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Fatigue is one of the most commonly reported symptoms in the context of the post-COVID-19 syndrome. Notably, fatigue is characterised by overlapping physical and psychopathological symptoms, and questions about its trajectory over time and possible predictors remained unanswered. Thus, in the present study we aim to investigate the prevalence, the course over time, and the risk factors of post-COVID fatigue. We included 495 patients recovered from COVID-19. For all of them we collected one month demographic, clinical and psychopathological characteristics. We evaluated fatigue severity at one, three, six, and twelve-months according to Fatigue Severity Scale (FSS). We explored the potential predictor of long-term post-COVID fatigue (six or twelve months FSS) by implementing 5000 non-parametric bootstraps enhanced elastic net penalised regression. We found that 22%, 27%, 30%, and 34% of patients self-rated fatigue symptoms in the pathological range at one, three, six, and twelve months respectively. We detected a worsening of fatigue symptomatology over time. From the elastic net regression results, only depressive symptomatology at one month (ZSDS and BDI-13) predicted the presence of post-COVID-19 long-term fatigue. No other clinical or demographic variable was found to predict post-COVID fatigue. We suggest that, rather independent of COVID-19 severity, depression after COVID-19 is associated with persistent fatigue. Clarifying mechanisms and risk factors of post-COVID fatigue will allow to identify the target population and to tailor specific treatment and rehabilitation interventions to foster recovery.

Recently, we defined “CML-like” subtype of BCR::ABL1-positive acute lymphoblastic leukemia (ALL), resembling lymphoid blast crisis of chronic myeloid leukemia (CML). Here we retrospectively analyzed prognostic relevance of minimal residual disease (MRD) and other features in 147 children with BCR::ABL1-positive ALL (diagnosed I/2000–IV/2021, treated according to EsPhALL (n = 133) or other (n = 14) protocols), using DNA-based monitoring of BCR::ABL1 genomic breakpoint and clonal immunoglobulin/T-cell receptor gene rearrangements. Although overall prognosis of CML-like (n = 48) and typical ALL (n = 99) was similar (5-year-EFS 60% and 49%, respectively; 5-year-OS 75% and 73%, respectively), typical ALL presented more relapses while CML-like patients more often died in the first remission. Prognostic role of MRD was significant in the typical ALL (p = 0.0005 in multivariate analysis for EFS). In contrast, in CML-like patients MRD was not significant (p values > 0.2) and inapplicable for therapy adjustment. Moreover, in the typical ALL, risk-prediction could be further improved by considering initial hyperleukocytosis. Early distinguishing typical BCR::ABL1-positive ALL and CML-like patients is essential to enable optimal treatment approach in upcoming protocols. For the typical ALL, tyrosine-kinase inhibitors and concurrent chemotherapy with risk-directed intensity should be recommended; in the CML-like disease, no relevant prognostic feature applicable for therapy tailoring was found so far.

Ocular involvement in systemic diseases is frequent in cats; however, without concurrent clinical and ophthalmic examinations with gross and/or histologic analysis of the eye, these findings can be underdiagnosed. This article aims to provide gross, histologic, and immunohistochemical characteristics of ocular lesions from cats submitted to necropsy, focusing on those caused by systemic infectious agents. Cats that died due to a systemic infectious disease were selected based on necropsy diagnosis and presence of ocular lesions. Gross, histologic, and immunohistochemical findings were recorded. From April 2018 to September 2019, 849 eyes of 428 cats were evaluated. Histologic abnormalities were seen in 29% of cases, which were classified as inflammatory (41%), neoplastic (32%), degenerative (19%), and metabolic/vascular (8%). Macroscopic changes were present in one-third of eyes with histologic lesions. Of these, 40% were attributed to inflammatory or neoplastic diseases associated with infectious agents. The most important infectious agents causing ocular disease in this study were feline leukemia virus, feline infectious peritonitis virus, and Cryptococcus sp. The most common ocular abnormalities associated with infectious agents were uveitis (anterior, posterior, or panuveitis), optic neuritis, and meningitis of the optic nerve. Ocular lesions secondary to systemic infections in cats are frequent; however, these are not always diagnosed because gross lesions are less common than histologic lesions. Therefore, both gross and histologic evaluation of the eyes of cats is recommended, mainly for cases in which the clinical suspicion or necropsy diagnosis suggests that an infectious agent might be related to the cause of death.

