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Thermal treatments that use ultrasound devices as a tool have as a key point the temperature control to be applied in a specific region of the patient's body. This kind of procedure requires caution because the wrong regulation can either limit the treatment or aggravate an existing injury. Therefore, determining the temperature in a region of interest in real-time is a subject of high interest. Although this is still an open problem, in the field of ultrasound analysis, the use of machine learning as a tool for both imaging and automated diagnostics are application trends. In this work, a data-driven approach is proposed to address the problem of estimating the temperature in regions of a B-mode ultrasound image as a supervised learning problem. The proposal consists in presenting a novel data modeling for the problem that includes information retrieved from conventional B-mode ultrasound images and a parametric image built based on changes in backscattered energy (CBE). Then, we compare the performance of classic models in the literature. The computational results presented that, in a simulated scenario, the proposed approach that a Gradient Boosting model would be able to estimate the temperature with a mean absolute error of around 0.5°C, which is acceptable in practical environments both in physiotherapic treatments and high intensity focused ultrasound (HIFU).

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Cervical cancer (CC) poses a significant burden on individuals in developing regions, exhibiting heterogeneous responses to standard chemoradiation therapy, and contributing to substantial mortality rates. Unraveling host immune dynamics holds promise for innovative therapies and discovery of clinically relevant biomarkers. We studied prospectively locally advanced CC patients pre-treatment, stratifying them as responders (R) or non-responders (NR). R patients had increased tumor-infiltrating lymphocytes (TILs), while NR patients showed elevated PD-1 scores, CD8+ and PD-L2+ TILs, and PD-L1 immune reactivity. NR patients exhibited higher systemic soluble mediators correlating with TIL immune markers. R patients demonstrated functional polarization of CD4 T cells (Th1, Th2, Th17, and Treg), while CD8+ T cells and CD68+ macrophages predominated in the NR group. Receiver operating characteristic analysis identified potential CC response predictors, including PD-L1-immunoreactive (IR) area, PD-L2, CD8, FGF-basic, IL-7, IL-8, IL-12p40, IL-15, and TNF-alpha. Dysfunctional TILs and imbalanced immune mediators contribute to therapeutic insufficiency, shedding light on local and systemic immune interplay. Our study informs immunological signatures for treatment prediction and CC prognosis.

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Galactinol synthase (GolS) catalyzes the first and rate-limiting step in the synthesis of raffinose family of oligosaccharides (RFOs), which serve as storage and transport sugars, signal transducers, compatible solutes and antioxidants in higher plants. The present work aimed to assess the potential functions of citrus GolS in mechanisms of stress response and tolerance. By homology searches, eight GolS genes were found in the genomes of Citrus sinensis and C. clementina. Phylogenetic analysis showed that there is a GolS ortholog in C. clementina for each C. sinensis GolS, which have evolved differently from those of Arabidopsis thaliana. Transcriptional analysis indicated that most C. sinensis GolS (CsGolS) genes show a low-level tissue-specific and stress-inducible expression in response to drought and salt stress treatments, as well as to 'Candidatus Liberibacter asiaticus' infection. CsGolS6 overexpression resulted in improved tobacco tolerance to drought and salt stresses, contributing to an increased mesophyll cell expansion, photosynthesis and plant growth. Primary metabolite profiling revealed no significant changes in endogenous galactinol, but different extents of reduction of raffinose in the transgenic plants. On the other hand, a significant increase in the levels of metabolites with antioxidant properties, such as ascorbate, dehydroascorbate, alfa-tocopherol and spermidine, was observed in the transgenic plants. These results bring evidence that CsGolS6 is a potential candidate for improving stress tolerance in citrus and other plants.

