Associations of early life body size and pubertal timing with breast density and postmenopausal breast cancer risk: a mediation analysis.

Purpose: Whether breast density mediates associations between early life body size and pubertal timing with postmenopausal breast cancer is underexplored.

Methods: We studied 33,939 Danish women attending the Capital Mammography Screening Program at ages 50-69 years. Early life anthropometry and pubertal timing information came from the Copenhagen School Health Records Register.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

The simple morphology of the sunfish heart.

The evolutionary conservation of the building plan of the heart suggests this organ is under substantial form-function constraints. Its form varies to such a degree, however, that it questions whether we understand the form-function relations of the heart. A previously published image of the heart of the sunfish (Mola mola, Tetraodontiformes) indicates the presence of an exceptionally simple topology of the chambers.

Increasing Life Expectancy in Patients with Genitourinary Malignancies: Impact of Treatment Burden on Disease Management and Quality of Life.

Background And Objective: Treatment burden refers to the overall impact of medical treatments on a patient's well-being and daily life. Our objective is to evaluate the impact of treatment burden on quality of life (QoL) in patients with genitourinary (GU) malignancies, highlighting the importance of patient-reported outcomes (PROs) in clinical trials to inform treatment decisions and improve patient care.

Methods: We conducted a narrative review of clinical trials focused on GU malignancy (prostate, bladder, and kidney) between January 2000 and June 2024, analyzing related PROs and findings regarding treatment burden.

Unmasking Primary Carnitine Deficiency as a Mimic of Hypertrophic Cardiomyopathy.

Primary carnitine deficiency may mimic hypertrophic cardiomyopathy and be mistakenly attributed to genotype-negative sarcomeric protein dysfunction in hypertrophic cardiomyopathy. Although rare, timely diagnosis may have significant implications on management and should prompt testing of family members.

Pembrolizumab Versus chemotherapy in microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer: 5-year follow-up from the randomized phase 3 KEYNOTE-177 study.

Background: Results from the phase 3 KEYNOTE-177 study established pembrolizumab as a new first-line standard of care for microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Previous results from KEYNOTE-177 showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with pembrolizumab versus chemotherapy ± bevacizumab/cetuximab in MSI-H/dMMR mCRC. Results after >5 years of follow-up are reported.

Temporal Dynamics of Plasma Neurofilament Light in Blood Donors With Preclinical Multiple Sclerosis.

Background And Objectives: Multiple sclerosis (MS) is a CNS disease, characterized by demyelination, inflammation, and neurodegeneration. Recent advances in technology allow measurement of the axonal damage marker neurofilament light chain in peripheral blood. Two studies have shown that patients with MS have elevated neurofilament light levels before their first symptom, but longitudinal studies are lacking.

Double-Stacked One-Third Tubular Plating for Suprasyndesmotic Fibula Fractures Technique Description and Clinical Case Series.

Fixation for suprasyndesmotic fibula fractures (AO/OTA type 44C, consistent with Weber C) is classically achieved using a single one-third tubular plate. However, these fractures may sometimes require stronger fixation due to the diaphyseal fracture location and the lack of structural support from injured ligaments. To increase stability, 3.

In situ-crosslinked Zippersomes enhance cardiac repair by increasing accumulation and retention.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here, we show that EVs decorated with the next-generation of high-affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7-fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs.

The association between being breastfed in infancy and risks of cancer in adulthood-a UK Biobank study.

Background: Being breastfed has established benefits for infant health, but its long-term effects on adult diseases, including cancer, remain underexplored. We examined associations between being breastfed in infancy and the risks of common cancers.

Methods: Data from 339,115 participants (191,117 women) enrolled in the UK Biobank with self-reported breastfeeding data were linked to national cancer registries.

Mechanical memory based biofabrication of hierarchical elastic cardiac tissue.

Mimicking the multilayered, anisotropic, elastic structure of cardiac tissues for controlled guidiance of 3D cellular orientation is essential in designing bionic scaffolds for cardiac tissue biofabrication. Here, a hierarchically organized, anisotropic, wavy and conductive polycaprolactone/Au scaffold was created in a facile fashion based on mechanical memory during fabrication. The bionic 3D scaffold shows good biocompatibility, excellent biomimetic mechanical properties that guide myoblast alignment, support the hyperelastic behavior observed in native cardiac muscle tissue, and promote myotube maturation, which holds potential for cardiac muscle engineering and the establishment of anculture platform for drug screening.

A partial loss-of-function variant in STAT6 protects against type 2 asthma.

Background: Signal transducer and activator of transcription 6 (STAT6) is central to type 2 (T2) inflammation, and common noncoding variants at the STAT6 locus associate with various T2 inflammatory traits, including diseases, and its pathway is widely targeted in asthma treatment.

Objective: We sought to test the association of a rare missense variant in STAT6, p.L406P, with T2 inflammatory traits, including the risk of asthma and allergic diseases, and to characterize its functional consequences in cell culture.

