Search

Abstract Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, providing significant benefit to patients across various tumour types, including melanoma. However, around 40% of melanoma patients do not benefit from ICI treatment, and accurately predicting ICI response remains challenging. We now describe a novel and simple approach that integrates immune-associated transcriptome signatures and tumour volume burden to better predict ICI response in melanoma patients. RNA sequencing was performed on pre-treatment (PRE) tumour specimens derived from 32 patients with advanced melanoma treated with combination PD1 and CTLA4 inhibitors. Of these 32 patients, 11 also had early during treatment (EDT, 5–15 days after treatment start) tumour samples. Tumour volume was assessed at PRE for all 32 patients, and at first computed tomography (CT) imaging for the 11 patients with EDT samples. Analysis of the Hallmark IFNγ gene set revealed no association with ICI response at PRE (AUC ROC curve = 0.6404, p = 0.24, 63% sensitivity, 71% specificity). When IFNg activity was evaluated with tumour volume (ratio of gene set expression to tumour volume) using logistic regression to predict ICI response, we observed high discriminative power in separating ICI responders from non-responders (AUC = 0.7760, p = 0.02, 88% sensitivity, 67% specificity); this approach was reproduced with other immune-associated transcriptomic gene sets. These findings were further replicated in an independent cohort of 23 melanoma patients treated with PD1 inhibitor. Hence, integrating tumour volume with immune-associated transcriptomic signatures improves the prediction of ICI response, and suggest that higher levels of immune activation relative to tumour burden are required for durable ICI response.

Sarcosaprophagous dipterans are well known due to their forensic and medical-sanitary importance, as they are possible vectors of pathogens and cause myiasis. However, their potential as bioindicators of anthropogenic actions is still little explored, especially in environments with high human interference (e.g., coastal environments). Thus, this work aims to compare the abundance and frequency of dipteran of forensic importance between two mangrove landscapes with different human impact levels: i) Baía Formosa, characterized as less anthropized, and ii) Extremoz, as a more anthropized mangrove. Adult flies were collected by using suspended traps containing decomposing animal tissue (chicken liver) as baits. A diverse assemblage of sarcosaprophagous Diptera was registered in the two mangroves, consisting of 18 species from four families: Calliphoridae (n = 1,738; S = 4), Sarcophagidae (n= 214; S = 9), Muscidae (n = 46; S = 3) and Fanniidae (n = 26; S = 2). Chrysomya megacephala was the most abundant species in Baía Formosa and Oxysarcodexia intona in Extremoz. In addition, this study reveals that human impact levels can modulate the structure and composition of flies’ assemblages in mangrove environments.

Food waste management is a growing global concern, driven by the imperative to address environmental sustainability, resource conservation, and global hunger. This article aims to provide a theoretical analysis of the historical evolution of food waste management, delving into the definition of the term and its international relevance. Additionally, it critically examines the need for sustainable approaches. The methodology comprises a comprehensive literature review from 2013 to 2023, utilizing keywords related to food waste, sustainability, and the circular economy. The databases used include Science Direct and MDPI. Findings reveal a shift from individual to institutional food waste sources, underscoring the necessity for alternative approaches. Environmental analysis highlights the adverse impacts of conventional practices, while strategies such as food rescue, fermentation, and anaerobic digestion emerge as promising solutions. Understanding consumer behavior is crucial, and smart labels are introduced as potential tools to reduce food waste. The article identifies the challenges and limitations of current food waste management practices, emphasizing the need for sustainable treatments. Sustainable approaches in managing food industry residues, including food rescue, fermentation, and anaerobic digestion, are discussed as alternatives to conventional methods. The article concludes by proposing future research directions, emphasizing the importance of understanding consumer behavior, exploring the potential of smart labels, and addressing gaps in current knowledge to achieve a more sustainable and responsible approach to food consumption and waste management.