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Water reservoirs have been constructed in hot semi-arid regions, which may be used to produce fish. The present study described major features of the economic, social, and environmental characteristics of a net-cage Nile tilapia production system, stocked with 100 and 120 fish/m3, implemented in a reservoir in the hot semi-arid region of Brazil during an extended drought event. The production cycle was reduced from 6-8 to 4 months because of the lack of water in the reservoir. This resulted in the harvest of small fish weighting ~300-350 g that reached a low value in the market. As a consequence, indicators of financial feasibility showed low values, which were not attractive for entrepreneurs. Nevertheless, for both stocking densities, the monthly income was about US$ 1,500.00, which is 5-fold the minimum wage in the region. In general, the activity has a positive social impact, despite the low contribution to development of the local economy and food security because most supply came from outside and fish were sold to distant regions. Various age and ethnic groups were represented among the employees, but the enterprise was operated only by men. Phosphorus accumulations in the reservoir were 2.1 and 2.0 kg/t of fish produced and particulate material accumulations of 110 and 100 kg/t of fish production for 125 fish/m3 and 100 fish/m3, respectively. The study indicated that the Nile tilapia culture in hot semi-arid region is strongly affected by long drought events and adaptations in the planning and management should be done when implementing the systems. However, it seems that the activity has some resilience to still provide food, generate wealth, and promote social development for local population with low environmental impact.

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Heterobaric leaves have bundle sheath extensions (BSEs) that compartmentalize the parenchyma, whereas homobaric leaves do not. The presence of BSEs affects leaf hydraulics and photosynthetic rate. The tomato (Solanum lycopersicum) obscuravenosa (obv) mutant lacks BSEs. Here, we identify the obv gene and the causative mutation, a nonsynonymous amino acid change that disrupts a C2H2 zinc finger motif in a putative transcription factor. This mutation exists as a polymorphism in the natural range of wild tomatoes but has increased in frequency in domesticated tomatoes, suggesting that the latter diversified into heterobaric and homobaric leaf types. The obv mutant displays reduced vein density, leaf hydraulic conductance and photosynthetic assimilation rate. We show that these and other pleiotropic effects on plant development, including changes in leaf insertion angle, leaf margin serration, minor vein density, and fruit shape, are controlled by OBV via changes in auxin signaling. Loss of function of the transcriptional regulator AUXIN RESPONSE FACTOR 4 (ARF4) also results in defective BSE development, revealing an additional component of a genetic module controlling aspects of leaf development important for ecological adaptation and subject to breeding selection.

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PDE4B (phosphodiesterase-4B) has an important role in cancer and in pharmacology of some disorders, such as inflammatory diseases. Remarkably in Native Americans, PDE4B variants are associated with acute lymphoblastic leukemia (ALL) relapse, as this gene modulates sensitivity of glucocorticoids used in ALL chemotherapy. PDE4B allele rs6683977.G, associated with genomic regions of Native American origin in US-Hispanics (admixed among Native Americans, Europeans, and Africans), increases ALL relapse risk, contributing to an association between Native American ancestry and ALL relapse that disappeared with an extra-phase of chemotherapy. This result insinuates that indigenous populations along the Americas may have high frequencies of rs6683977.G, but this has never been corroborated. We studied ancestry and PDE4B diversity in 951 healthy individuals from nine Latin American populations. In non-admixed Native American populations rs6683977.G has frequencies greater than 90%, is in linkage disequilibrium with other ALL relapse associated and regulatory variants in PDE4B-intron-7, conforming haplotypes showing their highest worldwide frequencies in Native Americans (>0.82). Our findings inform the discussion on the pertinence of an extra-phase of chemotherapy in Native American populations, and exemplifies how knowledge generated in US-Hispanics is relevant for their even more neglected and vulnerable Native American ancestors along the American continent.

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As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.

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Efficient use of natural resources (e.g., light, water, and nutrients) can be improved with a tailored developmental program that maximizes the lifetime and fitness of plants. In plant shoots, a developmental phase represents a time window in which the meristem triggers the development of unique morphological and physiological traits, leading to the emergence of leaves, flowers, and fruits. Whereas developmental phases in plant shoots have been shown to enhance food production in crops, this phenomenon has remained poorly investigated in roots. In light of recent advances, we suggest that root development occurs in three main phases: root apical meristem appearance, foraging, and senescence. We provide compelling evidence suggesting that these phases are regulated by at least four developmental pathways: autonomous, non-autonomous, hormonal, and periodic. Root developmental pathways differentially coordinate organ plasticity, promoting morphological alterations, tissue regeneration, and cell death regulation. Furthermore, we suggest how nutritional checkpoints may allow progression through the developmental phases, thus completing the root life cycle. These insights highlight novel and exciting advances in root biology that may help maximize the productivity of crops through more sustainable agriculture and the reduced use of chemical fertilizers.

