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Facial hair is an important social and psychologic aspect of clinical appearance for men. The purpose of this review is to provide a comprehensive overview of the causes of alopecia of the beard including the prevalence, pathophysiology, clinical presentation, and treatment. In this review, we highlight more common causes of beard alopecia including alopecia areata and pseudofolliculitis barbae, infectious causes such as tinea barbae and herpes simplex folliculitis, and rare causes including dermatopathia pigmentosa reticularis and frontal fibrosing alopecia. This review serves as an important resource for clinicians when faced with patients suffering from beard alopecia. [ABSTRACT FROM AUTHOR]

Soil acidification is a major problem in the inland Pacific Northwest. A potential solution is the application of lime to neutralize acidity and raise pH. As lime is an expensive input, precision variable rate application is necessary. However, high-resolution mapping of pH and buffer pH for lime prescription requires costly sampling and analysis. To reduce the amount of sampling needed, remote sensing, which correlates with soil pH and buffer pH, can be used to determine optimal sampling locations and allow optimal interpolation. We used soil and crop data from the Washington State University R.J. Cook Agronomy Farm to develop an optimal sampling plan for a farmer's property, followed that sampling design, and used the measured pH and buffer pH to fit a Bayesian hierarchical model using remote sensing variables specific to that farmer's land. Following this, a new model was developed for the research farm with similar covariates. Ultimately, on the farmer's field, we observed a root mean square error (RMSE) of 0.2487 for soil pH at a depth of 0–10 cm and 0.1221 for modified Mehlich buffer at 0–10 cm of depth. For the research farm, where buffer pH was not measured, we saw an RMSE of 0.3272 for soil pH at 0–10 cm of depth and 0.3381 for soil pH at 10–20 cm of depth. The ability make predictions of soil acidity with uncertainty using this technique allows for prescription lime application while optimizing soil sampling and testing. Further, this paper serves as a case study of on-farm research. [ABSTRACT FROM AUTHOR]

Simple Summary: Previously, it has been shown that the use of growth hormone–releasing hormone (GHRH) antagonistic peptide analogs significantly suppresses the proliferation of various human cancer cell lines. However, the potential of the GHRH antagonist MIA-602 in addressing the resistance of acute promyelocytic leukemia (APL), as well as its ability to produce synergistic effects in acute myeloid leukemia (AML), have not yet been studied. Our findings indicate that the APL double-resistant cell line (NB4-RAA) and the K-562 AML cell line possess the GHRH receptor (GHRH-R) and are thus susceptible to treatment. We further described neural cell adhesion molecule 1 (NCAM1 classified as CD56) and its association with resistance to standard APL treatment in our in vitro model. GHRH is a hypothalamic peptide shown to stimulate the proliferation of malignant cells in humans. We have previously shown that the use of GHRH antagonist MIA-602 successfully suppressed the growth of many human cancer cell lines, spanning more than 20 types of cancers. In this study, we demonstrate the presence of GHRH-R in the NB4, NB4-RAA, and K-562 model cell lines. Furthermore, we demonstrate the inhibited proliferation of all three cell lines in vitro after incubation with MIA-602. The treatment of xenografts of human APL cell lines with MIA-602 led to a significant reduction in tumor growth. Additionally, combination therapy with both doxorubicin (DOX) and MIA-602 showed a marked synergistic effect in reducing the proliferation of the K-562 AML cell line. These findings suggest that MIA-602 could be utilized to address resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) therapies, as well as in augmenting anthracycline-based regimens. [ABSTRACT FROM AUTHOR]

Knowledge of crop abiotic and biotic stress is important for optimal irrigation management. While spectral reflectance and infrared thermometry provide a means to quantify crop stress remotely, these measurements can be cumbersome. Computer vision offers an inexpensive way to remotely detect crop stress independent of vegetation cover. This paper presents a technique using computer vision to detect disease stress in wheat. Digital images of differentially stressed wheat were segmented into soil and vegetation pixels using expectation maximization (EM). In the first season, the algorithm to segment vegetation from soil and distinguish between healthy and stressed wheat was developed and tested using digital images taken in the field and later processed on a desktop computer. In the second season, a wireless camera with near real-time computer vision capabilities was tested in conjunction with the conventional camera and desktop computer. For wheat irrigated at different levels and inoculated with wheat streak mosaic virus (WSMV), vegetation hue determined by the EM algorithm showed significant effects from irrigation level and infection. Unstressed wheat had a higher hue (118.32) than stressed wheat (111.34). In the second season, the hue and cover measured by the wireless computer vision sensor showed significant effects from infection (p = 0.0014), as did the conventional camera (p < 0.0001). Vegetation hue obtained through a wireless computer vision system in this study is a viable option for determining biotic crop stress in irrigation scheduling. Such a low-cost system could be suitable for use in the field in automated irrigation scheduling applications. [ABSTRACT FROM AUTHOR]

Chronic musculoskeletal (MSK) pain is one of the most common medical complaints worldwide and musculoskeletal injuries have an enormous social and economical impact. Current pharmacological and surgical treatments aim to relief pain and restore function; however, unsatiscactory outcomes are commonly reported. In order to find an accurate treatment to such pathologies, over the last years, there has been a significantly increasing interest in cellular therapies, such as adipose-derived mesenchymal stem cells (AMSCs). These cells represent a relatively new strategy in regenerative medicine, with many potential applications, especially regarding MSK disorders, and preclinical and clinical studies have demonstrated their efficacy in muscle, tendon, bone and cartilage regeneration. Nevertheless, several worries about their safety and side effects at long-term remain unsolved. This article aims to review the current state of AMSCs therapy in the treatment of several MSK diseases and their clinical applications in veterinary and human medicine. [ABSTRACT FROM AUTHOR]

The polypropylene (PP) synthesis process is crucial in the plastics industry, requiring precise control as it directly impacts the catalytic activity and the final product's performance. This study investigates the effects of trace amounts of four different mercaptans on the polymerization of propylene using a fourth-generation Ziegler-Natta (ZN) catalyst. Various concentrations of these mercaptans were tested, and results showed that their presence significantly reduced the melt flow index (MFI) of the final PP. The most notable MFI decrease occurred at 37.17 ppm of propyl mercaptan and 52.60 ppm of butyl mercaptan. Methyl and ethyl mercaptan also reduced the MFI at lower concentrations, indicating that mercaptans act as inhibitors by slowing down the polymerization process and reducing the fluidity of molten PP. The highest MFI increase was observed at lower concentrations of each mercaptan, suggesting that smaller molecular inhibitors require less concentration. This trend was also seen in the catalyst's productivity, where lower concentrations of methyl mercaptan reduced PP production more effectively than higher concentrations of butyl mercaptan. Fourier transform infrared spectroscopy (FTIR) identified interactions between the mercaptans and the ZN catalyst. Computational analysis further supported these findings, providing insights into the molecular interactions and suggesting possible inhibition mechanisms that could impact the final properties of polypropylene.

