Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab.

In PIVOT IO 001 (NCT03635983), the combination of the investigational interleukin-2 agonist bempegaldesleukin (BEMPEG) with nivolumab (NIVO) had no added clinical benefit over NIVO monotherapy in unresectable/metastatic melanoma. Pre-defined baseline and on-treatment changes in selected biomarkers were analyzed to explore the potential mechanisms underlying the clinical observations. In each treatment arm, higher baseline tumor mutational burden or immune infiltration/inflammation was associated with improved efficacy compared with lower levels. On-treatment peripheral biomarker changes showed that BEMPEG + NIVO increased all immune cell subset counts interrogated, including regulatory T cells. This was followed by attenuation of the increase in CD8 + T cells, conventional CD4 + T cells, and systemic interferon gamma levels at later treatment cycles in the combination arm. Changes in tumor biomarkers were comparable between arms. These biomarker results help provide a better understanding of the mechanism of action of BEMPEG + NIVO and may help contextualize the clinical observations from PIVOT IO 001.

Novel powdery mildew of cotton (Gossypium hirsutum) caused by Phyllactinia gossypina sp. nov. in Brazil.

Cotton (Gossypium hirsutum, Malvaceae) is the most important fiber crop in the world. There are published records of many fungal pathogens attacking Gossypium spp., causing numerous diseases, including powdery mildews. Recently, in 2022, non-cultivated spontaneous G. hirsutum plants bearing powdery mildews symptoms were found at roadsides in two municipalities of the state of Minas Gerais (Brazil): Varginha and Ubá. Such localities are situated ca. 260 km apart, suggesting a broader distribution of this fungus-host association in Brazil. Samples were taken to the laboratory, and an Ovulariopsis-like, asexual stage of Phyllactinia, was identified forming amphigenous colonies, that were more evident, white and cottony, abaxially. Morphological and molecular data- of the ITS and LSU regions- have shown that colonies from those two samples were of the same fungus species, belonging to a previously unknown species of Erysiphaceae (Ascomycota). The fungus fits into the Phyllactinia clade and is described herein as the new species Phyllactinia gossypina sp. nov. This new species belongs to the 'basal Phyllactinia group', a lineage that includes species known only from the Americas. This report expands the list of pathogenic fungi on cotton. It is early to anticipate whether this new powdery mildew represents a threat to cultivated cotton, which is a major crop in Brazil. Nevertheless, further studies about its infectivity to commercial cotton varieties are recommended, since all known Erysiphaceae are specialized obligate plant parasites and several species cause major losses to important crops.

Cordyceps cateniannulata: An endophyte of coffee, a parasite of coffee leaf rust and a pathogen of coffee pests.

Here, we report on a Cordyceps species entering into a multi-trophic, multi-kingdom association. Cordyceps cateniannulata, isolated from the stem of wild Coffea arabica in Ethiopia, is shown to function as an endophyte, a mycoparasite and an entomopathogen. A detailed polyphasic taxonomic study, including a multilocus phylogenetic analysis, confirmed its identity. An emended description of C. cateniannulata is provided herein. Previously, this species was known as a pathogen of various insect hosts in both the Old and New World. The endophytic status of C. cateniannulata was confirmed by re-isolating it from inoculated coffee plants. Inoculation studies have further shown that C. cateniannulata is a mycoparasite of Hemileia vastatrix, as well as an entomopathogen of major coffee pests; infecting and killing Hypothenemus hampei and Leucoptera coffeella. This is the first record of C. cateniannulata from Africa, as well as an endophyte and a mycoparasite. The implications for its use as a biocontrol agent are discussed.

Immunohistochemistry assessment of tissue neutrophil-to-lymphocyte ratio predicts outcomes in melanoma patients treated with anti-programmed cell death 1 therapy.

