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The Zenith Total Delay (ZTD) is one of the primary error sources derived from the neutral atmosphere associated with the GNSS (Global Navigation Satellite Systems) technique. Zenith Wet Delay (ZWD) is the smallest part of the ZTD, but the high variability is caused by spatial-temporal variation, making the modelling of this component a challenging task. Although ZWD is considered an error in GNSS positioning, it is also a variable composed mainly of water vapour and can, therefore, be used for atmospheric investigations, and assists in climate studies for precipitation events. In this work, a model was trained to estimate the delay wet component from surface atmospheric parameters. The training data comes from 29 radiosonde stations around Brazil, for a six-year period (2017 to 2022), with data collected at 12 h UTC (Universal Time Coordinated). The model was validated using the holdout technique, with 70% of the data used in training and 30% for validation (cross-validation analysis). The generated model achieved a RMSE (Root Mean Squared Error) of approximately 38 mm, with an 81% of determination coefficient.

Objective The study aimed to evaluate the top large language models (LLMs) in validated medical knowledge tests in Portuguese.Methods This study compared 31 LLMs in the context of solving the national Brazilian medical examination test. The research compared the performance of 23 open-source and 8 proprietary models across 399 multiple-choice questions.Results Among the smaller models, Llama 3 8B exhibited the highest success rate, achieving 53.9%, while the medium-sized model Mixtral 8×7B attained a success rate of 63.7%. Conversely, larger models like Llama 3 70B achieved a success rate of 77.5%. Among the proprietary models, GPT-4o and Claude Opus demonstrated superior accuracy, scoring 86.8% and 83.8%, respectively.Conclusions 10 out of the 31 LLMs attained better than human level of performance in the Revalida benchmark, with 9 failing to provide coherent answers to the task. Larger models exhibited superior performance overall. However, certain medium-sized LLMs surpassed the performance of some of the larger LLMs.

Introduction: The time elapsed from diagnosis to hematopoietic stem cell transplantation (HSCT) is influenced by numerous factors. In Brazil, patients using the public health system are also dependent on the availability of HSCT-specific beds in the hematology ward. Objective and Methods: We conducted a cohort study of listed patients who underwent allogeneic HSCT at a Brazilian public hospital to investigate the impact of the waitlist time on post-HSCT survival. Results: The median time from diagnosis to HSCT was 19 months (IQR, 10 - 43), of which 6 months (IQR, 3 - 9) were spent on the waitlist. The time on the waitlist for HSCT appeared to influence mainly the survival of adult patients (≥ 18 years), with an increasing risk according to this time (RR, 3.53 and 95%CI, 1.81 - 6.88 for > 3 and ≤ 6 months; RR 5.86 and 95%CI, 3.26 - 10.53 for > 6 and ≤ 12 months, and; RR 4.24 and 95%CI, 2.32 - 7.75 for > 12 months). Conclusion: Patients who remained on the waitlist for less than 3 months had the highest survival (median survival, 856 days; IQR, 131 - 1607). The risk of reduced survival was about 6-fold higher (95%CI, 2.8 - 11.5) in patients with malignancies.

O processo de urbanização e o envelhecimento populacional são tendências globais que demandam adaptação e aprimoramento dos espaços urbanos e serviços visando promover o envelhecimento ativo e saudável, além de atender às demandas das pessoas idosas. A concentração de pessoas em áreas urbanas provocou um rápido e desordenado crescimento das cidades, o que representa um desafio ao direito à cidade para pessoas idosas. A necessidade de criar ambientes acessíveis e inclusivos impulsionou governos a aderir ao Programa Cidades e Comunidades Amigáveis à Pessoa Idosa, da Organização Mundial de Saúde, como política pública local para a promoção do envelhecimento ativo e saudável. O presente artigo tem como objetivo analisar, nos Planos Municipais de Ação de cidades brasileiras que integram a Rede Global Cidades e Comunidades Amigáveis à Pessoa Idosa, as ações propostas voltadas aos aspectos de infraestrutura urbana e habitacional. Para isso, foi realizada uma pesquisa descritiva e exploratória, utilizando-se de procedimentos bibliográficos e documentais. A análise dos Planos Municipais de Ação destaca a relevância atribuída à infraestrutura urbana e habitacional e evidencia a necessidade de políticas públicas com abordagem estratégica e articulada para enfrentar os desafios do envelhecimento populacional.

