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White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) “OCD vs. healthy controls” (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) “unmedicated OCD vs. healthy controls” (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) “medicated OCD vs. unmedicated OCD” (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6–79.1 in adults; 35.9–63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification

INTRODUCTION: We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS: Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD-NM scale. This was assessed in 522 mutation carriers and 310 mutation-negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS: The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION: Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights: The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD-NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS). No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD-NM rating scale. Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains. A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales.

Multiple sclerosis (MS) is a neurological disease characterized by multifocal lesions and smoldering pathology. Although single -cell analyses provided insights into cytopathology, evolving cellular processes underlying MS remain poorly understood. We investigated the cellular dynamics of MS by modeling temporal and regional rates of disease progression in mouse experimental autoimmune encephalomyelitis (EAE). By performing single -cell spatial expression profiling using in situ sequencing (ISS), we annotated disease neighborhoods and found centrifugal evolution of active lesions. We demonstrated that disease -associated (DA)-glia arise independently of lesions and are dynamically induced and resolved over the disease course. Single -cell spatial mapping of human archival MS spinal cords confirmed the differential distribution of homeostatic and DA-glia, enabled deconvolution of active and inactive lesions into sub -compartments, and identified new lesion areas. By establishing a spatial resource of mouse and human MS neuropathology at a single -cell resolution, our study unveils the intricate cellular dynamics underlying MS.

Los sistemas alternativos de resolución de conflictos han ido ganando cada vez más protagonismo en nuestra sociedad, y, por tanto, también en la universidad. La Ley Orgánica 2/2006, de 3 de mayo, de Educación, establece que nuestro sistema educativo tiene entre sus fines conseguir una educación residenciada en el ejercicio de la tolerancia y de la libertad dentro de los principios democráticos de convivencia, así como en la prevención de conflictos, la mediación y la resolución pacífica de los mismos. La reciente Ley 3/2022, de 24 de febrero, de convivencia universitaria (BOE núm. 48, de 25 de febrero de 2022), establece que “el fomento de la convivencia en el seno de la comunidad universitaria excede un régimen disciplinario y no puede afrontarse, al menos exclusiva ni preferentemente, mediante el mismo. Por tanto, las universidades, en el ejercicio de su autonomía universitaria consagrada en el artículo 27.10 de la Constitución Española, han establecido y pueden desarrollar con mayor intensidad medidas y actuaciones que favorezcan y estimulen la convivencia activa y la corresponsabilidad entre todos los miembros de la comunidad universitaria. Asimismo, las universidades pueden potenciar el uso de medios alternativos de resolución de conflictos que pueden resultar más eficaces para afrontar determinadas conductas y conflictos entre miembros de la comunidad universitaria”. El Título I de la citada ley emplaza a las universidades públicas y privadas a desarrollar medios alternativos de solución de los conflictos, que tendrán carácter preferente al sistema disciplinario de resolución de conflictos. Los principios sobre los que se configurarán estos medios alternativos son los de voluntariedad, confidencialidad, equidad, imparcialidad, buena fe y respeto mutuo, flexibilidad, calidad y transparencia. Así mismo afirma que para garantizar estos principios y concretarlos en el marco de los procedimientos, se podrán elaborar manuales de actuación y se fomentará la formación

This work presents a literature review about control techniques for parallel connected power inverters under microgrid applications. Some control strategies, based on droop control for parallel inverters of distributed generation units in an ac distribution system will be presented in this work. Finally, an important method called Virtual Oscillating Control (VOC) is suggested for connecting voltage source inverters. Inverters are able to work in parallel with a constant-voltage constant frequency system, as well as with other inverters and also in standalone operation. The different power sources can share the load also under unbalanced conditions. Throughout this work several simulation results are presented in order to demonstrate the behaviour the behavior of the different control strategies tested., Peer Reviewed, Postprint (published version)

Research into the neurobiological and psychosocial mechanisms involved in fibromyalgia has progressed remarkably in recent years. Despite this, current accounts of fibromyalgia fail to capture the complex, dynamic, and mutual crosstalk between neurophysiological and psychosocial domains. We conducted a comprehensive review of the existing literature in order to: a) synthesize current knowledge on fibromyalgia; b) explore and highlight multi-level links and pathways between different systems; and c) build bridges connecting disparate perspectives. An extensive panel of international experts in neurophysiological and psychosocial aspects of fi-bromyalgia discussed the collected evidence and progressively refined and conceptualized its interpretation. This work constitutes an essential step towards the development of a model capable of integrating the main factors implicated in fibromyalgia into a single, unified construct which appears indispensable to foster the under-standing, assessment, and intervention for fibromyalgia.

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive 'threat' system and underactive 'soothing' system, might keep the 'salience network' (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/.

Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context1-5. However, current methods capture only one layer of omics information at a time, precluding the possibility of examining the mechanistic relationship across the central dogma of molecular biology. Here, we present two technologies for spatially resolved, genome-wide, joint profiling of the epigenome and transcriptome by cosequencing chromatin accessibility and gene expression, or histone modifications (H3K27me3, H3K27ac or H3K4me3) and gene expression on the same tissue section at near-single-cell resolution. These were applied to embryonic and juvenile mouse brain, as well as adult human brain, to map how epigenetic mechanisms control transcriptional phenotype and cell dynamics in tissue. Although highly concordant tissue features were identified by either spatial epigenome or spatial transcriptome we also observed distinct patterns, suggesting their differential roles in defining cell states. Linking epigenome to transcriptome pixel by pixel allows the uncovering of new insights in spatial epigenetic priming, differentiation and gene regulation within the tissue architecture. These technologies are of great interest in life science and biomedical research.

Aims: analysing the quality of sleep of the medical students at a private university and its association with the nonprescription use of nootropics (methylphenidate, lisdexamfetamine and modafinil).Methods: the sleep quality was analyzed by using the Pittsburgh Sleep Quality Index. A sociodemographic questionnaire was considered to identify the psychosocial characteristics of the participants and the use of nootropics. Results were represented as mean and standard deviation (for quantitative variables) or frequency (for qualitative variables), and associations were analyzed using the chi-square test. Results: 362 students answered the questionnaire. The medium levels of global PSQI in students with recent unprescribed use of nootropics was like that observed for students who had never used nootropics (7.76 vs. 7.73; p=0.96). The PSQI analysis by specific domain also showed no statistically significant difference for any domain. It was observed that 23.6% of women and 33,9% of men had good sleep quality, with this difference being statistically significant (p=0.04). The use of six doses or more of alcoholic beverages was related to higher levels of PSQI (7.47 vs. 8.19; p=0.047). Students with poor sleep quality had less satisfaction with their professional choice (OR = 1.84; 95% CI= 1.09 - 3.11), lower perception of skills acquisition (OR= 1.96; 95%CI = 1.16 - 3.31) and a higher proportion of thoughts related to dropping out of the course (OR = 0.46; 95%CI = 0.27 - 0.77). Recent and non-prescription use of nootropics was associated with marijuana use and the desire to drop out of the course. Conclusions: sleep quality was worse in females and in those with higher alcohol intake, and was associated with lower satisfaction with professional choice and desire to drop out of the course. No association was found between non-prescription use of nootropics and sleep quality in medical students., Objetivos: analisar a qualidade do sono de estudantes de medicina em uma universidade privada brasileira e sua associação com o uso não prescrito de nootrópicos (metilfenidato, lisdexanfetamina e modafinil). Métodos: a qualidade do sono foi analisada utilizando-se o questionário de Pittsburgh (PSQI). Considerou-se um questionário sociodemográfico para identificaçãopsicossocial dos participantes e uso de nootrópicos. Os resultados foram representados como média e desvio-padrão (para as variáveis quantitativas) ou frequência (para as qualitativas), e as associações foram analisadas pelo teste de qui-quadrado.Resultados: responderam ao questionário 362 alunos. Os níveis médios de PSQI global em estudantes com uso recente não prescrito de nootrópicos foi semelhante ao observado para estudantes que nunca usaram nootrópicos (7,76 vs. 7,73; p=0,96). A análise do PSQI por domínio específico também não mostrou diferença estatisticamente significativa. Observou-se que 23,6% das mulheres e 33,9% dos homens tiveram boa qualidade do sono, sendo essa diferença estatisticamente significativa (p=0,04). O uso de seis doses ou mais de bebida alcoólica esteve relacionado com níveis mais altos do PSQI (7,47 vs. 8,19; p=0,047). Alunos com qualidade do sono ruim apresentaram menor satisfação com a escolha profissional (OR = 1.84; IC95%= 1.09 - 3.11), menor percepção de aquisição de habilidades (OR = 1.96; IC95% = 1.16 - 3.31) e maior proporção de pensamentos relacionados a abandonar o curso (OR = 0,46; IC95% = 0,27 - 0,77). O uso recente e não prescrito de nootrópicos esteve associado ao uso de maconha e ao desejo de abandonar o curso.

Objetivamos compreender os sentidos da experiência formativa de migrantes guineenses na Universidade Federal do Ceará (UFC). Inicialmente, problematizamos as causas da migração e suas consequências psicológicas. Apresentamos uma fundamentação teórica sobre o fenômeno da migração. Expomos o panorama de Guiné-Bissau e os fatores que levam guineenses a migrarem para estudar na UFC. Empregamos um roteiro semi-estruturado de entrevista com quatro estudantes guineenses e analisamos suas experiências segundo uma metodologia fenomenológica empírica. Estabelecemos e discutimos os seguintes eixos temáticos: diferenças educacionais entre Brasil e Guiné-Bissau; dificuldades financeiras e adaptativas; aprendizagens interculturais. As experiências abordadas tratam não somente de uma formação acadêmico-profissional, mas de uma identidade cultural Guiné-Brasil. Assim como os estudantes guineenses estão se trans-formando, a partir de uma abertura ao Brasil, via universidade, é preciso que o movimento seja bilateralmente retroalimentado. Historicamente, o que antes era o fado incerto para escravos, deve-se firmar com o futuro promissor para aqueles estudantes compromissados em (re)construir um país melhor, seja ele Guiné-Bissau ou o Brasil., We aim to understand the meanings of the training experience of Guinean migrants at the Federal University of Ceará (FUC). Initially, we problematize the migration causes and its psychological consequences. We present a theoretical foundation on the migration phenomenon. We expose the Guinea-Bissau panorama and the factors that lead Guineans to migrate to study at FUC. We used a semi-structured interview script with four Guinean students and analyzed their experiences according to an empirical phenomenological methodology. We established and discussed the following themes: educational differences between Brazil and Guinea-Bissau; financial and adaptive difficulties; intercultural learning. The experiences approached not only deal with academic-professional training, but with a Guinea-Brazil cultural identity. Just as Guinean students are transforming, from an opening to Brazil, via university, it's necessary that the movement be bilaterally feedback. Historically, what was once the uncertain fate for slaves, must be signed with a promising future for those students committed to (re)building a better country, be it Guinea-Bissau or Brazil.

