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Background Follicular lymphoma (FL), the most common indolent non-Hodgkin’s Lymphoma, is a heterogeneous disease and a paradigm of the contribution of immune tumor microenvironment to disease onset, progression, and therapy resistance. Patient-derived models are scarce and fail to reproduce immune phenotypes and therapeutic responses.Methods To capture disease heterogeneity and microenvironment cues, we developed a patient-derived lymphoma spheroid (FL-PDLS) model culturing FL cells from lymph nodes (LN) with an optimized cytokine cocktail that mimics LN stimuli and maintains tumor cell viability.Results FL-PDLS, mainly composed of tumor B cells (60% on average) and autologous T cells (13% CD4 and 3% CD8 on average, respectively), rapidly organizes into patient-specific three-dimensional (3D) structures of three different morphotypes according to 3D imaging analysis. RNAseq analysis indicates that FL-PDLS reproduces FL hallmarks with the overexpression of cell cycle, BCR, or mTOR signaling related gene sets. FL-PDLS also recapitulates the exhausted immune phenotype typical of FL-LN, including expression of BTLA, TIGIT, PD-1, TIM-3, CD39 and CD73 on CD3+ T cells. These features render FL-PDLS an amenable system for immunotherapy testing. With this aim, we demonstrate that the combination of obinutuzumab (anti-CD20) and nivolumab (anti-PD1) reduces tumor load in a significant proportion of FL-PDLS. Interestingly, B cell depletion inversely correlates with the percentage of CD8+ cells positive for PD-1 and TIM-3.Conclusions In summary, FL-PDLS is a robust patient-derived 3D system that can be used as a tool to mimic FL pathology and to test novel immunotherapeutic approaches in a context of personalized medicine.

O hipoadrenocorticismo é uma endocrinopatia definida como a deficiência na produção de glicocorticoides e/ou mineralocorticoides. É pouco comum em cães, tendo causas primárias e secundárias, sendo que dentro das causas primárias há a apresentação típica e atípica. Os sinais clínicos são pouco específicos e de grande variabilidade, podendo o paciente apresentar somente quadros esporádicos de hiporexia, vômitos e diarreia ou até mesmo choque hipovolêmico e óbito. O diagnóstico é baseado nos dados de anamnese, sinais clínicos, exames laboratoriais e de imagem, sendo o teste de estimulação com ACTH (hormônio adrenocorticotrófico) o teste hormonal de escolha para o diagnóstico da doença. O tratamento baseia-se na reposição hormonal exógena, com base na necessidade do paciente. Este relato tem como objetivo relatar o caso de um canino, macho, Dogue alemão, cinco anos e seis meses, castrado, com histórico de hiporexia, emagrecimento progressivo, vômito e fezes pastosas intermitentes e anemia há quase um ano. Com base nos achados dos exames laboratoriais e de imagem, a suspeita de hipoadrenocorticismo foi levantada e o diagnóstico concluído com base no teste de estimulação com ACTH e dosagem de ACTH basal. O tratamento instituído foi a reposição exógena de glicocorticoide, tendo o paciente, após pouco tempo de tratamento, melhora clínica e hematológica considerável. Concluiu-se que o hipoadrenocorticismo é uma doença de diagnóstico muitas vezes desafiador, no entanto com excelente prognóstico caso o tratamento seja instituído de forma rápida e assertiva, o que melhora a qualidade de vida tanto do paciente como de seu tutor.

Despite medications, heart failure worsens with time with many patients dying within five years of diagnosis. Here the authors show that blocking purinergic receptors in the carotid body stops heart failure progression, improves its function, reduces sleep apneas and systemic inflammation in male rats.

