion of patients with ventricular fibrillation.

Introduction: Peak currents are the final arbiter of defibrillation in patients with ventricular fibrillation (VF). However, biphasic defibrillators continue to use energy in joules for electrical conversion in hopes that their impedance compensation properties will address transthoracic impedance (TTI), which must be overcome when a fixed amount of energy is delivered. However, optimal peak currents for conversion of VF remain unclear.

X-ray structural analysis of tau-tubulin kinase 1 and its interactions with small molecular inhibitors.

Tau-tubulin kinase 1 (TTBK1) is a serine/threonine/tyrosine kinase that putatively phosphorylates residues including S422 in tau protein. Hyperphosphorylation of tau protein is the primary cause of tau pathology and neuronal death associated with Alzheimer's disease. A library of 12 truncation variants comprising the TTBK1 kinase domain was screened for expression in Escherichia coli and insect cells.

Advances in recombinant protein expression for use in pharmaceutical research.

Protein production for structural and biophysical studies, functional assays, biomarkers, mechanistic studies in vitro and in vivo, but also for therapeutic applications in pharma, biotech and academia has evolved into a mature discipline in recent years. Due to the increased emphasis on biopharmaceuticals, the growing demand for proteins used for structural and biophysical studies, the impact of genomics technologies on the analysis of large sets of structurally diverse proteins, and the increasing complexity of disease targets, the interest in innovative approaches for the expression, purification and characterisation of recombinant proteins has steadily increased over the years. In this review, we summarise recent developments in the field of recombinant protein expression for research use in pharma, biotech and academia.

Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure.

The ROCK-I serine/threonine protein kinase mediates the effects of RhoA to promote the formation of actin stress fibres and integrin-based focal adhesions. ROCK-I phosphorylates the unconventional G-protein RhoE on multiple N- and C-terminal sites. These phosphorylation events stabilise RhoE, which functions to antagonise RhoA-induced stress fibre assembly.

Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.

Over 30 mutations of the B-RAF gene associated with human cancers have been identified, the majority of which are located within the kinase domain. Here we show that of 22 B-RAF mutants analyzed, 18 have elevated kinase activity and signal to ERK in vivo. Surprisingly, three mutants have reduced kinase activity towards MEK in vitro but, by activating C-RAF in vivo, signal to ERK in cells.