Acetylene and methylacetylene are impurities commonly found in the raw materials used for the production of polymers such as polypropylene and polyethylene. Experimental evidence indicates that both acetylene and methylacetylene can decrease the productivity of the Ziegler-Natta catalyst and alter the properties of the resulting polymer. However, there is still a lack of understanding regarding the mechanisms through which these substances affect this process. Therefore, elucidating these mechanisms is crucial to develop effective solutions to this problem. In this study, the inhibition mechanisms of the Ziegler-Natta catalyst by acetylene and methylacetylene are presented and compared with the incorporation of the first propylene monomer (chain initiation) to elucidate experimental effects. The Density Functional Theory (DFT) method was used, along with the B3LYP-D3 functional and the 6-311++G(d,p) basis set. The recorded adsorption energies were -11.10, -13.99, and -0.31 kcal mol -1 , while the activation energies were 1.53, 2.83, and 28.36 kcal mol -1 for acetylene, methylacetylene, and propylene, respectively. The determined rate constants were 4.68 × 10 11 , 5.29 × 10 11 , and 2.3 × 10 -8 M -1 s -1 for acetylene, methylacetylene, and propylene, respectively. Based on these values, it is concluded that inhibition reactions are more feasible than propylene insertion only if an ethylene molecule has not been previously adsorbed, as such an event reinforces propylene adsorption.

Parkinson's disease (PD) is a gradually worsening neurodegenerative disorder affecting the nervous system, marked by a slow progression and varied symptoms. It is the second most common neurodegenerative disease, affecting over six million people in the world. Its multifactorial etiology includes environmental, genomic, and epigenetic factors. Clinical symptoms consist of non-motor and motor symptoms, with motor symptoms being the classic presentation. Therapeutic approaches encompass pharmacological, non-pharmacological, and surgical interventions. Traditional pharmacological treatment consists of administering drugs (MAOIs, DA, and levodopa), while emerging evidence explores the potential of antidiabetic agents for neuroprotection and gene therapy for attenuating parkinsonian symptoms. Non-pharmacological treatments, such as exercise, a calcium-rich diet, and adequate vitamin D supplementation, aim to slow disease progression and prevent complications. For those patients who have medically induced side effects and/or refractory symptoms, surgery is a therapeutic option. Deep brain stimulation is the primary surgical option, associated with motor symptom improvement. Levodopa/carbidopa intestinal gel infusion through percutaneous endoscopic gastrojejunostomy and a portable infusion pump succeeded in reducing "off" time, where non-motor and motor symptoms occur, and increasing "on" time. This article aims to address the general aspects of PD and to provide a comparative comprehensive review of the conventional and the latest therapeutic advancements and emerging treatments for PD. Nevertheless, further studies are required to optimize treatment and provide suitable alternatives.

The standard of care for glioblastoma (GBM) involves surgery followed by adjuvant radio- and chemotherapy, but often within months, patients relapse, and this has been linked to glioma stem cells (GSCs), self-renewing cells with increased therapy resistance. The identification of the epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR) as key players in gliomagenesis inspired the development of inhibitors targeting these tyrosine kinases (TKIs). However, results from clinical trials testing TKIs have been disappointing, and while the role of GSCs in conventional therapy resistance has been extensively studied, less is known about resistance of GSCs to TKIs. In this study, we have used compartmentalised proteomics to analyse the adaptive response of GSCs to ponatinib, a TKI with activity against PDGFR. The analysis of differentially expressed proteins revealed that GSCs respond to ponatinib by broadly rewiring lipid metabolism, involving fatty acid beta-oxidation, cholesterol synthesis, and sphingolipid degradation. Inhibiting each of these metabolic pathways overcame ponatinib adaptation of GSCs, but interrogation of patient data revealed sphingolipid degradation as the most relevant pathway in GBM. Our data highlight that targeting lipid metabolism, and particularly sphingolipid degradation in combinatorial therapies, could improve the outcome of TKI therapies using ponatinib in GBM.

A postextraction socket becomes a clinical challenge due to the fact that a series of changes associated with bone remodelling and resorption of the socket that occur after extraction, which limits the aesthetic and functional prognosis of implant-supported rehabilitations. It has been studied that the use of the autologous tooth-derived graft (ATDG) has regenerative properties and could therefore be useful for solving this type of problem. There is no consensus in the scientific literature on a standardized protocol for the use of the autologous tooth. Therefore, the aim of the present study was to evaluate the most relevant parameters to achieve the best properties of ground ATDG using three methods, namely Gouge forceps, electric grinder, and manual, that made up the study group (SG) and compared with the control group (CG) consisting of Bio-Oss ® . The sample obtained by the electric grinder had the highest value of specific surface area (2.4025 ± 0.0218 m 2 /g), while the particle size as average diameter (751.9 µm) was the lowest and most homogeneous of the three groups. Therefore, the electric grinder allowed for obtaining ATDG with more regenerative properties due to its specific surface-area value and particle size in accordance with the xenograft with the greatest bibliographical support (Bio-Oss ® ). The higher specific surface increases the reaction with the physiological media, producing faster biological mechanisms.

The microstructure and wear properties of a Mg-1wt.% Zn-1wt.% Ca (ZX11) alloy with different heat treatments have been investigated. The ZX11 alloy was tested in the as-cast state and after different heat treatment conditions: solution-treated (at 450 °C for 24 h), peak-aged (solution-treated + aged at 180 °C for 3 h), and over-aged (solution-treated + aged at 180 °C for 24 h). The microstructure of the as-cast sample showed a continuous intermetallic phase at the grain boundaries, while the heat-treated samples exhibited discrete precipitated particles within the grains. To evaluate the wear behavior, the samples were tested using a pin-on-disc configuration, where the wear rates and friction coefficients were measured at different loads and sliding speeds. An AZ31 magnesium alloy was used as the counterbody. The worn surfaces and the wear debris were studied to identify the main wear mechanisms corresponding to each test condition. The results indicated the presence of abrasion, oxidation, and adhesive wear mechanisms in all testing conditions. In the as-cast state, delamination and plastic deformation were the dominant wear mechanisms, while they were less relevant in the heat-treated conditions. The peak-aged samples exhibited the lowest wear rates, suggesting that modifying the distribution of intermetallic precipitates contributed to enhancing the wear resistance of the alloy.

The attention on blockchain technology (BCT) to create new forms of relational reliance has seen an explosion of new applications and initiatives, to assure decentralized security and trust. Its potential as a game-changing technology relates to how data gets distributed and replicated over several organizations and countries. This paper provides an introduction to BCT, as well as a review of its technological aspects. A concrete application of outsource access control and pricing procedures in cellular networks, based on a decentralized access control-as-a-service solution for private cellular networks, is also presented. The application can be used by service and content providers, to provide new business models. The proposed method removes the single point of failure from conventional centralized access control systems, increasing scalability while decreasing operational complexity, regarding access control and pricing procedures. Design and implementation details of the new method in a real-world scenario using a private cellular network and a BCT system that enables smart contracts are also provided.

