The Unified Phenotype Ontology (uPheno): A framework for cross-species integrative phenomics.

Phenotypic data are critical for understanding biological mechanisms and consequences of genomic variation, and are pivotal for clinical use cases such as disease diagnostics and treatment development. For over a century, vast quantities of phenotype data have been collected in many different contexts covering a variety of organisms. The emerging field of phenomics focuses on integrating and interpreting these data to inform biological hypotheses. A major impediment in phenomics is the wide range of distinct and disconnected approaches to recording the observable characteristics of an organism. Phenotype data are collected and curated using free text, single terms or combinations of terms, using multiple vocabularies, terminologies, or ontologies. Integrating these heterogeneous and often siloed data enables the application of biological knowledge both within and across species. Existing integration efforts are typically limited to mappings between pairs of terminologies; a generic knowledge representation that captures the full range of cross-species phenomics data is much needed. We have developed the Unified Phenotype Ontology (uPheno) framework, a community effort to provide an integration layer over domain-specific phenotype ontologies, as a single, unified, logical representation. uPheno comprises (1) a system for consistent computational definition of phenotype terms using ontology design patterns, maintained as a community library; (2) a hierarchical vocabulary of species-neutral phenotype terms under which their species-specific counterparts are grouped; and (3) mapping tables between species-specific ontologies. This harmonized representation supports use cases such as cross-species integration of genotype-phenotype associations from different organisms and cross-species informed variant prioritization.

A new lineage nomenclature to aid genomic surveillance of dengue virus.

Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system. Here, we propose adding 2 sub-genotypic levels of virus classification, named major and minor lineages. These lineages have high thresholds for phylogenetic distance and clade size, rendering them stable between phylogenetic studies. We present assignment tools to show that the proposed lineages are useful for regional, national, and subnational discussions of relevant DENV diversity. Moreover, the proposed lineages are robust to classification using partial genome sequences. We provide a standardized neutral descriptor of DENV diversity with which we can identify and track lineages of potential epidemiological and/or clinical importance. Information about our lineage system, including methods to assign lineages to sequence data and propose new lineages, can be found at: dengue-lineages.org.

Meanings attributed to changes experienced by individuals after COVID-19 hospitalization.

OBJECTIVES: to understand the meanings attributed to the experiences of individuals after hospitalization for COVID-19. METHODS: qualitative study, with a theoretical framework based on Symbolic Interactionism and a methodological approach grounded in Grounded Theory. Nineteen participants who had moderate and severe forms of COVID-19 after hospitalization were interviewed. Data collection took place between April and November 2021 through online interviews, and the data were analyzed using initial and focused coding in the MAXQDA software. RESULTS: the data illustrate new meanings attributed to different aspects of life after hospitalization, including relationships with others, the environment, physical and mental health, finances, identity, and interactions with a new social reality. CONCLUSIONS: the meanings are intrinsically linked to the value of interpersonal relationships, the perception of their impact, and the consequences after hospitalization. This allows professionals to understand the importance of this information to improve care and prepare for future epidemics.

The Impact of Fibroblast Growth Factor Receptor Alterations in Clinical Outcomes of Patients With Advanced Urothelial Carcinoma: Real-World Data From a Latin American Population.

INTRODUCTION: Fibroblast growth factor receptor (FGFR) mutations and fusions are relevant biomarkers in metastatic urothelial carcinoma (mUC). However, the prevalence of genomic alterations and their impact on clinical outcomes in a Latin American population remains unknown. This study aimed to explore the prevalence of FGFR mutations and/or fusions in patients with mUC in Latin America (LATAM) and its association with clinicopathological characteristics, Bellmunt's prognostic model, and survival outcomes. PATIENTS AND METHODS: A multicenter retrospective cohort study from 2016 to 2019 of patients with mUC from several LACOG LATAM institutions. FGFR alterations were analyzed by real-time PCR and/or next-generation sequencing in tumor samples and clinicopathologic characteristics and survival outcomes data were collected. The prevalence of FGFR, patient characteristics, and treatment in real-world settings were summarized. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate the associations of FGFR mutation and/or fusion status with median overall survival (mOS), median time to treatment failure (mTTF), and clinicopathological characteristics. RESULTS: In total, 222 patients were screened. Of these, 196 patients were considered eligible and were included in the analysis. FGFR mutations and/or fusions were found in 35 (17.9%) patients. There was no statistical difference in mOS and mTTF in FGFR-altered and non-altered patients (13.1 vs. 16.8 months, P = .20 and 3.9 vs. 4.1 months, P = .96, respectively). Bellmunt's prognostic model correctly predicted overall survival (P = .049). CONCLUSIONS: This is the largest study evaluating the prevalence of FGFR alterations in patients with mUC in the LATAM population. FGFR alterations in mUC were found in 17.9% of the patients, and the presence of this biomarker was not associated with OS. We validated Bellmunt's prognostic model in this cohort.

