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Oxygenated organic molecules (OOMs) play an important role in the formation of atmospheric aerosols. Due to various analytical challenges with respect to measuring organic vapors, uncertainties remain regarding the formation and fate of OOMs. The chemical ionization Orbitrap (CI-Orbitrap) mass spectrometer has recently been shown to be a powerful technique that is able to accurately identify gaseous organic compounds due to its greater mass resolution. Here, we present the ammonium-ion-based CI-Orbitrap (NH4+-Orbitrap) as a technique capable of measuring a wide range of gaseous OOMs. The performance of the NH4+-Orbitrap is compared with that of state-of-the-art mass spectrometers, including a nitrate-ion-based chemical ionization atmospheric pressure interface coupled to a time-of-flight mass spectrometer (NO3--LTOF), a new generation of proton transfer reaction-TOF mass spectrometer (PTR3-TOF), and an iodide-based CI-TOF mass spectrometer equipped with a Filter Inlet for Gases and AEROsols (I−-CIMS). The instruments were deployed simultaneously in the Cosmic Leaving OUtdoors Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN) during the CLOUD14 campaign in 2019. Products generated from α-pinene ozonolysis under various experimental conditions were simultaneously measured by the mass spectrometers. The NH4+-Orbitrap was able to identify the widest range of OOMs (i.e., O ≥ 2), from less-oxidized species to highly oxygenated organic molecules (HOMs). Excellent agreement was found between the NH4+-Orbitrap and the NO3--LTOF with respect to characterizing HOMs and with the PTR3-TOF for the less-oxidized monomeric species. OOM concentrations measured by NH4+-Orbitrap were estimated using calibration factors derived from the OOMs with high time-series correlations during the side-by-side measurements. As with the other mass spectrometry techniques used during this campaign, the detection sensitivity of the NH4+-Orbitrap to OOMs is greatly affected by relative humidity, which may be related to changes in ionization efficiency and/or multiphase chemistry. Overall, this study shows that NH4+-ion-based chemistry associated with the high mass resolution of the Orbitrap mass analyzer can measure almost all inclusive compounds. As a result, it is now possible to cover the entire range of compounds, which can lead to a better understanding of the oxidation processes.

Abstract The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02–0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56–0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5–0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07–1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97–1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95–1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19.

Abstract Primary cilia are antenna-like organelles which sense extracellular cues and act as signalling hubs. Cilia dysfunction causes a heterogeneous group of disorders known as ciliopathy syndromes affecting most organs. Cilia disassembly, the process by which cells lose their cilium, is poorly understood but frequently observed in disease and upon cell transformation. Here, we uncover a role for the PI3Kα signalling enzyme in cilia disassembly. Genetic PI3Kα-hyperactivation, as observed in PIK3CA-related overgrowth spectrum (PROS) and cancer, induced a ciliopathy-like phenotype during mouse development. Mechanistically, PI3Kα and PI3Kβ produce the PIP3 lipid at the cilia transition zone upon disassembly stimulation. PI3Kα activation initiates cilia disassembly through a kinase signalling axis via the PDK1/PKCι kinases, the CEP170 centrosomal protein and the KIF2A microtubule-depolymerising kinesin. Our data suggest diseases caused by PI3Kα-activation may be considered ‘Disorders with Ciliary Contributions’, a recently-defined subset of ciliopathies in which some, but not all, of the clinical manifestations result from cilia dysfunction.

Abstract Cancer therapy-related cardiac dysfunction (CTRCD), which commonly includes left ventricular dysfunction and heart failure, is the main adverse effect of anticancer therapy. In recent years several candidate genes studies and genome-wide association studies have identified common genetic variants associated with CTRCD, but evidence remains limited and few genetic variants are robust. A genome-wide meta-analysis of CTRCD was performed with 852 oncology patients receiving cancer therapy. DNA samples were genotyped and imputed to perform a GWAS meta-analysis for case–control (N = 852 (380 cases and 472 controls) and extreme phenotypes (N = 618 (78 cases and 472 controls) looking for genetic variants that predispose to CTRCD. The results were validated in a replicate cohort of 1,191 oncology patients (245 cases and 946 controls). Functional mapping of the replicated loci was then performed. The meta-analysis showed 9 and 17 loci suggestively associated (P-value

Abstract Background Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. Methods We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. Results We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920–0.952, p

