IL-33 is associated with alveolar dysfunction in patients with viral lower respiratory tract disease.

Interleukin (IL)-33 is released following tissue damage, causing airway inflammation and remodelling via reduced IL-33 (IL-33)/serum stimulation-2 (ST2) and oxidised IL-33 (IL-33)/receptor for advanced glycation end products (RAGE)/epidermal growth factor receptor (EGFR) pathways. This study aimed to identify associations of IL-33 with clinical outcomes and pathological mechanisms during viral lower respiratory tract disease (LRTD). Ultra-sensitive immunoassays were developed to measure IL-33, IL-33 and IL-33/sST2 complexes in samples from patients hospitalised with COVID-19.

Responding to COVID-19: an exploration of EU country responses and directions for further research.

Background: During COVID-19, scientists advising policymakers were forced to deal with high uncertainty and risks in an environment of unknowns. Evidence on which policies and measures were effective in responding to the pandemic remains underdeveloped to answer the key question 'what worked and why?'. This study aims to provide a basis for studies to go further to answer this critical question, by starting to look efficacy or how countries ensured that health services remained available and what measures were enacted to protect and treat their populations and workers.

Targeted protein degradation using chimeric human E2 ubiquitin-conjugating enzymes.

Proteins can be targeted for degradation by engineering biomolecules that direct them to the eukaryotic ubiquitination machinery. For instance, the fusion of an E3 ubiquitin ligase to a suitable target binding domain creates a 'biological Proteolysis-Targeting Chimera' (bioPROTAC). Here we employ an analogous approach where the target protein is recruited directly to a human E2 ubiquitin-conjugating enzyme via an attached target binding domain.

Robust Prediction of Relative Binding Energies for Protein-Protein Complex Mutations Using Free Energy Perturbation Calculations.

Computational free energy-based methods have the potential to significantly improve throughput and decrease costs of protein design efforts. Such methods must reach a high level of reliability, accuracy, and automation to be effectively deployed in practical industrial settings in a way that impacts protein design projects. Here, we present a benchmark study for the calculation of relative changes in protein-protein binding affinity for single point mutations across a variety of systems from the literature, using free energy perturbation (FEP+) calculations.

Russian dilemma for global arctic science.

Polar regions are critically implicated in our understanding of global climate change. This is particularly the case for the Arctic, where positive feedback loops and climate tipping points enhance complexity and urgency. Half of the Arctic and much of the world's permafrost zone lie within Russian territory.

Forced displacement and the health workforce crisis: Venezuelan healthcare workers in Peru.

The migration of health workforces tends to be economically based benefiting high-income countries, while draining lower-income countries of workers and skills However, national instability or civil conflict may also have the effect of forcing out health workers. However, few articles focus on the experiences of these types of migrants. Peru has become the second largest Latin American destination for Venezuelan forced displaced migrants, a number of which are health workers.

A simeprevir-inducible molecular switch for the control of cell and gene therapies.

Chemical inducer of dimerization (CID) modules can be used effectively as molecular switches to control biological processes, and thus there is significant interest within the synthetic biology community in identifying novel CID systems. To date, CID modules have been used primarily in engineering cells for in vitro applications. To broaden their utility to the clinical setting, including the potential to control cell and gene therapies, the identification of novel CID modules should consider factors such as the safety and pharmacokinetic profile of the small molecule inducer, and the orthogonality and immunogenicity of the protein components.

Global change research needs international collaboration.

Tackling the grand challenges of global climate change for the sustainability of ecological and societal systems requires data and expertise from Russia, the world's largest country that has the longest Arctic shoreline and the largest forest biome, peatland and permafrost zones. Academic relations and scientific collaborations with Russian scholars and institutions must continue despite the ensuing geopolitical crisis since 2022.

Oxidised IL-33 drives COPD epithelial pathogenesis ST2-independent RAGE/EGFR signalling complex.

Background: Epithelial damage, repair and remodelling are critical features of chronic airway diseases including chronic obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged airway epithelia causes inflammation its receptor, serum stimulation-2 (ST2). Oxidation of IL-33 to a non-ST2-binding form (IL-33) is thought to limit its activity.

Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction.

Interleukin (IL)-33 is a broad-acting alarmin cytokine that can drive inflammatory responses following tissue damage or infection and is a promising target for treatment of inflammatory disease. Here, we describe the identification of tozorakimab (MEDI3506), a potent, human anti-IL-33 monoclonal antibody, which can inhibit reduced IL-33 (IL-33) and oxidized IL-33 (IL-33) activities through distinct serum-stimulated 2 (ST2) and receptor for advanced glycation end products/epidermal growth factor receptor (RAGE/EGFR complex) signalling pathways. We hypothesized that a therapeutic antibody would require an affinity higher than that of ST2 for IL-33, with an association rate greater than 10 M s, to effectively neutralize IL-33 following rapid release from damaged tissue.

Health workforce governance and professions: a re-analysis of New Zealand's primary care workforce policy actors.

Background: This article contributes to the health workforce planning literature by exploring the dynamics of health professions in New Zealand's Primary Care sector and deriving broad lessons for an international audience. Professions tend influence health policy and governance decisions and practices to retain their place, status and influence. Therefore, understanding their power dynamics and the positions that they have on workforce policies and issues assists workforce governance or health system reform plans.

The implications of COVID-19 for health workforce planning and policy: the case of Peru.

