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Luigino Dal Maso,1 Armando Santoro,2,3 Elisabetta Iannelli,4,5 Paolo De Paoli,6 Carla Minoia,7 Monica Pinto,8 Alexia Francesca Bertuzzi,3 Diego Serraino,1 Roberta De Angelis,9 Annalisa Trama,10 Riccardo Haupt,11 Gabriella Pravettoni,12,13 Maria Perrone,14 Francesco De Lorenzo,4,5 Paolo Tralongo15 On behalf of the Alliance Against Cancer (ACC) Survivorship Care and Nutritional Support Working Group1Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 2Department of Biomedical Sciences, Humanitas University, Milan, Italy; 3IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy; 4Italian Federation of Cancer Patients Organisations (FAVO), Rome, Italy; 5Italian Association of Cancer Patients (Aimac), Rome, Italy; 6Alleanza Contro il Cancro, Rome, Italy; 7SC Haematology, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy; 8Rehabilitation Medicine Unit, Strategic Health Services Department, Istituto Nazionale Tumori-IRCCS Fondazione G. Pascale, Naples, Italy; 9Department of Oncology and Molecular Medicine, Italian National Institute of Health (ISS), Rome, Italy; 10Evaluative Epidemiology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy; 11DOPO Clinic, Department of Pediatric Haematology/Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy; 12Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; 13Applied Research Division for Cognitive and Psychological Science, IEO European Institute of Oncology IRCCS, Milan, Italy; 14Psychology Unit, IRCCS Regina Elena Cancer Institute, Rome, Italy; 15Medical Oncology Unit, Umberto I Hospital, Department of Oncology, RAO, Siracusa, ItalyCorrespondence: Luigino Dal Maso, Epidemiologia Oncologica, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via Franco Gallini 2, Aviano (PN), 33081, Italy, Tel +39 0434 659354, Email epidemiology@cro.it Paolo Tralongo, Medical Oncology Unit, Umberto I Hospital, Department of Oncology, RAO, Via Giuseppe Testaferrata 1, Siracusa, 96100, Italy, Tel +39 0931 724 464, Email paolo.tralongo@asp.sr.itAbstract: A multidisciplinary panel of experts and cancer patients developed a position paper to highlight recent evidence on “cancer cure” (ie, the possibility of achieving the same life expectancy as the general population) and discuss the consequences of this concept on follow-up and rehabilitation strategies. The aim is to inform clinicians, patients, and health-care policy makers about strategies of survivorship care for cured cancer patients and consequences impacting patient lives, spurring public health authorities and research organizations to implement resources to the purpose. Two identifiable, measurable, and reproducible indicators of cancer cure are presented. Cure fraction (CF) is > 60% for breast and prostate cancer patients, > 50% for colorectal cancer patients, and > 70% for patients with melanoma, Hodgkin lymphoma, and cancers of corpus uteri, testis (> 90%), and thyroid. CF was > 65% for patients diagnosed at ages 15– 44 years and 30% for those aged 65– 74 years. Time-to-cure was consistently < 1 year for thyroid and testicular cancer patients and < 10 years for patients with colorectal and cervical cancers, melanoma, and Hodgkin lymphoma. The working group agrees that the evidence allows risk stratification of cancer patients and implementation of personalized care models for timely diagnosis, as well as treatment of possible cancer relapses or related long-term complications, and preventive measures aimed at maintaining health status of cured patients. These aspects should be integrated to produce an appropriate follow-up program and survivorship care plan(s), avoiding stigma and supporting return to work, to a reproductive life, and full rehabilitation. The “right to be forgotten” law, adopted to date only in a few European countries, may contribute to these efforts for cured patients.Keywords: cancer cure, survivorship, time-to-cure, personalized care models, right to be forgotten

Roberto Burro,1 Ugo Savardi,1 Maria Antonietta Annunziata,2 Paolo De Paoli,2 Ivana Bianchi3 1Department of Human Sciences, University of Verona, 37129 Verona, Italy; 2National Cancer Institute IRCCS “Centro di Riferimento Oncologico” (CRO), 33080 Aviano (PN), Italy; 3Department of Humanities (section Philosophy and Human Sciences), University of Macerata, 62100 Macerata, Italy Background: Healthcare staff should be aware of the importance that patients may attach to the words that are used to convey information. This is relevant in terms of the patients’ understanding. Modeling how people understand the information conveyed in a medical context may help health practitioners to better appreciate the patients’ approach. Purpose: 1) Analyze the participants’ self-reported perception of the type of information provided in an oncological scenario in terms of three dimensions: impairment to their health, risks associated with the disease itself and commitment required to undergo the treatment; and 2) show the benefits of using Rasch scaling for the analysis of the data. Starting from a survey, Rasch scaling produces a unidimensional logit-interval scale relating to the extent to which each item conveys a latent dimension. These were related to structure, in particular concerning communication by means of opposite vs. unipolar language. Subjects and methods: The participants rated 82 items of information in a questionnaire regarding their perception of impairment to their health (H) and the risks (R) and commitment relating to the treatment prescribed (T). Results: The scaling produced an item bank for healthcare staff to consult in order to estimate the importance the recipient would be likely to attach to the vocabulary used and the likely impact of the information in terms of the patient’s condition. Furthermore, the use of opposites was generally associated with a clearer impression of whether the information given was generally only very negative or slightly negative, whereas ‘neutral’ information was often perceived as being very negative. Actual findings: Is possible to estimate people’s understanding more precisely (in terms of H, R and T) which can help healthcare practitioners to modulate the way they convey information. Limitations: The participants in the study were healthy volunteers and the context was simulated. Keywords: Rasch model, simulated oncological scenario, perceived severity of impairment to health, perception of risk, perceived commitment to the treatment, opposites

