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Melanoma represents a critical clinical challenge owing to its unfavorable outcomes. This type of skin cancer exhibits unique adaptability to the brain microenvironment, but its underlying molecular mechanisms are poorly understood. Recent findings have suggested that melanoma brain metastases may share biological processes similar to those found in various neurodegenerative diseases. To further characterize melanoma brain metastasis development, we explore the relationship between the transcriptional profiles of melanoma brain metastases and the neurodegenerative diseases Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We take an in silico approach to unveil a neurodegenerative signature of melanoma brain metastases compared with those of melanoma nonbrain metastasis (53 dysregulated genes were enriched in 11 functional terms, such as associated terms to the extracellular matrix and development) and with those of nontumor-bearing brain controls (195 dysregulated genes, mostly involved in development and cell differentiation, chromatin remodeling and nucleosome organization, and translation). Two genes, ITGA10 and DNAJC6, emerged as key potential markers being dysregulated in both scenarios. Finally, we developed an open-source, user-friendly web tool (https://bioinfo.cipf.es/metafun-mbm/) that allows interactive exploration of the complete results., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The relationship between exposure to air pollution and the severity of coronavirus disease 2019 (COVID-19) pneumonia and other outcomes is poorly understood. Beyond age and comorbidity, risk factors for adverse outcomes including death have been poorly studied. The main objective of our study was to examine the relationship between exposure to outdoor air pollution and the risk of death in patients with COVID-19 pneumonia using individual-level data. The secondary objective was to investigate the impact of air pollutants on gas exchange and systemic inflammation in this disease. This cohort study included 1548 patients hospitalised for COVID-19 pneumonia between February and May 2020 in one of four hospitals. Local agencies supplied daily data on environmental air pollutants (PM 10 , PM 2.5 , O 3 , NO 2 , NO and NO X ) and meteorological conditions (temperature and humidity) in the year before hospital admission (from January 2019 to December 2019). Daily exposure to pollution and meteorological conditions by individual postcode of residence was estimated using geospatial Bayesian generalised additive models. The influence of air pollution on pneumonia severity was studied using generalised additive models which included: age, sex, Charlson comorbidity index, hospital, average income, air temperature and humidity, and exposure to each pollutant. Additionally, generalised additive models were generated for exploring the effect of air pollution on C-reactive protein (CRP) level and SpO 2 /FiO 2 at admission. According to our results, both risk of COVID-19 death and CRP level increased significantly with median exposure to PM 10 , NO 2 , NO and NO X , while higher exposure to NO 2 , NO and NO X was associated with lower SpO 2 /FiO 2 ratios. In conclusion, after controlling for socioeconomic, demographic and health-related variables, we found evidence of a significant positive relationship between air pollution and mortality in patients hospitalised for COVID-19 pneumonia. Additionally, inflammation (CRP) and gas exchange (SpO 2 /FiO 2 ) in these patients were significantly related to exposure to air pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Aims: To determine the association between sleep quality and lack of glycemic control in a Mexican population of type 2 diabetes patients., Methods: Cross-sectional study. Two hundred two patients between 20 and 60 years old with a previous diagnosis of diabetes were included. Sleep quality was assessed with the Pittsburgh Sleep Quality Index and lack of glycemic control as a glycated hemoglobin A1c level ≥ 7 %. Univariate and multivariate analyses using logistic regression were performed., Results: The study population showed poor sleep quality and a lack of glycemic control of 70.3 % and 69.8 %, respectively. The prevalence of patients with both conditions was 52.5 %. In multivariate analysis, poor sleep quality was significantly associated with a