Mammography screening: Eliciting the voices of informed citizens.

Background: Many medical organisations recommend continuing with existing mammography screening programmes but some recommend stopping or de-intensifying them. In Denmark women aged 50-69 are offered biennial mammograms free-of-charge.

Objectives: The aim of this study was to determine whether or not an informed public would recommend continuation of the Danish mammography screening programme, and to determine whether this recommendation was in line with what participants considered to be acceptable levels of mortality reduction and overdiagnosis.

Ultrasensitive Characterization of Native Bacterial Biofilms via Dynamic Nuclear Polarization-Enhanced Solid-State NMR.

Bacterial biofilms are major contributors to persistent infections and antimicrobial resistance, posing significant challenges to treatment. However, obtaining high-resolution structural information on native bacterial biofilms has remained elusive due to the methodological limitations associated with analyzing complex biological samples. Solid-state NMR (ssNMR) has shown promise in this regard, but its conventional application is hindered by sensitivity constraints for unlabeled native samples .

Evaluation of allosteric NMDA receptor modulation by GluN2A-selective antagonists using pharmacological equilibrium modeling.

NMDA-type ionotropic glutamate receptors are critically involved in excitatory neurotransmission and their dysfunction is implicated in many brain disorders. Allosteric modulators with selectivity for specific NMDA receptor subtypes are therefore attractive as therapeutic agents, and sustained drug discovery efforts have resulted in a wide range of new allosteric modulators. However, evaluation of allosteric NMDA receptor modulators is limited by the lack of operational ligand-receptor models to describe modulator binding dissociation constants (K) and effects on agonist binding affinity (α) and efficacy (β).

The curious case of the Dana platypus and what it can teach us about how lead shotgun pellets behave in fluid preserved museum specimens and may limit their scientific value.

Fluid preserved animal specimens in the collections of natural history museums constitute an invaluable archive of past and present animal diversity. Well-preserved specimens have a shelf-life spanning centuries and are widely used for e.g.

High-Sensitivity Analysis of Native Bacterial Biofilms Using Dynamic Nuclear Polarization-Enhanced Solid-State NMR.

Bacterial biofilms cause persistent infections that are difficult to treat and contribute greatly to antimicrobial resistance. However, high-resolution structural information on native bacterial biofilms remain very limited. This limitation is primarily due to methodological constraints associated with analyzing complex native samples.

FATAL: A Forensic AuTopsy Annotation tooL for digital recording of autopsy findings.

The findings from forensic autopsies, where cause of death must be established and reported to legal authorities, are reported in paper-based formats. Practitioners are required to map 3D injury findings to 2D space. Here, we design and describe a digital Forensic AuTopsy Annotation tooL (FATAL), that can be used by practitioners to record systematically detailed autopsy findings onto an interactive 3D body model.

The I-OPTA Questionnaire: A National Assessment of Patients with Neovascular Age-Related Macular Degeneration.

Introduction: Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible vision loss in developed countries. However, a significant gap persists in understanding this population, exacerbated by their advanced age and visual impairments, which can hinder research participation and access to healthcare. The purpose of this study was to describe the content of the questionnaire and the participating patients with nAMD.

Lung densitometry in postmortem computed tomography - comparison across different fatal asphyxia groups.

Asphyxia as a cause of death poses a diagnostic challenge in forensic medicine due to both the diversity of underlying mechanisms, and lack of specific markers. Acute emphysema or acute alveolar dilation have long been debated as potential findings in these asphyxia cases. To further explore the supplementary findings in our forensic asphyxia cases, this study applied lung densitometry to pulmonary postmortem computed tomography (PMCT) data.

Structure of biofilm-forming functional amyloid PSMα1 from .

Biofilm-protected pathogenic causes chronic infections that are difficult to treat. An essential building block of these biofilms are functional amyloid fibrils that assemble from phenol-soluble modulins (PSMs). PSMα1 cross-seeds other PSMs into cross-β amyloid folds and is therefore a key element in initiating biofilm formation.

Multi-sample non-negative spatial factorization.

Analyzing multi-sample spatial transcriptomics data requires accounting for biological variation. We present multi-sample non-negative spatial factorization (mNSF), an alignment-free framework extending single-sample spatial factorization (NSF) to multi-sample datasets. mNSF incorporates sample-specific spatial correlation modeling and extracts low-dimensional data representations.

