Temporal trends and educational inequalities in obesity, overweight and underweight in pre-pregnant women and their male partners: a decade (2010-2019) with no progress in Sweden.

BACKGROUND: Trends in overweight and obesity among expectant parents can provide useful information about the family environment in which children will grow up and about possible social inequalities that may be passed on to them. Therefore, we aimed to assess whether the prevalence of underweight, overweight and obesity changed over time in pre-pregnant women and their male partners in northern Sweden, and if there were any educational inequalities. METHODS: This study is based on cross-sectional data from a repeated survey of the population in Västerbotten, Sweden. The study population included 18,568 pregnant women and 18,110 male partners during the period 2010-2019. Multinomial logistic regression models were fitted separately for pregnant women and male partners to assess whether the prevalence of age-adjusted underweight, normal weight, overweight and obesity had evolved between 2010 and 2019, and whether trends differed by educational level. RESULTS: Among women, obesity prevalence increased from 9.4% in 2010 to 11.7% in 2019. Among men, it went from 8.9 to 12.8%. Educational inequalities were sustained across the study period. In 2019, the prevalence of obesity was 7.8 percentage points (pp) (CI = 4.4-11.3) higher among women with low compared to high education. The corresponding figure for men was 6.4 pp (CI = 3.3-9.6). CONCLUSIONS: It is not obvious that the prevalence of obesity among parents-to-be will decrease under current dispositions. Public health policies and practice should therefore be strengthened.

The cutaneous beta human papillomavirus type 8 E6 protein induces CCL2 through the CEBPα/miR-203/p63 pathway to support an inflammatory microenvironment in epidermodysplasia verruciformis skin lesions.

Human papillomavirus type 8 (HPV8), a cutaneous genus beta HPV type, has co-carcinogenic potential at sun-exposed sites in patients suffering from the inherited skin disease epidermodysplasia verruciformis (EV). We had previously shown that Langerhans cells responsible for epithelial immunosurveillance were strongly reduced at infected sites and that the HPV8 E7 protein interferes with the CCAAT/enhancer-binding protein (C/EBP)ß to suppress the Langerhans cell chemokine CCL20. At the same time, however, we observed that EV lesions are heavily infiltrated with inflammatory immune cells, which is similar to the situation in HPV8 E6 transgenic mice. To identify critical inflammatory factors, we used a broad multiplex approach and found that the monocyte attracting chemokine CCL2 was significantly and strongly induced by HPV8 E6 but not E7-expressing HaCaT cells, which were used as a model for UV-damaged skin keratinocytes. Conditioned media from HPV8 E6-expressing keratinocytes enhanced CCL2-receptor (CCR2)-dependent monocyte recruitment in vitro, and macrophages predominated in the stroma but were also detected in the epidermal compartment of EV lesions in vivo. CCL2 induction by HPV8 E6 was even stronger than stimulation with the proinflammatory cytokine TNF-α, and both HPV8 E6 and TNF-α resulted in substantial suppression of the transcription factor C/EBPα. Using RNAi-mediated knockdown and overexpression approaches, we demonstrated a mechanistic role of the recently identified C/EBPα/miR-203/p63 pathway for HPV8 E6-mediated CCL2 induction at protein and transcriptional levels. Epithelial co-expression of p63 and CCL2 was confirmed in HPV8 E6-expressing organotypic air-liquid interface cultures and in lesional EV epidermis in vivo. In summary, our data demonstrate that HPV8 oncoproteins actively deregulate epidermal immune homeostasis through modulation of C/EBP factor-dependent pathways. While HPV8 E7 suppresses immunosurveillance required for viral persistence, the present study provides evidence that E6 involves the stemness-promoting factor p63 to support an inflammatory microenvironment that may fuel carcinogenesis in EV lesions.

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. In this work, we present a framework for modelling multi-hazard risks globally in a consistent way, considering hazards, exposures, vulnerabilities, and assumptions on recovery. We illustrate the approach using river floods and tropical cyclones impacting people and physical assets on a global scale in a changing climate. To ensure physical consistency, we combine single hazard models that were driven by the same climate model realizations. Our results show that incorporating common physical drivers and recovery considerably alters the multi-hazard risk. We finally demonstrate how our framework can accommodate more than two hazards and integrate diverse assumptions about recovery processes based on a national case study. This framework is implemented in the open-source climate risk assessment platform CLIMADA and can be applied to various hazards and exposures, providing a more comprehensive approach to risk management than conventional methods.

