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Over the past twenty years, a substantial amount of research has been performed to expand the modeling capabilities of energy geostructures: innovative earth-contact structures that provide combined structural support and renewable energy supply. Several analytical and semi-analytical solutions have been made available for describing the thermo-mechanical behavior of cylindrical energy geostructures such as energy piles. However, no analytical solutions for capturing the thermo-mechanical behavior of plane energy geostructures such as energy walls and slabs have been developed until recently. This paper summarizes the essential features of the first analytical solution available for describing the thermo-mechanical behavior of plane energy geostructures. This analytical solution extends Winkler’s model for a beam resting on an elastic soil mass to non-isothermal conditions, allowing to quantify the effects of temperature variations, axial loads, transversal loads and bending moments applied to plane energy geostructures. Such an analytical solution can be used in the analysis of an elementary unit represented by a single beam as well as complex plane energy geostructures using the superposition principle. Based on the preceding capabilities, the proposed analytical solution may effectively serve the analysis or design of plane energy geostructures under the influence of mechanical and/or thermal loads.

The subsurface represents space and resource of ever-growing importance to meet human activity needs associated with the availability of built environments and energy. So-called energy geostructures represent a breakthrough technology in this context. By integrating the structural support role of earth-contact structures with the heating-cooling role of shallow geothermal heat exchangers, energy geostructures can sustain or enclose built environments while providing them with renewable thermal energy. Despite such promising features, the integrated roles of energy geostructures pose various challenges to understand their behavior and performance, and to address the related analysis and design. Appropriate formulation and application of scientific theory are crucial for the successful analysis and design of energy geostructures. This Bright Spark Lecture Paper presents selected theory for addressing the behavior and performance of energy geostructures, and discusses the application of this theory to analysis and design. In this context, the work focuses on energy piles and barrettes, energy tunnels, as well as energy walls and slabs. The ultimate goal of this paper is to provide competence for facilitating future research and development of energy geostructures across science and engineering.

To date, the majority of the available studies on the volume change behavior of soils under non- isothermal conditions have focused on fine-grained soils. Only a limited number of investigations have been made available about coarse-grained soils despite their abundance in practice, with contradictory features. To enrich the current knowledge about the volume change behavior of coarse-grained soils under non-isothermal conditions, this investigation presents the results of oedometric tests with temperature control performed on saturated sand. The influence of relative density on the volume change behavior of the tested material under non-isothermal conditions is investigated under a minimal level of applied vertical effective stress. The results show an expansive volume change upon heating and contractive volume change upon cooling for all relative densities. The magnitude of the contraction is more significant than that of the expansion, leading to a residual contractive volume change after one cycle of heating and cooling. The results of this study enrich the current literature about the volume change behavior of coarse-grained soils under non-isothermal conditions. Such competence may be considered for applications at the interface of geomechanics and energy wherein temperature variations occur and characterize the response of coarse-grained soils.

The application of a direct current electric field to porous materials such as soils in the form of an electrokinetic treatment induces a variety of multiphysical phenomena. Critical phenomena involved during an electrokinetic treatment of soils are electrical migration (i.e., movement of ions), electroosmosis (i.e., movement of water), electrolysis (i.e., breakdown of chemical compounds), and electrochemical reactions (i.e., oxidation/reduction and precipitation/mineralization reactions). Such phenomena lead to changes in the structure of soils. As changes in the structure of soils induce variations in their properties and behaviors (e.g., thermo-hydro-mechanical), electrokinetic treatments represent resourceful means to address broad geoengineering challenges. The purpose of this paper is to highlight the potential of electrokinetic treatments as versatile techniques capable of providing solutions for diverse geoengineering applications via a controllable change of the properties and behaviors of soils. From this perspective, this work specifically encompasses electrokinetically induced phenomena in soils and expands on opportunities in the context of geoenergy applications, among others, which can be mediated by electrokinetic treatments.

