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Abstract Background In the last decade the development of new PSMA-ligand based radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research. The most promising derivative in terms of interaction with the antigen and clinical properties has been found to be “PSMA-617”, and its lutetium-177 radiolabelled version has recently been approved by EU and USA regulatory agencies for therapeutic purposes. For the above reasons, the development of new derivatives of PSMA-617 radiolabelled with fluorine-18 may still be of great interest. This paper proposes the comparison of two different PSMA-617 derivatives functionalized with NODA and RESCA chelators, respectively, radiolabelled via [18F]AlF2+ complexation. Results The organic synthesis of two PSMA-617 derivatives and their radiolabelling via [18F]AlF2+ complexation resulted to proceed efficiently and successfully. Moreover, stability in solution and in plasma has been evaluated. The whole radiosynthesis procedure has been fully automated, and the final products have been obtained with radiochemical yield and purity potentially suitable for clinical studies. The biodistribution of the two derivatives was performed both in prostate cancer and glioma tumour models. Compared with the reference [18F]F-PSMA-1007 and [18F]F-PSMA-617-RESCA, [18F]F-PSMA-617-NODA derivative showed a higher uptake in both tumors, faster clearance in non-target organs, and lower uptake in salivary glands. Conclusion PSMA-617 NODA and RESCA derivatives were radiolabelled successfully via [18F]AlF2+ chelation, the former being more stable in solution and human plasma. Moreover, preclinical biodistribution studies showed that [18F]F-PSMA-617-NODA might be of potential interest for clinical applications.

A growing body of literature suggests that developmental exposure to individual or mixtures of environmental chemicals (ECs) is associated with autism spectrum disorder (ASD). However, investigating the effect of interactions among these ECs can be challenging. We introduced a combination of the classical exposure-mixture Weighted Quantile Sum (WQS) regression and a machine-learning method termed Signed iterative Random Forest (SiRF) to discover synergistic interactions between ECs that are (1) associated with higher odds of ASD diagnosis, (2) mimic toxicological interactions, and (3) are present only in a subset of the sample whose chemical concentrations are higher than certain thresholds. In a case-control Childhood Autism Risks from Genetics and Environment (CHARGE) study, we evaluated multiordered synergistic interactions among 62 ECs measured in the urine samples of 479 children in association with increased odds for ASD diagnosis (yes vs no). WQS-SiRF identified two synergistic two-ordered interactions between (1) trace-element cadmium (Cd) and the organophosphate pesticide metabolite diethyl-phosphate (DEP); and (2) 2,4,6-trichlorophenol (TCP-246) and DEP. Both interactions were suggestively associated with increased odds of ASD diagnosis in the subset of children with urinary concentrations of Cd, DEP, and TCP-246 above the 75th percentile. This study demonstrates a novel method that combines the inferential power of WQS and the predictive accuracy of machine-learning algorithms to discover potentially biologically relevant chemical-chemical interactions associated with ASD.

Introdução: A mobilização e participação da comunidade é fundamental em programas de prevenção/controlo de doenças transmitidas por vetores. Em Portugal, mosquitos do género Aedes aegypti estão estabelecidos na Ilha da Madeira, tendo ocorrido em 2012 o primeiro surto de febre de dengue (DENV-1) nesta região, com 1084 casos confirmados laboratorialmente. Objetivos do estudo: Caracterizar opiniões e atitudes da população madeirense face à utilização de mosquitos geneticamente modificados (MGM) como estratégia de controlo vetorial. Materiais e métodos: Foi aplicado um questionário a adultos residentes nas freguesias com cota abaixo dos 200 metros do município do Funchal, Região Autónoma da Madeira (S.Martinho, Stª Maria Maior, Sé, S.Pedro, Stª Luzia, Imaculado Coração de Maria) em março-abril 2019. Selecionaram-se aleatoriamente as residências para aplicação do questionário; em cada residência foi selecionado aleatoriamente um indivíduo; utilizou-se uma amostragem estratificada por sexo. Os participantes indicaram o seu grau de concordância com afirmações existentes no questionário. Resultados: Participaram no estudo 1270 indivíduos, idade média 53,5 anos, 44,6% do género masculino, 52,4% com ≥ 12 anos de escolaridade. Concordância com as afirmações: “Se libertassem MGM na minha rua, sentiria receio” concordam (C) 58,8%, discordam (D) 16,8, indiferente (I) 8%; “O medo dos efeitos da utilização dos MGM faz com que prefira técnicas tradicionais” C 46,8%, D 20,5%, I 13,4%; “os MGM devem ser rejeitados por não serem naturais” C 33,7%, D 29,6%, I 11,9%; “Como a maioria dos casos de dengue não são graves devemos continuar a utilizar estratégias tradicionais” C 47,9%, D 30,5%, I 8,3%. As mulheres (p = 0,017) e os menos letrados (p < 0,001) mostram mais receio da utilização de MGM. A análise conjunta das 4 questões indica que 37% têm atitude anti-MGM, 17% são moderadamente contra MGM, 7% mostra atitude moderadamente favorável, 16% são totalmente a favor, 23% têm atitude indiferente/indefinida. 53/151 respondentes (35,1%) consideravam que após libertação de MGM a população pode sentir-se mais incomodada/picada. Conclusões: Mais de metade dos participantes no estudo encontra-se no espetro anti-MGM e 1/4 tem uma atitude indefinida quanto à utilização de MGM para controlo de vetores. Se no futuro se optar por esta estratégia de controlo de vetores na Madeira há que compreender os motivos geradores desta atitude de oposição e desenvolver ações educativas abrangentes. Palavras-chave: Dengue, Ilha da Madeira, Controlo Vetorial, Atitudes. Conflitos de interesse: Sem qualquer conflito de interesses para nenhum dos autores. Ética e financiamentos: Sem qualquer conflito de interesses para nenhum dos autores.

