Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and ...tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9–4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = −0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.
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•We described the early-life exposome in Colombian children under five.•Exposome varied considerably by city and time (pregnancy and childhood).•Health studies with air pollutants should consider other exposure groups.•It is very complex to summarize exposome into a few exposure components.•Due to time-space variations, more exposome studies are needed in Latin America.
Transcription factor NRF2 orchestrates a cellular defense against oxidative stress and, so far, has been involved in tumor progression by providing a metabolic adaptation to tumorigenic demands and ...resistance to chemotherapeutics. In this study, we discover that NRF2 also propels tumorigenesis in gliomas and glioblastomas by inducing the expression of the transcriptional co-activator TAZ, a protein of the Hippo signaling pathway that promotes tumor growth. The expression of the genes encoding NRF2 (NFE2L2) and TAZ (WWTR1) showed a positive correlation in 721 gliomas from The Cancer Genome Atlas database. Moreover, NRF2 and TAZ protein levels also correlated in immunohistochemical tissue arrays of glioblastomas. Genetic knock-down of NRF2 decreased, while NRF2 overexpression or chemical activation with sulforaphane, increased TAZ transcript and protein levels. Mechanistically, we identified several NRF2-regulated functional enhancers in the regulatory region of WWTR1. The relevance of the new NRF2/TAZ axis in tumorigenesis was demonstrated in subcutaneous and intracranial grafts. Thus, intracranial inoculation of NRF2-depleted glioma stem cells did not develop tumors as determined by magnetic resonance imaging. Forced TAZ overexpression partly rescued both stem cell growth in neurospheres and tumorigenicity. Hence, NRF2 not only enables tumor cells to be competent to proliferate but it also propels tumorigenesis by activating the TAZ-mediated Hippo transcriptional program.
Scheme showing the main findings of this study: NRF2 induces target genes such as GCLC, NQO1, HMOX1, etc. that in cancer cells may provide a cytoprotective response to stressful signals including radiotherapy and chemotherapy. In addition, we show here that NRF2 also induces the expression of WWTR1, encoding the transcription factor TAZ, that provides direct input into cancer progression by activating a battery of genes that participate in proliferative responses and cancer stem cell renewal. The combined expression of NRF2 and its target TAZ are characteristic of poor prognosis in glioblastomas. Display omitted
•Expression of NRF2 and TAZ positively correlate in gliomas and glioblastomas.•NRF2 regulates the expression of WWTR1 encoding the transcription co-activator TAZ in glioma stem cells.•TAZ provides a redox-independent mechanism of NRF2 induction of glioblastomas.•Downregulation of the new NRF2/TAZ axis may provide a novel therapy for glioblastomas.
Background:
Spondyloarthritis (SpA) is a group of related but phenotypically distinct inflammatory disorders that include axial SpA (axSpA) and psoriatic arthritis (PsA). Information on the ...characteristics and management of these patients in the real world remains scarce.
Objectives:
To explore the characteristics and management disease activity assessment and treatment with secukinumab (SEC) or other biologic disease-modifying antirheumatic drugs (bDMARDs) of axSpA and PsA patients using natural language processing (NLP) in Electronic Health Records (EHRs).
Design:
National, multicenter, observational, and retrospective study.
Methods:
We analyzed free-text and structured clinical information from EHR at three hospitals. All adult patients with axSpA, PsA or non-classified SpA from 2018 to 2021 with minimum follow-up of three months were included when starting SEC or other bDMARDs. Clinical variables were extracted using EHRead® technology based on Systemized Nomenclature of Medicine-Clinical Terms (SNOMED CT) terminology.