Abstract The two species of the microbiotheriid marsupial genus Dromiciops (Dromiciops bozinovici: “Panchos's monito del monte” and Dromiciops gliroides: “monito del monte”) exhibit a marked latitudinal genetic differentiation. Nevertheless, it is unclear whether this differentiation results from neutral processes or can be explained, to some extent, by local adaptation to different environmental conditions. Here, we used an SNP panel gathered by Rad‐seq and searched for footprints of local adaptation (putative loci under selection) by exploring genetic associations with environmental variables in the two species of Dromiciops in Chilean and Argentinean populations. We applied three methods for detecting outlier SNPs and two genotype–environment associations approaches to quantify associations between allelic frequencies and environmental variables. Both species display strong genetic structure. D. bozinovici exhibited three distinct genetic groups, marking the first report of such structuring in this species using SNPs. In contrast, D. gliroides displayed four genetic clusters, consistent with previous studies. Both species exhibited an association of their genetic structure with environmental variables. D. bozinovici exhibited significant associations of allelic frequencies with elevation, precipitation during the warmest periods, and seasonality in the thermal regime. For D. gliroides, genetic variation appeared to be associated with more variables than D. bozinovici, including precipitation and temperature‐related variables, isothermality, and elevation. All the outlier SNPs were mapped to the D. gliroides reference genome to explore if they fell within functionally known genes. These results represent a necessary first step toward identifying the genome regions that harbor genes associated with climate adaptations in Dromiciops. Notably, we identified genes involved in various functions, including carbohydrate synthesis (ALG8), muscle and neuronal regulation (MEF2D), and stress responses (PTGES3). Ultimately, this study contributes valuable insights that can inform targeted conservation strategies aimed at preserving the genetic diversity of Dromiciops in the face of environmental challenges.

Ionosphere is an important layer of Earth’s atmosphere which can interfere in the transmission of radio signals, affecting several activities, such as the ones related to global navigation satellite systems (GNSS) positioning. In this intend, many efforts have been made in the last decades in order to better understand and model this region of atmosphere. The observation of ionosphere and its irregularities can be performed by several techniques, including classic methods such as ionosondes. Besides that, the use of GNSS signals as source of atmospheric observations have allowed the development of different methodologies and techniques to obtain ionospheric information. Among those, the use of data collected by receivers embedded in low earth orbiting (LEO) satellites, such as the ones used in radio occultation (RO) missions can be relevant due to the amount and distribution of the data obtained. Besides that, GNSS receivers has also been used in ground stations networks to continuously monitor the ionosphere. In this sense, the present work aims to compare irregularities observed by two different techniques using data from ground-based (GNSS monitoring stations) and satellite-embedded (RO mission) receivers. The study is performed over one of the most challenging scenarios, the Brazilian region, considering seasonal variability in two months (low and high solar flux) from 2014 (solar cycle peak). The results obtained show agreement in the general behavior of the ionospheric irregularities observed by the two different techniques.