Introdução: Em 2005 foram detetados, pela primeira vez, mosquitos da espécie Aedes aegypti em Portugal, na Região Autónoma da Madeira. Em 2012 a região sofreu um surto de dengue, sendo registados 1084 casos. É consensual a necessidade do envolvimento das comunidades nas intervenções de controlo vetorial. Objetivos do estudo: Caracterizar conhecimentos da população da Madeira sobre a utilização de mosquitos geneticamente modificados (MGM) como estratégia de controlo vetorial. Materiais e métodos: Foi aplicado um questionário a adultos residentes nas freguesias do município do Funchal com cota abaixo dos 200 metros (São Martinho, Santa Maria Maior, Sé, São Pedro, Santa Luzia, Imaculado Coração de Maria) em março-abril 2019. Selecionaram-se aleatoriamente as residências para aplicação do questionário; em cada residência foi selecionado aleatoriamente um indivíduo; utilizou-se uma amostragem estratificada por sexo. Resultados: Participaram no estudo 1270 indivíduos, idade média 53,5 anos, 44,6% do género masculino, 29% com 12° ano de escolaridade, 23,4% com licenciatura/mestrado. No subgrupo (11,9%, IC a 95% [10,2; 13,8] 151/1270) que ouviu falar/leu sobre MGM, 42% conhecem as técnicas de supressão e 36% as de substituição; Fontes de informação: TV 57,6%, internet 51%, jornais 40,4%. Respostas: “Os MGM não são compatíveis com uso de estratégias tradicionais” Desconheço (D) 15,2%, verdade (V) 16,5%, falso (F) 56,3%, possível (P) 6,6%; “Libertar MGM pode não ser suficiente para controlar o número de mosquitos e de doentes” D 5,3%, V 61,5%, F 3,3%, P 25,2%; “Utilizar MGM diminui o número de mosquitos e doentes apenas em situações/lugares específicos” D 13,9%, V 43%, F 11,3%, P 25,8%; “Com o tempo os MGM perdem eficácia” D 35,7%, V 15,2%, F 23,2%, P 17,2%; “Os custos de libertação de MGM são superiores aos das estratégias tradicionais” D 32%, V 43%, F 16%. Quem tem maior nível de escolaridade ouviu falar/leu sobre MGM (p < 0,001) e responde mais vezes adequadamente às questões colocadas (p < 0,005). Conclusões: A grande maioria da população da Madeira nunca ouviu falar/leu sobre MGM. Verifica-se elevado nível de desconhecimento do possível controlo de vetores com utilização de MGM e compatibilidade com as estratégias tradicionais. Torna-se essencial aumentar a informação da população para garantir os pressupostos de transparência, entendimento mútuo e envolvimento ativo da comunidade se no futuro se desejar utilizar esta abordagem de controlo de vetores no território. Palavras-chave: Dengue, Ilha da Madeira, Controlo Vetorial, Conhecimentos. Conflito de interesse: Sem qualquer conflito de interesses para nenhum dos autores. Ética e financiamentos: Sem qualquer conflito de interesses para nenhum dos autores.