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Over recent years, Macrobrachium amazonicum has become a popular species for shrimp farming due to their fast growth, high survival rates, and marketability. Several studies have focused on the development of new technology for the culture of this species, but many aspects of their nutrition and physiology remain unknown. Thus, the goal of the present study was to obtain transcripts of putative genes encoding digestive enzymes, based on a library of the cDNA from the hepatopancreas of M. amazonicum, sequenced in the Ion TorrentTM platform. We identified fragments of nine genes related to digestive enzymes, acting over proteins, carbohydrates and lipids. Endo and exoproteases were also recorded in the hepatopancreas, indicating adaptation to the digestion of protein-richfoods. Nonetheless, the enzymes involved in the carbohydrate metabolism formed the largest functional group in M. amazonicum, including enzymes related to the digestion of starch, chitin, and cellulose. These findings indicate that the species has a genetic apparatus of a well-adapted omnivorous animal. This information may provide important insights for the selection of ingredients for the formulation of a more appropriate diet to the enzymatic repertoire of M. amazonicum.(AU)

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The animals from bycatch of the shrimp fisheries can be a source of natural products and bioactive compounds. Thus, the present study aimed to evaluate the bioactivity of protein hydrolysates prepared from the two most abundant crabs from the bycatch of shrimp fisheries in Brazil (Callinectes ornatus and Hepatus pudibundus). Samples of C. ornatus and H. pudibundus were collected in the region of Ubatuba, State of São Paulo, Brazil. Muscles with small pieces of exoskeleton of both species were hydrolyzed using two enzymes, Alcalase 2.4 L® or Protamex®. The in vitro antioxidant capacity was analyzed used three methods: DPPH, sulfhydryl groups, and peroxyl radicals. Additionally, the cytotoxicity of the hydrolysates was investigated using pre-osteoblasts cells. The results showed that the degree of hydrolysis (DH) of H. pudibundus was superior to DH of C. ornatus using both enzymes and was higher when using the enzyme Alcalase 2.4 L® (32.0% ± 1.9). The analysis suggested that the hydrolysates have antioxidant activity. Besides that, no cytotoxic effect was observed on cell viability. Thus, protein hydrolysates of C. ornatus and H. pudibundus have bioactivity, which add value to these bycatch species and suggests their potential use as nutraceutical ingredient in the food industry.

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BACKGROUND: Chromoblastomycosis (CBM), represents one of the primary implantation mycoses caused by melanized fungi widely found in nature. It is characterized as a Neglected Tropical Disease (NTD) and mainly affects populations living in poverty with significant morbidity, including stigma and discrimination. METHODS AND FINDINGS: In order to estimate the global burden of CBM, we retrospectively reviewed the published literature from 1914 to 2020. Over the 106-year period, a total of 7,740 patients with CBM were identified on all continents except Antarctica. Most of the cases were reported from South America (2,619 cases), followed by Africa (1,875 cases), Central America and Mexico (1,628 cases), Asia (1,390 cases), Oceania (168 cases), Europe (35 cases), and USA and Canada (25 cases). We described 4,022 (81.7%) male and 896 (18.3%) female patients, with the median age of 52.5 years. The average time between the onset of the first lesion and CBM diagnosis was 9.2 years (range between 1 month to 50 years). The main sites involved were the lower limbs (56.7%), followed by the upper limbs (19.9%), head and neck (2.9%), and trunk (2.4%). Itching and pain were reported by 21.5% and 11%, respectively. Malignant transformation was described in 22 cases. A total of 3,817 fungal isolates were cultured, being 3,089 (80.9%) Fonsecaea spp., 552 (14.5%) Cladophialophora spp., and 56 Phialophora spp. (1.5%). CONCLUSIONS AND SIGNIFICANCE: This review represents our current knowledge on the burden of CBM world-wide. The global incidence remains unclear and local epidemiological studies are required to improve these data, especially in Africa, Asia, and Latin America. The recognition of CBM as NTD emphasizes the need for public health efforts to promote support for all local governments interested in developing specific policies and actions for preventing, diagnosing and assisting patients.