Background: Recent literature on neonatal anesthesia focuses on the importance of keeping physiology within the ranges of normality to improve the long-term neurological outcome. The Neonate and Children audit of Anesthesia pRactice IN Europe (NECTARINE) showed a derangement of one or more than one physiological parameters during anesthesia needing a medical intervention in 35.2% of 6592 anesthesia procedure performed in infants up to 60 weeks postmenstrual age. Methods: Subanalysis of the Italian NECTARINE cohort providing a snapshot of anesthesia management, incidence of clinical events requiring intervention during anesthesia, and morbidity and mortality at 30 and 90 days. Secondary aim was to compare outcomes between Italy and Europe. Results: Twenty-three Italian centers recruited 501 patients (63% male, 37% female) undergoing 611 procedures (441 surgical and 170 non-surgical) with a mean gestational age at birth of 38 weeks. Events requiring a medical intervention during anesthesia occurred in 177 cases (28.9%), lower than those reported in Europe (35.3%). The majority of events concerned episodes of cardiovascular instability, most commonly due to hypotension. The incidence of mortality at 30 days was 2.7%, consistent with the European incidence. Conclusions: Anesthetizing neonates is challenging. It is crucial that neonatal anesthesia practice is performed in specialized centers to maximize the potential positive outcome. We recommend a certification of quality for Institutions providing care for very young patients.

14 p.-4 fig.-3 tab., Background C3 glomerulopathy is a rare kidney disease, which makes it difficult to collect large cohorts of patients to better understand its variability. The aims of this study were to describe the clinical profiles and patterns of progression of kidney disease., Methods This was a retrospective, observational cohort study. Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. Study population was divided into clinical profiles by combining the following predictors: eGFR under/above 30 ml/min per 1.73 m2, proteinuria under/above 3.5 g/d, and histologic chronicity score under/above 4. The change in eGFR and proteinuria over time was evaluated in a subgroup with consecutive measurements of eGFR and proteinuria., Results One hundred and fifteen patients with a median age of 30 years (interquartile range 19–50) were included. Patients were divided into eight clinical profiles. Kidney survival was significantly higher in patients with a chronicity score, Conclusions Kidney survival is significantly higher in patients with a chronicity score, Work in this study was supported by the Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and PI19/1624, and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to MP), the Autonomous Region of Madrid (S2017/BMD-3673) (to MP). SRdeC is supported by Ministerio de Economia y Competitividad grant PID2019-104912RB-I00 y Autonomous Region of Madrid grant S2017/BMD-3673.

A new coronavirus, SARS-CoV-2, was identified at the end of 2019. It swiftly spread all over the world, affecting more than 600 million people and causing over 6 million deaths worldwide. Different COVID-19 vaccines became available by the end of 2020. Healthcare workers and more vulnerable people (such as the elderly and those with comorbidities) were initially prioritized, followed by the entire population, including pregnant and breastfeeding women. Despite the safety and efficacy of COVID-19 vaccines, a certain level of skepticism was expressed, including among pregnant and breastfeeding women. There were several reasons for this reluctancy, among them, fear of side-effects for both women and fetuses. Nevertheless, acceptance, as well as hesitancy, were time, country and vaccine specific. This review will collect available evidence assessing knowledge, attitudes, behaviour, practice and acceptance/hesitancy of pregnant/breastfeeding women in relation to the COVID-19 vaccination. The PubMed/MEDLINE, Scopus and EMBASE databases will be consulted. A predefined search strategy that combines both free text and MESH terms will be used. The systematic review will adhere to the PRISMA guidelines and the results will be reported in both narrative and summary tables. A meta-analysis will be conducted if data are available.

