Replacing serum with dried blood microsampling for pharmacokinetics, viral neutralisation and immunogenicity bioanalysis supporting future paediatric development of RSM01, a candidate respiratory syncytial virus neutralising monoclonal antibody.

Background: Virus neutralising antibodies in serum are considered key correlates of protection for vaccines and monoclonal antibodies against respiratory syncytial virus (RSV). RSM01 is a novel, highly-potent, half-life-extended and fully-human monoclonal antibody candidate targeting the RSV prefusion F protein. Currently in Phase 1 development, RSM01 is primarily being developed to potentially provide an effective and affordable RSV prevention strategy in low- and middle-income countries.

Two decades of body length measurements of larval and juvenile fish populations in English rivers.

Long-term datasets provide context and understanding of complex ecological processes, including temporal variations in species diversity and ecosystem dynamics. This dataset is comprised of body length measurements (mm) of more than 380,000 larval or juvenile fish of 30 species from five English river catchments collected almost monthly over two decades. Such information can be used to determine growth rates, future recruitment success, population structure and compliance with monitoring protocols and conservation objectives.

Perinatal iron deficiency alters the cardiac proteome and mitochondrial function in neonatal offspring.

Iron deficiency (ID) is common during gestation and early infancy and can alter developmental trajectories with lasting consequences on cardiovascular health. Iron plays a critical role in systemic oxygen transport (via hemoglobin) and aerobic respiration (as a component of mitochondrial complexes). Perinatal ID has been shown to cause cardiac dysfunction in neonates, but the mechanisms underlying these changes have not been characterized.

Maternal ketone supplementation throughout gestation improves neonatal cardiac dysfunction caused by perinatal iron deficiency.

Iron deficiency (ID) is common during gestation and in early infancy and has been shown to adversely affect cardiac development and function, which could lead to lasting cardiovascular consequences. Ketone supplementation has been shown to confer cardioprotective effects in numerous disease models. Here, we tested the hypothesis that maternal ketone supplementation during gestation would mitigate cardiac dysfunction in ID neonates.

Estimating rates of change to interpret quantitative wastewater surveillance of disease trends.

Background: Wastewater monitoring data can be used to estimate disease trends to inform public health responses. One commonly estimated metric is the rate of change in pathogen quantity, which typically correlates with clinical surveillance in retrospective analyses. However, the accuracy of rate of change estimation approaches has not previously been evaluated.

"It Helps Make the Fuzzy Go Away": Autistic Adults' Perspectives on Nature's Relationship with Well-being Through the Life Course.

Background: While previous work highlights the links between nature and various positive well-being-related outcomes, the experiences of autistic people in nature have received limited empirical research. Our study aimed at gathering autistic adults' perspectives on the relationship between nature and well-being in both childhood and adulthood.

Methods: We used an online survey to capture the views of 127 autistic adults across the United Kingdom.

Spatial ecology and population dynamics of brown trout Salmo trutta L. in reservoirs and headwater tributaries.

This investigation compared the spatial ecology and population dynamics of brown trout Salmo trutta L. between reservoirs with (impact; Langsett Reservoir) and without (control; Grimwith Reservoir) barriers to fish movements into headwater tributaries, and the effectiveness of a fish pass intended to remediate connectivity. Passive integrated transponder (PIT) telemetry revealed that fish that emigrated from Langsett and Grimwith tributaries were 1-3 and 0-2 years old, respectively, and predominantly did so in spring and autumn-early winter in both systems.

The chromatin regulator Ankrd11 controls cardiac neural crest cell-mediated outflow tract remodeling and heart function.

ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ abnormalities, including cardiac defects. However, the role of ANKRD11 in heart development is unknown. The neural crest plays a leading role in embryonic heart development, and its dysfunction is implicated in congenital heart defects.

A seven-step guide to spatial, agent-based modelling of tumour evolution.

Spatial agent-based models are frequently used to investigate the evolution of solid tumours subject to localized cell-cell interactions and microenvironmental heterogeneity. As spatial genomic, transcriptomic and proteomic technologies gain traction, spatial computational models are predicted to become ever more necessary for making sense of complex clinical and experimental data sets, for predicting clinical outcomes, and for optimizing treatment strategies. Here we present a non-technical step by step guide to developing such a model from first principles.

Using a combination of quantitative culture, molecular, and infrastructure data to rank potential sources of fecal contamination in Town Creek Estuary, North Carolina.

Estuarine water quality is declining worldwide due to increased tourism, coastal development, and a changing climate. Although well-established methods are in place to monitor water quality, municipalities struggle to use the data to prioritize infrastructure for monitoring and repair and to determine sources of contamination when they occur. The objective of this study was to assess water quality and prioritize sources of contamination within Town Creek Estuary (TCE), Beaufort, North Carolina, by combining culture, molecular, and geographic information systems (GIS) data into a novel contamination source ranking system.

Physicochemical characterisation of casings in relation to mushroom (Agaricus bisporus) cropping performance.