Roberto Burro,1 Ugo Savardi,1 Maria Antonietta Annunziata,2 Paolo De Paoli,2 Ivana Bianchi3 1Department of Human Sciences, University of Verona, Verona, Italy; 2National Cancer Institute IRCCS ‘Centro di Riferimento Oncologico’ (CRO), Aviano, Italy; 3Department of Humanities (Section Philosophy and Human Sciences), University of Macerata, Macerata, Italy Background: An extensive body of literature has demonstrated that many patients who have been asked to participate in clinical trials do not fully understand the informed consent forms. A parallel independent study has demonstrated that opposites have a special status in human cognitive organization: they are common to all-natural languages and are intuitively and naturally understood and learnt.Purpose: The study investigates whether, and how, the use of opposites impacts on doctor–patient communication: does using the terms “small–large” to describe a nodule (ie, bipolar communication) rather than speaking in terms of centimeters (ie, unipolar communication) affect a patient’s understanding of the situation? And is it better to speak of “common–rare” side effects (ie, bipolar communication) instead of the number of people who have suffered from particular side effects (ie, unipolar communication)?Methods: Two questionnaires were created and used, one presenting the information in terms of opposites (ie, bipolar communication) and another using unipolar communication.Results: The participants’ perception of their situation (in terms of feeling healthy–ill, being at high–low risk, and their treatment requiring high–low commitment) varied in the two conditions. Moreover, self-reported levels of understanding and satisfaction with how the information was communicated were higher when opposites were used.Limitations: Since this is the first study that addresses the merits of using bipolar structures versus unipolar structures in doctor–patient communication, further work is needed to consolidate and expand on the results, involving not only simulated but also real diagnostic contexts.Conclusion: The encouraging results imply that further testing of the use of opposites in informed consent forms and in doctor–patient communication is strongly advisable. Keywords: opposites, bipolar, unipolar, informed consent, doctor–patient communication, understanding, satisfaction

Enriching geospatial data, particularly through address geocoding, is fundamental to many geospatial analytical solutions, facilitating resource allocation, accessibility assessment, and urban development planning. This paper explores the address geocoding approaches from traditional GIS-based methods to advanced data-driven solutions, emphasising their accuracy, efficiency, and complementarity. Geospatial data enrichment challenges are explored using the SemTUI framework and QGIS platform. SemTUI employs a data-driven approach that facilitates interactive semantic enrichment and address reconciliation. QGIS is utilised for address geocoding, using the MMQGIS plugin with two geocoding web services provided by OSM and Google. The comparison between SemTUI and QGIS workflows highlights their complementary strengths. SemTUI offers intuitive interfaces and an automated solution, while QGIS provides advanced geospatial visualisation and analysis capabilities. Practical applications in supply-demand analysis of social amenities and walkability index calculation demonstrate the significance of geocoding in urban planning. Further research efforts are focused on enhancing the integration between SemTUI and QGIS to improve the precision and performance of address geocoding and further spatial data analysis.

Abstract The growth factor Neuregulin-1 (NRG1) has pleiotropic roles in proliferation and differentiation of the stem cell niche in different tissues. It has been implicated in gut, brain and muscle development and repair. Six isoform classes of NRG1 and over 28 protein isoforms have been previously described. Here we report a new class of NRG1, designated NRG1-VII to denote that these NRG1 isoforms arise from a myeloid-specific transcriptional start site (TSS) previously uncharacterized. Long-read sequencing was used to identify eight high-confidence NRG1-VII transcripts. These transcripts presented major structural differences from one another, through the use of cassette exons and alternative stop codons. Expression of NRG1-VII was confirmed in primary human monocytes and tissue resident macrophages and induced pluripotent stem cell-derived macrophages (iPSC-derived macrophages). Isoform switching via cassette exon usage and alternate polyadenylation was apparent during monocyte maturation and macrophage differentiation. NRG1-VII is the major class expressed by the myeloid lineage, including tissue-resident macrophages. Analysis of public gene expression data indicates that monocytes and macrophages are a primary source of NRG1. The size and structure of class VII isoforms suggests that they may be more diffusible through tissues than other NRG1 classes. However, the specific roles of class VII variants in tissue homeostasis and repair have not yet been determined.

Not available.

RESUMO: A partir de pesquisas nacionais e internacionais do período de 1943 a 2022, este manuscrito teve por objetivo discutir perspectivas de inclusão de pessoas autistas em aulas de ciências. Trata-se de uma investigação bibliográfica que resultou em 19 artigos (oito nacionais e 11 internacionais) submetidos a uma análise sob orientação teórico-metodológica da Teoria Histórico-Cultural e do Materialismo Histórico-Dialético. Percebemos que, majoritariamente, as pesquisas de intervenção pedagógica ocorreram em salas de Atendimento Educacional Especializado sem a relação com os pares da sala de aula comum. Muitas delas como ações pedagógicas estanques sem uma proposta articulada e continuada em projetos escolares. Identificamos poucas justificativas acerca do ensino de conhecimentos de ciências em contribuições para a superação de interrupções explicitadas - a dificuldade de pessoas com autismo em relação a comunicação e vínculos sociais. Apontamos a necessidade de ampliação de investigações na área de ensino de ciências com estudantes no espectro autista.

Alicerçados na Teoria Histórico-Cultural, objetivamos analisar as contribuições de intervenções em aulas de ciências no ensino de estudantes autistas em processos inclusivos. Em nossa investigação, no período de 1943 até 2022, identificamos 19 trabalhos (oito nacionais e 11 internacionais) que desenvolveram ações pedagógicas na Educação Básica em aulas de ciências com estudantes autistas em escolas comuns. A partir das contribuições dos artigos e referenciais teóricos, defendemos que a organização de atividades de estudos, em aulas de ciências, articuladas em projetos de inclusão escolar que integram o(a) estudante autista em múltiplas experiências sociais, pode se beneficiar de conhecimentos científicos como uma ferramenta importante para promover a ampliação da comunicação, com ou sem fala, e para fomentar o desenvolvimento da consciência do mundo e de si, além de aprimorar a compreensão do que significa ser autista e assumir protagonismos. Convidamos as pesquisas da área a aprofundarem e ampliarem as contribuições.

Abstract Background A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating. Knowing which tools are most effective remains unclear. To evaluate the performance of computational methods, and to encourage innovation in method development, we designed a Critical Assessment of Genome Interpretation (CAGI) community challenge to place variant prioritization models head-to-head in a real-life clinical diagnostic setting. Methods We utilized genome sequencing (GS) data from families sequenced in the Rare Genomes Project (RGP), a direct-to-participant research study on the utility of GS for rare disease diagnosis and gene discovery. Challenge predictors were provided with a dataset of variant calls and phenotype terms from 175 RGP individuals (65 families), including 35 solved training set families with causal variants specified, and 30 unlabeled test set families (14 solved, 16 unsolved). We tasked teams to identify causal variants in as many families as possible. Predictors submitted variant predictions with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on the rank position of causal variants, and the maximum F-measure, based on precision and recall of causal variants across all EPCR values. Results Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performers recalled causal variants in up to 13 of 14 solved families within the top 5 ranked variants. Newly discovered diagnostic variants were returned to two previously unsolved families following confirmatory RNA sequencing, and two novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant in an unsolved proband with phenotypes consistent with asparagine synthetase deficiency. Conclusions Model methodology and performance was highly variable. Models weighing call quality, allele frequency, predicted deleteriousness, segregation, and phenotype were effective in identifying causal variants, and models open to phenotype expansion and non-coding variants were able to capture more difficult diagnoses and discover new diagnoses. Overall, computational models can significantly aid variant prioritization. For use in diagnostics, detailed review and conservative assessment of prioritized variants against established criteria is needed.

