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Abstract Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare complication, which develops within 3–6 weeks after SARS-CoV2 infection. The coronavirus disease 2019 (COVID-19) vaccine was firstly introduced in adults and adolescents and later in patients aged 5–11 years old. Although a reduced incidence of MIS-C and with less severe symptoms has been reported in vaccinated adolescents, there is little knowledge in children younger than 12 years of age. In addition, it is not understood whether MIS-C in vaccinated patients can be triggered by Covid19 vaccination or be secondary to a recent asymptomatic Sars-Cov2 infection. Case presentation We describe the case of a Caucasian 6-year-old girl, one month after double COVID-19 vaccination, who presented fever, acute abdominal pain, rash, pharyngotonsillitis, cheilitis, cervical lymphadenopathy without a prior detected Sars-Cov2 infection. She also had lymphopenia, increase in inflammatory markers, cardiac and pulmonary involvement. Therefore, we dosed both anti Sars-Cov2 Spike and Nucleocapsid antibodies, which were positive and allowed us to confirm the diagnosis of MIS-C. We promptly administered intravenous immunoglobulins and methylprednisone, resulting in the initial regression of fever. During the hospitalization, the child also developed pancreatitis and severe neurological involvement, including irritability, drowsiness, distal tremor, dyskinesia and buccal asymmetry with complete resolution after 2 months. After 3 months from the onset of the symptoms, she reported a transient loss of hair compatible with telogen effluvium. After 12 months of follow-up, she did not show any symptomatic sequelae. Conclusions This case raises the question of whether COVID-19 vaccination may be involved in the pathogenesis of MIS-C in children between the ages of 5 and 11 years old.

Abstract Iron storage proteins, e.g., vertebrate ferritin, and the ferritin-like bacterioferritin (Bfr) and bacterial ferritin (Ftn), are spherical, hollow proteins that catalyze the oxidation of Fe2+ at binuclear iron ferroxidase centers (FOC) and store the Fe3+ in their interior, thus protecting cells from unwanted Fe3+/Fe2+ redox cycling and storing iron at concentrations far above the solubility of Fe3+. Vertebrate ferritins are heteropolymers of H and L subunits with only the H subunits having FOC. Bfr and Ftn were thought to coexist in bacteria as homopolymers, but recent evidence indicates these molecules are heteropolymers assembled from Bfr and Ftn subunits. Despite the heteropolymeric nature of vertebrate and bacterial ferritins, structures have been determined only for recombinant proteins constituted by a single subunit type. Herein we report the structure of Acinetobacter baumannii bacterioferritin, the first structural example of a heteropolymeric ferritin or ferritin-like molecule, assembled from completely overlapping Ftn homodimers harboring FOC and Bfr homodimers devoid of FOC but binding heme. The Ftn homodimers function by catalyzing the oxidation of Fe2+ to Fe3+, while the Bfr homodimers bind a cognate ferredoxin (Bfd) which reduces the stored Fe3+ by transferring electrons via the heme, enabling Fe2+ mobilization to the cytosol for incorporation in metabolism.

Abstract Irradiation (IR) induces immunogenic cell death (ICD) in tumors, but it rarely leads to the abscopal effect (AE); even combining IR with immune checkpoint inhibitors has shown only anecdotal success in inducing AEs. In this study, we aimed to enhance the IR-induced immune response and generate reproducible AEs using the anti-alcoholism drug, disulfiram (DSF), complexed with copper (DSF/Cu) to induce tumor ICD. We measured ICD in vitro and in vivo. In mouse tumor models, DSF/Cu was injected intratumorally followed by localized tumor IR, creating an in situ cancer vaccine. We determined the anticancer response by primary tumor rejection and assessed systemic immune responses by tumor rechallenge and the occurrence of AEs relative to spontaneous lung metastasis. In addition, we analyzed immune cell subsets and quantified proinflammatory and immunosuppressive chemokines/cytokines in the tumor microenvironment (TME) and blood of the vaccinated mice. Immune cell depletion was investigated for its effects on the vaccine-induced anticancer response. The results showed that DSF/Cu and IR induced more potent ICD under hypoxia than normoxia in vitro. Low-dose intratumoral (i.t.) injection of DSF/Cu and IR(12Gy) demonstrated strong anti-primary and -rechallenged tumor effects and robust AEs in mouse models. These vaccinations also increased CD8+ and CD4+ cell numbers while decreasing Tregs and myeloid-derived suppressor cells in the 4T1 model, and increased CD8+, dendritic cells (DC), and decreased Treg cell numbers in the MCa-M3C model. Depleting both CD8+ and CD4+ cells abolished the vaccine’s anticancer response. Moreover, vaccinated tumor-bearing mice exhibited increased TNFα levels and reduced levels of immunosuppressive chemokines/cytokines. In conclusion, our novel approach generated an anticancer immune response that results in a lack of or low tumor incidence post-rechallenge and robust AEs, i.e., absence of or decreased spontaneous lung metastasis in tumor-bearing mice. This approach is readily translatable to clinical settings and may increase IR-induced AEs in cancer patients.

