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1. Chorioretinal biomarkers in hypothalamic amenorrhea

Author

Savastano, Maria Cristina, Fossataro, Claudia, Carlà, Matteo Mario, Cestrone, Valentina, Biagini, Ilaria, Sammarco, Leonardo, Giannuzzi, Federico, Fasciani, Romina, Apa, Rosanna, Lanzone, Antonio, Diterlizzi, Alice, Policriti, Martina, Di Stasio, Enrico, Killian, Raphael, Rizzo, Clara, and Rizzo, Stanislao

Published
2024
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7. Targeting de novo lipid synthesis induces lipotoxicity and impairs DNA damage repair in glioblastoma mouse models.

Author

Jha, Roshani, Mnatsakanyan, Hayk, Pechdimaljian, Caline, Carvalho, Litia, Neustadt, Rudolph, Moses, Charlotte, Alnasser, Ahmad, Tardiff, Daniel, Su, Baolong, Williams, Kevin, Chung, Chee, Badr, Christian, Eyme, Katharina, Bensinger, Steven, and Sammarco, Alessandro

Subjects
Animals, Mice, Glioblastoma, AMP-Activated Protein Kinases, Cell Line, Tumor, Brain Neoplasms, Xenograft Model Antitumor Assays, DNA Damage, Lipids, Neoplastic Stem Cells
Abstract

Deregulated de novo lipid synthesis (DNLS) is a potential druggable vulnerability in glioblastoma (GBM), a highly lethal and incurable cancer. Yet the molecular mechanisms that determine susceptibility to DNLS-targeted therapies remain unknown, and the lack of brain-penetrant inhibitors of DNLS has prevented their clinical evaluation as GBM therapeutics. Here, we report that YTX-7739, a clinical-stage inhibitor of stearoyl CoA desaturase (SCD), triggers lipotoxicity in patient-derived GBM stem-like cells (GSCs) and inhibits fatty acid desaturation in GSCs orthotopically implanted in mice. When administered as a single agent, or in combination with temozolomide (TMZ), YTX-7739 showed therapeutic efficacy in orthotopic GSC mouse models owing to its lipotoxicity and ability to impair DNA damage repair. Leveraging genetic, pharmacological, and physiological manipulation of key signaling nodes in gliomagenesis complemented with shotgun lipidomics, we show that aberrant MEK/ERK signaling and its repression of the energy sensor AMP-activated protein kinase (AMPK) primarily drive therapeutic vulnerability to SCD and other DNLS inhibitors. Conversely, AMPK activation mitigates lipotoxicity and renders GSCs resistant to the loss of DNLS, both in culture and in vivo, by decreasing the saturation state of phospholipids and diverting toxic lipids into lipid droplets. Together, our findings reveal mechanisms of metabolic plasticity in GSCs and provide a framework for the rational integration of DNLS-targeted GBM therapies.

Published
2023

8. The evolutionary consequences of interactions between the epigenome, the genome and the environment

Author

Pierre Baduel, Iris Sammarco, Rowan Barrett, Marta Coronado‐Zamora, Amélie Crespel, Bárbara Díez‐Rodríguez, Janay Fox, Dario Galanti, Josefa González, Alexander Jueterbock, Eric Wootton, and Ewan Harney

Subjects
DNA methylation, epigenetics, gene–environment interactions, natural populations, transgenerational effects, transposable elements, Evolution, QH359-425
Abstract

Abstract The epigenome is the suite of interacting chemical marks and molecules that helps to shape patterns of development, phenotypic plasticity and gene regulation, in part due to its responsiveness to environmental stimuli. There is increasing interest in understanding the functional and evolutionary importance of this sensitivity under ecologically realistic conditions. Observations that epigenetic variation abounds in natural populations have prompted speculation that it may facilitate evolutionary responses to rapid environmental perturbations, such as those occurring under climate change. A frequent point of contention is whether epigenetic variants reflect genetic variation or are independent of it. The genome and epigenome often appear tightly linked and interdependent. While many epigenetic changes are genetically determined, the converse is also true, with DNA sequence changes influenced by the presence of epigenetic marks. Understanding how the epigenome, genome and environment interact with one another is therefore an essential step in explaining the broader evolutionary consequences of epigenomic variation. Drawing on results from experimental and comparative studies carried out in diverse plant and animal species, we synthesize our current understanding of how these factors interact to shape phenotypic variation in natural populations, with a focus on identifying similarities and differences between taxonomic groups. We describe the main components of the epigenome and how they vary within and between taxa. We review how variation in the epigenome interacts with genetic features and environmental determinants, with a focus on the role of transposable elements (TEs) in integrating the epigenome, genome and environment. And we look at recent studies investigating the functional and evolutionary consequences of these interactions. Although epigenetic differentiation in nature is likely often a result of drift or selection on stochastic epimutations, there is growing evidence that a significant fraction of it can be stably inherited and could therefore contribute to evolution independently of genetic change.

Published
2024
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9. Adenosine A2A receptor as a potential regulator of Mycobacterium leprae survival mechanisms: new insights into leprosy neural damage

Author

Plinio Marcos Freire dos Santos, Chyntia Carolina Díaz Acosta, Thabatta Leal Silveira Andrezo Rosa, Michelle Harumi Ishiba, André Alves Dias, Antonio Marcos Rodrigues Pereira, Luísa Domingos Gutierres, Melissa Pontes Pereira, Matheus da Silva Rocha, Patrícia Sammarco Rosa, Daniele F. F. Bertoluci, José Roberto Meyer-Fernandes, Fabricio da Mota Ramalho Costa, Maria Angela M. Marques, John T. Belisle, Roberta Olmo Pinheiro, Luciana Silva Rodrigues, Maria Cristina Vidal Pessolani, and Marcia Berrêdo-Pinho

Subjects
Leprosy, schwann cell, M. leprae, adenosinergic system, A2A receptor, lipid droplet, Therapeutics. Pharmacology, RM1-950
Abstract

BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae, which can lead to a disabling neurodegenerative condition. M. leprae preferentially infects skin macrophages and Schwann cells–glial cells of the peripheral nervous system. The infection modifies the host cell lipid metabolism, subverting it in favor of the formation of cholesterol-rich lipid droplets (LD) that are essential for bacterial survival. Although researchers have made progress in understanding leprosy pathogenesis, many aspects of the molecular and cellular mechanisms of host–pathogen interaction still require clarification. The purinergic system utilizes extracellular ATP and adenosine as critical signaling molecules and plays several roles in pathophysiological processes. Furthermore, nucleoside surface receptors such as the adenosine receptor A2AR involved in neuroimmune response, lipid metabolism, and neuron–glia interaction are targets for the treatment of different diseases. Despite the importance of this system, nothing has been described about its role in leprosy, particularly adenosinergic signaling (AdoS) during M. leprae–Schwann cell interaction.MethodsM. leprae was purified from the hind footpad of athymic nu/nu mice. ST88-14 human cells were infected with M. leprae in the presence or absence of specific agonists or antagonists of AdoS. Enzymatic activity assays, fluorescence microscopy, Western blotting, and RT-qPCR analysis were performed. M. leprae viability was investigated by RT-qPCR, and cytokines were evaluated by enzyme-linked immunosorbent assay.ResultsWe demonstrated that M. leprae-infected Schwann cells upregulated CD73 and ADA and downregulated A2AR expression and the phosphorylation of the transcription factor CREB (p-CREB). On the other hand, activation of A2AR with its selective agonist, CGS21680, resulted in: 1) reduced lipid droplets accumulation and pro-lipogenic gene expression; 2) reduced production of IL-6 and IL-8; 3) reduced intracellular M. leprae viability; 4) increased levels of p-CREB.ConclusionThese findings suggest the involvement of the AdoS in leprosy neuropathogenesis and support the idea that M. leprae, by downmodulating the expression and activity of A2AR in Schwann cells, decreases A2AR downstream signaling, contributing to the maintenance of LD accumulation and intracellular viability of the bacillus.

Published
2024
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10. Advanced Simulation Model for Studying Biofuel-producing Microalgae Populations

Author

Bartolomeo Cosenza, Michele Miccio, Gabriele Pannocchia, and Ignazio Sammarco

Subjects
Chemical engineering, TP155-156, Computer engineering. Computer hardware, TK7885-7895
Abstract

b Dipartimento di Ingegneria Industriale (DIIn), Università degli Studi di Salerno, via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy, michele.miccio@unisa.itc Università degli Studi di Palermo, Italyignazio.sammarco@you.unipa.itMicroalgae play a crucial role in various sectors, such as biofuel production or environmental monitoring. The ability to accurately classify and analyze microalgae species from optical images is vital for advancing research and applications. Generally, the data regarding the population of microalgae constitute a valuable input for machine-learning algorithms whose aim is to classify real data derived from optical images of microalgae cells. However, obtaining a diverse dataset of microalgae populations to train machine-learning models can be challenging and resource-intensive. This paper presents a machine-learning algorithm based on a dataset of algal records generated by a simulation model. The simulation model uses a combination of mathematical models, probabilistic distributions, and biological knowledge to create realistic data on microalgae populations. The dataset generated from the developed model serves as a resource for training and validation of the subsequent machine-learning model proposed for the microalgae classification task. The machine learning model, trained on this synthetic data, can subsequently be applied to efficiently classify and analyze optical images of real microalgae populations, leading to improved precision and reliability in the identification of species useful to produce biofuels.