Este artigo apresenta um mapeamento da produção científica sobre as políticas públicas para a agricultura familiar, a partir da análise bibliométrica da literatura presentes na base Google Scholar. Ao demonstrar a evolução e o perfil bibliográfico dessa produção se verifica se tais publicações indicam a construção de um espaço coletivo capaz de socializar os conhecimentos já acumulados e, ao mesmo tempo, estimular novas teorias e abordagens. Foram analisadas 512 publicações científicas (trabalhos publicados em anais, artigos e livros) presentes na base de dados Google Scholar, no período de 1947 até 2021, vinculadas ao tema. Destacaram-se como resultados principais: a existência de três períodos com relação à evolução do número de publicações sobre o tema e a presença de autores e temas clássicos. Nas fases mais recentes observa-se grande aumento do número de autores, mas poucos autores têm centralidade e tem grande influência sobre os demais. Constatou-se uma dispersão expressiva quanto ás temáticas centrais, o que indica a inexistência de um campo específico de estudos, mas sugere o inicio de um caminho à construção de um coletivo de autores. Por fim, a pesquisa possibilitou um retrato amplo e multifacetado do tema políticas públicas para a agricultura familiar no Brasil.

Covid-19 restrictions in Italy have significantly reduced the ‘in-presence’ time spent with classmates and teachers. As a result, this new way of relating to one another has challenged many students by increasing anxiety and depression. In such reality, protective factors such as sense of belonging (SB) and Grit (GR) can reduce anxiety (ANX). Considering the pandemic context, the scope of this study is to explore the relationship between SB/GR and ANX, as a risk factor and to understand whether the relationship between these variables changes based on students’ grade level (GL): middle school (MS) versus high school (HS). For this purpose, a total of 451 students from North/Central Italy, 71% F (M=15.07, ±2.46), of which 266 from HS, answered an online questionnaire in Spring 2021. Data was analyzed by doing a correlation analysis, difference between groups based on GL and hierarchical regression with SPSS 27. Results for the correlation analysis confirm that SB and GR are positively related; when controlling for differences in GL via t-test analysis, SB and GR are higher for MS. When measuring the SB/GR (Panorama Education, 2016) and its impact on the state of ANX (Spielberger et al., 1983) via the hierarchical regression, SB/GR decrease while ANX increases in particular for HS students. These results highlight that anxiety has had a greater impact specially on HS students. For these reasons we encourage schools to create environments in which they find strategies, as a community, to assist students in developing a sense of belonging and grit.

Pancreatic ductal adenocarcinoma (PDAC) harbouring germline BRCA1-2 pathogenic variants (gBRCA1-2pv) is a distinct nosological entity. Information on second-line therapy (2LT) outcome in this setting is lacking.Data of gBRCA1-2pv metastatic PDAC patients treated with chemotherapy were collected. A primary analysis of 2LT RECIST response, median progression-free survival (mPFSEighty-four gBRCA1-2pv metastatic PDAC patients were enrolled. The primary analysis, including 43 patients, highlighted a significant improvement of mPFSThis study highlighted the beneficial role of platinum agents in gBRCA1-2pv PDAC patients also in second-line treatment setting. However, our data suggest that early use of 3- and 4-drug platinum-based chemotherapy combinations provides a survival outcome advantage.

Background: Hypertrophic pyloric stenosis in otherwise healthy neonates frequently requires urgent surgical procedure but anaesthesia care may result in respiratory complications, such as hypoxaemia, pulmonary aspiration of gastric contents, and postoperative apnoea. The primary aim was to study whether or not the incidence of difficult airway management and of hypoxaemia in neonates undergoing pyloric stenosis repair was higher than that in neonates undergoing other surgeries. Methods: Data on neonates and infants undergoing anaesthesia and surgery for pyloric stenosis were extracted from the NEonate and Children audiT of Anesthesia pRactice In Europe (NECTARINE) database, for secondary analysis. Results: We identified 310 infants who had anaesthesia for surgery for pyloric stenosis. Difficult airway management (more than two attempts at laryngoscopy) was higher in children with pyloric stenosis when compared with the entire NECTARINE cohort (7.9% [95% confidence interval {CI}, 5.22–11.53] vs 4.4% [95% CI, 1.99–6.58]; relative risk [RR]=1.81 [95% CI, 1.21–2.69]; P=0.004), whereas transient hypoxaemia with oxygen saturation

Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single-nucleotide polymorphism rs55705857, which confers a sixfold greater risk of isocitrate dehydrogenase ( IDH) –mutant low-grade glioma (LGG). We reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the Myc promoter and increased Myc expression. Mutating the orthologous mouse rs55705857 locus accelerated tumor development in an Idh1 R132H -driven LGG mouse model from 472 to 172 days and increased penetrance from 30% to 75%. Our work reveals mechanisms of the heritable predisposition to lethal glioma in ~40% of LGG patients.