Airborne and spaceborne platforms are the primary data sources for large-scale forest mapping, but visual interpretation for individual species determination is labor-intensive. Hence, various studies focusing on forests have investigated the benefits of multiple sensors for automated tree species classification. However, transferable deep learning approaches for large-scale applications are still lacking. This gap motivated us to create a novel dataset for tree species classification in central Europe based on multi-sensor data from aerial, Sentinel-1 and Sentinel-2 imagery. In this paper, we introduce the TreeSatAI Benchmark Archive, which contains labels of 20 European tree species (i.e., 15 tree genera) derived from forest administration data of the federal state of Lower Saxony, Germany. We propose models and guidelines for the application of the latest machine learning techniques for the task of tree species classification with multi-label data. Finally, we provide various benchmark experiments showcasing the information which can be derived from the different sensors including artificial neural networks and tree-based machine learning methods. We found that residual neural networks (ResNet) perform sufficiently well with weighted precision scores up to 79 % only by using the RGB bands of aerial imagery. This result indicates that the spatial content present within the 0.2 m resolution data is very informative for tree species classification. With the incorporation of Sentinel-1 and Sentinel-2 imagery, performance improved marginally. However, the sole use of Sentinel-2 still allows for weighted precision scores of up to 74 % using either multi-layer perceptron (MLP) or Light Gradient Boosting Machine (LightGBM) models. Since the dataset is derived from real-world reference data, it contains high class imbalances. We found that this dataset attribute negatively affects the models' performances for many of the underrepresented classes (i.e., scarce tree species). However, the class-wise precision of the best-performing late fusion model still reached values ranging from 54 % (Acer) to 88 % (Pinus). Based on our results, we conclude that deep learning techniques using aerial imagery could considerably support forestry administration in the provision of large-scale tree species maps at a very high resolution to plan for challenges driven by global environmental change. The original dataset used in this paper is shared via Zenodo (https://doi.org/10.5281/zenodo.6598390, Schulz et al., 2022). For citation of the dataset, we refer to this article.

The different conditions of soil vegetation cover combined with irrigation management and/or agricultural production systems can influence soil moisture content and crop yields. This study investigated the impact of agricultural production systems and center pivot irrigation management on soil moisture content during the cultivation of soybean and off-season corn crops. Two field experiments were conducted during the 2018–2019 growing season in tropical Cerrado soil conditions; one experiment consisted of the application of three irrigation water depths (0%, 50%, and 100% of the crop evapotranspiration) during soybean cultivation in a no-tillage system under ruzigrass (Urochloa ruziziensis) straw, and the second experiment consisted of the intercropped or nonintercropped cultivation of corn hybrids with ruzigrass in an agricultural area with and without the influence of eucalyptus reforestation. The volumetric soil moisture was measured using an electronic soil moisture meter (Hidrofarm), and the 1000-grain mass and yield of the soybean and corn were measured in the two trials. Irrigation and the no-till system did not influence soybean yields. The soybean cultivars NA 5909 RG and TMG 7067 IPRO presented TGM above 180 g, and this represented on average a 22% higher TGM than the BMX DESAFIO RR and CD 2737 RR. The presence of eucalyptus forest promoted a 1.5% increase in soil moisture in the corn crop. Soil management systems, such as irrigation, use cover crops, which may not increase the productivity of soybean and corn crops as expected.

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/ uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Objective: This study aimed to describe the clinical and laboratory findings of patients diagnosed with pleural tuberculosis at two hospitals in southern Brazil. Methods: Patients aged < 18 years were evaluated retrospectively. The patients’ medical and epidemiological history, tuberculin skin test results, radiological and pathological findings, and pleural fluid analysis results were retrieved. Results: Ninety-two patients with pleural tuberculosis were identified. The mean age was 10.9 years old. Twenty-one percent were children aged six years or less. The most common symptoms were fever (88%), cough (72%), and chest pain (70%). Unilateral pleural effusion was observed in 96% of the cases. Lymphocyte predominance was found in 90% of the pleural fluid samples. The adenosine deaminase activity of the pleural fluid was greater than 40 U/L in 85% of patients. A diagnosis of community-acquired pneumonia with antibiotic prescriptions was observed in 76% of the study population. Conclusions: Tuberculosis etiology must be considered in unilateral pleural effusion in a child with contact with a case of tuberculosis. Pleural fluid biomarkers contribute to the diagnosis of pleural tuberculosis in children and adolescents.

Abstract The objectives of this work were to investigate the occurrence of parasites in feces of cats, compare different coproparasitological techniques for their diagnosis and determine associations with parasitism. The samples were processed using three different coproparasitological techniques: centrifugal flotation in sucrose, centrifugal flotation in ZnSO4 and simple sedimentation. The parasitic association between parasitism and variables such as age, sex and fecal consistency was performed using the chi-square test or the G test with a significance level of 5%. A total of 237 samples were analyzed, of which 93 (39.2%) were positive, being Ancylostoma spp. (17.3%), Giardia intestinalis (12.2%), Platynosomum illiciens (8.0%), Cystoisospora spp. (6.3%), Toxoplasma gondii/ Hammondia hammondi (3.4%), Diphyllobothriidae (2.1%), Toxocara spp. (1.7%), Dipylidium caninum (1.3%) and Mesocestoides spp. (0.8%). In the parasitism association analysis, it was possible to verify a statistical difference in the age category for Cystoisospora spp. (p=0.001) observing a strong relationship between parasitism and young animals, the association with sex proved to be important for P. illiciens (p