In this manuscript I build upon an initial body of research developing procedures for leveraging large language models (LLMs) in qualitative data analysis, by carrying out thematic analysis (TA) with LLMs. TA is used to identify patterns by means of initial labelling of qualitative data followed by the organisation of the labels/codes by themes. First, I propose a new set of LLM prompts for initial coding and generation of themes. These new prompts are different from the typical prompts deployed for such analysis in that they are entirely open-ended and rely on TA language. Second, I investigate the process of removing duplicate initial codes through a comparative analysis of the codes of each interview against a cumulative codebook. Third, I explore the construction of thematic maps from the themes elicited by the LLM. Fourth, I evaluate the themes produced by the LLM against the themes produced manually by humans. For conducting this research, I employed a commercial LLM via an application program interface (API). Two datasets of open access semi-structured interviews were analysed to demonstrate the methodological possibilities of this approach. I conclude with practical reflections on performing TA with LLM, enhancing our knowledge of the field.

RESUMO Este ensaio teórico teve por objetivo identificar contribuições da organização do conhecimento científico na sistematização do ensino em ciências, para a constituição humana típica e atípica. Isso foi realizado a partir de ponderações entre textos da área de Ensino de Ciências e pressupostos da Teoria Histórico-Cultural. Assim, apresentamos reflexões acerca de discussões que polarizam a educação de pessoas com deficiência ou autismo no direcionamento curricular, em relação às habilidades funcionais e acadêmicas. A partir da análise de limitações, possibilidades e estratégias educacionais para aulas de ciências, concluímos que as habilidades funcionais, que envolvem conhecimentos cotidianos, não podem configurar critério de exclusão curricular de habilidades acadêmicas, do conhecimento científico, para a educação de pessoas com desenvolvimento atípico. Compreendemos que uma educação científica escolar com vias ao desenvolvimento integral é indissociável das habilidades da vida diária.

IntroductionSurgical-related injuries are frequent, in fact the reported percentage of musculoskeletal disorders in surgeons is between 47% and 87%. These conditions are caused by long periods of standing, incorrect postures, repeated movements, little rest between operations, the lack of integrated operator rooms, the correct number and arrangement of monitors and the use of non-ergonomic instruments. This survey aims to assess the Italian overview both highlighting how prevalent surgical-related injury is in our surgeons and whether there is an operating room ergonomics education program in Italian surgical specialty schools.MethodsAn anonymous questionnaire was designed through SurveyMonkey© web application. This survey was composed of 3 different sections concerning the general characteristics of the participants, their surgical background and any training performed, and any injuries or ailments related to the surgical activity. The survey was carried out in the period 1th of December 2022 and the 6th of February 2023.ResultsAt the close of our survey, 300 responses were collected. Among the participants, the two most represented specialties were Gynecology and Obstetrics (42.3%) and General Surgery (39.7%) and surgeons were mainly employed in the Northern regions of Italy (54.8%). Analyzing the participants’ background, 61.7% of the respondents had laparoscopic training during their training and only 53.1% had a pelvic trainer during their residency. In accordance with 98.7% of the respondents, during surgery we have the feeling of being in an uncomfortable position that causes discomfort or muscle pain, and regarding the frequency of these discomforts, the majority of our study population experiences these problems monthly (46.2%), while in 29.6% it is experienced weekly, 12.1% annually and finally 12.1% daily. The surgical approach that is most correlated with these disorders is laparoscopy (62.7%) while the one that causes the least discomfort is robotic surgery (1.4%). These discomforts cause 43.9% of our population to take a break or do short exercises to reduce pain during surgery, and the body areas most affected are the back (61.6%), neck (40.6%) and shoulders (37.8%).ConclusionDespite this, our survey allows us to highlight some now-known gaps present in the surgical training program of our schools and the lack of protection toward our surgeons during their long career.

GoTriple is a novel discovery platform for Social Sciences and Humanities (SSH) in Europe. Discovery is a phase of research where scholars seek to locate resources for their work, such as publications or previous projects. The paper details the work done for involving the SSH community in the codesign of GoTriple, focusing on the research discovery activities. It is an investigation of the user needs and barriers toward digital discovery for the SSH community, conducted through codesign. This work encompassed interviews, a questionnaire, codesign workshops and evaluation activities. The paper reports on some outcomes for the codesign and how user needs were identified and served by novel designs supporting discovery for SSH. This process of design is both concerned with creating digital tools for discovery and with the creation of a community of users that could make the platform thrive. The main contribution of the work is therefore the identification of the user needs for digital discovery in SSH and a series of insights on the design with the user community. The paper comprises a report on how codesign principles do support such work.

Abstract After the introduction of highly active antiretroviral therapies (HAART), an increased incidence of insulin resistance, diabetes mellitus (DM), and cardiovascular diseases has been described. The impact of such conditions on mortality in the post-HAART era has been also assessed in various modes in the literature. In this paper, we report on the death risks for DM, myocardial infarction, and chronic ischemic heart diseases that were investigated among 9662 Italian AIDS cases diagnosed between 1999 and 2005. Death certificates reporting DM, myocardial infarction, and chronic ischemic heart diseases were reviewed to identify the underlying cause of death, and to compare the observed numbers of deaths with the expected ones from the sex- and age-matched, general population of Italy. Person-years at risk of death were computed from date of AIDS diagnosis up to date of death or to December 31, 2006. Standardized mortality ratios (SMR) and their 95% confidence intervals (CI) were computed. DM and cardiovascular diseases were the cause of death for 43 out of 3101 deceased AIDS cases (i.e., 1.4% of all deaths). In comparison with the general population, the risks of death were 6.4-fold higher for DM (95% CI:3.5-10.8), 2.3-fold higher for myocardial infarction (95% CI:1.4-3.7) and 3.0 for chronic ischemic heart diseases (95% CI: 1.5-5.2).

Objective: A decrease in the use of radioactive iodine (RAI) treatment for thyroid cancer has been described in the last decade in the US following subsequent updates of the American Thyroid Association guidelines. By contrast, population-based data from European countries are lacking. The study aims to assess the frequency and long-term trends in the use of RAI in Italy. Methods: From the Italian national hospital discharge database, the proportion of RAI treatment after total thyroidectomy with thyroid cancer diagnosis has been assessed by sex and age class during 2001–2018. Results: Throughout the whole study period, RAI was performed after 58% of 149,419 total thyroidectomies. The use of RAI was higher for men and younger patients; it peaked in 2007 (64% in women and 68% in men) and declined thereafter (2018: 46% in women and 53% in men), with a similar pattern observed across all ages and areas. Conclusion: National data show that in Italy trends in RAI treatment paraleled those observed in the US. Further monitoring of the use of RAI is warranted in Italy, as elsewhere, to assess the impact of international guidelines on real-life clinical management of thyroid cancer.