Lager yeasts are limited to a few strains worldwide, imposing restrictions on flavour and aroma diversity and hindering our understanding of the complex evolutionary mechanisms during yeast domestication. The recent finding of diverse S. eubayanus lineages from Patagonia offers potential for generating new lager yeasts with different flavour profiles. Here, we leverage the natural genetic diversity of S. eubayanus and expand the lager yeast repertoire by including three distinct Patagonian S. eubayanus lineages. We used experimental evolution and selection on desirable traits to enhance the fermentation profiles of novel S. cerevisiae x S. eubayanus hybrids. Our analyses reveal an intricate interplay of pre-existing diversity, selection on species-specific mitochondria, de-novo mutations, and gene copy variations in sugar metabolism genes, resulting in high ethanol production and unique aroma profiles. Hybrids with S. eubayanus mitochondria exhibited greater evolutionary potential and superior fitness post-evolution, analogous to commercial lager hybrids. Using genome-wide screens of the parental subgenomes, we identified genetic changes in IRA2, IMA1, and MALX genes that influence maltose metabolism, and increase glycolytic flux and sugar consumption in the evolved hybrids. Functional validation and transcriptome analyses confirmed increased maltose-related gene expression, influencing greater maltotriose consumption in evolved hybrids. This study demonstrates the potential for generating industrially viable lager yeast hybrids from wild Patagonian strains. Our hybridization, evolution, and mitochondrial selection approach produced hybrids with high fermentation capacity and expands lager beer brewing options.

ABSTRACTEvaluating domestication signatures beyond model organisms is essential for a thorough understanding of the genotype-phenotype relationship in wild and human-related environments. Structural variations (SVs) can significantly impact phenotypes playing an important role in the physiological adaptation of species to different niches, including during domestication. A detailed characterization of the fitness consequences of these genomic rearrangements, however, is still limited in non-model systems, largely due to the paucity of direct comparisons between domesticated and wild isolates. Here, we used a combination of sequencing strategies to explore major genomic rearrangements in a Lachancea cidri yeast strain isolated from cider (CBS2950) and compared them to those in eight wild isolates from primary forests. Genomic analysis revealed dozens of SVs, including a large reciprocal translocation (~16 kb and 500 kb) present in the cider strain, but absent from all wild strains. Interestingly, the number of SVs was higher relative to single-nucleotide polymorphisms in the cider strain, suggesting a significant role in the strain’s phenotypic variation. The set of SVs identified directly impacts dozens of genes and likely underpins the greater fermentation performance in the L. cidri CBS2950. In addition, the large reciprocal translocation affects a proline permease (PUT4) regulatory region, resulting in higher PUT4 transcript levels, which agrees with higher ethanol tolerance, improved cell growth when using proline, and higher amino acid consumption during fermentation. These results suggest that SVs are responsible for the rapid physiological adaptation of yeast to a human-related environment and demonstrate the key contribution of SVs in adaptive fermentative traits in non-model species.IMPORTANCEThe exploration of domestication signatures associated with human-related environments has predominantly focused on studies conducted on model organisms, such as Saccharomyces cerevisiae, overlooking the potential for comparisons across other non-Saccharomyces species. In our research, employing a combination of long- and short-read data, we found domestication signatures in Lachancea cidri, a non-model species recently isolated from fermentative environments in cider in France. The significance of our study lies in the identification of large array of major genomic rearrangements in a cider strain compared to wild isolates, which underly several fermentative traits. These domestication signatures result from structural variants, which are likely responsible for the phenotypic differences between strains, providing a rapid path of adaptation to human-related environments.

Introduction: Although extracorporeal photopheresis (ECP) is a promising second-line therapy in the treatment of chronic graft-versus-host disease (cGVHD), its use is limited by its high cost. This study aims to describe the clinical evolution of patients who underwent ECP therapy for cGVHD and to perform an economic analysis of the therapy Methods: This was a case series between 2016 and 2020 describing the clinical response to ECP and a micro-cost analysis of the therapy using time-driven activity-based costing. Results: Six patients underwent ECP for corticosteroid-dependent cGVHD The cost per ECP session is 14,960.90 Brazilian reais (BRL), which primarily consists of the ECP kit with an activator (82.78%), followed by the hospital's physical structure (14.66%), human resources (2.48%) and exams/inputs (0.08%). The number of sessions performed ranged from 2 to 42. The total cost of the therapy per patient ranged from BRL 30,000 to 500,000. Conclusion: The response of the patient with cGVHD to treatment with ECP was variable. These micro-costing results can be used to develop remuneration and cost control strategies in hematopoietic stem cell transplantation programs, as well as in further economic studies.