Published
2024

11. Enhancing the Functional Performance of Patients with Late-Stage Age-Related Macular Degeneration Implanted with a Miniature Telescope using Rehabilitation Training

Author

Paola Sasso, Alfonso Savastano, Faustino Vidal-Aroca, Angelo Maria Minnella, Giuseppe Francione, Leonardo Sammarco, Valentina Cima, Ritangela Ghiraldelli, Roberta Mattei, and Stanislao Rizzo

Subjects
Late-stage age-related macular degeneration (AMD), Geographic atrophy, Visual impairment, Implantable ophthalmic device, Intraocular lens, Low vision, visual rehabilitation, speed reading, reading acuity, smaller-incision new generation implantable miniature telescope, SING IMT, Ophthalmology, RE1-994
Abstract

Abstract Introduction In this work, our aim is to report the functional outcomes of cataract surgery with smaller-incision new-generation miniature telescope (SING IMT) implantation followed by rehabilitation training in patients with central visual loss due to late-stage age-related macular degeneration (AMD). Methods This retrospective study included patients who were monocularly implanted with SING IMT and then followed a rehabilitation program based on 6 biweekly sessions focused on visual abilities, reading, writing, visual motor integration and mobility. A total of 11 participants were included in this study. Reading acuity (RA), reading speed (RS), and fixation stability (FS) were assessed biweekly at 6-, 8-, 10-, 12-, 14-, and 16-week follow-up visits after SING IMT implantation and at a final assessment at 24 weeks. Best-corrected distance visual acuity (BCDVA) was also measured at baseline and at the same postoperative timepoints. Results Mean baseline BCDVA was 12.5 ± 8.6 letter score. Both RA and RS were found to be significantly improved from the first rehabilitation session (6 weeks after surgery) to the last session (24 weeks after surgery). At the end of the rehabilitation program, mean RA was 0.45 ± 0.19 LogMAR and mean RS was 30.9 ± 17.6 words per minute. Moreover, all patients achieved a FS of 15 s or more after the last rehabilitation session. Most patients (55%) achieved an improvement of 15 letters in BCDVA at the end of the study. Conclusions This study suggests that rehabilitation training can improve visual functions of patients with late-stage AMD implanted with SING IMT in real-world tasks such as reading skills.

Published
2024
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12. Spatial transcriptomic interrogation of the murine bone marrow signaling landscape

Author

Xue Xiao, Conan Juan, Tingsheng Drennon, Cedric R. Uytingco, Neda Vishlaghi, Dimitri Sokolowskei, Lin Xu, Benjamin Levi, Mimi C. Sammarco, and Robert J. Tower

Subjects
Biology (General), QH301-705.5, Physiology, QP1-981
Abstract

Abstract Self-renewal and differentiation of skeletal stem and progenitor cells (SSPCs) are tightly regulated processes, with SSPC dysregulation leading to progressive bone disease. While the application of single-cell RNA sequencing (scRNAseq) to the bone field has led to major advancements in our understanding of SSPC heterogeneity, stem cells are tightly regulated by their neighboring cells which comprise the bone marrow niche. However, unbiased interrogation of these cells at the transcriptional level within their native niche environment has been challenging. Here, we combined spatial transcriptomics and scRNAseq using a predictive modeling pipeline derived from multiple deconvolution packages in adult mouse femurs to provide an endogenous, in vivo context of SSPCs within the niche. This combined approach localized SSPC subtypes to specific regions of the bone and identified cellular components and signaling networks utilized within the niche. Furthermore, the use of spatial transcriptomics allowed us to identify spatially restricted activation of metabolic and major morphogenetic signaling gradients derived from the vasculature and bone surfaces that establish microdomains within the marrow cavity. Overall, we demonstrate, for the first time, the feasibility of applying spatial transcriptomics to fully mineralized tissue and present a combined spatial and single-cell transcriptomic approach to define the cellular components of the stem cell niche, identify cell‒cell communication, and ultimately gain a comprehensive understanding of local and global SSPC regulatory networks within calcified tissue.

Published
2023
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15. A Serverless Cloud Integration For Quantum Computing

Author

Grossi, M., Crippa, L., Aita, A., Bartoli, G., Sammarco, V., Picca, E., Said, N., Tramonto, F., and Mattei, F.

Subjects
Computer Science - Emerging Technologies, Quantum Physics
Abstract

Starting from the idea of Quantum Computing which is a concept that dates back to 80s, we come to the present day where we can perform calculations on real quantum computers. This sudden development of technology opens up new scenarios that quickly lead to the desire and the real possibility of integrating this technology into current software architectures. The usage of frameworks that allow computation to be performed directly on quantum hardware poses a series of challenges. This document describes a an architectural framework that addresses the problems of integrating an API exposed Quantum provider in an existing Enterprise architecture and it provides a minimum viable product (MVP) solution that really merges classical quantum computers on a basic scenario with reusable code on GitHub repository. The solution leverages a web-based frontend where user can build and select applications/use cases and simply execute it without any further complication. Every triggered run leverages on multiple backend options, that include a scheduler managing the queuing mechanism to correctly schedule jobs and final results retrieval. The proposed solution uses the up-to-date cloud native technologies (e.g. Cloud Functions, Containers, Microservices) and serves as a general framework to develop multiple applications on the same infrastructure., Comment: 8 pages, 4 figures. Conceptualization, Methodology, Software, Writing - Original Draft, Review & Editing: MG, LC, AA. Methodology, Software Design, Writing, Review & Editing: GB, VS. Software and Formal analysis, Writing, Review & Editing: EP, NS, FT. Supervision and validation: FM

Published
2021

18. Human Skin as an Ex Vivo Model for Maintaining Mycobacterium leprae and Leprosy Studies

Author

Natália Aparecida de Paula, Marcel Nani Leite, Daniele Ferreira de Faria Bertoluci, Cleverson Teixeira Soares, Patrícia Sammarco Rosa, and Marco Andrey Cipriani Frade

Subjects
Mycobacterium leprae, leprosy, hOSEC, ex vivo skin culture, animal-use alternatives, tissue culture techniques, Medicine
Abstract

The in vitro cultivation of M. leprae has not been possible since it was described as causing leprosy, and the limitation of animal models for clinical aspects makes studies on leprosy and bacteria–human host interaction a challenge. Our aim was to standardize the ex vivo skin model (hOSEC) to maintenance and study of M. leprae as an alternative animal model. Bacillary suspensions were inoculated into human skin explants and sustained in DMEM medium for 60 days. Explants were evaluated by RT-PCR-16SrRNA and cytokine gene expression. The viability and infectivity of bacilli recovered from explants (D28 and D60) were evaluated using the Shepard’s model. All explants were RT-PCR-16SrRNA positive. The viability and infectivity of recovered bacilli from explants, analyzed after 5 months of inoculation in mice, showed an average positivity of 31%, with the highest positivity in the D28 groups (80%). Furthermore, our work showed different patterns in cytokine gene expression (TGF-β, IL-10, IL-8, and TNF-α) in the presence of alive or dead bacilli. Although changes can be made to improve future experiments, our results have demonstrated that it is possible to use the hOSEC to maintain M. leprae for 60 days, interacting with the host system, an important step in the development of experimental models for studies on the biology of the bacillus, its interactions, and drug susceptibility.

Published
2024
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19. First-Line Treatments and Management of Metastatic Renal Cell Carcinoma Patients: An Italian Interdisciplinary Uro-Oncologic Group Algorithm

Author

Francesco Bloise, Fiorella Manfredi, Luca Zatteri, Giovanni Dima, Chiara Carli, Rosanna Di Vita, Maria Olivieri, Enrico Sammarco, Marco Ferrari, Alessia Salfi, Adele Bonato, Debora Serafin, Natalia Coccia, Laura Doni, Luca Galli, Michele Sisani, Giandomenico Roviello, Martina Catalano, and Federico Paolieri

Subjects
metastatic renal cell carcinoma, first-line therapy, tyrosine kinase inhibitors, immune checkpoints inhibitors, treatment algorithm, Cytology, QH573-671
Abstract

The treatment landscape for metastatic renal cell carcinoma (mRCC) has undergone significant transformations in recent years. The introduction of novel combination therapies involving tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors has resulted in improved oncological outcomes compared to traditional TKI monotherapy. In this evolving paradigm, the pivotal role of the multidisciplinary tumor board is underscored, particularly in shaping the therapeutic trajectory for patients eligible for locoregional interventions like cytoreductive nephrectomy and metastasectomy. In cases where systemic treatment is deemed appropriate, the absence of direct comparisons among the various combination therapies complicates the selection of a first-line approach. The clinician is faced with the challenge of making decisions based on patient-specific factors such as performance status, risk classification according to the International Metastatic Renal Cell Carcinoma Database Consortium, comorbidities, and disease characteristics, including the number and location of metastases and tumor histology. Considering these concerns, we propose, as a member of a Tuscany Interdisciplinary Uro-Oncologic Group, an algorithm to streamline the decision-making process for mRCC patients, offering guidance to clinicians in their day-to-day clinical practice.

Published
2024
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20. Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis

Author

Tiziana Fioretti, Fabrizio Martora, Ilaria De Maggio, Adelaide Ambrosio, Carmelo Piscopo, Sabrina Vallone, Felice Amato, Diego Passaro, Fabio Acquaviva, Francesca Gaudiello, Daniela Di Girolamo, Valeria Maiolo, Federica Zarrilli, Speranza Esposito, Giuseppina Vitiello, Luigi Auricchio, Elena Sammarco, Daniele De Brasi, Roberta Petillo, Antonella Gambale, Fabio Cattaneo, Rosario Ammendola, Paola Nappa, and Gabriella Esposito

Subjects
congenital nonsyndromic ichthyosis, molecular diagnosis, splicing variant, X-linked ichthyosis, Biology (General), QH301-705.5
Abstract

Inherited ichthyoses are a group of clinically and genetically heterogeneous rare disorders of skin keratinization with overlapping phenotypes. The clinical picture and family history are crucial to formulating the diagnostic hypothesis, but only the identification of the genetic defect allows the correct classification. In the attempt to molecularly classify 17 unrelated Italian patients referred with congenital nonsyndromic ichthyosis, we performed massively parallel sequencing of over 50 ichthyosis-related genes. Genetic data of 300 Italian unaffected subjects were also analyzed to evaluate frequencies of putative disease-causing alleles in our population. For all patients, we identified the molecular cause of the disease. Eight patients were affected by autosomal recessive congenital ichthyosis associated with ALOX12B, NIPAL4, and TGM1 mutations. Three patients had biallelic loss-of-function variants in FLG, whereas 6/11 males were affected by X-linked ichthyosis. Among the 24 different disease-causing alleles we identified, 8 carried novel variants, including a synonymous TGM1 variant that resulted in a splicing defect. Moreover, we generated a priority list of the ichthyosis-related genes that showed a significant number of rare and novel variants in our population. In conclusion, our comprehensive molecular analysis resulted in an effective first-tier test for the early classification of ichthyosis patients. It also expands the genetic, mutational, and phenotypic spectra of inherited ichthyosis and provides new insight into the current understanding of etiologies and epidemiology of this group of rare disorders.