The reprogramming of metabolism is a recognized cancer hallmark. It is well known that different signaling pathways regulate and orchestrate this reprogramming that contributes to cancer initiation and development. However, recent evidence is accumulating, suggesting that several metabolites could play a relevant role in regulating signaling pathways. To assess the potential role of metabolites in the regulation of signaling pathways, both metabolic and signaling pathway activities of Breast invasive Carcinoma (BRCA) have been modeled using mechanistic models. Gaussian Processes, powerful machine learning methods, were used in combination with SHapley Additive exPlanations (SHAP), a recent methodology that conveys causality, to obtain potential causal relationships between the production of metabolites and the regulation of signaling pathways. A total of 317 metabolites were found to have a strong impact on signaling circuits. The results presented here point to the existence of a complex crosstalk between signaling and metabolic pathways more complex than previously was thought.

Single-cell RNA sequencing is increasing our understanding of the behavior of complex tissues or organs, by providing unprecedented details on the complex cell type landscape at the level of individual cells. Cell type definition and functional annotation are key steps to understanding the molecular processes behind the underlying cellular communication machinery. However, the exponential growth of scRNA-seq data has made the task of manually annotating cells unfeasible, due not only to an unparalleled resolution of the technology but to an ever-increasing heterogeneity of the data. Many supervised and unsupervised methods have been proposed to automatically annotate cells. Supervised approaches for cell-type annotation outperform unsupervised methods except when new (unknown) cell types are present. Here, we introduce SigPrimedNet an artificial neural network approach that leverages (i) efficient training by means of a sparsity-inducing signaling circuits-informed layer, (ii) feature representation learning through supervised training, and (iii) unknown cell-type identification by fitting an anomaly detection method on the learned representation. We show that SigPrimedNet can efficiently annotate known cell types while keeping a low false-positive rate for unseen cells across a set of publicly available datasets. In addition, the learned representation acts as a proxy for signaling circuit activity measurements, which provide useful estimations of the cell functionalities.

Acute myeloid leukemia (AML) is a heterogeneous disease classified into three risk categories (favorable, intermediate and adverse) with significant differences in outcomes. Definitions of risk categories evolve overtime, incorporating advances in molecular knowledge of AML. In this study, we analyzed the impacts of evolving risk classifications in 130 consecutive AML patients in a single-center real-life experience. Complete cytogenetic and molecular data were collected using conventional qPCR and targeted Next Generation Sequencing (NGS). Five-year OS probabilities were consistent among all classification models (roughly 50-72%, 26-32% and 16-20% for favorable, intermediate and adverse risk groups, respectively). In the same way, the medians of survival months and prediction power were similar in all models. In each update, around 20% of patients were re-classified. The adverse category consistently increased over time (31% in MRC, 34% in ELN2010, 50% in ELN2017), reaching up to 56% in the recent ELN2022. Noteworthily, in multivariate models, only age and the presence of TP53 mutations remained statistically significant. With updates in risk-classification models, the percentage of patients assigned to the adverse group is increasing, and so will the indications for allogeneic stem cell transplantation.

Thraustochytrids are aquatic unicellular protists organisms that represent an important reservoir of a wide range of bioactive compounds, such as essential polyunsaturated fatty acids (PUFAs) such as arachidonic acid (ARA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), which are involved in the regulation of the immune system. In this study, we explore the use of co-cultures of Aurantiochytrium sp. and bacteria as a biotechnological tool capable of stimulating PUFA bioaccumulation. In particular, the co-culture of lactic acid bacteria and the protist Aurantiochytrium sp. T66 induce PUFA bioaccumulation, and the lipid profile was evaluated in cultures at different inoculation times, with two different strains of lactic acid bacteria capable of producing the tryptophan dependent auxins, and one strain of Azospirillum sp., as a reference for auxin production. Our results showed that the Lentilactobacillus kefiri K6.10 strain inoculated at 72 h gives the best PUFA content (30.89 mg g -1 biomass) measured at 144 h of culture, three times higher than the control (8.87 mg g -1 biomass). Co-culture can lead to the generation of complex biomasses with higher added value for developing aquafeed supplements.

Pluripotency describes the ability of stem cells to differentiate into derivatives of the three germ layers. In reporting new human pluripotent stem cell lines, their clonal derivatives or the safety of differentiated derivatives for transplantation, assessment of pluripotency is essential. Historically, the ability to form teratomas in vivo containing different somatic cell types following injection into immunodeficient mice has been regarded as functional evidence of pluripotency. In addition, the teratomas formed can be analyzed for the presence of malignant cells. However, use of this assay has been subject to scrutiny for ethical reasons on animal use and due to the lack of standardization in how it is used, therefore questioning its accuracy. In vitro alternatives for assessing pluripotency have been developed such as ScoreCard and PluriTest. However, it is unknown whether this has resulted in reduced use of the teratoma assay. Here, we systematically reviewed how the teratoma assay was reported in publications between 1998 (when the first human embryonic stem cell line was described) and 2021. Our analysis of >400 publications showed that in contrast to expectations, reporting of the teratoma assay has not improved: methods are not yet standardized, and malignancy was examined in only a relatively small percentage of assays. In addition, its use has not decreased since the implementation of the ARRIVE guidelines on reduction of animal use (2010) or the introduction of ScoreCard (2015) and PluriTest (2011). The teratoma assay is still the preferred method to assess the presence of undifferentiated cells in a differentiated cell product for transplantation since the in vitro assays alone are not generally accepted by the regulatory authorities for safety assessment. This highlights the remaining need for an in vitro assay to test malignancy of stem cells.

Cardiovascular diseases (CVD) represent a serious health problem worldwide, of which atrial fibrillation (AF) is one of the most common conditions. Early and timely diagnosis of CVD is essential for successful treatment. When implemented in the healthcare system this can ease the existing socio-economic burden on health institutions and government. Therefore, developing technologies and tools to diagnose CVD in a timely way and detect AF is an important research topic. ECG monitoring patches allowing ambulatory patient monitoring over several days represent a novel technology, while we witness a significant proliferation of ECG monitoring patches on the market and in the research labs, their performance over a long period of time is not fully characterized. This paper analyzes the signal quality of ECG signals obtained using a single-lead ECG patch featuring self-adhesive dry electrode technology collected from six cardiac patients for 5 days. In particular, we provide insights into signal quality degradation over time, while changes in the average ECG quality per day were present, these changes were not statistically significant. It was observed that the quality was higher during the nights, confirming the link with motion artifacts. These results can improve CVD diagnosis and AF detection in real-world scenarios.