Introdução: Streptococcus pneumoniae é um importante colonizador nasofaríngeo, e potencial causador de infecções graves e invasivas em crianças. Desde 2010, a vacina pneumocócica conjugada 10 (PVC-10) está disponível pelo Programa Nacional de Imunizações. O objetivo deste estudo foi descrever a colonização de S. pneumoniae e identificar outros patógenos durante o primeiro ano da pandemia de COVID-19. Métodos: Foram recrutados em um estudo observacional prospectivo, crianças (≤10 anos) em dois hospitais do Sul do Brasil entre maio e novembro de 2020. A presença de sintomas respiratórios (dor de garganta, tosse e febre ≥37,8°C) foram critérios de inclusão dos participantes. Em todas as amostras coletadas foi realizado um painel para identificação de infecções respiratórias por RT-PCR. Nas amostras positivas para S. pneumoniae foi realizada a identificação dos 21 sorotipos mais prevalentes na América Latina. Foram coletadas informações clínicas e dados sobre vacinação. Resultados: Foram incluídos 347 participantes, com idade mediana de 3,6 anos (IQR: 1,5-7,2). Colonização pneumocócica foi identificada em 111 (32%) crianças. 43/111 (38.7%) tinham

Introdução: O Streptococcus pneumoniae é uma das principais bactérias associadas a coinfecções virais. Informações quanto à colonização pneumocócica e coinfecções são limitadas, incluindo uma possível associação com SARS-CoV-2. O objetivo deste estudo foi descrever as frequências de colonização de S. pneumoniae e identificação outros agentes respiratórios patogênicos comuns, durante o primeiro ano da pandemia de COVID-19. Métodos: Estudo observacional prospectivo em participantes com idade >10 anos, com sintomas respiratórios, entre maio e novembro/2020. Foi realizado um painel respiratório abrangente para detecção de agentes respiratórios por RT-PCR, e nos positivos para S. pneumoniae seguiu-se com a identificação de 21 sorotipos. Foram coletadas informações clínicas e dados sobre gravidade/hospitalização. Resultados: Foram incluídos 1.297 participantes; a idade mediana foi de 36,8 anos (IQR = 27,5-47,3). 134/1.297 (10,3%) participantes estavam colonizados por S. pneumoniae e 33/134 (26,4%) tiveram sorotipos identificados. O sorotipo 19A foi o mais prevalente (21,2%, 7/33), seguido por: 23A (15,2%, 5/33) e 6C/6D (12,1%, 4/33). Os principais patógenos respiratórios identificados foram SARS-CoV-2 (36,4%, 472/1.296), rinovírus (34,8%, 449/1.291), Mycoplasma pneumoniae (1,4%, 18/1.291), e em menor percentual coronavírus HKU1 e NL63, enterovírus, metapneumovírus, adenovírus, representando 1,9% (25/1.291). A detecção de rinovírus foi associada à não-colonização pneumocócica (p < 0,001), enquanto que nos outros patógenos detectados não houve associação significativa para colonização. Não foram detectados: Bordetella pertussis, bocavírus; coronavírus (229E e OC43); vírus influenza A (H1 e H3); vírus influenza B; vírus parainfluenza (1, 2 e 3); e vírus sincicial respiratório (A e B). Não houve associação entre gravidade clínica e colonização pneumocócica. 5,5% (71/1.297) indivíduos foram hospitalizados; 4% (46/1.297) precisaram de oxigênio suplementar e houve 1% (15/1.297) de óbitos. 14,3% (185/1.297) referiram uso de antibióticos na semana anterior à inclusão no estudo, sendo que 94% (173/185) não eram colonizados (p = 0,049). Conclusão: Não houve associação da colonização com patógenos respiratórios ou desfechos por hospitalização. O sorotipo 19A foi o mais prevalente nessa população, sendo um potencial agente de infecção invasiva. A avaliação da prevalência é fundamental para monitorar o cenário epidemiológico e orientar a tomada de decisões em saúde pública.