AbstractThe Salmo trutta species complex includes threatened or intensively managed taxa. Domestic-Atlantic strains are widely farmed and massively introduced into the wild to support fisheries, although such practices seriously threaten native populations of Mediterranean brown trout through anthropogenic hybridization. Characterizing the distribution and genetic composition of wild populations across river catchments is crucial to identify conservation priorities and define appropriate management strategies. Here, we genotyped 586 brown trout at the diagnostic nuclear LDH-C1 gene and the mitochondrial D-loop fragment, to assess the conservation status of 33 sites in a protected area spanning river catchments from both the Adriatic and Tyrrhenian slopes in the northern Apennines (Italy). The results indicated a critical situation of widespread domestic-Atlantic introgression. Further analyses at 15 microsatellite loci on 159 individuals from 12 natural sites (along with 113 references from hatcheries) revealed similarity to hatchery stocks, higher genetic diversity and bottleneck signals in introgressed/exotic populations, consistently with relatively recent introductions of domestic-Atlantic individuals into wild sites. Conversely, the only native sites from a single river catchment on the Adriatic slope showed genetic distinctiveness, reduced diversity and demographic stability. We also found genetic evidence of a human-mediated introduction of allochthonous Mediterranean trout in a single wild site, as well as of a putative between-slopes translocation. We provide further insight into the occurrence and consequences of human manipulations on wild Mediterranean brown trout populations, contextually offering a reliable baseline for an ongoing conservation project aiming at preserving native populations of this endangered taxon.

This review highlights -omics research in Solanaceae family, with a particular focus on resilient traits. Extensive research has enriched our understanding of Solanaceae genomics and genetics, with historical varietal development mainly focusing on disease resistance and cultivar improvement but shifting the emphasis towards unveiling resilience mechanisms in genebank-preserved germplasm is nowadays crucial. Collecting such information, might help researchers and breeders developing new experimental design, providing an overview of the state of the art of the most advanced approaches for the identification of the genetic elements laying behind resilience. Building this starting point, we aim at providing a useful tool for tackling the global agricultural resilience goals in these crops.

Abstract Background The aging of the Italian population will unavoidably lead to a growing number of persons diagnosed and living with cancer. A comprehensive description of the burden of cancer mortality among Italian elderly (65-84 years of age) in the last four decades has not been carried out yet. Cancer mortality rates were used to describe time trends between 1970-2008. Methods Mortality counts, provided by the Italian National Institute of Statistics, were grouped according to data availability: in quinquennia from 1970-74 through 1995-99, and in 2000-03 and 2006-08 groups. Age-standardized rates (world population) were computed by calendar periods while annual percent changes (APCs) were computed for elderly and middle aged (35-64 years) people for the period 1995-2008. Results The number of cancer deaths in elderly nearly doubled between 1970-74 (31,400 deaths/year in men, and 24,000 in women) and 2006-08 (63,000 deaths/year in men, and 42,000 in women). Overall cancer mortality rates peaked during the quinquennia 1985-89 and 1990-94 (about 1,500/100,000 in men and 680 in women) and declined thereafter. Throughout 1995-2008 cancer mortality rates decreased by -1.6%/year in men and -0.9%/year in women. These decreases were mainly driven by cancers of the stomach, bladder, prostate, and lung (APC = -3.3%, -2.7%, -2.5%, -2.2%, respectively) in men, and by cancers of the stomach, bladder, and breast (APC = -3.5%, -1.9%, -1.1%, respectively) in women. Conversely, increases in mortality rates between 1995 and 2008 were recorded for lung cancer (APC = +0.6%) in women, cutaneous melanoma (APC = +1.7%) in men, and pancreatic cancer (APC = +0.6% in men and +0.9% in women). Conclusions Overall favorable trends in cancer mortality were observed among Italian elderly between 1995 and 2008. Early diagnosis, improved efficacy of anti-cancer treatments and management of comorbidities are the most likely explanations of these positive observations. However, enduring preventive interventions against the most common risk factor (e.g. cigarette smoking), early diagnosis, and access to care should be reconsidered and extended to match the reductions of cancer mortality recorded in the elderly with those in the middle aged.

Abstract The interleukin-1 family members, IL-1β and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1β processing in myeloid cells have been defined, those involved in IL-18 processing, particularly in non-myeloid cells, are still not well understood. Here we report that the host defence molecule NOD1 regulates IL-18 processing in mouse epithelial cells in response to the mucosal pathogen, Helicobacter pylori. Specifically, NOD1 in epithelial cells mediates IL-18 processing and maturation via interactions with caspase-1, instead of the canonical inflammasome pathway involving RIPK2, NF-κB, NLRP3 and ASC. NOD1 activation and IL-18 then help maintain epithelial homoeostasis to mediate protection against pre-neoplastic changes induced by gastric H. pylori infection in vivo. Our findings thus demonstrate a function for NOD1 in epithelial cell production of bioactive IL-18 and protection against H. pylori-induced pathology.

Abstract Long-read single-cell RNA sequencing (scRNA-seq) enables the quantification of RNA isoforms in individual cells. However, long-read scRNA-seq using the Oxford Nanopore platform has largely relied upon matched short-read data to identify cell barcodes. We introduce BLAZE, which accurately and efficiently identifies 10x cell barcodes using only nanopore long-read scRNA-seq data. BLAZE outperforms the existing tools and provides an accurate representation of the cells present in long-read scRNA-seq when compared to matched short reads. BLAZE simplifies long-read scRNA-seq while improving the results, is compatible with downstream tools accepting a cell barcode file, and is available at https://github.com/shimlab/BLAZE .