Elevated neutrophil-to-lymphocyte ratio (NLR) is associated with diminished immunotherapy response in metastatic melanoma. Although NLR assessment in peripheral blood is established, tissue dynamics remain insufficiently explored. This study aimed to evaluate tissue NLR (tNLR)'s predictive potential through immunohistochemistry in immunotherapy-treated melanoma. Fifty melanoma patients who underwent anti-programmed cell death 1 (PD-1) therapy were assessed. Hematological, clinical and tumor features were collected from medical records. Responses were categorized using the Response Evaluation Criteria in Solid Tumors for immunotherapy (iRECIST) guidelines. Immunohistochemistry for tumor-infiltrating T cells (cluster differentiation 3) and neutrophils (myeloperoxidase) was performed on formalin-fixed paraffin-embedded tumor samples. NLR, derived NLR (dNLR) and tNLR were calculated. Overall survival (OS) and survival following immunotherapy (SFI) were calculated from diagnosis or immunotherapy start to loss of follow-up or death. Patients with high tNLR presented improved OS ( P =  0.038) and SFI with anti-PD-1 therapy ( P =  0.006). Both NLR and dNLR were associated with OS ( P =  0.038 and P =  0.046, respectively) and SFI ( P =  0.001 and P =  0.019, respectively). NLR was also associated with immunotherapy response ( P =  0.007). In conclusion, tNLR emerged as a novel potential biomarker of enhanced survival post anti-PD-1 therapy, in contrast to classical NLR and dNLR markers.

Physiological Responses of C4 Perennial Bioenergy Grasses to Climate Change: Causes, Consequences, and Constraints.

C4 perennial bioenergy grasses are an economically and ecologically important group whose responses to climate change will be important to the future bioeconomy. These grasses are highly productive and frequently possess large geographic ranges and broad environmental tolerances, which may contribute to the evolution of ecotypes that differ in physiological acclimation capacity and the evolution of distinct functional strategies. C4 perennial bioenergy grasses are predicted to thrive under climate change-C4 photosynthesis likely evolved to enhance photosynthetic efficiency under stressful conditions of low [CO2], high temperature, and drought-although few studies have examined how these species will respond to combined stresses or to extremes of temperature and precipitation. Important targets for C4 perennial bioenergy production in a changing world, such as sustainability and resilience, can benefit from combining knowledge of C4 physiology with recent advances in crop improvement, especially genomic selection.

Lexical quality measures in the assessment of reading proficiency in Brazilian university students / Medidas de qualidade lexical na avaliação da proficiência de leitura em alunos universitários brasileiros

ABSTRACT Purpose: to assess the reading ability of university students using tasks to measure Lexical Quality (LQ) and evaluate the influence of socioeconomic status (SES) on both the reading performance and the components of Lexical Quality (LQ). Methods: 44 students from two federal universities took online linguistic tests, 19 from the Federal University of the Great ABC Region (UFABC) and 25 from the Federal University of Ceará (UFC), Brazil. Two-ranked Mann-Whitney (Wilcoxon rank-sum test) and Pearson's Correlation tests at p<0,05 were applied to analyze the data. Results: high and medium correlations were obtained among the different components of LQ, such as vocabulary and spelling recognition. In addition, significant differences were found between the performances of the two universities' students and their distinct socioeconomic levels. Conclusion: shorter reading times were correlated to higher accuracy in the Test of Word Reading Efficiency for Adults. The number of correct answers in the homonym test was correlated to the higher accuracy of the Test of Word Reading Efficiency for Adults, and both were correlated to the reaction time measures of these tests. The influence of socioeconomic status on reading performance and Lexical Quality components tasks was also found.

RESUMO Objetivos: comparar o desempenho de alunos universitários brasileiros a partir de tarefas com habilidades de qualidade lexical e avaliar a influência do nível socioeconômico no desempenho da leitura e nos componentes que formam a qualidade lexical. Métodos: testes linguísticos on-line foram aplicados em 44 estudantes de duas universidades federais, sendo 19 da Universidade Federal do ABC e 25 da Universidade Federal do Ceará. Para análise foram utilizados os testes Mann-Whitney (Wilcoxon rank-sum test) de duas vias e a Correlação de Pearson com p<0,05. Resultados: foram obtidas correlações altas e médias entre os diferentes componentes da qualidade lexical, tais como vocabulário e reconhecimento ortográfico, além de terem sido encontradas diferenças significativas entre o desempenho dos alunos das duas universidades e de diferentes níveis socioeconômicos. Conclusão: menor tempo de leitura apresentou correlação com maior quantidade de acertos na leitura de palavras em voz alta, a quantidade de acertos no teste de homônimos correlacionou-se a quantidade de acertos no teste de leitura de palavras em voz alta e ambas correlacionaram-se com o tempo de resposta destes testes. Houve, também, influência do nível socioeconômico no desempenho da leitura e nos componentes que formam a qualidade lexical.

Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results.