Introduction: The patterns of oligoprogression after first-line immune checkpoint inhibitors (ICIs) for metastatic NSCLC are yet to be well established. An increasing volume of data suggests that directed radiotherapy improves survival outcomes in patients with progression after ICIs. Methods: A retrospective cohort study was performed on patients with metastatic NSCLC who had completed first-line programmed death-(ligand) 1 inhibitor therapy with or without chemotherapy at two high-volume cancer centers. We sought to characterize the frequency and location of oligoprogression and determine the overall survival (OS) after radiotherapy in this population. Results: A total of 159 patients were included in the study. At first progression, 62 (39.0%) were classified as undergoing oligoprogression. Multivariate analysis confirmed the presence of brain metastases was associated with an increased likelihood of oligoprogression (OR = 2.44, p = 0.04) with most (63.2%) of these patients experiencing progression intracranially. The presence of liver metastases was associated with a decreased likelihood of oligoprogression (OR = 0.17, p < 0.01). For patients with oligoprogression, those who received radiotherapy had a longer median progression-free survival-2 (PFS2) (17 versus 11.5 mo, HR = 0.51, p = 0.02) and a longer median OS (23 versus 13 mo, HR = 0.40, p < 0.001) compared with those who did not receive radiotherapy. No difference in PFS2 or OS outcomes was observed between patients who received radiotherapy versus those who did not for systemic progression. Conclusions: In patients with oligoprogressive metastatic NSCLC after treatment with first-line ICIs, radiotherapy significantly improves OS and PFS2 outcomes. Patients with baseline brain metastases are more likely to experience oligoprogression. Further prospective studies in directed, less heterogeneous populations of patients with metastatic NSCLC will be fundamental to optimize management.

O contexto atual do ensino da Álgebra tem indicado ações que promovam o desenvolvimento do pensamento algébrico. Uma dessas formas de promoção seria explorar a busca de regularidades e generalizações. Se, por um lado, pesquisas e normativas apontam para a necessidade dessa abordagem, por outro, no contexto da prática no ensino dessa temática ainda predomina a forma mecânica, em que se valoriza a manipulação de símbolos e regras, com a visão letrista sendo a dominante. Diante dessas questões, o presente artigo se propõe a discutir como os alunos percebem e consolidam a noção de regularidade, e como indicam a generalização em atividades de Álgebra. Nessa trajetória, analisam-se as respostas a um teste aplicado a 41 alunos do 7º ano do Ensino Fundamental. Constatou-se que os alunos têm facilidade na percepção de regularidades, contudo apresentam dificuldades para expressar a generalização na existência de um padrão e em situações nas quais não há regularidade.

Introdução: Recém-nascidos hospitalizados em Unidades de Terapia Intensiva Neonatal (UTIN) são especialmente vulneráveis a aquisição de IRAS. O MRSA é um dos principais microrganismos causadores de infecções nesta população. Objetivo: Relatar a ocorrência de casos de colonização e infecção por MRSA em recém-nascidos e a colonização de profissionais de uma UTI Neonatal e as medidas de controle e prevenção implantadas. Método: Trata-se de um relato de caso, ocorrido em um hospital universitário de Blumenau/SC. Durante outubro, foram identificados 4 recém-nascidos com resultados de swab nasal com infecção de pele e com MRSA, sendo 2 pacientes com isolamento de MRSA em amostra clínica (hemocultura) e 1 paciente com identificação no aspirado traqueal. Diante deste quadro, foram realizadas as seguintes ações pelo Serviço de Controle de Infecção (SCI): 1) Investigação epidemiológica dos recém-nascidos e dos profissionais assistenciais da UTIN, com coleta de swab nasal a fim de identificar possíveis colonizados. 2) Descolonização e implantação das Medidas de Precaução de Contato para os recém-nascidos com cultura positiva para MRSA. 3) Descolonização dos profissionais com swab nasal positivo para MRSA. A descolonização dos profissionais foi realizada com banho de Clorexidina degermante a 2% e aplicação de Mupirocina em vestíbulo nasal, procedimento com duração de 7 dias. Os recém-nascidos foram descolonizados apenas com a aplicação de Mupirocina em vestíbulo nasal, conforme protocolo institucional. 4) Implementação de check-list de desinfecção concorrente. 5) Divulgação de nova metodologia visual de higiene de mãos na prática com uso de incubadora. Resultados: Foram coletados um total de 27 swabs nasal, sendo 17 amostras de profissionais e 10 amostras de recém-nascidos. Das 17 amostras dos profissionais, 3 positivaram para MRSA (17,6%). Os profissionais realizaram a descolonização conforme a orientação do SCIRAS. Dos recém-nascidos, 4 amostras positivaram para MRSA (40%). Após as intervenções realizadas, não foram identificados novos casos de infecção ou colonização de MRSA na UTIN. Conclusão: A implantação de Medidas de Precaução de Contato de pacientes infectados/colonizados por MRSA, bem como a investigação epidemiológica de recém-nascidos hospitalizados e funcionários e a descolonização de portadores deste germe, bem check-list da desinfecção concorrente, e nova metodologia visual de higiene de mãos com uso de incubadora, foram medidas eficazes para controlar a transmissão de MRSA em nossa UTIN.