Chemokine Receptor N-Terminus Charge Dictates Reliance on Post-Translational Modifications for Effective Ligand Capture and Following Boosting by Defense Peptides.

The chemokine receptors CCR1 and CCR5 display overlapping expression patterns and ligand dependency. Here we find that ligand activation of CCR5, not CCR1, is dependent on N-terminal receptor O-glycosylation. Release from O-glycosylation dependency is obtained by increasing CCR5 N-terminus acidity to the level of CCR1.

ACE2 and TMPRSS2 in human kidney tissue and urine extracellular vesicles with age, sex, and COVID-19.

SARS-CoV-2 virus infects cells by engaging with ACE2 requiring protease TMPRSS2. ACE2 is highly expressed in kidneys. Predictors for severe disease are high age and male sex.

Immunoregulatory effects of soluble antigens of Leishmania sp. in human lymphocytes in vitro.

The clinical manifestations of cutaneous leishmaniasis (CL) depend not only on the infecting species involved, but also on the immune response of the individual. Although not yet well understood in humans, parasite survival and persistence are related to the cytokine profile and T cell proliferation, with the Th1 profile being related to cure, and the Th2 profile to disease progression. Considering the need for studies focused on the species with the highest circulation in the state of Amazonas, this study aimed to analyze the immunoregulation stimulated by soluble antigens (SLAs) of Leishmania (L.

Identification of natriuretic peptide receptor A-related gene expression signatures in podocytes in vivo reveals baseline control of protective pathways.

Natriuretic peptide receptor-A (NPR-A) is the principal receptor for the natriuretic peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Targeted deletion of NPR-A in mouse glomerular podocytes significantly enhances renal injury in vivo in the DOCA-salt experimental model. It was therefore hypothesized that natriuretic peptides exert a direct protective effect on glomerular barrier integrity through activation of NPR-A and modulation of gene expression patterns in podocytes.

A serosurvey examining exposure to and tick-borne encephalitis virus in Danish blood donors, August 2022.

Objectives: (Bbsl) and tick-borne encephalitis virus (TBEV) are tick-borne pathogens. This study aimed to investigate the seroprevalence of these pathogens in Danish blood donors.

Methods: A total of 1000 plasma samples equally distributed (n = 200) from all five Danish regions were analyzed.

Sex differences in nucleus accumbens core circuitry engaged by binge-like ethanol drinking.

Growing parity in Alcohol Use Disorder (AUD) diagnoses in men and women necessitates consideration of sex as a biological variable. In humans and rodents, the nucleus accumbens core (NAcc) regulates alcohol binge drinking, a risk factor for developing AUD. We labeled NAcc inputs with a viral retrograde tracer and quantified whole-brain c-Fos to determine the regions and NAcc inputs differentially engaged in male and female mice during binge-like ethanol drinking.

A direct comparison of a next generation hyperspectral camera to state-of-the-art.

Hyperspectral camera technology is advancing rapidly, and this paper seeks to compare a state-of-the-art industrial dual-camera setup to a single-camera system employing the latest chip technology (IMX990 from Sony). The hyperspectral cameras are compared over both the Visual and Short-Wave Infrared range (400-1700 nm) of the electromagnet spectrum. The spectral range and resolution, as well as spatial parameters and spectroscopic information are quantified with comparable optics, electronics, and test targets.

How the trabecular layer impacts on left ventricular function.

The ventricular trabecular layer is crucial in embryonic life. In adults, the proportion of trabecular-to-compact myocardium varies substantially between individuals, within individuals over time, and yet exhibits almost no correlation to pump function since most individuals with excessive trabeculation are asymptomatic. The question of how functional is the myocardium of the trabecular layer, relative to the myocardium of the compact layer, has been difficult to answer but it is often assumed to be inferior.

Trajectories and predictive significance of inflammatory parameters for clinical outcome in COVID-19 patients treated with tocilizumab.

Purpose: The IL-6 receptor inhibitor tocilizumab reduces mortality and morbidity in severe cases of COVID-19 through its effects on hyperinflammation and was approved as adjuvant therapy. Since tocilizumab changes the levels of inflammatory markers, we aimed to describe these changes in patients treated with tocilizumab, analyse their value in predicting death and bacterial superinfection and determine their influence on mortality rates.

Methods: A retrospective analysis of 76 patients who were treated with tocilizumab for severe COVID-19 in 2020 and 2021 was conducted.

Astrocyte-Neuron Interactions Contributing to Amyotrophic Lateral Sclerosis Progression.

Amyotrophic lateral sclerosis (ALS) is a complex disease impacting motor neurons of the brain, brainstem, and spinal cord. Disease etiology is quite heterogeneous with over 40 genes causing the disease and a vast ~90% of patients having no prior family history. Astrocytes are major contributors to ALS, particularly through involvement in accelerating disease progression.