Abstract The development and maintenance of adequate shared infrastructures is considered a major goal for academic centers promoting translational research programs. Among infrastructures favoring translational research, centralized facilities characterized by shared, multidisciplinary use of expensive laboratory instrumentation, or by complex computer hardware and software and/or by high professional skills are necessary to maintain or improve institutional scientific competitiveness. The success or failure of a shared resource program also depends on the choice of appropriate institutional policies and requires an effective institutional governance regarding decisions on staffing, existence and composition of advisory committees, policies and of defined mechanisms of reporting, budgeting and financial support of each resource. Shared Resources represent a widely diffused model to sustain cancer research; in fact, web sites from an impressive number of research Institutes and Universities in the U.S. contain pages dedicated to the SR that have been established in each Center, making a complete view of the situation impossible. However, a nation-wide overview of how Cancer Centers develop SR programs is available on the web site for NCI-designated Cancer Centers in the U.S., while in Europe, information is available for individual Cancer centers. This article will briefly summarize the institutional policies, the organizational needs, the characteristics, scientific aims, and future developments of SRs necessary to develop effective translational research programs in oncology. In fact, the physical build-up of SRs per se is not sufficient for the successful translation of biomedical research. Appropriate policies to improve the academic culture in collaboration, the availability of educational programs for translational investigators, the existence of administrative facilitations for translational research and an efficient organization supporting clinical trial recruitment and management represent essential tools, providing solutions to overcome existing barriers in the development of translational research in biomedical research centers.

Abstract Background Engagement of CD40 promotes survival of undifferentiated nasopharyngeal carcinoma (UNPC) cells and similar effects are induced by the EBV oncoprotein LMP-1 that is expressed in a fraction of cases. Considering that CD40 may be activated also by the soluble isoform of CD40L (sCD40L), we investigated the serum levels of sCD40L in a series of 61 UNPC patients from Italy, a non-endemic area for this disease. Results At diagnosis, serum samples of UNPC patients contained significantly higher levels of sCD40L than age-matched healthy controls (p < 0.001). High levels of sCD40L (i.e., >18 ng/ml) were more frequently found in patients + lymphoid cells admixed to neoplastic UNPC cells were detected in cases with high serum levels of sCD40L, suggesting that sCD40L is probably produced within the tumor mass. Conclusion sCD40L may contribute to CD40 activation in UNPC cells, particularly of LMP-1-negative cases, further supporting the crucial role of CD40 signalling in the pathogenesis of UNPC. sCD40L levels may be useful to identify UNPC patients with occult distant metastases at presentation.

The multifaceted nature of climate change is increasing the urgency to select resilient grapevine varieties, or generate new, fitter cultivars, to withstand a multitude of new challenging conditions. The attainment of this goal is hindered by the limiting pace of traditional breeding approaches, which require decades to result in new selections. On the other hand, marker-assisted breeding has proved useful when it comes to traits governed by one or few genes with great effects on the phenotype, but its efficacy is still restricted for complex traits controlled by many loci. On these premises, innovative strategies are emerging which could help guide selection, taking advantage of the genetic diversity within the Vitis genus in its entirety. Multiple germplasm collections are also available as a source of genetic material for the introgression of alleles of interest via adapted and pioneering transformation protocols, which present themselves as promising tools for future applications on a notably recalcitrant species such as grapevine. Genome editing intersects both these strategies, not only by being an alternative to obtain focused changes in a relatively rapid way, but also by supporting a fine-tuning of new genotypes developed with other methods. A review on the state of the art concerning the available genetic resources and the possibilities of use of innovative techniques in aid of selection is presented here to support the production of climate-smart grapevine genotypes.

BackgroundKnowledge about the dynamics of transmission of SARS-CoV-2 and the clinical aspects of COVID-19 has steadily increased over time, although evidence of the determinants of disease severity and duration is still limited and mainly focused on older adult and fragile populations.MethodsThe present study was conceived and carried out in the Emilia-Romagna (E-R) and Veneto Regions, Italy, within the context of the EU’s Horizon 2020 research project called ORCHESTRA (Connecting European Cohorts to increase common and effective response to SARS-CoV-2 pandemic) (www.orchestra-cohort.eu). The study has a multicenter retrospective population-based cohort design and aimed to investigate the incidence and risk factors of access to specific healthcare services (outpatient visits and diagnostics, drug prescriptions) during the post-acute phase from day-31 to day-365 after SARS-CoV-2 infection, in a healthy population at low risk of severe acute COVID-19. The study made use of previously recorded large-scale healthcare data available in the administrative databases of the two Italian Regions. The statistical analysis made use of methods for competing risks. Risk factors were assessed separately in the two Regions and results were pooled using random effects meta-analysis.ResultsThere were 35,128 subjects in E-R and 88,881 in Veneto who were included in the data analysis. The outcome (access to selected health services) occurred in a high percentage of subjects in the post-acute phase (25% in E-R and 21% in Veneto). Outpatient care was observed more frequently than drug prescriptions (18% vs. 12% in E-R and 15% vs. 10% in Veneto). Risk factors associated with the outcome were female sex, age greater than 40 years, baseline risk of hospitalization and death, moderate to severe acute COVID-19, and acute extrapulmonary complications.ConclusionThe outcome of interest may be considered as a proxy for long-term effects of COVID-19 needing clinical attention. Our data suggest that this outcome occurs in a substantial percentage of cases, even among a previously healthy population with low or mild severity of acute COVID-19. The study results provide useful insights into planning COVID-19-related services.

Designing interactive prototypes involves multiple tools and skills. In addition, several design cycles are required to iterate through idea generation, evaluation of design alternatives, and development. Consequently, prototyping tools should offer flexibility and adaptability to allow designers to quickly test and evaluate different ideas, design alternatives, materials, interactions, etc. To meet these requirements, we designed Protobject – a rapid prototyping tool aimed at making the early stages of prototyping interactive products more flexible. Protobject allows designers to reinvent and reuse existing objects for prototyping purposes by making them interactive. After introducing the features of Protobject and discussing the differences with similar tools, we present a user evaluation through two workshop sessions held in Milan during Brera Design Days and attended by 22 people. The results suggest that Protobject facilitates cooperation between people with different skills by allowing them to envision interactive prototypes together.

Es innegable que la noción de epoché fue crucial para el surgimiento y el posterior desarrollo de la tradición fenomenológica. Si bien la resignificación que Husserl hace de ésta es sumamente original, él mismo se detiene a reconocer en la filosofía antigua el mérito de haber encontrado el camino idóneo para acceder a la subjetividad trascendental. En el siguiente trabajo buscaré, por un lado, definir la epoché tal como se origina en el pensamiento de los sofistas para luego pasar a analizar el modo en el que Husserl logra reversionar dicha noción hasta convertirla en el método predilecto que nos permite arribar a la esfera trascendental. Por otro lado, continuaré rastreando la evolución de la epoché para llegar a su abandono en la filosofía de Sartre. En relación con esto último, me interesa preguntarme si el existencialismo reniega de la suspensión del juicio por considerarla inapropiada o si, más bien, se trata de una supresión parcial del método fenomenológico. Me propongo defender esta segunda tesis, alegando que, en realidad, la epoché no es una noción que esté totalmente ausente en la filosofía de Sartre sino que se mantiene vigente en términos de angustia existencial.