Antimicrobials serve as crucial treatments in both veterinary and human medicine, aiding in the control and prevention of infectious diseases. However, their misuse or overuse has led to the emergence of antimicrobial resistance, posing a significant threat to public health. This review focuses on extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in animals and their associated food products, which contribute to the proliferation of antimicrobial-resistant strains. Recent research has highlighted the presence of ESBL-producing E. coli in animals and animal-derived foods, with some studies indicating genetic similarities between these isolates and those found in human infections. This underscores the urgent need to address antimicrobial resistance as a pressing public health issue. More comprehensive studies are required to understand the evolving landscape of ESBLs and to develop strategic public health policies grounded in the One Health approach, aiming to control and mitigate their prevalence effectively.

Objective: Changes in the epidemiology of respiratory infections during the restrictions imposed as a response to the coronavirus disease 2019 (COVID-19) pandemic have been reported elsewhere. The present study's aim was to describe the prevalence of a large array of respiratory pathogens in symptomatic children and adolescents during the pandemic in Southern Brazil. Methods: Hospitalized and outpatients aged 2 months to 18 years with signs and symptoms of acute COVID-19 were prospectively enrolled in the study from May to November 2020 in two hospitals in a large metropolitan area in a Brazilian city. All participants performed a real-time PCR panel assessing 20 respiratory pathogens (three bacteria and 17 viruses). Results: 436 participants were included, with 45 of these hospitalized. Rhinovirus was the most prevalent pathogen (216/436) followed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 97/436), with a coinfection of these two viruses occurring in 31/436 participants. The remaining pathogens were found in 24 symptomatic participants (adenovirus, n = 6; Chlamydophila pneumoniae, n = 1; coronavirus NL63, n = 2; human enterovirus, n = 7; human metapneumovirus, n = 2; Mycoplasma pneumoniae, n = 6). Hospitalization was more common among infants (p = 0.004) and those with pathogens other than SARS-CoV-2 (p = 0.001). Conclusion: During the period of social distancing in response to COVID-19, the prevalence of most respiratory pathogens was unusually low. Rhinovirus remained as the main virus co-circulating with SARS-CoV-2. COVID-19 in symptomatic children was less associated with hospitalization than with other respiratory infections in children and adolescents.

ABSTRACT Objective: To evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Subjects and methods: Adults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought treatment in two hospital (public and private) emergency departments were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at days D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results: A total of 1,050 participants were screened, and 297 completed the 28-day follow-up and were diagnosed with COVID-19 by RT-PCR. The median age was 37.2 (IQR 29.7-44.6) years, and 179 (60.0%) were female. The duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. Ninety-five (32.0%) individuals had obesity, and 233 (78.5%) had no previous medical conditions. Twenty-three participants (7.7%) required hospitalization during the follow-up period. After adjusting, obesity (BMI ≥ 30.0 kg/m2) (OR = 2.69, 95% CI 1.63-4.83, P < 0.001) and older age (OR = 1.05, 95% CI 1.01-1.09, P < 0.001) were significantly associated with higher risks of hospitalization. Conclusion: Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need to promote additional protection for individuals with obesity, such as vaccination, and to encourage lifestyle changes.

Abstract Since its identification, Saccharomyces eubayanus has been recognized as the missing parent of the lager hybrid, S. pastorianus. This wild yeast has never been isolated from fermentation environments, thus representing an interesting candidate for evolutionary, ecological and genetic studies. However, it is imperative to develop additional molecular genetics tools to ease manipulation and thus facilitate future studies. With this in mind, we generated a collection of stable haploid strains representative of three main lineages described in S. eubayanus (PB-1, PB-2 and PB-3), by deleting the HO gene using CRISPR-Cas9 and tetrad micromanipulation. Phenotypic characterization under different conditions demonstrated that the haploid derivates were extremely similar to their parental strains. Genomic analysis in three strains highlighted a likely low frequency of off-targets, and sequencing of a single tetrad evidenced no structural variants in any of the haploid spores. Finally, we demonstrate the utilization of the haploid set by challenging the strains under mass-mating conditions. In this way, we found that S. eubayanus under liquid conditions has a preference to remain in a haploid state, unlike S. cerevisiae that mates rapidly. This haploid resource is a novel set of strains for future yeast molecular genetics studies.

