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We reviewed 33 original research studies assessing brain perfusion, using consensus guidelines from a "white paper" issued by the International Society for Magnetic Resonance in Medicine Perfusion Study Group and the European Cooperation in Science and Technology Action BM1103 ("Arterial Spin Labelling Initiative in Dementia"; https://www.cost.eu/actions/BM1103/). The studies were published between 2011 and 2023 and included participants with subjective cognitive decline plus; neurocognitive disorders, including mild cognitive impairment (MCI), Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB) and vascular cognitive impairment (VCI); as well as schizophrenia spectrum disorders, bipolar and major depressive disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, panic disorder and alcohol use disorder. Hypoperfusion associated with cognitive impairment was the major finding across the spectrum of cognitive decline. Regional hyperperfusion also was reported in MCI, AD, frontotemporal dementia phenocopy syndrome and VCI. Hypoperfused structures found to aid in diagnosing AD included the precunei and adjacent posterior cingulate cortices. Hypoperfused structures found to better diagnose patients with FTLD were the anterior cingulate cortices and frontal regions. Hypoperfusion in patients with DLB was found to relatively spare the temporal lobes, even after correction for partial volume effects. Hyperperfusion in the temporal cortices and hypoperfusion in the prefrontal and anterior cingulate cortices were found in patients with schizophrenia, most of whom were on medication and at the chronic stage of illness. Infratentorial structures were found to be abnormally perfused in patients with bipolar or major depressive disorders. Brain perfusion abnormalities were helpful in diagnosing most neurocognitive disorders. Abnormalities reported in VCI and the remaining mental disorders were heterogeneous and not generalisable. [ABSTRACT FROM AUTHOR]

Skeletal muscle is a highly plastic tissue, able to change its mass and functional properties in response to several stimuli. Skeletal muscle mass is influenced by the balance between protein synthesis and breakdown, which is regulated by several signaling pathways. The relative contribution of Akt/mTOR signaling, ubiquitin-proteasome pathway, autophagy among other signaling pathways to protein turnover and, therefore, to skeletal muscle mass, differs depending on the wasting or loading condition and muscle type. By modulating mitochondria biogenesis, PGC-1α has a major role in the cell's bioenergetic status and, thus, on protein turnover. In fact, rates of protein turnover regulate differently the levels of distinct protein classes in response to atrophic or hypertrophic stimuli. Mitochondrial protein turnover rates may be enhanced in wasting conditions, whereas the increased turnover of myofibrillar proteins triggers muscle mass gain. The present review aims to update the knowledge on the molecular pathways implicated in the regulation of protein turnover in skeletal muscle, focusing on how distinct muscle proteins may be modulated by lifestyle interventions with emphasis on exercise training. The comprehensive analysis of the anabolic effects of exercise programs will pave the way to the tailored management of muscle wasting conditions. [ABSTRACT FROM AUTHOR]

We introduce a unified framework based on bi-level optimization schemes to deal with parameter learning in the context of image processing. The goal is to identify the optimal regularizer within a family depending on a parameter in a general topological space. Our focus lies on the situation with non-compact parameter domains, which is, for example, relevant when the commonly used box constraints are disposed of. To overcome this lack of compactness, we propose a natural extension of the upper-level functional to the closure of the parameter domain via Gamma-convergence, which captures possible structural changes in the reconstruction model at the edge of the domain. Under two main assumptions, namely, Mosco-convergence of the regularizers and uniqueness of minimizers of the lower-level problem, we prove that the extension coincides with the relaxation, thus admitting minimizers that relate to the parameter optimization problem of interest. We apply our abstract framework to investigate a quartet of practically relevant models in image denoising, all featuring nonlocality. The associated families of regularizers exhibit qualitatively different parameter dependence, describing a weight factor, an amount of nonlocality, an integrability exponent, and a fractional order, respectively. After the asymptotic analysis that determines the relaxation in each of the four settings, we finally establish theoretical conditions on the data that guarantee structural stability of the models and give examples of when stability is lost. [ABSTRACT FROM AUTHOR]

Significance: Infertility is a major global health problem, with nearly half of the cases being associated with male factors. Although reactive oxygen species (ROS) are crucial for sperm cell normal physiological processes, an imbalance between ROS production and antioxidants can lead to oxidative stress that can impair sperm function. Indeed, high semen ROS levels are reported in 30%–80% of infertile men. Recent Advances: Male oxidative stress infertility is an uprising classification for idiopathic infertility. Proteomic approaches, including quantitative mass spectrometry (MS)-based proteomics, are being utilized to explore the molecular mechanisms associated with oxidative stress in male infertility. Critical Issues: In this review, proteome data were collected from articles available on PubMed centered on MS-based proteomic studies, performed in seminal plasma and sperm cell samples, and enrolling men with impaired semen parameters. The bioinformatic analysis of proteome data with Cytoscape (ClueGO+CluePedia) and STRING tools allowed the identification of the biological processes more prevalent in asthenozoospermia, with focus on the ones related to oxidative stress. Future Directions: The identification of the antioxidant proteins in seminal plasma and sperm cells that can protect sperm cells from oxidative stress is crucial not only for a better understanding of the molecular mechanisms associated with male infertility but specially to guide new therapeutic possibilities. Antioxid. Redox Signal. 37, 501–520. [ABSTRACT FROM AUTHOR]

Background: Inflammation is widely recognized as the driving force of cachexia induced by chronic diseases; however, therapies targeting inflammation do not always reverse cachexia. Thus, whether inflammation per se plays an important role in the clinical course of cachectic patients is still a matter of debate. Aims: To give new insights into cachexia's pathogenesis and diagnosis, we performed a comprehensive literature search on the contribution of inflammatory markers to this syndrome, focusing on the noncommunicable diseases cancer and cardiovascular diseases. Methods: A systematic review was performed in PubMed using the keywords ("cancer" OR "cardiac" cachexia AND "human" OR "patient" AND "plasma" or "serum"). A total of 744 studies were retrieved and, from these, 206 were selected for full-text screening. In the end, 98 papers focusing on circulating biomarkers of cachexia were identified, which resulted in a list of 113 different mediators. Results: Data collected from the literature highlight the contribution of interleukin-6 (IL-6) and C-reactive protein (CRP) to cachexia, independently of the underlying condition. Despite not being specific, once the diagnosis of cachexia is established, CRP might help to monitor the effectiveness of anti-cachexia therapies. In cardiac diseases, B-type natriuretic peptide (BNP), renin, and obestatin might be putative markers of body wasting, whereas in cancer, growth differentiation factor (GDF) 15, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) C seem to be better markers of this syndrome. Independently of the circulating mediators, NF-κB and JAK/STAT signaling pathways play a key role in bridging inflammation with muscle wasting; however, therapies targeting these pathways were not proven effective for all cachectic patients. Conclusion: The critical and integrative analysis performed herein will certainly feed future research focused on the better comprehension of cachexia pathogenesis toward the improvement of its diagnosis and the development of personalized therapies targeting specific cachexia phenotypes. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the most lethal diseases in men, which justifies the search for new diagnostic tools. The aim of the present study was to gain new insights into the progression of prostate carcinogenesis by analyzing the urine proteome. To this end, urine from healthy animals and animals with prostate adenocarcinoma was analyzed at two time points: 27 and 54 weeks. After 54 weeks, the incidence of pre-neoplastic and neoplastic lesions in the PCa animals was 100%. GeLC-MS/MS and subsequent bioinformatics analyses revealed several proteins involved in prostate carcinogenesis. Increased levels of retinol-binding protein 4 and decreased levels of cadherin-2 appear to be characteristic of early stages of the disease, whereas increased levels of enolase-1 and T-kininogen 2 and decreased levels of isocitrate dehydrogenase 2 describe more advanced stages. With increasing age, urinary levels of clusterin and corticosteroid-binding globulin increased and neprilysin levels decreased, all of which appear to play a role in prostate hyperplasia or carcinogenesis. The present exploratory analysis can be considered as a starting point for studies targeting specific human urine proteins for early detection of age-related maladaptive changes in the prostate that may lead to cancer. [ABSTRACT FROM AUTHOR]