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. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan. CONCLUSIONS: The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability.

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. METHODS: Applying RT-PCR, we analyzed the expression of two core CCGs (brain and muscle ARNT-like 1 (Bmal1) and Period-2 (Per2)) over several time points (0-60 h) in HaCaT cells with and without 1,25-dihydroxyvitamin D (D3) and/or UV-B and conducted a cosinor analysis to evaluate the effects of those conditions on the circadian rhythm and an extended mixed-effects linear modeling to account for both fixed effects of experimental conditions and random inter-individual variability. Next, we investigated the expression of these two genes in keratinocytes representing different stages of skin photocarcinogenesis, comparing normal (Normal Human Epidermal Keratinocytes-NHEK; p53 wild type), precancerous (HaCaT keratinocytes; mutated p53 status), and malignant (Squamous Cell Carcinoma SCL-1; p53 null status) keratinocytes after 12 h under the same conditions. RESULTS: We demonstrated that in HaCaT cells, Bmal1 showed a robust circadian rhythm, while the evidence for Per2 was limited. Overall expression of both genes, but especially for Bmal1, was increased following UV-B treatment, while Per2 showed a suppressed overall expression following D3. Both UVB and 1,25(OH)2D3 suggested a significant phase shift for Bmal1 (p < 0.05 for the acrophase), while no specific effect on the amplitude could be evidenced. Differential effects on the expression of BMAL1 and Per2 were found when we compared different treatment modalities (UV-B and/or D3) or cell types (NHEK, HaCaT, and SCL-1 cells). CONCLUSIONS: Comparing epidermal keratinocytes representing different stages of skin photocarcinogenesis, we provide further evidence for an independently operating timekeeping system in human skin, which is regulated by UV-B and disturbed during skin photocarcinogenesis. Our finding that this pattern of circadian rhythm was differentially altered by treatment with UV-B, as compared with treatment with D3, does not support the hypothesis that the expression of these CCGs may be regulated via UV-B-induced synthesis of vitamin D but might be introducing a novel photoprotective property of vitamin D through the circadian clock.

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. This is because only a single anthocyanin, delphinidin 3-O-rutinoside, can be produced in N. benthamiana by activation of anthocyanin biosynthesis using transcription factors. The production of other anthocyanins would necessitate the suppression of certain endogenous flavonoid biosynthesis genes while transiently expressing others. In this work, we present a series of tools for the reconstitution of anthocyanin biosynthetic pathways in N. benthamiana leaves. These tools include constructs for the expression or silencing of anthocyanin biosynthetic genes and a mutant N. benthamiana line generated using CRISPR. By infiltration of defined sets of constructs, the basic anthocyanins pelargonidin 3-O-glucoside, cyanidin 3-O-glucoside and delphinidin 3-O-glucoside could be obtained in high amounts in a few days. Additionally, co-infiltration of supplementary pathway genes enabled the synthesis of more complex anthocyanins. These tools should be useful to identify genes involved in the biosynthesis of complex anthocyanins. They also make it possible to produce novel anthocyanins not found in nature. As an example, we reconstituted the pathway for biosynthesis of Arabidopsis anthocyanin A5, a cyanidin derivative and achieved the biosynthesis of the pelargonidin and delphinidin variants of A5, pelargonidin A5 and delphinidin A5.

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. We find that accounting for TC impacts substantially increases the global SCC by more than 20%; median global SCC increases from US$ 173 to US$ 212 per tonne of CO2 under a middle-of-the-road future emission and socioeconomic development scenario. This increase is mainly driven by the strongly TC-affected major greenhouse gas emitting countries India, USA, China, Taiwan, and Japan. This suggests that the benefits of climate policies could currently be substantially underestimated. Adequately accounting for the damages of extreme weather events in policy evaluation may therefore help to prevent a critical lack of climate action.

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 huntingtin (HTT) 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. Lifelong hepatocyte HTT loss is associated with multiple physiological changes, including increased circulating bile acids, cholesterol and urea, hypoglycemia, and impaired adhesion. HTT loss causes a clear shift in the normal zonal patterns of liver gene expression, such that pericentral gene expression is reduced. These alterations in liver zonation in livers lacking HTT are observed at the transcriptional, histological, and plasma metabolite levels. We have extended these phenotypes physiologically with a metabolic challenge of acetaminophen, for which the HTT loss results in toxicity resistance. Our data reveal an unexpected role for HTT in regulating hepatic zonation, and we find that loss of HTT in hepatocytes mimics the phenotypes caused by impaired hepatic ß-catenin function.

