Clinical Manifestations.

Background: Cortical atrophy in Alzheimer's disease (AD) is typically thought to commence in the medial temporal lobe. However, growing evidence suggests that this may not be true for all patients. Here, we explored atrophy patterns in patients with mild cognitive impairment (MCI) and AD and whether atrophy patterns are associated with specific clinical and neuropathological outcomes.

Clinical Manifestations.

Background: Cognitive assessments are essential for detecting and monitoring cognitive changes in neurological populations. Compared to standard pen-and-paper tests, online cognitive tasks offer a more accessible, scalable, repeatable and cost-effective approach to assessment. Cognitron is an online cognitive assessment platform with previously demonstrated validity and reliability (1).

Evaluation of Phoenix Sepsis Score Criteria: Exploratory Analysis of Characteristics and Outcomes in an Emergency Transport PICU Cohort From the United Kingdom, 2014-2016.

Objectives: To assess characteristics and outcomes of children with suspected or confirmed infection requiring emergency transport and PICU admission and to explore the association between the 2024 Phoenix Sepsis Score (PSS) criteria and mortality.

Design: Retrospective analysis of curated data from a 2014-2016 multicenter cohort study.

Setting: PICU admission following emergency transport in South East England, United Kingdom, from April 2014 to December 2016.

SCXRD, CSP-NMRX and microED in the quest for three elusive polymorphs of meloxicam.

Crystal structure determination is a crucial aspect of almost every branch of the chemical sciences, bringing us closer to understanding crystallization, polymorphism, phase transitions, and the relationship between a structure and its physicochemical and functional properties. Unfortunately, many molecules notoriously crystallize as microcrystalline powders, providing a significant challenge in establishing their structures. In this work, we describe the crystal structure determination of three elusive polymorphs of the anti-inflammatory drug meloxicam (MLX) using three approaches, of which only one was successful for each crystal phase.

The Role of WNT5a and TGF-β1 in Airway Remodelling and Severe Asthma.

Background: Airway remodelling is a feature of severe asthma with airway epithelial damage observed frequently. We evaluated the role of WNT5a and TGF-β in asthmatic airway biopsies and in sputum and bronchial brushings assessed their role in remodelling.

Methods: WNT5a and TGF-β protein expression were assessed in the lamina propria epithelium of people with asthma (GINA 1-3, n-8 and GINA 4-5, n-14) and healthy subjects (n-9), alongside relevant remodelling markers.

Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice.

Maternal immunisation against respiratory viruses provides protection in early life, but as antibodies wane, there can be a gap in coverage. This immunity gap might be filled by inducing pathogen-specific lung tissue-resident T cells (TRM). However, the neonatal mouse lung has a different inflammatory environment to the adult lung which affects T cell recruitment.

Precision Medicine for Pulmonary Vascular Disease: The Future Is Now (2023 Grover Conference Series).

Pulmonary vascular disease is not a single condition; rather it can accompany a variety of pathologies that impact the pulmonary vasculature. Applying precision medicine strategies to better phenotype, diagnose, monitor, and treat pulmonary vascular disease is increasingly possible with the growing accessibility of powerful clinical and research tools. Nevertheless, challenges exist in implementing these tools to optimal effect.

Real-World Results in Treating Diabetic Macular Edema With Faricimab at a London-Based Tertiary Eye Hospital.

Diabetic macular edema (DMO) poses a significant risk to vision, primarily caused by the leakage of retinal vessels. Traditional treatments involve anti-vascular endothelial growth factor (VEGF) agents and corticosteroids, though responses vary, necessitating frequent treatments. This retrospective study at a London-based tertiary eye hospital evaluates the efficacy of faricimab, a bispecific antibody inhibiting angiopoietin 2 (Ang-2) and VEGF-A, in treating DMO.

Outcomes of Knee Dislocations and Subluxations in Polytrauma Patients at a Major Trauma Center.

Background This is a retrospective service evaluation of outcomes of polytrauma patients sustaining knee dislocations and subluxations within a major trauma center (MTC). Polytrauma patients with knee dislocations are complex to manage and often sustain multiple life-threatening injuries. Although treatments have progressed, no consensus remains on management timing and strategy.

Practices supporting cue-based breastfeeding of preterm infants in neonatal intensive care units across Europe.

Background: Emerging knowledge about supportive neurodevelopmental neonatal care shows the need for an individual approach to establish breastfeeding. However, evidence on how cue-based breastfeeding is supported in neonatal intensive care units (NICUs) is scarce. Therefore, the aim was to describe supporting practices for cue-based breastfeeding.

China's municipal wastewater policies enhanced seafood safety and offset health risks from atmospheric mercury emissions in the past four decades.

The neurotoxin methylmercury in seafood threatens food safety worldwide. China has implemented stringent wastewater policies, established numerous treatment facilities and enforced rigorous water quality standards to address pollution in its waterways. However, the impact of these policies on seafood safety and methylmercury exposure remains unknown.