The coronavirus disease 2019 pandemic has accelerated the adoption of remote and hybrid forms of work in organizations. Despite the benefits that these flexible working models can bring to both employees and organizations, they are accompanied by a darker side. Heavy digital presence, increased workload, and blurred boundaries between work and life are some of the hindrances derived from remote working that directly affect employee well-being. Aware of the negative consequences that can lead to individual and organizational performance, companies are expected to define and adapt policies and regulations to protect employees and promote their well-being. However, literature addressing these research topics is scarce, and many contributions are dispersed across different fields. Therefore, we address this research gap by performing a bibliometric analysis of the contributions to remote employee well-being and complementing it with a content analysis. A sample of 64 publications was collected from two different databases. This study provides a performance measurement analysis of publications and citations and a scientific mapping of collaboration networks and emerging thematic trends. Furthermore, the content analysis allows us to understand how the organizational perspective on the well-being of employees in remote working settings has been addressed in the literature, clearly identifying opportunities for future research. Finally, the major challenges and research agendas are discussed.

O presente artigo científico traz em seu escopo um pequeno, porém considerável Estado da Arte de pesquisas sobre o tema Musicoterapia, publicadas em 35 revistas científicas. Como método de pesquisa utilizou-se a pesquisa via internet e como abordagem, a pesquisa quantitativa. A investigação objetivou mostrar a incidência que o tema Musicoterapia apresenta nas pesquisas científicas publicadas em 35 revistas científicas. Como questão de pesquisa, a presente investigação lançou a seguinte questão: Qual a incidência de artigos científicos com a temática da Musicoterapia em 35 revistas científicas das áreas da Saúde e da Música/Arte? Como resultado observa-se a escassez de artigos científicos produzidos e publicados em revistas científicas das áreas da saúde e da arte/música.

Bartonelloses represent a group of potentially fatal diseases associated with various clinical manifestations including endocarditis. Caused by bacteria belonging to the genus Bartonella, these microorganisms have a remarkable ability to infect mammals, and their transmission is commonly associated with hematophagous vectors such as fleas, lice, mosquitoes, and ticks. The aim of this study was to evaluate the occurrence of Bartonella sp. DNA in 81 triatomines of the species Triatoma sordida collected in the field in peri‑domiciliary areas of the Brazilian city of Seabra, located in the state of Bahia. Nested PCR was conducted targeting the ftsZ gene and real-time PCR targeting the gltA gene, both representing specific reactions for Bartonella henselae. Additionally, conventional PCR targeting kDNA was employed to evaluate the presence of Trypanosoma cruzi. Of the samples tested, 23/81 (28.39 %) bugs showed positive PCR for B. henselae. No sample showed positive PCR for T. cruzi. The high prevalence of triatomines with a positive PCR for B. henselae emphasizes the close relationship between these insects and the bacteria, indicating the need for further studies to investigate the vectorial potential of these kissing bugs.

RESUMO: O presente artigo analisa o esvaziamento das Diretrizes Curriculares Nacionais para a Educação Básica (DCN) na Base Nacional Comum Curricular (BNCC). Trata-se de uma pesquisa documental de abordagem crítica inserida nos debates curriculares ancorados nos fundamentos teórico-metodológicos da Pedagogia Histórico-Crítica. Objetiva-se analisar e refletir sobre as diretrizes para a educação de grupos pouco reconhecidos e considerados nas políticas educacionais curriculares brasileiras, no sentido de fomentar o debate em torno dos processos de formação dos sujeitos que se pretende formar. As categorias de análise foram: 1) modalidades da educação (Escolar Indígena; Escolar Quilombola; do Campo; Especial; de Jovens e Adultos; Profissional e Tecnológica); e 2) eixos temáticos contemporâneos (Educação Ambiental; Educação em Direitos Humanos; Educação para jovens e adultos em situação de privação de liberdade nos estabelecimentos penais; Educação das Relações Étnico-Raciais e o Ensino de História e Cultura Afro-Brasileira e Africana; Atendimento escolar de crianças, adolescentes e jovens em situação de itinerância). Os resultados apontam que há um silenciamento e um retrocesso na BNCC, no que tange a algumas modalidades e eixos temáticos que já tinham seus direitos assegurados na DCN. Em contrapartida, na BNCC, mesmo apresentando os princípios de igualdade e universalidade, os sujeitos são homogeneizados, sem considerar as diferenças e subjetividades que existem ou podem existir. Posiciona-se aqui em defesa de uma educação que, considerando efetivamente a diversidade e as profundas desigualdades da sociedade brasileira, advogue por uma formação omnilateral dos sujeitos na perspectiva da transformação social.