Published
2024
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21. Response of Fragaria vesca to projected change in temperature, water availability and concentration of CO2 in the atmosphere

Author

Iris Sammarco, Zuzana Münzbergová, and Vít Latzel

Subjects
Medicine, Science
Abstract

Abstract The high rate of climate change may soon expose plants to conditions beyond their adaptation limits. Clonal plants might be particularly affected due to limited genotypic diversity of their populations, potentially decreasing their adaptability. We therefore tested the ability of a widely distributed predominantly clonally reproducing herb (Fragaria vesca) to cope with periods of drought and flooding in climatic conditions predicted to occur at the end of the twenty-first century, i.e. on average 4 °C warmer and with twice the concentration of CO2 in the air (800 ppm) than the current state. We found that F. vesca can phenotypically adjust to future climatic conditions, although its drought resistance may be reduced. Increased temperature and CO2 levels in the air had a far greater effect on growth, phenology, reproduction, and gene expression than the temperature increase itself, and promoted resistance of F. vesca to repeated flooding periods. Higher temperature promoted clonal over sexual reproduction, and increased temperature and CO2 concentration in the air triggered change in expression of genes controlling the level of self-pollination. We conclude that F. vesca can acclimatise to predicted climate change, but the increased ratio of clonal to sexual reproduction and the alteration of genes involved in the self-(in)compatibility system may be associated with reduced genotypic diversity of its populations, which may negatively impact its ability to genetically adapt to novel climate in the long-term.

Published
2023
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22. Avaliação do perfil de citocinas séricas e óxido nítrico na hanseníase experimental murina

Author

Adriana Sierra Assencio Almeida Barbosa, Thayna Sosolote Lima, Beatriz Gomes Carreira Sartori, Suzana Madeira Diório, Sônia Maria Usó Ruiz Silva, Vania Nieto Brito-de-Souza, Maria Renata Sales Nogueira, Patrícia Sammarco Rosa, Sílvia Cristina Barboza Pedrini, and Fátima Regina Vilani-Moreno

Subjects
Hanseníase, Modelos animais, Citocinas, Óxido nítrico, Imunidade, Infectious and parasitic diseases, RC109-216
Abstract

Introdução: a hanseníase é uma doença in fecciosa crônica causada pelo Mycobacterium leprae (M. leprae), um parasita intracelular obrigatório. Assim, a resistência do hospedeiro a esse patógeno depende da imunidade celular. O uso de modelos experimentais tem permitido o estudo da hanseníase do ponto de vista imunológico, microbiológico e terapêutico, entretanto, as diferenças na progressão da infecção entre os modelos mais empregados (camundongos imunocompetentes, BALB/c, e camundongos congenitamente atímicos, nude) são pouco estudadas. Objetivo: comparar a evolução da infecção pelo M. leprae em camundongos BALB/c e nude quanto à multiplicação bacilar e avaliação do perfil inflamatório sistêmico pela quantificação sérica de citocinas e óxido nítrico (NO). Métodos: os camundongos foram inoculados com M. leprae nos coxins plantares e avaliados aos 3, 5 e 8 meses após a infecção. Resultados: camundongos nude apresentaram multiplicação bacilar progressiva nos coxins plantares. Em camundongos BALB/c, o número de bacilos foi maior aos 5 meses. Em relação à quantificação de citocinas, nos camundongos BALB/c houve aumento de IL-2 e IL-17A e diminuição de IL-6 e NO aos 8 meses de inoculação. Nos camundongos nude, verificou-se o aumento do TNF aos 8 meses de inoculação e manutenção dos níveis de NO. Conclusão: os resultados encontrados sugerem que em camundongos BALB/c ocorre a ativação de uma resposta imune capaz de controlar a multiplicação do M. leprae, em contrapartida em camundongos nude a infecção é progressiva a despeito de altos níveis de TNF.

Published
2024
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23. Vehicle Telematics Via Exteroceptive Sensors: A Survey

Author

Ortiz, Fernando Molano, Sammarco, Matteo, Costa, Luís Henrique M. K., and Detyniecki, Marcin

Subjects
Electrical Engineering and Systems Science - Signal Processing, Computer Science - Human-Computer Interaction
Abstract

Whereas a very large number of sensors are available in the automotive field, currently just a few of them, mostly proprioceptive ones, are used in telematics, automotive insurance, and mobility safety research. In this paper, we show that exteroceptive sensors, like microphones or cameras, could replace proprioceptive ones in many fields. Our main motivation is to provide the reader with alternative ideas for the development of telematics applications when proprioceptive sensors are unusable for technological issues, privacy concerns, or lack of availability in commercial devices. We first introduce a taxonomy of sensors in telematics. Then, we review in detail all exteroceptive sensors of some interest for vehicle telematics, highlighting advantages, drawbacks, and availability in off-the-shelf devices. Successively, we present a list of notable telematics services and applications in research and industry like driving profiling or vehicular safety. For each of them, we report the most recent and important works relying on exteroceptive sensors, as long as the available datasets. We conclude showing open challenges using exteroceptive sensors both for industry and research., Comment: 18 pages, 4 figures, 7 tables

Published
2020

24. ENLIGHT: A consensus checklist for reporting laboratory-based studies on the non-visual effects of light in humansResearch in context

Author

Manuel Spitschan, Laura Kervezee, Renske Lok, Elise McGlashan, Raymond P. Najjar, Annette E. Allen, Marilyne Andersen, Salvador Bará, Peter Blattner, Christine Blume, Diane B. Boivin, María-Ángeles Bonmatí-Carrión, Kai Broszio, Timothy M. Brown, Sarah Laxhmi Chellappa, Jeanne F. Duffy, Taisuke Eto, Erin Flynn-Evans, Steve Fotios, Virginie Gabel, Corrado Garbazza, Gena Glickman, Marijke C. Gordijn, John P. Hanifin, Lauren Hartstein, Michael Herf, Shigekazu Higuchi, Cassie J. Hilditch, Kevin W. Houser, Anya Hurlbert, Monique K. LeBourgeois, Steven Lockley, Robert Lucas, Claudia R.C. Moreno, Mirjam Münch, Ludovic S. Mure, Stuart Peirson, Shadab Rahman, Victoria L. Revell, Roberto G. Rodriguez, Kathryn Roecklein, A.V. Rukmini, John Sammarco, Nayantara Santhi, Luc J.M. Schlangen, Isabel Schöllhorn, Katherine M. Sharkey, Debra J. Skene, Tracey L. Sletten, Karin C.H.J. Smolders, Oliver Stefani, Julia E. Stone, Petteri Teikari, Michael Terman, Khanh Tran Quoc, Kazuo Tsubota, Ljiljana Udovicic, Gilles Vandewalle, Jennifer A. Veitch, CélineVetter, Lisa M. Wu, Johannes Zauner, and Jamie Zeitzer

Subjects
Reporting guidelines, Non-visual effects of light, Circadian rhythms, Sleep, Interventions, Light, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: There is no consensus on reporting light characteristics in studies investigating non-visual responses to light. This project aimed to develop a reporting checklist for laboratory-based investigations on the impact of light on non-visual physiology. Methods: A four-step modified Delphi process (three questionnaire-based feedback rounds and one face-to-face group discussion) involving international experts was conducted to reach consensus on the items to be included in the checklist. Following the consensus process, the resulting checklist was tested in a pilot phase with independent experts. Findings: An initial list of 61 items related to reporting light-based interventions was condensed to a final checklist containing 25 items, based upon consensus among experts (final n = 60). Nine items were deemed necessary to report regardless of research question or context. A description of each item is provided in the accompanying Explanation and Elaboration (E&E) document. The independent pilot testing phase led to minor textual clarifications in the checklist and E&E document. Interpretation: The ENLIGHT Checklist is the first consensus-based checklist for documenting and reporting ocular light-based interventions for human studies. The implementation of the checklist will enhance the impact of light-based research by ensuring comprehensive documentation, enhancing reproducibility, and enabling data aggregation across studies. Funding: Network of European Institutes for Advanced Study (NETIAS) Constructive Advanced Thinking (CAT) programme; Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust, 204686/Z/16/Z); Netherlands Organisation for Health Research and Development VENI fellowship (2020–09150161910128); U.S. Department of Defense Grant (W81XWH-16-1-0223); National University of Singapore (NUHSRO/2022/038/Startup/08); and National Research Foundation Singapore (NRF2022-THE004-0002).

Published
2023
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26. Correction to: Surgical treatment of colonic Crohn’s disease: a national snapshot study

Author

Celentano, Valerio, Pellino, Gianluca, Rottoli, Matteo, Poggioli, Gilberto, Sica, Giuseppe, Giglio, Mariano Cesare, Campanelli, Michela, Coco, Claudio, Rizzo, Gianluca, Sionne, Francesco, Colombo, Francesco, Sampietro, Gianluca, Lamperti, Giulia, Foschi, Diego, Ficari, Ferdinando, Vacca, Ludovica, Cricchio, Marta, Giudici, Francesco, Selvaggi, Lucio, Sciaudone, Guido, Peltrini, Roberto, Manfreda, Andrea, Bucci, Luigi, Galleano, Raffaele, Ghazouani, Omar, Zorcolo, Luigi, Deidda, Simona, Restivo, Angelo, Braini, Andrea, Di Candido, Francesca, Sacchi, Matteo, Carvello, Michele, Martorana, Stefania, Bordignon, Giovanni, Angriman, Imerio, Variola, Angela, Barugola, Giuliano, Di Ruscio, Mirko, Tanzanu, Marta, Geccherle, Andrea, Tropeano, Francesca Paola, Luglio, Gaetano, Sasia, Diego, Migliore, Marco, Giuffrida, Maria Carmela, Marrano, Enrico, Moretto, Gianluigi, Impellizzeri, Harmony, Gallo, Gaetano, Vescio, Giuseppina, Sammarco, Giuseppe, Terrosu, Giovanni, Calini, Giacomo, Bondurri, Andrea, Maffioli, Anna, Zaffaroni, Gloria, Resegotti, Andrea, Mistrangelo, Massimiliano, Allaix, Marco Ettore, Botti, Fiorenzo, Prati, Matteo, Boni, Luigi, Perotti, Serena, Mineccia, Michela, Giuliani, Antonio, Romano, Lucia, Graziano, Giorgio Maria Paolo, Pugliese, Luigi, Pietrabissa, Andrea, Delaini, GianGaetano, Spinelli, Antonino, and Selvaggi, Francesco