Impact of the COVID-19 Pandemic on Pharmacist Interventions: A Retrospective Study with Inpatients in a University Hospital.

Background: Despite growing interest in understanding the challenges faced by multidisciplinary health teams during the COVID-19 pandemic, there is a lack of studies specifically focusing on changes in pharmacist interventions and drug-related problems. Objectives: To analyze and compare the interventions performed by pharmacists during comprehensive medication management in the adult intensive care unit and general internal medicine ward of the University Hospital of the University of São Paulo, Brazil, for defined periods before the onset of the COVID-19 pandemic and during the pandemic itself. Methods: All pharmacist interventions performed in relation to inpatient prescriptions from March to December 2019 (before the pandemic) and from March to December 2021 (during the pandemic) were collected and tabulated. These interventions were then classified according to the Pharmaceutical Care Network Europe (PCNE) system, version 9.1, and categorized based on first-level codes of the Anatomical Therapeutic Chemical classification system. Results: The analysis revealed substantial changes in the patterns of pharmacist interventions and the therapeutic classes of drugs for COVID-19-positive and COVID-19-negative patients during the pandemic relative to patients in the pre-pandemic period. Among COVID-19-positive patients, interventions were predominantly related to enhancing patient safety (PCNE code P2), drug selection (C1), dose selection (C3), prescribing and dispensing processes (C5), the drug-use process (C6), and patient transfers between different levels of care (C8). The drug-related problems addressed by pharmacist interventions primarily involved COVID-19-positive patients in the pandemic period and were related to systemic hormonal preparations (excluding sex hormones and insulins), anti-infective agents for systemic use, nervous system and drugs for the blood and blood-forming organs. Conclusion: The results of this study highlight the adaptability and competence of pharmacists in responding to critical scenarios such as the COVID-19 pandemic. These scenarios are characterized by new work dynamics, the hiring of additional professionals, an increase in the number of beds, the rapid evolution of evidence-based information, and drug shortages that necessitate the use of alternative medications. Pharmacists play a crucial role in ensuring patient safety during these difficult times.