Abstract The biological underpinnings of therapeutic resistance to immune checkpoint inhibitors (ICI) in adolescent and young adult (AYA) melanoma patients are incompletely understood. Here, we characterize the immunogenomic profile and spatial architecture of the tumor microenvironment (TME) in AYA (aged ≤ 30 years) and older adult (aged 31–84 years) patients with melanoma, to determine the AYA-specific features associated with ICI treatment outcomes. We identify two ICI-resistant spatiotypes in AYA patients with melanoma showing stroma-infiltrating lymphocytes (SILs) that are distinct from the adult TME. The SILhigh subtype was enriched in regulatory T cells in the peritumoral space and showed upregulated expression of immune checkpoint molecules, while the SILlow subtype showed a lack of immune activation. We establish a young immunosuppressive melanoma score that can predict ICI responsiveness in AYA patients and propose personalized therapeutic strategies for the ICI-resistant subgroups. These findings highlight the distinct immunogenomic profile of AYA patients, and individualized TME features in ICI-resistant AYA melanoma that require patient-specific treatment strategies.

ABSTRACT Purpose: To evaluate the effects on peripheral neural regeneration of the end-to-side embracing repair technique compared to the autograft repair technique in Wistar rats. Methods: Fifteen male Wistar rats were divided into three groups with five animals each: denervated group (GD), autograft group (GA), and embracing group (EG). For the evaluation, the grasping test, electroneuromyography (ENMG), and muscle weight assessment were used. Results: Muscle weight assessment and ENMG did not show significant neural regeneration at the end of 12 weeks in the DG and GE groups, but only in GA. The grasping test showed an increase in strength between the surgery and the fourth week in all groups, and only the GA maintained this trend until the 12th week. Conclusions: The present study indicates that the neural regeneration observed in the end-to-side embracing neurorrhaphy technique, in the repair of segmental neural loss, is inferior to autograft repair in Wistar rats.

Resumo: Este documento de consenso, preparado em conjunto pela Sociedade Portuguesa de Cardiologia, Sociedade Portuguesa de Ginecologia, Sociedade Portuguesa de Obstetrícia e Medicina Materno‐Fetal, Sociedade Portuguesa de Contraceção e Associação Portuguesa de Medicina Geral e Familiar, tem como objetivo a melhoria dos cuidados de saúde prestados às mulheres na vertente da saúde cardiovascular. Inclui uma breve revisão do estado da arte das doenças cardiovasculares nas mulheres e da associação a outras situações do foro da ginecologia, obstetrícia e doenças endócrinas e contém recomendações para ajudar os cardiologistas e outros profissionais de saúde envolvidos nos cuidados de saúde das mulheres. Abstract: The main objective of this consensus statement from the Portuguese Society of Cardiology, the Portuguese Society of Gynecology, the Portuguese Society of Obstetrics and Maternal‐Fetal Medicine, Portuguese Society of Contraception, Portuguese Association of General Practice and Family Medicine is to improve cardiovascular care for women. It includes a brief review of the state‐of‐the‐art of cardiovascular diseases in women and of the links to other fields such as Gynaecology, Obstetrics and Endocrinology. It also provides final recommendations to help clinicians working in care of women's health.

Os arquivos municipais realizam uma importante mediação da informação arquivística no âmbito da cidade e são fontes muito importantes para a pesquisa histórica e para a construção de memória e identidade dos diferentes grupos sociais. Essas instituições são essenciais para a cidadania e vida comunitária. Os arquivos públicos municipais têm a função de divulgar e difundir informações, contribuindo para a democratização do acesso ao conhecimento. O objetivo desta pesquisa é investigar a mediação e a representação da informação arquivística no espectro das cidades, considerando os recursos de pesquisa que permitem os usuários terem acesso a informações sobre o patrimônio arquivístico do lugar onde vivem. A metodologia adotada para reconhecer o cenário de mediação e representação da informação arquivística nos arquivos municipais combina uma articulação conceitual com base na literatura da Arquivologia, mais um levantamento empírico de sites dos arquivos de cidades brasileiras. Ao combinar essas perspectivas de observação e análise é possível obter uma compreensão mais abrangente sobre como os arquivos públicos estão disponibilizando informações para seus usuários. Os resultados apontam para a necessidade de avanço nos instrumentos de pesquisa disponíveis pelas instituições que anunciam ter essa finalidade para os acervos que organizam e preservam. Dentre os resultados destaca-se o alcance da mediação observada para arquivos em comparação com os estaduais. Além disso, aportamos aos indicadores de existência de arquivos municipais a sua correspondência de população. Os arquivos municipais são mediadores da informação arquivística nas cidades e há necessidade de aprimoramento dos recursos de pesquisa disponíveis nessas instituições.