Objectives: Sexually transmitted infections are a prevalent global health care problem. Treatment guidelines have recently been updated as a result of antimicrobial resistance and public health trends. The aim of the study was to assess the appropriateness of empirical antibiotic therapy prescribed for cervicitis and urethritis in the emergency department. Methods: We designed a retrospective observational cohort study. We included adult patients with suspected cervicitis or urethritis who attended the emergency department of a tertiary hospital in 2020. We excluded patients with suspected pelvic inflammatory disease, pregnancy or prostatitis and those requiring admission to hospital. Appropriateness of empirical antibiotic therapy was evaluated taking into account 4 aspects: indication, dosing, duration of therapy, and route of administration. Data were obtained from the electronic medical record, the electronic prescription program, and the discharge summary. Results: The study population comprised 176 patients; mean age was 28.9 years (SD = 7.7), and 90.9% were men. The most prescribed treatment was the combination of ceftriaxone and azithromycin (83.0%). Treatment was inappropriate in 71.6% of patients. A total of 159 drug errors were recorded. The most frequent cause was undertreatment (36.4%) related to underdosing (46.5%), particularly with regard to ceftriaxone. The percentage of errors was 11.9% for indication, 84.9% for dosing, 3.1% for duration, and 0% for route of administration. Conclusions: A high percentage of patients who attended the emergency department for suspected cervicitis or urethritis received an inappropriate empirical antibiotic regimen. The main reason was undertreatment due to underdosing.

Cancer Biomarkers are the key to unlocking the promise of precision oncology, selecting which patients will respond to a more personalised treatment while sparing non-responders the therapy-related toxicity. In this paper, we highlight the primacy of cancer biomarkers, but focus on their importance to patients and to health systems. We also highlight how cancer biomarkers represent value for money. We emphasise the need for cancer biomarkers infrastructure to be embedded into European health systems. We also highlight the need to deploy multiple biomarker testing to deliver the optimal benefit for patients and health systems and consider cancer biomarkers from the perspective of cost, value and regulation. Cancer biomarkers must also be situated in the context of the upcoming In Vitro Diagnostics Regulation, which may pose certain challenges (e.g. non-compliance of laboratory developed tests, leading to cancer biomarker shortages and increased costs) that need to be overcome. Cancer biomarkers must be embedded in the real world of oncology delivery and testing must be implemented across Europe, with the intended aim of narrowing, not widening the inequity gap for patients. Cancer patients must be placed firmly at the centre of a cancer biomarker informed precision oncology care agenda.

O empreendedorismo é um tema que ocupa a agenda de pesquisa de diversas áreas do conhecimento e que se materializa como fenômeno em permanente reconfiguração. Presente na literatura desde meados do século XIX, vem ganhando novas dimensões e abordagens analíticas desde as décadas finais do século XX, em razão da própria importância do empreendedorismo para o desenvolvimento econômico das nações. Em contraponto, não poucos autores vêm identificando certa banalização do tema, por vezes apresentado como solução mágica para garantir ou gerar trabalho e renda. Nesse contexto, este artigo busca contribuir com o conhecimento, apontando os enfoques predominantes e os caminhos mais relevantes observados na literatura recente. Para a sua realização, partiu-se do levantamento dos estudos mais clássicos sobre o tema, com a posterior incorporação da literatura mais recente, em periódicos nas bases Scopus e Web of Science. A pesquisa bibliográfica identificou forte tendencia multidimensional do tema, com os seguintes enfoques predominantes: econômico, sociológico, cultural e comportamental, gerencial ou administrativo e educacional. Embora a abordagem e o alcance do artigo não possibilitem respostas definitivas, fica claro que a influência das mudanças históricas pelas quais vêm passando as condições de produção do capitalismo podem ser fatores indicativos da diversidade e da multidimensionalidade do conceito e de tipos de empreendedorismo, que vão se reconfigurando historicamente.