Contexte: Malgré un intérêt croissant pour la compréhension des défis auxquels les équipes de santé multidisciplinaires ont été confrontées pendant la pandémie de COVID-19, peu d'études portent sur les changements chez les interventions des pharmaciens et les problèmes liés aux médicaments en particulier. Objectifs: Analyser et comparer les interventions réalisées par les pharmaciens lors de la gestion globale des médicaments dans l'unité de soins intensifs pour adultes et le service de médecine interne générale de l'hôpital universitaire de l'Université de São Paulo, Brésil, pendant des périodes définies avant le début de la pandémie de COVID-19 et pendant la pandémie elle-même. Méthodologie: Toutes les interventions des pharmaciens réalisées en lien avec les prescriptions hospitalières de mars à décembre 2019 (avant la pandémie) et de mars à décembre 2021 (pendant la pandémie) ont été collectées et compilées. Ces interventions ont ensuite été classées selon le système du Pharmaceutical Care Network Europe (PCNE), version 9.1, et catégorisées sur la base des codes de premier niveau du système de classification anatomique, thérapeutique et chimique. Résultats: L'analyse a révélé des changements substantiels dans les types d'intervention des pharmaciens et dans les classes thérapeutiques de médicaments pour les patients positifs pour la COVID-19 et négatifs pour la COVID-19 pendant la pandémie par rapport aux patients d'avant la pandémie. Parmi les patients positifs pour la COVID-19, les interventions étaient principalement liées à l'amélioration de la sécurité des patients (code PCNE P2), au choix des médicaments (C1), à la sélection des doses (C3), au processus de prescription et de délivrance (C5), au processus d'utilisation des médicaments (C6), et aux transferts de patients entre différents niveaux de soins (C8). Les problèmes liés aux médicaments traités par les interventions des pharmaciens concernaient principalement les patients positifs pour la COVID-19 pendant la période de la pandémie et se rapportaient aux préparations hormonales systémiques (à l'exclusion des hormones sexuelles et des insulines), aux agents anti-infectieux à usage systémique, au système nerveux ainsi qu'au sang et aux organes hématopoïétiques. Conclusion: Les résultats de cette étude mettent en évidence l'adaptabilité et la compétence des pharmaciens pour répondre à des scénarios critiques tels que la pandémie de COVID-19. Ces scénarios se caractérisent par une nouvelle dynamique de travail, l'embauche de professionnels supplémentaires, une augmentation du nombre de lits, l'évolution rapide des informations fondées sur des données probantes et des pénuries de médicaments nécessitant le recours à des médicaments alternatifs. Les pharmaciens jouent un rôle crucial pour assurer la sécurité des patients pendant ces périodes difficiles.

Ozone Therapy in the Integrated Treatment of Female Dogs with Mammary Cancer: Oxidative Profile and Quality of Life.

Considering the high frequency of malignant breast tumors, there is a growing search for new therapeutic strategies that control neoplastic growth and dissemination, combined with fewer adverse reactions. Therefore, this study evaluated the effects of ozone therapy in female dogs with mammary cancer undergoing chemotherapy treatment. Twenty-five canines diagnosed with malignant mammary neoplasia were divided into two groups: one treated with carboplatin alone (n = 11) and the other with carboplatin associated with ozone therapy (n = 14). Clinical and laboratory evaluations, mastectomy, analysis of the oxidative profile based on total antioxidant capacity (TAC) and serum concentrations of malondialdehyde (MDA), survival rate, and quality of life were performed. Animals in the ozone therapy group had higher concentrations of red blood cells and platelets, significantly improving the survival rate and quality of life. Furthermore, adverse reactions were less intense and frequent in this group, which was associated with an increase in TAC and a reduction in MDA. These results indicate that the combination of carboplatin and ozone therapy represents a promising complementary treatment for female dogs with mammary cancer, as it was associated with fewer adverse reactions and a better oxidative profile.

Impact of aging on maximal oxygen uptake in female runners and sedentary controls.

The present study aimed to compare V̇O2max (absolute, adjusted to total body mass, and adjusted to lean mass) in recreational runners and sedentary women < and > 50 yr and verify the effect of aging and physical activity level on the three types of V̇O2 max expression. The study included 147 women:85 runners (45.7 ± 14.1 yr) and 62 sedentary controls (48.8 ± 9.8 yr). They were subjected to cardiopulmonary exercise testing for V̇O2 max measurement and a body composition test by dual-emission X-ray absorptiometry system. V̇O2max were expressed as absolute values (L/min), relative to total body mass values (mL/kg/min), and relative to lean mass values (mL/kgLM/min). The two-way analysis of variance revealed a significant interaction [F(2,131) = 4.43, p < 0.001] and effects of age group [F(2,131) = 32.79, p < 0.001] and physical activity group [F(2,131) = 55.64, p < 0.001] on V̇O2max (mL/min). V̇O2max (mL/kg/min) and V̇O2 max (mL/kgLM/min) were significantly influenced by age and physical activity levels. The multiple regression model explains 76.2 % of the dependent variable V̇O2max (mL/kg/min), age (ß = -0.335, t = -7.841, p < 0.001), and physical activity group (ß = -0.784, t = -18.351, p < 0.001). In conclusion, female runners had higher V̇O2 max values than sedentary women at all ages, even though aging has a greater impact on V̇O2 max in the runners group. In addition to cardiorespiratory fitness, women's metabolic lean mass function, as measured by V̇O2max adjusted by lean mass, is significantly influenced by aging. Finally, physical activity has a greater impact on V̇O2 max levels than aging.