The gonad has become a central organ for understanding aging in C. elegans, as removing the proliferating stem cells in the germline results in significant lifespan extension. Similarly, when starvation in late larval stages leads to the quiescence of germline stem cells the adult nematode enters reproductive diapause, associated with an extended lifespan. This review summarizes recent advancements in identifying the mechanisms behind gonad-mediated lifespan extension, including comparisons with other nematodes and the role of lipid signaling and transcriptional changes. Given that the gonad also mediates lifespan regulation in other invertebrates and vertebrates, elucidating the underlying mechanisms may help to gain new insights into the mechanisms and evolution of aging.

IntroductionBrain metastases commonly occur in patients with non-small cell lung cancer (NSCLC). Standard first-line treatment for NSCLC, without an EGFR, ALK or ROS1 mutation, is either chemoimmunotherapy or anti-PD-1 monotherapy. Traditionally, patients with symptomatic or untreated brain metastases were excluded from the pivotal clinical trials that established first-line treatment recommendations. The intracranial effectiveness of these treatment protocols has only recently been elucidated in small-scale prospective trials.MethodsPatients with NSCLC and brain metastases, treated with first-line chemoimmunotherapy or anti-PD-1 monotherapy were selected from the Australian Registry and biObank of thoracic cancers (AURORA) clinical database covering seven institutions. The primary outcome was a composite time-to-event (TTE) outcome, including extracranial and intracranial progression, death, or need for local intracranial therapy, which served as a surrogate for disease progression. The secondary outcome included overall survival (OS), intracranial objective response rate (iORR) and objective response rate (ORR).Results116 patients were included. 63% received combination chemoimmunotherapy and 37% received anti-PD-1 monotherapy. 69% of patients received upfront local therapy either with surgery, radiotherapy or both. The median TTE was 7.1 months (95% CI 5 - 9) with extracranial progression being the most common progression event. Neither type of systemic therapy or upfront local therapy were predictive of TTE in a multivariate analysis. The median OS was 17 months (95% CI 13-27). Treatment with chemoimmunotherapy was predictive of longer OS in multivariate analysis (HR 0.35; 95% CI 0.14 – 0.86; p=0.01). The iORR was 46.6%. The iORR was higher in patients treated with chemoimmunotherapy compared to immunotherapy (58% versus 31%, p=0.01). The use of chemoimmunotherapy being predictive of iORR in a multivariate analysis (OR 2.88; 95% CI 1.68 - 9.98; p=0.04).ConclusionThe results of this study of real-world data demonstrate the promising intracranial efficacy of chemoimmunotherapy in the first-line setting, potentially surpassing that of immunotherapy alone. No demonstrable difference in survival or TTE was seen between receipt of upfront local therapy. Prospective studies are required to assist clinical decision making regarding optimal sequencing of local and systemic therapies.

The self-cure of rhesus macaques from a schistosome infection and their subsequent strong immunity to a cercarial challenge should provide novel insights into the way these parasites can be eliminated by immunological attack. High-density arrays comprising overlapping 15-mer peptides from target proteins printed on glass slides can be used to screen sera from host species to determine antibody reactivity at the single epitope level. Careful selection of proteins, based on compositional studies, is crucial to encompass only those exposed on or secreted from the intra-mammalian stages and is intended to focus the analysis solely on targets mediating protection. We report the results of this approach using two pools of sera from hi- and lo-responder macaques undergoing self-cure, to screen arrays comprising tegument, esophageal gland, and gastrodermis proteins. We show that, overall, the target epitopes are the same in both groups, but the intensity of response is twice as strong in the high responders. In addition, apart from Sm25, tegument proteins elicit much weaker responses than those originating in the alimentary tract, as was apparent in IFNγR KO mice. We also highlight the most reactive epitopes in key proteins. Armed with this knowledge, we intend to use multi-epitope constructs in vaccination experiments, which seek to emulate the self-cure process in experimental animals and potentially in humans.