Published
2022
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30. Orbital cellulitis and massive chemosis as first sign of a cilio-choroidal malignant melanoma without extraocular extension: A case report

Author

Matteo Mario Carlà, Carmela Grazia Caputo, Maria Grazia Sammarco, Federico Giannuzzi, Chiara Fantozzi, Gustavo Savino, Maria Antonietta Blasi, and Monica Maria Pagliara

Subjects
Orbital cellulitis, Choroidal melanoma, Ocular ultrasound, Conjunctival chemosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Purpose: To describe a case of cilio-choroidal melanoma presenting as aseptic orbital cellulitis with massive conjunctival chemosis. Methods: Case report. Results: A 51-year-old man with a left retro-iris pigmented lesion had acute lid edema, conjunctival chemosis, and extensive hyphema. Ultrasound revealed a large, lobulated, wide-base choroidal-starting lesion affecting the ciliary bodies and vitreous chamber. MRI revealed low-intermediate T2-signal and intermediate-high T1-signal, with substantial post-contrastographic enhancement. After one week of systemic corticosteroids, the chemosis reduced significantly, and the patient was referred for enucleation, even without histologic confirmation. Post-surgical histopathology found 90% necrotic tissue, few viable cells, and no scleral or vascular invasion, with genetic analysis showing monosomy of chromosome 3 and 8q gain. Conclusion: Choroidal melanoma, particularly if necrotic, may occasionally present as aseptic orbital cellulitis, even without extraocular spread.

Published
2023
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31. Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries

Author

Mwayi Kachapila, Mark Monahan, Adesoji O. Ademuyiwa, Yakubu Momohsani Adinoyi, Bruce M. Biccard, Christina George, Dhruva N. Ghosh, James Glasbey, Dion G. Morton, Osaheni Osayomwanbo, Rupert Pearse, Tracy E. Roberts, Atul Suroy, Saidu Yusuf Yakubu, Raymond Oppong, Aneel Bhangu, Maria Lorena Aguilera, Philip Alexander, Sara W. Al-Saqqa, Giuliano Borda-Luque, Ainhoa Costas-Chavarri, Thomas M. Drake, Faustin Ntirenganya, J. Edward Fitzgerald, Stuart J. Fergusson, J.C. Allen Ingabire, Lawani Ismaïl, Hosni Khairy Salem, Anyomih Theophilus Teddy Kojo, Marie Carmela Lapitan, Richard Lilford, Andre L. Mihaljevic, Dion Morton, Alphonse Zeta Mutabazi, Dmitri Nepogodiev, Adewale O. Adisa, Riinu Ots, Francesco Pata, Thomas Pinkney, Tomas Poškus, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Sarah Rayne, Catherine A. Shaw, Sebastian Shu, Richard Spence, Neil Smart, Stephen Tabiri, Ewen M. Harrison, Azmina Verjee, Emmy Runigamugabo, Chetan Khatri, Midhun Mohan, Zahra Jaffry, Afnan Altamini, Andrew Kirby, Kjetil Søreide, Gustavo Recinos, Jen Cornick, Maria Marta Modolo, Dushyant Iyer, Sebastian King, Tom Arthur, Sayeda Nazmum Nahar, Ade Waterman, Michael Walsh, Arnav Agarwal, Augusto Zani, Mohammed Firdouse, Tyler Rouse, Qinyang Liu, Juan Camilo Correa, Peep Talving, Mengistu Worku, Alexis Arnaud, Vassilis Kalles, Basant Kumar, Sunil Kumar, Radhian Amandito, Roy Quek, Luca Ansaloni, Ahmed Altibi, Donatas Venskutonis, Justas Zilinskas, Tomas Poskus, John Whitaker, Vanessa Msosa, Yong Yong Tew, Alexia Farrugia, Elaine Borg, Zineb Bentounsi, Tanzeela Gala, Ibrahim Al-Slaibi, Haya Tahboub, Osaid H. Alser, Diego Romani, Sebestian Shu, Piotr Major, Aurel Mironescu, Matei Bratu, Amar Kourdouli, Aliyu Ndajiwo, Abdulaziz Altwijri, Mohammed Ubaid Alsaggaf, Ahmad Gudal, Al Faifi Jubran, Sam Seisay, Bettina Lieske, Irene Ortega, Jenifa Jeyakumar, Kithsiri J. 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Samalavicius, Kristijonas Jasaitis, Audrius Parseliunas, Viktorija Nevieraite, Margarita Montrimaite, Evelina Slapelyte, Edvinas Dainius, Romualdas Riauka, Zilvinas Dambrauskas, Andrejus Subocius, Linas Venclauskas, Antanas Gulbinas, Saulius Bradulskis, Simona Kasputyte, Deimante Mikuckyte, Mindaugas Kiudelis, Tomas Jankus, Steponas Petrikenas, Matas Pažuskis, Zigmantas Urniežius, Mantas Vilčinskas, Vincas Jonas Banaitis, Vytautas Gaižauskas, Edvard Grisin, Povilas Mazrimas, Rokas Rackauskas, Mantas Drungilas, Karolis Lagunavicius, Vytautas Lipnickas, Dovilè Majauskyté, Valdemaras Jotautas, Tomas Abaliksta, Laimonas Uščinas, Gintaras Simutis, Adomas Ladukas, Donatas Danys, Erikas Laugzemys, Saulius Mikalauskas, Elena Zdanyte Sruogiene, Petras Višinskas, Reda Žilinskienė, Deividas Dragatas, Andrius Burmistrovas, Zygimantas Tverskis, Arturas Vaicius, Ruta Mazelyte, Antanas Zadoroznas, Nerijus Kaselis, Greta Žiubrytė, Finaritra Casimir Fleur Prudence Rahantasoa, Luc Hervé Samison, Fanjandrainy Rasoaherinomenjanahary, Todisoa Emmanuella Christina Tolotra, Cornelius Mukuzunga, Chimwemwe Kwatiwani, Nelson Msiska, Feng Yih Chai, Siti Mohd Desa Asilah, Khuzaimah Zahid Syibrah, Pui Xin Chin, Afizah Salleh, Nur Zulaika Riswan, April Camilla Roslani, Hoong-Yin Chong, Nora Abdul Aziz, Keat-Seong Poh, Chu-Ann Chai, Sandip Kumar, Mustafa Mohammed Taher, Nik Ritza Kosai, Dayang Nita Abdul Aziz, Reynu Rajan, Rokayah Julaihi, Durvesh Lacthman Jethwani, Muhammad Taqiyuddin Yahaya, Nik Azim Nik Abdullah, Susan Wndy Mathew, Kuet Jun Chung, Milaksh Kumar Nirumal, R. Goh Ern Tze, Syed Abdul Wahhab Eusoffee Wan Ali, Yiing Yee Gan, Jesse Ron Swire Ting, Samuel S.Y. Sii, Kean Leong Koay, Yi Koon Tan, Alvin Ee Zhiun Cheah, Chui Yee Wong, Tuan Nur'Azmah Tuan Mat, Crystal Yern Nee Chow, Prisca A.L. Har, Yishan Der, Fitjerald Henry, Xinwei Low, Ya Theng Neo, Hian Ee Heng, Shu Ning Kong, Cheewei Gan, Yi Ting Mok, Yee Wen Tan, Kandasami Palayan, Mahadevan Deva Tata, Yih Jeng Cheong, Kuhaendran Gunaseelan, Wan Nurul 'Ain Wan Mohd Nasir, Pigeneswaren Yoganathan, Eu Xian Lee, Jian Er Saw, Li Jing Yeang, Pei Ying Koh, Shyang Yee Lim, Shuang Yi Teo, Nicole Grech, Daniela Magri, Kristina Cassar, Christine Mizzi, Malcolm Falzon, Nihaal Shaikh, Ruth Scicluna, Stefan Zammit, Sean Mizzi, Svetlana Doris Brincat, Thelma Tembo, Vu Thanh Hien Le, Tara Grima, Keith Sammut, Kurt Carabott, Ciskje Zarb, Andre Navarro, Thea Dimech, Georgette Marie Camilleri, Isaac Bertuello, Jeffrey Dalli, Karl Bonavia, Samantha Corro-Diaz, Marisol Manriquez-Reyes, Amina Abdelhamid, Abdelmalek Hrora, Sarah Benammi, Houda Bachri, Meryem Abbouch, Khaoula Boukhal, Redouane Mammar Bennai, Abdelkader Belkouchi, Mohamed Sobhi Jabal, Chaymae Benyaiche, Maarten Vermaas, Lucia Duinhouwer, Javier Pastora, Greta Wood, Maria Soledad Merlo, Akinlabi Ajao, Omobolaji Ayandipo, Taiwo Lawal, Abdussemiu Abdurrazzaaq, Muslimat Alada, Abdulrasheed Nasir, James Adeniran, Olufemi Habeeb, Ademola Popoola, Ademola Adeyeye, Ademola Adebanjo, Opeoluwa Adesanya, Adewale Adeniyi, Henry Mendel, Bashir Bello, Umar Muktar, Adedapo Osinowo, Thomas Olagboyega Olajide, Oyindamola Oshati, George Ihediwa, Babajide Adenekan, Victor Nwinee, Felix Alakaloko, Adesoji Ademuyiwa, Olumide Elebute, Abdulrazzaq Lawal, Chris Bode, Mojolaoluwa Olugbemi, Alaba Adesina, Olubukola Faturoti, Oluwatomi Odutola, Oluwaseyi Adebola, Clement Onuoha, Ogechukwu Taiwo, Omolara Williams, Fatai Balogun, Olalekan Ajai, Mobolaji Oludara, Iloba Njokanma, Roland Osuoji, Stephen Kache, Jonathan Ajah, Jerry Makama, Ahmed Adamu, Suleiman Baba, Mohammad Aliyu, Shamsudeen Aliyu, Yahaya Ukwenya, Halima Aliyu, Tunde Sholadoye, Muhammad Daniyan, Oluseyi Ogunsua, Lofty-John Anyanwu, Abdurrahaman Sheshe, Aminu Mohammad, Samson Olori, Philip Mshelbwala, Babatunde Odeyemi, Garba Samson, Oyediran Kehinde Timothy, Sani Ali Samuel, Anthony Ajiboye, Isaac Amole, Olajide Abiola, Akin Olaolorun, Torhild Veen, Arezo Kanani, Kristian Styles, Ragnar Herikstad, Johannes Wiik Larsen, Jon Arne Søreide, Elisabeth Jensen, Mads Gran, Eirik Kjus Aahlin, Tina Gaarder, Peter Wiel Monrad-Hansen, Pål Aksel Næss, Giedrius Lauzikas, Joachim Wiborg, Silje Holte, Knut Magne Augestad, Gurpreet Singh Banipal, Michela Monteleone, Thomas Tetens Moe, Johannes Kurt Schultz, Taher Al-Taher, Ayah Hamdan, Ayman Salman, Rana Saadeh, Aseel Musleh, Dana Jaradat, Soha Abushamleh, Sakhaa Hanoun, Amjad Abu Qumbos, Aseel Hamarshi, Ayman, Taher, Israa Qawasmi, Khalid Qurie, Marwa Altarayra, Mohammad Ghannam, Alaa Shaheen, Azher Herebat, Aram Abdelhaq, Ahmad Shalabi, Maram Abu-Toyour, Fatema Asi, Ala Shamasneh, Anwar Atiyeh, Mousa Mustafa, Rula Zaa'treh, Majd Dabboor, Enas Alaloul, Heba Baraka, Jehad Meqbil, Alaa Al-Buhaisi, Mohamedraed Elshami, Samah Afana, Sahar Jaber, Said Alyacoubi, Yousef Abuowda, Tasneem Idress, Eman Abuqwaider, Sara Al-Saqqa, Alaa Bowabsak, Alaa El Jamassi, Doaa Hasanain, Hadeel Al-Farram, Maram Salah, Aya Firwana, Marwa Hamdan, Israa Awad, Ahmad Ashour, Fayez Elian Al Barrawi, Ahmed Al-Khatib, Maha Al-Faqawi, Mohamed Fares, Amjad Elmashala, Mohammad Adawi, Ihdaa Adawi, Reem Khreishi, Rose Khreishi, Ahed Ghaben, Najwa Nadeem, Muhammad Saqlain, Jibran Abbasy, Abdul Rehman Alvi, Noman Shahzad, Kamran Faisal Bhopal, Zainab Iftikhar, Muhammad Talha Butt, Syed Asaat Ul Razi, Asdaq Ahmed, Ali Khan Niazi, Ibrahim Raza, Fatima Baluch, Ahmed Raza, Ahmad Bani-Sadar, Muhammad Adil, Awais Raza, Mahnoor Javaid, Muhammad Waqar, Maryam Ali Khan, Mohammad Mohsin Arshad, Mohammadasim Amjad, Gustavo Miguel Machain Vega, Jorge Torres Cardozo, Marcelo O´Higgins Roche, Gustavo Rodolfo Pertersen Servin, Helmut Alfredo Segovia Lohse, Larissa Ines Páez Lopez, Ramón Augusto Melo Cardozo, Fernando Espinoza, Angel David Pérez Rojas, Diana Sanchez, Camila Sanchez Samaniego, Shalon Guevara Torres, Alexander Canta Calua, Cesar Razuri, Nadia Ortiz, Xianelle Rodriguez, Nahilia Carrasco, Fridiz Saravia, Hector Shibao Miyasato, María Valcarcel-Saldaña, Ysabel Esthefany Alejos Bermúdez, Juan Carpio, Walter Ruiz Panez, Pedro Angel Toribio Orbegozo, Carolina Guzmán Dueñas, Kevin Turpo Espinoza, Ana Maria Sandoval Barrantes, Jorge Armando Chungui Bravo, Lorena Fuentes-Rivera, Carmen Fernández, Bárbara Málaga, Joselyn Ye, Ricardo Velasquez, Jannin Salcedo, Ana Lucia Contreras-Vergara, Angelica Genoveva Vergara Mejia, Maria Soledad Gonzales Montejo, Marilia Del Carmen Escalante Salas, Willy Alcca Ticona, Marvin Vargas, George Christian Manrique Sila, Robinson Mas, Arazzelly del Pilar Paucar, Armando José Román Velásquez, Alina Robledo-Rabanal, Ludwing Alexander Zeta Solis, Kenny Turpo Espinoza, José Luis Hamasaki Hamaguchi, Erick Samuel Florez Farfan, Linda Alvi Madrid Barrientos, Juan Jaime Herrera Matta, John Jemuel V. Mora, Menold Archee P. Redota, Manuel Francisco Roxas, Maria Jesusa B. Maño, Marie Dione Parreno-Sacdalan, Christel Leanne Almanon, Maciej Walędziak, Rafał Roszkowski, Michał Janik, Anna Lasek, Dorota Radkowiak, Mateusz Rubinkiewicz, Cristina Fernandes, Jose Costa-Maia, Renato Melo, Liviu Muntean, Aurel Sandu Mironescu, Lucian Corneliu Vida, Mariuca Popa, Hogea Mircea, Mihaela Vartic, Bogdan Diaconescu, Matei Razvan Bratu, Ionut Negoi, Mircea Beuran, Cezar Ciubotaru, Norbert Uzabumwana, Dieudonne Duhoranenayo, Elio Jovine, Nicola Zanini, Giovanni Landolfo, Murad Aljiffry, Faisal Idris, Mohammed Saleh A. Alghamdi, Ashraf Maghrabi, Abdulmalik Altaf, Aroub Alkaaki, Ahmad Khoja, Abrar Nawawi, Sondos Turkustani, Eyad Khalifah, Adel Albiety, Sarah Sahel, Reham Alshareef, Mohammed Najjar, Ahmed Alzahrani, Ahmed Alghamdi, Wedyan Alhazmi, Ghiath Al Saied, Mohammed Alamoudi, Muhammed Masood Riaz, Mazen Hassanain, Basmah Alhassan, Abdullah Altamimi, Reem Alyahya, Norah Al Subaie, Fatema Al Bastawis, Afnan Altamimi, Thamer Nouh, Roaa Khan, Milan Radojkovic, Ljiljana Jeremic, Milica Nestorovic, Jia Hao Law, Keith Say Kwang Tan, Ryan Choon Kiat Tan, Joel Kin Tan, Lau Wen Liang Joel, Xue Wei Chan, Faith Qi Hui Leong, Choon Seng Chong, Sharon Koh, Kai Yin Lee, Kuok Chung Lee, Kent Pluke, Britta Dedekind, Puyearashid Nashidengo, Mark Ian Hampton, Johanna Joosten, Sanju Sobnach, Liana Roodt, Anthony Sander, James Pape, Niveshni Maistry, Phumudzo Ndwambi, Kamau Kinandu, Myint Tun, Frederick Du Toit, Quinn Ellison, D.C. Grobler, Sule Burger, Lawrence Bongani Khulu, Rachel Moore, Vicky Jennings, Astrid Leusink, Nazmie Kariem, Juan Gouws, Kathryn Chu, Heather Bougard, Fazlin Noor, Angela Dell, Stephanie Van Straten, Arvin Khamajeet, Serge Kapenda Tshisola, Kalangu Kabongo, Victor Kong, Yoshan Moodley, Frank Anderson, Thandinkosi Madiba, Flip du Plooy, Leila Hartford, Gareth Chilton, Parveen Karjiker, Matlou Ernest Mabitsela, Sibongile Ruth Ndlovu, Maria Badicel, Robert Jaich, Jaime Ruiz-Tovar, Luis Garcia-Florez, Jorge L. Otero-Díez, Virginia Ramos Pérez, Nuria Aguado Suárez, Javier Minguez García, Sara Corral Moreno, Maria Vicenta Collado, Virginia Jiménez Carneros, Javier García Septiem, Mariana Gonzalez, Antonio Picardo, Enrique Esteban, Esther Ferrero, Eloy Espin-Basany, Ruth Blanco-Colino, Valeria Andriola, Lorena Solar García, Elisa Contreras, Carmen García Bernardo, Janet Pagnozzi, Sandra Sanz, Alberto Miyar de León, Asnel Dorismé, Joseluis Rodicio, Aida Suarez, Jessica Stuva, Tamara Diaz Vico, Laura Fernandez-Vega, Carla Soldevila-Verdeguer, Fatima Sena-Ruiz, Natalia Pujol-Cano, Paula Diaz-Jover, José Maria Garcia-Perez, Juan Jose Segura-Sampedro, Cristina Pineño-Flores, David Ambrona-Zafra, Andrea Craus-Miguel, Patricia Jimenez-Morillas, Angela Mazzella, A.B. Jayathilake, S.P.B. Thalgaspitiya, L.S. Wijayarathna, P.M.S.N. Wimalge, Hakeem Ayomi Sanni, Ogheneochuko Okenabirhie, Anmar Homeida, Abobaker Younis, Omer Abdelbagi Omer, Mustafa Abdulaziz, Ali Mussad, Ali Adam, Ida Björklund, Sandra Ahlqvist, Anders Thorell, Fredrik Wogensen, Arestis Sokratous, Michaela Breistrand, Hildur Thorarinsdottir, Johanna Sigurdadottir, Maziar Nikberg, Abbas Chabok, Maria Hjertberg, Peter Elbe, Deborah Saraste, Wiktor Rutkowski, Louise Forlin, Karoliina Niska, Malin Sund, Dennis Oswald, Georgios Peros, Rafael Bluelle, Katharina Reinisch, Daniel Frey, Adrian Palma, Dimitri Aristotle Raptis, Lucius Zumbühl, Markus Zuber, Roger Schmid, Gabriela Werder, Antonio Nocito, Alexandra Gerosa, Silke Mahanty, Lukas Werner Widmer, Julia Müller, Alissa Gübeli, Grzegorz Zuk, Osman Bilgin Gulcicek, Talar Vartanoglu, Emin Kose, Servet Rustu Karahan, Mehmet Can Aydin, Nuri Alper Sahbaz, Ilkay Halicioglu, Halil Alis, Ipek Sapci, Can Adıyaman, Ahmet Murat Pektaş, Turgut Bora Cengiz, Ilkan Tansoker, Vedatcan Işler, Muazzez Cevik, Deniz Mutlu, Volkan Ozben, Berk Baris Ozmen, Sefa Bayram, Sinem Yolcu, Berna Buse Kobal, Ömer Faruk Toto, Haluk Cem Çakaloğlu, Kagan Karabulut, Vahit Mutlu, Bahar Busra Ozkan, Saban Celik, Anil Semiz, Selim Bodur, Enisburak Gül, Busra Murutoglu, Reyyan Yildirim, Bahadir Emre Baki, Ekin Arslan, Mehmet Ulusahin, Ali Guner, Nathan Walker, Nikhita Shrimanker, Simon Cole, Ryan Breslin, Ravi Srinivasan, Mohamed Elshaer, Kristina Hunter, Ahmed Al-Bahrani, Ignatius Liew, Nora Grace Mairs, Alistair Rocke, Lachlan Dick, Mobeen Qureshi, Debkumar Chowdhury, Naomi Wright, Clare Skerritt, Dorothy Kufeji, Adrienne Ho, Tharindra Dissanayake, Athula Tennakoon, Wadah Ali, Shujing Jane Lim, Charlene Tan, Stephen O'Neill, Catrin Jones, Stephen Knight, Dima Nassif, Abhishek Sharma, Oliver Warren, Rebecca White, Aia Mehdi, Nathan Post, Eliana Kalakouti, Enkhbat Dashnyam, Frederick Stourton, Ioannis Mykoniatis, Chelise Currow, Francisca Wong, Ashish Gupta, Veeranna Shatkar, Joshua Luck, Suraj Kadiwar, Alexander Smedley, Rebecca Wakefield, Philip Herrod, James Blackwell, Jonathan Lund, Fraser Cohen, Ashwath Bandi, Stefano Giuliani, Giles Bond-Smith, Theodore Pezas, Neda Farhangmehr, Tomas Urbonas, Miklos Perenyei, Philip Ireland, Natalie Blencowe, Kirk Bowling, David Bunting, Lydia Longstaff, Kenneth Keogh, Hyunjin Jeon, Muhammad Rafaih Iqbal, Shivun Khosla, Anna Jeffery, James Perera, Ahmad Aboelkassem Ibrahem, Tariq Alhammali, Yahya Salama, Shaun Oram, Thomas Kidd, Fraser Cullen, Christopher Owen, Michael Wilson, Seehui Chiu, Hannah Sarafilovic, Jennifer Ploski, Elizabeth Evans, Athar Abbas, Sylvia Kamya, Norzawani Ishak, Carly Bisset, Cedar Andress, Ye Ru Chin, Priya Patel, David Evans, Aidan Haslegrave, Adam Boggon, Kirsten Laurie, Katie Connor, Thomas Mann, Anahita Mansuri, Rachel Davies, Ewen Griffiths, Aized Raza Shahbaz, Calvin Eng, Farhat Din, Ariadne L'Heveder, Esther H.G. Park, Ramanish Ravishankar, Kirsten McIntosh, Jih Dar Yau, Luke Chan, Susan McGarvie, Lingshan Tang, Hui Lim, Suhhuey Yap, Jay Park, Zhan Herr Ng, Shahrukh Mirza, Yun Lin Ang, Luke Walls, Chloe Roy, Simon Paterson-Brown, Julian Camilleri-Brennan, Kenneth Mclean, Michelle S. D'Souza, Savva Pronin, David Ewart Henshall, Eunice Zuling Ter, Dina Fouad, Ashish Minocha, William English, Catrin Morgan, Dominic Townsend, Laura Maciejec, Shareef Mahdi, Onyinye Akpenyi, Elisabeth Hall, Hanaan Caydiid, Zakaria Rob, Tom Abbott, Hew D. Torrance, Robin Johnston, Mohammed Akil Gani, Gianpiero Gravante, Shivanchan Rajmohan, Kiran Majid, Shiva Dindyal, Christopher Smith, Madanmohan Palliyil, Sanjay Patel, Luke Nicholson, Neil Harvey, Katie Baillie, Sam Shillito, Suzanne Kershaw, Rebecca Bamford, Peter Orton, Elke Reunis, Robert Tyler, Wai Cheong Soon, Guled M. Jama, Dharminder Dhillon, Khyati Patel, Shayanthan Nanthakumaran, Rachel Heard, Kar Yan Chen, Behrad Barmayehvar, Uttaran Datta, Sivesh K. Kamarajah, Sharad Karandikar, Sobhana Iftekhar Tani, Eimear Monaghan, Philippa Donnelly, Michael Walker, Jehangirshaw Parakh, Sarah Blacker, Anil Kaul, Arjun Paramasivan, Sameh Farag, Ashrafun Nessa, Salwa Awadallah, Jieqi Lim, James Chean Khun Ng, Ravi P. Kiran, Alice Murray, Eric Etchill, Mohini Dasari, Juan Puyana, Nadeem Haddad, Martin Zielinski, Asad Choudhry, Celeste Caliman, Mieshia Beamon, Therese Duane, Mamta Swaroop, Jonathan Myers, Rebecca Deal, Erik Schadde, Mark Hemmila, Lena Napolitano, Kathleen To, Alex Makupe, Joseph Musowoya, Niels Van Der Naald, Dayson Kumwenda, Alex Reece-Smith, Kars Otten, Anna Verbeek, Marloes Prins, Alibeth Andres Baquero Suarez, Ruben Balmaceda, Chelsea Deane, Emilio Dijan, Mahmoud Elfiky, Laura Koskenvuo, Aurore Thollot, Bernard Limoges, Carmen Capito, Challine Alexandre, Henri Kotobi, Julien Leroux, Kalitha Pinnagoda, Nicolas Henric, Olivier Azzis, Olivier Rosello, Poddevin Francois, Sara Etienne, Philippe Buisson, Sophian Hmila, Joe-Nat Clegg-Lamptey, Osman Imoro, Owusu Emmanuel Abem, Dimitrios Papageorgiou, Vasiliki Soulou, Sabrina Asturias, Lenin Peña, Donal B. O’Connor, Alberto Realis Luc, Alfio Alessandro Russo, Andrea Ruzzenente, Antonio Taddei, Camilla Cona, Corrado Bottini, Giovanni Pascale, Giuseppe Rotunno, Leonardo Solaini, Marco Maria Pascale, Margherita Notarnicola, Mario Corbellino, Michele Sacco, Paolo Ubiali, Roberto Cautiero, Tommaso Bocchetti, Elena Muzio, Vania Guglielmo, Eugenio Morandi, Patrizio Mao, Emilia De Luca, Farah Mahmoud Ali, Justas Žilinskas, Kestutis Strupas, Paulius Kondrotas, Robertas Baltrunas, Juozas Kutkevicius, Povilas Ignatavicius, Choy Ling Tan, Jia Yng Siaw, Sir Young Yam, Ling Wilson, Mohamed Rezal Abdul Aziz, John Bondin, Carmina Diaz Zorrilla, Anass Majbar, Danjuma Sale, Lawal Abdullahi, Olabisi Osagie, Omolara Faboya, Adedeji Fatuga, Agboola Taiwo, Emeka Nwabuoku, Marte Bliksøen, Zain Ali Khan, Jazmin Coronel, Cesar Miranda, Idelso Vasquez, Luis M. Helguero-Santin, Jennifer Rickard, Adesina Adedeji, Saleh Alqahtani, Max Rath, Michael Van Niekerk, Modise Zacharia Koto, Roel Matos-Puig, Leif Israelsson, Tobias Schuetz, Mahmut Arif Yuksek, Meric Mericliler, Mehmet Uluşahin, Bernhard Wolf, Cameron Fairfield, Guo Liang Yong, Katharine Whitehurst, Natalie Redgrave, Caroluce K. Musyoka, James Olivier, Kathryn Lee, Michael Cox, Muhamed M.H. Farhan-Alanie, Rory Callan, Chali Chibuye, Tebian Hassanein Ahmed Ali, Syrine Rekhis, Muna Rommaneh, Zi Hao Sam, Thays Brunelli Pugliesi, Gabriel Pardo, and Ruth Blanco