Abstract Background Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of skin and several internal organs, including lungs. Macrophages are the main cells involved in the immune-inflammatory damage of skin and lungs, and alternatively activated (M2) macrophages seem to have a profibrotic role through the release of profibrotic cytokines (IL10) and growth factors (TGFβ1). Nintedanib is a tyrosine kinase inhibitor targeting several fibrotic mediators and it is approved for the treatment of SSc-related interstitial lung disease (ILD). The study aimed to evaluate the effect of nintedanib in downregulating the profibrotic M2 phenotype in cultured monocyte-derived macrophages (MDMs) obtained from SSc-ILD patients. Methods Fourteen SSc patients, fulfilling the 2013 ACR/EULAR criteria for SSc, 10 SSc patients affected by ILD (SSc-ILD pts), 4 SSc patients non affected by ILD (SSc pts no-ILD), and 5 voluntary healthy subjects (HSs), were recruited at the Division of Clinical Rheumatology-University of Genova, after obtaining Ethical Committee approval and patients’ informed consent. Monocytes were isolated from peripheral blood, differentiated into MDMs, and then maintained in growth medium without any treatment (untreated cells), or treated with nintedanib (0.1 and 1µM) for 3, 16, and 24 h. Gene expression of macrophage scavenger receptors (CD204, CD163), mannose receptor-1 (CD206), Mer tyrosine kinase (MerTK), identifying M2 macrophages, together with TGFβ1 and IL10, were evaluated by quantitative real-time polymerase chain reaction. Protein synthesis was investigated by Western blotting and the level of active TGFβ1 was evaluated by ELISA. Statistical analysis was carried out using non-parametric Wilcoxon test. Results Cultured untreated SSc-ILD MDMs showed a significant increased protein synthesis of CD206 (p

1. Antonini, E., Bellotti, L., Bernasconi, L., Cahenzli, F., Chiappini, M., Ielmini, P., Juri, C., & Mc Leod, P. (2023). Matematica in natura. Giochi matematici da vivere all’aperto. Dipartimento formazione e apprendimento / Alta scuola pedagogica, SUPSI. https://www.matematicando.supsi.ch/risorse-didattiche/matematica-in-natura/ 2. Arrigo, G. (2023). Insegnare matematica con i concetti fondanti nella scuola primaria. LS Scuola. 3. Cameron, P. (2008). Paura della matematica. Adelphi. 4. Demartini, S., & Sbaragli, S. (2024). A spasso con i numeri naturali. RSI Kids e Dipartimento formazione e apprendimento / Alta scuola pedagogica della SUPSI. https://www.matematicando.supsi.ch/iniziative/a-spasso-con-i-numeri-naturali/ 5. Sbaragli, S., Barbero, M., Crivelli, L., Di Domenico, A., Franchini, E., Magnone, S., Mina, C., Panero, M., & Poretti, C. (2023). MaMa: matematica per la scuola elementare – Geometria. Dipartimento dell’educazione, della cultura e dello sport. https://mama.edu.ti.ch/ 6. Zan, R. (2022). Problemi al centro con Ebix e Ibby. Giunti Scuola.

Abstract The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquire early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogram and reverse the immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells of healthy donors or metastatic female breast cancer patients, induce robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a promising therapy for solid tumors.

Two coding variants of apolipoprotein L1 (APOL1), called G1 and G2, explain much of the excess risk of kidney disease in African Americans. While various cytotoxic phenotypes have been reported in experimental models, the proximal mechanism by which G1 and G2 cause kidney disease is poorly understood. Here, we leveraged 3 experimental models and a recently reported small molecule blocker of APOL1 protein, VX-147, to identify the upstream mechanism of G1-induced cytotoxicity. In HEK293 cells, we demonstrated that G1-mediated [Na.sup.+] import/[K.sup.+] efflux triggered activation of GPCR/IP3- mediated calcium release from the ER, impaired mitochondrial ATP production, and impaired translation, which were all reversed by VX- 147. In human urine-derived podocyte-like epithelial cells (HUPECs), we demonstrated that G1 caused cytotoxicity that was again reversible by VX-147. Finally, in podocytes isolated from APOL1G1 transgenic mice, we showed that IFN-[gamma]- mediated induction of G1 caused [K.sup.+] efflux, activation of GPCR/IP3 signaling, and inhibition of translation, podocyte injury, and proteinuria, all reversed by VX-147. Together, these results establish APOL1-mediated [Na.sup.+]/[K.sup.+] transport as the proximal driver of APOL1-mediated kidney disease., Introduction Two African apolipoprotein L1 (APOL1) variants, named G1 (p.S342G and p.I384M) and G2 (deletion of p.N388/Y389), appear to have evolved to confer protection against the African sleeping sickness parasite [...]