Towards a standard benchmark for variant and gene prioritisation algorithms: PhEval - Phenotypic inference Evaluation framework.

Background: Computational approaches to support rare disease diagnosis are challenging to build, requiring the integration of complex data types such as ontologies, gene-to-phenotype associations, and cross-species data into variant and gene prioritisation algorithms (VGPAs). However, the performance of VGPAs has been difficult to measure and is impacted by many factors, for example, ontology structure, annotation completeness or changes to the underlying algorithm. Assertions of the capabilities of VGPAs are often not reproducible, in part because there is no standardised, empirical framework and openly available patient data to assess the efficacy of VGPAs - ultimately hindering the development of effective prioritisation tools. Results: In this paper, we present our benchmarking tool, PhEval, which aims to provide a standardised and empirical framework to evaluate phenotype-driven VGPAs. The inclusion of standardised test corpora and test corpus generation tools in the PhEval suite of tools allows open benchmarking and comparison of methods on standardised data sets. Conclusions: PhEval and the standardised test corpora solve the issues of patient data availability and experimental tooling configuration when benchmarking and comparing rare disease VGPAs. By providing standardised data on patient cohorts from real-world case-reports and controlling the configuration of evaluated VGPAs, PhEval enables transparent, portable, comparable and reproducible benchmarking of VGPAs. As these tools are often a key component of many rare disease diagnostic pipelines, a thorough and standardised method of assessment is essential for improving patient diagnosis and care.

Understanding potential opportunities and risks associated with feeding supplemental rumen available fats to mitigate enteric methane emissions in lactating dairy cows.

Supplemental dietary rumen available fats show promise as enteric methane (eCH4) mitigators for lactating dairy cows. However, concerns include variability in eCH4 response and possible negative effects on dairy cow performance. Successful implementation of this mitigation option requires better prediction of responses specifically to rumen available fatty acids (FA) as well as understanding the modulating effects of other dietary and animal characteristics. Using meta-analytic and meta-regression techniques, 35 published studies with diet definition were used to assess changes in eCH4 emissions and lactation performance associated with supplemental fat, specific supplemental rumen available FA types, and other dietary characteristics. Enteric CH4 (g/d) was reduced by 3.77% per percentage unit of supplemental rumen available ether extract (EE). Supplemental rumen available PUFA (C18:2 and C18:3) and UFA (C18:1, C18:2, C18:3) mitigated eCH4 (g/d) emissions in dairy cows by 6.88 and 4.65% per percentage unit increase, respectively. The anti-methanogenic effects of PUFA, MUFA and MCFA increased with correspondingly greater basal dietary levels of each FA type. Higher rumen-degradable starch (RDS; >18% DM) in the basal diet promoted greater reductions in eCH4 yield (eCH4/DMI, g/kg) with supplemental rumen available PUFA and UFA. Both milk fat percentage and yield (kg/d) were reduced with rumen available fat supplementation with a reduction of 7.8% and 6.0%, respectively, relative to control diets. Our results highlight the importance of determining basal levels of the rumen available FA before providing supplemental rumen available FA as an option for enteric eCH4 mitigation. Dairy nutritionists can use estimates generated from this analysis to predict changes in eCH4 emissions and dairy cow performance associated with dietary supplementation of rumen available EE and specific rumen available FA types for the purpose of eCH4 mitigation.

Post-mortem detection of hemoplasmas (hemotropic Mycoplasma spp.) in South American fur seal (Arctocephalus australis) sampled in Rio Grande do Sul State, southern Brazil.