Background. Cancer patients are among the main consumers of traditional, complementary, integrative, and alternative medicine (TCIM) such as natural products (herbals, integrators, etc.) and mind and body practices (yoga, acupuncture, etc.). Methods. A questionnaire on TCIM was submitted to 415 Italian cancer patients. The questionnaire consisted of three sections: (i) biographical and clinical information; (ii) use of natural substances; and (iii) use of mind-body practices. Results. 406 patients completed the questionnaire. The prevalence of TCIM use was 72.3%. Of them, 75.6% started to use TCIM after a tumor diagnosis. The main reasons for using TCIM were to mitigate side effects (65.0%), to regain physical and mental balance (35.9%), to relieve pain (18.3%), and to improve the efficacy of cancer therapy (16.0%). 44.7% of patients taking natural products used them during conventional therapies (chemotherapy, radiotherapy, etc.), and in 67.5% of cases without consulting a doctor. As a consequence, only about 50% of patients taking natural substances used these compounds appropriately, and the most common errors were related with the purpose of reducing the side effects of the therapy (52.3%) and for boosting immune system (32.1%). Conclusions. There is an impelling need to provide patients with scientifically validated information to raise awareness about the benefits and risks of using TCIM.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder displaying the modification of complex human behaviors, characterized by social interaction impairments, stereotypical/repetitive activities and emotional dysregulation. In this study, fecal microbiota transplant (FMT) via gavage from autistic children donors to mice, led to the colonization of ASD-like microbiota and autistic behaviors compared to the offspring of pregnant females exposed to valproic acid (VPA). Such variations seemed to be tightly associated with increased populations of Tenericutes plus a notable reduction (p 0.001) of Actinobacteria and Candidatus S. in the gastrointestinal region of FMT mice as compared to controls. Indeed altered behaviors of FMT mice was reported when evaluated in the different maze tests (light dark, novel object, three chamber tests, novel cage test). Contextually, FMT accounted for elevated expression levels of the pro-inflammatory factors IL-1β, IL-6, COX-1 and TNF-α in both brain and small intestine. Villous atrophy and inflammatory infiltration (Caspase 3 and Ki67) were increased in the small intestine of FMT and VPA mice compared to controls. Moreover, the observed FMT-dependent alterations were linked to a decrease in the methylation status. Overall, findings of the present study corroborate a key role of gut microbiota in ASD. However, further investigations are required before any possible manipulation of gut bacteria with appropriate diets or probiotics can be conducted in ASD individuals.

Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n=36) and relapsed (n=27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.

Objectives: Here, we aim at describing the pattern of care, survival outcome and prognostic factors of ABC patients (pts) receiving third-line chemotherapy. Methods: Institutional registries across three academic medical centers were retrospectively reviewed. Kaplan–Meier estimators were used to calculate survival, the log-rank test to make comparisons, and the Cox proportional hazard models to assess the progostic impact of variables. Results: Among 101 pts included in the analysis. 68 (67.3%), 19 (18.8%) and 14 (13.8%) had intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, respectively. Atotal of 63 (62.3%) pts received monochemotherapy, while 38 (37.6%) were treated with adoublet. The median OS and PFS were 5 and 3 months, respectively. Disease control rate was achieved in 23 (22.7%) pts, with 2 (2%) partial responses. Grade 3–4 treatment-related adverse events were reported in 22 (21.7%) pts. At multivariate analysis, ECOG PS (p

Background: Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent liver cancer. The overall survival of iCCA and other biliary tract cancers (BTC) remains poor. Recently, the ABC-06 trial reported the superiority of FOLFOX vs clinical observation as a second-line treatment. Still, the survival benefit was less than expected. We hypothesized that the pattern of progression of iCCA can drive post-progression survival (PPS), similar to hepatocellular carcinoma. Methods: Multicentre retrospective evaluation of consecutive iCCA patients who progressed after frontline systemic treatment with gemcitabine as monotherapy or in combination with platinum. Radiological assessment of progression was evaluated according to RECIST 1.1. The progression pattern was divided according to the presence/absence of new extrahepatic lesions (NEH). Results: We included 206 patients from 5 centres. The median OS was 14.1months and its independent predictors (hazard ratio [HR], 95% confidence interval [CI]) were previous surgery 0.699 [0.509-0.961], performance status >2.445 [1.788-3.344], permanent first-line discontinuation 16.072 [5.102-50.633], registration of ascites 2.226 [1.448-3.420] or bilirubin >3mg/dl 3.004 [1.935-4.664] during the follow-up, and disease progression 2.523 [1.261-5.050]. The appearance of NEH independently predicted OS 2.18 [1.55-3.06] in patients with radiological progression. Amongst 138 patients eligible for second-line treatment, PPS was 16.8 and 5.9months in cases without and with NEH, respectively (P=.001). Progression owing to NEH lesions was an independent predictor of PPS 1.873 [1.333-2.662], together with performance status, time to progression to the frontline treatment, bilirubin >3mg/dl and ascites. Conclusions: PPS of iCCA is influenced by progression pattern, with important implications for second-line trial design and analysis.