This essay seeks to show the experience of A Casa Tombada, a non-profit private educational and cultural center,created in 2015, in the city of São Paulo/SP, dedicated to continuing education and research in the fields of art,culture and of education, as a place of study and binding. In 2020, with the covid-19 pandemic, the physicalspace of A Casa Tombada was replaced by the virtual one, and courses and meetings had to be recreated. Thisevent allowed us to bring the word home even closer to the words study and binding. At the end of this essay,we can state that such practices occur between A Casa Tombada (institution) and the home of each participant,through the event called “class”. This essay has the interlocution of: Luiza Christov, Jorge Larrosa, Oyèró nkẹOyěwùmí, Maria Filomena Molder among others., Este ensaio busca dar a ver a experiência d’A Casa Tombada, um centro educacional e cultural privado sem finslucrativos, originado em 2015 na cidade de São Paulo/SP, dedicado à formação continuada e pesquisa noscampos da arte, da cultura e da educação, como um lugar de estudo e de vinculação. Em 2020, com a pandemiado covid-19, o espaço físico d’A Casa Tombada foi substituído pelo virtual, e os cursos e encontros tiveram queser recriados. Esse acontecimento nos permitiu aproximar ainda mais a palavra casa das palavras estudo e vinculação. Ao final deste ensaio podemos afirmar que tais práticas acontecem entre A Casa Tombada (instituição) e a casa de cada participante, por meio do acontecimento chamado “aula”. Este ensaio conta coma interlocução de: Luiza Christov, Jorge Larrosa, Oyèró nkẹ Oyěwùmí, Maria Filomena Molder dentre outros., Este ensayo busca mostrar la experiencia de A Casa Tombada, un centro educativo y cultural privado sin finesde lucro, creado en 2015, en la ciudad de São Paulo/SP, dedicado a la educación continua y la investigación enlas áreas de arte, cultura y educación, como lugar de estudio y vinculación. En 2020, con la pandemia del covid-19, se sustituyó el espacio físico de A Casa Tombada por el virtual, y hubo que recrear cursos y encuentros. Esteevento nos permitió llevar la palabra a casa aún más cerca de las palabras estudio y vinculación. Al final de esteensayo podemos afirmar que tales prácticas se dan entre A Casa Tombada (institución) y el domicilio de cadaparticipante, a través del evento denominado “clase”. Este ensayo cuenta con la interlocución de: Luiza Christov,Jorge Larrosa, Oyèró nkẹ Oyěwùmí, Maria Filomena Molder entre otros.

Background: A growing body of real-world evidence (RWE) aims to better reflect outcomes of cancer patients treated in real-world settings. We aimed to conduct a first comprehensive mapping review of the RWE produced over the past 3 years in terms of tumor type, treatment strategies, setting, and data sources, focusing on targeted therapies (TT) in solid tumors. Methods: We conducted a systematic review in PubMed of RWE studies published between 01/2020 and 12/2022. We identified non-interventional studies using observational data, focusing on solid tumors exposure to targeted therapies, excluding immunotherapies. Abstract and full-text screening were performed by 11 independent reviewers. Results: A total of 7,774 publications were retrieved with 1,251 considered eligible and extracted. The number of publications per year progressively increased during this period (328 in 2020; 421 in 2021; 502 in 2022). Most studies (50%) were performed in Asia, followed by Europe (25%) and North America (17%). Only 8% of studies had patients treated in more than one country. Treatment effectiveness and safety were assessed in 71% and 42% of studies respectively. Main data sources were medical records. Conclusions: RWE publications on TT for solid tumors are heterogeneous and mostly rely on retrospective data such as medical records. Population-based and international studies are rare. Collaborative efforts towards international representativeness and the use of routinely collected and/or standardized data sources must be encouraged to increase the relevance and future quality of publications and their potential impact on oncology practice.