Abstract Prostate cancer exhibits high prevalence and accounts for a high number of cancer-related deaths. The discovery and characterization of molecular determinants of aggressive prostate cancer represents an active area of research. The Immediate Early Response (IER) family of genes, which regulate Protein Phosphatase 2A (PP2A) activity, has emerged among the factors that influence cancer biology. Here, we show that the less studied member of this family, Immediate Early Response 5 like (IER5L), is upregulated in aggressive prostate cancer. Interestingly, the upregulation of IER5L expression exhibits a robust association with metastatic disease in prostate and is recapitulated in other cancer types. In line with this observation, IER5L silencing reduces foci formation, migration and invasion ability in a variety of human and murine prostate cancer cell lines. In vivo, using zebrafish and immunocompromised mouse models, we demonstrate that IER5L-silencing reduces prostate cancer tumor growth, dissemination, and metastasis. Mechanistically, we characterize the transcriptomic and proteomic landscapes of IER5L-silenced cells. This approach allowed us to identify DNA replication and monomeric G protein regulators as downstream programs of IER5L through a pathway that is consistent with the regulation of PP2A. In sum, we report the alteration of IER5L in prostate cancer and beyond and provide biological and molecular evidence of its contribution to tumor aggressiveness.

Abstract Background and objective Weight stigma has negative consequences for both physiological and psychological health. Studies on weight stigma in adolescence, particularly from general populations, are scarce in the Mediterranean area. The main aim of this study is to describe the prevalence of experienced and internalized weight stigma among a representative sample of adolescents from the Spanish city of Terrassa, and to determine its association with sociodemographic variables and weight status. Methods Drawing on data from the initial assessment of a longitudinally funded project on weight stigma in adolescents, a cross-sectional survey-based study was conducted using random multistage cluster sampling. Weight stigma experiences, their frequency and sources, and weight bias internalization with the Modified Weight Bias Internalization Scale (WBISM) were assessed in a sample of 1016 adolescents. Adjusted odds ratios (AOR) between sociodemographic variables, weight status and having experienced weight stigma, and having reported high scores of WBISM (WBISM ≥ 4) were estimated by multiple logistic regression models. Results The prevalence of weight-related stigma experiences was 43.2% in the sample (81.8 in adolescents with obesity) and the prevalence of high levels of weight bias internalization was 19.4% (50.7 in adolescents with obesity). Other kids and school were the most prevalent sources of weight stigma, with society and family being other significant sources of stigma reported by girls. A significantly higher risk of having experienced weight stigma was observed in girls (AOR = 2.6) and in older adolescents (AOR = 1.9). Compared to normal weight adolescents, all weight statuses showed higher risk, being 3.4 times higher in adolescents with underweight and reaching 11.4 times higher risk in those with obesity. Regarding high levels of weight bias internalization, girls had a risk 6.6 times higher than boys. Once again, a “J-shaped” pattern was observed, with a higher risk at the lowest and highest weight statuses. The risk was 6.3 times higher in adolescents with underweight, and 13.1 times higher in adolescents with obesity compared to those with normal weight. Conclusions Considering the high prevalence of experienced and internalized weight stigma among adolescents in Spain, especially in adolescents with obesity and girls, it seems important to implement preventive strategies in different settings and address all sources of stigma.

The Atlantic Meridional Overturning Circulation (AMOC) is a key component of the Earth's climate. However, there are few long time series of observations of the AMOC, and the study of the mechanisms driving its variability depends mainly on numerical simulations. Here, we use four ocean circulation estimates produced by different data-driven approaches of increasing complexity to analyse the seasonal to decadal variability of the subpolar AMOC across the Greenland–Portugal OVIDE (Observatoire de la Variabilité Interannuelle à DÉcennale) line since 1993. We decompose the MOC strength variability into a velocity-driven component due to circulation changes and a volume-driven component due to changes in the depth of the overturning maximum isopycnal. We show that the variance of the time series is dominated by seasonal variability, which is due to both seasonal variability in the volume of the AMOC limbs (linked to the seasonal cycle of density in the East Greenland Current) and to seasonal variability in the transport of the Eastern Boundary Current. The decadal variability of the subpolar AMOC is mainly caused by changes in velocity, which after the mid-2000s are partly offset by changes in the volume of the AMOC limbs. This compensation means that the decadal variability of the AMOC is weaker and therefore more difficult to detect than the decadal variability of its velocity-driven and volume-driven components, which is highlighted by the formalism that we propose.