A CuCoBe–diamond composite was used to reinforce a laser textured 410 stainless steel piston ring by hot-pressing. Different hot-pressing parameters were used to optimize the sintering process of the CuCoBe particles (P = 25 and 50 MPa, T = 820 and 980 °C, and t = 15 and 30 min). The results showed an increase in the hardness of the hot-pressed samples (50.5% and 48.5% for P = 25 and 50 MPa, respectively). Three textures with different track widths and distances between them were produced by laser on the compression piston rings' surface. The composite powders were used for the reinforcement of the textures by hot-pressing at the optimized sintering parameters (T = 980 °C, P = 25 and 50 MPa, and t = 15 min). The tribological results revealed that larger texture dimensions led to enhanced tribological performance. [ABSTRACT FROM AUTHOR]

As people age, their skeletal muscle (SkM) experiences a decline in mitochondrial functionality and density, which leads to decreased energy production and increased generation of reactive oxygen species. This cascade of events, in turn, might determine the loss of SkM mass, strength and quality. Even though the mitochondrial processes dysregulated by aging, such as oxidative phosphorylation, mitophagy, antioxidant defenses and mtDNA transcription, are the same in both sexes, mitochondria age differently in the SkM of men and women. Indeed, the onset and magnitude of the impairment of these processes seem to be influenced by sex-specific factors. Sexual hormones play a pivotal role in the regulation of SkM mass through both genomic and non-genomic mechanisms. However, the precise mechanisms by which these hormones regulate mitochondrial plasticity in SkM are not fully understood. Although the presence of estrogen receptors in mitochondria is recognized, it remains unclear whether androgen receptors affect mitochondrial function. This comprehensive review critically dissects the current knowledge on the interplay of sex in the aging of SkM, focusing on the role of sex hormones and the corresponding signaling pathways in shaping mitochondrial plasticity. Improved knowledge on the sex dimorphism of mitochondrial aging may lead to sex-tailored interventions that target mitochondrial health, which could be effective in slowing or preventing age-related muscle loss. [Display omitted] [ABSTRACT FROM AUTHOR]

Sexual dimorphism greatly influences adipose tissue remodeling, which is characterized by changes in the activity, number, and/or size of adipocytes in response to distinct stimuli, including lifestyle and anti-obesity drugs. This sex dependence seems to be due to the anatomical and endocrine disparities between men and women. At the molecular level, sex hormones are believed to mediate such differences and involve estrogen and androgen receptor-induced gene expression. The signaling pathways that regulate adipose tissue metabolism and function include peroxisome proliferator-activated receptor gamma, uncoupling protein 1 (UCP1), 5' adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial oxidative phosphorylation (OXPHOS), among other molecular players. Sex hormone-related pathways also interplay with adrenergic signaling, probably the most well-characterized molecular mechanism implicated in the remodeling of white adipose tissue. This review overviews and integrates the signaling pathways behind sexual dimorphism in adipose tissue remodeling, hoping to increase the knowledge on the pathogenesis of diseases, such as obesity and related comorbidities, and consequently, to drive future studies to investigate the regulation of this tissue homeostasis, either in men or women. [ABSTRACT FROM AUTHOR]

In this work, we study the effective behavior of a two-dimensional variational model within finite crystal plasticity for high-contrast bilayered composites. Precisely, we consider materials arranged into periodically alternating thin horizontal strips of an elastically rigid component and a softer one with one active slip system. The energies arising from these modeling assumptions are of integral form, featuring linear growth and non-convex differential constraints. We approach this non-standard homogenization problem via Gamma-convergence. A crucial first step in the asymptotic analysis is the characterization of rigidity properties of limits of admissible deformations in the space BV of functions of bounded variation. In particular, we prove that, under suitable assumptions, the two-dimensional body may split horizontally into finitely many pieces, each of which undergoes shear deformation and global rotation. This allows us to identify a potential candidate for the homogenized limit energy, which we show to be a lower bound on the Gamma-limit. In the framework of non-simple materials, we present a complete Gamma-convergence result, including an explicit homogenization formula, for a regularized model with an anisotropic penalization in the layer direction. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS), characterized by a set of conditions that include obesity, hypertension, and dyslipidemia, is associated with increased cardiovascular risk. Exercise training (EX) has been reported to improve MetS management, although the underlying metabolic adaptations that drive its benefits remain poorly understood. This work aims to characterize the molecular changes induced by EX in skeletal muscle in MetS, focusing on gastrocnemius metabolic remodelling. 1H NMR metabolomics and molecular assays were employed to assess the metabolic profile of skeletal muscle tissue from lean male ZSF1 rats (CTL), obese sedentary male ZSF1 rats (MetS-SED), and obese male ZF1 rats submitted to 4 weeks of treadmill EX (5 days/week, 60 min/day, 15 m/min) (MetS-EX). EX did not counteract the significant increase of body weight and circulating lipid profile, but had an anti-inflammatory effect and improved exercise capacity. The decreased gastrocnemius mass observed in MetS was paralleled with glycogen degradation into small glucose oligosaccharides, with the release of glucose-1-phosphate, and an increase in glucose-6-phosphate and glucose levels. Moreover, sedentary MetS animals' muscle exhibited lower AMPK expression levels and higher amino acids' metabolism such as glutamine and glutamate, compared to lean animals. In contrast, the EX group showed changes suggesting an increase in fatty acid oxidation and oxidative phosphorylation. Additionally, EX mitigated MetS-induced fiber atrophy and fibrosis in the gastrocnemius muscle. EX had a positive effect on gastrocnemius metabolism by enhancing oxidative metabolism and, consequently, reducing susceptibility to fatigue. These findings reinforce the importance of prescribing EX programs to patients with MetS. • EX had an anti-inflammatory effect in animals with metabolic syndrome (MetS). • EX changed the metabolic profile of gastrocnemius from MetS rats. • EX counteracted the MetS-induced decrease of the amino acids Asp, Glu and Gly. • EX improved fatty acid oxidation and OXPHOS in the muscle of MetS subjects. • Data support the prescription of supervised EX to patients with MetS. [ABSTRACT FROM AUTHOR]