O presente trabalho tem por objetivo analisar a Complementação da União (COUN) ao Fundeb permanente, modalidade VAAR, que foi criada pela Emenda Constitucional nº 108/2020 e regulamentada pelas leis nº 14.113/2020 e nº 14.276/2021, especificamente sobre a metodologia de verificação da redução das desigualdades educacionais socioeconômicas e raciais, da condicionalidade III. Aborda-se o tema a partir do referencial do gerencialismo, no que concerne à alocação de recursos financeiros por desempenho na gestão pública educacional. A metodologia utilizada neste trabalho foi de abordagem qualitativa, a partir de análise documental com dados do Ministério da Educação. Argumenta-se que a COUN-VAAR pode se tornar um instrumento influente no financiamento da educação se dada a devida ênfase à sua capacidade de verificar a Redução de Desigualdades e não apenas medir os Resultados.

En la situació actual de l’educació, la reflexió sobre la pràctica és una necessitat per garantir evidències d’èxit. A l’Escola Espai-3 utilitzem la robòtica i la intel·ligència artificial (IA) per tal d’estudiar-ne els avantatges a les aules de primària. En moltes ocasions, la robòtica necessita la inteŀligència artificial per dur a terme determinades accions. La càmera Smart AI Lens d’Elecfreaks, juntament amb la placa Micro:bit, ofereix l’oportunitat a l’alumnat de primària d’endinsar-se en el món fascinant de la programació de robots. Després d’haver creat mitjançant Scratch un assistent personal basat en la IA, aquesta experiència té com a objectiu principal introduir els estudiants en la relació entre la robòtica i la inteŀligència artificial mitjançant la creació i programació de robots utilitzant la càmera Smart AI Lens i la placa Micro:bit. Els resultats obtinguts permeten valorar la motivació, la millora conductual i la disposició a l’aprenentatge de l’alumnat participant, que mostra una millora creixent en les competències treballades i un clima de centre harmoniós i sostenible.

Summary: Super killer (SKI) complex is a well-known cytoplasmic 3′–5′ mRNA decay complex that functions with the exosome to degrade excessive and aberrant mRNAs, is implicated with the extraction of mRNA at stalled ribosomes, tackling aberrant translation. Here, we show that SKIV2L and TTC37 of the hSKI complex are present within the nucleus, localize on chromatin and at some telomeres during the G2 cell cycle phase. In cells, SKIV2L prevents telomere replication stress, independently of its helicase domain, and increases the stability of telomere DNA-RNA hybrids in G2. We further demonstrate that purified hSKI complex binds telomeric DNA and RNA substrates in vitro and SKIV2L association with telomeres is dependent on DNA-RNA hybrids. Taken together, our results provide a nuclear function for SKIV2L of the hSKI complex in overcoming replication stress at telomeres mediated by its recruitment to DNA-RNA hybrid structures in G2 and thus maintaining telomere stability.

The article addresses the identification and prediction of research topics in human–robot interaction (HRI), fundamental in Industry 4.0 (I4.0) and future Industry 5.0 (I5.0). In the absence of research agendas in the scientific literature, the study proposes a multilayered model to create a precise agenda to guide the scientific community in new developments in collaborative robotics and HRI technologies. The methodology is divided into four stages, which make up the three layers of the model. In the first two stages, scientific articles on HRI for the period 2020–2021 were collected and analyzed using data mining techniques together with VantagePoint and Gephi software to identify keywords and their relationships. These initial stages form layer 1 of the model, where the main scientific themes are recognized. In the third stage, article titles and abstracts are cleaned and processed using natural language processing (NLP) techniques, generating word embeddings models that highlight relevant HRI-related terms, forming layer 2. The fourth and final stage uses Recurrent Neural Networks (RNN) with long short-term memory (LSTM) architecture to predict future topics, consolidating the previously identified terms and forming layer 3 of the model. The results show that in layer 1 HRI has intensive application in various sectors through advanced computational algorithms, with trust as a key feature. In layer 2, terms such as vision, sensors, communication, collaboration and anthropomorphic aspects are fundamental, while layer 3 anticipates future topics such as design, performance, method and controllers, essential to improve robot interaction. The study concludes that the methodology is effective in defining a robust and relevant research agenda. By identifying future trends and needs, this work fills a gap in the scientific literature, providing a valuable tool for the research community in the field of HRI.

Herein, we report the case of primary amyloidosis with multi-organ involvement in a female patient in her 50s. The patient had a history of relapsing polychondritis, chronic kidney disease, and monoclonal gammopathy of undetermined significance (MGUS). The clinical manifestations included neuropathic pain, sensorimotor polyneuropathy, intrahepatic cholestatic liver injury, gastrointestinal symptoms, dysautonomia, and myocardial thickening. Initial histologic evaluations of the abdominal fat pad aspirate and bone marrow biopsy were negative for amyloid deposition. However, due to a high index of suspicion, a second bone marrow biopsy was performed, confirming the presence of the amyloid protein. Given the patient's complex medical history, other types of amyloidosis, such as AA amyloidosis, AL amyloidosis, and ß2-microglobulin amyloidosis, should also be considered as differential diagnoses. The type of amyloid protein was subsequently identified through laser microdissection of amyloid fibrils followed by liquid chromatography–tandem mass spectrometry as AL-lambda (amyloid light-chain) amyloidosis. The patient presented unfavorable evolution, with progressive dysautonomia, being admitted to the ICU, culminating in refractory circulatory shock, and undergoing an empirical broad-spectrum antibiotic therapy. After a few days, she presented pulseless ventricular tachycardia, culminating in her death, before undergoing specific treatment. This article highlights the crucial role of precise identification in guiding appropriate therapeutic strategies for this complex, yet potentially severe, diseases.