PURPOSE: Despite marked advances in the treatment of unresectable or metastatic melanoma, the need for novel therapies remains. Bempegaldesleukin (BEMPEG), a pegylated interleukin-2 (IL-2) cytokine prodrug, demonstrated efficacy in the phase II PIVOT-02 trial. PIVOT IO 001 (ClinicalTrials.gov identifier: NCT03635983) is a phase III, randomized, open-label study that builds on the PIVOT-02 results in first-line melanoma. METHODS: Patients with previously untreated, unresectable, or metastatic melanoma were randomly assigned 1:1 to receive BEMPEG plus nivolumab (NIVO) or NIVO monotherapy. Primary end points were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review and overall survival (OS). Secondary and exploratory end points included additional efficacy measures, safety, and pharmacokinetics (PKs) and pharmacodynamics analyses. RESULTS: In 783 patients (n = 391, BEMPEG plus NIVO; n = 392, NIVO monotherapy), the median follow-up was 11.6 months in the intent-to-treat population. The ORR with BEMPEG plus NIVO was 27.7% versus 36.0% with NIVO (two-sided P = .0311). The median PFS with BEMPEG plus NIVO was 4.17 months (95% CI, 3.52 to 5.55) versus 4.99 months (95% CI, 4.14 to 7.82) with NIVO (hazard ratio [HR], 1.09; 97% CI, 0.88 to 1.35; P = .3988). The median OS was 29.67 months (95% CI, 22.14 to not reached [NR]) with BEMPEG plus NIVO versus 28.88 months (95% CI, 21.32 to NR) with NIVO (HR, 0.94; 99.929% CI, 0.59 to 1.48; P = .6361). Grade 3-4 treatment-related adverse events (AEs) and serious AE rates were higher with the combination (21.7% and 10.1%, respectively) versus NIVO (11.5% and 5.5%, respectively). BEMPEG PK exposure and absolute lymphocyte count changes after BEMPEG plus NIVO were comparable between PIVOT IO 001 and PIVOT-02. CONCLUSION: The PIVOT IO 001 study did not meet its primary end points of ORR, PFS, and OS. Increased toxicity was observed with BEMPEG plus NIVO versus NIVO.

PD-L1 Tumor Expression as a Predictive Biomarker of Immune Checkpoint Inhibitors' Response and Survival in Advanced Melanoma Patients in Brazil.

Immune checkpoint blockade (ICB) agents are prominent immunotherapies for the treatment of advanced melanoma. However, they fail to promote any durable clinical benefit in a large cohort of patients. This study assessed clinical and molecular predictors of ICB response and survival in advanced melanoma. A retrospective analysis was performed on 210 patients treated with PD-1 or CTLA-4 inhibitors at Barretos Cancer Hospital, Brazil. PD-L1 expression was assessed by immunohistochemistry using formalin-fixed paraffin-embedded tumor tissues collected prior to ICB therapy. Patients were divided into responders (complete and partial response and stable disease for more than 6 months) and non-responders (stable disease for less than 6 months and progressive disease). Among them, about 82% underwent anti-PD-1 immunotherapy, and 60.5% progressed after the ICB treatment. Patients that received ICB as first-line therapy showed higher response rates than previously treated patients. Higher response rates were further associated with superficial spreading melanomas and positive PD-L1 expression (>1%). Likewise, PD-L1 positive expression and BRAF V600 mutations were associated with a higher overall survival after ICB therapy. Since ICBs are expensive therapies, evaluation of PD-L1 tumor expression in melanoma patients should be routinely assessed to select patients that are most likely to respond.

Assessing the Biocontrol Potential of Clonostachys Species Isolated as Endophytes from Coffea Species and as Mycoparasites of Hemileia Rusts of Coffee in Africa.