Results:
Out of 887,735 patients, 758 were included, of which 328 had axSpA 58.5% male; mean (SD) age of 50.7 (12.7) years, 365 PsA 54.8% female, 53.9 (12.4) years, and 65 non-classified SpA. Mean (SD) time since diagnosis was 36.8 (61.0) and 24.1 (35.2) months for axSpA and PsA, respectively. Only 116 axSpA patients (35.3%) had available Ankylosing Spondylitis Disease Activity Score (ASDAS) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at bDMARD onset, of which 61 presented active disease. Disease Activity in PSoriatic Arthritis (DAPSA) or Disease Assessment Score - 28 joints (DAS-28) values at bDMARD onset were available for only 61 PsA (16.7%) patients, with 23 of them having active disease. The number of patients with available tender joint count or swollen joint count assessment was 68 (20.7%) and 59 (18%) for axSpA, and 115 (31.5%) and 119 (32.6%) for PsA, respectively. SEC was used in 63 (19.2%) axSpA patients and in 63 (17.3%) PsA patients.
Conclusion:
Using NLP, the study showed that around one-third of axSpA and one-sixth of PsA patients have disease activity assessments with ASDAS/BASDAI or DAPSA/DAS-28, respectively, highlighting an area of improvement in these patients’ management.
Plain language summary
Investigating axial spondyloarthritis and psoriatic arthritis patients using natural language processing
We conducted a study in Spain to better understand patients with specific rheumatic conditions known as axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). To analyze their characteristics, we used a computer technology called EHRead, which uses Natural Language Processing (NLP) to analyze free text from electronic health records. Out of a large group of patients, we focused on 758 individuals who had axSpA or PsA. Most of the axSpA patients were men, and they were around 51 years old on average. For the PsA patients, most were women, and their average age was about 54 years. We analyzed outcomes and treatments of these patients. Our findings showed that we can describe and assess a cohort of patients from real world using NLP. Besides, only about one-third of axSpA patients and one-sixth of PsA patients had their respective outcomes completely assessed, which indicates that there is potential room for improvement in the management of axSpA and PsA. The most promising feature in our study is the use of NLP, an artificial intelligence technology that helps us understand information in medical records written in free text. This can help us explore the characteristics of patients and their management in the real world, bringing an opportunity to enhance the care of patients with axSpA and PsA.
El proceso abreviado es una figura jurídica empleada en varios sistemas judiciales internacionales con el propósito de simplificar y acelerar la tramitación de ciertos delitos. En líneas generales, ...el proceso abreviado tiende a ser aplicado en delitos de menor complejidad, en los cuales la culpabilidad del acusado es manifiesta y no existen disputas sustanciales sobre los hechos. Su finalidad es garantizar un juicio rápido y eficaz sin menoscabar los derechos procesales del acusado. A medida que los sistemas legales evolucionan, la implementación y características del proceso abreviado pueden variar de un país a otro, siendo las leyes y regulaciones locales las que determinan su utilización y aplicación.
Maximal-safe resection has been shown to improve overall survival in elderly patients with glioblastoma in observational studies, however, the only clinical trial comparing resection versus biopsy in ...elderly patients with surgically-accessible glioblastoma showed no improvements in overall survival. A meta-analysis is needed to assess whether surgical resection of glioblastoma in older patients improves surgical outcomes when compared to biopsy alone.PURPOSEMaximal-safe resection has been shown to improve overall survival in elderly patients with glioblastoma in observational studies, however, the only clinical trial comparing resection versus biopsy in elderly patients with surgically-accessible glioblastoma showed no improvements in overall survival. A meta-analysis is needed to assess whether surgical resection of glioblastoma in older patients improves surgical outcomes when compared to biopsy alone.A search was conducted until October 9th, 2023, to identify published studies reporting the clinical outcomes of glioblastoma patients > 65 years undergoing resection or biopsy (PubMed, MEDLINE, EMBASE, and COCHRANE). Primary outcomes were overall survival (OS), progression-free survival (PFS), and complications. We analyzed mean difference (MD) and hazard ratio (HR) for survival outcomes. Postoperative complications were analyzed as a dichotomic categorical variable with risk ratio (RR).METHODSA search was conducted until October 9th, 2023, to identify published studies