Background: While Real-world Evidence (RWE) has documented value for safety monitoring and disease epidemiology, its objective contribution to safety and efficacy evaluations for regulatory purposes is still unclear. Here, we aim to describe the prevalence and type of RWE considered by European Medicines Agency (EMA) as contribution to efficacy and safety-related evidence generation among approved oncology targeted therapies... Methods: On March 10, 2023, we screened the medicines listing of EMA to identify all anti-cancer targeted therapies for solid malignancies with a decision date (initial marketing authorizations and extension of indications) between 2018-2022. We screened the European public assessment reports (EPARs) using a standardized approach to collect data on RWE. When generated pre-authorization, the RWE contribution to the final regulatory decision was classified as definitive, supportive, or non-supportive. For... Results: Out of a total of 1976 medicines, we identified 55 oncology targeted therapies, corresponding to 75 EPARs (indications), which are described in the table. The use of RWE in regulatory deliberations occurred in 24/75 (32%) EPARs, increasing from 30% in 2018-2020, to 34% in 2021-2022. Pre-authorization RWE was described in 20/24 (83%) EPARs, among which none were definitive, 8 RWE studies (in 7 EPARs) non-supportive, and 20 RWE studies (in 15 EPARs) were supportive of the decision. Published RWE... Conclusions: Over the past 5 years, RWE involvement in the approval of oncology targeted therapies in Europe tends to increase, with the majority being supportive for EMA regulatory decision making complementary to traditional clinical trials...

Exploration of the physical environment is an indispensable precursor to data acquisition and enables knowledge generation via analytical or direct trialing. Artificial Intelligence lacks the exploratory capabilities of even the most underdeveloped organisms, hindering its autonomy and adaptability. Supported by cognitive psychology, this works links human behavior and artificial agents to endorse self-development. In accordance with reported data, paradigms of epistemic and achievement emotion are embedded to machine-learning methodology contingent on their impact when decision making. A study is subsequently designed to mirror previous human trials, which artificial agents are made to undergo repeatedly towards convergence. Results demonstrate causality, learned by the vast majority of agents, between their internal states and exploration to match those reported for human counterparts. The ramifications of these findings are pondered for both research into human cognition and betterment of artificial intelligence., Comment: 21 pages, 5 figures, journal

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products.

Species of the genus Candida, characterized as commensals of the human microbiota, are opportunistic pathogens capable of generating various types of infections with high associated costs. Considering the limited pharmacological arsenal and the emergence of antifungal-resistant strains, the repositioning of drugs is a strategy used to search for new therapeutic alternatives, in which minocycline and doxycycline have been evaluated as potential candidates. Thus, the objective was to evaluate the in vitro antifungal activity of two tetracyclines, minocycline and doxycycline, and their possible mechanism of action against fluconazole-resistant strains of Candida spp. The sensitivity test for antimicrobials was performed using the broth microdilution technique, and the pharmacological interaction with fluconazole was also analysed using the checkerboard method. To analyse the possible mechanisms of action, flow cytometry assays were performed. The minimum inhibitory concentration obtained was 4-427 µg ml-1 for minocycline and 128-512 µg ml-1 for doxycycline, and mostly indifferent and additive interactions with fluconazole were observed. These tetracyclines were found to promote cellular alterations that generated death by apoptosis, with concentration-dependent reactive oxygen species production and reduced cell viability. Therefore, minocycline and doxycycline present themselves as promising study molecules against Candida spp.

Heritage is ubiquitous in the late-modern world. It is a product of modernity as well as one of the main producing factors of modernity (Harrison 2013; Santamarina Campos 2013). Existing heritage regimes illustrate a shift from political projects based on distinction and the creation of national identities to economic projects linked to transnational capital: from a nation-building project to national identities to be consumed (Comaroff and Comaroff 2009; Santamarina Campos and Mármol 2017, 365). In this chapter, we map UNESCO’s Intangible Cultural Heritage (ICH) trajectories in Portugal and Spain using the concept of heritage regime(s) to understand these trajectories.

[EN] This article explores Lisbon’s Fado Museum as an affective, material, symbolic, and performative site of memory in which different audiences such as tourists and the local fado community converge, without necessarily intersecting. We argue that the Fado Museum has evolved from a mere exhibiting space to become a multivalent “heritage infrastructure” that facilitates new spaces of agency in which novel forms of relating to —and dwelling in— heritage emerge. By recognizing the importance of the Fado Museum in the institutionalization and legimitization of fado as city heritage —and its significance to the social and symbolic production of Alfama as a fado neighborhood—, we ultimately aim to problematize the function of this kind of heritage infrastructures in the complex relationship between tourism, heritagization, and urban regeneration in the era of overtourism., [FR] Cet article explore le musée du fado de Lisbonne en tant que site affectif, matériel, symbolique et performatif de la mémoire dans lequel convergent, sans nécessairement se croiser, différents publics tels que les touristes et la communauté locale du fado. Nous soutenons que le musée du fado a évolué d’un simple espace d’exposition à une « infrastructure patrimoniale » polyvalente qui facilite de nouveaux espaces d’action dans lesquels émergent de nouvelles formes de relation avec le patrimoine et d’habitation de celui-ci. En reconnaissant l’importance du musée du fado dans l’institutionnalisation et la légitimation du fado en tant que patrimoine de la ville - et son importance pour la production sociale et symbolique de l’Alfama en tant que quartier du fado -, nous visons finalement à problématiser la fonction de ce type d’infrastructures patrimoniales dans la relation complexe entre le tourisme, la patrimonialisation et la régénération urbaine à l’ère du surtourisme., [PT] Este artigo aborda o Museu do Fado, situado em Lisboa, como um espaço mobilizador de imaginários turísticos e de memórias afetivas, simbólicas e performativas no qual convergem, sem necessariamente se cruzarem, diferentes públicos como os turistas, aficionados de fado e a comunidade fadista local. Argumentamos que o Museu do Fado evoluiu de um mero espaço expositivo para se tornar numa “infra-estrutura patrimonial” multivalente que facilita novos espaços de agentividade nos quais emergem formas inovadoras de se relacionar com – e habitar – o património. Ao reconhecer a importância do Museu do Fado na institucionalização e na legitimação do fado como património da cidade e reconhecendo também o seu significado na produção social e simbólica de Alfama como bairro do fado, pretendemos problematizar a função deste tipo de infra-estrutura patrimonial na complexa relação entre turismo, patrimonialização e revitalização urbana na era do overtourism.