The covalent functionalization of synthetic peptides allows the modification of different biomaterials (metallic, polymeric, and ceramic), which are enriched with biologically active sequences to guide cell behavior. Recently, this strategy has also been applied to decellularized biological matrices. In this study, the covalent anchorage of a synthetic peptide (REDV) to a pericardial matrix decellularized via Schiff base is realized starting from concentrated peptide solutions (10 -4 M and 10 -3 M). The use of a labeled peptide demonstrated that as the concentration of the working solution increased, the surface density of the anchored peptide increased as well. These data are essential to pinpointing the concentration window in which the peptide promotes the desired cellular activity. The matrices were extensively characterized by Water Contact Angle (WCA) analysis, Differential Scanning Calorimetry (DSC) analysis, geometric feature evaluation, biomechanical tests, and preliminary in vitro bioassays.

In 25% of patients with mitochondrial myopathies, pathogenic mitochondrial DNA (mtDNA) mutation are the cause. For heteroplasmic mtDNA mutations, symptoms manifest when the mutation load exceeds a tissue-specific threshold. Therefore, lowering the mutation load is expected to ameliorate disease manifestations. This can be achieved by fusing wild-type mesoangioblasts with mtDNA mutant myotubes. We have tested this in vitro for female carriers of the m.3271T>C or m.3291T>C mutation (mutation load >90%) using wild-type male mesoangioblasts. Individual fused myotubes were collected by a newly-developed laser capture microdissection (LCM) protocol, visualized by immunostaining using an anti-myosin antibody. Fusion rates were determined based on male-female nuclei ratios by fluorescently labelling the Y-chromosome. Using combined 'wet' and 'air dried' LCM imaging improved fluorescence imaging quality and cell yield. Wild-type mesoangioblasts fused in different ratios with myotubes containing either the m.3271T>C or the m.3291T>C mutation. This resulted in the reduction of the mtDNA mutation load proportional to the number of fused wild-type mesoangioblasts for both mtDNA mutations. The proportional reduction in mtDNA mutation load in vitro after fusion is promising in the context of muscle stem cell therapy for mtDNA mutation carriers in vivo, in which we propose the same strategy using autologous wild-type mesoangioblasts.

The wear behavior of the Mg-3wt.% Zn-0.4wt.% Ca (ZX30) alloy was tested using a pin-on-disc configuration with AZ31 alloy discs as counterparts under dry sliding conditions. The ZX30 alloy was tested in different states: as-cast, solution-treated, peak-aged, and over-aged. Wear rates and friction coefficients were measured at different loads and sliding speeds. Abrasion and oxidation were the main wear mechanisms found in all the conditions tested. Moreover, aluminum oxides were detected on the worn surfaces, which indicates the presence of an adhesive wear mechanism. The wear behavior of the studied ZX30 alloy showed a greater tendency towards oxidative wear than other Mg alloys, and the microstructure observed strongly affected the wear behavior.

Innovative cross-over study designs were explored in non-human primate (NHP) studies to determine the value of this approach for the evaluation of drug efficacy against tuberculosis (TB). Firstly, the pharmacokinetics (PK) of each of the drugs Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E), that are standardly used for the treatment of tuberculosis, was established in the blood of macaques after oral dosing as a monotherapy or in combination. Two studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of different drug combinations using cross-over designs. The first employed a balanced, three-period Pigeon design with an extra period; this ensured that treatment by period interactions and carry-over could be detected comparing the treatments HR, HZ and HRZ using H37Rv as the challenge strain of Mycobacterium tuberculosis (M. tb). Although the design accounted for considerable variability between animals, the three regimens evaluated could not be distinguished using any of the alternative endpoints assessed. However, the degree of pathology achieved using H37Rv in the model during this study was less than expected. Based on these findings, a second experiment using a classical AB/BA design comparing HE with HRZ was conducted using the M. tb Erdman strain. More extensive pathology was observed, and differences in computerized tomography (CT) scores and bacteriology counts in the lungs were detected, although due to the small group sizes, clearer differences were not distinguished. Type 1 T helper (Th1) cell response profiles were characterized using the IFN-γ ELISPOT assay and revealed differences between drug treatments that corresponded to decreases in disease burden. Therefore, the studies performed support the utility of the NHP model for the determination of PK/PD of TB drugs, although further work is required to optimize the use of cross-over study designs.

Background: Transcranial direct current stimulation (tDCS) has emerged as a prevention method or minimizer of the normal cognitive deterioration that occurs during the aging process. tDCS can be used to enhance cognitive functions such as immediate memory, learning, or working memory in healthy subjects. The objective of this study was to analyze the effect of two 20-min sessions of anodal transcranial direct stimulation on immediate memory, learning potential, and working memory in healthy older adults., Methods: A randomized, single-blind, repeated-measures, sham-controlled design was used. The sample is made up of 31 healthy older adults, of whom 16 were in the stimulation group and 15 were in the sham group. The anode was placed on position F7, coinciding with the left dorsolateral prefrontal cortex region, and the cathode was placed on Fp2, the right supraorbital area (rSO)., Results: When comparing the results of the treatment group and the sham group, differences were observed in working memory and learning potential; however, no differences in immediate memory were found., Conclusion: The results showed that tDCS is a non-invasive and safe tool to enhance cognitive processes in healthy older adults interested in maintaining some cognitive function.

Cancer maintenance, metastatic dissemination and drug resistance are sustained by cancer stem cells (CSCs). Triple negative breast cancer (TNBC) is the breast cancer subtype with the highest number of CSCs and the poorest prognosis. Here, we aimed to identify potential drugs targeting CSCs to be further employed in combination with standard chemotherapy in TNBC treatment. The anti-CSC efficacy of up to 17 small drugs was tested in TNBC cell lines using cell viability assays on differentiated cancer cells and CSCs. Then, the effect of 2 selected drugs (8-quinolinol -8Q- and niclosamide -NCS-) in the cancer stemness features were evaluated using mammosphere growth, cell invasion, migration and anchorage-independent growth assays. Changes in the expression of stemness genes after 8Q or NCS treatment were also evaluated. Moreover, the potential synergism of 8Q and NCS with PTX on CSC proliferation and stemness-related signaling pathways was evaluated using TNBC cell lines, CSC-reporter sublines, and CSC-enriched mammospheres. Finally, the efficacy of NCS in combination with PTX was analyzed in vivo using an orthotopic mouse model of MDA-MB-231 cells. Among all tested drug candidates, 8Q and NCS showed remarkable specific anti-CSC activity in terms of CSC viability, migration, invasion and anchorage independent growth reduction in vitro. Moreover, specific 8Q/PTX and NCS/PTX ratios at which both drugs displayed a synergistic effect in different TNBC cell lines were identified. The sole use of PTX increased the relative presence of CSCs in TNBC cells, whereas the combination of 8Q and NCS counteracted this pro-CSC activity of PTX while significantly reducing cell viability. In vivo, the combination of NCS with PTX reduced tumor growth and limited the dissemination of the disease by reducing circulating tumor cells and the incidence of lung metastasis. The combination of 8Q and NCS with PTX at established ratios inhibits both the proliferation of differentiated cancer cells and the viability of CSCs, paving the way for more efficacious TNBC treatments.