Like many countries Peru is confronting uncertainties due to the COVID-19 pandemic and its consequences. This is having impacts not only on health systems but also on the planning and preparation of its workforces. In this case article we summarise the progress Peru has been making to improve its workforce capacity and planning and review how Peru has coped with the stresses put on its health system arising from the pandemic.

In vitro evolution of antibody affinity via insertional scanning mutagenesis of an entire antibody variable region.

We report a systematic combinatorial exploration of affinity enhancement of antibodies by insertions and deletions (InDels). Transposon-based introduction of InDels via the method TRIAD (transposition-based random insertion and deletion mutagenesis) was used to generate large libraries with random in-frame InDels across the entire single-chain variable fragment gene that were further recombined and screened by ribosome display. Knowledge of potential insertion points from TRIAD libraries formed the basis of exploration of length and sequence diversity of novel insertions by insertional-scanning mutagenesis (InScaM).

Rethinking workforce planning for integrated care: using scenario analysis to facilitate policy development.

Background: A goal of health workforce planning is to have the most appropriate workforce available to meet prevailing needs. However, this is a difficult task when considering integrated care, as future workforces may require different numbers, roles and skill mixes than those at present. With this uncertainty and large variations in what constitutes integrated care, current health workforce policy and planning processes are poorly placed to respond.

Is subarctic forest advance able to keep pace with climate change?

Recent climate warming and scenarios for further warming have led to expectations of rapid movement of ecological boundaries. Here we focus on the circumarctic forest-tundra ecotone (FTE), which represents an important bioclimatic zone with feedbacks from forest advance and corresponding tundra disappearance (up to 50% loss predicted this century) driving widespread ecological and climatic changes. We address FTE advance and climate history relations over the 20th century, using FTE response data from 151 sites across the circumarctic area and site-specific climate data.

Preclinical development of a high affinity α-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular α-synuclein and attenuate α-synuclein spreading in vivo.

There are no approved drug therapies that can prevent or slow the progression of Parkinson's disease (PD). Accumulation and aggregation of α-synuclein protein is observed throughout the nervous system in PD. α-Synuclein is a core component of Lewy bodies and neurites that neuropathologically define PD, suggesting that α-synuclein may be a key causative agent in PD.

The evolution of New Zealand's health workforce policy and planning system: a study of workforce governance and health reform.

Introduction: While considerable attention has been given to improving health workforce planning practice, few articles focus on the relationship between health workforce governance and health reform. By outlining a sequence of health reforms, we reveal how New Zealand's health workforce governance and practices came under pressure, leading to a rethink and the introduction of innovative approaches and initiatives.

Case Description: New Zealand's health system was quite stable up to the late 1980s, after which 30 years of structural and system reform was undertaken.

Anti-PrP antibody rescues cognition and synapses in transgenic alzheimer mice.

Objective: Amyloid-beta oligomers (Aßo) trigger the development of Alzheimer's disease (AD) pathophysiology. Cellular prion protein (PrPC) initiates synaptic damage as a high affinity receptor for Aßo. Here, we evaluated the preclinical therapeutic efficacy of a fully human monoclonal antibody against PrPC.

Humanised effector-null FcγRIIA antibody inhibits immune complex-mediated proinflammatory responses.

Objective: Immune complexes (ICs) play a critical role in the pathology of autoimmune diseases. The aim of this study was to generate and characterise a first-in-class anti-FcγRIIA antibody (Ab) VIB9600 (previously known as MEDI9600) that blocks IgG immune complex-mediated cellular activation for clinical development.

Methods: VIB9600 was humanised and optimised from the IV.

New perspectives on IL-33 and IL-1 family cytokines as innate environmental sensors.

Interleukin (IL)-1 family cytokines are important initiators of innate immunity and host defence; however, their uncontrolled activities can cause tissue-damaging inflammation. Consequently, IL-1 family cytokines have sophisticated regulatory mechanisms to control their activities including proteolytic processing for their activation and the deployment of soluble receptors and receptor antagonists to limit their activities. IL-33 is a promoter of type 2 immunity and allergic inflammation through its alarmin activity that can rapidly initiate local immune responses by stimulating innate immune cells following exposure to environmental insults, pathogens, or sterile injury.

Assessing and managing communication needs in people with serious mental illness.

Effective communication is essential to maintain mental health and resilience. Communication can be challenging for people who experience serious mental illness (SMI), which can be a barrier to social, employment and educational opportunities, as well as increasing their risk of experiencing abuse. Therefore, it is important that nurses who work with individuals experiencing SMI understand the assessment and management of specific communication, speech and language needs.

New Zealand's health workforce planning should embrace complexity and uncertainty.

Concerns over New Zealand's health workforce sufficiency, distribution and sustainability continue. Proposed solutions tend to focus on supplying medical professionals to meet predicted numbers or to resolve distributional problems. This is despite quantitative forecasts being known to have poor reliability.

The promise of complementarity: Using the methods of foresight for health workforce planning.

Health workforce planning aims to meet a health system's needs with a sustainable and fit-for-purpose workforce, although its efficacy is reduced in conditions of uncertainty. This PhD breakthrough article offers foresight as a means of addressing this uncertainty and models its complementarity in the context of the health workforce planning problem. The article summarises the findings of a two-case multi-phase mixed method study that incorporates actor analysis, scenario development and policy Delphi.