Towards the diagnosis of osteoporosis - contributions from coincidental diagnostic imaging findings in chiropractors' practice.

Background: Osteoporosis is significantly associated with fractures and burdens the health of especially older people. Osteoporotic fractures cause pain, disability, and increased mortality. Early diagnosis of osteoporosis allows earlier initiation of treatment, thereby reducing the risk of osteoporotic fractures.

Removing unwanted variation between samples in Hi-C experiments.

Hi-C data are commonly normalized using single sample processing methods, with focus on comparisons between regions within a given contact map. Here, we aim to compare contact maps across different samples. We demonstrate that unwanted variation, of likely technical origin, is present in Hi-C data with replicates from different individuals, and that properties of this unwanted variation change across the contact map.

Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.

Many Mendelian developmental disorders caused by coding variants in epigenetic regulators have now been discovered. Epigenetic regulators are broadly expressed, and each of these disorders typically shows phenotypic manifestations from many different organ systems. An open question is whether the chromatin disruption-the root of the pathogenesis-is similar in the different disease-relevant cell types.

Genotype prediction of 336,463 samples from public expression data.

Tens of thousands of RNA-sequencing experiments comprising hundreds of thousands of individual samples have now been performed. These data represent a broad range of experimental conditions, sequencing technologies, and hypotheses under study. The Recount project has aggregated and uniformly processed hundreds of thousands of publicly available RNA-seq samples.

Intrinsically disordered Pseudomonas chaperone FapA slows down the fibrillation of major biofilm-forming functional amyloid FapC.

Functional bacterial amyloids play a crucial role in the formation of biofilms, which mediate chronic infections and contribute to antimicrobial resistance. This study focuses on the FapC amyloid fibrillar protein from Pseudomonas, a major contributor to biofilm formation. We investigate the initial steps of FapC amyloid formation and the impact of the chaperone-like protein FapA on this process.

Differential Effects of Lipid Bilayers on αPSM Peptide Functional Amyloid Formation.

Phenol-soluble modulins (PSMs) are key virulence factors of , and they comprise the structural scaffold of biofilm as they self-assemble into functional amyloids. They have been shown to interact with cell membranes as they display toxicity towards human cells through cell lysis, with αPSM3 being the most cytotoxic. In addition to causing cell lysis in mammalian cells, PSMs have also been shown to interact with bacterial cell membranes through antimicrobial effects.

A mouse model of Weaver syndrome displays overgrowth and excess osteogenesis reversible with KDM6A/6B inhibition.

Weaver syndrome is a Mendelian disorder of the epigenetic machinery (MDEM) caused by germline pathogenic variants in EZH2, which encodes the predominant H3K27 methyltransferase and key enzymatic component of Polycomb repressive complex 2 (PRC2). Weaver syndrome is characterized by striking overgrowth and advanced bone age, intellectual disability, and distinctive facies. We generated a mouse model for the most common Weaver syndrome missense variant, EZH2 p.

Pumping the brakes on RNA velocity by understanding and interpreting RNA velocity estimates.

Background: RNA velocity analysis of single cells offers the potential to predict temporal dynamics from gene expression. In many systems, RNA velocity has been observed to produce a vector field that qualitatively reflects known features of the system. However, the limitations of RNA velocity estimates are still not well understood.

Precision pharmacological reversal of strain-specific diet-induced metabolic syndrome in mice informed by epigenetic and transcriptional regulation.

Diet-related metabolic syndrome is the largest contributor to adverse health in the United States. However, the study of gene-environment interactions and their epigenomic and transcriptomic integration is complicated by the lack of environmental and genetic control in humans that is possible in mouse models. Here we exposed three mouse strains, C57BL/6J (BL6), A/J, and NOD/ShiLtJ (NOD), to a high-fat, high-carbohydrate diet, leading to varying degrees of metabolic syndrome.

Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.

Many Mendelian developmental disorders caused by coding variants in epigenetic regulators have now been discovered. Epigenetic regulators are broadly expressed, and each of these disorders typically exhibits phenotypic manifestations from many different organ systems. An open question is whether the chromatin disruption - the root of the pathogenesis - is similar in the different disease-relevant cell types.