Resumo: O artigo examina interpretações de práticas autoritárias no Brasil. Analisa os ataques à democracia e a implantação de um estado de exceção, elucidando aspectos antidemocráticos persistentes na relação Estado-sociedade. Através de revisão da literatura, parte do período pós-golpe de 2016, que retirou Dilma Rousseff da Presidência da República, segue os anos de gestão Temer e chega até os ataques de janeiro de 2023, passando pelo período correspondente ao governo de Jair Bolsonaro.

This study examined the independent effects of working memory (WM) and the interactive effects of WM/L2 proficiency and WM/task complexity on L2 written performance. The study followed a within--between-participant factorial design, with two levels of task complexity as the within-participant variable and L2 proficiency and WM as between-participants variables. The outcome measure was L2 writing performance as measured by CAF indices. Two groups of undergraduate students from a degree in English studies were invited to complete the simple and complex version of the "Fire-Chief" task. Task complexity was operationalized in terms of reasoning demands, and tasks were counterbalanced to avoid unwanted order effects. Participants also completed the Oxford Placement Test and a working memory test (n-back). Regarding independent effects, results show that WM did not have an effect on L2 writing performance. In contrast, L2 proficiency was the variable most connected to various dimensions of the text produced. As for interactive effects, no significant interaction between WM, proficiency, or task complexity was found. In contrast, L2 proficiency emerged as the sole significant predictor of L2 writing performance at both levels of task complexity.

This research in the Industry 5.0 field focuses on a human-centered simulation of the FAS200 SMC educational production line, utilizing Tecnomatix Process Simulate Human software for developing a virtual human environment. A key aspect of this study is the integration of inertial sensors, enhancing the accuracy and depth of ergonomic analysis. These sensors play a pivotal role in capturing precise human movement data, crucial for ergonomic assessments. Adopting a defined working methodology, the study extensively employs the RULA method to evaluate operator postures in the production line. This approach has led to significant ergonomic improvements, evidenced by a 40 percent reduction in the RULA index at each workstation. The integration of inertial sensors has been instrumental in achieving these results, providing detailed insights into human movements and interactions with the production environment. The research transcends traditional ergonomic assessments by incorporating a new human-centered approach, emphasizing the well-being of individuals working alongside machines. This approach, bolstered by the use of inertial sensors, marks a significant advancement in ergonomic studies, aligning with the principles of Industry 5.0. The findings hold substantial potential for application in industrial settings, signaling a shift towards more human-friendly and efficient industrial practices.

Abstract Introduction Takayasu’s arteritis (TAK) patients are at an elevated risk of metabolic syndrome and cardiovascular diseases (CVD). Currently, there are no well-validated biomarkers to assess this risk in this population. Previous research in different cohorts has linked serum levels of osteoprotegerin (OPG) and its polymorphisms to accelerated atherosclerosis and a marker of poor prognosis in CVD. Thus, we assessed this protein as a potential biomarker of CVD in TAK patients. Objectives To evaluate the serum levels of OPG and its SNPs (single nucleotide polymorphisms) in TAK patients and healthy controls, and to associate these parameters with clinical data. Methods This bicentric cross-sectional study included TAK patients who were compared with healthy individuals (control group). The serum levels of OPG and the frequency of OPG SNPs [1181G > C (rs2073618), 245 A > C (rs3134069), 163T > C (rs3102735), and 209 C > T (rs3134070)] were compared between the both groups and associated with clinical data. Results In total, 101 TAK patients and 93 controls were included in the study. The serum levels of OPG (3.8 ± 1.9 vs. 4.3 ± 1.8pmol/L, respectively; P = 0.059), and its four polymorphisms were comparable between both groups. In an additional analysis of only TAK patients, serum OPG levels and its four genes were not associated with any CVD parameters, except for higher OPG levels among patients without dyslipidemia. Conclusion No significant differences were observed in serum OPG levels or in the genotype frequencies of OPG SNPs between the patient and control groups. Similarly, no correlation was found between laboratory parameters and clinical data on CVD risk in TAK patients.