In recent years, Artificial Intelligence (AI) methods, specifically Machine Learning (ML) models, have been providing outstanding results in different areas of knowledge, with the health area being one of its most impactful fields of application. However, to be applied reliably, these models must provide users with clear, simple, and transparent explanations about the medical decision-making process. This systematic review aims to investigate the use and application of explainability in ML models used in brain disease studies. A systematic search was conducted in three major bibliographic databases, Web of Science, Scopus, and PubMed, from January 2014 to December 2023. A total of 133 relevant studies were identified and analyzed out of a total of 682 found in the initial search, in which the explainability of ML models in the medical context was studied, identifying 11 ML models and 12 explainability techniques applied in the study of 20 brain diseases.

Chromatin three-dimensional (3D) organization inside the cell nucleus determines the separation of euchromatin and heterochromatin domains. Their segregation results in the definition of active and inactive chromatin compartments, whereby the local concentration of associated proteins, RNA and DNA results in the formation of distinct subnuclear structures. Thus, chromatin domains spatially confined in a specific 3D nuclear compartment are expected to share similar epigenetic features and biochemical properties, in terms of accessibility and solubility. Based on this rationale, we developed the 4f-SAMMY-seq to map euchromatin and heterochromatin based on their accessibility and solubility, starting from as little as 10 000 cells. Adopting a tailored bioinformatic data analysis approach we reconstruct also their 3D segregation in active and inactive chromatin compartments and sub-compartments, thus recapitulating the characteristic properties of distinct chromatin states. A key novelty of the new method is the capability to map both the linear segmentation of open and closed chromatin domains, as well as their compartmentalization in one single experiment., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Metabolic alterations in cancers can be exploited for diagnostic, prognostic, and therapeutic purposes. This is exemplified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET), an imaging tool that relies on enhanced glucose uptake by tumors for diagnosis and staging. By performing transcriptomic analysis of breast cancer (BC) samples from patients stratified by FDG-PET, a 54-gene signature (PETsign) is identified that recapitulates FDG uptake. PETsign is independently prognostic of clinical outcome in luminal BCs, the most common and heterogeneous BC molecular subtype, which requires improved stratification criteria to guide therapeutic decision-making. The prognostic power of PETsign is stable across independent BC cohorts and disease stages including the earliest BC stage, arguing that PETsign is an ab initio metabolic signature. Transcriptomic and metabolomic analysis of BC cells reveals that PETsign predicts enhanced glycolytic dependence and reduced reliance on fatty acid oxidation. Moreover, coamplification of PETsign genes occurs frequently in BC arguing for their causal role in pathogenesis. CXCL8 and EGFR signaling pathways feature strongly in PETsign, and their activation in BC cells causes a shift toward a glycolytic phenotype. Thus, PETsign serves as a molecular surrogate for FDG-PET that could inform clinical management strategies for BC patients., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

A cerebral arteriovenous malformation (AVM) is a tangle of abnormal blood vessels that irregularly connects arteries and veins. Stereotactic radiosurgery (SRS) has been shown to be an effective treatment for AVM patients, but the factors associated with AVM obliteration remains a matter of debate. In this study, we aimed to develop a model that can predict whether patients with AVM will be cured 36 months after intervention by means of SRS and identify the most important predictors that explain the probability of being cured. A machine learning (ML) approach was applied using decision tree (DT) and logistic regression (LR) techniques on historical data (sociodemographic, clinical, treatment, angioarchitecture, and radiosurgery procedure) of 202 patients with AVM who underwent SRS at the Instituto de Radiocirugía del Perú (IRP) between 2005 and 2018. The LR model obtained the best results for predicting AVM cure with an accuracy of 0.92, sensitivity of 0.93, specificity of 0.89, and an area under the curve (AUC) of 0.98, which shows that ML models are suitable for predicting the prognosis of medical conditions such as AVM and can be a support tool for medical decision-making. In addition, several factors were identified that could explain whether patients with AVM would be cured at 36 months with the highest likelihood: the location of the AVM, the occupation of the patient, and the presence of hemorrhage.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges because of subsequent waves and long-term consequences of great concern. Here, we chart the molecular basis of COVID-19 pathogenesis by analyzing patients' immune responses at single-cell resolution across disease course and severity. This approach confirms cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identifies a severity-associated activation of the receptor for advanced glycation endproducts (RAGE) pathway in monocytes. In vitro THP1-based experiments indicate that monocytes bind the SARS-CoV-2 S1-receptor binding domain (RBD) via RAGE, pointing to RAGE-Spike interaction enabling monocyte infection. Thus, our results demonstrate that RAGE is a functional receptor of SARS-CoV-2 contributing to COVID-19 severity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