Hemotropic mycoplasmas are bacteria that attaches to erythrocytes surface, which some species presents zoonotic concerns. In the suborder Pinnipedia, genera Otaria and Arctocephalus are prominent in Brazil. This study investigated the occurrence of hemoplasmas in Arctocephalus sp. and Otaria flavescens found dead along the coast of a Southern Brazilian State. DNA from 135 spleen samples were extracted and subjected to conventional PCR protocols, targeting the 16 S rRNA and 23 S rRNA gene. Three (2.22 %) Arctocephalus australis were positive in the 16 S rRNA gene, and no samples amplified in the 23 S rRNA gene. Samples from this study clustered with Zalophus californianus and Arctocephalus tropicalis mycoplasmas on a Bayesian phylogenetic analysis. Genetic diversity analysis suggested distinct genotypes, indicating A. australis as a new host for hemoplasma, and also a potential putative novel hemoplasma genotype. These findings raises future awareness for pinnipeds conservation, and adds Mycoplasma spp. to be taken into consideration when clinically evaluating rescued animals.

Models to predict nitrogen excretion from beef cattle fed a wide range of diets compiled from South America.

The objective of this meta-analysis was to develop and evaluate models for predicting nitrogen (N) excretion in feces, urine, and manure in beef cattle in South America. The study incorporated a total of 1,116 individual observations of N excretion in feces and 939 individual observations of N excretion in feces and in urine (g/d), representing a diverse range of diets, animal genotypes, and management conditions in South America. The dataset also included data on dry matter intake (DMI; kg/d) and nitrogen intake (NI; g/d), concentrations of dietary components, as well as average daily gain (ADG; g/d) and average body weight (BW; kg). Models were derived using linear mixed-effects regression with a random intercept for the study. Fecal N excretion was positively associated with DMI, NI, nonfibrous carbohydrates, average BW, and ADG and negatively associated with EE and CP concentration in the diet. The univariate model predicting fecal N excretion based on DMI (model 1) performed slightly better than the univariate model, which used NI as a predictor variable (model 2) with a root mean square error (RMSE) of 38.0 vs. 39.2%, the RMSE-observations SD ratio (RSR) of 0.81 vs. 0.84, and concordance correlation coefficient (CCC) of 0.53 vs. 0.50, respectively. Models predicting urinary N excretion were less accurate than those derived to predict fecal N excretion, with an average RMSE of 43.7% vs. 37.0%, respectively. Urinary and manure N excretion were positively associated with DMI, NI, CP, average BW, and ADG and negatively associated with neutral detergent fiber concentration in the diet. As opposed to fecal N excretion, the univariate model predicting urinary N excretion using NI (model 10) performed slightly better than the univariate model using DMI (model 9) as predictor variable with an RMSE of 36.0% vs. 39.7%, RSR 0.85 vs. 0.93, and CCC of 0.43 vs. 0.29, respectively. The models developed in this study are applicable for predicting N excretion in beef cattle across a broad spectrum of dietary compositions and animal genotypes in South America. The univariate model using DMI as a predictor is recommended for fecal N prediction, while the univariate model using NI is recommended for predicting urinary and manure N excretion because the use of more complex models resulted in little to no benefits. However, it may be more useful to consider more complex models that incorporate nutrient intakes and diet composition for decision-making when N excretion is a factor to be considered. Three extant equations evaluated in this study have the potential to be used in tropical conditions typical of South America to predict fecal N excretion with good precision and accuracy. However, none of the extant equations are recommended for predicting urine or manure N excretion because of their high RMSE, and low precision and accuracy.

Clinical Characteristics of Children with THRA Mutations: Variable Phenotype and Good Response to Recombinant Human Growth Hormone Therapy.