Summary Although the typical genomic and phenotypic changes that characterize the evolution of organisms under the human domestication syndrome represent textbook examples of rapid evolution, the molecular processes that underpin such changes are still poorly understood. Domesticated yeasts for brewing, where short generation times and large phenotypic and genomic plasticity were attained in a few generations under selection, are prime examples. To experimentally emulate the lager yeast domestication process, we created a genetically complex (panmictic) artificial population of multiple Saccharomyces eubayanus genotypes, one of the parents of lager yeast. Then, we imposed a constant selection regime under a high ethanol concentration in 10 replicated populations during 260 generations (6 months) and compared them with propagated controls exposed solely to glucose. Propagated populations exhibited a selection differential of 60% in growth rate in ethanol, mostly explained by the proliferation of a single lineage (CL248.1) that competitively displaced all other clones. Interestingly, the outcome does not require the entire time‐course of adaptation, as four lineages monopolized the culture at generation 120. Sequencing demonstrated that de novo genetic variants were produced in all propagated lines, including SNPs, aneuploidies, INDELs and translocations. In addition, the different propagated populations showed correlated responses resembling the domestication syndrome: genomic rearrangements, faster fermentation rates, lower production of phenolic off‐flavours and lower volatile compound complexity. Expression profiling in beer wort revealed altered expression levels of genes related to methionine metabolism, flocculation, stress tolerance and diauxic shift, likely contributing to higher ethanol and fermentation stress tolerance in the evolved populations. Our study shows that experimental evolution can rebuild the brewing domestication process in ‘fast motion’ in wild yeast, and also provides a powerful tool for studying the genetics of the adaptation process in complex populations.

Tracing how free-ranging organisms interact with their environment to maintain water balance is a difficult topic to study for logistical and methodological reasons. We use a novel combination of triple-oxygen stable isotope analyses of water extracted from plasma (δ16O, δ17O, δ18O) and bulk tissue carbon (δ13C) and nitrogen (δ15N) isotopes of feathers and blood to estimate the proportional contribution of marine resources, seawater, and metabolic water used by two species of unique songbirds (genus Cinclodes) to maintain their water balance in a seasonal coastal environment. We also assessed the physiological adjustments that these birds use to maintain their water balance. In agreement with previous work on these species, δ13C and δ15N data show that the coastal resident and invertivore C. nigrofumosus consumes a diet rich in marine resources, while the diet of migratory C. oustaleti shifts seasonally between marine (winter) to freshwater aquatic resources (summer). Triple-oxygen isotope analysis (Δ17O) of blood plasma, basal metabolic rate (BMR), and total evaporative water loss (TEWL) revealed that ~25% of the body water pool of both species originated from metabolic water, while the rest originated from a mix of seawater and fresh water. Δ17O measurements suggest that the contribution of metabolic water tends to increase in summer in C. nigrofumosus, which is coupled with a significant increase in BMR and TEWL. The two species had similar BMR and TEWL during the austral winter when they occur sympatrically in coastal environments. We also found a positive and significant association between the use of marine resources as measured by δ13C and δ15N values and the estimated δ18O values of ingested (pre-formed) water in both species, which indicates that Cinclodes do not directly drink seawater but rather passively ingest when consuming marine invertebrates. Finally, results obtained from physiological parameters and the isotope-based estimates of marine (food and water) resource use are consistent, supporting the use of the triple-oxygen isotopes to quantify the contribution of water sources to the total water balance of free-ranging birds.