COVID-19 survivors are at increased risk of persistent psychopathology after the infection. Despite long-term sequelae are an increasing concern, long-term neuropsychiatric consequences remain largely unclear. This cohort study aimed at investigating the psychopathological impact of COVID-19 in Italy one year after infection, outlining the trajectory of symptomatology at one, six-, and twelve-months follow-up. We evaluated 402, 216, and 192 COVID-19 survivors respectively at one, six, and 12 months. A subgroup of 95 patients was evaluated longitudinally both at one, six, and 12 months. Validated self-report questionnaires were administered to assess depression, fatigue, anxiety, and post-traumatic distress. Socio-demographics and setting of care information were gathered for each participant. At six and twelve months, respectively 94 (44%) and 86 (45%) patients self-rated in the clinical range in at least one psychopathological dimension. Pathological fatigue at twelve months was detected in 63 patients (33%). Considering the longitudinal cohort an interaction effect of sex and time was observed for depression (F = 8.63, p < 0.001) and anxiety (F = 5.42, p = 0.005) with males showing a significant increasing trend of symptoms, whereas an opposite course was observed in females. High prevalence of psychiatric sequelae six and 12 months after COVID-19 was reported for the first time. These findings confirm the need to provide integrated multidisciplinary services to properly address long-lasting mental health sequelae of COVID-19 and to treat them with the aim of reducing the disease burden and related years of life lived with disability.

Invited talk about double-barred galaxiesfor the conference "Galactic bars: driving and decoding galaxy evolution" (Granada, 3-7 July, 2023).

Background and aimsTo investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).MethodsWe conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU)admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.ResultsWe identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with ahigher likelihood of ICU admission, need ofMV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need ofMV and ICU admission, respectively.ConclusionsBlood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

Re-emerging arboviruses represent a serious health problem due to their rapid vector-mediated spread, mainly in urban tropical areas. The 2013–2015 Zika virus (ZIKV) outbreak in South and Central America has been associated with cases of microcephaly in newborns and Guillain–Barret syndrome. We previously showed that the conjugate gallic acid—Hecate (GA-FALALKALKKALKKLKKALKKAL-CONH2)—is an efficient inhibitor of the hepatitis C virus. Here, we show that the Hecate peptide is degraded in human blood serum into three major metabolites. These metabolites conjugated with gallic acid were synthesized and their effect on ZIKV replication in cultured cells was evaluated. The GA-metabolite 5 (GA-FALALKALKKALKKL-COOH) was the most efficient in inhibiting two ZIKV strains of African and Asian lineage at the stage of both virus entry (virucidal and protective) and replication (post-entry). We also demonstrate that GA-metabolite 5 does not affect cell growth after 7 days of continuous treatment. Thus, this study identifies a new synthetic antiviral compound targeting different steps of ZIKV replication in vitro and with the potential for broad reactivity against other flaviviruses. Our work highlights a promising strategy for the development of new antivirals based on peptide metabolism and bioconjugation.