ABSTRACT This work evaluated the initial performance and genetic diversity of Coffea canephora genotypes cultivated in environments at contrasting altitudes. Fourteen morphophysiological traits and seven descriptors of the genus Coffea spp. of coffee trees cultivated at altitudes of 140 m and 700 m were evaluated. The design used was Federer’s augmented block in a 2 × 112 factorial scheme with six blocks. The first factor was the two environments, and the second was the 112 genotypes, with eight common treatments, being five conilon coffee clones and three arabica coffee cultivars. The data were analyzed by the method of REML/BLUP and genetic correlation method. Genetic diversity was evaluated by estimating the distance matrix, applying the Gower methodology followed by the clustering method by Tocher and UPGMA. The phenotypic means were higher in the environment at an altitude of 700 m, except for plant height, number of leaves, and canopy height (CH). Genotypic effects were significant for most traits except for leaf width, CH, unit leaf area, and total leaf area. A wide genetic diversity was verified, with distances varying from 0.037 to 0.593 for the pairs of genotypes 26 × 93 and T7 × 76, respectively. Most of the traits studied showed high genotypic correlation with the environment and expressive genetic correlation between the evaluated traits thereby demonstrating the possibility of indirect selection. There is an adaptation of conilon coffee genotypes to high altitudes and the possibility of developing a specific cultivar for the southern state of Espírito Santo.

Abstract The objective of this work was to evaluate the combining ability of S3 forage maize (Zea mays) progenies for traits related to forage yield and bromatological quality, with and without the ear, as well as to evaluate the ability of testers to discriminate progenies for these traits. The trials were carried out in the 2017/2018 and 2018/2019 crop seasons, in the municipality of Guarapuava, in the state of Paraná, Brazil. Topcross hybrids obtained from the crosses of 28 S3 maize progenies with three testers were evaluated. The following forage qualitative traits of the whole plant and of the plant without the ear were evaluated: neutral and acid detergent fibers, lignin, and in situ dry mass digestibility, as well as digestible dry mass yield of the whole plant. The progenies that stood out for forage qualitative traits were 85.1 and 42.1 for the whole plant and for the plant without the ear, respectively. For the qualitative and productive traits of whole-plant forage, progenies 91.1, 106.2, 126.2, 138.1, 152.1, 235.1, and 251.1 are promising to continue in the breeding program aiming to generate hybrids with a high yield and fiber quality. Testers LEM3 and AG8025 are efficient in discriminating progenies for forage yield and bromatological traits.

IntroductionOnce established in the human population, the 2009 H1N1 pandemic virus (H1N1pdm09) was repeatedly introduced into swine populations globally with subsequent onward transmission among pigs.MethodsTo identify and characterize human-to-swine H1N1pdm09 introductions in Brazil, we conducted a large-scale phylogenetic analysis of 4,141 H1pdm09 hemagglutinin (HA) and 3,227 N1pdm09 neuraminidase (NA) gene sequences isolated globally from humans and swine between 2009 and 2022.ResultsPhylodynamic analysis revealed that during the period between 2009 and 2011, there was a rapid transmission of the H1N1pdm09 virus from humans to swine in Brazil. Multiple introductions of the virus were observed, but most of them resulted in self-limited infections in swine, with limited onward transmission. Only a few sustained transmission clusters were identified during this period. After 2012, there was a reduction in the number of human-to-swine H1N1pdm09 transmissions in Brazil.DiscussionThe virus underwent continuous antigenic drift, and a balance was established between swine-to-swine transmission and extinction, with minimal sustained onward transmission from humans to swine. These results emphasize the dynamic interplay between human-to-swine transmission, antigenic drift, and the establishment of swine-to-swine transmission in shaping the evolution and persistence of H1N1pdm09 in swine populations.

