ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide.

Use of an extended KDIGO definition to diagnose acute kidney injury in patients with COVID-19: A multinational study using the ISARIC-WHO clinical characterisation protocol.

Background: Acute kidney injury (AKI) is one of the most common and significant problems in patients with Coronavirus Disease 2019 (COVID-19). However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional Kidney Disease Improving Global Outcomes (KDIGO) definition can fail to identify patients for whom hospitalisation coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr).

Urine collection devices to reduce contamination in urine samples for diagnosis of uncomplicated UTI: a single-blind randomised controlled trial in primary care.

Background: Urine collection devices (UCDs) are being marketed and used in clinical settings to reduce urine sample contamination, despite inadequate supporting evidence.

Aim: To determine whether UCDs, compared with standardised instructions for urine sample collection, reduce the proportion of contaminated samples.

Design And Setting: Single-blind randomised controlled trial in general practices in England and Wales.

The Suspected CANcer (SCAN) pathway: protocol for evaluating a new standard of care for patients with non-specific symptoms of cancer.

Introduction: Cancer survival in England lags behind most European countries, due partly to lower rates of early stage diagnosis. We report the protocol for the evaluation of a multidisciplinary diagnostic centre-based pathway for the investigation of 'low-risk but not no-risk' cancer symptoms called the Suspected CANcer (SCAN) pathway. SCAN is a new standard of care being implemented in Oxfordshire; one of a number of pathways implemented during the second wave of the Accelerate, Coordinate, Evaluate (ACE) programme, an initiative which aims to improve England's cancer survival rates through establishing effective routes to early diagnosis.

An open randomised study of autoinflation in 4- to 11-year-old school children with otitis media with effusion in primary care.

Background: Otitis media with effusion (OME) is a very common problem in primary care, but one that lacks an evidence-based non-surgical treatment.

Objective: To determine the clinical effectiveness of nasal balloon autoinflation for the treatment of OME in children.

Design: A pragmatic, two-arm, open randomised controlled trial.

Effect of nasal balloon autoinflation in children with otitis media with effusion in primary care: an open randomized controlled trial.

Background: Otitis media with effusion is a common problem that lacks an evidence-based nonsurgical treatment option. We assessed the clinical effectiveness of treatment with a nasal balloon device in a primary care setting.

Methods: We conducted an open, pragmatic randomized controlled trial set in 43 family practices in the United Kingdom.

Diffuse transition state structure for the unfolding of a leucine-rich repeat protein.

Tandem-repeat proteins, such as leucine-rich repeats, comprise arrays of small structural motifs that pack in a linear fashion to produce elongated architectures. They lack contacts between residues that are distant in primary sequence, a feature that distinguishes them from the complex topologies of globular proteins. Here we have investigated the unfolding pathway of the leucine-rich repeat domain of the mRNA export protein TAP (TAPLRR) using Φ-value analysis.

Activation of ubiquitin ligase SCF(Skp2) by Cks1: insights from hydrogen exchange mass spectrometry.

Skp2 is the substrate recognition subunit of the multi-subunit ubiquitin ligase SCF(Skp2). It consists of an N-terminal F-box domain that binds to the Skp1 subunit and thereby tethers it to the SCF catalytic core, and an elongated C-terminal domain comprising ten Leucine-rich repeats (LRR) that binds the substrate. A small accessory protein, Cks1, is required for SCF(Skp2) to target certain substrates, including the Cyclin-dependent kinase inhibitor p27.

Folding and fibril formation of the cell cycle protein Cks1.

The Saccharomyces cerevisiae Cks protein Cks1 has a COOH-terminal glutamine-rich sequence not present in other homologues. Cks proteins domain swap to form dimers but unique to Cks1 is the anti-parallel arrangement of protomers within the dimer. Despite the differences in Cks1 compared with other Cks proteins, we find the domain swapping properties are very similar.

Role of conformational heterogeneity in domain swapping and adapter function of the Cks proteins.

Cks proteins are adapter molecules that coordinate the assembly of multiprotein complexes. They share the ability to domain swap by exchanging a beta-strand, beta4. Here we use NMR spectroscopy and molecular dynamics simulations to investigate the dynamic properties of human Cks1 and its response on assembly with components of the SCF(Skp2) ubiquitin ligation machinery.