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The Epstein–Barr virus (EBV) is linked to various B-cell lymphomas, including Burkitt lymphoma (BL), classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) at frequencies ranging, by routine techniques, from 5 to 10% of cases in DLBCL to >95% in endemic BL. Using higher-sensitivity methods, we recently detected EBV traces in a few EBV-negative BL cases, possibly suggesting a “hit-and-run” mechanism. Here, we used routine and higher-sensitivity methods (qPCR and ddPCR for conserved EBV genomic regions and miRNAs on microdissected tumor cells; EBNA1 mRNA In situ detection by RNAscope) to assess EBV infection in a larger lymphoma cohort [19 BL, 34 DLBCL, 44 cHL, 50 follicular lymphomas (FL), 10 T-lymphoblastic lymphomas (T-LL), 20 hairy cell leukemias (HCL), 10 mantle cell lymphomas (MCL)], as well as in several lymphoma cell lines (9 cHL and 6 BL). qPCR, ddPCR, and RNAscope consistently documented the presence of multiple EBV nucleic acids in rare tumor cells of several cases EBV-negative by conventional methods that all belonged to lymphoma entities clearly related to EBV (BL, 6/9 cases; cHL, 16/32 cases; DLBCL, 11/30 cases), in contrast to fewer cases (3/47 cases) of FL (where the role of EBV is more elusive) and no cases (0/40) of control lymphomas unrelated to EBV (HCL, T-LL, MCL). Similarly, we revealed traces of EBV infection in 4/5 BL and 6/7 HL cell lines otherwise conventionally classified as EBV negative. Interestingly, additional EBV-positive cases (1 DLBCL, 2 cHL) relapsed as EBV-negative by routine methods while showing EBNA1 expression in rare tumor cells by RNAscope. The relapse specimens were clonally identical to their onset biopsies, indicating that the lymphoma clone can largely loose the EBV genome over time but traces of EBV infection are still detectable by high-sensitivity methods. We suggest EBV may contribute to lymphoma pathogenesis more widely than currently acknowledged.

MYC is the most altered oncogene in human cancer, and belongs to a large family of genes, including MYCN and MYCL. Recently, while assessing the degree of correlation between MYC gene rearrangement and MYC protein expression in aggressive B-cell lymphomas, we observed few Burkitt lymphoma (BL) cases lacking MYC protein expression despite the translocation involving the MYC gene. Therefore, in the present study we aimed to better characterize such cases. Our results identified two sub-groups of MYC protein negative BL: one lacking detectable MYC protein expression but presenting MYCN mRNA and protein expression; the second characterized by the lack of both MYC and MYCN proteins but showing MYC mRNA. Interestingly, the two sub-groups presented a different pattern of SNVs affecting MYC gene family members that may induce the switch from MYC to MYCN. Particulary, MYCN-expressing cases show MYCN SNVs at interaction interface that stabilize the protein associated with loss-of-function of MYC. This finding highlights MYCN as a reliable diagnostic marker in such cases. Nevertheless, due to the overlapping clinic, morphology and immunohistochemistry (apart for MYC versus MYCN protein expression) of both sub-groups, the described cases represent bona fide BL according to the current criteria of the World Health Organization.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Antimicrobial resistance (AMR) poses a global threat to human, animal and environmental health. Among the multidisciplinary tasks aimed at collectively tackling the AMR crisis, surveillance, research and education stand as major priorities. Based on a crowdsourcing research strategy, the MicroMundo project, a partner of the Tiny Earth initiative in Spain and Portugal, has been developed and consolidated with success in the academic environment. The objectives are focused on promoting research and, especially, on bringing knowledge of One Health and microbiology concepts, as well as AMR awareness to the community. Following a service‐learning approach, MicroMundo integrates university and secondary/high school students in a citizen science‐based research project to collectively isolate microorganisms with the potential to produce new antibiotics from soil environments. Over the last 7 years, 32 MicroMundo hubs operating across 31 different Portuguese and Spanish universities have recruited thousands of teenagers in this quest. Here we review the outcome of this unprecedented effort from a scientific and an educational perspective. We review here the activity over the years of MicroMundo, a consolidated citizen science and service‐learning Project operating from over 30 Spanish and Portuguese universities, which involves students from different educational levels in the search for antibiotic activities in microorganisms isolated from soil samples.

Functional non-retentive fecal incontinence (FNRFI) is a common problem in pediatric age. FNRFI is defined as unintended loss of stool in a 4-year-old or older child after organic causes have been excluded. FNRFI tends to affects up to 3% of children older than 4 years, with males being affected more frequently than females. Clinically, children affected by FNRFI have normal intestinal movements and stool consistency. Literature data show that children with fecal incontinence have increased levels of separation anxiety, specific phobias, general anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder. In terms of possible relationship between incontinence and sleep, disorders of sleep organization have been observed in the pathogenesis of enuresis so generating the hypothesis that the orexinergic system may have a crucial role not only for the sleep organization per se but also for the sphincterial control in general. This study aimed to focus on specific neurophysiological aspects to investigate on the possible relationship between sleep organizational abnormalities and FNRFI. Specifically, we aimed to measure orexin serum levels in children with FNRFI and assess their polysomnographic sleep macrostructure patterns. Two study groups were considered: FNFRI (n = 45) and typically developed (TD) (n = 45) group. In both groups, sleep patterns and respiratory events were assessed by polysomnographic recordings (PSG) during a period of two nights at least, and plasma levels of Orexin-A were measured in each participant. The findings of this initial investigation seem to support a major role of Orexin-A in sleep organization alterations in children with FNFRI. Also, our data suggest that sleep habits evaluation should be considered as screening and complementary tool for the diagnosis of fecal incontinence in children.

[EN]Antimicrobial resistance (AMR) poses a global threat to human, animal and environmental health. Among the multidisciplinary tasks aimed at collectively tackling the AMR crisis, surveillance, research and education stand as major priorities. Based on a crowdsourcing research strategy, the MicroMundo project, a partner of the Tiny Earth initiative in Spain and Portugal, has been developed and consolidated with success in the academic environment. The objectives are focused on promoting research and, especially, on bringing knowledge of One Health and microbiology concepts, as well as AMR awareness to the community. Following a service-learning approach, MicroMundo integrates university and secondary/high school students in a citizen science-based research project to collectively isolate microorganisms with the potential to produce new antibiotics from soil environments. Over the last 7 years, 32 MicroMundo hubs operating across 31 different Portuguese and Spanish universities have recruited thousands of teenagers in this quest. Here we review the outcome of this unprecedented effort from a scientific and an educational perspective.

Antimicrobial resistance (AMR) poses a global threat to human, animal and environmental health. Among the multidisciplinary tasks aimed at collectively tackling the AMR crisis, surveillance, research and education stand as major priorities. Based on a crowdsourcing research strategy, the MicroMundo project, a partner of the Tiny Earth initiative in Spain and Portugal, has been developed and consolidated with success in the academic environment. The objectives are focused on promoting research and, especially, on bringing knowledge of One Health and microbiology concepts, as well as AMR awareness to the community. Following a service-learning approach, MicroMundo integrates university and secondary/high school students in a citizen science-based research project to collectively isolate microorganisms with the potential to produce new antibiotics from soil environments. Over the last 7 years, 32 MicroMundo hubs operating across 31 different Portuguese and Spanish universities have recruited thousands of teenagers in this quest. Here we review the outcome of this unprecedented effort from a scientific and an educational perspective.