Mitochondrial fatty acid β-oxidation disorders (FAOD) are among the diseases detected by newborn screening in most developed countries. Alterations of mitochondrial functionality are characteristic of these metabolic disorders. However, many questions remain to be clarified, namely how the interplay between the signaling pathways harbored in mitochondria contributes to the disease-related phenotype. Herein, we overview the role of mitochondria on the regulation of cell homeostasis through the production of ROS, mitophagy, apoptosis, and mitochondrial biogenesis. Emphasis is given to the signaling pathways involving MnSOD, sirtuins and PGC-1α, which seem to contribute to FAOD phenotype, namely to multiple acyl-CoA dehydrogenase deficiency (MADD). The association between phenotype and genotype is not straightforward, suggesting that specific molecular mechanisms may contribute to MADD pathogenesis, making MADD an interesting model to better understand this interplay. However, more work needs to be done envisioning the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Exosomes are involved in a wide variety of biochemical processes in human body homeostasis. Exosomes also provide important information regarding communications among several organ systems. Additionally, they can serve as molecular vehicles to deliver drugs. Therefore, exosomes have received wide attention in current biomedical research for unraveling pathogenic mechanisms of diseases, searching for novel biomarkers, and discovering new drugs. This paper reviews and discusses the significance of urinary exosomes for a better understanding of human disease pathophysiology and their potential use as therapeutic targets. Isolation methods of exosomes and the latest technological advances are also discussed. Furthermore, novel urinary exosomal biomarkers are highlighted with special emphasis on their clinical applicability (particularly sensitivity, specificity, reliability, and other aspects). Finally, future trends for this field are analyzed and our perspectives are provided. [ABSTRACT FROM AUTHOR]

Sarcopenia is associated with reduced quality of life and premature mortality. The sex disparities in the processes underlying sarcopenia pathogenesis, which include mitochondrial dysfunction, are ill-understood and can be decisive for the optimization of sarcopenia-related interventions. To improve the knowledge regarding the sex differences in skeletal muscle aging, the gastrocnemius muscle of young and old female and male rats was analyzed with a focus on mitochondrial remodeling through the proteome profiling of mitochondria-enriched fractions. To the best of our knowledge, this is the first study analyzing sex differences in skeletal muscle mitochondrial proteome remodeling. Data demonstrated that age induced skeletal muscle atrophy and fibrosis in both sexes. In females, however, this adverse skeletal muscle remodeling was more accentuated than in males and might be attributed to an age-related reduction of 17beta-estradiol signaling through its estrogen receptor alpha located in mitochondria. The females-specific mitochondrial remodeling encompassed increased abundance of proteins involved in fatty acid oxidation, decreased abundance of the complexes subunits, and enhanced proneness to oxidative posttranslational modifications. This conceivable accretion of damaged mitochondria in old females might be ascribed to low levels of Parkin, a key mediator of mitophagy. Despite skeletal muscle atrophy and fibrosis, males maintained their testosterone levels throughout aging, as well as their androgen receptor content, and the age-induced mitochondrial remodeling was limited to increased abundance of pyruvate dehydrogenase E1 component subunit beta and electron transfer flavoprotein subunit beta. Herein, for the first time, it was demonstrated that age affects more severely the skeletal muscle mitochondrial proteome of females, reinforcing the necessity of sex-personalized approaches towards sarcopenia management, and the inevitability of the assessment of mitochondrion-related therapeutics. [Display omitted] • Females' age-related muscle atrophy is linked to reduced 17beta-estradiol signaling. • Males' age-related muscle atrophy occurs independently of testosterone signaling. • Age affects more severely the skeletal muscle mitochondrial proteome of females. • Age rises fatty acid oxidation and impairs oxidative phosphorylation only in females. • Age increases the proneness of mitochondrial proteins to oxidation only in females. [ABSTRACT FROM AUTHOR]

We consider a homogenization problem associated with quasi-crystalline multiple integrals of the form ... where ue varepsilon is subject to constant-coefficient linear partial diferential constraints. The quasi-crystalline structure of the underlying composite is encoded in the dependence on the second variable of the Lagrangian, fR, and is modeled via the cut-and-project scheme that interprets the heterogeneous microstructure to be homogenized as an irrational subspace of a higher-dimensional space. A key step in our analysis is the character- ization of the quasi-crystalline two-scale limits of sequences of the vector felds ue that are in the kernel of a given constant-coefcient linear partial diferential operator, Aue that is, = 0. Our results provide a generalization of related ones in the literature concerning the A = curl case to more general diferential operators A with constant coefcients and without coercivity assumptions on the Lagrangian fR. [ABSTRACT FROM AUTHOR]

The norm in classical Sobolev spaces can be expressed as a difference quotient. This expression can be used to generalize the space to the fractional smoothness case. Because the difference quotient is based on shifting the function, it cannot be used in generalized Orlicz spaces. In its place, we introduce a smoothed difference quotient and show that it can be used to characterize the generalized Orlicz–Sobolev space. Our results are new even in Orlicz spaces and variable exponent spaces. [ABSTRACT FROM AUTHOR]

In this paper, we characterize the asymptotic behavior of a first-order stationary mean-field game (MFG) with a logarithm coupling, a quadratic Hamiltonian, and a periodically oscillating potential. This study falls into the realm of the homogenization theory, and our main tool is the two-scale convergence. Using this convergence, we rigorously derive the two-scale homogenized and the homogenized MFG problems, which encode the so-called macroscopic or effective behavior of the original oscillating MFG. Moreover, we prove existence and uniqueness of the solution to these limit problems. [ABSTRACT FROM AUTHOR]

Understanding the reasons for the consumption of certain plant resources instead of others has important implications for biological conservation. This study aimed to answer the following question: What are the factors that determine the consumption and trade of certain wild fruit species among extractivists from two rural communities in northeastern Brazil? This study developed a participatory approach to identify the fruit species known and/or used by extractivists. The selected species were presented to the extractivists using semistructured interviews. A Likert scale (from 1 to 5) was used by interviewees to assign scores to 17 wild fruits in terms of local consumption, commercial potential, taste, nutritional potential, absence of adverse effects, postharvest durability, additional uses, temporal availability (fruit), spatial availability (fruit), spatial availability (plant), ease of collection, and ease of cultivation. Multiple regression analyses were performed to show the variables that best explained (1) the number of users, (2) the consumption intensity among users, (3) the number of traders, and (4) the commercial potential. The results showed that the spatial availability of the individual was the most outstanding variable to explain both the number of users and traders. However, for extractivists that trespass the availability barrier, taste is the most important driver of the consumption intensity and the commercial potential of plants. In contexts in which edible wild plants do not form the base of the local diet, taste may be more relevant in relation to other variables such nutritional potential. [ABSTRACT FROM AUTHOR]