Background: Immune checkpoint-inhibitors (ICIs) are changing outcomes in different cancer settings, notably for patients with non-small-cell lung cancer (NSCLC). There are, however, still important gaps of evidence for clinical practice when using these novel treatments. In this study, we assessed physicians’ opinion and experience on challenges for clinical practice with ICIs monotherapy in NSCLC. Methods: A survey was conducted on experienced physicians treating patients with NSCLC with ICIs. Two rounds of pilot tests were carried out for validation among a group of experts. Topics under analysis were in relation to treatment of elderly populations, performance status, brain metastases, use of steroids or antibiotics, the effects of gut microbiome, autoimmune diseases, human immunodeficiency virus infection, solid organ transplants, use of anti-programmed cell death protein 1 versus anti-programmed death-ligand 1 drugs, atypical tumour responses, predictors of response, duration of treatment and a final open question on additional relevant challenges. Results: Two hundred and twenty-one answers were collected, including 106 (48%) valid answers from experts for final analysis (physicians who have treated at least 20 patients with NSCLC with ICIs). The vast majority agreed that the selected topics in this study are important challenges ahead and more evidence is needed. Moreover, predictors of response, treating brain metastasis, shorter duration of treatment, the effects of gut microbiome and concomitant use of steroids were voted the most important topics to be further addressed in prospective clinical research. Conclusions: This survey contributed to understanding which are the main challenges for clinical practice with ICIs monotherapy in NSCLC. It can also contribute to guide further clinical research, considering the opinions and experience of those who regularly treat NSCLC patients with ICIs., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: COVID-19 has significantly affected patients with cancer and revealed unanticipated challenges in securing optimal cancer care across different disciplines. The European Society for Medical Oncology COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international, real-world database, collecting data on the natural history, management, and outcomes of patients with cancer and SARS-CoV-2 infection. Methods: This is the 2nd CoCARE analysis, jointly with Belgian (Belgian Society of Medical Oncology, BSMO) and Portuguese (Portuguese Society of Medical Oncology, PSMO) registries, with data from January 2020 to December 2021. The aim is to identify significant prognostic factors for COVID-19 hospitalization and mortality (primary outcomes), as well as intensive care unit admission and overall survival (OS) (secondary outcomes). Subgroup analyses by pandemic phase and vaccination status were carried out. Results: The cohort includes 3294 patients (CoCARE: 2049; BSMO: 928, all hospitalized by eligibility criteria; PSMO: 317), diagnosed in four distinct pandemic phases (January to May 2020: 36%; June to September 2020: 9%; October 2020 to February 2021: 41%; March to December 2021: 12%). COVID-19 hospitalization rate was 54% (CoCARE/PSMO), ICU admission 14%, and COVID-19 mortality 22% (all data). At a 6-month median follow-up, 1013 deaths were recorded with 73% 3-month OS rate. No significant change was observed in COVID-19 mortality among hospitalized patients across the four pandemic phases (30%-33%). Hospitalizations and ICU admission decreased significantly (from 78% to 34% and 16% to 10%, respectively). Among 1522 patients with known vaccination status at COVID-19 diagnosis, 70% were non-vaccinated, 24% had incomplete vaccination, and 7% complete vaccination. Complete vaccination had a protective effect on hospitalization (odds ratio = 0.24; 95% confidence interval [0.14-0.38]), ICU admission (odds ratio = 0.29 [0.09-0.94]), and OS (hazard ratio = 0.39 [0.20-0, SCOPUS: ar.j, info:eu-repo/semantics/published

Oligodendrogenesis in the human central nervous system has been observed mainly at the second trimester of gestation, a much later developmental stage compared to oligodendrogenesis in mice. Here, we characterize the transcriptomic neural diversity in the human forebrain at post-conception weeks (PCW) 8–10. Using single-cell RNA sequencing, we find evidence of the emergence of a first wave of oligodendrocyte lineage cells as early as PCW 8, which we also confirm at the epigenomic level through the use of single-cell ATAC-seq. Using regulatory network inference, we predict key transcriptional events leading to the specification of oligodendrocyte precursor cells (OPCs). Moreover, by profiling the spatial expression of 50 key genes through the use of in situ sequencing (ISS), we identify regions in the human ventral fetal forebrain where oligodendrogenesis first occurs. Our results indicate evolutionary conservation of the first wave of oligodendrogenesis between mice and humans and describe regulatory mechanisms involved in human OPC specification.