lack of glycemic control (OR = 2.3, p = 0.030). Other associated variables were napping (p = 0.015), diabetes duration (p = 0.011), insulin use (p = 0.024), and diastolic blood pressure ≥ 85 mmHg (p = 0.029)., Conclusions: The prevalence of lack of glycemic control in the study population is high. Poor sleep quality significantly doubles the risk of lack of glycemic control, even in the presence of other risk factors., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest in publishing the results of this study., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Biological differences between the sexes have a major impact on disease and treatment outcome. In this paper, we evaluate the prognostic value of sex in stage IV non-small-cell lung cancer (NSCLC) in the context of routine clinical data, and compare this information with other external datasets., Methods: Clinical data from stage IV NSCLC patients from Hospital Puerta de Hierro (HPH) were retrieved from electronic health records using big data analytics (N = 397). In addition, data from the Spanish Lung Cancer Group (GECP) Tumor Registry (N = 1382) and from a published study available from the cBioPortal (MSK) (N = 601) were analyzed. Survival curves were estimated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to assess the prognostic value of sex. A meta-analysis to compare the outcome for males and females in terms of overall survival (OS) and progression free survival (PFS) was performed., Results: The median OS time was 12 months for males and 19 months for females (overall HR = 0.77; 95% CI: 0.68-0.87; P < 0.001). Similarly, females with stage IV NSCLC harboring an EGFR-sensitizing mutation lived significantly longer than males (median OS: males, 19 months; females, 32 months) with a lower risk of death compared with males (overall HR = 0.75; 95% CI: 0.67-0.84). In addition, female patients benefited more from EGFR inhibitors in terms of PFS and OS (overall HR = 0.45; 95% CI: 0.32-0.64, and HR = 0.62; 95% CI: 0.48-0.80, respectively). Median PFS was 21 months in females and 12 months in males (P < 0.001)., Conclusions: Using routine clinical data we confirmed the previous finding that among stage IV NSCLC patients, females had a significantly better prognosis than males. The effect size of the sex was notable, highlighting the fact that survival rates are usually estimated and patients are generally managed without considering the sexes separately, which may lead to suboptimal results., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The long-term non-progressors (LTNPs) are a heterogeneous group of HIV-positive individuals characterized by their ability to maintain high CD4 + T-cell counts and partially control viral replication for years in the absence of antiretroviral therapy. The present study aims to identify host single nucleotide polymorphisms (SNPs) associated with non-progression in a cohort of 352 individuals., Methods: DNA microarrays and exome sequencing were used for genotyping about 240 000 functional polymorphisms throughout more than 20 000 human genes. The allele frequencies of 85 LTNPs were compared with a control population. SNPs associated with LTNPs were confirmed in a population of typical progressors. Functional analyses in the affected gene were carried out through knockdown experiments in HeLa-P4, macrophages and dendritic cells., Results: Several SNPs located within the major histocompatibility complex region previously related to LTNPs were confirmed in this new cohort. The SNP rs1127888 (UBXN6) surpassed the statistical significance of these markers after Bonferroni correction (q = 2.11 × 10 -6 ). An uncommon allelic frequency of rs1127888 among LTNPs was confirmed by comparison with typical progressors and other publicly available populations. UBXN6 knockdown experiments caused an increase in CAV1 expression and its accumulation in the plasma membrane. In vitro infection of different cell types with HIV-1 replication-competent recombinant viruses caused a reduction of the viral replication capacity compared with their corresponding wild-type cells expressing UBXN6., Conclusions: A higher prevalence of Ala31Thr in UBXN6 was found among LTNPs within its N-terminal region, which is crucial for UBXN6/VCP protein complex formation. UBXN6 knockdown affected CAV1 turnover and HIV-1 replication capacity., (Copyright © 2019. Published by Elsevier Ltd.)

Charcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (<1%) were found in 12 cases. There were no candidate variants in 18 cases, and amplification failed for one sample. The DNAJB2 c.352+1G>A mutation was also detected in three additional families. On haplotype analysis, all of the patients from these five families shared the same haplotype; therefore, the DNAJB2 c.352+1G>A mutation may be a founder event. Our gene panel allowed us to perform a very rapid and cost-effective screening of genes involved in Charcot-Marie-Tooth disease/hereditary motor neuropathy. Our diagnostic strategy was robust in terms of both coverage and read depth for all of the genes and patient samples. These findings demonstrate the difficulty in achieving a definitive molecular diagnosis because of the complexity of interpreting new variants and the genetic heterogeneity that is associated with these neuropathies., (Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin affecting a large number of patients worldwide. Psoriasis is characterized by a T helper type 1 and/or T helper type 17 immunological response, whereas acute atopic dermatitis lesions exhibit T helper type 2-dominant inflammation. Current single gene and signaling pathways-based models of inflammatory skin diseases are incomplete. Previous work allowed us to model psoriasis in skin-humanized mice through proper combinations of inflammatory cell components and disruption of barrier function. Herein, we describe and characterize an animal model for atopic dermatitis using similar bioengineered-based approaches, by intradermal injection of human T helper type 2 lymphocytes in regenerated human skin after partial removal of stratum corneum. In this work, we have extensively compared this model with the previous and an improved version of the psoriasis model, in which T helper type 1 and/or T helper type 17 lymphocytes replace exogenous cytokines. Comparative expression analyses revealed marked differences in specific epidermal proliferation and differentiation markers and immune-related molecules, including antimicrobial peptides. Likewise, the composition of the dermal inflammatory infiltrate presented important differences. The availability of accurate and reliable animal models for these diseases will contribute to the understanding of the pathogenesis and provide valuable tools for drug development and testing., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Genome-wide expression analysis using microarrays has been used as a research strategy to discovery new biomarkers and candidate genes for a number of diseases. We aim to find new biomarkers for the prediction of acute coronary syndrome (ACS) with a differentially expressed mRNA profiling approach using whole genomic expression analysis in a peripheral blood cell model from patients with early ACS., Methods and Results: This study was carried out in two phases. On phase 1 a restricted clinical criteria (ACS-Ph1, n=9 and CG-Ph1, n=6) was used in order to select potential mRNA biomarkers candidates. A subsequent phase 2 study was performed using selected phase 1 markers analyzed by RT-qPCR using a larger and independent casuistic (ACS-Ph2, n=74 and CG-Ph2, n=41). A total of 549 genes were found to be differentially expressed in the first 48 h after the ACS-Ph1. Technical and biological validation further confirmed that ALOX15, AREG, BCL2A1, BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4 and TREML4, are differentially expressed in both phases of this study., Conclusions: Transcriptomic analysis by microarray technology demonstrated differential expression during a 48 h time course suggesting a potential use of some of these genes as biomarkers for very early stages of ACS, as well as for monitoring early cardiac ischemic recovery., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Although the estimated frequency of coronary artery disease (CAD) in patients on dialysis is very high, there is considerable variation in the studies published to date regarding the rate of acute myocardial infarction (AMI) in these patients., Objective: To establish the incidence of AMI and to analyse the characteristics and consequences of this entity on the clinical progression of incident dialysis patients., Methods: We recorded AMI in the patients treated in our dialysis unit between 01/01/1999 and 31/12/07. The variables assessed were: prior diagnosis of diabetes, hypertension, CAD (AMI or lesions observed in coronary angiography), ischaemic cerebrovascular accident, advanced peripheral artery disease (PAD), atrial fibrillation and tobacco use. Biochemical analyses included: urea, creatinine, haematocrit, calcium, phosphorous, iPTH, lipids and albumin. Follow-up lasted until transplant, death, loss to follow-up or study end in Dec. 2010., Results: Of the 576 patients recruited (aged 64.6 ± 16 years), 24.7% had diabetes, 82.3% were on haemodialysis (17.7% on peritoneal dialysis), and 34 (5.9%) had a previous diagnosis of CAD. In a follow-up lasting a mean of 40.2 ± 32 months (1931.5 patient-years), 40 patients (6.9%) suffered an AMI. The incidence was 2.13/100 patient-years. The patients without CAD had an incidence of 1.84/100 patient-years and those with a previous diagnosis of CAD had an incidence of 7.53/100 patient-years. In 22.5% of patients, AMI happened in the first 3 months of dialysis, and 37.5% in the 1st year. Of the 40 AMI, 15 were with ST-segment elevation (incidence: 0.79/100 patient-years) and 25 were non ST-segment elevation (incidence: 1.33/100 patient-years). The factors that predicted the occurrence of AMI in dialysis were older age (OR: 1.037; 95% CI: 1.009-1.067; P=.011), previous CAD (OR: 3.35; 95% CI: 1.48-7.16; P=.004), and diabetes as a cause of nephropathy (OR: 2.96; 95% CI: 1.49-5.86; P=.002). In-hospital mortality was 30%, with 72.5% of deaths occurring in the 1st year and 82.5% in the 2nd; 80% of the patients who underwent a coronary angiography had multi-vessel disease., Conclusions: The incidence of AMI in incident dialysis patients is high. In previous coronary disease patients, the incidence is 3-fold higher. Post-infarction mortality is very high and multi-vessel disease is very frequent.