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Modeling passenger comfort in turboprop aircraft using objective measures
BACKGROUND: A quantitative comfort model will aid in evaluating comfort levels of various target groups before the actual flight of an airplane. However, constructing the model is always a challenge due to the complexity of the phenomenon. OBJECTIVES: In this paper, we present quantitative comfort…
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Investigating the causal effect of potential therapeutic agents for colorectal cancer prevention: a Mendelian randomization analysis
BACKGROUND: Conventional observational studies have identified several potential therapeutic agents that may lower risk of colorectal cancer development. However, these studies are susceptible to unmeasured and residual confounding and reverse causation, undermining robust causal inference…
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Cryo-EM visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2
The five RAD51 paralogs play critical roles in the recombinational repair of DNA breaks and replication fork maintenance. Mutations in the genes that encode them cause heritable breast and ovarian cancers, and the cancer-prone disease Fanconi anemia. Here, we show that the RAD51 paralogs form two…
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The Neural Bases of Graphical Perception: A Novel Instance of Cultural Recycling?
Graphical representations of quantitative data abound in our culture, and yet the brain mechanisms of graphicacy, by which viewers quickly extract statistical information from a data graphic, are unknown. Here, using scatterplots as stimuli, we tested two hypotheses about the brain areas underlying…
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Human TET2-mutant clonal hematopoiesis expansion is driven by distinct inflammatory signaling responses in stem cells versus myeloid progeny
Clonal hematopoiesis (CH) increases with age and is associated with severe outcome in the course of infections or tumor development. Understanding the environmental conditions that favor mutant clones and the CH-immune system response to such environments is key to designing therapeutic strategies…
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MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify
Maturity Onset Diabetes of the Young (MODY) can present after the age of 40 years, but its prevalence, clinical characteristics, and the utility of simple clinical features for selecting cases in this age group remain poorly defined. We analysed whole-exome and clinical data from 51,619 individuals…
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Medium-chain triglyceride supplementation in infants with biliary atresia: a review of the evidence for impacts on fat absorption, growth, nutritional status and clinical outcomes
Biliary atresia is a rare bile duct disease resulting in intestinal bile salt depletion due to poor bile flow. Medium-chain triglyceride (MCT) supplementation is widely recommended and used as the main dietary management in infants, however evidence for its use is limited and there is uncertainty…
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Alcohol Use and Risk of Dementia in Diverse Populations
OBJECTIVES: To investigate the causal relationship between alcohol consumption and dementia. DESIGN: Prospective cohort analysis combined with linear and nonlinear Mendelian randomization. SETTING: Two large-scale population-based cohorts: the US Million Veteran Program and UK Biobank. Genetic…
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A nowhere-to-hide mechanism ensures complete piRNA-directed DNA methylation
The mouse PIWI-interacting RNA (piRNA) pathway provides sustained anti-transposon immunity to the developing male germline by directing transposon DNA methylation (1–3). The first step in this process is the recruitment of SPOCD1 to young LINE1 loci (4). Thereafter, piRNA-mediated tethering of the…
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Infertility and Unrealized Ideal Family Size
Research indicates that people often end their childbearing years with fewer children than they had expected in young adulthood. However, our understanding of the role of infertility in explaining this discrepancy remains limited. Using data from 10 low-fertility countries included in the second…
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Skin epidermal and microvascular properties at the sacrum and heel assessed with optical coherence tomography
INTRODUCTION: The sacrum and posterior heel are two common areas where skin is exposed to pressure and shear forces which could lead to damage in the form of pressure ulcers. Despite their vulnerability, relatively few studies have explored their structural and physiological properties which…
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Directionality range in Emlen funnels
Our understanding of bird orientation guided by magnetic and visual cues is primarily based on Emlen funnel experiments. Migration-motivated birds jump in the direction they want to fly, and their feet leave marks on paper lining the funnel, which yields the preferred direction. Despite the…
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Mycobacterial α-glucans hijack Dectin-1 to facilitate intracellular bacterial survival
Mycobacteria possess a cell envelope that can act as a shield against host defense. This study shows that mycobacteria survive in host macrophages by targeting the innate host receptor Dectin-1 through a non-canonical ligand. Compared to WT mice, Dectin-1-deficient mice were more resistant to…
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Sensing Heat, Finding Cool: The Search for Water in Summertime Paris, New York, and London, 1880–1930
At the turn of the twentieth century, Paris, New York, and London were epicenters of urban modernity, but these cities and their inhabitants were ill-equipped to cope with summer heat. Urbanites experienced thermal discomfort directly through their personal sensory registers, and the search for…
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Transplacental Transfer of Lumefantrine, Mefloquine, and Piperaquine: A Comparison of Concentrations in Mothers, Neonates, and Cord Blood
BACKGROUND: Malaria in pregnancy causes adverse effects on the mother and fetus, requiring effective antimalarial treatment. Understanding the transplacental transfer of antimalarials is vital to assessing fetal safety and the risk of congenital malaria. METHODS: We assessed a triad of blood…
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Characteristics of Individuals With Advanced HIV Disease and Risk Factors for Mortality in a Contemporary Cohort in South Africa
BACKGROUND: Advanced HIV disease is a major contributor to the slowing decline in HIV-related deaths globally. However, limited data exist on which individuals with advanced HIV are at highest risk of death. METHODS: A retrospective cohort study was nested within a larger cohort of 13 primary care…
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Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors
Adoptive T cell therapy using T cells engineered with novel T cell receptors (TCRs) targeting tumour-specific peptides is a promising immunotherapy. However, these TCR-T cells can cross-react with off-target peptides, leading to severe autoimmune toxicities. Current efforts focus on identifying…
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Remodelling of the bone marrow vasculature induced by venetoclax and azacitidine damage
The Bcl2 inhibitor venetoclax in combination with the hypomethylating agents azacitidine (ven/aza) has become increasingly utilized clinically for the treatment of many hematological malignancies. Whilst its effects on malignant cells have been extensively studied, its impact to the surrounding…
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Submillimeter diffusion MRI using an in-plane segmented 3D multi-slab acquisition and denoiser-regularized reconstruction
Diffusion MRI (dMRI) enables brain connectivity mapping but is constrained by spatial resolution. Previous post-mortem studies have demonstrated the potential of submillimeter dMRI in enabling more precise delineations of curved and crossing white matter pathways. However, achieving such resolution…
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