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it is, to some extent, a process of exclusion. AOSD has life-threating complications ranging from asymptomatic to severe, such as macrophage activation syndrome (MAS), which is also referred to as hemophagocytic lymphohistocytosis (HLH). This condition is correlated with cytokine storm production and monocyte/macrophage overactivation and typically occurs with rash, pyrexia, pancytopenia, hepatosplenomegaly and systemic involvement. Exitus occurs in approximately 10% of cases. For the treatment of MAS-HLH, the Histiocyte Society currently suggests high-dose corticosteroids, with the possible addition of cyclosporine A, anti-interleukin (IL)-1, or IL-6 biological drugs; the inclusion of etoposide is recommended for the most severe conditions. In all cases, a multidisciplinary collaboration involving the resources and expertise of several specialists (e.g., rheumatologist, infectiologist, critical care medicine specialist) is advised. Herein, we provide a detailed description of the clinical case of a previously healthy young woman in which MAS developed as a dramatic onset manifestation of AOSD and whose diagnosis posed a real clinical challenge; the condition was finally resolved by applying the HLH-94 protocol (i.e., etoposide in combination with dexamethasone).

Abstract Background Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

ObjectivesTo describe the procedures to derive complete prevalence and several indicators of cancer cure from population-based cancer registries.Materials and methodsCancer registry data (47% of the Italian population) were used to calculate limited duration prevalence for 62 cancer types by sex and registry. The incidence and survival models, needed to calculate the completeness index (R) and complete prevalence, were evaluated by likelihood ratio tests and by visual comparison. A sensitivity analysis was conducted to explore the effect on the complete prevalence of using different R indexes. Mixture cure models were used to estimate net survival (NS); life expectancy of fatal (LEF) cases; cure fraction (CF); time to cure (TTC); cure prevalence, prevalent patients who were not at risk of dying as a result of cancer; and already cured patients, those living longer than TTC at a specific point in time. CF was also compared with long-term NS since, for patients diagnosed after a certain age, CF (representing asymptotical values of NS) is reached far beyond the patient’s life expectancy.ResultsFor the most frequent cancer types, the Weibull survival model stratified by sex and age showed a very good fit with observed survival. For men diagnosed with any cancer type at age 65–74 years, CF was 41%, while the NS was 49% until age 100 and 50% until age 90. In women, similar differences emerged for patients with any cancer type or with breast cancer. Among patients alive in 2018 with colorectal cancer at age 55–64 years, 48% were already cured (had reached their specific TTC), while the cure prevalence (lifelong probability to be cured from cancer) was 89%. Cure prevalence became 97.5% (2.5% will die because of their neoplasm) for patients alive >5 years after diagnosis.ConclusionsThis study represents an addition to the current knowledge on the topic providing a detailed description of available indicators of prevalence and cancer cure, highlighting the links among them, and illustrating their interpretation. Indicators may be relevant for patients and clinical practice; they are unambiguously defined, measurable, and reproducible in different countries where population-based cancer registries are active.

Em pesquisa na Base Nacional Comum Curricular (2018), BNCC, investigamos mediações com o público da Educação Especial, as pessoas com deficiência, em uma perspectiva histórico-cultural. Os dados foram escassos e, portanto, buscamos nos descritores de inclusão e diversidade possibilidades de reflexões, instrumentos e estratégias que favorecessem a discussão das particularidades das pessoas com deficiência no documento orientador mais recente da educação básica brasileira. No processo metodológico, categorizamos esses descritores para a análise documental voltada à educação das infâncias. Identificamos que o documento não apresentou posicionamento nem orientações sobre a inclusão escolar das deficiências, ou a interseccionalidade com outras singularidades marginalizadas. A BNCC foi moldada à formação do desenvolvimento psicofisiológico típico e hegemônico. Para uma perspectiva diversa, pode-se inferir, que os(as) profissionais da educação não devem se orientar exclusivamente pelo documento em função das ausências assinaladas. Sendo assim, o trabalho pedagógico precisa colocar em tela discussões e práticas que contemplem a inclusão das pessoas com deficiência com vias à emancipação humana.

Background and Aims: The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. Methods: Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. Results: We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. Conclusion: This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

IntroductionThe COVID-19 pandemic has led to the disruption of surgical training. Lack of communication, guidelines for managing clinical activity as well as concerns for safety in the workplace appeared to be relevant issues. This study aims to investigate how surgical training has been reorganized in Italy, almost 2 years after the outbreak of COVID-19 pandemic.Materials and methodsA 16-item-electronic anonymous questionnaire was designed through SurveyMonkey© web application. This survey was composed of different sections concerning demographic characteristics and impacts of the second COVID-19 pandemic wave on surgical and research/didactic activities. Changes applied in the training programme and activities carried out were also investigated. The survey was carried out in the period between June and October 2021.ResultsFour hundred and thirty responses were collected, and 399 were considered eligible to be included in the study analysis. Three hundred and thirty-five respondents continued working in Surgical Units, with a significant reduction (less than one surgical session per week) of surgical sessions in 49.6% of them. With concern to didactic and research activities, 140 residents maintained their usual activity, while 116 reported a reduction. A sub-group analysis on resident moved to COVID-19 departments showed a reduction of research activities in 35% of them. During the period considered in this survey, the surgical training program was not substantially modified for most of participants (74.6%).ConclusionOur survey demonstrated that surgical residency programs haven't improved 2 years after the beginning of the pandemic. Further improvements are needed to guarantee completeness of surgical training, even in emergency conditions.

The final shape and size of plant organs are determined by a network of genes that modulate cell proliferation and expansion. Among those, SCI1 (Stigma/style Cell-cycle Inhibitor 1) functions by inhibiting cell proliferation during pistil development. Alterations in SCI1 expression levels can lead to remarkable stigma/style size changes. Recently, we demonstrated that SCI1 starts to be expressed at the specification of the Nicotiana tabacum floral meristem and is expressed at all floral meristematic cells. To elucidate how SCI1 regulates cell proliferation, we screened a stigma/style cDNA library through the yeast two-hybrid (Y2H) system, using SCI1 as bait. Among the interaction partners, we identified the 14-3-3D protein of the Non-Epsilon group. The interaction between SCI1 and 14-3-3D was confirmed by pulldown and co-immunoprecipitation experiments. 14-3-3D forms homo- and heterodimers in the cytoplasm of plant cells and interacts with SCI1 in the nucleus, as demonstrated by Bimolecular Fluorescence Complementation (BiFC). Analyses of SCI1-GFP fluorescence through the cell-cycle progression revealed its presence in the nucleoli during interphase and prophase. At metaphase, SCI1-GFP fluorescence faded and was no longer detected at anaphase, reappearing at telophase. Upon treatment with the 26S proteasome inhibitor MG132, SCI1-GFP was stabilized during cell division. Site-directed mutagenesis of seven serines into alanines in the predicted 14-3-3 binding sites on the SCI1 sequence prevented its degradation during mitosis. Our results demonstrate that SCI1 degradation at the beginning of metaphase is dependent on the phosphorylation of serine residues and on the action of the 26S proteasome. We concluded that SCI1 stability/degradation is cell-cycle regulated, consistent with its role in fine-tuning cell proliferation.