Peat-based casings have been used for button mushroom (Agaricus bisporus) cultivation for decades but there is environmental pressure to find sustainable alternatives. This work aimed to characterise the physicochemical properties of peat and peat-substituted casings and to determine their influence on mushroom cropping to enable alternatives to be identified. British milled peat and German wet-dug peat casings produced smaller mushrooms than Irish wet-dug peat casing although yield was unaffected.

Exploring young people's attitudes to HIV prevention medication (PrEP) in England: a qualitative study.

Introduction: Young people aged 18-24 years old are a key demographic target for eliminating HIV transmission globally. Pre-exposure prophylaxis (PrEP), a prevention medication, reduces HIV transmission. Despite good uptake by gay and bisexual men who have sex with men, hesitancy to use PrEP has been observed in other groups, such as young people and people from ethnic minority backgrounds.

Nitrogen balance and supply in Australasian mushroom composts.

Mushrooms are an important source of protein in the human diet. They are increasingly viewed as a sustainable meat replacement in an era of growing populations, with button mushrooms (Agaricus bisporus) the most popular and economically important mushroom in Europe, Australia and North America. Button mushrooms are cultivated on a defined, straw-derived compost, and the nitrogen (N) required to grow these high-protein foods is provided mainly by the addition of poultry manure and horse manure.

A new universal system of tree shape indices.

The comparison and categorization of tree diagrams is fundamental to large parts of biology, linguistics, computer science, and other fields, yet the indices currently applied to describing tree shape have important flaws that complicate their interpretation and limit their scope. Here we introduce a new system of indices with no such shortcomings. Our indices account for node sizes and branch lengths and are robust to small changes in either attribute.

Selective sweep probabilities in spatially expanding populations.

Evolution during range expansions shapes biological systems from microbial communities and tumours up to invasive species. A fundamental question is whether, when a beneficial mutation arises during a range expansion, it will evade clonal interference and sweep through the population to fixation. However, most theoretical investigations of range expansions have been confined to regimes in which selective sweeps are effectively impossible, while studies of selective sweeps have either assumed constant population size or have ignored spatial structure.

Multiparametric Renal Magnetic Resonance Imaging for Prediction and Annual Monitoring of the Progression of Chronic Kidney Disease over Two Years.

Background: Multiparametric renal Magnetic Resonance Imaging (MRI) provides a non-invasive method to assess kidney structure and function, but longitudinal studies are limited.

Methods: A total of 22 patients with CKD category G3-4 (estimated glomerular filtration rate (eGFR) 15-59 mL/min/1.73 m) were recruited.

Preventing evolutionary rescue in cancer.

First-line cancer treatment frequently fails due to initially rare therapeutic resistance. An important clinical question is then how to schedule subsequent treatments to maximize the probability of tumour eradication. Here, we provide a theoretical solution to this problem by using mathematical analysis and extensive stochastic simulations within the framework of evolutionary rescue theory to determine how best to exploit the vulnerability of small tumours to stochastic extinction.

Use of Photoacoustic Imaging to Study the Effects of Anemia on Placental Oxygen Saturation in Normoxic and Hypoxic Conditions.

We aimed to evaluate fetal and placental oxygen saturation (sO2) in anemic and non-anemic pregnant rats throughout gestation using photoacoustic imaging (PAI). Female Sprague-Dawley rats were fed an iron-restricted or iron-replete diet before and during pregnancy. On gestational days 13, 18, and 21, PAI was coupled with high resolution ultrasound to measure oxygenation of the fetus, whole placenta, mesometrial triangle, as well as the maternal and fetal faces of the placenta.

Targeting Cytotoxic Agents through EGFR-Mediated Covalent Binding and Release.

A major drawback of cytotoxic chemotherapy is the lack of selectivity toward noncancerous cells. The targeted delivery of cytotoxic drugs to tumor cells is a longstanding goal in cancer research. We proposed that covalent inhibitors could be adapted to deliver cytotoxic agents, conjugated to the β-position of the Michael acceptor, via an addition-elimination mechanism promoted by covalent binding.

Electronic alerts in acute kidney injury: why does evidence of benefit remain elusive?

Purpose Of Review: Acute kidney injury (AKI) is a common syndrome characterized by a sudden reduction in kidney function. It is strongly associated with high mortality and longer, more expensive hospital stays. As AKI often presents silently, a lack of recognition can prevent recommended standards of care.

Separating signal from noise in wastewater data: An algorithm to identify community-level COVID-19 surges in real time.

Wastewater monitoring has provided health officials with early warnings for new COVID-19 outbreaks, but to date, no approach has been validated to distinguish signal (sustained surges) from noise (background variability) in wastewater data to alert officials to the need for heightened public health response. We analyzed 62 wk of data from 19 sites participating in the North Carolina Wastewater Monitoring Network to characterize wastewater metrics around the Delta and Omicron surges. We found that wastewater data identified outbreaks 4 to 5 d before case data (reported on the earlier of the symptom start date or test collection date), on average.