INTRODUCTION: Mutations in the thyroid hormone receptor alpha (THRA) gene are a rare cause of thyroid hormone resistance, which leads to a pleomorphic phenotypic spectrum. Hormonal profiles are variable and subtle, making laboratory diagnoses challenging. Genetic evaluation can be a helpful tool in diagnosing these cases. CASE PRESENTATION: Three patients (P1, P2, and P3) from unrelated families presented to their endocrinologists with short stature and abnormalities in thyroid function results. P1 showed hypoactivity and mild thyroid-stimulating hormone (TSH) elevation. P2 presented with a mild developmental delay and a hormonal profile initially interpreted as central hypothyroidism. Patient P3 had severe symptoms, including hypotonia, developmental delay, normal TSH, hypercholesterolemia, severe hypertriglyceridemia, high amylase levels, and mild pericardial effusion. All the patients had low free thyroxine (FT4) levels, mild constipation, and short stature. The patients underwent exome sequencing analysis that identified three different heterozygous variants in the THRA gene (P1 and P2 had missense variants, and P3 had a stop codon variant). All patients were treated with levothyroxine replacement, improving their clinical symptoms, such as constipation, and neurological symptoms. P1 and P2 were also treated with the recombinant human growth hormone (rhGH). The improvements in growth velocity and height standard deviation scores (SDS) were remarkable. Notably, P1 had a total height gain of 2.5 SDS, reaching an adult height within the normal range. CONCLUSION: THRA gene defects can lead to growth disorders with different phenotypes. Children with THRA mutations can benefit from adequate treatment with levothyroxine and may respond well to rhGH treatment.

Assessment of infection of Stomoxys calcitrans larvae by entomopathogenic nematodes Heterorhabditis amazonensis NEPT11.

This study aimed to evaluate the virulence of Heterorhabditis amazonenses NEPT11 against larvae of Stomoxys calcitrans. Groups of 10 third-instar fly larvae were deposited in Petri dishes, to which were added 50, 100 and 200 EPNs/larva in 4ml of distilled water. The volume of the control group was the same as the treated group, but without EPNs. Larval mortality was observed daily, until larvae died or adults emerged. The Petri dishes were kept on laboratory shelves at 27 ± 1 °C and 70 ± 10% RH. The experiment was replicated six times. A regression analysis revealed quadratic behavior with increasing concentrations, indicating that the concentration of 200 EPNs/larva (48%) was the most efficient among the tested concentrations, while concentrations of 50 and 100 EPNs/larva killed 26.6 and 40% of larvae, respectively. In general, none of the treatments resulted in a mortality rate of more than 50%, but all the treated groups exhibited a higher mortality than that of the control group. It is concluded that the EPN H. amazonensis NEPT11 shows a promising potential to control third-instar larvae of S. calcitrans. However, further studies are needed in different situations to better understand the activity of this organism against the immature stages of the stable fly.

Este estudo teve como objetivo avaliar a ação do NEP Heterorhabditis amazonenses NEPT11 frente larvas de S. calcitrans. Grupos de 10 larvas de terceiro instar da mosca foram depositados em placas de Petri, em seguida, adicionou-se 50, 100, 200, 300 e 400 NEPs/larva em 4ml de água destilada. O volume do grupo controle foi o mesmo dos tratados, porém sem NEPs. A mortalidade das larvas foi observada diariamente, até a morte das larvas ou emergência de adultos. As placas foram mantidas em estantes de laboratório a 27 ± 1 °C e 70 ± 10% UR. O experimento teve seis repetições. Por meio da análise de regressão, foi observado comportamento quadrático com o aumento das concentrações, sendo a concentração de 200 NEPs/larva (48%) a de maior eficiência entre as concentrações testadas, já as concentrações de 50 e 100 NEPs/larva mataram 26,6 e 40% das larvas, respectivamente. De modo geral, nenhum tratamento proporcionou mortalidade superior a 50%, todavia, todos os grupos tratados apresentaram mortalidade superior à observada no controle. Conclui-se que H. amazonenses NEPT11 mostrou-se promissor no controle de larvas de terceiro instar de S. calcitrans, porém mais estudos devem ser feitos para o melhor entendimento da ação deste organismo frente aos estágios imaturos da mosca-dos-estábulos.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

Dirofilaria immitis and Onchocercidae spp. in wild felids from Brazil.