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain., Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis., Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins., Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.

Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these modifications are reversible, activation and inactivation of FOXO factors is attainable through pharmacological treatment. One major regulatory input of FOXO signaling is mediated by protein kinases. Here, we use specific inhibitors against different kinases including PI3K, mTOR, MEK and ALK, and other receptor tyrosine kinases (RTKs) to determine their effect on FOXO3 activity. While we show that inhibition of PI3K efficiently drives FOXO3 into the cell nucleus, the dual PI3K/mTOR inhibitors dactolisib and PI-103 induce nuclear FOXO translocation more potently than the PI3Kδ inhibitor idelalisib. Furthermore, specific inhibition of mTOR kinase activity affecting both mTORC1 and mTORC2 potently induced nuclear translocation of FOXO3, while rapamycin, which specifically inhibits the mTORC1, failed to affect FOXO3. Interestingly, inhibition of the MAPK pathway had no effect on the localization of FOXO3 and upstream RTK inhibition only weakly induced nuclear FOXO3. We also measured the effect of the test compounds on the phosphorylation status of AKT, FOXO3 and ERK, on FOXO-dependent transcriptional activity and on the subcellular localization of other FOXO isoforms. We conclude that mTORC2 is the most important second layer kinase negatively regulating FOXO activity.

Studies of horse evolution arose during the middle of the 19th century, and several hypotheses have been proposed for their taxonomy, paleobiogeography, paleoecology and evolution. The present contribution represents a collaboration of 19 multinational experts with the goal of providing an updated summary of Pliocene and Pleistocene North, Central and South American, Eurasian and African horses. At the present time, we recognize 114 valid species across these continents, plus 4 North African species in need of further investigation. Our biochronology and biogeography sections integrate Equinae taxonomic records with their chronologic and geographic ranges recognizing regional biochronologic frameworks. The paleoecology section provides insights into paleobotany and diet utilizing both the mesowear and light microscopic methods, along with calculation of body masses. We provide a temporal sequence of maps that render paleoclimatic conditions across these continents integrated with Equinae occurrences. These records reveal a succession of extinctions of primitive lineages and the rise and diversification of more modern taxa. Two recent morphological-based cladistic analyses are presented here as competing hypotheses, with reference to molecular-based phylogenies. Our contribution represents a state-of-the art understanding of Plio-Pleistocene Equus evolution, their biochronologic and biogeographic background and paleoecological and paleoclimatic contexts., Competing Interests: The authors declare no conflict of interest.

Background: Multiparametric Flow Cytometry (MFC) is an essential tool to study the involved cell lineages, the aberrant differentiation/maturation patterns and the expression of aberrant antigens in acute myeloid leukemia (AML). The characterization of leukemia-associated immunophenotypes (LAIPs) at the moment of diagnosis is critical to establish reproducible strategies for the study of measurable residual disease using MFC (MFC-MRD). Methods: In this study, we identify and characterize LAIPs by comparing the leukemic populations of 145 AML patients, using the EuroFlow AML/ MDS MFC panel, with six databases of normal myeloid progenitors (MPCs). Principal component analysis was used to identify and characterize the LAIPs, which were then used to generate individual profiles for MFC-MRD monitoring. Furthermore, we investigated the relationship between the expression patterns of LAIPs and the different subtypes of AML. The MFC-MRD study was performed by identifying residual AML populations that matched with the LAIPs at diagnosis. To further validate this approach, the presence of MRD was also assessed by qPCR (qPCR-MRD). Finally, we studied the association between MFC-MRD and progression-free survival (PFS). Results: The strategy used in this study allowed us to describe more than 300 different LAIPs and facilitated the association of specific phenotypes with certain subtypes of AML. The MFC-MRD monitoring based on LAIPs with good/strong specificity was applicable to virtually all patients and showed a good correlation with qPCR-MRD and PFS. Conclusions: The described methodology provides an objective method to identify and characterize LAIPs. Furthermore, it provides a theoretical basis to develop highly sensitive MFC-MRD strategies.

(1) Background: The main basis for the public recognition of the merits of scientists has always been the system of scientific publications and citations. Our goal is to identify and analyze the most cited articles in the Public, Environmental & Occupational Health category. (2) Methods: We searched the Web of Science for all articles published in the "Public, Environmental & Occupational Health" category up to March 2022 and selected the 100 most cited articles. We recorded the number of citations, the journal, the year of publication, quartile, impact factor, institution, country, authors, topic, type of publication and collaborations. (3) Results: 926,665 documents were analyzed. The top 100 had 401,620 citations. The journal with the most articles was the Journal of Clinical Epidemiology and the one with the highest number of citations was Medical Care. The year with the highest number of articles in the top 100 was 1998. The country with the highest percentage of publications was the USA and the most productive institution was Harvard. The most frequent keywords were bias, quality, and extension. The largest collaboration node was between the USA, Canada, Germany, Spain, Australia, France, and Sweden. (4) Conclusions: This bibliometric study on Public, Environmental & Occupational Health provides valuable information not only to identify topics of interest in the analyzed category, but also to identify the differences in the topics they study.

A Digital Twin (DT) is a set of computer-generated models that map a physical object into a virtual space. Both physical and virtual elements exchange information to monitor, simulate, predict, diagnose and control the state and behavior of the physical object within the virtual space. DTs supply a system with information and operating status, providing capabilities to create new business models. In this paper, we focus on the construction of DTs. More specifically, we focus on determining (methodologically) how to design, create and connect physical objects with their virtual counterpart. We explore the problem into several phases: from functional requirement selection and architecture planning to integration and verification of the final (digital) models. We address as well how physical components exchange real-time information with DTs, as well as experimental platforms to build DTs (including protocols and standards). We conclude with a discussion and open challenges.

Nowadays, even with all the tremendous advances in medicine and health protocols, cardiovascular diseases (CVD) continue to be one of the major causes of death. In the present work, we focus on a specific abnormality: ST-segment deviation, which occurs regularly in high-performance athletes and elderly people, serving as a myocardial infarction (MI) indicator. It is usually diagnosed manually by experts, through visual interpretation of the printed electrocardiography (ECG) signal. We propose a methodology to detect ST-segment deviation and quantify its scale up to 1 mV by extracting statistical, point-to-point beat characteristics and signal quality indexes (SQIs) from single-lead ECG. We do so by applying automated machine learning methods to find the best hyperparameter configuration for classification and regression models. For validation of our method, we use the ST-T database from Physionet; the results show that our method obtains 98.30% accuracy in the case of a multiclass problem and 99.87% accuracy in the case of binarization.