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. The median duration of intervention was 136.78 days (range, 1088 days); the mean weighted baseline 25(OH)D concentration and mean age were 33.01 vs. 33.84 nmol/L and 46.8 vs. 44.8 years in the vitamin D and placebo groups, respectively. Using random-effects models, 25(OH)D levels were increased by 36.28 nmol/L (95% CI 31.97-40.59) in the vitamin D group compared to the placebo, with a relative serum increment of 1.77 nmol/L per 2.5 µg of vitamin D daily. Notably, the relative serum 25(OH)D increment was affected by various factors, including the dosage and baseline serum 25(OH)D concentration, decreasing with increasing vitamin D doses and with increasing baseline serum levels. We estimate that supplementation in all healthy adults in Europe with appr. 25 µg of vitamin D (1000 IU) daily would raise serum 25(OH)D levels in 95% of the population to ≥50 nmol/L. Our work provides health authorities with reliable data that can help to re-evaluate recommendations for oral vitamin D supplementation.

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°â€ˆ× 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects. FINDINGS: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions. INTERPRETATION: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate. FUNDING: Australian Research Council and Australian National Health and Medical Research Council.

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 huntingtin ( HTT ) 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. Lifelong hepatocyte HTT loss is associated with multiple physiological changes, including increased circulating bile acids, cholesterol and urea, hypoglycemia, and impaired adhesion. HTT loss causes a clear shift in the normal zonal patterns of liver gene expression, such that pericentral gene expression is reduced. These alterations in liver zonation in livers lacking HTT are observed at the transcriptional, histological and plasma metabolite level. We have extended these phenotypes physiologically with a metabolic challenge of acetaminophen, for which the HTT loss results in toxicity resistance. Our data reveal an unexpected role for HTT in regulating hepatic zonation, and we find that loss of HTT in hepatocytes mimics the phenotypes caused by impaired hepatic ß-catenin function.

3D bioprinting ofE. coliMG1655 biofilms on human lung epithelial cells for building complexin vitroinfection 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, complexin vitromodels 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. To approach that problem, we chose 3D bioprinting. However, printing living bacterial biofilms in defined shapes on human cell models, requires bioinks with very specific properties. Hence, this work aims to develop a 3D bioprinting biofilm method to build robustin vitroinfection models. Based on rheology, printability and bacterial growth, a bioink containing 3% gelatin and 1% alginate in Luria-Bertani-medium was found optimal forEscherichia coliMG1655 biofilms. Biofilm properties were maintained after printing, as shown visually via microscopy techniques as well as in antibiotic susceptibility assays. Metabolic profile analysis of bioprinted biofilms showed high similarity to native biofilms. After printing on human bronchial epithelial cells (Calu-3), the shape of printed biofilms was maintained even after dissolution of non-crosslinked bioink, while no cytotoxicity was observed over 24 h. Therefore, the approach presented here may provide a platform for building complexin vitroinfection models comprising bacterial biofilms and human host cells.

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. We aimed to assess what characteristics of families and children from pregnancy, over birth, and up to 3 years of age are associated with social-emotional problems in boys and girls. This study used regional data from the Salut Programme, a universal health promotion programme implemented in Antenatal and Child Health Care, and data from national Swedish registers. The study population included 6033 3-year-olds and their parents during the period 2010-2018. Distinct logistic regression models for boys and girls were used to assess associations between the family social context, parents' lifestyle, parent's mental health, children's birth characteristics, and indicators of proximal processes (the independent variables); and children's social-emotional problems as measured by the parent-completed Ages and Stages Questionnaire: Social-Emotional between 33 and 41 months of age (the outcome). Overall, a less favourable family social context, detrimental lifestyle of the parents during pregnancy, and parents' mental illness from pregnancy onwards were associated with higher odds of social-emotional problems in 3-year-olds. Higher screentime and infrequent shared book-reading were associated with higher odds of social-emotional problems. The multifaceted determinants of children's social-emotional problems imply that many diverse targets for intervention exist. Additionally, this study suggests that Bronfenbrenner's process-person-context-time theoretical framework could be relevant for public health research and policy.