Mechanistic modelling of allergen-induced airways disease in early life.

Asthma affects approximately 300 million individuals worldwide and the onset predominantly arises in childhood. Children are exposed to multiple environmental irritants, such as viruses and allergens, that are common triggers for asthma onset, whilst their immune systems are developing in early life. Understanding the impact of allergen exposures on the developing immune system and resulting alterations in lung function in early life will help prevent the onset and progression of allergic asthma in children.

European consensus on endoscopic surgery for bilateral vocal fold immobility: classification and nomenclature.

Introduction: There are inconsistencies in how different endoscopic procedures to manage Bilateral Vocal Fold Immobility (BVFI) have been described in the literature. This limits our ability to compare functional outcomes. There is no unifying international terminology available that precisely describes the anatomical boundaries and extent of the different types of treatment.

MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis.

The eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP hydrolysis is essential for consecutive steps in pre-replicative complex (pre-RC) assembly. Currently it is unknown how MCM2-7 ring closure and ATP-hydrolysis are controlled.

Design principles for engineering bacteria to maximise chemical production from batch cultures.

Bacteria can be engineered to manufacture chemicals, but it is unclear how to optimally engineer a single cell to maximise production performance from batch cultures. Moreover, the performance of engineered production pathways is affected by competition for the host's native resources. Here, using a 'host-aware' computational framework which captures competition for both metabolic and gene expression resources, we uncover design principles for engineering the expression of host and production enzymes at the cell level which maximise volumetric productivity and yield from batch cultures.

Universal, untargeted detection of bacteria in tissues using metabolomics workflows.

Fast and reliable identification of bacteria directly in clinical samples is a critical factor in clinical microbiological diagnostics. Current approaches require time-consuming bacterial isolation and enrichment procedures, delaying stratified treatment. Here, we describe a biomarker-based strategy that utilises bacterial small molecular metabolites and lipids for direct detection of bacteria in complex samples using mass spectrometry (MS).

A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae.

Genetic control - the deliberate introduction of genetic traits to control a pest or vector population - offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings, but hesitancy due to their invasive and persistent nature may delay their implementation. Here, instead, we describe a self-limiting strategy, designed to have geographically and temporally restricted effect, based on a Y chromosome-linked genome editor (YLE).

Comparative 3D ultrastructure of Plasmodium falciparum gametocytes.

Despite the enormous significance of malaria parasites for global health, some basic features of their ultrastructure remain obscure. Here, we apply high-resolution volumetric electron microscopy to examine and compare the ultrastructure of the transmissible male and female sexual blood stages of Plasmodium falciparum as well as the more intensively studied asexual blood stages revisiting previously described phenomena in 3D. In doing so, we challenge the widely accepted notion of a single mitochondrion by demonstrating the presence of multiple mitochondria in gametocytes.

Structural and electronic features enabling delocalized charge-carriers in CuSbSe.

Inorganic semiconductors based on heavy pnictogen cations (Sb and Bi) have gained significant attention as potential nontoxic and stable alternatives to lead-halide perovskites for solar cell applications. A limitation of these novel materials, which is being increasingly commonly found, is carrier localization, which substantially reduces mobilities and diffusion lengths. Herein, CuSbSe is investigated and discovered to have delocalized free carriers, as shown through optical pump terahertz probe spectroscopy and temperature-dependent mobility measurements.

On the longevity and inherent hermeticity of silicon-ICs: evaluation of bare-die and PDMS-coated ICs after accelerated aging and implantation studies.

Silicon integrated circuits (ICs) are central to the next-generation miniature active neural implants, whether packaged in soft polymers for flexible bioelectronics or implanted as bare die for neural probes. These emerging applications bring the IC closer to the corrosive body environment, raising reliability concerns, particularly for chronic use. Here, we evaluate the inherent hermeticity of bare die ICs, and examine the potential of polydimethylsiloxane (PDMS), a moisture-permeable elastomer, as a standalone encapsulation material.

Degradation bottlenecks and resource competition in transiently and stably engineered mammalian cells.

Degradation tags, otherwise known as degrons, are portable sequences that can be used to alter protein stability. Here, we report that degron-tagged proteins compete for cellular degradation resources in engineered mammalian cells leading to coupling of the degradation rates of otherwise independently expressed proteins when constitutively targeted human degrons are adopted. We show the effect of this competition to be dependent on the context of the degrons.

Dynamics of specialization in neural modules under resource constraints.

The brain is structurally and functionally modular, although recent evidence has raised questions about the extent of both types of modularity. Using a simple, toy artificial neural network setup that allows for precise control, we find that structural modularity does not in general guarantee functional specialization (across multiple measures of specialization). Further, in this setup (1) specialization only emerges when features of the environment are meaningfully separable, (2) specialization preferentially emerges when the network is strongly resource-constrained, and (3) these findings are qualitatively similar across several different variations of network architectures.