Subjects
abdominal surgery, cost-effectiveness analysis, global surgery, high fraction of inspired oxygen, low-and middle-income countries, surgical site infection, Anesthesiology, RD78.3-87.3
Abstract

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.

Published
2023
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32. Contract Statements Knowledge Service for Chatbots

Author

Ruf, Boris, Sammarco, Matteo, and Detyniecki, Marcin

Subjects
Computer Science - Artificial Intelligence, Computer Science - Computation and Language, Computer Science - Human-Computer Interaction
Abstract

Towards conversational agents that are capable of handling more complex questions on contractual conditions, formalizing contract statements in a machine readable way is crucial. However, constructing a formal model which captures the full scope of a contract proves difficult due to the overall complexity its set of rules represent. Instead, this paper presents a top-down approach to the problem. After identifying the most relevant contract statements, we model their underlying rules in a novel knowledge engineering method. A user-friendly tool we developed for this purpose allows to do so easily and at scale. Then, we expose the statements as service so they can get smoothly integrated in any chatbot framework.

Published
2019

33. Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells

Author

Lucero, Rocco, Zappulli, Valentina, Sammarco, Alessandro, Murillo, Oscar D, Cheah, Pike See, Srinivasan, Srimeenakshi, Tai, Eric, Ting, David T, Wei, Zhiyun, Roth, Matthew E, Laurent, Louise C, Krichevsky, Anna M, Breakefield, Xandra O, and Milosavljevic, Aleksandar

Subjects
Neurosciences, Brain Disorders, Cancer, Clinical Research, Brain Cancer, Biotechnology, Genetics, Stem Cell Research - Nonembryonic - Human, Stem Cell Research, Rare Diseases, Brain, Endothelial Cells, Extracellular Vesicles, Glioblastoma, Glioma, Humans, MicroRNAs, Neovascularization, Pathologic, angiogenesis, biomarker, cancer stem cell, deconvolution, exRNA, extracellular vesicle, glioblastoma, miRNA, reprogramming, tumor microenvironment, Biochemistry and Cell Biology, Medical Physiology
Abstract

Glioblastoma (GBM) is characterized by aberrant vascularization and a complex tumor microenvironment. The failure of anti-angiogenic therapies suggests pathways of GBM neovascularization, possibly attributable to glioblastoma stem cells (GSCs) and their interplay with the tumor microenvironment. It has been established that GSC-derived extracellular vesicles (GSC-EVs) and their cargoes are proangiogenic in vitro. To further elucidate EV-mediated mechanisms of neovascularization in vitro, we perform RNA-seq and DNA methylation profiling of human brain endothelial cells exposed to GSC-EVs. To correlate these results to tumors in vivo, we perform histoepigenetic analysis of GBM molecular profiles in the TCGA collection. Remarkably, GSC-EVs and normal vascular growth factors stimulate highly distinct gene regulatory responses that converge on angiogenesis. The response to GSC-EVs shows a footprint of post-transcriptional gene silencing by EV-derived miRNAs. Our results provide insights into targetable angiogenesis pathways in GBM and miRNA candidates for liquid biopsy biomarkers.

