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In an industrial context, selecting an appropriate crystal plasticity (CP) model that balances efficiency and accuracy when modelling deformation texture (DT) is crucial. This study compared DTs in IF-steel after undergoing cold rolling reductions using different CP models for two input texture scenarios. Three mean-field (MFCP) models were utilised in their most basic configurations, without considering grain fragmentation or strain hardening, in addition to a dislocation-density-based full-field (FFCP) model. The study quantitatively compared the results from the MFCP models with those from the FFCP models. Furthermore, all CP model results were compared with experimental textures obtained from electron back-scatter diffraction (EBSD) experiments. The findings revealed that certain MFCP models could predict deformation textures as accurately as the FFCP models. Notably, one of the MFCP models exhibited a superior match with experimental textures for cold rolling reductions at 60%. Upon closer examination of specific crystallographic components, it was observed that MFCP models tended to predict a stronger {111}〈211〉 component, while the full-field model favours the {111}〈011〉 component. It is crucial to emphasise the importance of quantifying the texture within individual grains when assessing the macro-level deformation texture in rolling simulations.

In this paper we present measurements performed with a Micromegas X-ray detector setup. The detector is a prototype in the context of the BabyIAXO helioscope, which is under construction to search for an emission of the hypothetical axion particle from the Sun. An important component of such a helioscope is a low background X-ray detector with a high efficiency in the 1–10 keV energy range. The goal of the measurement was to study techniques for background discrimination. In addition to common techniques we used a multi-layer veto system designed to tag cosmic-ray induced neutron background. Over an effective time of 52 days, a background level of 8.6 × 10−7 counts keV−1 cm−2 s−1 was reached in a laboratory at above ground level. This is the lowest background level achieved at surface level. In this paper we present the experimental setup, show simulations of the neutron-induced background, and demonstrate the process to identify background signals in the data. Finally, prospects to reach lower background levels down to 10–7 counts keV−1 cm−2 s−1 are discussed.

Haloscopes aim at detecting axions by converting them into photons using high-quality resonant cavities, where the cavity resonance should be tuned with the unknown axion mass. Here, the authors improve exclusion limits using four phase-matched resonant cavities and a fast frequency scanning technique.

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Abstract This article describes BabyIAXO, an intermediate experimental stage of the International Axion Observatory (IAXO), proposed to be sited at DESY. IAXO is a large-scale axion helioscope that will look for axions and axion-like particles (ALPs), produced in the Sun, with unprecedented sensitivity. BabyIAXO is conceived to test all IAXO subsystems (magnet, optics and detectors) at a relevant scale for the final system and thus serve as prototype for IAXO, but at the same time as a fully-fledged helioscope with relevant physics reach itself, and with potential for discovery. The BabyIAXO magnet will feature two 10 m long, 70 cm diameter bores, and will host two detection lines (optics and detector) of dimensions similar to the final ones foreseen for IAXO. BabyIAXO will detect or reject solar axions or ALPs with axion-photon couplings down to g aγ ∼ 1.5 × 10 −11 GeV −1, and masses up to m a ∼ 0.25 eV. BabyIAXO will offer additional opportunities for axion research in view of IAXO, like the development of precision x-ray detectors to identify particular spectral features in the solar axion spectrum, and the implementation of radiofrequency-cavity-based axion dark matter setups.

Los cultivos de cobertura (CC) se utilizan tradicionalmente para controlar problemas de erosión, mejorar la captación, distribución y almacenaje de agua, reducir la compactación, mejorar los balances de carbono y nitrógeno del suelo. Este trabajo pretendió aportar resultados zonales en cuanto a las contribuciones de CC sobre efi ciencia de uso de los recursos y productividad del girasol. Durante 2017 y 2018 se ensayaron en Coronel Suárez (Sudoeste de Buenos Aires) seis CC como antecesores de girasol. Se evaluaron: agua en el suelo, materia seca, nitrógeno y rendimiento.La diferencia en el contenido de agua edáfi ca al secado de los CC respecto al barbecho conven-cional (BC) varió entre -8 y 15 mm. Las efi ciencias de uso de agua (EUA) con respecto al testigo, oscilaron entre 5,59 kg MS mm -1 en vicia (V 1 ) y de 16,16 kg MS mm -1 en avena (A). Los mayores rendimientos de girasol se obtuvieron con V 1 (2379 kg ha -1 ) y los menores con A (1561 kg ha -1 ).

Remote sensing analysis is routinely used to map flooding extent either retrospectively or in near-real time. For flood emergency response, remote-sensing-based flood mapping is highly valuable as it can offer continued observational information about the flood extent over large geographical domains. Information about the floodwater depth across the inundated domain is important for damage assessment, rescue, and prioritizing of relief resource allocation, but cannot be readily estimated from remote sensing analysis. The Floodwater Depth Estimation Tool (FwDET) was developed to augment remote sensing analysis by calculating water depth based solely on an inundation map with an associated digital elevation model (DEM). The tool was shown to be accurate and was used in flood response activations by the Global Flood Partnership. Here we present a new version of the tool, FwDET v2.0, which enables water depth estimation for coastal flooding. FwDET v2.0 features a new flood boundary identification scheme which accounts for the lack of confinement of coastal flood domains at the shoreline. A new algorithm is used to calculate the local floodwater elevation for each cell, which improves the tool's runtime by a factor of 15 and alleviates inaccurate local boundary assignment across permanent water bodies. FwDET v2.0 is evaluated against physically based hydrodynamic simulations in both riverine and coastal case studies. The results show good correspondence, with an average difference of 0.18 and 0.31 m for the coastal (using a 1 m DEM) and riverine (using a 10 m DEM) case studies, respectively. A FwDET v2.0 application of using remote-sensing-derived flood maps is presented for three case studies. These case studies showcase FwDET v2.0 ability to efficiently provide a synoptic assessment of floodwater. Limitations include challenges in obtaining high-resolution DEMs and increases in uncertainty when applied for highly fragmented flood inundation domains.