In this paper, we study first-order stationary monotone meanfield games (MFGs) with Dirichlet boundary conditions. Whereas Dirichlet conditions may not be satisfied for Hamilton-Jacobi equations, here we establish the existence of solutions to MFGs that satisfy those conditions. To construct these solutions, we introduce a monotone regularized problem. Applying Schaefer's fixed-point theorem and using the monotonicity of the MFG, we verify that there exists a unique weak solution to the regularized problem. Finally, we take the limit of the solutions of the regularized problem and, using Minty's method, we show the existence of weak solutions to the original MFG. [ABSTRACT FROM AUTHOR]

• Targeted screening approach (PIS 97) was applied to monitor sulfate-based lipids in human biofluids and cells. • Sulfate-based lipids (SL) in lipid extracts included steroid sulfates, sulfoglycolipids and other SL. • Other SL included N-acyl taurine, hypurate conjugates, and polyphenol metabolites. • Lipid extracts exhibit a heterogeneous distribution of SL across human fluids and cells. • Sulphur/phosphorous estimates show seminal fluid and epithelial cells as highly enriched in SL. Sulfate-based lipids (SL) have been proposed as players in inflammation, immunity and infection. In spite of the many biochemical processes linked to SL, analysis on this class of lipids has only focused on specific SL sub-classes in individual fluids or cells leaving a range of additional SL in other biological samples unaccounted for. This study describes the mass spectrometry screening of SL in lipid extracts of human fluids (saliva, plasma, urine, seminal fluid) and primary human cells (RBC, neutrophils, fibroblasts and skin epidermal) using targeted precursor ion scanning (PIS) approach. The PIS 97 mass spectra reveal a wide diversity of SL including steroid sulfates, sulfoglycolipids and other unidentified SL, as well as metabolites such as taurines, sulfated polyphenols and hypurate conjugates. Semi-quantification of SL revealed that plasma exhibited the highest content of SL whereas seminal fluid and epithelial cells contained the highest sulphur to phosphorous (S/P) ratio. The complexity of biofluids and cells sulfateome presented in this study highlight the importance of expanding the panel of synthetic sulfate-based lipid standards. Also, the heterogenous distribution of SL provides evidence for the interplay of sulfotransferases/sulfatases, opening new avenues for biomarker discovery in oral health, cardiovascular, fertility and dermatology research areas. [ABSTRACT FROM AUTHOR]

Limiting cancer-induced cardiac damage has become an increasingly important issue to improve survival rates and quality of life. Exercise training has been shown to reduce cardiovascular complications in several diseases; however, its therapeutic role against cardiovascular consequences of cancer is in its infancy. In order to add new insights on the potential therapeutic effect of exercise training on cancer-related cardiac dysfunction, we used an animal model of urothelial carcinoma submitted to 13 weeks of treadmill exercise after 20 weeks of exposure to the carcinogenic N -butyl- N -(4-hydroxybutyl)-nitrosamine (BBN). Data showed that 13 weeks of treadmill exercise reverted cancer-induced cardiomyocytes atrophy and fibrosis, improved cardiac oxidative capacity given by citrate synthase activity and MnSOD content, and increased the levels of the mitochondrial biogenesis markers PGC-1α and mtTFA. Moreover, exercise training reverted cancer-induced decrease of cardiac c-kit levels suggesting enhanced regenerative ability of heart. These cardiac adaptations to exercise were related to a lower incidence of malignant urothelial lesions and less signs of inflammation. Taken together, data from the present study support the beneficial effect of exercise training when started after cancer diagnosis, envisioning the improvement of the cardiovascular function. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis. Pulmonary artery smooth muscle cells (PASMCs) play a crucial role in PAH pathophysiology, displaying a hyperproliferative, and apoptotic-resistant phenotype. In the present study, we evaluated the potential therapeutic role of terameprocol (TMP), an inhibitor of cellular proliferation and promoter of apoptosis, in a well-established pre-clinical model of PAH induced by monocrotaline (MCT) and studied the biological pathways modulated by TMP in PASMCs. Wistar rats injected with MCT or saline (SHAM group) were treated with TMP or vehicle. On day 21 after injection, we assessed bi-ventricular hemodynamics and cardiac and pulmonary morphometry. The effects of TMP on PASMCs were studied in a primary culture isolated from SHAM and MCT-treated rats, using an iTRAQ-based proteomic approach to investigate the molecular pathways modulated by this drug. In vivo, TMP significantly reduced pulmonary and cardiac remodeling and improved cardiac function in PAH. In vitro, TMP inhibited proliferation and induced apoptosis of PASMCs. A total of 65 proteins were differentially expressed in PASMCs from MCT rats treated with TMP, some of which involved in the modulation of transforming growth factor beta pathway and DNA transcription. Anti-proliferative effect of TMP seems to be explained, at least in part, by the down-regulation of the transcription factor HMGB1. Our findings support the beneficial role of TMP in PAH and suggest that it may be an effective therapeutic option to be considered in the clinical management of PAH. [ABSTRACT FROM AUTHOR]

Exercise training provides several cardiovascular benefits in both physiological and pathological conditions; however, its use as a therapeutic tool for pulmonary arterial hypertension (PAH) has been poorly explored. This study aimed to extend the comprehension of the cardioprotective effects of exercise training in the set of PAH focusing on the metabolic changes promoted by exercise in the right ventricle (RV). The monocrotaline animal model of PAH was used and male Wistar rats were submitted to two weeks of treadmill exercise training (5 days/week, 60 min/day, 25 m/min) following disease establishment. Trained rats showed an improved diastolic function (lower end-diastolic pressure and tau) despite the presence of cardiac overload (increased peak systolic pressure, end-diastolic pressure and arterial elastance). This enhanced hemodynamic response was paralleled by an increased uptake of glucose to cardiomyocytes through glucose transporter type 4 (GLUT4) followed by increased lactate dehydrogenase (LDH) activity. Exercise did not reverse the decrease of fatty acid oxidation related to PAH but increased the content of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Two weeks of exercise did not modulate the changes in amino acid metabolism secondary to PAH. Our work suggests that continuous aerobic exercise of moderate intensity, despite its short-term duration and application in a late stage of the disease, supports the RV response to PAH by promoting a shift in the cardiac metabolic phenotype. [Display omitted] • Two weeks of exercise training improved right ventricle diastolic function in MCT rats. • Exercise increased glucose uptake through GLUT4 and its oxidation to lactate. • Exercise did not reverse MCT-induced decrease reliance of RV on fatty acid oxidation. • Exercise moderately impacted amino acid metabolism in the RV of MCT rats. • Metabolic adaptations of trained RV are regulated by PGC-1α and PPAR-γ. [ABSTRACT FROM AUTHOR]