reporting the clinical outcomes of glioblastoma patients > 65 years undergoing resection or biopsy (PubMed, MEDLINE, EMBASE, and COCHRANE). Primary outcomes were overall survival (OS), progression-free survival (PFS), and complications. We analyzed mean difference (MD) and hazard ratio (HR) for survival outcomes. Postoperative complications were analyzed as a dichotomic categorical variable with risk ratio (RR).From 784 articles, 20 cohort studies and 1 randomized controlled trial met our inclusion criteria, considering 20,523 patients for analysis. Patients undergoing surgical resection had an overall survival MD of 6.13 months (CI 95%=2.43-9.82, p = < 0.001) with a HR of 0.43 (95% CI = 0.35-0.52, p = < 0.00001). The progression-free survival MD was 2.34 months (95%CI = 0.79-3.89, p = 0.003) with a 0.50 h favoring resection (95%CI = 0.37-0.68, p = < 0.00001). The complication RR was higher in the resection group favoring biopsy (1.49, 95%CI = 1.06-2.10).RESULTSFrom 784 articles, 20 cohort studies and 1 randomized controlled trial met our inclusion criteria, considering 20,523 patients for analysis. Patients undergoing surgical resection had an overall survival MD of 6.13 months (CI 95%=2.43-9.82, p = < 0.001) with a HR of 0.43 (95% CI = 0.35-0.52, p = < 0.00001). The progression-free survival MD was 2.34 months (95%CI = 0.79-3.89, p = 0.003) with a 0.50 h favoring resection (95%CI = 0.37-0.68, p = < 0.00001). The complication RR was higher in the resection group favoring biopsy (1.49, 95%CI = 1.06-2.10).Our meta-analysis suggests that upfront resection is associated with improved overall survival and progression-free survival in elderly patients with newly diagnosed glioblastoma over biopsy. However, postoperative complications are more common with resection. Future clinical trials are essential to provide more robust evaluation in this challenging patient population.CONCLUSIONSOur meta-analysis suggests that upfront resection is associated with improved overall survival and progression-free survival in elderly patients with newly diagnosed glioblastoma over biopsy. However, postoperative complications are more common with resection. Future clinical trials are essential to provide more robust evaluation in this challenging patient population.
The nature of e-commerce prevents the perception of the intrinsic and sensory attributes of wine. In the virtual environment, visual cues allow consumers to perceive the product, determine their ...attitude and form a preference. Users will choose one product or another based on the visual appeal of the advertisements they have seen. Wine marketers must consider the importance of the advertisement elements and attract the consumer’s attention. Optimizing the elements included in these messages can help capture consumers’ attention and achieve a higher click-through rate on the ads. The main objective of this work is to analyse the awareness that different advertisements achieve. Specifically, we use a 2 × 2 × 2 experimental design where we manipulate the packaging format (single bottle vs. pack), labelling (bottle without label vs. labelled bottle) for wine ads (white and red). To analyse attention, we used an eye-tracking methodology. The main results suggest that attention is captured more quickly with an individual bottle without a label than with a particular bottle with a label in Google ads. However, ads showing packs of bottles with labels get more attention than ads using packs of bottles without labels.
Hepatocellular carcinoma (HCC) is a primary liver tumor with high lethality and increasing incidence worldwide. While tumor resection or liver transplantation is effective in the early stages of the ...disease, the therapeutic options for advanced HCC remain limited and the benefits are temporary. Thus, novel therapeutic targets and more efficacious treatments against this deadly cancer are urgently needed. Here, we investigated the pathogenetic and therapeutic role of eukaryotic initiation factor 4A1 (eIF4A1) in this tumor type. We observed consistent eIF4A1 upregulation in HCC lesions compared with non-tumorous surrounding liver tissues. In addition,
levels were negatively correlated with the prognosis of HCC patients. In HCC lines, the exposure to various eIF4A inhibitors triggered a remarkable decline in proliferation and augmented apoptosis, paralleled by the inhibition of several oncogenic pathways. Significantly, anti-growth effects were achieved at nanomolar concentrations of the eIF4A1 inhibitors and were further increased by the simultaneous administration of the pan mTOR inhibitor, Rapalink-1. In conclusion, our results highlight the pathogenetic relevance of eIF4A1 in HCC and recommend further evaluation of the potential usefulness of pharmacological combinations based on eIF4A and mTOR inhibitors in treating this aggressive tumor.