Abstract TREX-DM is conceived to look for low-mass Weakly Interacting Massive Particles (WIMPs) using a gas Time Projection Chamber equipped with Micromegas readout planes at the Canfranc Underground Laboratory. The detector can hold in the active volume $$\sim 20~l$$ ∼20l of pressurized gas up to 10 bar, corresponding to 0.30 kg of Ar or 0.16 kg of Ne. The Micromegas are read with a self-triggered acquisition, being thresholds below 0.4 keV (electron equivalent) at reach. A low background level in the lowest energy region is another essential requirement. To assess the expected background, all the relevant sources have been considered, including the measured fluxes of gamma radiation, muons and neutrons at the Canfranc Laboratory, together with the activity of most of the components used in the detector and ancillary systems, obtained in a complete assay program. The background contributions have been simulated by means of a dedicated application based on Geant4 and a custom-made code for the detector response. The background model developed for the detector presently installed in Canfranc points to levels from 1 to 10 counts $$\hbox {keV}^{-1}\ \hbox {kg}^{-1}\ \hbox {day}^{-1}$$ keV-1kg-1day-1 in the region of interest, making TREX-DM competitive in the search for low-mass WIMPs. A roadmap to further decrease it down to 0.1 counts $$\hbox {keV}^{-1}\ \hbox {kg}^{-1}\ \hbox {day}^{-1}$$ keV-1kg-1day-1 is underway.

Abstract This paper presents a general procedure based on fracture mechanics models in order to analyze the level of cracking and structural safety in reinforced concrete elements at early ages, depending on the stripping time. Our procedure involves the development of a thermo-mechanical numerical model based on the finite element method that accounts for the change in the mechanical properties of concrete with time. Moreover, fracture mechanisms are analyzed by means of a material damage model, which is characterized via specific experimental results obtained for standard specimens and notched beams under three-point bending testing. The loading conditions are both thermal and mechanical, and are obtained from the hydration process for a given concrete dosage. The presented methodology allows for the determination of the optimal stripping time, whereas it helps assessing the analysis of the cracking and the stress states of the elements under consideration. A practical application, namely the analysis of a retaining wall, is used to validate our methodology, showing its suitability in engineering practice.

The increase of Social Media on the Internet has brought an unprecedented revolution which has changed the existing social communication systems to date. Currently, a high percentage of population in the developed world has a smartphone with Internet connection that allows being permanently connected. This enables new ways of approaching some types of tasks that have traditionally required of simultaneity in space and time, such as the development of creative proposals by a large number of people. Technological advances have allowed, in a few years, the size reduction of a computer to today's mobile devices. Among the multitude of specifications offered by next-generation devices, the continuous evolution of the imaging capture systems is a highlight. The existence of both front-facing and rear cameras, both capable for taking pictures or record video has become widespread in the majority of mobile devices. This paper proposes the use of Social Live Streaming Tools in mobile devices in order to facilitate the development of creative workshops, using the virtual territory as co-creation area with the aim of promoting one-to-many communications, so that a lecturer can perform a mass communication, in real time and delocalized, without losing the possibility of interact with the audience. These tools also allow the possibility for each member of a creative team to swap between different roles (viewer at some times or lecturer at others), thus stimulating the creative process through social participation.

The 2006 Guinsaugon landslide in Saint Bernard, Southern Leyte, is one of the largest known landslides in the Philippines in recent history. It consists of a 15–20 million m3 rockslide-debris avalanche from an approximately 675 m high mountain weakened by continuous movement of the Philippine Fault. The catastrophic Guinsaugon landslide killed 1221 people and displaced 19 000 residents over its 4.5 km path. To investigate the present-day morphology of the scar and potential failure that may occur, analysis of a 5 m resolution InSAR-derived digital elevation model was conducted using Coltop3D and Matterocking software, leading to the generation of a landslide hazard map for the province of Southern Leyte in central Philippines. The dip and dip direction of discontinuity sets that contribute to gravitational failure in mountainous areas of the province were identified and measured using a lower Schmidt–Lambert color scheme. After measurement of the morpho-structural orientations, potential sites of failure were analyzed. Conefall was then utilized to compute the extent of rock mass runout. Results of the analysis show instability in the scarp area of the 2006 Guinsaugon landslide and in adjacent slopes because of the presence of steep discontinuities that range from 45 to 60°. Apart from the 2006 Guinsaugon landslide site, runout models simulated farther rock mass extent in its adjacent slopes, revealing a high potential for fatal landslides to happen in the municipality of Saint Bernard. Concerned agencies may use maps produced in the same manner as this study to identify possible sites where structurally controlled landslides can occur. In a country like the Philippines, where fractures and faults are common, this type of simulated hazard maps would be useful for disaster prevention and facilitate disaster risk reduction efforts for landslide-susceptible areas.