In addition to energy recovery, the anaerobic digestion of agro-industrial byproducts can also produce different high-value-added compounds. Two-stage and single-stage reactors were compared for microbial communities’ selection and long-chain fatty acid (LCFA) accumulation to investigate which microbial genera are most linked to the production of these compounds. The microbial communities present in the two reactors’ configuration in the steady state were characterised by 16S rRNA amplicon sequencing, while LCFAs were extracted and quantified from digestate samples by gas chromatography. The results showed the differentiation of the microbially dominant families in the two setups: Defluviitaleaceae and Clostridiaceae in the acidogenic and methanogenic reactor of the two-stage reaction respectively, while Dysgonomonadaceae in the single-stage set-up. LCFA accumulation was significantly detected only in the acidogenic reactor, with palmitic (2764 mg/kg), linoleic (1795 mg/kg) and stearic (1751 mg/kg) acids as the most abundant. The dominance of Defluviitaleaceae UCG 011, along with the low abundance of the LCFA oxidiser Syntrophomonas spp. in the acidogenic reactor, could be linked to the accumulation of such compounds. Therefore, the different microbial communities shaped by the two reactors’ configuration affected the accumulation of LCFAs, indicating that the two-stage anaerobic digestion of agro-industrial byproducts was more effective than single-stage digestion.

Abstract Brain tumors are the leading cause of cancer‐related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient‐derived organoids (PDOs) from ependymomas, medulloblastomas, low‐grade glial tumors, and patient‐derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.

ABSTRACTThis paper presents the results of the 2021 and 2022 field activities carried out at San Nicola Island (Tremiti Islands, Southern Adriatic Sea) by two groups of students as part of the Environmental Geomorphology Field Mapping course held within the Master's Degree in Geological Sciences and Technologies of Earth and Planets at University ‘G. d'Annunzio’ of Chieti-Pescara. Field activities were carried out following an integrated approach that involved morphometric, geological, and geomorphological analyses, supported by the combination of traditional methods with modern survey instruments and techniques. The Main Map (1:2,500 scale) comprehensively depicts the landscape of San Nicola Island, which is affected by both long- and short-term evolutionary processes, as witnessed by widespread slope landforms. The cartographic products presented in this work can represent a useful tool in territorial planning and management, as well as a valuable base for further scientific studies.

We analysed the spatially explicit floristic information available in the herbarium of Ulisse Aldrovandi (1551–1586) to track floristic changes in the surroundings of Bologna across five centuries. Aldrovandi's data were compared with the Flora della Provincia di Bologna by Girolamo Cocconi (1883) and the Floristic Database of Emilia-Romagna (1965–2021). We explored potential variations in native range and life forms composition, and habitat affinity of the species in the three floras, also contrasting between native and alien species. Native species, mainly in terms of variations of hydro-hygrophytes, chamaephytes and therophytes, provide clear signals of human disturbance and habitat loss. Signals of climate change are provided by the high-mountain species, that were comparably rare between Aldrovandi and current flora and more represented in Cocconi, probably reflecting the effect of the Little Ice Age. Our findings also indicate the increasing importance of alien species from the Renaissance onwards. In this perspective, Aldrovandi's herbarium preserves the memory of the first signs of a radical transformation of the European flora and habitats. Finally, the study warns about the risk of dismissing herbaria and herbarium specimens collection, which would cause irreparable lacunas in our botanical memory, hindering our ability to predict biodiversity trajectories.

Abstract The protection of marine habitats from human-generated underwater noise is an emerging challenge. Baseline information on sound levels, however, is poorly available, especially in the Mediterranean Sea. To bridge this knowledge gap, the SOUNDSCAPE project ran a basin-scale, cross-national, long-term underwater monitoring in the Northern Adriatic Sea. A network of nine monitoring stations, characterized by different natural conditions and anthropogenic pressures, ensured acoustic data collection from March 2020 to June 2021, including the full lockdown period related to the COVID-19 pandemic. Calibrated stationary recorders featured with an omnidirectional Neptune Sonar D60 Hydrophone recorded continuously 24 h a day (48 kHz sampling rate, 16 bit resolution). Data were analysed to Sound Pressure Levels (SPLs) with a specially developed and validated processing app. Here, we release the dataset composed of 20 and 60 seconds averaged SPLs (one-third octave, base 10) output files and a Python script to postprocess them. This dataset represents a benchmark for scientists and policymakers addressing the risk of noise impacts on marine fauna in the Mediterranean Sea and worldwide.