Published
2020

34. Dysfunctional Extracellular Matrix Remodeling Supports Perianal Fistulizing Crohn′s Disease by a Mechanoregulated Activation of the Epithelial-to-Mesenchymal TransitionSummary

Author

Giulia Rizzo, Federica Rubbino, Sudharshan Elangovan, Giusy Sammarco, Sara Lovisa, Silvia Restelli, Samuel Elias Pineda Chavez, Luca Massimino, Luigi Lamparelli, Marianna Paulis, Annalisa Maroli, Giulia Roda, Mohammad Shalaby, Michele Carvello, Caterina Foppa, Sheona P. Drummond, Paola Spaggiari, Federica Ungaro, Antonino Spinelli, Alberto Malesci, Alessandro Repici, Anthony J. Day, Alessandro Armuzzi, Silvio Danese, and Stefania Vetrano

Subjects
Perianal Fistula, Crohn′s Disease, TSG-6, Extracellular Matrix, EMT, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and Aims: Perianal fistula represents one of the most disabling manifestations of Crohn′s disease (CD) due to complete destruction of the affected mucosa, which is replaced by granulation tissue and associated with changes in tissue organization. To date, the molecular mechanisms underlying perianal fistula formation are not well defined. Here, we dissected the tissue changes in the fistula area and addressed whether a dysregulation of extracellular matrix (ECM) homeostasis can support fistula formation. Methods: Surgical specimens from perianal fistula tissue and the surrounding region of fistulizing CD were analyzed histologically and by RNA sequencing. Genes significantly modulated were validated by real-time polymerase chain reaction, Western blot, and immunofluorescence assays. The effect of the protein product of TNF-stimulated gene-6 (TSG-6) on cell morphology, phenotype, and ECM organization was investigated with endogenous lentivirus-induced overexpression of TSG-6 in Caco-2 cells and with exogenous addition of recombinant human TSG-6 protein to primary fibroblasts from region surrounding fistula. Proliferative and migratory assays were performed. Results: A markedly different organization of ECM was found across fistula and surrounding fistula regions with an increased expression of integrins and matrix metalloproteinases and hyaluronan (HA) staining in the fistula, associated with increased newly synthesized collagen fibers and mechanosensitive proteins. Among dysregulated genes associated with ECM, TNFAI6 (gene encoding for TSG-6) was as significantly upregulated in the fistula compared with area surrounding fistula, where it promoted the pathological formation of complexes between heavy chains from inter-alpha-inhibitor and HA responsible for the formation of a crosslinked ECM. There was a positive correlation between TNFAI6 expression and expression of mechanosensitive genes in fistula tissue. The overexpression of TSG-6 in Caco-2 cells promoted migration, epithelial–mesenchymal transition, transcription factor SNAI1, and HA synthase (HAs) levels, while in fibroblasts, isolated from the area surrounding the fistula, it promoted an activated phenotype. Moreover, the enrichment of an HA scaffold with recombinant human TSG-6 protein promoted collagen release and increase of SNAI1, ITGA4, ITGA42B, and PTK2B genes, the latter being involved in the transduction of responses to mechanical stimuli. Conclusions: By mediating changes in the ECM organization, TSG-6 triggers the epithelial–mesenchymal transition transcription factor SNAI1 through the activation of mechanosensitive proteins. These data point to regulators of ECM as new potential targets for the treatment of CD perianal fistula.

Published
2023
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35. Multidisciplinary ocular and periocular cancers meetings: implementation in a tertiary referral center and analysis over a 12-months period

Author

Gustavo Savino, Fabrizio Piccinni, Monica Maria Pagliara, Maria Grazia Sammarco, Carmela Grazia Caputo, Alessandro Moro, Giorgio Barbera, Luca Tagliaferri, Bruno Fionda, Giovanni Schinzari, Ernesto Rossi, Luca Zagaria, Ketty Peris, Alessandro Di Stefani, Teresa Musarra, Luca Ausili Cefaro, Matia Martucci, and Maria Antonietta Blasi

Subjects
Ophthalmology, Oncology, Ocular oncology, Ocular oncology multidisciplinary tumor board, Multidisciplinary team, Ocular MDTB, RE1-994
Abstract

Abstract Purpose The complexity of multimodal approaches in cancer management has lately led to the establishment of multidisciplinary tumor boards (MDTBs) to define targeted, patient-centered treatment strategies. However, few data are available regarding the application of this approach in Ocular Oncology. Hereby, the Authors analyze the implementation and outcomes of a trained MDTB in a tertiary ocular oncology referral center. Methods A retrospective descriptive analysis of MDTB meetings discussing patients with ocular and periocular cancers, over a 12-months period, was carried out. Data were grouped by main site involved, topics discussed and final clinical decisions therefore taken. Meetings were held by a constant ‘Core team’ or – when required – by a broader ‘Extended team’. Results During the observational period 86 cases were discussed. In 27 patients ocular surface tissues were involved (31%), in 25 patients orbital tissues (29%), in 22 patients eyelids (26%), and in 12 patients intraocular tissues (14%). In 13 cases (15%) naïve or referred new patients, in 34 cases (40%) imaging or histopathologic reports and in 39 cases (45%) treatment plans were discussed. Regarding final decisions, a treatment plan was scheduled in 47 cases (55%) and a diagnostic ascertainment was required in 27 patients (31%); locally advanced and/or systemic diseases were referred or teamed up with other specialists in 12 cases (14%). Conclusions Ocular Oncology multidisciplinary team, by sharing expertise of different specialists, ensures a comprehensive evaluation of patients improving the accuracy of diagnosis and staging upon which planning a proper treatment. Further studies are needed to assess if this approach may also improve the outcomes and prognosis of patients.

Published
2022
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36. Epigenetic targeting of transposon relics: beating the dead horses of the genome?

Author

Iris Sammarco, Janto Pieters, Susnata Salony, Izabela Toman, Grygoriy Zolotarov, and Clément Lafon Placette

Subjects
transposable elements, epigenetic silencing, transposable elements relics, recombination, gene regulation, host genome defence, adaptive epimutations, Genetics, QH426-470
Abstract

Transposable elements (TEs) have been seen as selfish genetic elements that can propagate in a host genome. Their propagation success is however hindered by a combination of mechanisms such as mutations, selection, and their epigenetic silencing by the host genome. As a result, most copies of TEs in a given genome are dead relics: their sequence is too degenerated to allow any transposition. Nevertheless, these TE relics often, but not always, remain epigenetically silenced, and if not to prevent transposition anymore, one can wonder the reason for this phenomenon. The mere self-perpetuating loop inherent to epigenetic silencing could alone explain that even when inactive, TE copies remain silenced. Beyond this process, nevertheless, antagonistic selective forces are likely to act on TE relic silencing. Especially, without the benefit of preventing transposition, TE relic silencing may prove deleterious to the host fitness, suggesting that the maintenance of TE relic silencing is the result of a fine, and perhaps case-by-case, evolutionary trade-off between beneficial and deleterious effects. Ultimately, the release of TE relics silencing may provide a ‘safe’ ground for adaptive epimutations to arise. In this review, we provide an overview of these questions in both plants and animals.

Published
2022
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40. Prediction of the occurrence of leprosy reactions based on Bayesian networks

Author

Rafael Saraiva de Andrade Rodrigues, Eduardo Ferreira José Heise, Luis Felipe Hartmann, Guilherme Eduardo Rocha, Marcia Olandoski, Mariane Martins de Araújo Stefani, Ana Carla Pereira Latini, Cleverson Teixeira Soares, Andrea Belone, Patrícia Sammarco Rosa, Maria Araci de Andrade Pontes, Heitor de Sá Gonçalves, Rossilene Cruz, Maria Lúcia Fernandes Penna, Deborah Ribeiro Carvalho, Vinicius Medeiros Fava, Samira Bührer-Sékula, Gerson Oliveira Penna, Claudia Maria Cabral Moro, Julio Cesar Nievola, and Marcelo Távora Mira

Subjects
leprosy, leprosy reactions, risk, Bayesian networks, artificial intelligence, Medicine (General), R5-920
Abstract

IntroductionLeprosy reactions (LR) are severe episodes of intense activation of the host inflammatory response of uncertain etiology, today the leading cause of permanent nerve damage in leprosy patients. Several genetic and non-genetic risk factors for LR have been described; however, there are limited attempts to combine this information to estimate the risk of a leprosy patient developing LR. Here we present an artificial intelligence (AI)-based system that can assess LR risk using clinical, demographic, and genetic data.MethodsThe study includes four datasets from different regions of Brazil, totalizing 1,450 leprosy patients followed prospectively for at least 2 years to assess the occurrence of LR. Data mining using WEKA software was performed following a two-step protocol to select the variables included in the AI system, based on Bayesian Networks, and developed using the NETICA software.ResultsAnalysis of the complete database resulted in a system able to estimate LR risk with 82.7% accuracy, 79.3% sensitivity, and 86.2% specificity. When using only databases for which host genetic information associated with LR was included, the performance increased to 87.7% accuracy, 85.7% sensitivity, and 89.4% specificity.ConclusionWe produced an easy-to-use, online, free-access system that identifies leprosy patients at risk of developing LR. Risk assessment of LR for individual patients may detect candidates for close monitoring, with a potentially positive impact on the prevention of permanent disabilities, the quality of life of the patients, and upon leprosy control programs.