In this work we present a search for (solar) chameleons with the CERN Axion Solar Telescope (CAST). This novel experimental technique, in the field of dark energy research, exploits both the chameleon coupling to matter (βm) and to photons (βγ) via the Primakoff effect. By reducing the X-ray detection energy threshold used for axions from 1 keV to 400 eV CAST became sensitive to the converted solar chameleon spectrum which peaks around 600 eV. Even though we have not observed any excess above background, we can provide a 95% C.L. limit for the coupling strength of chameleons to photons of βγ≲1011 for 1

La intensificación de la agricultura en la región semiárida se caracterizó por una disminución del área des- tinada a pasturas, a favor de la superficie con monocultivo de trigo. En este contexto, la rotación de cultivos, la fertilización, el manejo de los residuos y el agua edáfica son aspectos fundamentales para el aumento de la productividad del trigo en esta región. Se planteó como objetivo cuantificar los cambios cuali y cuantitativos en sistemas de producción sobre algunas propiedades de un suelo de la región semiárida bonaerense, luego de 22 años de producción. El trabajo se realizó en la EEA del INTA Bordenave. Se estudiaron las siguientes secuencias de cultivos: TT LC (monocultivo de trigo con labranza conservacionista (LC), 1983-2006); TT SD (monocultivo de trigo con LC, 1983-1999, y con siembra directa (SD), 1999-2006) y TP (manejo tradicional, un año trigo y un año alternativamente con pastoreo de los rastrojos, 1983-2006). En cada uno se evaluó el carbono orgánico total (COT), el nitrógeno total (Nt), el fósforo extraíble (Pe) y el pH en agua. Se realizó un fraccionamiento por tamaño de partícula, en las que se determinó el CO y N. En general, los niveles de COT mostraron un efecto significativo de la rotación, fertilización y la labranza. En los tratamientos no fertilizados, el manejo tradicional presentó los niveles más altos de COT y el monocultivo las mayores pérdidas. En las parcelas fertilizadas, los niveles de COT fueron significativamente más altos en SD, principalmente en los primeros 5 cm del suelo, mientras que en los suelos con labranza no se observaron diferencias. En 0-20 cm se observó mayor concentración de COP en monocultivo que en manejo tradicional. El Nt fue significativa- mente más alto en el manejo tradicional respecto del monocultivo de trigo sin fertilizante. La SD fue el único sistema que produjo diferencias significativas por efecto de la fertilización. A su vez, la fertilización produjo una tendencia a la acumulación del Pe frente a los no fertilizados en la profundidad (5-10 y 10-20), que fue- ron significativos en los tratamientos con monocultivo. Para las condiciones edafo-climáticas de la región, la inclusión de la SD como práctica de manejo mejoró la condición orgánica del suelo sólo cuando se combinó con el uso de fertilizantes.

La industria del automóvil se enfrenta a una creciente demanda de vehículos de pasajeros más eficientes. Con el fin de disminuir el consumo de energía y la contaminación ambiental, el peso del vehículo tiene que ser reducido, al mismo tiempo que se garantizan altos niveles de seguridad. Ante esta situación, la elección de material se convierte en una decisión crucial en el diseño del vehículo. Como respuesta a las necesidades del sector automovilístico, nuevos aceros avanzados y de alta resistencia, han sido desarrollados por la industria siderúrgica. Dichos tipos de acero ofrecen un excelente equilibrio de precio, peso y propiedades mecánicas.

Chimeric antigen receptor T cell (CAR T cell) therapy has emerged as a prominent adoptive cell therapy and a therapeutic approach of great interest in the fight against cancer. This approach has shown notorious efficacy in refractory hematological neoplasm, which has bolstered its exploration in the field of solid cancers. However, successfully managing solid tumors presents considerable intrinsic challenges, which include the necessity of guiding the modified cells toward the tumoral region, assuring their penetration and survival in adverse microenvironments, and addressing the complexity of identifying the specific antigens for each type of cancer. This review focuses on outlining the challenges faced by CAR T cell therapy when used in the treatment of solid tumors, as well as presenting optimizations and emergent approaches directed at improving its efficacy in this particular context. From precise localization to the modulation of the tumoral microenvironment and the adaptation of antigen recognition strategies, diverse pathways will be examined to overcome the current limitations and buttress the therapeutic potential of CAR T cells in the fight against solid tumors.

Photoaging (PA) is considered a silent disease affecting millions of people globally and is defined as skin damage due to prolonged exposure to ultraviolet radiation (UVR) from the sun. Physiologically, the skin is in a state of renewal and synthesis of components of the extracellular matrix (ECM). However, exposure to UVR affects the production of the ECM, and the functioning and response of skin cells to UVR begins to change, thus expressing clinical and phenotypic characteristics of PA. The primary mechanisms involved in PA are direct damage to the DNA of skin cells, increases in oxidative stress, the activation of cell signaling pathways responsible for the loss of skin integrity, and cytotoxicity. The medical and scientific community has been researching new therapeutic tools that counteract PA, considering that the damage caused by UVR exceeds the antioxidant defense mechanisms of the skin. Thus, in recent years, certain nutraceuticals and phytochemicals have been found to exhibit potential antioxidant and photoprotective effects. Therefore, the main objective of this review is to elucidate the molecular bases of PA and the latest pharmaceutical industry findings on antioxidant treatment against the progression of PA.