During surveys conducted in South America and Africa to identify natural fungal enemies of coffee leaf rust (CLR), Hemileia vastatrix, over 1500 strains were isolated, either as endophytes from healthy tissues of Coffea species or as mycoparasites growing on rust pustules. Based on morphological data, eight isolates-three isolated from wild or semiwild coffee and five from Hemileia species on coffee, all from Africa-were provisionally assigned to the genus Clonostachys. A polyphasic study of their morphological, cultural and molecular characteristics-including the Tef1 (translation elongation factor 1 alpha), RPB1 (largest subunit of RNA polymerase II), TUB (ß-tubulin) and ACL1 (ATP citrate lyase) regions-confirmed these isolates as belonging to three species of the genus Clonostachys: namely C. byssicola, C. rhizophaga and C. rosea f. rosea. Preliminary assays were also conducted to test the potential of the Clonostachys isolates to reduce CLR severity on coffee under greenhouse conditions. Foliar and soil applications indicated that seven of the isolates had a significant effect (p < 0.05) in reducing CLR severity. In parallel, in vitro tests that involved conidia suspensions of each of the isolates together with urediniospores of H. vastatrix resulted in high levels of inhibition of urediniospore germination. All eight isolates showed their ability to establish as endophytes in C. arabica during this study, and some proved to be mycoparasites of H. vastatrix. In addition to reporting the first records of Clonostachys associated with healthy coffee tissues and with Hemileia rusts of coffee, this work provides the first evidence that Clonostachys isolates have potential as biological control agents against CLR.

Coordination of photosynthetic traits across soil and climate gradients.

"Least-cost theory" posits that C3 plants should balance rates of photosynthetic water loss and carboxylation in relation to the relative acquisition and maintenance costs of resources required for these activities. Here we investigated the dependency of photosynthetic traits on climate and soil properties using a new Australia-wide trait dataset spanning 528 species from 67 sites. We tested the hypotheses that plants on relatively cold or dry sites, or on relatively more fertile sites, would typically operate at greater CO2 drawdown (lower ratio of leaf internal to ambient CO2 , Ci :Ca ) during light-saturated photosynthesis, and at higher leaf N per area (Narea ) and higher carboxylation capacity (Vcmax 25 ) for a given rate of stomatal conductance to water vapour, gsw . These results would be indicative of plants having relatively higher water costs than nutrient costs. In general, our hypotheses were supported. Soil total phosphorus (P) concentration and (more weakly) soil pH exerted positive effects on the Narea -gsw and Vcmax 25 -gsw slopes, and negative effects on Ci :Ca . The P effect strengthened when the effect of climate was removed via partial regression. We observed similar trends with increasing soil cation exchange capacity and clay content, which affect soil nutrient availability, and found that soil properties explained similar amounts of variation in the focal traits as climate did. Although climate typically explained more trait variation than soil did, together they explained up to 52% of variation in the slope relationships and soil properties explained up to 30% of the variation in individual traits. Soils influenced photosynthetic traits as well as their coordination. In particular, the influence of soil P likely reflects the Australia's geologically ancient low-relief landscapes with highly leached soils. Least-cost theory provides a valuable framework for understanding trade-offs between resource costs and use in plants, including limiting soil nutrients.

Práticas corporais de aventura na educação infantil: experiências docentes mediadas pelo Programa Residência Pedagógica / Adventure body practices in child hood education: Teacher experiences mediated by the Pedagogical Residency Program / Prácticas corporales de aventura em La educación infantil: experiencias docentes mediadas por el Programa Residencia Pedagógica

Objetivo: relatar uma experiência pedagógica em educação física estruturada por cinco residentes, uma preceptora e um docente orientador do Programa Residência Pedagógica (PRP) em um Centro Municipal de Educação Infantil de Seropédica/RJ. Metodologia: trata-se de um relato de experiência, proveniente de cinco mediações pedagógicas tematizando ludicamente as Práticas Corporais de Aventura (PCAs) com crianças de três a seis anos de idade, entre os meses de maio e junho de 2023. Resultados e discussão: observou-se que as crianças possuem algumas referências sobre as PCAs e mostram-se interessadas em experienciarem esse tipo de prática corporal. Para tanto, é necessário ouvir as suas falas e valorizar sua participação ativa para guiar o planejamento docente. Considerações Finais: a experiência evidenciou ser possível tematizar as PCAs em consonância com a perspectiva da Sociologia da Infância, mostrando-se potente para promover o protagonismo infantil, contribuindo para o adensamento da formação inicial e continuada dos participantes vinculados ao PRP, em especial, na direção de compreender as peculiaridades que cercam o trabalho educativo com crianças pequenas

Objective: to report a Physical Education pedagogical experience structured by Five residents, one preceptor and one advisor professor of the Pedagogical Residency Program (PRP) at a Child hood Education City Center in Seropédica, RJ. Methodology: an experience report from Five pedagogical mediation using a playful approach to the Adventure Bodily Practices (ABPs) with children aged three to six, during the months of May and June, 2023. Results and discussions: it has been observed that children do possess some references on PCAs and show to be interested in experiencing that kind of bodily practice. Therefore, it becomes necessary to listen to the mand to value their active participation as a guide to teacher planning. Final considerations: this experience proves the possibility of the matizing PCAs in accordance with the Sociology of Child hood's perspective, which unfolds as an effective promoter for children's protagonism, contributing with the consolidation of the initial and continued training of the PRP participants, and especially going towards the comprehension of the peculiarities that surround the educational work with small children