Better methods to interrogate host-pathogen interactions during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections are imperative to help understand and prevent this disease. Here we implemented RNA-sequencing (RNA-seq) using Oxford Nanopore Technologies (ONT) long-reads to measure differential host gene expression, transcript polyadenylation and isoform usage within various epithelial cell lines permissive and non-permissive for SARS-CoV-2 infection. SARS-CoV-2-infected and mock-infected Vero (African green monkey kidney epithelial cells), Calu-3 (human lung adenocarcinoma epithelial cells), Caco-2 (human colorectal adenocarcinoma epithelial cells) and A549 (human lung carcinoma epithelial cells) were analyzed over time (0, 2, 24, 48 hours). Differential polyadenylation was found to occur in both infected Calu-3 and Vero cells during a late time point (48 hpi), with Gene Ontology (GO) terms such as viral transcription and translation shown to be significantly enriched in Calu-3 data. Poly(A) tails showed increased lengths in the majority of the differentially polyadenylated transcripts in Calu-3 and Vero cell lines (up to ~101 nt in mean poly(A) length, padj = 0.029). Of these genes, ribosomal protein genes such as RPS4X and RPS6 also showed downregulation in expression levels, suggesting the importance of ribosomal protein genes during infection. Furthermore, differential transcript usage was identified in Caco-2, Calu-3 and Vero cells, including transcripts of genes such as GSDMB and KPNA2, which have previously been implicated in SARS-CoV-2 infections. Overall, these results highlight the potential role of differential polyadenylation and transcript usage in host immune response or viral manipulation of host mechanisms during infection, and therefore, showcase the value of long-read sequencing in identifying less-explored host responses to disease.

The accumulation of fragmented extracellular DNA reduces conspecific seed germination and plantlet growth in a concentration-dependent manner. This self-DNA inhibition was repeatedly reported, but the underlying mechanisms are not fully clarified. We investigated the species-specificity of self-DNA inhibition in cultivated vs. weed congeneric species (respectively, Setaria italica and S. pumila) and carried out a targeted real-time qPCR analysis under the hypothesis that self-DNA elicits molecular pathways that are responsive to abiotic stressors. The results of a cross-factorial experiment on root elongation of seedlings exposed to self-DNA, congeneric DNA, and heterospecific DNA from Brassica napus and Salmon salar confirmed a significantly higher inhibition by self-DNA as compared to non-self-treatments, with the latter showing a magnitude of the effect consistent with the phylogenetic distance between the DNA source and the target species. Targeted gene expression analysis highlighted an early activation of genes involved in ROS degradation and management (FSD2, ALDH22A1, CSD3, MPK17), as well as deactivation of scaffolding molecules acting as negative regulators of stress signaling pathways (WD40-155). While being the first exploration of early response to self-DNA inhibition at molecular level on C4 model plants, our study highlights the need for further investigation of the relationships between DNA exposure and stress signaling pathways by discussing potential applications for species-specific weed control in agriculture.

Shallow open-loop geothermal systems function by creating heat and cold reserves in an aquifer, via doublets of pumping and reinjection wells. Three adjacent buildings in the center of Brussels have adopted this type of aquifer thermal energy storage (ATES) system. Two of them exploit the same aquifer consisting of Cenozoic sands, and started operation in 2014 and 2017, respectively. A previous hydrogeological model developed by Bulté et al. (2021) has shown how the thermal imbalance of one of the systems jeopardizes the thermal state of this upper aquifer. Here, the interactions with a more recent third ATES system located in the deep aquifer of the Palaeozoic bedrock are studied and modelled. After being calibrated on groundwater flow conditions in both aquifers, a 3D hydrogeological model was used to simulate the cumulative effect of the three geothermal installations in the two exploited aquifers. The results of the simulations showed that although the hydraulic interactions between the two aquifers are very weak (as shown by the different observed potentiometric heads), heat exchanges occur between the two aquifers through the aquitard. Fortunately, these heat exchanges are not sufficient to have a significant impact on the efficiency of the individual geothermal systems. Additionally, this study shows clearly that adding a third system in the lower aquifer with a mean power of 286 kW for heating between October and March and an equivalent mean cooling power between April and September is efficient.

This paper extends the modified Cam-Clay model to describe the behaviour of unsaturated soils by replacing the effective stress with the scaled stress. The scaled stress accounts for the mechanical effect of capillarity by factoring Bishop’s stress with a power function of degree of saturation. The extendedmodified Cam-Clay model postulates the existence of a yield curve in the mean scaled stress 𝑝̅– deviatoric scaled stress 𝑞̅ plane. Coherently with the modified Cam-Clay model, the stress-strain behaviour is predicted by means of an elastic law inside the yield curve. As the scaled stress state evolves onto the yield curve, the behaviour becomes elasto-plastic and this is modelled by a plastic flow rule combined with a volumetric hardening law. The extended modified Cam-Clay model is then validated against experimental data published in the literature. Results show that the proposed approach is capable of well predicting the mechanical behaviour of unsaturated soils during triaxial loading. Future work will be directed at further validating the present formulation along different stress paths as well as accounting for the combined effect of partial saturation and cementation within a critical state framework based on bounding surface plasticity.

Previous research on indicators for measuring the success of Open Science tends to operate at a macro/global level and very rarely addresses the need to measure success at the level of a single project. However, this previous research has the merit of arguing for the definition of indicators that offer an alternative to more traditional bibliometric measures or indicators that focus on mere performance. This paper is the outcome of work conducted for a specific project that aims to build a discovery platform for social sciences and humanities, the platform GoTriple. GoTriple is designed taking inspiration from Open Science principles and has been built through a user-centered approach. The paper details the practice-led work conducted by the GoTriple team for assessing the meaning of the term success for the project and to identify indicators. To this end, this paper proposes the concept of compass indicators and presents how the project team arrived at the definition of this concept. The paper also highlights a distinction between compass indicators, which are modest measures, and key performance indicators, which tend to be tied up with measurable objectives. Compass indicators are defined as indicators that do not aim to achieve a specified numerical target of success but rather explain the journey of a project toward achieving certain desirable outcomes and offer insights to take action. Compass indicators defined for the project embrace areas such as diversity, inclusivity, collaboration, and the general use of the platform. In the final discussion, the paper offers reflections on the potential relevance of the notion of compass indicators and closes with a discussion of the next steps for this work.