Diatoms are one of the main species of interest due to their possible impact on the maintenance of ecosystems, as well as their photosynthetic capacity and biotechnological applications. Reliable, easy, rapid identification of diatoms remains a highly desirable goal to avoid the difficulty for experts in the visual analysis of frustules; a method commonly used to compare the distinctive traits of diatoms, such as ornaments and the marks from images taken by optical and electronic microscopy for identification. This study proposed three simple morphometric methods based on fractal dimension measurements in conjunction with 2D cross-correlation parameters to analyze diatom images. This novel approach demonstrates the differentiation feasibility between a wide variety of diatom species with heterogeneity in their structures and shapes, which could possibly expand the application of this preprocessing process for the identification of new types of images or other biological species.

Background. The nitrogen source in a liquid culture medium for the propagation of entomopathogenic fungi is considered an essential element in fermentation, however, it is one of the most expensive, which makes the search for alternative sources of this nutrient important. Objective. This research compared the production of blastospores obtained by designing different culture media for the GHA strain of Beauveria bassiana based on the nitrogen source used. Methodology. Six media were designed in liquid form, made with various nitrogen sources (sesame flour, amaranth flour, canary seed flour, linseed flour, peanut pericarp flour, oatmeal) with glucose corn as a carbon source for all of them. Additionally, the yield of blastospores obtained at different incubation times, the pH and the viability of the post-fermentation propagules were evaluated. Results. The M8 medium made with peptone and yeast extract as nitrogen sources was the one that obtained the highest concentration with 1.28 × 109 blastospores / mL at 168 hours of incubation. Regarding the fermentation parameters evaluated, the pH ranged between 5.1- 5.5 and the determination of this parameter did not present significant difference with respect to the culture medium used or the day on which it was determined (p ≥ 0.05) while post-fermentation viability was determined. In two solid media, and according to the results in potato dextrose agar the viability ranged between 31-90% on average while in water agar it was 25-90%, the determination of this parameter did not present significant difference with respect to the medium of culture for production of blastospores or to the solid medium in which it was determined (p ≥ 0.05). Implications. The alternate nitrogen sources used did not significantly increase the production of blastospores compared to conventional sources such as peptone and yeast extract, which in a synergistic effect did manage to enhance the production of blastospores. Conclusion. The use of yeast extract and casein peptone in conjunction can increase the yield of blastsopores in a liquid culture medium.

Bacterial resistance is responsible for a wide variety of health problems, both in children and adults. The persistence of symptoms and infections are mainly treated with β-lactam antibiotics. The increasing resistance to those antibiotics by bacterial pathogens generated the emergence of extended-spectrum β-lactamases (ESBLs), an actual public health problem. This is due to rapid mutations of bacteria when exposed to antibiotics. In this case, β-lactamases are enzymes used by bacteria to hydrolyze the beta-lactam rings present in the antibiotics. Therefore, it was necessary to explore novel molecules as potential β-lactamases inhibitors to find antibacterial compounds against infection caused by ESBLs. A computational methodology based on molecular docking and molecular dynamic simulations was used to find new microalgae metabolites inhibitors of β-lactamase. Six 3D β-lactamase proteins were selected, and the molecular docking revealed that the metabolites belonging to the same structural families, such as phenylacridine (4-Ph), quercetin (Qn), and cryptophycin (Cryp), exhibit a better binding score and binding energy than commercial clinical medicine β-lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam. These results indicate that 4-Ph, Qn, and Cryp molecules, homologous from microalgae metabolites, could be used, likely as novel β-lactamase inhibitors or as structural templates for new in-silico pharmaceutical designs, with the possibility of combatting β-lactam resistance

Background and Objective: Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies., Methods: We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024. Network meta-analyses of first-line mHSPC, M0CRPC, and mCRPC therapies were constructed for the five cardiotoxicity metrics defined by the International Cardio-Oncology Society: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Additional Bayesian network meta-analyses also accounted for prior treatment history., Key Findings and Limitations: Thirteen RCTs (16 292 patients) were included. For mHSPC, androgen deprivation therapy (ADT) plus docetaxel (DTX) plus abiraterone acetate (AA) with prednisone (P) demonstrated a significant increase in hypertension and arrhythmias versus ADT + DTX (risk ratio [RR] 2.85, 95% confidence interval [CI] 1.67-4.89, and RR 2.01, 95% CI 1.17-3.44, respectively); however, no corresponding differences were observed between ADT + DTX plus darolutamide (DAR) and ADT + DTX (RR 1.55, 95% CI 0.73-3.30, and RR 0.94, 95% CI 0.63-1.40, respectively). For mCRPC assuming a history of mHSPC treatment, ADT + AA + P plus olaparib (OLA) demonstrated a statistically significant decrease in hypertension versus ADT + AA + P (RR 0.20, 95% CI 0.16-0.26). M0CRPC results were unremarkable., Conclusions and Clinical Implications: For mHSPC, ADT + DTX + DAR demonstrates less cardiotoxicity than ADT + DTX + AA + P due to a lower risk of hypertension and arrhythmias from decreased mineralocorticoid excess. In addition, OLA counterintuitively offers decreased hypertension when superimposed on ADT + AA + P for mCRPC treatment after prior androgen deprivation from mHSPC therapy., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