Here, we consider stationary monotone mean-field games (MFGs) and study the existence of weak solutions induced by monotonicity. First, we introduce a regularized problem that preserves the monotonicity. Next, using variational inequality techniques, we prove the existence of solutions to the regularized problem. Then, using Minty's method, we establish the existence of weak solutions for the original MFG. Finally, we examine the properties of these weak solutions in several examples. Our methods provide a general framework to construct weak solutions to stationary MFGs with local, nonlocal, or congestion terms. [ABSTRACT FROM AUTHOR]

Platinum-based drugs are among the most effective anticancer therapies, integrating the standard of care for numerous human malignancies. However, platinum-based chemotherapy induces severe side-effects in cancer patients, such as cachexia. Weight loss, as well as fatigue and systemic inflammation are characteristics of this syndrome that adversely affects the survival and the quality of life of cancer patients. The signalling pathways involved in chemotherapy-induced cachexia are still to be fully understood, but the activity of several mediators associated with muscle wasting, such as myostatin and pro-inflammatory cytokines are increased by platinum-based drugs like cisplatin. Indeed, the molecular mechanisms behind chemotherapy-induced muscle wasting seem to be similar to the ones promoted by cancer in treatment-naive patients. Although some therapeutic agents are under investigation for treating muscle wasting in cancer patients, no effective treatment is yet available. Herein, we review the molecular mechanisms proposed to be involved in chemotherapy-related muscle wasting with a focus on the typical platinum-based drug cisplatin. Therapeutic strategies presently under investigation are also reviewed, providing an overview of the current efforts to preserve muscle mass and quality of life among cancer patients. [ABSTRACT FROM AUTHOR]

Mean-field games (MFGs) are models for large populations of competing rational agents that seek to optimize a suitable functional. In the case of congestion, this functional takes into account the difficulty of moving in high-density areas. Here, we study stationary MFGs with congestion with quadratic or power-like Hamiltonians. First, using explicit examples, we illustrate two main difficulties: the lack of classical solutions and the existence of areas with vanishing densities. Our main contribution is a new variational formulation for MFGs with congestion. With this formulation, we prove the existence and uniqueness of solutions. Finally, we consider applications to numerical methods. [ABSTRACT FROM AUTHOR]

Cancer-induced cardiac cachexia is an insidious syndrome with a dramatic impact on a patient’s quality of life and survival. Since exercise training provides several cardiovascular benefits in both physiological and pathological conditions (e.g., athletes and patients with heart failure, respectively), its use as a preventive and/or therapeutic tool for cancer-induced cardiac cachexia has been hypothesized. Existing evidence on the effects of exercise training in this particular setting is limited, but points towards a beneficial outcome. We report the current knowledge on cancer-induced cardiac cachexia and discuss the molecular pathways that may be modulated by exercise training in this setting, providing insights into possible future roads of study, namely in stem cell research and cardiac regeneration. [ABSTRACT FROM AUTHOR]

Objective: There are few quantitative studies on art therapy for the treatment of depression. The objective of this study was to evaluate if art therapy is beneficial as an adjuvant treatment for depression in the elderly. Methods: A randomized, controlled, single-blind study was carried out in a sample of elderly women with major depressive disorder (MDD) stable on pharmacotherapy. The experimental group (EG) was assigned to 20 weekly art therapy sessions (90 min/session). The control group (CG) was not subjected to any adjuvant intervention. Patients were evaluated at baseline and after 20 weeks, using the Geriatric Depression Scale (GDS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and cognitive measures. Results: Logistic regression analysis adjusted for age revealed that women in EG (n=31) had significant improvement in GDS (p = 0.007), BDI (p = 0.025), and BAI (p = 0.032) scores as compared with controls (n=25). No difference was found in the cognitive measures. Conclusion: Art therapy as an adjunctive treatment for MDD in the elderly can improve depressive and anxiety symptoms. Clinical trial registration: RBR-2YXY7Z [ABSTRACT FROM AUTHOR]

The common bottlenose dolphin (Tursiops truncatus) is a top marine predator widely dispersed in coastal and pelagic habitats and with a generalist feeding behavior. Yet, information on the trophic ecology of animals inhabiting pelagic environments is still scarce. Using carbon (δ13C: 13C/12C) and nitrogen (δ15N: 15N/14N) stable isotope ratios, we identified and quantified the main groups of prey assimilated by bottlenose dolphins inhabiting an oceanic habitat (Madeira Island, East Atlantic). Bottlenose dolphins assimilated pelagic, schooling fish (such as blue jack mackerel, Trachurus picturatus) and mesopelagic and demersal squids, which reinforces the pelagic dietary composition of insular/oceanic dolphins. Also, intra-seasonal differences were found in their stable isotope ratios, which suggest intraspecific variability in the feeding behavior among individuals living in the same area. Sex was not the main factor contributing to these differences, suggesting the lack of trophic niche segregation between adult males and females in this offshore environment. Nonetheless, further studies including different life stages and information on the ecophysiological requirements are necessary to disclose the factors responsible for the observed variability. This study showed that insular dolphins fed primarily on economically important pelagic prey, highlighting the need of developing management strategies that integrate conservation in fisheries plans. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a prevalent malignancy affecting men worldwide. Animal models play a crucial role in studying PCa pathology and discovering novel approaches to prevent, detect and treat this disease. However, the challenge of translational medicine is the limited reproducibility and inadequate recapitulation of human conditions in animal models. Therefore, a comprehensive understanding of the macroscopic and microscopic anatomy of the prostate gland among distinct animal species is essential for better translating research findings to clinical practice. This review aims to compare and describe the macroscopic and microscopic anatomy of the prostate gland in humans, rats, and dogs, emphasizing the relevant features. Despite the anatomical differences between these species, rats are a valuable model to study human prostate diseases, once they share some features implicated in carcinogenesis in humans. Dogs, on the other hand, are considered the best model for studying PCa due to the development of spontaneous cancer with a higher incidence when compared with other animals and the development of bone metastases. Moreover, the lymphatic system and the sentinel lymph node role and mapping are similar in dogs and humans. However, it is important to recognize that no animal model can directly mimic all aspects of PCa as the human prostate is anatomically different from that of rats and dogs. Therefore, it is essential to analyze and understand the intra- and interspecies variability when translating research findings into clinical practice. This review highlights the importance of a thorough understanding of the anatomical differences between the prostate gland in humans, rats, and dogs when selecting the appropriate animal model for studying PCa. [ABSTRACT FROM AUTHOR]