Background: Oligodendrocytes are glial cells that support and insulate axons in the central nervous system through the production of myelin. Oligodendrocytes arise throughout embryonic and early postnatal development from oligodendrocyte precursor cells (OPCs), and recent work demonstrated that they are a transcriptional heterogeneous cell population, but the regional and functional implications of this heterogeneity are less clear. Here, we apply in situ sequencing (ISS) to simultaneously probe the expression of 124 marker genes of distinct oligodendrocyte populations, providing comprehensive maps of the corpus callosum, cingulate, motor, and somatosensory cortex in the brain, as well as gray matter (GM) and white matter (WM) regions in the spinal cord, at postnatal (P10), juvenile (P20), and young adult (P60) stages. We systematically compare the abundances of these populations and investigate the neighboring preference of distinct oligodendrocyte populations. Results: We observed that oligodendrocyte lineage progression is more advanced in the juvenile spinal cord compared to the brain, corroborating with previous studies. We found myelination still ongoing in the adult corpus callosum while it was more advanced in the cortex. Interestingly, we also observed a lateral-to-medial gradient of oligodendrocyte lineage progression in the juvenile cortex, which could be linked to arealization, as well as a deep-to-superficial gradient with mature oligodendrocytes preferentially accumulating in the deeper layers of the cortex. The ISS experiments also exposed differences in abundances and population dynamics over time between GM and WM regions in the brain and spinal cord, indicating regional differences within GM and WM, and we found that neighboring preferences of some oligodendroglia populations are altered from the juvenile to the adult CNS. Conclusions: Overall, our ISS experiments reveal spatial heterogeneity of oligodendrocyte lineage progression in the brain and

O presente artigo tem por objetivo principal explorar detalhadamente, e de modo exclusivamente bibliográfico, a teoria da Folkcomunicação (Beltrão, 2004), pertencente ao ramo das Ciências Sociais e Humanas, alinhada, sobretudo, com as Ciências da Comunicação; e que possui sua origem genuinamente brasileira, ao ter sido fundada e desenvolvida pelo jornalista e escritor brasileiro Luiz Beltrão durante a década de 1960. A característica da sua procedência brasileira é, portanto, a principal motivação e justificativa para a realização de uma pesquisa bibliográfica aprofundada sobre a referida teoria, com o intuito de dar a conhecer os principais interesses e fundamentos desta formulação, conceito e disciplina, que se comporta como teoria cultural dedicada a compreender a complexa e estreita relação da cultura popular com os meios de comunicação de massa (Breguez, 2013). O universo folkmidiático contempla a cultura em sua completude, dando a notar a extensa complexidade dos elementos, manifestações e desenhos culturais possíveis no mundo contemporâneo (Marques de Melo, 2008). Ao fazer uso de uma gama investigativa de material científico, que aborda conceitos, processos e perspectivas facilitadores de uma compreensão da teoria brasileira de Luiz Beltrão da Folkcomunicação em seu aspecto amplo, geral e completo, compreendemos que os processos históricos e a inegável realidade da dinamicidade coletiva refletem numa constante metamorfose de interesses, empirias, práticas e investigações (Maciel, 2013), que contribuem para uma permanente e recorrente atualização de estudos e conceitos científicos., The main objective of this article is to explore in detail, and in an exclusively bibliographic way, the theory of Folkcommunication (Beltrão, 2004), belonging to the field of Social and Human Sciences, aligned, above all, with Communication Sciences; and which has its genuine Brazilian origin, having been founded and developed by the Brazilian journalist and writer Luiz Beltrão during the 1960s. The characteristic of its Brazilian origin is, therefore, the main motivation and justification for carrying out an in-depth bibliographic research on the aforementioned theory, in order to make known the main interests and foundations of this formulation, concept and discipline, which behaves as a cultural theory dedicated to understanding the complex and close relationship between popular culture and the mass media (Breguez, 2013). The folkmedia universe contemplates culture in its entirety, highlighting the extensive complexity of the elements, manifestations and cultural designs possible in the contemporary world (Marques de Melo, 2008). By making use of an investigative range of scientific material, which approaches concepts, processes and perspectives that facilitate an understanding of the Brazilian theory of Luiz Beltrão da Folkcommunication in its broad, general and complete aspect, we understand that the historical processes and the undeniable reality of the dynamics collective reflection in a constant metamorphosis of interests, empirical studies, practices and investigations (Maciel, 2013), which contribute to a permanent and recurrent updating of scientific studies and concepts.