Spain is a secondary centre of the diversification of the melon ( Cucumis melo L.), with high diversity represented in highly appreciated landraces belonging to the Flexuosus and Ibericus groups. A collection of 47 accessions of Flexuosus, Chate, Piel de Sapo, Tendral, Amarillo, Blanco, and Rochet was analysed using a genotyping-by-sequencing (GBS) approach. A total of 66,971 quality SNPs were identified. Genetic analysis differentiated Ibericus accessions and exotic materials (Ameri, Momordica, Kachri, and Agrestis), while Flexuous accessions shared ancestry between them. Within the Ibericus group, no clear genomic distinction could be identified for the different landraces evaluated, with accessions of different landraces showing high genetic similarity. The morphological characterization confirmed that the external colour and fruit shape had been used as recognition patterns for Spanish melon landraces, but variability within a landrace exists. Differences were found in the sugars and acid and volatile profiles of the materials. Flexuosus and Chate melons at the immature commercial stage accumulated malic acid and low levels of hexoses, while Ibericus melons accumulated high contents of sucrose and citric acid. Specific trends could be identified in the Ibericus landraces. Tendral accumulated low levels of sugars and citric acid and high of malic acid, maintaining higher firmness, Rochet reached higher levels of sugars, and Amarillo tended to lower malic acid contents. Interestingly, high variability was found within landraces for the acidic profile, offering possibilities to alter taste tinges. The main volatile organic compounds (VOCs) in Flexuosus and Chate were aldehydes and alcohols, with clear differences between both groups. In the Ibericus landraces, general trends for VOC accumulation could be identified, but, again, a high level of variation exists. This situation highlights the necessity to develop depuration programs to promote on-farm in situ conservation and, at the same time, offers opportunities to establish new breeding program targets and to take advantage of these sources of variation.

Accurate diagnosis of colorectal cancer (CRC) still relies on invasive colonoscopy. Noninvasive methods are less sensitive in detecting the disease, particularly in the early stage. In the current work, a metabolomics analysis of fecal samples was carried out by ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS). A total of 1380 metabolites were analyzed in a cohort of 120 fecal samples from patients with normal colonoscopy, advanced adenoma (AA) and CRC. Multivariate analysis revealed that metabolic profiles of CRC and AA patients were similar and could be clearly separated from control individuals. Among the 25 significant metabolites, sphingomyelins (SM), lactosylceramides (LacCer), secondary bile acids, polypeptides, formiminoglutamate, heme and cytidine-containing pyrimidines were found to be dysregulated in CRC patients. Supervised random forest (RF) and logistic regression algorithms were employed to build a CRC accurate predicted model consisting of the combination of hemoglobin (Hgb) and bilirubin E,E, lactosyl-N-palmitoyl-sphingosine, glycocholenate sulfate and STLVT with an accuracy, sensitivity and specificity of 91.67% (95% Confidence Interval (CI) 0.7753-0.9825), 0.7 and 1, respectively.

This paper is a detailed review of the chemistry of medium-size reactive systems using the following hydrogen abstraction reactions with ethane, X + C 2 H 6 → HX + C 2 H 5 ; X ≡ H, F( 2 P), Cl( 2 P), O( 3 P) and OH, and focusing attention mainly on the theoretical developments. These bimolecular reactions range from exothermic to endothermic systems and from barrierless to high classical barriers of activation. Thus, the topography of the reactive systems changes from reaction to reaction with the presence or not of stabilized intermediate complexes in the entrance and exit channels. The review begins with some reflections on the inherent problems in the theory/experiment comparison. When one compares kinetics or dynamics theoretical results with experimental measures, one is testing both the potential energy surface describing the nuclei motion and the kinetics or dynamics method used. Discrepancies in the comparison may be due to inaccuracies of the surface, limitations of the kinetics or dynamics methods, and experimental uncertainties that also cannot be ruled out. The paper continues with a detailed review of some bimolecular reactions with ethane, beginning with the reactions with hydrogen atoms. The reactions with halogens present a challenge owing to the presence of stabilized intermediate complexes in the entrance and exit channels and the influence of the spin-orbit states on reactivity. Reactions with O( 3 P) atoms lead to three surfaces, which is an additional difficulty in the theoretical study. Finally, the reactions with the hydroxyl radical correspond to a reactive system with ten atoms and twenty-four degrees of freedom. Throughout this review, different strategies in the development of analytical potential energy surfaces describing these bimolecular reactions have been critically analyzed, showing their advantages and limitations. These surfaces are fitted to a large number of ab initio calculations, and we found that a huge number of calculations leads to accurate surfaces, but this information does not guarantee that the kinetics and dynamics results match the experimental measurements.

Zika virus (ZIKV) establishes persistent infections in multiple human tissues, a phenomenon that likely plays a role in its ability to cause congenital birth defects and neurological disease. Multiple nonstructural proteins encoded by ZIKV, in particular NS5, are known to suppress the interferon (IFN) response by attacking different steps in this critical antiviral pathway. Less well known are the potential roles of structural proteins in affecting the host immune response during ZIKV infection. Capsid proteins of flaviviruses are of particular interest because a pool of these viral proteins is targeted to the nuclei during infection and, as such, they have the potential to affect host cell gene expression. In this study, RNA-seq analyses revealed that capsid proteins from six different flaviviruses suppress expression of type I IFN and IFN-stimulated genes. Subsequent interactome and in vitro ubiquitination assays showed that ZIKV capsid protein binds to and prevents activating ubiquitination of RIG-I CARD domains by TRIM25, a host factor that is important for the induction arm of the IFN response. The other flavivirus capsid proteins also interacted with TRIM25, suggesting that these viral proteins may attenuate antiviral signaling pathways at very early stages of infection, potentially even before nonstructural proteins are produced.

The last decade has seen an explosion of interest in drones-introducing new networking technologies, such as 5G wireless connectivity and cloud computing. The resulting advancements in communication capabilities are already expanding the ubiquitous role of drones as primary solution enablers, from search and rescue missions to information gathering and parcel delivery. Their numerous applications encompass all aspects of everyday life. Our focus is on networked and collaborative drones. The available research literature on this topic is vast. No single survey article could do justice to all critical issues. Our goal in this article is not to cover everything and include everybody but rather to offer a personal perspective on a few selected research topics that might lead to fruitful future investigations that could play an essential role in developing drone technologies. The topics we address include distributed computing with drones for the management of anonymity, countering threats posed by drones, target recognition, navigation under uncertainty, risk avoidance, and cellular technologies. Our approach is selective. Every topic includes an explanation of the problem, a discussion of a potential research methodology, and ideas for future research.