Background Exercise training has been recognized as a non-pharmacological therapeutic approach in several chronic diseases; however it remains to be tested if exercise preconditioning can positively interfere with the natural history of pulmonary arterial hypertension (PAH). This is important since the majority of these patients are diagnosed at advanced stages of the disease, when right ventricle (RV) impairment is already present. Objectives In the current study, we evaluated the preventive effect of exercise preconditioning on RV failure secondary to PAH, with a focus on the signaling pathways modulated by pro-inflammatory cytokines from TNF superfamily. Methods We analyzed the RV muscle from adult male Wistar rats exposed to a 4-week treadmill exercise training or sedentary regime, prior to the administration of monocrotaline (MCT) to induce PAH or with saline solution (controls). Results Data indicate that exercise preconditioning prevented cardiac hypertrophy and RV diastolic dysfunction. At a molecular level, exercise modulated the TWEAK/NF-κB signaling axis and prevented the shift in MHC isoforms towards an increased expression of beta-MHC. Exercise preconditioning also prevented the increase of atrogin-1 expression, and induced a shift of MMP activity from MMP-9 to MMP-2 activity. Conclusions Altogether, data support exercise as a preventive strategy for the management of PAH, which is of particular relevance for the familial form of PAH that is manifested by greater severity or earlier onset. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is responsible for the premature death mainly because of progressive and severe heart failure. This disease is characterized by increased pulmonary vascular tone, inflammatory cell infiltration, vascular remodeling and occlusion of vessels with thrombi, frequently leading to right heart failure. Aiming to better comprehend the complexity of PAH and find novel therapeutic strategies or improve the existing ones, a variety of preclinical models have emerged. Although there is no ideal preclinical model of PAH currently available, animal models have been used to assist in the identification of the molecular pathways underlying PAH development and progression, and in the identification of novel therapeutics. Among preclinical models of PAH, monocrotaline (MCT) animal model offers the advantage of mimic several key aspects of human PAH, including vascular remodeling, proliferation of smooth muscle cells, endothelial dysfunction, upregulation of inflammatory cytokines, and right ventricle failure, requiring a single drug injection. This review summarizes the advantages and limitations of MCT animal model to the study of the molecular mechanisms underlying PAH pathogenesis, envisioning to improve the diagnosis and management of this complex disease. [ABSTRACT FROM AUTHOR]

Objective This study explored whether a cartoon show with healthy eating messages positively affected children's food choices and food preferences. Design Experimental between-subjects design. Setting Four elementary schools in Portugal were investigated. Participants Children (aged 4–8 years; n = 142) were randomly assigned to 1 of 2 groups: a comparison group (n = 73) was exposed to cartoons with no reference to food and an intervention group (n = 69) was exposed to cartoons with healthy eating messages. After viewing, each child was given the opportunity to eat ad libitum for 10 minutes from a small selection of snack foods. Main Outcome Measure Number of healthy and unhealthy food items chosen. Food preferences were measured using an adapted version of the Leeds Food Preference Checklist. Analysis Generalized linear models were used to test for differences between groups. Results were considered significant at P  ≤ .05. Results Children in the experimental group chose significantly more healthy food items than did those in the comparison group (B = –.600; SE = .19; P  < .05). Conclusions and Implications Future studies may address the effect of prolonged exposure to healthy eating cartoons. Cartoons can be used to promote healthy food choices and can be a part of health promotion campaigns. [ABSTRACT FROM AUTHOR]

Abstract: Management and conservation issues are addressed through the identification of areas of particular importance, which requires the acquisition of baseline information on species distribution and dynamics. These types of data are particularly difficult to obtain at high resolution for large marine vertebrates like cetaceans, given that dedicated surveys are complex and logistically expensive. This study uses daily presence–absence sighting data of cetaceans collected year‐round from whale‐watching boats to support the theory that fine‐scale data obtained from platforms of opportunity can provide valuable information on species occurrence and group dynamics. Data from 7,551 (daily) sightings comprising 22 species were collected from 3,527 surveyed days over 11 years (mean of 321 days per year, SD = 17) in the pelagic environment of Madeira Island. Cetaceans were observed on 92% of the surveyed days, and a mean of 15.4 (SD = 1.5), 8.2 (SD = 2.0) and 2.1 (SD = 1.2) species were recorded per year, month, and day, respectively. There were significant differences in the number of species per month (p < .001), with the highest diversity recorded in June. At least nine species, comprising 96% of all sightings, were found to use the Madeiran waters on a regular basis, such as the Atlantic spotted dolphin (Stenella frontalis), the short‐beaked common dolphin (Delphinus delphis), the bottlenose dolphin (Tursiops truncatus), and others featured in the Red List of the International Union for Conservation of Nature as Endangered, Vulnerable, and Data Deficient. In addition, 10 species were found to use the Madeiran waters for travelling, feeding, resting, socializing and calving, which suggests that the southern and southeastern waters of Madeira Island constitute an area of interest for cetaceans. This study characterizes the cetaceans’ community structure (occurrence, aggregation sizes, behaviours, proportion of calves, and inter‐specific relationships) of a poorly studied region, providing important information for managers. Finally, the advantages and limitations of using fine‐scale data from a type of platform of opportunity that is increasing along coastlines globally are discussed. [ABSTRACT FROM AUTHOR]

A variational model for imaging segmentation and denoising color images is proposed. The model combines Meyer's 'u+v' decomposition with a chromaticity-brightness framework and is expressed by a minimization of energy integral functionals depending on a small parameter $$\varepsilon >0$$ . The asymptotic behavior as $$\varepsilon \rightarrow 0^+$$ is characterized, and convergence of infima, almost minimizers, and energies are established. In particular, an integral representation of the lower semicontinuous envelope, with respect to the $$L^1$$ -norm, of functionals with linear growth and defined for maps taking values on a certain compact manifold is provided. This study escapes the realm of previous results since the underlying manifold has boundary, and the integrand and its recession function fail to satisfy hypotheses commonly assumed in the literature. The main tools are $$\Gamma $$ -convergence and relaxation techniques. [ABSTRACT FROM AUTHOR]

The article offers information on a study related to bottlenose whale (Hyperoodon ampullatus) found in Madeira Archipelago, Northeast Atlantic. Topics discussed include sighting of this species in Madeira in autumn due to spatial migration; high abundance of cetacean species found in three archipelagos of Madeira, Azores, and the Canary Islands; and its main threats includes interactions with fishing gear and ocean noise.