This study examines the complex interplay of genetic and environmental interactions that shape chronic illness risk. Evidence is mounting for the role of genetic expression and the immune response in the pathogenesis of chronic disease. In the Rio Grande Valley of south Texas, where 90% of the population is Mexican American, chronic illnesses (including obesity, diabetes, nonalcoholic liver disease, and depression) are reaching epidemic proportions. This study leverages an ongoing family study of the genetic determinants of risk for obesity, diabetes, hypertension, hyperlipidemia, and depression in a Mexican American population. Data collected included blood pressure, BMI, hepatic transaminases, HbA1c, depression (BDI-II), acculturation/marginalization (ARSMA-II), and liver health as assessed by elastography. Heritability and genotype-by-environment (G×E) interactions were analyzed, focusing on the marginalization/separation measure of the ARSMA-II. Significant heritabilities were found for traits such as HbA1c (h 2 = 0.52), marginalization (h 2 = 0.30), AST (h 2 = 0.25), ALT (h 2 = 0.41), and BMI (h 2 = 0.55). Genotype-by-environment interactions were significant for HbA1c, AST/ALT ratio, BDI-II, and CAP, indicating that genetic factors interact with marginalization to influence these traits. This study found that acculturation stress exacerbates the genetic response to chronic illness. These findings underscore the importance of considering G×E interactions in understanding disease susceptibility and may inform targeted interventions for at-risk populations. Further research is warranted to elucidate the underlying molecular pathways and replicate these findings in diverse populations.

Snake venoms contain various molecules known for activating innate immunity and causing local effects associated with increased vascular permeability, such as vascular leakage and edema, common symptoms seen in snakebite envenomings. We have demonstrated that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability. This study aimed to explore the functional role of CRiSP isolated from Mojave rattlesnake ( Crotalus scutulatus scutulatus ) venom (Css-CRiSP) on the activation of inflammatory responses in different models. We measured the release of inflammatory mediators in cultured human dermal blood endothelial cells (HDBEC), lymphatic endothelial cells (HDLEC) and monocyte-derived macrophages (MDM) at 0.5, 1, 3, 6, and 24 h after treatment with Css-CRiSP (1 μM). We also determined the acute inflammatory response in BALB/c mice 30 min after intraperitoneal injection of the toxin (2 μg/mouse). Css-CRiSP induced the production of IL-8 and IL-6, but not TNF-α, in HDBEC and HDLEC in a time-dependent manner. In addition, Css-CRiSP significantly enhanced the production of IL-6, TNF-α, IL-8, and IL-1β in MDM. Moreover, it caused a remarkable increase of chemotactic mediators in the exudates of experimental mice. Our results reveal that Css-CRiSPs can promote a sustained release of inflammatory mediators on cell lines and an acute activation of innate immunity in a murine model. These findings contribute to the growing body of evidence supporting the involvement of svCRiSPs in the augmentation of envenomation effects, specifically, the role of svCRiSPs in inducing vascular dysfunction, initiating early inflammatory responses, and facilitating the activation of leukocytes and releasing mediators. These findings will lead to a better understanding of the pathophysiology of envenoming by Mojave rattlesnakes, allowing the development of more efficient therapeutic strategies., Competing Interests: 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., (© 2023 The Authors.)

Increased vascular permeability is a frequent outcome of viperid snakebite envenomation, leading to local and systemic complications. We reported that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability both in vitro and in vivo. They also induce acute activation of several adhesion and signaling molecules that may play a critical role in the pathophysiology of snakebites. Extracellular vesicles (EVs) have gained interest for their diverse functions in intercellular communication, regulating cellular processes, blood-endothelium interactions, vascular permeability, and immune modulation. They also hold potential as valuable biomarkers for diagnosing, predicting, and monitoring therapeutic responses in different diseases. This study aimed to identify proteins in peritoneal exudate and plasma EVs isolated from BALB/c mice following a 30 min post-injection of Crotalus scutulatus scutulatus venom and its purified CRiSP (Css-CRiSP). EVs were isolated from these biofluids using the EVtrap method. Proteomic analysis of exudate- and plasma-derived EVs was performed using LC-MS/MS. We observed significant upregulation or downregulation of proteins involved in cell adhesion, cytoskeleton rearrangement, signal transduction, immune responses, and vesicle-mediated transports. These findings suggest that svCRiSPs play a crucial role in the acute effects of venom and contribute to the local and systemic toxicity of snakebites.

Polyphenols are a diverse and widely distributed class of secondary metabolites, which possess numerous beneficial properties including a modulation of glucose and lipid metabolism. This placebo-controlled human intervention study was performed to explore effects of polyphenol-rich beverage (PRB) uptake on lipid metabolism, as well as DNA integrity. In this case, 36 healthy men were randomly divided to consume either 750 mL of a PRB (containing 51% chokeberry, cranberry, and pomegranate) or a placebo drink daily for eight weeks. Only PRB consumption was found to decrease fat and protein intakes significantly compared to the preceding one-week washout period. During the intervention with PRB an increased fat-free mass was shown after four weeks, whereas a significant elevation in body weight and leptin was observed in placebo group. Blood lipids were not significantly altered after PRB consumption, while triglyceride levels increased after placebo drink intake. In platelets, a significant inhibition of phosphodiesterase (PDE) activity was observed, more pronounced in test group. Consuming the PRB decreased total DNA strand breaks in whole blood as well as H 2 O 2 -induced breaks in isolated lymphocytes. Overall, our study suggested beneficial effects on lipid metabolism by reduced energy intake, modulation of biomarkers such as PDE activity and improved DNA integrity associated with PRB consumption.