The use of human pluripotent stem cells (hPSCs) in regenerative medicine has great potential. However, it is important to exclude that these cells can undergo malignant transformation, which could lead to the development of malignant tumours. This property of hPSCs is currently being tested using the teratoma assay, through which cells are injected into immunodeficient mice. Transplantation of stem cells in immunocompromised recipient animals certainly has a much higher incidence of tumour formation. On the other hand, the results obtained in immunodeficient mice could indicate a risk of tumour formation that is practically not present in the human immunocompetent recipient. The presence of a humanised immune system might be more representative of the human situation; therefore, we investigated if the demonstrated malignant features of chosen and well-characterised stem cell lines could be retrieved and if new features could arise in a humanised mouse model. Hu-CD34NSG TM (HIS) mice were compared side by side with immunocompromised mice (NSG) after injection of a set of benign (LU07) and malignant (LU07+dox and 2102Ep) cell lines. Analysis of the tumour development, histological composition, pathology evaluation, and malignancy-associated miRNA expression levels, both in tumour and plasma samples, revealed no differences among mouse groups. This indicates that the HIS mouse model is comparable to, but not more sensitive than, the NSG immunodeficient model for studying the malignancy of stem cells. Since in vivo teratoma assay is cumbersome, in vitro methods for the detection of malignancy are urgently needed.

The mechanical properties of thermoplastic materials depend on temperature and strain rate. This study examined the development of a procedure to predict tensile moduli at different strain rates and temperatures, using experimental data from three-point-bending dynamic mechanical analysis (DMA). The method integrated different classical concepts of rheology to establish a closed formulation that will allow researchers save an important amount of time. Furthermore, it implied a significant decrease in the number of tests when compared to the commonly used procedure with a universal testing machine (UTM). The method was validated by means of a prediction of tensile moduli of polyamide PA66 in the linear elastic range, over a temperature range that included the glass-transition temperature. The method was applicable to thermo-rheologically simple materials under the hypotheses of isotropy, homogeneity, small deformations, and linear viscoelasticity. This method could be applicable to other thermoplastic materials, although it must be tested using these other materials to determine to what extent it can be applied reliably.

This retrospective study aimed to provide some clinical outcomes regarding effectiveness, toxicity, and quality of life in PCa patients treated with dose-escalated moderately hypofractionated radiation therapy (HFRT). Patients received HFRT to a total dose of 66 Gy in 22 fractions (3 Gy/fraction) delivered via volume modulated arc therapy (VMAT) in 2011-2016. Treatment effectiveness was measured by the biochemical failure-free survival rate. Toxicity was assessed according to the criteria of the Radiation Therapy Oncology Group (RTOG) and quality of life according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC). In this regard, quality of life (QoL) was measured longitudinally, at a median of 2 and 5 years after RT. Enrolled patients had low-risk (40.2%), intermediate-risk (47.5%), and high-risk (12.3%) PCa. Median follow-up was 75 months. The biochemical failure-free survival rate was 94.2%. The incidence of acute grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicity was 9.84% and 28.69%, respectively. The incidence rate of late grade 2 or higher GI and GU toxicity was 1.64% and 4.10%, respectively. Expanded Prostate Cancer Index Composite (EPIC) scores showed that the majority of patients maintained their QoL. HFRT to 66 Gy with VMAT was associated with adequate biochemical control, low toxicity and good reported GU and GI quality of life.

Rollators are widely used in clinical rehabilitation for gait assessment, but gait analysis usually requires a great deal of expertise and focus from medical staff. Smart rollators can capture gait parameters autonomously while avoiding complex setups. However, commercial smart rollators, as closed systems, can not be modified; plus, they are often expensive and not widely available. This work presents a low cost open-source modular rollator for monitorization of gait parameters and support. The whole system is based on commercial components and its software architecture runs over ROS2 to allow further customization and expansion. This paper describes the overall software and hardware architecture and, as an example of extended capabilities, modules for monitoring dynamic partial weight bearing and for estimation of spatiotemporal gait parameters of clinical interest. All presented tests are coherent from a clinical point of view and consistent with input data.

Carbon-based nanocomposites featuring enhanced electrical properties have seen increased adoption in applications involving electromagnetic interference shielding and electrostatic dissipation. As the commercialization of these materials grows, a thorough understanding of how thermal activation affects the rheology and electrical performance of CNT-epoxy blends can inform quality decisions throughout the production process. The aim of this work was the identification of the effects that thermal activation has on the electrical and rheological properties of uncured epoxy mixtures and how those may be tied to the resulting cured composites. Herein, three distinct CNT-loaded composite mixtures were characterized for changes in electrical resistivity and viscosity resulting from varying activation times. Electrical conductivity decreased as activation time increased. Uncured mixture viscosity exhibited a strong dependence on CNT loading and applied strain, with activation time being found to significantly reduce the viscosity of the uncured mixture and surface profile of cured composite films. In all cases, cured composites featured improved electrical conductivity over the uncured mixtures. Factors contributing to the observed behavior are discussed. Raman analysis, optical microscopy of CNT networks, and data from silica bead mixing and dispersion studies are presented to contextualize the results.

Chronic infections are one of the most serious adverse outcomes of prosthetic surgery. Prosthetic revision surgery using a bone cement loaded with antibiotics between the two stages of the surgery is commonly performed. However, this method often fails to reach the minimum inhibitory concentration and promotes antibiotic resistance, thus emphasizing the need for improving the current available therapies., Materials and Methods: In this study, we performed a study of the in vivo response of a polymer-based construct of poly (lactic- co -glycolic acid) (PLGA) in the solid phase of Palacos R ® in combination with vancomycin, daptomycin, and/or linezolid. To test its effectiveness, we applied an in vivo model, using both histological and immunohistochemical analyses to study the bone tissue., Results: The presence of PLGA in the combination of vancomycin with daptomycin showed the most promising results regarding the preservation of bone cytoarchitecture and S. aureus elimination. Conversely, the combination of vancomycin plus linezolid was associated with a loss of bone cytoarchitecture, probably related to an increased macrophage response and inefficient antimicrobial activity., Conclusions: The modification of Palacos R ® bone cement with PLGA microspheres and its doping with the antibiotic daptomycin in combination with vancomycin improve the tissue response to bone infection.

Conductive polymers have fundamental relevance as well as novel technological applications in the organic optoelectronics field. Their photophysical and transport properties strongly depend on the molecular arrangement, and nanoscale characterization is needed to fully understand the optoelectronic processes taking place in organic devices. In this work, we study the electrostatic properties of poly-3-octylthiophene isolated structures: disordered low-packed polymer chains and crystalline layered lamellar assemblies. We characterize the electronic ground state using Kelvin probe microscopy. This allows us to resolve a rich variety of surface potential regions that emerge over the different polymer structures. These SP regions are correlated with different molecular aggregates.