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. 3-4 Weeks after the therapy switch she developed high fever, chills, progredient general weakness, headaches, abdominal complaints, generalised rash as well as thrombocytopaenia, eosinophilia, elevated liver enzymes, declining kidney, and pulmonary function as well as a maculopapular exanthema. She was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS) and quickly started recovery after initiation of a high steroid substitution. Under steroid dose reduction, the exanthema worsened and toxic epidermal necrolysis (TEN) was histologically diagnosed. After a series of unsuccessful therapeutic approaches (high dose steroid, human immunoglobulins and ciclosporin) the patient received a single dose of the TNF-alpha inhibitor etanercept, which led to a quick recovery. This case demonstrates that DRESS and TEN can present a spectrum of possibly transitioning SCARs providing a diagnostic and therapeutic challenge. Nevertheless, in a such complicated therapeutic setting, etanercept may be lifesaving even after multiple previous unsuccessful therapies. This effective approach provides evidence SCARs due to BRAF/MEK targeted therapy may be driven by TNF-alpha.

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 25.1% of patients (110/439) as high-risk (stage IA, 13.3% [43/323], IB, 53.2% [42/79], and IIA, 67.6% [25/37]). A Kaplan-Meier analysis demonstrated high-risk patients to have significantly worse DFS, MSS and OS versus low-risk counterparts (P < 0.001). In multivariable Cox regression modelling also including key clinicopathological/demographic factors, 7-marker signature data independently prognosticated the studied end-points. Models with the 7-marker signature risk category plus clinicopathological/demographic covariates substantially outperformed models with clinicopathological/demographic variables alone in predicting all studied outcomes (areas under the receiver operator characteristic curve 74.1% versus 68.4% for DFS, 81.5% versus 71.2% for MSS, 80.9% versus 73.0% for OS; absolute differences 5.7%, 10.3% and 7.9%, respectively, favouring 7-marker signature risk category-containing models). CONCLUSION: In patients with AJCC early-stage disease, the 7-marker signature reliably prognosticates melanoma-related outcomes, independent of AJCC classification, and provides a valuable complement to clinicopathological/demographic factors.

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). Four intersectional groups were created: high and low educated men, and high and low educated women. Prevalence differences corresponding to joint, referent, and excess intersectional inequalities, were estimated for three outcomes: inadequate fruit and vegetable intake combined, inadequate fruit intake, and inadequate vegetable intake. The discriminatory accuracy of the intersectional groups was estimated by the area under the receiver operating characteristic curve. RESULTS: Low educated men had the highest prevalence of inadequate intake of fruits and vegetables combined (81.4%), fruits (83.4%), and vegetables (84.9%), while high educated women had the lowest (47.7, 60.2, and 51.8%, respectively). The joint disparities between high educated women and low educated men were both significant and substantial for all outcomes (34.6 percentage points (pp.), 25.2 pp., and 31.2 pp., adjusted), although differences in magnitude were noted between fruit and vegetable intake. The joint disparities were mostly explained by the two referent disparities for gender and education. The excess intersectional disparity - the part of the joint disparity not explained by either referent disparity - was negative for all three outcomes (-5.5 pp., - 4.2 pp., and - 4.6 pp. respectively, adjusted). The discriminatory accuracy of the intersectional groups was moderate (0.67, 0.65, and 0.68 respectively). CONCLUSIONS: An intersectional approach can provide a more detailed view of inequalities in fruit and vegetable consumption between groups combining several social positions. The moderate discriminatory accuracy observed here suggests that interventions and policies aiming to reduce diet inequalities should not solely be targeted at certain groups, but also be universal.

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)(bdc)]·nH2O, 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. CAU-10-H displays four different phases during pressurization in water up to 4.08(1) GPa. Upon immersion in water at ambient conditions, the unit cell volume expands by 1.3(1)%, by increasing water content from 78.7(1) to 85.6(1) H2O per unit cell. Upon pressurization to 1.08(1) GPa, the water content increases gradually to 112.5(1) H2O per unit cell and reduces the symmetry to P1 phase. At 1.72(1) GPa, a correlated "gate-opening/channel-closing" transition to a centrosymmetric Pnma phase occurs to increase the unit cell volume by 6.9(1)% and water content to 138.8(1) H2O per unit cell. Further increase in pressure to 4.08(1) GPa then leads to a gradual decrease in water content to 119.2(1) H2O per unit cell and redistribution of the inserted water molecules during a "gate-closing/channel-opening" transition to an I41/amd phase. After pressure removal, CAU-10-H reverts to its initial state in terms of crystallinity and water content. This pressure-induced water adsorption/desorption and concerted movements of gate-constraining ligands provides a detailed understanding of the water-MOF interplay, which can be used as a basis for designing new materials, possibly utilizing pressure as a tool for chemical modifications.