The CAST-CAPP axion haloscope, operating at CERN inside the CAST dipole magnet, has searched for axions in the 19.74 μeV to 22.47 μeV mass range. The detection concept follows the Sikivie haloscope principle, where Dark Matter axions convert into photons within a resonator immersed in a magnetic field. The CAST-CAPP resonator is an array of four individual rectangular cavities inserted in a strong dipole magnet, phase-matched to maximize the detection sensitivity. Here we report on the data acquired for 4124 h from 2019 to 2021. Each cavity is equipped with a fast frequency tuning mechanism of 10 MHz/ min between 4.774 GHz and 5.434 GHz. In the present work, we exclude axion-photon couplings for virialized galactic axions down to g aγγ  = 8 × 10 -14 GeV -1 at the 90% confidence level. The here implemented phase-matching technique also allows for future large-scale upgrades., (© 2022. The Author(s).)

Objective: To determine the extent to which Black race is associated with the infant mortality rate (< 365 day, IMR) of births to US-born and foreign-born Latinx women., Methods: Stratified and multivariable binominal log-linear regression analyses were performed on the 2010-2013 National Center for Health Statistics linked birth-death certificate files of singleton infants., Results: The IMR of births to US-born Black Latinx women (N = 54,542) exceeded that of births to US-born White Latinx women (N = 1,320,084): 5.7/1000 vs 4.2/1000, RR = 1.4 (1.2, 1.5). In contrast, the IMR of births to foreign-born Black Latinx women (N = 35,544) approximated that of births to foreign-born White Latinx women (N = 1,372,172): 3.8/1000 vs 3.6/1000, RR = 1.0 (0.9, 1.2) The adjusted (controlling for maternal age, education, prenatal care, high parity, and region of residence) RR of infant mortality for births to US-born and foreign-born Black (versus non-Latinx White) Latinx women equaled 1.4 (1.2, 1.6) and 1.0 (0.8, 1.2), respectively. The adjusted RR of infant mortality for births to US-born and foreign-born White (versus non-Latinx White) Latinx women equaled 1.0 (0.9, 1.0) and 0.8 (0.7, 0.8), respectively., Conclusions: Black race is associated with a 1.4-fold higher IMR among births to US-born Latinx women. A similar phenomenon does not occur among foreign-born Latinx women. These intriguing findings highlight that the social construct of Black race across the life-course of Latinx women are detrimental to infant outcome., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The Swedish version of the patient-reported Clinical Outcomes in Routine Evaluation Outcome Measures (CORE-OM) has demonstrated high reliability and acceptable convergent validity in explanatory factor analyses. However, the fundamental scale properties have not yet been validated according to item response theory. The aim of this study was to analyze the measurement properties of the Swedish CORE-OM in a cohort of psychiatric out-patients with depression and anxiety in a multicultural area and to explore combinations of items based on shorter versions of the scale (CORE-10, CORE-6D) to improve measurement properties., Methods: Data from CORE-OM assessments of 337 patients were analyzed using Rasch analysis. The patients had a mean age of 30 ± 14 years, the majority were women (72%). Requirements for measurement properties were checked: overall model fit, item fit residuals, targeting, internal consistency, differential item functioning and thresholds. Sensitivity to change was also analyzed., Results: The CORE-OM showed high internal consistency (person separation index = 0.947) and adequate targeting, but there was overall model misfit (item trait interaction χ 2  = 917.53, p < 0.001), indication of local dependency, and differential item functioning in 9 items. The risk items showed problems with disordered thresholds. The emotional component of the shorter CORE-6D showed the best fit for our sample. Adding 3 items to include depressive and trauma-related content resulted in a unidimensional 8-item set with acceptable reliability, model fit, targeting and sensitivity to change., Conclusion: For out-patients with diagnosed depression or anxiety in a multicultural area, the Swedish CORE-OM showed high internal consistency, but also validity problems. Based on the shorter CORE-6D version, a unidimensional 8-item set could be an alternative brief measure of psychological distress for this population, but further validity studies are required. Qualitative studies exploring the CORE-OM items in non-native speakers are also warranted., (© 2022. The Author(s).)

A finite axion-nucleon coupling, nearly unavoidable for QCD axions, leads to the production of axions via the thermal excitation and subsequent de-excitation of 57 Fe isotopes in the sun. We revise the solar bound on this flux adopting the up to date emission rate, and investigate the sensitivity of the proposed International Axion Observatory IAXO and its intermediate stage BabyIAXO to detect these axions. We compare different realistic experimental options and discuss the model dependence of the signal. Already BabyIAXO has sensitivity far beyond previous solar axion searches via the nucleon coupling and IAXO can improve on this by more than an order of magnitude., (© The Author(s) 2022.)

Background: This study investigated the effects of an aronia juice-based food supplement on background and total DNA strand breaks in whole blood, and on H 2 O 2 -induced DNA strand breaks in isolated peripheral blood lymphocytes., Methods: Ninety-one healthy volunteers were randomly selected to consume either the food supplement (2 × 25 mL drinking ampules, n = 45) or no supplement ( n = 46) daily for eight weeks., Results: Background DNA strand breaks decreased significantly after four and eight weeks of supplement consumption, compared to baseline ( p < 0.05), but the overall effect was low, and neither group showed a decrease in total DNA strand breaks. Conversely, supplement consumption clearly reduced H 2 O 2 -induced DNA strand breaks ex vivo ( p < 0.001), with statistically significant reductions after four and eight weeks, compared to the control group ( p < 0.05)., Conclusions: Thus, although consuming antioxidant supplements might produce only marginal immediate benefits under healthy conditions, potential preventive effects warrant further investigation.

