Malignant Melanoma: Vitamin D Status as a Risk and Prognostic Factor - Meta-analyses and Systematic Review.

Background/aim: Solar ultraviolet radiation represents the most important environmental risk factor for skin cancer. However, vitamin D synthesis from sun exposure has been reported to exert anti-carcinogenic effects on melanocytes in vitro. This justifies the ongoing debate whether vitamin D status can be considered a risk and prognostic for primary cutaneous malignant melanoma.

Suppression of Huntington's Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding.

Huntington's disease (HD) arises from a CAG expansion in the () gene beyond a critical threshold. A major thrust of current HD therapeutic development is lowering levels of mutant mRNA (m) and protein (mHTT) with the aim of reducing the toxicity of these product(s). Human genetic data also support a key role for somatic instability (SI) in 's CAG repeat - whereby it lengthens with age in specific somatic cell types - as a key driver of age of motor dysfunction onset.

Decoding the diagnostic and therapeutic potential of microbiota using pan-body pan-disease microbiomics.

The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.

Autoantibody mediated deficiency of IL-36-receptor antagonist in a subset of patients with psoriasis and psoriatic arthritis.

Objective: Psoriatic arthritis (PsA) is known as a seronegative form of spondylarthropathy. The interleukin-36 cytokine family may have a major role in disease pathogenesis and particularly the related cutaneous manifestations. In light of our recent observations on (transient) autoantibody phenotypes neutralizing endogenous anti-inflammatory receptor antagonists (progranulin, IL-1Ra) in different inflammatory conditions, we set out to investigate the potential role of such antibodies targeting IL-36 cytokine family members in PsA and psoriasis without arthritic manifestations (Pso).

Msh3 and Pms1 Set Neuronal CAG-repeat Migration Rate to Drive Selective Striatal and Cortical Pathogenesis in HD Mice.

Unlabelled: Modifiers of Huntington's disease (HD) include mismatch repair (MMR) genes; however, their underlying disease-altering mechanisms remain unresolved. Knockout (KO) alleles for 9 HD GWAS modifiers/MMR genes were crossed to the Q140 Huntingtin (mHtt) knock-in mice to probe such mechanisms. Four KO mice strongly ( and ) or moderately ( and ) rescue a triad of adult-onset, striatal medium-spiny-neuron (MSN)-selective phenotypes: somatic DNA CAG-repeat expansion, transcriptionopathy, and mHtt protein aggregation.

A Novel 3D Printed Model of Infected Human Hair Follicles to Demonstrate Targeted Delivery of Nanoantibiotics.

Hair follicle-penetrating nanoparticles offer a promising avenue for targeted antibiotic delivery, especially in challenging infections like acne inversa or folliculitis decalvans. However, demonstrating their efficacy with existing preclinical models remains difficult. This study presents an innovative approach using a 3D organ culture system with human hair follicles to investigate the hypothesis that antibiotic nanocarriers may reach bacteria within the follicular cleft more effectively than free drugs.

Global multi-hazard risk assessment in a changing climate.

Natural hazards pose significant risks to people and assets in many regions of the world. Quantifying associated risks is crucial for many applications such as adaptation option appraisal and insurance pricing. However, traditional risk assessment approaches have focused on the impacts of single hazards, ignoring the effects of multi-hazard risks and potentially leading to underestimations or overestimations of risks.

Differential Regulation of Circadian Clock Genes by UV-B Radiation and 1,25-Dihydroxyvitamin D: A Pilot Study during Different Stages of Skin Photocarcinogenesis.

Background: Increasing evidence points at an important physiological role of the timekeeping system, known as the circadian clock (CC), regulating not only our sleep-awake rhythm but additionally many other cellular processes in peripheral tissues. It was shown in various cell types that environmental stressors, including ultraviolet B radiation (UV-B), modulate the expression of genes that regulate the CC (CCGs) and that these CCGs modulate susceptibility for UV-B-induced cellular damage. It was the aim of this pilot study to gain further insights into the CCs' putative role for UV-B-induced photocarcinogenesis of skin cancer.

Tropical cyclone-specific mortality risks and the periods of concern: A multicountry time-series study.

Background: More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale.

Methods And Findings: Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019.

A transient expression tool box for anthocyanin biosynthesis in Nicotiana benthamiana.

Transient expression in Nicotiana benthamiana offers a robust platform for the rapid production of complex secondary metabolites. It has proven highly effective in helping identify genes associated with pathways responsible for synthesizing various valuable natural compounds. While this approach has seen considerable success, it has yet to be applied to uncovering genes involved in anthocyanin biosynthetic pathways.

The social costs of tropical cyclones.