A configuração do campo de estudos em torno da música popular vem se definindo, no âmbito da escrita da história do Brasil, como parte da virada historiográfica decorrente da ascensão de paradigmas teóricos e metodológicos vinculados à história social e à história cultural em universidades de diferentes regiões do país. Contemplando pesquisas que versam sobre temas diversos dentro desse universo, tais como a polifonia paulistana na década de 19301, o samba e suas conexões com o Estado Novo2, a Tropicália e suas controvérsias3, a chamada “música cafona”4, o rap5 e a música sertaneja6, tais produções permitiram que, para além do eixo Sul-Sudeste, ocorresse uma crescente regionalização do debate que põe sons e sentidos no foco de historiadores.

O principal propósito deste artigo é apropriar-se historicamente do filme Recinfernália (1975), do filósofo, poeta, ator, cineasta e agitador cultural pernambucano Jomard Muniz de Britto. No texto se procurará abordar, principalmente, as contribuições do autor ao esforço de bricolagem e (re)invenção identitária da cidade do Recife, bricolagem que se realizaria através de uma intensa atividade artística voltada, entre outras coisas, para uma submissão da “pernambucanidade tropicológica” a um delírio que a obrigasse a transmutar-se em “pernambucália tropicalista”. No caso de Recinfernália, trata-se de um esforço de Jomard Muniz de Britto para reposicionar a identidade espacial da capital pernambucana, forçando-a a escapar da aparência de identificação consigo mesma que a tradição tropicológica, do ponto de vista do sujeito ora estudado, buscava impor ao Recife e mesmo ao objeto cultura brasileira. Em filme, portanto, Jomard consuma o programa tático de Michel de Certeau: a ver a cidade, espreitando-a, prefere misturarse com ela, praticando-a e por consequência borrando o cartão-postal

Certain cyanobacteria of the secondary metabolite-rich order Nostocales can establish permanent symbioses with a large number of cycads, by accumulating in their coralloid roots and shifting their metabolism to dinitrogen fixation. Here, we report the discovery of two new lipoglycopeptides, desmamides A (1) and B (2), together with their aglycone desmamide C (3), from the nostocalean cyanobacterium Desmonostoc muscorum LEGE 12446 isolated from a cycad (Cycas revoluta) coralloid root. The chemical structures of the compounds were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The desmamides are decapeptides featuring O-glycosylation of tyrosine (in 1 and 2) and an unusual 3,5-dihydroxy-2-methyldecanoic acid residue. The biosynthesis of the desmamides was studied by substrate incubation experiments and bioinformatics. We describe herein the dsm biosynthetic gene cluster and propose it to be associated with desmamide production. The discovery of this class of very abundant (>1.5% d.w.) bacterial lipoglycopeptides paves the way for exploration of their potential role in root endosymbiosis.

This article was inspired by the literary model that Ítalo Calvino erected in Invisible Cities and conceptually supported by the formulations of Walter Benjamin, for whom men inhabit the city as much as they are inhabited by it. The article takes the poetry of Roberto Piva as a historical sign through which one can derive a maddened pauliceia different and unfolded from that of Mário de Andrade: a scrappy, surreal city that confuses itself in the poetic delusions of Roberto Piva and his companions from the “rebellious periphery”, O presente artigo, inspirado no modelo literário que Ítalo Calvino erigiu em “As cidades invisíveis” e amparado conceitualmente nas formulações de, entre outros, Walter Benjamin, para quem os homens habitam a cidade tanto quanto são habitados por ela, toma a poesia de Roberto Piva como um signo histórico através do qual se pode derivar uma pauliceia desvairada diferente e desdobrada daquela de Mário de Andrade: uma cidade sucata, surreal, que se confaz nos delírios poéticos de Roberto Piva e de seus companheiros de “periferia rebelde”.

PURPOSEPatients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET).METHODSPatients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort.RESULTSThe model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning

Esta tese analisa o comércio entre Portugal e Inglaterra no período de 1890-1960 com o objetivo de avaliar a dependência comercial luso-inglesa, o seu processo e mecanismo de mudança enquadrado no ambiente económico, social e político dos diferentes subperíodos. A periodização assentou nas duas Grandes Guerras, fases de rutura dos fluxos comerciais. Analisamos a corrente exportadora e importadora para Inglaterra, nos produtos com maior peso na mesma, mas também as trocas internacionais com outros países, sempre que estas se manifestaram relevantes quantitativamente e qualitativamente. .Destacamos as principais alterações e fizemos notar as situações de continuidade. Recorremos às estatísticas de comércio externo do INE para o estudo quantitativo. Todo o trabalho de investigação foi acompanhado da visão da época transmitida pelo recurso a fontes primárias, que nos deram a conhecer a forma como os acontecimentos eram vividos, e que certamente não teríamos à distância do tempo.