Heart failure (HF) is growing in prevalence, due to an increase in aging and comorbidities. Heart failure with reduced ejection fraction (HFrEF) is more common in men, whereas heart failure with preserved ejection fraction (HFpEF) has a higher prevalence in women. However, the reasons for these epidemiological trends are not clear yet. Since HFpEF affects mostly postmenopausal women, sex hormones should play a pivotal role in HFpEF development. Furthermore, for HFpEF, contrary to HFrEF, effective therapeutic approaches are missing. Interestingly, studies evidenced that some therapies can have better results in women than in HFpEF men, emphasizing the necessity of understanding these observations at a molecular level. Thus, herein, we review the molecular mechanisms of estrogen and androgen actions in the heart in physiological conditions and explain how its dysregulation can lead to disease development. This clarification is essential in the road for an effective personalized management of HF, particularly HFpEF, towards the development of sex-specific therapeutic approaches. [ABSTRACT FROM AUTHOR]

Abstract: Pulmonary arterial hypertension (PAH) is a complex and multifactorial disease characterized by vascular remodeling, vasoconstriction, inflammation and thrombosis. Although the available therapies have resulted in improvements in morbidity and survival, PAH remains a severe and devastating disease with a poor prognosis and a high mortality, justifying the need of novel therapeutic targets. An increasing number of studies have demonstrated that endothelial cells (ECs), smooth muscle cells (SMCs) and fibroblasts of the pulmonary vessel wall, as well as platelets and inflammatory cells have a role in PAH pathogenesis. This review aims to integrate the interplay among different types of cells, during PAH development and progression, and the impact of current therapies in cellular modulation. The interplay among endothelial cells, smooth muscle cells and fibroblasts present in pulmonary vessels wall, platelets and inflammatory cells is regulated by several mediators produced by these cells, contributing to the pathophysiologic features of PAH. Current therapies are mainly focused in the pulmonary vascular tone and in the endothelial dysfunction. However, once they have not been effective, novel therapies targeting other PAH features, such as inflammation and platelet dysfunction are emerging. Further understanding of the interplay among different vascular cell types involved in PAH development and progression can contribute to find novel therapeutic targets, decreasing PAH mortality and morbidity in the future. [Copyright &y& Elsevier]

Highlights: [•] Survivin interacts with more than 46 distinct proteins. [•] Interactions are mostly related with apoptosis and cell proliferation. [•] Survivin interactions are regulated by post-translational modifications. [•] Survivin overexpression is therapeutically targeted to promote cell apoptosis. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) is an excellent source of biological information regarding the nervous system, once it is in close contact and accurately reflects alterations in this system. Several studies have analyzed differential protein profiles of CSF samples between healthy and diseased human subjects. However, the pathophysiological mechanisms and how CSF proteins relate to diseases are still poorly known. By applying bioinformatics tools, we attempted to provide new insights on the biological and functional meaning of proteomics data envisioning the identification of putative disease biomarkers. Bioinformatics analysis of data retrieved from 99 mass spectrometry (MS)-based studies on CSF profiling highlighted 1985 differentially expressed proteins across 49 diseases. A large percentage of the modulated proteins originate from exosome vesicles, and the majority are involved in either neuronal cell growth, development, maturation, migration, or neurotransmitter-mediated cellular communication. Nevertheless, some diseases present a unique CSF proteome profile, which were critically analyzed in the present study. For instance, 48 proteins were found exclusively upregulated in the CSF of patients with Alzheimer’s disease and are mainly involved in steroid esterification and protein activation cascade processes. A higher number of exclusively upregulated proteins were found in the CSF of patients with multiple sclerosis (76 proteins) and with bacterial meningitis (70 proteins). Whereas in multiple sclerosis, these proteins are mostly involved in the regulation of RNA metabolism and apoptosis, in bacterial meningitis the exclusively upregulated proteins participate in inflammation and antibacterial humoral response, reflecting disease pathogenesis. The exploration of the contribution of exclusively upregulated proteins to disease pathogenesis will certainly help to envision potential biomarkers in the CSF for the clinical management of nervous system diseases. [ABSTRACT FROM PUBLISHER]

Left-right patterning and asymmetric morphogenesis arise from a complex set of molecular and cellular interactions that are particularly dynamic and associated with mechanical forces. How do mechanical forces translate into tissular asymmetries? Are these forces asymmetrical de novo , or do they build up from pre-existing asymmetries? Advances in developmental genetics, live imaging and cell biology have recently shed light on the origins of mechanical forces generated at the cell scale and their implication in asymmetric patterning and morphogenesis is now emerging. Here we ask when and how, molecular asymmetries and mechanical forces contribute to left-right patterning and organ asymmetries. [ABSTRACT FROM AUTHOR]

Histamine is a biogenic amine, synthetized and released by mast cells, which acts as a vasodilator in several pathologic processes, namely in allergies and conjunctivitis. Its role on cancer is not fully understood. High levels of histamine have been associated with a bivalent behavior in regulation of several tumors ( i . e . cervical, ovarian, vaginal, uterine, vulvar, colorectal cancer, and melanoma), promoting or inhibiting their growth. Histamine receptors (H1, H2, H3 and H4) are present in a vast group of cells, including tumor cells, making them sensitive to histamine variations. In this work, we review the role of mast cells and histamine on cancer development and the possibility of use antihistamines in the clinical management of this disease. [ABSTRACT FROM AUTHOR]

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease. [ABSTRACT FROM AUTHOR]

The aim of this paper, which deals with a class of singular functionals involving difference quotients, is twofold: deriving suitable integral conditions under which a measurable function is polynomial and stating necessary and sufficient criteria for an integrable function to belong to a k th-order Sobolev space. One of the main theorems is a new characterization of W k , p ( Ω ) , k ∈ N and p ∈ ( 1 , + ∞ ) , for arbitrary open sets Ω ⊂ R n . In particular, we provide natural generalizations of the results regarding Sobolev spaces summarized in Brézis’ overview article [Brézis (2002)] to the higher-order case, and extend the work [Borghol (2007)] to a more general setting. [ABSTRACT FROM AUTHOR]

Exercise training is a well-known non-pharmacological strategy for the prevention and treatment of cardiovascular diseases. Despite the established phenotypic knowledge, the molecular signature of exercise-induced cardiac remodeling remains poorly characterized. The great majority of studies dedicated to this topic use conventional reductionist methods, which only allow analyzing individual protein candidates. Nowadays, several methodologies based on mass spectrometry are available and have been successfully applied for the characterization of heart proteome, representing an attractive approach for the wide characterization of the complex molecular networks that underlie exercise-induced cardiac remodeling. Still, few studies have used these methodologies to understand the impact of exercise training on the remodeling of cardiac proteome. The present study analyzes the few available data obtained from mass spectrometry (MS)-based proteomic studies assessing the impact of distinct types of exercise training on the protein profile of heart (left ventricle and isolated mitochondria) and the potential cross-tolerance between exercise training and diseases as myocardial infarction and obesity. Network analysis was performed with bioinformatics to integrate data from distinct research papers, based on distinct exercise training protocols, animal models and methodological approaches applied in the characterization of heart proteome. The analysis revealed that exercise training confers a unique proteome signature characterized by the up-regulation of lipid and organic metabolic processes, vasculogenesis and tissue regeneration. Data retrieved from this analysis also suggested that cardiac mitochondrial proteome is highly dynamic in response to exercise training due, in part, to the action of specific kinases as PKA and PKG. Regarding to the type of exercise, treadmill training seems to have a greater effect on the modulation of cardiac proteome than swimming. Data from the present review will certainly open new perspectives on cardiac proteomics and will help to envisage future studies targeting the identification of the regulatory mechanisms underlying cardiac adaptive and maladaptive remodeling. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we consider the long-term convergence (trend toward an equilibrium) of finite state mean-field games using Γ-convergence. Our techniques are based on the observation that an important class of mean-field games can be viewed as the Euler–Lagrange equation of a suitable functional. Therefore, using a scaling argument, one can convert a long-term convergence problem into a Γ-convergence problem. Our results generalize previous results related to long-term convergence for finite state problems. [Copyright &y& Elsevier]