Este trabalho aborda a inter-relação entre Direito e Economia, com foco nas implicações das políticas econômicas na concretização dos direitos sociais. Através de uma abordagem interdisciplinar, analisa-se a influência mútua entre essas áreas do conhecimento, identificando casos práticos de conflito ou harmonia entre interesses econômicos e direitos sociais. O estudo busca refletir sobre possíveis soluções para conciliar objetivos econômicos e a promoção dos direitos sociais. Utiliza-se metodologia de revisão bibliográfica e análise de textos acadêmicos, com o objetivo de contribuir para uma compreensão mais ampla e aprofundada dessa relação complexa.&nbsp

BackgroundTwo years after the outbreak of the pandemic, several studies look at the consequences for the well-being and mental health of young people. In particular, creativity and resilience are cited in the scientific literature as resources that promote this well-being in adolescents and young adults.PurposeThis mini-literature review was created with the aim of examining how many articles have explored the relationship between creativity and resilience in adolescents and young adults since the onset of the pandemic.MethodsParticular attention was paid to how many of the articles actually related to the consequences of the pandemic, in which country they were published, their target population, and the models, instruments and variables used to analyze them.ResultsOnly 4 articles emerged from the screening, of which only one was actually related to pandemic consequences. All articles were published in Asian countries with a target group of university students. Three of the articles used mediation models to examine the relationship between resilience as an independent variable and creativity as a dependent variable. All articles used self-assessment instruments for creativity and resilience, both at the individual and group level.SignificanceThis mini-review offers us the opportunity to reflect on the lack of studies that have addressed the issue of youth resources in the form of creativity and resilience since the beginning of the pandemic. The results show us a still underdeveloped interest in creativity in the scientific literature, in contrast to what the media reports on the promotion of creativity in daily life.

The Astronomy and Education project offers students the opportunity to participate in activities related to teaching and dissemination in Astronomy. Among the objectives presented in this perspective are: consolidate and expand scientific knowledge in the Guarapuava community; contribute to the improvement of the student's scientific learning; promoting nocturnal observation schedules; provide didactic material for lectures and practical workshops containing theoretical concepts appropriate to the student's level of education. These activities were: nocturnal observations with telescopes, as a way to reduce the distance between the student and Astronomy. Observations were made in several educational spaces, in addition to the university; speeches and exhibitions. With that it was intended to stimulate and awaken in the students, both university students and elementary and high school, scientific vocations and provide an increase in interest in Astronomy. By engaging in the design of project activies, it is expected to encourage students to expand their horizons of knowledge, as well as to bring positive results to the school comunity.

D-Xylose, a major constituent of plant biomass and second most abundant sugar on Earth, holds a considerable potential as a substrate for sustainable bio-production. Pseudomonas putida KT2440 is an attractive bacterial host for valorizing biogenic feedstocks but lacks a xylose utilization pathway. While several attempts to engineer P. putida for growth on xylose have been reported, a comprehensive understanding of xylose metabolism in this bacterium is lacking, hindering its further improvement and rational tailoring for specific biotechnological purposes. In this study, we elucidated the xylose metabolism in the genome-reduced P. putida strain, EM42, endowed with xylose isomerase pathway (xylAB) and transporter (xylE) from Escherichia coli and used the obtained knowledge in combination with adaptive laboratory evolution to accelerate the bacterium’s growth on the pentose sugar. Carbon flux analyses, targeted gene knock-outs, and in vitro enzyme assays portrayed xylose assimilation in P. putida and confirmed a partially cyclic upper xylose metabolism. Deletion of the local transcriptional regulator gene hexR de-repressed genes of several key catabolic enzymes and reduced the lag phase on xylose. Guided by metabolic modeling, we augmented P. putida with additional heterologous pentose phosphate pathway genes and subjected rationally prepared strains to adaptive laboratory evolution (ALE) on xylose. The descendants showed accelerated growth and reduced growth lag. Genomic and proteomic analysis of engineered and evolved mutants revealed the importance of a large genomic re-arrangement, transaldolase overexpression, and balancing gene expression in the synthetic xylABE operon. Importantly, omics analyses found that similar growth characteristics of two superior mutants were achieved through distinct evolutionary paths. This work provides a unique insight into how cell metabolism adjusts to a non-native substrate; it highlights the remarkable genomic and metabolic plasticity of P. putida and demonstrates the power of combining knowledge-driven engineering with ALE in generating desirable microbial phenotypes.HighlightsElucidated xylose catabolism via exogenous isomerase pathway inP. putidaEM42.Deletion of transcriptional regulator HexR improved growth on xylose.Knowledge-guided interventions and adaptive evolution accelerated growth.Omics analyses of selected mutants highlighted the genomic and metabolic plasticity ofP. putida.Two mutants with superior characteristics emerged from distinct evolutionary paths.