Objetivo: relatar una experiencia pedagógica em educación física estructurada por cinco residentes, una preceptora y un docente orientador del Programa Residencia Pedagógica (PRP) en un Centro Municipal de Educación Infantil de Seropédica/RJ. Metodología: se trata de un relato de experiencia, proveniente de cinco mediaciones pedagógicas tematizando lúdica mente lãs Prácticas Corporales de Aventura (PCAs), com niños de tres a seis años de edad, entre los meses de mayo y junio de 2023. Resultados y discusión: se observó que los niños tienen algunas referencias sobre las PCAs y muestran interésen experimentar este tipo de práctica corporal. Para ello, es necessário escuchar sus palabras y valorar su participación activa para guiar la planificación docente. Consideraciones Finales: esta experiência evidenció que es posible tematizar las PCAs em consonância com la perspectiva de la Sociología de la Infancia, mostrando se potente para promover el protagonismo infantil, contribuyendo al fortalecimiento de la formación inicial y continua de los participantes vinculados al PRP, en especial, em la dirección de compreender las peculiaridades que rodean el trabajo educativo com niños pequeños

Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients' survival.

Introduction: Glioblastoma (GBM), isocitrate dehydrogenase (IDH) wild-type (IDH wt), and grade 4 astrocytomas, IDH mutant (IDH mut), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities. Objectives: We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with IDH wt GBM and IDH mut tumors and identify prognostic biomarkers and a gene signature associated with patient survival. Methods: RNA was isolated from formalin-fixed, paraffin-embedded sections of 99 tumor specimens from patients treated with standard therapy. Gene expression profile was assessed using the Pan-Cancer Immune Profiling Panel (Nanostring Technologies, Inc., Seattle, WA, USA). Data analysis was performed using nSolverSoftware and validated in The Cancer Genome Atlas. In addition, we developed a prognostic signature using the cox regression algorithm (Least Absolute Shrinkage and Selection Operator). Results: We found 88 upregulated genes, high immunological functions, and a high macrophage score in IDH wt GBM compared to IDH mut tumors. Regarding IDH wt GBM, we found 24 upregulated genes in short-term survivors (STS) and overexpression of CD274 (programmed death-ligand 1, PD-L1). Immune pathways, CD45, cytotoxic, and macrophage scores were upregulated in STS. Two different prognostic groups were found based on the 12-gene signature (CXCL14, PSEN2, TNFRSF13C, IL13RA1, MAP2K1, TNFSF14, THY1, CTSL, ITGAE, CHUK, CD207, and IFITM1). Conclusion: The elevated expression of immune-oncology-related genes was associated with worse outcome in IDH wt GBM patients. Increased immune functions, CD45, cytotoxic cells, and macrophage scores were associated with a more aggressive phenotype and may provide promising possibilities for therapy. Moreover, a 12 gene-based signature could predict patients' prognosis.

Portfolio Efficiency Tests with Conditioning Information-Comparing GMM and GEL Estimators.

We evaluate the use of generalized empirical likelihood (GEL) estimators in portfolio efficiency tests for asset pricing models in the presence of conditional information. The use of conditional information is relevant to portfolio management as it allows for checking whether asset allocations are efficiently exploiting all the information available in the market. Estimators from the GEL family present some optimal statistical properties, such as robustness to misspecifications and better properties in finite samples. Unlike generalized method of moments (GMM) estimators, the bias for GEL estimators does not increase with the number of moment conditions included, which is expected in conditional efficiency analysis. Due to these better properties in finite samples, our main hypothesis is that portfolio efficiency tests using GEL estimators may have better properties in terms of size, power, and robustness. Using Monte Carlo experiments, we show that GEL estimators have better performance in the presence of data contaminations, especially under heavy tails and outliers. Extensive empirical analyses show the properties of the estimators for different sample sizes and portfolio types for two asset pricing models.

First Report of Cercospora apii sensu lato 'sp. Q' Leaf Spot on Hop in Brazil.