A disparity in gender incidence has been reported in both papillary thyroid carcinoma (PTC) and chronic lymphocytic thyroiditis (CLT) diseases frequently associated and whose incidence has been increasing in parallel. We aimed to analyze differences in morphometric variables between male and female PTC patients and their relationship with the presence of concurrent CLT. The nuclear texture features of 100 hematoxylin-eosin stained nuclei from 100 consecutive classic PTC patients enrolled in our service were compared with their clinical and pathological features, including the presence of CLT. All patients were submitted to a standard management protocol and followed-up for 13-248 months (Mo = 117 months). Chromatin in women tended to present a denser and more homogeneous structure, in a less mottled pattern, with higher values of energy ( p = 0.008) and diagonal moment ( p = 0.032) than men. Concurrent CLT was more prevalent in women (41.42%) than in men (13.33%, p = 0.04) and was associated with higher cluster prominence values ( p = 0.027), a parameter that indicates a predominance of high nuclear contrasted heterochromatin. A multivariate logistic regression analysis showed that higher cluster prominence was independently correlated with chromatin in patients who presented CLT but did not demonstrate any association between concurrent CLT and gender. We were unable to demonstrate any association between gender and any characteristic of tumor aggressiveness or patients outcome. Our results suggest that chromatin texture of hematoxylin-eosin stained nuclei in paraffin sections of PTC cells is related to both gender and concurrent CLT. [ABSTRACT FROM AUTHOR]

The application of whole genome sequencing of Mycobacterium tuberculosis directly on clinical samples has been investigated as a means to avoid the time-consuming need for culture isolation that can lead to a potential prolonged suboptimal antibiotic treatment. We aimed to provide a proof-of-concept regarding the application of the molecular capture of M. tuberculosis genomes directly from positive sputum samples as an approach for epidemiological and drug susceptibility predictions. Smear-positive sputum samples (n = 100) were subjected to the SureSelectXT HS Target Enrichment protocol (Agilent Technologies, Santa Clara, CA, USA) and whole-genome sequencing analysis. A higher number of reads on target were obtained for higher smear grades samples (i.e., 3+ followed by 2+). Moreover, 37 out of 100 samples showed ≥90% of the reference genome covered with at least 10-fold depth of coverage (27, 9, and 1 samples were 3+, 2+, and 1+, respectively). Regarding drug-resistance/susceptibility prediction, for 42 samples, ≥90% of the >9000 hits that are surveyed by TB-profiler were detected. Our results demonstrated that M. tuberculosis genome capture and sequencing directly from clinical samples constitute a potential valid backup approach for phylogenetic inferences and resistance prediction, essentially in settings when culture is not routinely performed or for samples that fail to grow. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells‐based regenerative orthopedic therapies have been used in cats as a promising and innovative therapeutic approach to enhance the repair of bone defects. Adipose tissue‐derived stromal cells (ADSCs) can be obtained from two main sites—subcutaneous and visceral—with established differences regarding structure, composition, cell content, and functionality. However, in cats, to the best of the authors' knowledge, no studies have been conducted to compare the functional activity of the ADSCs isolated from the two sites, and the impact of these differences on the induced osteogenic potential. Additionally, retinoic acid has been recently regarded as a new osteogenic inducer within cells of distinct species, with undisclosed functionality on cat‐derived cell populations. Thus, the present study aimed to evaluate the functional activity of ADSCs isolated from the subcutaneous and visceral adipose sites (SCAT and VAT, respectively) of the cat, as well as the effects of two osteogenic‐inducing conditions—the classic dexamethasone, β‐glycerophosphate and ascorbic acid‐supplemented media (Dex + β + AAM), and Retinoic Acid‐supplemented media (RAM). The adipose tissue of subcutaneous and visceral origin was isolated, characterized, and ADSCs were isolated and grown in the presence of the two osteogenic‐inducing conditions, and characterized in terms of proliferation, metabolic activity, morphology, and osteogenic activity. Our results demonstrated a distinct biological profile of the two adipose tissue sites regarding cell size, vascularization, and morphology. Further, osteogenic‐induced ADSCs from both sites presented an increased expression of alkaline phosphatase activity (ALP) and cytochemical staining, as compared with control. Overall, RAM induced higher levels of ALP activity than Dex + β + AAM, supporting an increased osteogenic activation. Additionally, VAT was the tissue with the best osteogenic potential, showing higher levels of ALP expression, particularly with RAM. In conclusion, different characteristics were found between the two adipose tissue sites—SCAT and VAT, which probably reflect the differences found in the functionality of isolated ADSCs from both tissues. Furthermore, for cat, VAT shows a greater osteogenic‐inductive capacity than SCAT, particularly with RAM, which can be of therapeutic relevance for regenerative medicine applications. [ABSTRACT FROM AUTHOR]

The implementation of Building Information Modelling (BIM) in the Architecture, Engineering, Construction and Operations (AECO) industry requires multidisciplinary teams equipped with new technical and managerial skills. Professionals that are inexperienced or unfamiliar with the BIM design process face difficulties in transposing complex concepts into BIM modelling and coordination practices, despite governments, industry bodies, and academia's efforts. With this issue in mind, this article's objective is to present the teaching-learning strategies and tools adopted in a practical case of modelling an existing building on a BIM platform. In terms of method, a phenomenological approach has been taken to report on an exploratory didactic experience. The Cognitive Load Theory (CLT) was used to assess learning based on the authors' perceptions. The research has been structured into the following five stages: Literature Review; Analysis of Brazilian and International BIM Standards and Guides; Didactic exercise; Experience Assessment; and Conclusions. The results reveal aspects of BIM processes that can be widely investigated in an academic environment, such as the BIM design and coordination process model, which can be explored as a tool in the BIM teaching-learning process. Also, difficulties related to teaching BIM management processes were identified, thus calling for different didactic approaches. The contributions made by the research come from reporting and analysing the process of learning complex BIM content from the perspective of inexperienced professionals. The work also contributes to the field through the BIM learning assessment proposal and the BIM process model resulted from the authors' practical experience. [ABSTRACT FROM AUTHOR]