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The emergence of diverse lineages harboring mutations with functional significance and potentially enhanced transmissibility imposes an increased difficulty on the containment of the SARS-CoV-2 pandemic [...].

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Cervical cancer (CC) represents a major global health issue, particularly impacting women from resource constrained regions worldwide. Treatment refractoriness to standard chemoradiotheraphy has identified cancer stem cells as critical coordinators behind the biological mechanisms of resistance, contributing to CC recurrence. In this work, we evaluated differential gene expression in cervical cancer stem-like cells (CCSC) as biomarkers related to intrinsic chemoradioresistance in CC. A total of 31 patients with locally advanced CC and referred to Mário Penna Institute (Belo Horizonte, Brazil) from August 2017 to May 2018 were recruited for the study. Fluorescence-activated cell sorting was used to enrich CD34+/CD45- CCSC from tumor biopsies. Transcriptome was performed using ultra-low input RNA sequencing and differentially expressed genes (DEGs) using Log2 fold differences and adjusted p-value < 0.05 were determined. The analysis returned 1050 DEGs when comparing the Non-Responder (NR) (n=10) and Responder (R) (n=21) groups to chemoradiotherapy. These included a wide-ranging pattern of underexpressed coding genes in the NR vs. R patients and a panel of lncRNAs and miRNAs with implications for CC tumorigenesis. A panel of biomarkers was selected using the rank-based AUC (Area Under the ROC Curve) and pAUC (partial AUC) measurements for diagnostic sensitivity and specificity. Genes overlapping between the 21 highest AUC and pAUC loci revealed seven genes with a strong capacity for identifying NR vs. R patients (ILF2, RBM22P2, ACO16722.1, AL360175.1 and AC092354.1), of which four also returned significant survival Hazard Ratios. This study identifies DEG signatures that provide potential biomarkers in CC prognosis and treatment outcome, as well as identifies potential alternative targets for cancer therapy.

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In this study, we evaluated the effect of complexation and microencapsulation with pea protein on the antioxidant activity of protein hydrolysates from bycatch in Brazil. The zeta potential values of complexes changed from negative to positive with the increase of pea protein as a result of positively charged complexes formation. The increase in the ratio of pea protein/hydrolysates also resulted in increased turbidity in all samples. Particle size measurements indicated that the complexes tended to form larger aggregates (ranged from 61.5 ± 1.7 µm to 183 ± 2.8 µm). The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of the pea protein/fish protein hydrolysate complexes was higher than that of the protein hydrolysates alone. Moreover, increasing levels of pea protein did not affect the antioxidant activity of fish protein hydrolysates. The complexes of the Paralonchurus brasiliensis were chosen for the microencapsulation process by spray-drying. The results revealed that spray-drying did not have a significant effect (P > 0.05) on the protein hydrolysate antioxidant activity when they were complexed with pea protein. Thus, this work suggests that the complexation with pea protein and subsequent microencapsulation by spray-drying is an efficient way to protect the biological activity of protein hydrolysates obtained from bycatch. This study provides evidence for the potential use of bycatch from shrimp fisheries as functional ingredients or nutraceuticals.

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BACKGROUND/OBJECTIVES: Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil. SUBJECTS/METHODS: Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European, and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of body mass index (BMI) in three Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambuí), and South (Pelotas). RESULTS: We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p = 2.76e-06). This variant is rare in Europeans but with frequencies of ~3% in West Africa and has a strong female-specific effect (95% CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among women with morbid obesity from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects. CONCLUSIONS: We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.