IntroductionThe pandemic caused by SARS-CoV-2 has had a major impact on health systems. Vaccines have been shown to be effective in improving the clinical outcome of COVID-19, but they are not able to fully prevent infection and reinfection, especially that caused by new variants.MethodsHere, we tracked for 450 days the humoral immune response and reinfection in 52 healthcare workers from Brazil. Infection and reinfection were confirmed by RT-qPCR, while IgM and IgG antibody levels were monitored by rapid test.ResultsOf the 52 participants, 19 (36%) got reinfected during the follow-up period, all presenting mild symptoms. For all participants, IgM levels dropped sharply, with over 47% of them becoming seronegative by the 60th day. For IgG, 90% of the participants became seropositive within the first 30 days of follow-up. IgG antibodies also dropped after this period reaching the lowest level on day 270 (68.5 ± 72.3, p

Visceral leishmaniasis (VL) is a chronic systemic disease. In Brazil this infection is caused by Leishmania (Leishmania) infantum. Extracellular vesicles (EVs) released by Leishmania species have different functions like the modulation of host immune systems and inflammatory responses, among others. This study evaluated the participation of EVs from L. (L.) infantum (Leish-EVs) in recognition of the humoral and cellular immune response of hosts with VL. Promastigotes were cultivated in 199 medium and, in the log phase of growth, they were centrifuged, washed, resus-pended in RPMI medium, and incubated for 2 to 24 h, at 25 °C or 37 °C to release Leish-EVs. This dynamic was evaluated using transmission (TEM) and scanning (SEM) electron microscopies, as well as nanoparticle tracking analysis (NTA). The results suggested that parasite penetration in mammal macrophages requires more Leish-EVs than those living in insect vectors, since promastigotes incubated at 37 °C released more Leish-EVs than those incubated at 25 °C. Infected THP-1 cells produced high EV concentration (THP-1 cells-EVs) when compared with those from the control group. The same results were obtained when THP-1 cells were treated with Leish-EVs or a crude Leishmania antigen. These data indicated that host–EV concentrations could be used to distinguish infected from uninfected hosts. THP-1 cells treated with Leish-EVs expressed more IL-12 than control THP-1 cells, but were unable to express IFN-γ. These same cells highly expressed IL-10, which inhibited TNF-α and IL-6. Equally, THP-1 cells treated with Leish-EVs up-expressed miR-21-5p and miR-146a-5p. In conclusion, THP-1 cells treated with Leish-EVs highly expressed miR-21-5p and miR-146a-5p and caused the dysregulation of IL-10. Indirectly, these results suggest that high expression of these miRNAs species is caused by Leish-EVs. Consequently, this molecular via can contribute to immunosuppression causing enhanced immunopathology in infected hosts.

Despite the excellent properties of silicone endotracheal prostheses, their main limitation is the formation of a polymicrobial biofilm on their surfaces. It can cause local inflammation, interfering with the local healing process and leading to further complications in the clinical scenario. The present study evaluated the inhibitory effect of cold atmospheric plasma (CAP) on multispecies biofilms grown on the silicone protheses’ surfaces. In addition to silicone characterization before and after CAP exposure, CAP cytotoxicity on immortalized human bronchial epithelium cell line (BEAS-2B) was evaluated. The aging time test reported that CAP could temporarily change the silicone surface wetting characteristics from hydrophilic (80.5°) to highly hydrophilic (C. albicans, S. aureus, and P. aeruginosa (0.636, 0.738, and 1.445, respectively) was detected after CAP exposure. Multispecies biofilms exposed to CAP showed significant viability reduction for C. albicans and S. aureus (1.385 and 0.831, respectively). The protocol was not cytotoxic to BEAS-2B. CAP can be a simple and effective method to delay multispecies biofilm formation inside the endotracheal prosthesis.

Nonconventional clinical presentations of diseases are common in older adults. Even dramatic events, such as foreign body (FB) inhalation, can occur in a subtle and non-specific manner. Pill aspiration is a rare yet overlooked cause of airway injury. It accounts for approximately 7% of all FB aspirations. In contrast, oral dysphagia and polypharmacology, mainly administrated in solid oral dosage forms (SDOF), like tablets and pills, are common conditions in older adults. Herein, we present a case of SDOF aspiration in a 78-year-old man. FB inhalation developed with general clinical deterioration and neurological impairment (delirium) rather than overt respiratory symptoms. Bronchoscopy provided remarkable images of this unexpected finding. Caregivers and healthcare workers must be aware of the risk of SDOF aspiration and adopt proper safety measures. Early recognition and bronchoscopy for diagnostic and therapeutic purposes can be lifesaving in such cases.