Among the species described within the Onchocercidae family, Dirofilaria immitis is regarded as the most common worldwide, causing severe and often fatal conditions in dogs, cats, and occasionally humans. Dirofilaria spp. are vectored by mosquitoes, simulids, and culicoids, with their epidemiology dependent on the geographical distribution of competent vectors. Eight species of Dirofilaria have been reported so far in Brazil, of which six parasitize non-human primates, deer, procyonids, and marsupials. Here, we investigated the occurrence of Onchocercidae in wild felids (i.e., Panthera onca, Puma concolor, Herpailurus yagouaroundi, Leopardus geoffroyi, Leopardus guttulus, Leopardus pardalis, Leopardus wiedii, Leopardus munoai) from different locations in Brazil. Overall, 82 samples (n = 63 blood; n = 19 tissues) were molecularly screened for cytochrome c oxidase subunit-1 (cox1) gene. Four (i.e., 4.8%) wild felid samples were positive, and at BLAST analysis, the obtained sequences showed varying percentage of nucleotide identity with the genera Brugia (i.e., 87-88%), Setaria (i.e., 89%), and D. immitis (i.e., 94.4%). Phylogenetic analyses clustered sequences obtained into three distinct clades, one with D. immitis and the remaining two with other Onchocercidae spp. Data herein obtained highlight the need for a more comprehensive understanding of the diversity and biology of Onchocercidae in South America in order to assess the potential impact that these species may have for domestic and wild animals, as well as humans.

Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study.

BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.

Da hospitalização para a prática corporal: análise qualitativa das vivências no projeto Respirar no Amazonas / From hospitalizaton to corporal practice: qualitative analysis of experiences in the projeto Respirar no Amazonas / Del hospitalización a la práctica corporal: análisis cualitativo de experiencias en el proyecto Respirar no Amazonas

A pandemia do coronavírus (covid-19) desencadeou uma avalanche de incessantes tentativas em busca por soluções para os diferentes desafios relacionados à saúde. Neste cenário, políticas públicas voltadas para auxiliar a população como o Projeto Respirar foram fundamentais para recuperar a funcionalidade cardiorrespiratória e física de pacientes. O objetivo deste estudo é apresentar as experiências de um grupo de ex-pacientes, e agora usuários do Projeto Respirar, desde a alta hospitalar até a alta ao final do projeto. A coleta de dados incluiu a realização de dois Grupos Focais. Os usuários relataram sentir muitos medos e incertezas no início da pandemia, contudo, após o ingresso no Projeto Respirar, mudanças aconteceram nas suas percepções de saúde, em seus comportamentos e hábitos (AU).

The coronavirus (covid-19) pandemic has triggered an avalan-che of incessant attempts to find solutions to different health-related challenges. In this scenario, public policies aimed at helping the popula-tion, such as the Breathing Project, were essential to recover the cardio-respiratory and physical functionality of patients. The objective of this study was to present the experiences of a group of former patients, who are now users of Projeto Respirar from hospital discharge to discharge at the end of the project. Data collection included conducting two Focus Groups. Users reported feeling many fears and uncertainties at the be-ginning of the pandemic, however, after joining Projeto Respirar, chan-ges occurred in their health perceptions, behaviors and habits (AU)

La pandemia del coronavirus (covid-19) ha desencadenado una avalancha de intentos incesantes por encontrar soluciones a diferentes desafíos relacionados con la salud. En ese escenario, las políticas públicas dirigidas a ayudar a la población, como el Proyecto Respiración, fueron fundamentales para recuperar la funcionalidad cardiorrespirato-ria y física de los pacientes. El objetivo de este estudio fue presentar las experiencias de un grupo de ex pacientes, que ahora son usuarios Projeto Respirar desde el alta hospitalaria hasta el alta al final del proyecto. La recopilación de datos incluyó la realización de dos Grupos Focales. Los usuarios reportaron sentir muchos miedos e incertidumbres al inicio de la pandemia, sin embargo, luego de unirse a Projeto Respirar, ocurrieron cambios en sus percepciones de salud, comportamientos y hábitos (AU).

Da hospitalização para a prática corporal: análise qualitativa das vivências no projeto Respirar no Amazonas / From hospitalizaton to corporal practice: qualitative analysis of experiences in the projeto Respirar no Amazonas / Del hospitalización a la práctica corporal: análisis cualitativo de experiencias en el proyecto Respirar no Amazonas

A pandemia do coronavírus (covid-19) desencadeou uma ava-lanche de incessantes tentativas em busca por soluções para os dife-rentes desafios relacionados à saúde. Neste cenário, políticas públicas voltadas para auxiliar a população como o Projeto Respirar foram fun-damentais para recuperar a funcionalidade cardiorrespiratória e física de pacientes. O objetivo deste estudo é apresentar as experiências de um grupo de ex-pacientes, e agora usuários do Projeto Respirar, desde a alta hospitalar até a alta ao final do projeto. A coleta de dados incluiu a realização de dois Grupos Focais. Os usuários relataram sentir muitos medos e incertezas no início da pandemia, contudo, após o ingresso no Projeto Respirar, mudanças aconteceram nas suas percepções de saú-de, em seus comportamentos e hábitos.