Tropical cyclones (TCs) can adversely affect economic development for more than a decade. Yet, these long-term effects are not accounted for in current estimates of the social cost of carbon (SCC), a key metric informing climate policy on the societal costs of greenhouse gas emissions. We here derive temperature-dependent damage functions for 41 TC-affected countries to quantify the country-level SCC induced by the persistent growth effects of damaging TCs.

Meta-Analysis of European Clinical Trials Characterizing the Healthy-Adult Serum 25-hydroxyvitamin D Response to Vitamin D Supplementation.

To obtain reliable data that allow health authorities to re-evaluate recommendations for oral vitamin D uptake, we conducted a meta-analysis to investigate the impact of supplementation on serum 25-hydroxyvitamin D (25(OH)D) levels in healthy adults in Europe. Of the publications identified (n = 4005) in our literature search (PUBMED, through 2 January 2022), 49 primary studies (7320 subjects, 73 study arms) were eligible for inclusion in our meta-analysis. The risk of bias was assessed using the Cochrane RoB tool based on seven categories, according to which each study is rated using three grades, and overall was rated as rather low.

Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.

Huntington's disease arises from a toxic gain of function in the () gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes.

Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series study.

Background: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019.

Methods: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5° × 0·5°.

Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.

Huntington's disease arises from a toxic gain of function in the ( ) gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes.

3D bioprinting ofMG1655 biofilms on human lung epithelial cells for building complexinfection models.

Biofilm-associated infections are causing over half a million deaths each year, raising the requirement for innovative therapeutic approaches. For developing novel therapeutics against bacterial biofilm infections, complexmodels that allow to study drug effects on both pathogens and host cells as well as their interaction under controlled, physiologically relevant conditions appear as highly desirable. Nonetheless, building such models is quite challenging because (1) rapid bacterial growth and release of virulence factors may lead to premature host cell death and (2) maintaining the biofilm status under suitable co-culture requires a highly controlled environment.

Multifaceted determinants of social-emotional problems in preschool children in Sweden: An ecological systems theory approach.

Social-emotional problems occurring early in life can place children at future risk of adverse health, social and economic outcomes. Determinants of social-emotional problems are multi-layered and originate from different contexts surrounding children, though few studies consider them simultaneously. We adopted a holistic approach by using Bronfenbrenner's process-person-context-time model as a structuring device.

Identification of high-risk patients with a seven-biomarker prognostic signature for adjuvant treatment trial recruitment in American Joint Committee on Cancer v8 stage I-IIA cutaneous melanoma.

Purpose: Many patients with resected American Joint Committee on Cancer (AJCC) early-stage cutaneous melanoma nonetheless die of melanoma; additional risk stratification approaches are needed.

Patients And Methods: Using prospectively-collected whole-tissue sections, we assessed in consecutive stage I-IIA patients (N = 439), a previously-validated, immunohistochemistry-based, 7-biomarker signature to prognosticate disease-free survival (DFS), melanoma-specific survival (MSS; primary end-point) and overall survival (OS), independent of AJCC classification.

Results: Seven-marker signature testing designated 25.

Etanercept leads to a rapid recovery of a Dabrafenib-/Trametinib-associated toxic epidermal necrolysis-like severe skin reaction.

Targeted therapy with BRAF- and MEK-Inhibitors (BRAFi, MEKi) provides an excellent therapeutic option for patients with malignant melanomas with a BRAF-Mutation. Mild cutaneous adverse events have been common under the BRAF- and MEK-Inhibitor therapy, on the contrary, severe cutaneous adverse reactions to drugs (SCARs) are rarely reported. We present the case of a 59- year-old female patient who after the resection of cutaneous in-transit metastases of a malignant melanoma received one adjuvant cycle of Nivolumab followed by a switch of the therapy to an oral BRAFi/MEKi therapy.

Disparities in fruit and vegetable intake at the intersection of gender and education in northern Sweden: a cross-sectional study.

Background: Even though the existence of inequalities in fruit and vegetable consumption has been well established, it is not clear how it is patterned across intersections of multiple social positions and identities. This study aims to investigate disparities in fruit and vegetable intake between groups at the intersection of education and gender in northern Sweden, and to estimate the discriminatory accuracy of the intersectional groups.

Methods: Cross-sectional data from the 2018 Health on Equal Terms survey conducted in four regions in northern Sweden was used (N = 21,853).

Structuration of Water in Microporous CAU-10-H under Gigapascal Pressure.

Employing metal-organic frameworks (MOFs) as water adsorbents has become a flourishing field in recent years. Aluminum isophthalate [Al(OH)()]·HO, referred to as CAU-10-H, is renowned for its high physical and chemical stability under external mechanical stimuli, which is crucial for use in sorption-based heat exchange. We report pressure-induced structural changes and water uptake/release of CAU-10-H in the gigapascal regime.