Mapping brain gene coexpression in daytime transcriptomes unveils diurnal molecular networks and deciphers perturbation gene signatures.

Brain tissue transcriptomes may be organized into gene coexpression networks, but their underlying biological drivers remain incompletely understood. Here, we undertook a large-scale transcriptomic study using 508 wild-type mouse striatal tissue samples dissected exclusively in the afternoons to define 38 highly reproducible gene coexpression modules. We found that 13 and 11 modules are enriched in cell-type and molecular complex markers, respectively. Importantly, 18 modules are highly enriched in daily rhythmically expressed genes that peak or trough with distinct temporal kinetics, revealing the underlying biology of striatal diurnal gene networks. Moreover, the diurnal coexpression networks are a dominant feature of daytime transcriptomes in the mouse cortex. We next employed the striatal coexpression modules to decipher the striatal transcriptomic signatures from Huntington's disease models and heterozygous null mice for 52 genes, uncovering novel functions for Prkcq and Kdm4b in oligodendrocyte differentiation and bipolar disorder-associated Trank1 in regulating anxiety-like behaviors and nocturnal locomotion.

Intercomparison of regional loss estimates from global synthetic tropical cyclone models.

Tropical cyclones (TCs) cause devastating damage to life and property. Historical TC data is scarce, complicating adequate TC risk assessments. Synthetic TC models are specifically designed to overcome this scarcity. While these models have been evaluated on their ability to simulate TC activity, no study to date has focused on model performance and applicability in TC risk assessments. This study performs the intercomparison of four different global-scale synthetic TC datasets in the impact space, comparing impact return period curves, probability of rare events, and hazard intensity distribution over land. We find that the model choice influences the costliest events, particularly in basins with limited TC activity. Modelled direct economic damages in the North Indian Ocean, for instance, range from 40 to 246 billion USD for the 100-yr event over the four hazard sets. We furthermore provide guidelines for the suitability of the different synthetic models for various research purposes.

Cross-talk of Aryl Hydrocarbon Receptor (AHR)- and Vitamin D Receptor (VDR)-signaling in Human Keratinocytes.

BACKGROUND/AIM: Vitamin D receptor (VDR), activated upon binding of 1,25(OH)2D3, was described as a tumor suppressor in the skin. New biological functions of non-classical vitamin D derivatives were recently identified, that are mediated via binding to alternate receptors, including the aryl hydrocarbon receptor (AHR) and that indicate functional interaction between AHR and VDR signaling in various human tissues. We aimed to gain further insights into the cross-talk of VDR and AHR signaling in skin photo-carcinogenesis. MATERIALS AND METHODS: Using real-time quantitative PCR, we analyzed in vitro effects of the complete carcinogen UVB and of 1,25(OH)2D3 on the expression of members of the AHR and VDR pathways in human keratinocytes revealing characteristics of different stages of skin photo-carcinogenesis. RESULTS: In precancerous HaCaT keratinocytes, induction of a target gene of AHR-mediated transcription (CYP1A1) was markedly stronger after treatment with UVB, as compared to treatment with 1,25(OH)2D3. In contrast, in SCL-1 cells (that reveal the complete phenotype of malignant transformation), expression of CYP1A1 was higher after treatment with 1,25(OH)2D3 as compared to treatment with UVB. The classical VDR target CYP24A1 was up-regulated by 1,25(OH)2D3, but not by UVB, in both cell lines. However, the combined treatment with UVB strongly enhanced the 1,25(OH)2D3-mediated up-regulation of CYP24A1 exclusively in SCL-1, but not in HaCaT cells. CONCLUSION: There is a differential regulation of VDR and AHR target genes by UVB and 1,25(OH)2D3 in HaCaT and SCL-1 cells, that points to a complex and highly orchestrated network of vitamin D derivatives (and other photoproducts) and its relevance for photo-carcinogenesis.