Impaired semantic knowledge is a characteristic feature of some forms of frontotemporal dementia (FTD), particularly the sporadic disorder semantic dementia. Less is known about semantic cognition in the genetic forms of FTD caused by mutations in the genes MAPT, C9orf72, and GRN. We developed a modified version of the Camel and Cactus Test (mCCT) to investigate the presence of semantic difficulties in a large genetic FTD cohort from the Genetic FTD Initiative (GENFI) study. Six-hundred-forty-four participants were tested with the mCCT including 67 MAPT mutation carriers (15 symptomatic, and 52 in the presymptomatic period), 165 GRN mutation carriers (33 symptomatic, 132 presymptomatic), and 164 C9orf72 mutation carriers (56 symptomatic, 108 presymptomatic) and 248 mutation-negative members of FTD families who acted as a control group. The presymptomatic mutation carriers were further split into those early and late in the presymptomatic period (more than vs. within 10 years of expected symptom onset). Groups were compared using a linear regression model, adjusting for age and education, with bootstrapping. Performance on the mCCT had a weak negative correlation with age (rho = -0.20) and a weak positive correlation with education (rho = 0.13), with an overall abnormal score (below the 5th percentile of the control population) being below 27 out of a total of 32. All three of the symptomatic mutation groups scored significantly lower than controls: MAPT mean 22.3 (standard deviation 8.0), GRN 24.4 (7.2), C9orf72 23.6 (6.5) and controls 30.2 (1.6). However, in the presymptomatic groups, only the late MAPT and late C9orf72 mutation groups scored lower than controls (28.8 (2.2) and 28.9 (2.5) respectively). Performance on the mCCT correlated strongly with temporal lobe volume in the symptomatic MAPT mutation group (rho > 0.80). In the C9orf72 group, mCCT score correlated with both bilateral temporal lobe volume (rho > 0.31) and bilateral frontal lobe volume (rho

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

The power calculation is an indispensable element in droop-controlled inverters because the bandwidth of the measured power has a direct impact on the controller performance. This paper proposes a fast and accurate power calculation algorithm based on the combined Second Order Generalized Integrator (SOGI) filters in stationary coordinates for a three-phase system, which takes into consideration the use of nonlinear loads. The power calculation scheme is formed by the two-stage SOGI filters that are employed for obtaining the active and reactive powers required to perform a droop-based inverter operation, respectively. From the two-stage structure, the first SOGI is used as a band-pass filter (BPF) for filtering harmonics and obtaining the fundamental current of the nonlinear load; The second SOGI is used as a low-pass filter (LPF) for extracting the DC-component, which corresponds with the average power. A small-signal model of a two droop-controlled inverters system is built to obtain the dynamical response and stability margin of the system. And compared it with the dynamical behaviour of a standard droop-control method. Next, the proposed power calculation system is designed in order to achieve the same ripple amplitude voltage as that obtained with the standard droop-control method by adjusting the bandwidth gains. Through simulation and hardware in the loop (HIL) validation, the proposed approach presents a faster and more accurate performance when sharing nonlinear loads, and also drives the inverters’ output voltage with lower distortion., Peer Reviewed, Postprint (published version)

Cine cardiac magnetic resonance (CMR) imaging is considered the gold standard for cardiac function evaluation. However, cine CMR acquisition is inherently slow and in recent decades considerable effort has been put into accelerating scan times without compromising image quality or the accuracy of derived results. In this paper, we present a fully-automated, quality-controlled integrated framework for reconstruction, segmentation and downstream analysis of undersampled cine CMR data. The framework enables active acquisition of radial k-space data, in which acquisition can be stopped as soon as acquired data are sufficient to produce high quality reconstructions and segmentations. This results in reduced scan times and automated analysis, enabling robust and accurate estimation of functional biomarkers. To demonstrate the feasibility of the proposed approach, we perform realistic simulations of radial k-space acquisitions on a dataset of subjects from the UK Biobank and present results on in-vivo cine CMR k-space data collected from healthy subjects. The results demonstrate that our method can produce quality-controlled images in a mean scan time reduced from 12 to 4 seconds per slice, and that image quality is sufficient to allow clinically relevant parameters to be automatically estimated to within 5% mean absolute difference.

Considering that the industrial sector consumes almost one-third of the energy demand globally, it is an urgent call to reduce the carbon footprints in this sector. Among different approaches to meet this goal, such as the employment of carbon capture technologies and increasing energy efficiency within industries, transitioning to renewable electricity (RE) would be another outlook to reduce the carbon footprints and increase the energy security of the industries. Collective power generation within communities has shown to be feasible and promising in the industrial sector, where groups of industries collaborate to generate energy and meet their energy demand. In this research, we investigated how the initiation and continuation of industrial community energy systems (InCES) among companies can take place and which financial incentives the government can introduce to support these initiatives. We built an agent-based model that incorporates cost-benefit analysis and cultural factors in the decision making process of industries, to assess the feasibility of initiating/joining an InCES by industries. This study shows that the FIT mechanism had the worst performance in incentivizing the establishment of an InCES among industries. In contrast, the TAX incentive showed the best performance in mobilizing the investments towards InCES. Similarly, the TAX incentive showed relatively superior performance in electricity generation, the number of established InCESs, and the number of companies joining each InCES. Despite the better performance of the TAX incentive, it was also the most expensive option for the governments as a significant share of the establishment costs of an InCES was put on the shoulders of the governments., Energie and Industrie, Economics of Technology and Innovation