Introduction Within the hub and spoke organizational model provided by the Emilia Romagna Region for assistance to people with autism spectrum disorder (ASD), Cesena ward of psychiatry represents the hospital Hub. Here, a dedicated team (doctors, psychologist, case manager) creates individualized pathways to ensure second-level specialist diagnostics and the management of comorbidities affecting subjects diagnosed with Autism Spectrum Disorder and Intellectual Disability (ID). Objectives We report the case of a 23-year-old man, who from the age of 6 was opposed to any instrumental diagnostic investigation. Methods In order to guarantee the patient’s full collaboration in carrying out essential diagnostic activities, short behavioural paths were created including video modelling. The Vi.Co app was used and a new app was created to target behaviors that could not be included in Vi.Co Results It was thus possible to make the patient compliant with the execution of blood samples, ECG, MRI of the brain in sedation and CT dental scan. Conclusions In our case, communication support systems and behavioral strategies have proved to be excellent allies in significantly improving the quality of care for our young patient. Considering the worst prognosis of pathologies and the reduced life expectancy of subjects suffering from ASD and ID, known in the literature, in our opinion, the first essential step becomes facilitating access to care for these patients. Disclosure No significant relationships.

In this review we present some of the recent advances in the field of silicon nitride photonic integrated circuits. The review focuses on the material deposition techniques currently available, illustrating the capabilities of each technique. The review then expands on the functionalisation of the platform to achieve nonlinear processing, optical modulation, nonvolatile optical memories and integration with III-V materials to obtain lasing or gain capabilities.

The paper offers a conceptual analysis and a case study research on the design of e-participation in environmental policy-making for young people. This is achieved by connecting the concept of environmental action with e-participation design. Through a literature review, four core dimensions of environmental action for young people are identified: ownership, participation, stakes in the future and experience. Through a case study of research conducted for an applied project aimed at designing and piloting a novel e-participation solution, the paper shows how young people, implicitly see the connections between these four dimensions of environmental action and the e-participation process. The dimensions of environmental action have, then been used as the basis for co-creation activities and for a subsequent evaluation of e-participation. The results support the position that environmental action can underpin the design and can increase e-participation capacity in environmental policy-making for young people.

Background Protein supplementation has been suggested to augment endurance training adaptations by increasing mixed muscle and myofibrillar protein synthesis and lean body mass. However, a potential beneficial effect on mitochondrial adaptations is yet to be clarified. The aim of the present study was to investigate the effect of consuming whey protein hydrolysate before and whey protein hydrolysate plus carbohydrate (PRO-CHO) after each exercise session during a six-week training period compared to similarly timed intake of isocaloric CHO supplements on biomarkers of mitochondrial biogenesis, VO2max and performance in trained runners. Methods Twenty-four trained runners (VO2max 60.7 ± 3.7 ml O2 kg− 1 min1) completed a six-week block randomized controlled intervention period, consisting of progressive running training. Subjects were randomly assigned to either PRO-CHO or CHO and matched in pairs for gender, age, VO2max, training and performance status. The PRO-CHO group ingested a protein beverage (0.3 g kg− 1) before and protein-carbohydrate beverage (0.3 g protein kg− 1 and 1 g carbohydrate kg− 1) after each exercise session. The CHO group ingested an energy matched carbohydrate beverage. Resting muscle biopsies obtained pre and post intervention were analyzed for mitochondrial specific enzyme activity and mitochondrial protein content. Subjects completed a 6 K time trial (6 K TT) and a VO2max test pre, midway (only 6 K TT) and post intervention. Results Following six weeks of endurance training Cytochrome C (Cyt C) protein content was significantly higher in the PRO-CHO group compared to the CHO group (p

This document is the direct transcription of a Webinar organized by Prof. L. Corbetta of the University of Florence on July 7th, 2020.

Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently identified by clinical history or specific morphological and cytogenetic abnormalities. However, in the absence of these features, uncertainties remain to identify the secondary nature of some cases otherwise defined as de novo AML. To test whether a chromatin-spliceosome (CS) mutational signature might better inform the definition of the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients enrolled into a randomized clinical trial (NILG AML 02/06) and provided with accurate cytogenetic and molecular characterization. Among clinically defined de novo AML, 17.6% carried CS mutations (CS-AML) and showed clinical characteristics closer to sAML (older age, lower white blood cell counts and higher rate of multilineage dysplasia). Outcomes in this group were adverse, more similar to those of sAML as compared to de novo AML (overall survival, 30% in CS-AML and 17% in sAML vs 61% in de novo AML, P

Bortezomib-melphalan-prednisone (VMP) and continuous lenalidomide-dexamethasone (Rd) represent the standard treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (MM). To date, no randomized trial has compared VMP to Rd, and there is no evidence of the optimal treatment for newly diagnosed MM, particularly in patients with high-risk cytogenetics [del(17p), t(4;14) or t(14;16)]. We pooled together data from patients with newly diagnosed MM treated with VMP or Rd induction followed by lenalidomide maintenance 10 mg (Rd-R) enrolled in the GIMEMA-MM-03-05 and EMN01 trials, to evaluate the efficacy of these treatments in different subgroups of patients, focusing on those with standard- and high-risk cytogenetics. Overall, 474 patients were analyzed (VMP: 257 patients; Rd-R: 217 patients). No differences in progression-free survival (hazard ratio=0.96) and overall survival (hazard ratio=1.08) were observed between standard-risk patients treated with VMP or Rd-R, whereas among the high-risk patients, the probabilities of progression (hazard ratio=0.54) and death (hazard ratio=0.73) were lower in the patients treated with VMP than in those treated with Rd-R. In particular, standard-risk patients >75 years benefited less from VMP than from Rd-R (hazard ratio for progression-free survival=0.96; hazard ratio for overall survival=1.81). In this non-randomized analysis, VMP and Rd-R were equally effective in younger (≤75 years), standard-risk patients, while older ones (>75 years) benefited more from Rd-R. In high-risk patients, VMP improved progression-free survival and overall survival irrespective of age. The source trials are registered at ClinicalTrials.gov (NCT01063179 and NCT01093196).