This article provides a perspective on nature-based solutions. First, the argument is developed that nature-based solutions integrate social and ecological systems. Then, theoretical considerations relating to relational values, multifunctionality, transdisciplinarity, and polycentric governance are briefly outlined. Finally, a conceptual model of the social-ecological system of nature-based solutions is synthesised and presented. This conceptual model comprehensively defines the social and ecological external and internal systems that make up nature-based solutions, and identifies theoretical considerations that need to be addressed at different stages of their planning and implementation The model bridges the normative gaps of existing nature-based solution frameworks and could be used for consistent, comprehensive, and transferable comparisons internationally. The theoretical considerations addressed in this article inform practitioners, policymakers, and researchers about the essential components of nature-based solutions. The conceptual model can facilitate the identification of social and ecological interconnections within nature-based solutions and the range of stakeholders and disciplines involved.

The use of dyes at an industrial level has become problematic, since the discharge of dye effluents into water disturbs the photosynthetic activity of numerous aquatic organisms by reducing the penetration of light and oxygen, in addition to causing carcinogenic diseases and mutagenic effects in humans, as well as alterations in different ecosystems. Chitosan (CS) is suitable for removing anionic dyes since it has favorable properties, such as acquiring a positive charge and a typical macromolecular structure of polysaccharides. In this study, the optimization of CS beads crosslinked with glutaraldehyde (GA) for the adsorption of reactive blue dye 4 (RB4) in an aqueous solution was carried out. In this sense, the response surface methodology (RSM) was applied to evaluate the concentration of CS, GA, and sodium hydroxide on the swelling degree in the GA-crosslinked CS beads. In the same way, RSM was applied to optimize the adsorption process of the RB4 dye as a function of the initial pH of the solution, initial concentration of the dye, and adsorbent dose. The crosslinking reaction was investigated by scanning electron microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR), and X-ray diffractometry (XRD). The design described for the swelling degree showed an R 2 (coefficient of determination) adjusted of 0.8634 and optimized concentrations (CS 3.3% w/v , GA 1.7% v/v , and NaOH 1.3 M) that were conveniently applied with a concentration of CS at 3.0% w/v to decrease the viscosity and facilitate the formation of the beads. In the RB4 dye adsorption design, an adjusted R 2 (0.8280) with good correlation was observed, where the optimized conditions were: pH = 2, adsorbent dose 0.6 g, and initial concentration of RB4 dye 5 mg/L. The kinetic behavior and the adsorption isotherm allowed us to conclude that the GA-crosslinked CS beads' adsorption mechanism was controlled mainly by chemisorption interactions, demonstrating its applicability in systems that require the removal of contaminants with similar structures to the model presented.

The crosstalk between the colon mucosa and the microbiota represents a complex and delicate equilibrium. Gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer (CRC) are associated with a state of altered microbiota composition known as dysbiosis, which seems to play a causative role in some of these illnesses. Recent reports have shown that the colorectal microbiome is responsible for the response and safety to treatments against CRC, especially immunotherapy, hence opening the possibility to use bacteria as a predictive marker and also as a therapeutic agent. The review objective is to summarize updated reports about the the implication of the colorectal microbiome in the development of CRC, in treatment response and its potential as a therapeutic approach.

During endurance exercise, skin temperature (Tsk) plays a fundamental role in thermoregulatory processes. Environmental temperature is the biggest determinant of the Tsk. During exercise, the response of the skin temperature might be influenced by aerobic fitness (VO 2peak ). The aim of this study was to analyze and compare the dynamic of Tsk in high (HF) and moderately (MF) fit endurance runners during a progressive maximal stress test. Seventy-nine male endurance runners were classified into HF ( n = 35; VO 2peak = 56.62 ± 4.31 mL/kg/min) and MF ( n = 44; VO 2peak = 47.86 ± 5.29 mL/kg/min) groups. Tsk and cardiovascular data were continuously monitored during an incremental exercise, followed by a recovery period of five minutes. Results revealed that the MF group exhibited lower VO 2peak , Speed peak , ventilation (VE), muscle mass %, and higher BMI and fat mass % than the HF group (all p < 0.001). HF had significantly higher Tsk at baseline, and at 60% and 70% of peak workload (all p < 0.05). Tsk peak correlated with age, fat mass %, muscle mass %, VO 2peak , Speed peak , HR and VE (all p < 0.05). These findings indicate that VO 2peak was positively associated with increased Tsk during incremental exercise in male endurance runners.

The dominant anthocyanins in blackcurrant are delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside. Data on their absorption and distribution in the human body are limited. Therefore, we performed a human pilot study on five healthy male volunteers consuming a blackcurrant ( Ribes nigrum L.) extract. The rutinosides and their degradation products gallic acid and protocatechuic acid were determined in plasma and urine. The rutinosides' concentrations peaked in both plasma and urine samples within 2 h of extract ingestion. The recoveries of delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside from urine samples were 0.040 ± 0.011% and 0.048 ± 0.016%, respectively, over a 48 h period. Protocatechuic acid concentration increased significantly after ingestion of the blackcurrant extract. Our results show that after ingestion of a blackcurrant extract containing delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside, significant quantities of biologically active compounds circulated in the plasma and were excreted via urine. Furthermore, these results contribute to the understanding of anthocyanin metabolism in humans.