Hop - Humulus lupulus (Cannabaceae) - is an important and ancient, herbaceous, temperate, perennial crop. It is a vine which, although having other uses, is cultivated predominantly for the brewing industry (Laws 2013). Cultivation of hops in Brazil is relatively new and has increased in the last twenty years. There is only one published record of a fungal disease affecting hop in Brazil - powdery mildew (Fagherazzi et al 2021). In January 2021, leaf spots appeared on all eight hops plants ithe collection maintained in the Infectarium, a disease demonstration garden on the campus of the Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil (https://www.infectario.ufv.br/). Symptoms were small, sub-circular to irregular spots, up to 5 mm, with a whitish to grayish center, surrounded by a dark brown necrotic margin, followed by a narrow yellowish outer margin. Older lesions became larger, grayish-brown, coalesced leading to extensive necrosis and stem dieback. A sample was collected, dried in a plant press, and deposited in the Herbarium of UFV (Acc. No VIC 47534). A dematiaceous fungus was found sporulating in the center of the lesions, when examined with a dissecting microscope. Fungal structures were scraped with a scalpel, mounted in lactoglycerol and observed with a light microscope (Olympus BX51). A pure culture was obtained after conidia were transferred onto PDA plates with a sterile fine-pointed needle. A representative isolate was deposited in the culture collection of the UFV (COAD 3368). The fungus had the following morphology: conidiophores cylindrical, geniculate, proliferating sympodially, 53 to 380 µm × 3 to 6.5 µm, 3 to 15-septate, smooth, with thickened and dark conidial scars, brown; conidia acicular to filiform, 47 to 210 µm × 2.5 to 5 µm, 3 to 17-septate, thin­walled, smooth, with thickened and dark hila, hyaline. This combination is typical of Cercospora apii sensu lato, as described by Crous and Braun (2003). Genomic DNA was extracted from a 7-day-old culture of COAD 3368 and three loci were PCR amplified, namely: actin (ACT), with 512-F and 783-R primers; calmodulin (CAL), using the primers 228F and 2Rd; and histone H3 gene (HIS3), with the primers CYLH3F and CYLH3R. PCR products were sequenced by Macrogen (Seoul, South Korea) and the resulting sequences were deposited in GenBank (OM677624, OM677625 and OM677626, respectively). A multilocus Bayesian phylogenetic grouped COAD 3368 with Cercospora 'sp. Q' (Groenewald et al. 2013). This is a yet unresolved species complex within C. apii. Six 6­month­old healthy hop plants (cv. Cascade) were sprayed with a COAD 3368 conidial suspension (105 conidia/ mL) whereas another group of six plants was sprayed with sterile distilled water, serving as controls. Plants were placed in a dew chamber for 5 days and then transferred to a greenhouse bench, where they were observed daily. Thirty days after inoculation, symptoms similar to those observed in the field had developed on all inoculated plants, whereas control plants remained healthy. The fungus growing on inoculated hops produced typical Cercospora conidiophores and conidia. Upon reisolation, pure cultures with the same morphology of COAD 3368 were obtained. There are no previous records of Cercospora 'sp. Q' on hops worldwide. Fungi in Cercospora 'sp. Q' are known to have a broad host-range. A previous record of Cercospora 'sp. Q' leaf spots was published from its observation on Dioscorea cayennensis in the Infectarium (Torres et al. 2016). Damage to the hop plants was severe and it is possible that Cercospora leaf spot will become an emerging threat to commercial hop plantations in Brazil.

Palliative care in medical education: the students' perception / Cuidados Paliativos na formação médica: percepção dos estudantes

Abstract: Introduction: Population aging, longer life expectancy and the increase in the prevalence of chronic diseases have brought new health demands, among them, palliative care (PC). Although present in the clinical routine, this topic has not yet been included in most medical schools in Brazil. Objective: To know the teaching-learning process in PC according to the perception of medical students from schools that have this subject. Method: Qualitative method through interviews with 35 medical students from 14 medical schools located in the Northeast, Southeast and South regions of the country. Results: The reports were classified into three categories: conception of PC, changes perceived after exposure to PC teaching, challenges and successful strategies identified in PC teaching. Students recognize the value of teaching in PC and have a greater understanding of PC approach and its early indication for people with complex chronic conditions. The inclusion of the topic contributed to the overcoming of fears and taboos related to death, providing greater comfort to deal with human suffering, adding emotional skills. The formal education in PC allowed understanding the person in their biopsychosocial and spiritual dimension. They stressed the importance of communication skills to communicate difficult news, symptom management, teamwork and an individualized approach to the person and their family. Although they identify little theoretical-practical integration in the teaching-learning scenario in PC, they report an interest in the topic, and indicated successive experiences as strategies throughout the training, in a humanist axis. Conclusion: PC teaching brings contributions to medical training that go beyond the learning of the subject and reinforces the development of empathy and compassion, recognized as essential in this profession, as well as the relevance of assertiveness in the management of suffering and the comprehensive care of people with advanced diseases.