CD8 + T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8 + T effector memory cells (T EM ) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8 + T cells. As a consequence of the contact-mediated interaction with neutrophils, CD8 + T cells are skewed to produce high levels of GZMK, which in turn decreases E-cadherin on the intestinal epithelium and favors tumor progression. Overall, our results highlight the emergence of GZMK high CD8 + T EM in non-metastatic CRC tumors as a hallmark driven by the interaction with neutrophils, which could implement current patient stratification and be targeted by novel therapeutics., (© 2022. The Author(s).)

The aim of this study was to evaluate the systemic redox state and inflammatory markers in intensive care unit (ICU) or non-ICU severe COVID-19 patients during the hospitalization period. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients), 5-7 days after admission (T2: 5-7 days after hospital admission), and at the discharge time from the hospital (T3: 0-72 h before leaving hospital or death) to analyze systemic oxidative stress markers and inflammatory variables. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were analyzed in peripheral granulocytes and monocytes. THP-1 human monocytic cell line was incubated with plasma from non-ICU and ICU COVID-19 patients and cell viability and apoptosis rate were analyzed. Higher total antioxidant capacity, protein oxidation, lipid peroxidation, and IL-6 at hospital admission were identified in both non-ICU and ICU COVID-19 patients. ICU COVID-19 patients presented increased C-reactive protein, ROS levels, and protein oxidation over hospitalization period compared to non-ICU patients, despite increased antioxidant status. Granulocytes and monocytes of non-ICU and ICU COVID-19 patients presented lower MMP and higher ROS production compared to the healthy controls, with the highest values found in ICU COVID-19 group. Finally, the incubation of THP-1 cells with plasma acquired from ICU COVID-19 patients at T3 hospitalization period decreased cell viability and apoptosis rate. In conclusion, disturbance in redox state is a hallmark of severe COVID-19 and is associated with cell damage and death., (© 2022 John Wiley & Sons Ltd.)

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm in dogs and in humans. It is characterized by a remarkable degree of clinical heterogeneity that is not completely elucidated by molecular data. This poses a major barrier to understanding the disease and its response to therapy, or when treating dogs with DLBCL within clinical trials. We performed an integrated analysis of exome (n = 77) and RNA sequencing (n = 43) data in a cohort of canine DLBCL to define the genetic landscape of this tumor. A wide range of signaling pathways and cellular processes were found in common with human DLBCL, but the frequencies of the most recurrently mutated genes (TRAF3, SETD2, POT1, TP53, MYC, FBXW7, DDX3X and TBL1XR1) differed. We developed a prognostic model integrating exonic variants and clinical and transcriptomic features to predict the outcome in dogs with DLBCL. These results comprehensively define the genetic drivers of canine DLBCL and can be prospectively utilized to identify new therapeutic opportunities., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Gut Microbiota (GM) dysbiosis associates with Atherosclerotic Cardiovascular Diseases (ACVD), but whether this also holds true in subjects without clinically manifest ACVD represents a challenge of personalized prevention. We connected exposure to diet (self-reported by food diaries) and markers of Subclinical Carotid Atherosclerosis (SCA) with individual taxonomic and functional GM profiles (from fecal metagenomic DNA) of 345 subjects without previous clinically manifest ACVD. Subjects without SCA reported consuming higher amounts of cereals, starchy vegetables, milky products, yoghurts and bakery products versus those with SCA (who reported to consume more mechanically separated meats). The variety of dietary sources significantly overlapped with the separations in GM composition between subjects without SCA and those with SCA (RV coefficient between nutrients quantities and microbial relative abundances at genus level = 0.65, p -value = 0.047). Additionally, specific bacterial species ( Faecalibacterium prausnitzii in the absence of SCA and Escherichia coli in the presence of SCA) are directly related to over-representation of metagenomic pathways linked to different dietary sources (sulfur oxidation and starch degradation in absence of SCA, and metabolism of amino acids, syntheses of palmitate, choline, carnitines and Trimethylamine n -oxide in presence of SCA). These findings might contribute to hypothesize future strategies of personalized dietary intervention for primary CVD prevention setting.

