Population-based, first-tier genomic newborn screening in the maternity ward.

The rapid development of therapies for severe and rare genetic conditions underlines the need to incorporate first-tier genetic testing into newborn screening (NBS) programs. A workflow was developed to screen newborns for 165 treatable pediatric disorders by deep sequencing of regions of interest in 405 genes. The prospective observational BabyDetect pilot project was launched in September 2022 in a maternity ward of a public hospital in the Liege area, Belgium.

An online multidomain lifestyle intervention to prevent cognitive decline in at-risk older adults: a randomized controlled trial.

Effective, scalable dementia prevention interventions are needed to address modifiable risk factors given global burden of dementia and challenges in developing disease-modifying treatments. A single-blind randomized controlled trial assessed an online multidomain lifestyle intervention to prevent cognitive decline over 3 years. Participants were dementia-free community-dwelling Australians aged 55-77 years with modifiable dementia risk factors.

Aging and word predictability during reading: Evidence from eye movements and fixation-related potentials.

The use of context to facilitate the processing of words is recognized as a hallmark of skilled reading. This capability is also hypothesized to change with older age because of cognitive changes across the lifespan. However, research investigating this issue using eye movements or event-related potentials (ERPs) has produced conflicting findings.

Warning people that they are being microtargeted fails to eliminate persuasive advantage.

The practice of microtargeting in politics, involving tailoring persuasive messages to individuals based on personal vulnerabilities, has raised manipulation concerns. As microtargeting's persuasive benefits are well-established and its use facilitated by AI tools and personality-inference models, ethical and regulatory concerns are magnified. Here, we explore countering microtargeting effects by creating a warning signal deployed when users encounter personality-tailored political ads.

Hearing loss and risk of major osteoporotic fracture: a population-based cohort study in the United Kingdom.

Unlabelled: Using the UK Clinical Practice Research Datalink, our cohort study matched 237,297 individuals with hearing loss (HL) to 829,431 without HL. The study found an 8-10% higher risk of major osteoporotic fracture in individuals with HL compared to those without. Additionally, within the HL cohort, we identified risk factors for potential inclusion in fracture risk models.

Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Tumour hypoxia in driving genomic instability and tumour evolution.

Intratumour hypoxia is a feature of all heterogenous solid tumours. Increased levels or subregions of tumour hypoxia are associated with an adverse clinical prognosis, particularly when this co-occurs with genomic instability. Experimental evidence points to the acquisition of DNA and chromosomal alterations in proliferating hypoxic cells secondary to inhibition of DNA repair pathways such as homologous recombination, base excision repair and mismatch repair.

Who drives weight stigma? A multinational exploration of clustering characteristics behind weight bias against preconception, pregnant, and postpartum women.

Background: Weight bias is a global health challenge and community members are endorsed as the most common source of weight bias. The nature of weight biases specifically against preconception, pregnant, and postpartum (PPP) women from the perspective of community members is not known, especially in terms of cross-cultural trends. We investigated the magnitude of explicit and implicit weight bias and profiles of characteristics associated with harbouring weight bias.

fMRI data acquisition and analysis for task-free, anesthetized rats.

Templates for the acquisition of large datasets such as the Human Connectome Project guide the neuroimaging community to reproducible data acquisition and scientific rigor. By contrast, small animal neuroimaging often relies on laboratory-specific protocols, which limit cross-study comparisons. The establishment of broadly validated protocols may facilitate the acquisition of large datasets, which are essential for uncovering potentially small effects often seen in functional MRI (fMRI) studies.

The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow.

The default mode network (DMN) is implicated in many aspects of complex thought and behavior. Here, we leverage postmortem histology and in vivo neuroimaging to characterize the anatomy of the DMN to better understand its role in information processing and cortical communication. Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialized for unimodal, heteromodal and memory-related processing.

Ginsenoside Rd protects against acute liver injury by regulating the autophagy NLRP3 inflammasome pathway.

Ginsenoside Rd (Rd) is a bioactive compound predominantly found in Panax ginseng C.A. Meyer and Panax notoginseng (Burkill) F.

Enhancing immunity during ageing by targeting interactions within the tissue environment.

Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as 'inflammageing'.

Epidemiology, diagnosis and treatment of anterior prostate cancer.

Anterior prostate cancers (APCs) are a group of impalpable neoplasms located in regions anterior to the urethra, which comprise the transition zone, apical peripheral zone and anterior fibromuscular stroma. These regions are typically undersampled using conventional biopsy schemes, leading to a low detection rate for APC and a high rate of false negatives. Radical prostatectomy series suggest prevalence rates of at least 10-30%, but transperineal systematic biopsy is ideal for diagnosis, particularly where multiparametric MRI is unavailable.

Semi-mechanistic efficacy model for PARP + ATR inhibitors-application to rucaparib and talazoparib in combination with gartisertib in breast cancer PDXs.

Background: Promising cancer treatments, such as DDR inhibitors, are often challenged by the heterogeneity of responses in clinical trials. The present work aimed to build a computational framework to address those challenges.

Methods: A semi-mechanistic pharmacokinetic-pharmacodynamic model of tumour growth inhibition was developed to investigate the efficacy of PARP and ATR inhibitors as monotherapies, and in combination.

Investigating time-independent and time-dependent diffusion phenomena using steady-state diffusion MRI.

Diffusion MRI is a leading method to non-invasively characterise brain tissue microstructure across multiple domains and scales. Diffusion-weighted steady-state free precession (DW-SSFP) is an established imaging sequence for post-mortem MRI, addressing the challenging imaging environment of fixed tissue with short T and low diffusivities. However, a current limitation of DW-SSFP is signal interpretation: it is not clear what diffusion 'regime' the sequence probes and therefore its potential to characterise tissue microstructure.

A morphometric signature to identify ductal carcinoma in situ with a low risk of progression.

Ductal carcinoma in situ (DCIS) may progress to ipsilateral invasive breast cancer (iIBC), but often never will. Because DCIS is treated as early breast cancer, many women with harmless DCIS face overtreatment. To identify features associated with progression, we developed an artificial intelligence-based DCIS morphometric analysis pipeline (AIDmap) on hematoxylin-eosin-stained (H&E) tissue sections.

Hypertensive load predicts recovery of renal function for patients undergoing revascularisation for renal artery stenosis.

Renal ischaemia due to renal artery stenosis produces two differing responses - a juxtaglomerular hypertensive response and cortical renal dysfunction. The reversibility of renal impairment is not predictable, and thus renal revascularisation is controversial. This study aims to test the hypothesis that the hypertensive response to renal ischaemia reflects viable renal parenchyma, and thus could be used to predict the recovery in renal function.

The association between age at menarche (AAM) and cardiovascular disease (CVD) risk factors in the MASHAD cohort study.

Age at menarche may be associated with cardiovascular disease risk factors in different ethnic groups. The purpose of this study was to identify the association of cardiovascular disease (CVD) risk factors with age at menarche (AAM) in Mashhad, the second biggest city in Iran. This was a cross- sectional study based on cohort data of 2353 women (35-65 years) from Mashhad, Iran for whom the age at menarche was reported.

Nucleophilicity at copper(-I) in a compound with a Cu-Mg bond.

Copper is ubiquitous as a structural material, and as a reagent in (bio)chemical transformations. A vast number of chemical reactions rely on the near-inevitable preference of copper for positive oxidation states to make useful compounds. Here we show this electronic paradigm can be subverted in a stable compound with a copper-magnesium bond, which conforms to the formal oxidation state of Cu(-I).