Resumo: Introdução: O envelhecimento populacional, a maior expectativa de vida e o aumento da prevalência de doenças crônicas trouxeram novas demandas em saúde, como os cuidados paliativos (CP). Embora presente no cotidiano clínico, essa temática ainda não foi incluída na maioria das escolas médicas no Brasil. Objetivo: Este estudo teve como objetivo conhecer o ensino-aprendizagem em CP na percepção do estudante de Medicina de escolas que dispõem dessa disciplina. Método: Trata-se de estudo qualitativo realizado por meio de entrevistas com 35 estudantes de Medicina de 14 escolas médicas localizadas nas Regiões Nordeste, Sudeste e Sul do país. Resultado: Os relatos foram classificados em três categorias: concepção sobre CP, transformações percebidas após exposição ao ensino de CP, desafios e estratégias exitosas identificados no ensino de CP. Os estudantes reconhecem o valor do ensino de CP e têm maior compreensão sobre a abordagem em CP e sua indicação precoce às pessoas com condições crônicas complexas. A inserção do tema contribuiu para a superação de medos e tabus ligados à morte, conferindo maior conforto para lidar com o sofrimento humano, agregando competências emocionais. A educação formal em CP possibilitou a compreensão da pessoa na dimensão biopsicossocial e espiritual. Os discentes ressaltaram a importância das habilidades de comunicação de notícias difíceis, do manejo de sintomas, do trabalho em equipe e da abordagem individualizada à pessoa e à família dela. Embora tenham identificado pouca integração teórico-prática no cenário de ensino-aprendizagem de CP, os alunos referiram interesse na temática e apontaram como estratégias aproximações sucessivas ao longo da formação, em um eixo humanista. Conclusão: O ensino de CP traz contribuições à formação médica para além da aprendizagem do tema e reforça o desenvolvimento da empatia e compaixão, reconhecidas como essenciais nessa profissão, assim como a relevância da assertividade no manejo do sofrimento e do cuidado integral de pessoas com doenças avançadas.

Phosphorus toxicity, not deficiency, explains the calcifuge habit of phosphorus-efficient Proteaceae.

The calcifuge habit of plants is commonly explained in terms of high soil pH and its effects on nutrient availability, particularly that of phosphorus (P). However, most Proteaceae that occur on nutrient-impoverished soils in south-western Australia are calcifuge, despite their ability to produce cluster-roots, which effectively mobilize soil P and micronutrients. We hypothesize that the mechanism explaining the calcifuge habit in Proteaceae is their sensitivity to P and calcium (Ca), and that soil-indifferent species are less sensitive to the interaction of these nutrients. In this study, we analyzed growth, gas-exchange rate, and chlorophyll fluorescence of two soil-indifferent and four calcifuge Hakea and Banksia (Proteaceae) species from south-western Australia, across a range of P and Ca concentrations in hydroponic solution. We observed Ca-enhanced P toxicity in all analyzed species, but to different extents depending on distribution type and genus. Increasing P supply enhanced plant growth, leaf biomass, and photosynthetic rates of soil-indifferent species in a pattern largely independent of Ca supply. In contrast, positive physiological responses to increasing [P] in calcifuges were either absent or limited to low Ca supply, indicating that calcifuges were far more sensitive to Ca-enhanced P toxicity. In calcifuge Hakeas, we attributed this to higher leaf [P], and in calcifuge Banksias to lower leaf zinc concentration. These differences help to explain these species' contrasting sensitivity to Ca-enhanced P toxicity and account for the exclusion of most Proteaceae from calcareous habitats. We surmise that Ca-enhanced P toxicity is a major factor explaining the calcifuge habit of Proteaceae, and, possibly, other P-sensitive plants.

Low MGMT digital expression is associated with a better outcome of IDH1 wildtype glioblastomas treated with temozolomide.