The coronavirus (covid-19) pandemic has triggered an avalan-che of incessant attempts to find solutions to different health-related challenges. In this scenario, public policies aimed at helping the popula-tion, such as the Breathing Project, were essential to recover the cardio-respiratory and physical functionality of patients. The objective of this study was to present the experiences of a group of former patients, who are now users of Projeto Respirar from hospital discharge to discharge at the end of the project. Data collection included conducting two Focus Groups. Users reported feeling many fears and uncertainties at the be-ginning of the pandemic, however, after joining Projeto Respirar, chan-ges occurred in their health perceptions, behaviors and habits.

La pandemia del coronavirus (covid-19) ha desencadenado una avalancha de intentos incesantes por encontrar soluciones a dife-rentes desafíos relacionados con la salud. En ese escenario, las políticas públicas dirigidas a ayudar a la población, como el Proyecto Respiración, fueron fundamentales para recuperar la funcionalidad cardiorrespirato-ria y física de los pacientes. El objetivo de este estudio fue presentar las experiencias de un grupo de ex pacientes, que ahora son usuarios del Projeto Respirar desde el alta hospitalaria hasta el alta al final del proyec-to. La recopilación de datos incluyó la realización de dos Grupos Focales. Los usuarios reportaron sentir muchos miedos e incertidumbres al inicio de la pandemia, sin embargo, luego de unirse a Projeto Respirar, ocurrie-ron cambios en sus percepciones de salud, comportamientos y hábitos.

Maximal Oxygen Uptake, Muscular Oxidative Capacity, and Ventilatory Threshold in Amateur Triathletes: Eight-Month Training Follow-Up.

Purpose: Endurance sports performance is influenced by several factors, including maximal oxygen uptake (⩒O2max), the percentage of ⩒O2max that can be sustained in endurance events, running economy, and body composition. Traditionally, ⩒O2max can be measured as an absolute value, adjusted for body mass, reflecting the athlete's central capacity (maximal cardiac output), or adjusted for lean mass (LM), reflecting the athlete's peripheral capacity (muscular oxidative capacity). The present study aims to evaluate absolute, total body mass, and lower limb LM-adjusted ⩒O2max, ventilatory thresholds (VT), respiratory compensation points (RCP), and body composition during two training periods separated by 8 months. Patients and Methods: Thirteen competitive amateur triathletes [seven men (40.7±13.7 years old, 76.3±8.3kg, and 173.9±4.8cm) and six women (43.5±6.9 years old, 55.0±2.7kg, 164.9±5.2cm)] were evaluated for body composition with dual-energy X-ray absorptiometry and ⩒O2max, VT, RPC, and maximal aerobic speed (MAS) with a cardiorespiratory maximal treadmill test. Results: The absolute ⩒O2max (p = 0.003, d = 1.05), body mass-adjusted ⩒O2max (p < 0.001, d = 1.2859), and MAS (p = 0.047, d = 0.6139) values differed significantly across evaluation periods. Lower limb LM-adjusted ⩒O2max (p = 0.083, d = -0.0418), %⩒O2max at VT (p = 0.541, d = -0.1746), speed at VT (p = 0.337, d = -0.2774), % ⩒O2max at RCP (p = 0.776, d = 0.0806), and speed at RCP (p = 0.436, d = 0.2234) showed no difference. Conclusion: The sensitivities of ⩒O2max adjusted for body mass and ⩒O2max adjusted for LM to detect changes in physical training state differ. Furthermore, decreases in physical fitness level, as evaluated by ⩒O2max values, are not accompanied by changes in VT.