As of 16 May 2020, the number of confirmed cases and deaths in Brazil due to COVID-19 hit 233,142 and 15,633, respectively, making the country one of the most affected by the pandemic. The State of São Paulo (SSP) hosts the largest number of confirmed cases in Brazil, with over 60,000 cases to date. Here we investigate the spatial distribution and spreading patterns of COVID-19 in the SSP by mapping the spatial autocorrelation and the clustering patterns of the virus in relation to the population density and the number of hospital beds. Clustering analysis indicated that São Paulo City is a significant hotspot for both the confirmed cases and deaths, whereas other cities across the state were less affected. Bivariate Moran's I showed a low relationship between the number of deaths and population density, whereas the number of hospital beds was less related, implying that the fatality depends substantially on the actual patients' conditions. Multivariate Local Geary showed a positive relationship between the number of deaths and population density, with two cities near São Paulo City being negatively related; the relationship between the number of deaths and hospital beds availability in the São Paulo Metropolitan Area was basically positive. Social isolation measures throughout the State of São Paulo have been gradually increasing since early March, an action that helped to slow down the emergence of the new confirmed cases, highlighting the importance of the safe-distancing measures in mitigating the local transmission within and between cities in the state.

In this present research, we assessed the performance of band algorithms in estimating chlorophyll-a (Chl-a) concentration based on bands of two new sensors: Operational Land Imager onboard Landsat-8 satellite (OLI/Landsat-8), and MultiSpectral Instrument onboard Sentinel-2A (MSI/Sentinel-2A). Band combinations designed for Thematic Mapper onboard Landsat-5 satellite (TM/Landsat-5) and MEdium Resolution Imaging Spectrometer onboard Envisat platform (MERIS/Envisat) were adapted for OLI/Landsat-8 and MSI/Sentinel-2A bands. Algorithms were calibrated using in situ measurements collected in three field campaigns carried out in different seasons. The study area was the Barra Bonita hydroelectric reservoir (BBHR), a highly productive aquatic system. With exception of the three-band algorithm, the algorithms were spectrally few affected by sensors changes. On the other hands, algorithm performance has been hampered by the bio-optical difference in the reservoir sections, drought in 2014 and pigment packaging.

Tumors driven by activation of the transcription factor MYC generally show oncogene addiction. However, the gene expression programs that depend upon sustained MYC activity remain unknown. In this study, we employed a mouse model of liver carcinoma driven by a reversible tet-MYC transgene, combined with chromatin immunoprecipitation and gene expression profiling to identify MYC-dependent regulatory events. As previously reported, MYC-expressing mice exhibited hepatoblastoma- and hepatocellular carcinoma-like tumors, which regressed when MYC expression was suppressed. We further show that cellular transformation, and thus initiation of liver tumorigenesis, were impaired in mice harboring a MYC mutant unable to associate with the corepressor protein MIZ1 (ZBTB17). Notably, switching off the oncogene in advanced carcinomas revealed that MYC was required for the continuous activation and repression of distinct sets of genes, constituting no more than half of all genes deregulated during tumor progression and an even smaller subset of all MYC-bound genes. Altogether, our data provide the first detailed analysis of a MYC-dependent transcriptional program in a fully developed carcinoma and offer a guide to identifying the critical effectors contributing to MYC-driven tumor maintenance. Cancer Res; 76(12); 3463-72. ©2016 AACR., (©2016 American Association for Cancer Research.)