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Chromoblastomycosis (CBM) is a neglected implantation mycosis prevalent in tropical climate zones, considered an occupational disease that affects impoverished rural populations. This retrospective study described clinical aspects of CBM in a hyperendemic area in Brazil and constructed a worldwide haplotype network of Fonsecaea spp. strains. The variables were collected from medical records using a standard report form, reporting 191 patients with CBM from Maranhão, Brazil. The mean age was 56.1 years, 168 (88%) patients were male and predominantly farmers (85.8%). The mean time of evolution of the disease until diagnosis was 9.4 years. Lower limbs (81.2%) and upper limbs (14.2%) were the main sites affected. Most patients exhibited verrucous (55%) and infiltrative plaque (48.2%). Fonsecaea spp. were identified in 136 cases and a haplotype network constructed with ITS sequences of 185 global strains revealed a total of 59 haplotypes exhibiting high haplotypic and low nucleotide diversities. No correlation was observed between the different haplotypes of Fonsecaea species and dermatological patterns, severity of disease or geographic distribution inside Maranhão. Data from this area contributed to better understanding the epidemiology of CBM. For the first time, a robust haplotype network with Fonsecaea strains reveals an evolutionary history with a recent population expansion.

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Several plant species such as Pfaffia glomerata are widely used in traditional Brazilian medicine as stimulants and aphrodisiacs. In this regard, the aim of our study was to explore the effects of the long-term intake of the hydro-alcoholic root extract of P glomerata on the germ and somatic cells within the seminiferous tubules in adult Balb/c mice. The experimental groups were placed as: controls (water and DMSO), and treated with 300 and 400 mg/kg of the root extract. The number of germ and somatic cells, the proportion of pathological seminiferous tubules, and the germ cell apoptotic levels were evaluated. The volume and proportion of the seminiferous epithelium was decreased after the extract intake due to the increased germ cell apoptotic levels. Vacuolization of Sertoli cell cytoplasm was observed widely in pathological tubules, along with fully disorganized epithelia, showing multinucleated cells, which lead to decreased daily sperm production. Taken together, our results indicate that long-term intake of the P glomerata caused deleterious effects on spermatogenesis by inducing apoptosis and altering the seminiferous tubule's epithelial dynamics.

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Intraspecies or interspecies crossings transfer relevant alleles between plants. However, some interspecies crossings involving Passiflora species impede ovule fertilization and the viable development of seeds. Thus, the purpose of this study was to verify the viability of interspecific crossings and monitor pollen tube development. The experiment had six species of Passiflora in the reciprocal crossings. Histochemical tests aimed to evaluate the percentage of intraspecies or interspecies crossings that resulted in fruit development and pollen tube development. Ovule fertilization and fruit development occurred in determined directions of crossings when controlling the female or male genitor, but only one case of reciprocal crossing had success. In crossings with no fruit development, histological analysis showed that some callus developed in the stigma and style, confirming unilateral and interspecies incompatibility in the genus Passiflora to some species and some directions of crossings.

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Amyloid-ß (Aß) peptides play a significant role in the pathogenesis of Alzheimer's disease (AD). Neurotoxic effects promoted by Aß peptides involve glutamate transmission impairment, decrease of neurotrophic factors, mitochondrial dysfunction, oxidative stress, synaptotoxicity, and neuronal degeneration. Here, we assessed the early events evoked by Aß1-40 on the hippocampus. Additionally, we sought to unravel the molecular mechanisms of atorvastatin preventive effect on Aß-induced hippocampal damage. Mice were treated orally (p.o.) with atorvastatin 10 mg/kg/day during 7 consecutive days before the intracerebroventricular (i.c.v.) infusion of Aß1-40 (400 pmol/site). Twenty-four hours after Aß1-40 infusion, a reduced content of mature BDNF/proBDNF ratio was observed in Aß-treated mice. However, there is no alteration in synaptophysin, PSD-95, and doublecortin immunocontent in the hippocampus. Aß1-40 promoted an increase in reactive oxygen species (ROS) and nitric oxide (NO) generation in hippocampal slices, and atorvastatin prevented this oxidative burst. Mitochondrial OXPHOS was measured by high-resolution respirometry. At this time point, Aß1-40 did not alter the O2 consumption rates (OCR) related to phosphorylating state associated with complexes I and II, and the maximal OCR. However, atorvastatin increased OCR of phosphorylating state associated with complex I and complexes I and II, maximal OCR of complexes I and II, and OCR associated with mitochondrial spare capacity. Atorvastatin treatment improved mitochondrial function in the rodent hippocampus, even after Aß infusion, pointing to a promising effect of improving brain mitochondria bioenergetics. Therefore, atorvastatin could act as an adjuvant in battling the symptoms of AD to preventing or delaying the disease progression.

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