Heart failure (HF) is associated with a reduction of skeletal muscle mass. Whey protein isolate (WPI) has been beneficial in increasing muscle mass and strength, in addition to improving body composition. The goal of this research was to evaluate the effect of WPI on the body composition, muscle mass, and strength of chronic HF patients. For this purpose, twenty-five patients of both genders with predominantly NYHA I functional class and a median age of 65.5 (60.5–71.0) years were used to conduct a randomized, single-blind, placebo-controlled clinical trial and received 30 g per day of WPI for 12 weeks. Anthropometric measurements, body composition analysis, and biochemical exams were performed at the beginning and end of the study. An increase in skeletal muscle mass was observed in the intervention group after 12 weeks. A reduction in waist circumference, body fat percentage, and an increase in skeletal muscle index was observed when compared to the placebo group. No significant effect on muscle strength was observed after 12 weeks of intervention. These data demonstrate that WPI consumption contributed to the increase of skeletal muscle mass, strength, and reduction of body fat in HF patients.

Seismo-electromagnetic signals are electromagnetic signals generated by the propagation of a seismic wave in a porous media containing fluids (Gao & Hu, 2010).These signals can potentially provide useful information on the poro-elastic media and the hosted fluids (Garambois & Dietrich, 2002).Thus, there has been a growing interest in the study of SES in recent years, due to their potential.Researchers are focusing both on modelling and analysis of both passive and active experiments to investigate the characteristics of these signals (e.g. Honkura et al., 2000; Matsushima et al., 2002; Warden et al., 2013; Gao et al., 2016; Balasco et al., 2014; Dzieran et al., 2019).Passive experiments involve the observation and analysis of naturally occurring SES triggered by earthquakes, while active experiments involve the controlled generation of these signals using seismic source.The aim of our work is to present the results deriving from the analysis of SES recorded with both approaches. As for the passive one, the data set consists of the time series recorded by two magnetotelluric stations in continuous monitoring, co-located with two seismic stations, in seismically active areas of Southern Italy (the Gargano promontory and the Agri valley).As for the active one, the data set derives by an active seismic experiment carried out in the caldera of the Phlegrean Fields, the Italian super-volcano.

European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (ECBP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light onto how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation.

Simple Summary Immunotherapy has revolutionized the management of cancer by improving outcomes of triple-negative breast cancer (TNBC). Recently, programmed death-ligand 1 (PD-L1), was identified as a target for TNBC and several preclinical and clinical trials are currently focusing on combinatorial treatments of immunomodulatory mAbs with chemotherapy, radiotherapy, or other mAbs. Here, we tested in in vitro models novel combinations of immunomodulatory mAbs on TNBC cell lines and on cardiomyocytes, in comparison with the mAbs approved by FDA for cancer therapy, in order to identify at early stages the more potent anti-cancer combinations endowed with low or no cardiotoxic side effects. Abstract Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by a higher mortality rate among breast cancer subtypes. Poly(ADP-ribose) polymerase (PARP) inhibitors are used in clinics to treat a subgroup of TNBC patients, but other targeted therapies are urgently needed. Programmed death-ligand 1 (PD-L1), involved in tumor immune escape, was recently identified as a target for TNBC; accordingly, the anti-PD-L1 monoclonal antibody (mAb), atezolizumab, has been approved by FDA in combination with Paclitaxel for the therapy of metastatic TNBC. Here, we tested novel combinations of fully human immunomodulatory mAbs, including anti-PD-L1 mAbs generated in our laboratory and atezolizumab, on TNBC and other tumor cell lines. We evaluated their anti-tumor efficacy when used as single agents or in combinatorial treatments with anti-CTLA-4 mAbs in in vitro co-cultures of hPBMCs with tumor cells, by measuring tumor cell lysis and IL-2 and IFNγ cytokines secretion by lymphocytes. In parallel, by using co-cultures of hPBMCs and cardiomyocytes, we analyzed the potential cardiotoxic adverse side effects of the same antibody treatments by measuring the cardiac cell lysis and the secretion of pro-inflammatory cytokines. We identified novel combinations of immunomodulatory mAbs endowed with more potent anti-cancer activity on TNBC and lower cardiotoxic side effects than the combination of atezolizumab and ipilimumab.

Sin resumen.