Zonal Characteristics of Collagen Ultrastructure and Responses to Mechanical Loading in Articular Cartilage.

The biomechanical properties of articular cartilage arise from a complex bioenvironment comprising hierarchically organised collagen networks within the extracellular matrix (ECM) that interact with the proteoglycan-rich interstitial fluid. This network features a depth-dependent fibril organisation across different zones. Understanding how collagen fibrils respond to external loading is key to elucidating the mechanisms behind lesion and managing degenerative conditions like osteoarthritis.

Estimating direct tissue effects versus weight loss effects of incretin-based drugs for obesity on various chronic conditions.

The extent to which newer, incretin-based drugs for obesity improve disease outcomes via weight loss versus the direct effects of these drugs is the subject of intense interest. Although reductions in major adverse cardiovascular events appear to be predominantly driven by the direct tissue effects of such drugs, the associated weight loss effects must be relevant to the benefits observed in other major outcomes, albeit to differing extents. In this Personal View, we draw on evidence to support that weight loss is at least partly responsible (albeit to differing extents) for the reported benefits of incretin-based drugs for obesity in people living with heart failure with preserved ejection fraction, hypertension, chronic kidney disease, and type 2 diabetes.

Bigger is not necessarily better - 2-ring circular frames associated with shorter duration of treatment in the management of complex tibial fractures - a retrospective cohort study.

Frame configuration for the management of complex tibial fractures is highly variable and is dependent upon both fracture pattern and surgeon preference. The optimal number of rings to use when designing a frame remains uncertain. Traditionally larger, multi-ring-per-segment constructs have been assumed to offer optimal stability and therefore favourable conditions for fracture healing but there is little in-vivo evidence for this and the recent concept of reverse dynamisation challenges this approach.

Quantification of micro- and nano-plastics in atmospheric fine particles by pyrolysis-gas chromatography-mass spectrometry with chromatographic peak reconstruction.

The effects of micro- and nano-plastics (MNPs) on human health are of global concern because MNPs are ubiquitous, persistent, and potentially toxic, particularly when bound to atmospheric fine particles (PM). Traditional quantitative analysis of MNPs by pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS) is often inaccurate because of false positive signals caused by similar polymers and organic compounds. In this study, a reliable analytical strategy combining HNO digestion and chromatographic peak reconstruction was developed to improve the precision of pyrolysis-gas chromatography-mass spectrometry analysis of multiple MNPs bound to PM.

Environmental impact of peat alternatives in growing media for European mushroom production.

Button mushrooms are an important protein source with a production of >48 million metric tonnes in 2021. Several life cycle assessments (LCAs) have been employed in assessing mushroom cultivation. This paper assessed potential impacts of relevant alternatives (sphagnum moss, grass fibres, spent casing and bark) to peat as casing materials for mushroom production across Europe by using LCA using a cradle to farm gate approach.

Salivary cortisol measures across the clinical stages of psychosis: An individual participant data (IPD) meta-analysis.

Background: Studies of salivary cortisol levels in psychosis have yielded inconsistent findings, which may be attributable to heterogeneity in cortisol measurement, illness stage, and approaches to dealing with sampling factors and potential confounders. To address these issues, we performed an individual participant data (IPD) meta-analysis comparing individuals at different stages of psychosis to controls using five different salivary cortisol measures and explored potential effect modifiers.

Methods: Salivary cortisol data from five London-based cohorts were used to derive the cortisol awakening response, total daytime cortisol output, basal cortisol, and diurnal slope measures (wake-to-evening and peak-to-evening).

Cross-Cultural Sense-Making of Global Health Crises: A Text Mining Study of Public Opinions on Social Media Related to the COVID-19 Pandemic in Developed and Developing Economies.

Background: The COVID-19 pandemic reshaped social dynamics, fostering reliance on social media for information, connection, and collective sense-making. Understanding how citizens navigate a global health crisis in varying cultural and economic contexts is crucial for effective crisis communication.

Objective: This study examines the evolution of citizen collective sense-making during the COVID-19 pandemic by analyzing social media discourse across Italy, the United Kingdom, and Egypt, representing diverse economic and cultural contexts.

Effects of daylong exposure to indoor overheating on enterocyte damage and inflammatory responses in older adults: A randomized crossover trial.

We evaluated enterocyte damage (IFABP), microbial translocation (sCD14), and inflammatory responses (TNF-α, IL-6, CRP) in 16 older adults (66-78 years) during 8 hours rest in conditions simulating homes maintained at 22°C (control), the 26°C indoor temperature upper limit proposed by health agencies, and homes without air-conditioning during heatwaves (31°C, 36°C). Relative to 22°C, IFABP was elevated ~181 pg/mL after exposure to 31°C (P=0.07), and by ~378 pg/mL (P<0.

Perceptions of Academic Malpractice are not Always Biased by Halo Effects.

The attractiveness halo effect has been discussed for over a century. Physically attractive people are often judged more favourably and accrue many life advantages. Halo effects have been observed in university settings for decades, but perhaps their influence is waning due to increased awareness of unconscious bias.

Automating the practice of science: Opportunities, challenges, and implications.

Automation transformed various aspects of our human civilization, revolutionizing industries and streamlining processes. In the domain of scientific inquiry, automated approaches emerged as powerful tools, holding promise for accelerating discovery, enhancing reproducibility, and overcoming the traditional impediments to scientific progress. This article evaluates the scope of automation within scientific practice and assesses recent approaches.