Solid-state fermentation (SSF) is used in enzyme and antibiotic production, bioethanol and biodiesel as an alternative energy source, biosurfactants with environmental goals, and the production of ...organic acids and bioactive compounds. The present project determined the quantity of secondary metabolites and the antioxidant activity of the extracts obtained by the solid-state fermentation of apple and agave mezcalero bagasse over 28 days, inoculated with the Pleurotus ostreatus strain. The extraction was carried out with three solvents: acetone and water (80:20 v/v), 100% methanol and 100% water. The results showed a higher presence of phenolic compounds, flavonoids, total triterpenes and antioxidant activity in the apple bagasse from the SSF on day 21 in the extract of acetone and water (80:20 v/v), 100% methanol and aqueous; while the agave bagasse showed a significant presence of phenolic compounds and flavonoids only in the aqueous extract. In conclusion, the presence of secondary metabolites exhibiting antioxidant activities from the solid-state fermentation in the residues of the cider and mezcal industry is an alternative use for wasted raw material, plus, it reduces the pollution generated from the agroindustrial residues.
La agroindustria genera cantidades importantes de residuos lignocelulósicos. Estos son utilizados como sustrato en la producción de hongos del género Pleurotus, que a través de la fermentación en ...estado sólido (FES) producen metabolitos secundarios. El objetivo de este trabajo fue determinar la cantidad de compuestos fenólicos totales y la actividad antioxidante de extractos de metanol obtenidos de la FES en bagazo de manzana con la cepa Pleurotus ostreatus durante 28 días. La fermentación sólida se realizó en los días 0, 7, 14, 21 y 28 de los extractos de metanol. Posteriormente, se evaluaron el contenido de compuestos fenólicos totales y la actividad antioxidante por los métodos 1,1-difenil-2-picrilhidracilo (DPPH•) y 2,2’-azino-bis (3-etilbenzotiazolina)-6 sulfonato de amonio (ABTS+). Las 45 muestras fueron analizadas a través de un análisis de varianza y prueba de medias de Tukey. Los resultados mostraron la biosíntesis de compuestos fenólicos totales a partir del día 21 de la FES, con una concentración de 0,39 ± 0,07 mg equivalentes de ácido gálico/g sustrato en base seca (mg de EAG/g sustrato bs). La actividad antioxidante en ambos métodos también se manifestó en el día 21 con actividades equivalentes, de 342,10 ± 1,08 mg/mL para DPPH y 323,02 mg/mL en ABTS. En consecuencia, los compuestos fenólicos extraídos de la FES del residuo de manzana con la cepa P. ostreatus pueden considerarse como una alternativa de valorización de un subproducto que actualmente es considerado como un desecho agroindustrial.
On 2011 October 8, the Earth crossed the dust trails left by comet 21P/Giacobini-Zinner during its 19th and 20th century perihelion approaches with the comet being close to perihelion. The geometric ...circumstances of that encounter were thus favourable to produce a meteor storm, but the trails were much older than in the 1933 and 1946 historical encounters. As a consequence the 2011 October Draconid display exhibited several activity peaks with Zenithal Hourly Rates of about 400 meteors h−1. In fact, if the display had not been forecasted, it could have passed almost unnoticed as was strongly attenuated for visual observers due to the Moon. This suggests that most meteor storms of a similar nature could have passed historically unnoticed under unfavourable weather and Moon observing conditions. The possibility of obtaining information on the physical properties of cometary meteoroids penetrating the atmosphere under low geocentric velocity encounter circumstances motivated us to set up a special observing campaign. Added to the Spanish Fireball Network wide-field all-sky and CCD video monitoring, other high-sensitivity 1/2 arcsec black and white CCD video cameras were attached to the modified medium-field lenses for obtaining high-resolution orbital information. The trajectory, radiant and orbital data of October 16 Draconid meteors observed at multiple stations are presented. The results show that the meteors appeared from a geocentric radiant located at α = 263.0 ± 0
4 and δ = +55.3 ± 0
3 that is in close agreement with the radiant predicted for the 1873-1894 and the 1900 dust trails. The estimated mass of material from 21P/Giacobini-Zinner delivered to Earth during the 6 h outburst was around 950 ± 150 kg.
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