The tumor suppressor p53 is a transcription factor that coordinates the cellular response to DNA damage. Here we provide an integrated analysis of p53 genomic occupancy and p53-dependent gene regulation in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation, providing insight into general principles of p53 activity in vivo. In unstressed conditions, p53 bound few genomic targets; induction of p53 by ionizing radiation increased the number of p53 bound sites, leading to highly overlapping profiles in the different cell types. Comparison of these profiles with chromatin features in unstressed B cells revealed that, upon activation, p53 localized at active promoters, distal enhancers, and a smaller set of unmarked distal regions. At promoters, recognition of the canonical p53 motif as well as binding strength were associated with p53-dependent transcriptional activation, but not repression, indicating that the latter was most likely indirect. p53-activated targets constituted the core of a cell type-independent response, superimposed onto a cell type-specific program. Core response genes included most of the known p53-regulated genes, as well as many new ones. Our data represent a unique characterization of the p53-regulated response to ionizing radiation in vivo.

The efficacy of curative surgery for lung cancer could be largely improved by non-invasive screening programs, which can detect the disease at early stages. We previously showed that 18% of screening-identified lung cancers demonstrate a normal karyotype and, following high-density genome scanning, can be subdivided into samples with 1) numerous; 2) none; and 3) few copy number alterations. Whole exome sequencing was applied to the two normal karyotype, screening-detected lung cancers, constituting group 2, as well as normal controls. We identified mutations in both tumors, including KEAP1 (commonly mutated in lung cancers) in one, and TP53, PMS1, and MSH3 (well-characterized DNA-repair genes) in the other. The two normal karyotype screening-detected lung tumors displayed a typical lung cancer mutational profile that only next generation sequencing could reveal, which offered an additional contribution to the over-diagnosis bias concept hypothesized within lung cancer screening programs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To determine the most common tracheal points of resistance during orotracheal insertion of a fiberoptic tube in a mannequin by applying a maneuver algorithm to overcome the resistance., Method: Four study groups were established to compare 2 types of endotracheal tube: a standard tube and a reinforced flexible tube with an internal diameter of 7.5 mm. The tubes were used on their own or in combination with a Williams airway intubator. Two fiberoptic bronchoscopes were used, one to perform the test intubation and the other to observe the location of resistance and the effectiveness of the maneuvers for overcoming it. The degree of resistance was scored using a modified Jones scale, from 0 (intubation without resistance) to 4 (intubation impossible); location of resistance and time required for each intubation were also recorded., Results: A total of 250 oral intubations were performed. Resistance was encountered in 75.2% of the cases. The main locations of obstruction were the right arytenoid cartilage and the posterior commissure. In 89.6% of the cases, intubation of the trachea was achieved without maneuvering or with a 90 degrees counterclockwise rotation. Statistically significant differences were found in resistance and intubation time when the reinforced flexible tube was used with the Williams intubator., Conclusions: Rotating the tube 90 degrees counterclockwise was an effective maneuver for overcoming resistance. The combination of a reinforced flexible tube and a Williams intubator was associated with less resistance and shorter intubation times.

The aim of the present study was to investigate the effect of intraperitoneal administration of caffeic acid (0.5, 1, 2, 4 or 8 mg/kg) on elevated plus-maze and open field tasks in rats and its possible neuroprotection/neurotoxicity using the comet assay. Caffeic acid at 1 mg/kg increased the number of entries and the time spent in the open arms on plus-maze, suggesting an anxiolytic-like effect when used in lower doses without affecting locomotion and exploration on the open field. Furthermore, a protective effect against hydrogen peroxide-induced oxidative damage on brain tissue was observed through the treatment with caffeic acid at 1 and 8 mg/kg. However, in the highest dose, caffeic acid induced DNA damage in brain tissue.