Is Ockham's razor losing its edge? New perspectives on the principle of model parsimony.

The preference for simple explanations, known as the parsimony principle, has long guided the development of scientific theories, hypotheses, and models. Yet recent years have seen a number of successes in employing highly complex models for scientific inquiry (e.g.

Do the Shuffle: Expanding the Synthetic Biology Toolkit for Shufflon-like Recombination Systems.

Naturally occurring DNA inversion systems play an important role in the generation of genetic variation and adaptation in prokaryotes. Shufflon invertase (SI) from plasmid R64, recognizing asymmetric sites, has been adopted as a tool for synthetic biology. However, the availability of a single enzyme with moderate rates of recombination has hampered the more widespread use of SIs.

Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

Intraspecific Variation and Recent Loss of Ancient, Conserved Effector Genes in the Sudden Oak Death Pathogen .

Members of the genus are responsible for many important diseases in agricultural and natural ecosystems. causes devastating diseases of oak, and tanoak stands in US forests and larch in the UK. The four evolutionary lineages involved express different virulence phenotypes on plant hosts, and characterization of gene content is foundational to understanding the basis for these differences.

Adverse childhood experiences and psychological, sexual, and physical forms of intimate partner violence in Nepal.

Objective: To examine the prevalence of adverse childhood experiences (ACEs) and intimate partner violence (IPV) among married couples in Nepal as well as the relationships among ACEs, IPV (psychological, sexual, physical), and psychological distress.

Method: The sample comprised the control group ( = 720) of a cluster randomized intervention trial among married women in Nepal. Interviewers assessed ACEs, IPV, quality of life, self-efficacy, and depressive symptoms among participants.

A single-cell atlas of the Culex tarsalis midgut during West Nile virus infection.

The mosquito midgut functions as a key interface between pathogen and vector. However, studies of midgut physiology and virus infection dynamics are scarce, and in Culex tarsalis-an extremely efficient vector of West Nile virus (WNV)-nonexistent. We performed single-cell RNA sequencing on Cx.

Predicting real-world navigation performance from a virtual navigation task in older adults.

Virtual reality environments presented on tablets and smartphones offer a novel way of measuring navigation skill and predicting real-world navigation problems. The extent to which such virtual tests are effective at predicting navigation in older populations remains unclear. We compared the performance of 20 older participants (54-74 years old) in wayfinding tasks in a real-world environment in London, UK, and in similar tasks designed in a mobile app-based test of navigation (Sea Hero Quest).

Wild-type bone marrow cells repopulate tissue resident macrophages and reverse the impacts of homozygous CSF1R mutation.

Adaptation to existence outside the womb is a key event in the life of a mammal. The absence of macrophages in rats with a homozygous mutation in the colony-stimulating factor 1 receptor (Csf1r) gene (Csf1rko) severely compromises pre-weaning somatic growth and maturation of organ function. Transfer of wild-type bone marrow cells (BMT) at weaning rescues tissue macrophage populations permitting normal development and long-term survival.

The transcriptional and translational landscape of HCoV-OC43 infection.

The coronavirus HCoV-OC43 circulates continuously in the human population and is a frequent cause of the common cold. Here, we generated a high-resolution atlas of the transcriptional and translational landscape of OC43 during a time course following infection of human lung fibroblasts. Using ribosome profiling, we quantified the relative expression of the canonical open reading frames (ORFs) and identified previously unannotated ORFs.

Site-selective photo-crosslinking for the characterisation of transient ubiquitin-like protein-protein interactions.

Non-covalent protein-protein interactions are one of the most fundamental building blocks in cellular signalling pathways. Despite this, they have been historically hard to identify using conventional methods due to their often weak and transient nature. Using genetic code expansion and incorporation of commercially available unnatural amino acids, we have developed a highly accessible method whereby interactions between biotinylated ubiquitin-like protein (UBL) probes and their binding partners can be stabilised using ultraviolet (UV) light-induced crosslinks.

Using machine learning to forecast peak health care service demand in real-time during the 2022-23 winter season: A pilot in England, UK.

During winter months, there is increased pressure on health care systems in temperature climates due to seasonal increases in respiratory illnesses. Providing real-time short-term forecasts of the demand for health care services helps managers plan their services. During the Winter of 2022-23 we piloted a new forecasting pipeline, using existing surveillance indicators which are sensitive to increases in respiratory syncytial virus (RSV).

Polymicrogyria in infants with symptomatic congenital cytomegalovirus at birth is associated with epilepsy: A retrospective, descriptive cohort study.

Aim: To identify neonatal magnetic resonance imaging (MRI) features that predict the likelihood of children with congenital cytomegalovirus (cCMV) developing epilepsy, together with clinical features and a validated MRI scoring system.

Method: This was a retrospective descriptive cohort study of infants with cCMV referred to a paediatric infectious disease centre between April 2012 and March 2022, and followed up for at least 2 years. MRI was performed before 4 months of age and assessed by two paediatric neuroradiologists.

Comparison of stop-jump muscle synergies in amateur basketball players with and without asymptomatic patellar tendon abnormalities during simulated games.

: Asymptomatic patellar tendon abnormality (APTA) is considered a precursor to patellar tendinopathy (PT), but its pathogenesis remains unclear, especially regarding changes in muscle coordination. Therefore, it is essential to explore the muscle synergy patterns in individuals with APTA. This study recorded sEMG data during stop-jump tasks in 8 APTA and 8 healthy amateur male basketball players in a simulated basketball game.