Emotional intelligence has been associated with academic achievement, which entails that improving emotional intelligence could lead to better academic achievement. However, the mechanisms of this relationship are not well known. This paper focuses on assessing relevant factors associated with academic achievement (emotional well-being, motivation, and learning strategies) as potential mediators of this link. A cross-sectional study with a sample of 96 high school students was conducted. They were assessed using the Mayer-Salovey-Caruso Emotional Intelligence Test, the Psychological Well-being Questionnaire, the Learning Strategies and Motivation Questionnaire, and their final grades. Results of a serial mediation analysis revealed that emotional intelligence is not directly associated with academic achievement but through mediating factors. Serial indirect effects show that emotionally intelligent students have higher levels of emotional well-being, which predicts better learning strategies and is, in turn, associated with academic achievement. Emotional intelligence also predicts greater motivation and better learning strategies (without the mediation of emotional well-being), which is ultimately also associated with academic achievement. Theoretical and instructional implications are discussed.

BackgroundWith an increasing number of digital health apps available in app stores, it is important to assess these technologies reliably regarding their quality. This is done to mitigate the risks associated with their use. There are many different guidelines, methods, and metrics available to assess digital health apps with regard to their quality. ObjectiveThis study aimed to give a holistic summary of the current methods and “condition agnostic” frameworks that are broadly applicable for the quality assessment of all digital health apps. MethodsA systematic search of literature was conducted on 4 databases: Scopus, PubMed, ACM Digital Library, and IEEE Xplore. We followed the PICOS (Population, Patient, or Problem; Intervention; Comparison; Outcomes; and Study Design) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodologies when conducting this umbrella review. The search was conducted on January 26, 2024, for review articles published between 2018 and 2023. We identified 4781 candidate papers for inclusion; after title and abstract screening, 39 remained. After full-text analysis, we included 15 review articles in the full review. ResultsOf the 15 review articles, scoping reviews were the most common (n=6, 40%), followed by systematic reviews (n=4, 27%), narrative reviews (n=4, 27%), and a rapid review (n=1, 7%). A total of 4 (27%) review articles proposed assessment criteria for digital health apps. “Data privacy and/or security” was the most mentioned criterion (n=13, 87%) and “Cost” was the least mentioned criterion (n=1, 7%) for the assessment of digital health apps. The Mobile App Rating Scale was the most frequently used framework for quality assessment of digital health apps. ConclusionsThere is a lack of unity or consolidation across identified frameworks, as most do not meet all the identified criteria from the reviewed articles. Safety concerns associated with the use of digital health apps may be mitigated with the use of quality frameworks.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

The calls for health research to be collaborative are ubiquitous—even as part of a recent World Health Assembly resolution on clinical trials—yet the arguments in support of collaborative research have been taken for granted and are absent in the literature. This article provides three arguments to justify why health research ought to be collaborative and discusses trade-offs to be considered among the ethical values guiding each argument.

Aerogels based on natural polymers are of increasing interest in the biomedical field due to their biocompatibility, bioactivity, biodegradability and, in certain cases, extracellular matrix biomimicry. However, sterility has been a critical quality attribute limiting the use of aerogels in biomedicine. This work introduces a new and environmental-friendly technique based on the use of CO2 called in situ sterilization that enables the manufacturing of sterile aerogel in a one-pot process. Starch aerogel cylinders and alginate aerogel beads enclosed within sterilization pouches were produced using this approach. The study involved the redesign of the flow diagram for aerogel production and the study of the effect of key parameters in the process (additive type and content, agitation, CO2 flow regime type and duration) on the resulting material. The obtained materials were evaluated regarding their texture (helium pycnometry, N2 adsorption-desorption analysis, SEM) and their sterility against three standardized bioindicators. Finally, the sterile aerogel materials were put in contact with NIH-3T3 cells assessing their cytocompatibility. Under the optimal operating conditions with 4.5 h of processing time, the aerogels were sterile, cytocompatible and had a porosity of ca. 80 % and a specific surface area of ca. 80 m2/g and 200 m2/g, for starch and alginate aerogels, respectively. Results allowed to identify the feasible operating region as well as the optimum processing values to obtain the typical nanostructure of aerogels, whilst ensuring suitable regulatory sterilization levels for aerogel implantation and cytocompatibility of the sterile material with fibroblastic cells.