Purpose: Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT)., Methods: We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS)., Results: A total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001). In recipients allografted with donor CHIP, we found a high cumulative incidence of chronic GVHD (cGVHD; hazard ratio [HR], 1.73; 95% CI, 1.21 to 2.49; P = .003) and lower CIR/P (univariate: HR, 0.62; 95% CI, 0.40 to 0.97; P = .027; multivariate: HR, 0.63; 95% CI, 0.41 to 0.98; P = .042) but no effect on nonrelapse mortality. Serial quantification of 25 mutations showed engraftment of 24 of 25 clones and disproportionate expansion in half of them. Donor-cell leukemia was observed in two recipients. OS was not affected by donor CHIP status (HR, 0.88; 95% CI, 0.65 to 1.321; P = .434)., Conclusion: Allogeneic HSCT from donors with CHIP seems safe and results in similar survival in the setting of older, related donors. Future studies in younger and unrelated donors are warranted to extend these results. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that donor CHIP might foster cGVHD development and reduce relapse/progression risk.

Oxidative cell damage has been linked to the pathogenesis of numerous diseases such as atherosclerosis, type 2 diabetes, and cancer. The consumption of foods rich in polyphenols (e.g. anthocyanins) has been shown to exert preventive effects against such diseases. We investigated the biological effects of anthocyanin-rich fruit juice in a 9-week, placebo-controlled intervention study with 57 healthy male volunteers. The study design encompassed an initial 1 week of wash-out, followed by 8 weeks of intervention period with anthocyanin-rich fruit juice or placebo. The anthocyanin-rich fruit juice demonstrated DNA-protective and antioxidant effects; however, the placebo beverage, rich in vitamin C, showed similar effects based on the tested biomarkers. A significant reduction in background and total DNA strand breaks was observed in both groups within 24 h as well as after 8 weeks of intervention. Only anthocyanin-rich fruit juice consumption provided a significant reduction in body fat and an increase in fat-free mass. The activity of superoxide dismutase (SOD) was significantly elevated after consumption of anthocyanin-rich fruit juice. Both groups showed decreased levels of LDL and total cholesterol (TC) within the first week of the intervention. Similar results in both groups could be explained by the relatively high vitamin C contents of both beverages (>500 mg/L), which may have masked the effects of anthocyanins and other antioxidants in the studied juice. Taken together, anthocyanin-rich fruit juice as well as the placebo drink, both of which had high vitamin C content, can improve DNA integrity and might influence lipid metabolism in humans.

Clonal hematopoiesis of indeterminate potential (CHIP) occurs in an age-related manner and associates with an increased risk of hematologic cancer, atherosclerotic disease, and shorter overall survival. Little is known about the cell of origin, repartition patterns of clonal mutations within the hematopoietic differentiation tree, and its dynamics under evolutionary pressure. Using targeted sequencing, CHIP was identified in 121 out of 437 elderly individuals (27.7%). Variant allele frequencies (VAFs) of 91 mutations were studied in six peripheral blood cell fractions. VAFs were significantly higher in monocytes, granulocytes, and NK-cells compared to B- or T cells. In all cases with available bone marrow material, mutations could be identified in Lin - CD34 + CD38 - HSCs with subsequent expansion to myeloid primed progenitors. In 22 patients with solid cancer receiving (radio-)chemotherapy, longitudinal study of 32 mutations at 121 time points identified relative VAF changes of at least 50% in 13/32 mutations. VAFs of DNMT3A, were stable in 12/13 cases (P < .001). Cancer patients with a clonal mutation other than DNMT3A required more often red blood cell transfusions and dose reductions. Our results provide novel insights into cellular distribution of clonal mutations, their dynamics under chemotherapy, and advocate for systematic analyses for CHIP in cancer patients.

The aim of the present study was to explore the relation of controlled dietary acrylamide (AA) intake with the excretion of AA-related urinary mercapturic acids (MA), N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Excretion kinetics of these short-term exposure biomarkers were monitored under strictly controlled conditions within a duplicate diet human intervention study. One study arm (group A, n = 6) ingested AA via coffee (0.15-0.17 µg/kg bw) on day 6 and in a meal containing an upper exposure level of AA (14.1-15.9 μg/kg bw) on day 10. The other arm (group B) was on AA minimized diet (washout, 0.05-0.06 µg/kg bw) throughout the whole 13-day study period. On day 6, these volunteers ingested 13 C 3 D 3 -AA (1 μg/kg bw). In both arms, urinary MA excretion was continuously monitored and blood samples were taken to determine hemoglobin adducts. Ingestion of four cups of coffee resulted in a slightly enhanced short-term biomarker response within the background range of group B. At the end of the 13-day washout period, group B excreted an AAMA baseline level of 0.14 ± 0.10 µmol/d although AA intake was only about 0.06 µmol/d. This sustained over-proportional AAMA background suggested an endogenous AA baseline exposure level of 0.3-0.4 µg/kg bw/d. The excretion of 13 C 3 D 3 -AA was practically complete within 72-96 h which rules out delayed release of AA (or any other MA precursor) from deep body compartments. The results provide compelling support for the hypothesis of a sustained endogenous AA formation in the human body.

Objectives: The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients., Methods: IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease., Results: IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho < 0.6). Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid., Conclusions: We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)