INTRODUCTION: Glioblastoma (GBM) is the deadliest primary brain tumor. The standard treatment consists of surgery, radiotherapy, and temozolomide (TMZ). TMZ response is heterogeneous, and MGMT promoter (MGMTp) methylation has been the major predictive biomarker. We aimed to describe the clinical and molecular data of GBMs treated with TMZ, compare MGMT methylation with MGMT expression, and further associate with patient's outcome. METHODS: We evaluate 112 FFPE adult GBM cases. IDH1 and ATRX expression was analyzed by immunohistochemistry, hotspot TERT promoter (TERTp) mutations were evaluated by Sanger or pyrosequencing, and MGMTp methylation was assessed by pyrosequencing and MGMT mRNA expression using the nCounter® Vantage 3D™ DNA damage and repair panel. RESULTS: Of the 112 GBMs, 96 were IDH1WT, and 16 were IDH1MUT. Positive ATRX expression was found in 91.6% (88/96) of IDHWT and 43.7% (7/16) of IDHMUT. TERTp mutations were detected in 70.4% (50/71) of IDHWT. MGMTp methylation was found in 55.5% (35/63) of IDHWT and 84.6% (11/13) of IDHMUT, and as expected, MGMTp methylation was significantly associated with a better response to TMZ. MGMT expression was inversely correlated with MGMTp methylation levels (- 0.506, p < 0.0001), and MGMT low expression were significantly associated with better patient survival. It was also observed that integrating MGMTp methylation and expression, significantly improved the prognostication value. CONCLUSIONS: MGMT mRNA levels evaluated by digital expression were associated with the outcome of TMZ-treated GBM patients. The combination of MGMT methylation and mRNA expression may provide a more accurate prediction of TMZ response in GBM patients.

Postpartum Polyneuropathy in a Mare: A Case Report.

Obstetric paralysis is a generic term used to describe postpartum locomotor alterations resulting from nerve damage, widely reported in cattle, but rare in equines. The aim of this study is to report a case of a peripheral polyneuropathy in a primiparous mare, 3 years old, of Mangalarga Marchador breed, after a dystocia lasting approximately 12 hours. At the time of delivery, the head of the fetus was exposed in the vulva and there was flexion of the thoracic limbs. These events culminated in a framework of extreme abduction of the pelvic limbs, thus generating functional impotence and leading the animal to adopt a frog anddecubitus position. After three days of treatment with no improvement in the clinical framework, the animal was euthanized. In the postmortem examination, perineural hemorrhagic lesions were observed in the obturator and sciatic nerves, characterizing the diagnosis of obstetric paralysis. It is possible the outcome of the case would have been satisfactory if there had been an early fetotomy or postpartum treatment had been more prolonged; however, these measures depend on the availability of equipment, conditions of care, and consideration of the owner.

Tabagismo: um vício que mata mais que a COVID-19 / Tobacco consumption: a vice that kills more than COVID-19

Este manual tem como objetivo apresentar os malefícios do uso do tabaco e destacar medidas básicas a serem tomadas para abandonar este vício

This manual aims to present the harms of tobacco use and highlight basic measures to be taken to quit this addiction

Calcium modulates leaf cell-specific phosphorus allocation in Proteaceae from south-western Australia.

Over 650 Proteaceae occur in south-western Australia, contributing to the region's exceptionally high biodiversity. Most Proteaceae occur exclusively on severely nutrient-impoverished, acidic soils (calcifuge), whilst only few also occur on young, calcareous soils (soil-indifferent), higher in calcium (Ca) and phosphorus (P). The calcifuge habit of Proteaceae is explained by Ca-enhanced P toxicity, putatively linked to the leaf cell-specific allocation of Ca and P. Separation of these elements is essential to avoid the deleterious precipitation of Ca-phosphate. We used quantitative X-ray microanalysis to determine leaf cell-specific nutrient concentrations of two calcifuge and two soil-indifferent Proteaceae grown in hydroponics at a range of Ca and P concentrations. Calcium enhanced the preferential allocation of P to palisade mesophyll (PM) cells under high P conditions, without a significant change in whole leaf [P]. Calcifuges showed a greater PM [P] compared with soil-indifferent species, corresponding to their greater sensitivity. This study advances our mechanistic understanding of Ca-enhanced P toxicity, supporting the proposed model, and demonstrating its role in the calcifuge distribution of Proteaceae. This furthers our understanding of nutrient interactions at the cellular level and highlights its importance to plant functioning.