Mayaro virus (MAYV) is an emerging mosquito-transmitted virus that belongs to the genus Alphavirus within the family Togaviridae . Humans infected with MAYV often develop chronic and debilitating arthralgia and myalgia. The virus is primarily maintained via a sylvatic cycle, but it has the potential to adapt to urban settings, which could lead to large outbreaks. The interferon (IFN) system is a critical antiviral response that limits replication and pathogenesis of many different RNA viruses, including alphaviruses. Here, we investigated how MAYV infection affects the induction phase of the IFN response. Production of type I and III IFNs was efficiently suppressed during MAYV infection, and mapping revealed that expression of the viral non-structural protein 2 (nsP2) was sufficient for this process. Interactome analysis showed that nsP2 interacts with DNA-directed RNA polymerase II subunit A (Rpb1) and transcription initiation factor IIE subunit 2 (TFIIE2), which are host proteins required for RNA polymerase II-mediated transcription. Levels of these host proteins were reduced by nsP2 expression and during infection by MAYV and related alphaviruses, suggesting that nsP2-mediated inhibition of host cell transcription is an important aspect of how some alphaviruses block IFN induction. The findings from this study may prove useful in design of vaccines and antivirals, which are currently not available for protection against MAYV and infection by other alphaviruses.

In additive manufacturing (AM), the technology and processing parameters are key elements that determine the characteristics of samples for a given material. To distinguish the effects of these variables, we used the same AISI 316L stainless steel powder with different AM techniques. The techniques used are the most relevant ones in the AM of metals, i.e., direct laser deposition (DLD) with a high-power diode laser and selective laser melting (SLM) using a fiber laser and a novel CO 2 laser, a novel technique that has not yet been reported with this material. The microstructure of all samples showed austenitic and ferritic phases, which were coarser with the DLD technique than for the two SLM ones. The hardness of the fiber laser SLM samples was the greatest, but its bending strength was lower. In SLM with CO 2 laser pieces, the porosity and lack of melting reduced the fracture strain, but the strength was greater than in the fiber laser SLM samples under certain build-up strategies. Specimens manufactured using DLD showed a higher fracture strain than the rest, while maintaining high strength values. In all the cases, crack surfaces were observed and the fracture mechanisms were determined. The processing conditions were compared using a normalized parameters methodology, which has also been used to explain the observed microstructures.

The human parainfluenza virus 3 (HPIV3) poses a risk for pneumonia development in young children and immunocompromised patients. To investigate mechanisms of HPIV3 pathogenesis, we characterized the association state and host protein interactions of HPIV3 phosphoprotein (HPIV3 P), an indispensable viral polymerase cofactor. Sequence analysis and homology modeling predict that HPIV3 P possesses a long, disordered N-terminal tail (P TAIL ) a coiled-coil multimerization domain (P MD ), similar to the well-characterized paramyxovirus phosphoproteins from measles and Sendai viruses. Using a recombinantly expressed and purified construct of P MD and P TAIL , we show that HPIV3 P in solution is primarily an alpha-helical tetramer that is stable up to 60 °C. Pulldown and isothermal titration calorimetry experiments revealed that HPIV3 P binds the host hub protein LC8, and turbidity experiments demonstrated a new role for LC8 in increasing the solubility of HPIV3 P in the presence of crowding agents such as RNA. For comparison, we show that the multimerization domain of the Zaire Ebola virus phosphoprotein VP35 is also a tetramer and binds LC8 but with significantly higher affinity. Comparative analysis of the domain architecture of various virus phosphoproteins in the order Mononegavirales show multiple predicted and verified LC8 binding motifs, suggesting its prevalence and importance in regulating viral phosphoprotein structures. Our work provides evidence for LC8 binding to phosphoproteins with multiple association states, either tetrameric, as in the HPIV3 and Ebola phosphoproteins shown here, or dimeric as in rabies virus phosphoprotein. Taken together the data suggest that the association states of a virus-specific phosphoprotein and the complex formed by binding of the phosphoprotein to host LC8 are important regulators of viral function.

It is currently difficult to have a global state of the art vision of certain scientific topics. In the field of physical activity (PA) and exercise, this is due to information overload. The present study aims to provide a solution by analysing a large mass of scientific articles using text mining (TM). The purpose was to analyse what is being investigated in the PA health field on young people from primary, secondary and higher education. Titles and abstracts published in the Web of Science (WOS) database were analysed using TM on 24 November 2020, and after removing duplicates, 85,368 remained. The results show 9960 (unique) words and the most frequently used bi-grams and tri-grams. A co-occurrence network was also generated. 'Health' was the first term of importance and the most repeated bi-grams and tri-grams were 'body&#95;mass' and 'body&#95;mass&#95;index'. The analyses of the 20 topics identified focused on health-related terms, the social sphere, sports performance and research processes. It also found that the terms health and exercise have become more important in recent years.

In recent years, interest in home energy management systems (HEMS) has grown significantly, as well as the development of Voice Assistants that substantially increase home comfort. This paper presents a novel merging of HEMS with the Assistant paradigm. The combination of both concepts has allowed the creation of a high-performance and easy-to-manage expert system (ES). It has been developed in a framework that includes, on the one hand, the efficient energy management functionality boosted with an Internet of Things (IoT) platform, where artificial intelligence (AI) and big data treatment are blended, and on the other hand, an assistant that interacts both with the user and with the HEMS itself. The creation of this ES has made it possible to optimize consumption levels, improve security, efficiency, comfort, and user experience, as well as home security (presence simulation or security against intruders), automate processes, optimize resources, and provide relevant information to the user facilitating decision making, all based on a multi-objective optimization (MOP) problem model. This paper presents both the scheme and the results obtained, the synergies generated, and the conclusions that can be drawn after 24 months of operation.

Background and Objectives: Descriptions of end-of-life in COVID-19 are limited to small cross-sectional studies. We aimed to assess end-of-life care in inpatients with COVID-19 at Alicante General University Hospital (ALC) and compare differences according to palliative and non-palliative sedation. Material and Methods : This was a retrospective cohort study in inpatients included in the ALC COVID-19 Registry (PCR-RT or antigen-confirmed cases) who died during conventional admission from 1 March to 15 December 2020. We evaluated differences among deceased cases according to administration of palliative sedation. Results: Of 747 patients evaluated, 101 died (13.5%). Sixty-eight (67.3%) died in acute medical wards, and 30 (44.1%) received palliative sedation. The median age of patients with palliative sedation was 85 years; 44% were women, and 30% of cases were nosocomial. Patients with nosocomial acquisition received more palliative sedation than those infected in the community (81.8% [9/11] vs 36.8% [21/57], p = 0.006), and patients admitted with an altered mental state received it less (20% [6/23] vs. 53.3% [24/45], p = 0.032). The median time from admission to starting palliative sedation was 8.5 days (interquartile range [IQR] 3.0-14.5). The main symptoms leading to palliative sedation were dyspnea at rest (90%), pain (60%), and delirium/agitation (36.7%). The median time from palliative sedation to death was 21.8 h (IQR 10.4-41.1). Morphine was used in all palliative sedation perfusions: the main regimen was morphine + hyoscine butyl bromide + midazolam (43.3%). Conclusions : End-of-life palliative sedation in patients with COVID-19 was initiated quite late. Clinicians should anticipate the need for palliative sedation in these patients and recognize the breathlessness, pain, and agitation/delirium that foreshadow death.