This study was aimed to investigate the effects of the long-term oral exposure to aluminum sulfate on hematological parameters in rats. For this purpose, 24 adult female Wistar rats were divided in three groups with 8 animals each (control, citrate, and citrate plus aluminum groups). Rats from control and citrate groups had free access to tap water and to a sodium citrate solution (35 mM), respectively. Rats from citrate plus aluminum group received, as unique source of liquid, an aluminum sulfate solution (30 mM) diluted in the above-mentioned sodium citrate solution, ad libitum. After the treatment period (18 months), aluminum-exposed rats showed a significant decrease in the number of red blood cells, blood hemoglobin concentration and hematocrit when compared to rats from the control group. Serum iron levels were also significantly lower in citrate plus aluminum group, whereas total iron binding capacity did not change after citrate plus aluminum exposure. Erythrocyte thiobarbituric acid-reactive substances (TBARS) and nonprotein thiols (NPSH) levels, erythrocyte osmotic fragility and hepatic delta-aminolevulinic acid dehydratase (delta-ALA-D) activity did not change after treatment with citrate plus aluminum. Conversely, aluminum exposure increased delta-ALA-D activity in bone marrow. The present results indicate that long-term oral exposure to low doses of aluminum sulfate promotes alterations on erythrocyte parameters in rats, probably as a consequence of alterations in the iron status. In addition, although the details of the underlying mechanism remain unclear, our study reports, for the first time, a stimulatory effect of chronic aluminum exposure on bone marrow delta-ALA-D activity.

Objective: We measured the in vitro effects of mercuric chloride (Hg2+) and selenite (Se4+) on hepatic 2-thiobarbituric acid-reactive substances (TBARS) and non-protein sulfhydryl (NPSH) levels of rats fed diets enriched with polyunsaturated or saturated fatty acids with and without cholesterol., Methods: Male Wistar rats (21 d old) were assigned to one of four groups and fed diets containing 20% soybean oil, 20% soybean oil plus 1% cholesterol, 20% coconut oil, or coconut oil plus 1% cholesterol. After the feeding period (6 wk), body weight gain was equal in all groups. TBARS levels and NPSH content were measured after in vitro exposure to mercuric chloride (100 microM) and sodium selenite (25 microM) for 1 h., Results: The lipid peroxidation, measured as TBARS levels in the control group, were statistically higher in hepatic homogenates of rats fed diets containing soybean oil than in groups fed coconut oil (P = 0.009). However, cholesterol supplementation did not change TBARS levels. Selenite alone did not modify TBARS production, whereas mercury alone significantly increased TBARS levels. Moreover, Se4+ protected against mercury-induced lipid peroxidation only in rats fed diets containing coconut oil. In the control group, dietary fat acids did not change NPSH levels. Selenite produced higher oxidative effects toward NPSH content, whereas Hg2+ decreased NPSH levels only in liver from rats fed diets containing soybean oil. NPSH levels were higher after concomitant exposure to Se4+ and Hg2+ chloride that after exposure to Se4+ alone, suggesting an interaction between Hg2+ and Se4+. Catalase activity was higher in animals fed diets containing soybean oil. Dietary cholesterol decreased glutathione peroxidase activity., Conclusion: Together these results indicated that the protective effect of Se4+ against mercury-induced lipid peroxidation depends on dietary fat saturation.

S100B is a calcium-binding protein expressed and secreted by astrocytes, playing a neurotrophic role in neighboring cells. A protective role of the S100B against glutamate-induced excitotoxicity has recently been proposed. We investigated S100B secretion in rat hippocampal astrocytes exposed to high concentrations of glutamate during serum deprivation (stimulated condition) or not (basal condition), for 30 min. Glutamate at 1 mM had no effect on basal secretion of S100B, but it decreased S100B secretion in serum-deprived astrocytes after 1 h. Secretion was inhibited by Rp-cAMPS or H89. In addition, serum deprivation was accompanied by a transitory increase of intracellular content of cAMP. Our results suggest that high levels of glutamate in a serum-deprived condition could impair S100B secretion from hippocampal astrocytes., (Copyright 2002 Lippincott Williams & Wilkins.)