Published
2023
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42. ADP-Ribosylation Factor-Interacting Protein 2 Acts as a Novel Regulator of Mitophagy and Autophagy in Podocytes in Diabetic Nephropathy

Author

Haihua Guo, Manuel Rogg, Julia Keller, Ann-Kathrin Scherzinger, Julia Jäckel, Charlotte Meyer, Alena Sammarco, Martin Helmstädter, Oliver Gorka, Olaf Groß, Christoph Schell, and Wibke Bechtel-Walz

Subjects
ADP-ribosylation factor-interacting protein 2, Arfip2, podocyte, mitophagy, autophagy, diabetes, Therapeutics. Pharmacology, RM1-950
Abstract

(1) Background: Differentiated podocytes are particularly vulnerable to oxidative stress and cellular waste products. The disease-related loss of postmitotic podocytes is a direct indicator of renal disease progression and aging. Podocytes use highly specific regulated networks of autophagy and endocytosis that counteract the increasing number of damaged protein aggregates and help maintain cellular homeostasis. Here, we demonstrate that ARFIP2 is a regulator of autophagy and mitophagy in podocytes both in vitro and in vivo. (2) Methods: In a recent molecular regulatory network analysis of mouse glomeruli, we identified ADP-ribosylation factor-interacting protein 2 (Arfip2), a cytoskeletal regulator and cofactor of ATG9-mediated autophagosome formation, to be differentially expressed with age. We generated an Arfip2-deficient immortalized podocyte cell line using the CRISPR/Cas technique to investigate the significance of Arfip2 for renal homeostasis in vitro. For the in vivo analyses of Arfip2 deficiency, we used a mouse model of Streptozotozin-induced type I diabetes and investigated physiological data and (patho)histological (ultra)structural modifications. (3) Results: ARFIP2 deficiency in immortalized human podocytes impedes autophagy. Beyond this, ARFIP2 deficiency in human podocytes interferes with ATG9A trafficking and the PINK1-Parkin pathway, leading to the compromised fission of mitochondria and short-term increase in mitochondrial respiration and induction of mitophagy. In diabetic mice, Arfip2 deficiency deteriorates autophagy and leads to foot process effacement, histopathological changes, and early albuminuria. (4) Conclusions: In summary, we show that ARFIP2 is a novel regulator of autophagy and mitochondrial homeostasis in podocytes by facilitating ATG9A trafficking during PINK1/Parkin-regulated mitophagy.

Published
2024
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43. Antitumor Effect of Berberine Analogs in a Canine Mammary Tumor Cell Line and in Zebrafish Reporters via Wnt/β-Catenin and Hippo Pathways

Author

Alessandro Sammarco, Giorgia Beffagna, Roberta Sacchetto, Andrea Vettori, Federico Bonsembiante, Giulia Scarin, Maria Elena Gelain, Laura Cavicchioli, Silvia Ferro, Cristina Geroni, Paolo Lombardi, and Valentina Zappulli

Subjects
berberine derivates, dog, mammary tumors, zebrafish, Hippo, Wnt, Biology (General), QH301-705.5
Abstract

The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high lethality, and new therapeutics as well as new spontaneous animal models are needed to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors that share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, its active metabolite berberrubine, and eight analogs, on a canine mammary carcinoma cell line and in transgenic zebrafish models. We demonstrate both in vitro and in vivo the significant effects of specific analogs on cell viability via the induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction in CTGF expression. In particular, the berberine analogs NAX035 and NAX057 show the highest therapeutic efficacy, deserving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spontaneous neoplastic diseases are needed, aiming at improving veterinary treatments of cancer as well as translational cancer research.

Published
2023
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44. Line-Field Confocal Optical Coherence Tomography Evaluation of Eyelid Skin Lesions

Author

Alessandro Di Stefani, Simone Cappilli, Giovanni Cuffaro, Bruno Fionda, Monica Maria Pagliara, Andrea Paradisi, Costantino Ricci, Ernesto Rossi, Maria Grazia Sammarco, Giovanni Schinzari, Luca Tagliaferri, Maria Antonietta Blasi, Elisa Cinotti, Alessandro Moro, Gustavo Savino, Mariano Suppa, and Ketty Peris

Subjects
melanoma, histology of the skin, line-field confocal optical coherence tomography, eyelid, epithelial carcinomas, non-invasive diagnosis, Medicine (General), R5-920
Abstract

Background: Periocular malignancies may be clinically different from the examples arising at other sites, with possible delayed diagnosis and greater challenges for treatment and repair. Line-field confocal optical coherence tomography (LC-OCT) is a recently developed technique characterized by an unprecedented capacity to acquire high-definition images in vertical and horizontal modes. In this study, we aimed to investigate the LC-OCT morphological features of a series of eyelid skin lesions, correlating them to histopathological findings. Methods: Patients with biopsy-proven equivocal skin lesion in the eyelid area, previously investigated by means of LC-OCT, were included in the study. Percentage overall agreement was estimated for LC-OCT and histopathological diagnosis for study cases. Results: A total of 51 patients (28 women, 23 men; mean age 66.4 years old), for a total of 51 skin lesions, were assessed. The histopathological diagnosis consisted of 30 malignant and 21 benign tumors. Different entities were characterized by peculiar findings in LC-OCT, alike to histopathological features, allowing for an accurate “in vivo” classification in almost all cases, with a diagnostic concordance with histopathology of 92.1% (47/51). Conclusions: By integrating this new imaging technique into the assessment of suspicious tumors in this area, diagnostic accuracy may increase, improving strategies adopted in multidisciplinary meetings and patient-centered care.

Published
2023
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45. Insights into the Structure–Capacity of Food Antioxidant Compounds Assessed Using Coulometry

Author

Francesco Siano, Anna Sofia Sammarco, Olga Fierro, Domenico Castaldo, Tonino Caruso, Gianluca Picariello, and Ermanno Vasca

Subjects
antioxidant capacity, coulometry, electrogenerated bromine, biamperometric detection, CDAC, antioxidant mechanisms, Therapeutics. Pharmacology, RM1-950
Abstract

CDAC (coulometrically determined antioxidant capacity) involves the determination of the antioxidant capacity of individual compounds or their mixtures using constant-current coulometry, with electrogenerated Br2 as the titrant, and biamperometric detection of the endpoint via Br2 excess. CDAC is an accurate, sensitive, rapid, and cheap measurement of the mol electrons (mol e−) transferred in a redox process. In this study, the CDAC of 48 individual antioxidants commonly found in foods has been determined. The molar ratio CDAC (CDACχ, mol e− mol−1) of representative antioxidants is ranked as follows: tannic acid > malvidin-3-O-glucoside ≃ curcumin > quercetin > catechin ≃ ellagic acid > gallic acid > tyrosol > BHT ≃ hydroxytyrosol > chlorogenic acid ≃ ascorbic acid ≃ Trolox®. In many cases, the CDACχ ranking of the flavonoids did not comply with the structural motifs that promote electron or hydrogen atom transfers, known as the Bors criteria. As an accurate esteem of the stoichiometric coefficients for reactions of antioxidants with Br2, the CDACχ provides insights into the structure–activity relationships underlying (electro)chemical reactions. The electrochemical ratio (ER), defined as the antioxidant capacity of individual compounds relative to ascorbic acid, represents a dimensionless nutritional index that can be used to estimate the antioxidant power of any foods on an additive basis.

Published
2023
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46. Clinical nutrition in surgical oncology: Young AIOM-AIRO-SICO multidisciplinary national survey on behalf of NutriOnc research group

Author

Luigi Marano, Federica Marmorino, Isacco Desideri, Ludovico Carbone, Alessandro Rizzo, Viola Salvestrini, Franco Roviello, Saverio Cinieri, Vittorio Donato, Raffaele De Luca, NutriOnc Research Group, Silvia Sofia, Marco Milone, Benedetto Ielpo, Maria Teresa Mita, Silvia Ministrini, Mario Giuffrida, Roberta Tutino, Caterina Baldi, Giampaolo Perri, Anna Stella Lippolis, Chiara Marafante, Giusy Giannandrea, Marco Vito Marino, Letizia Laface, Salomone Di Saverio, Luca Aldrighetti, Nicola de’Angelis, Nick Salimian, Marco Caricato, Gianluca Pellino, Sara Vertaldi, Federica Cipriani, Gabriella Teresa Capolupo, Antonio Costanzo, Letizia Santandrea, Gaetano Gallo, Andrea Belli, Laura Mastrangelo, Fausto Rosa, Nicolò Pecorelli, Graziella Marino, Alessio Giordano, Nicola Cillara, Maria Lemma, Francesco Pata, Federico Cammillini, Gianmario Edoardo Poto, Giulia Grassi, Donato Francesco Altomare, Arcangelo Picciariello, Lorenzo Petagna, Luca Ippolito, Elio Treppiedi, Daniele Delogu, Abdallah Moukachar, Stefano Granieri, Giuseppe Cuticone, Osvaldo Carpineto Samorani, Daniela Rega, Leonardo Solaini, Stefano de Pascale, Francesca Ascari, Michele Manigrasso, Simona Badalucco, Salvatore Paiella, Sara Coppola, Roberta Iadarola, Giovanna Di Meo, Isacco Montroni, Fabio Vistoli, Valentina Ferraro, Edoardo Saladino, Federico Fazio, Roberta Rota, Francesco Orlando, Simone Famularo, Cinzia Bizzoca, Giorgio Dalmonte, Marco Inama, Luigi Verre, Leandro Siragusa, Casoni Pattacini Gianmaria, Michele Benedetti, Nicolò Tamini, Cristian Conti, Giorgio Ammerata, Serena Mantova, Vito Leonardo Pinto, Arianna Corvasce, Giorgio Micheletti, Teresa Perra, Marco Pellicciaro, Marco Materazzo, Michele Zuolo, Emanuele Doria, Antonio Brillantino, Luca Del Prete, Andrea Muratore, Claudio Luciani, Giulia Turri, Fabio Casciani, Giuliani Giuseppe, Graziana Barile, Oldrà Gaia, Valeria Restaino, Simona Deidda, Michele Ammendola, Andrea Fares Bucci, Patrizia Marsanic, Dario Cassetti, Luca Resca, Daniele Fusario, Eleonora Andreucci, Anna Michelotti, Brunella Amoruso, Isabella Franco, Laura Noto, Andrea Spallanzani, Raimondo Calogero Scalia, Teresa Del Giudice, Valeria Merz, Gianmarco Motta, Alessandro Parisi, Mikol Modesti, Antonella Argentiero, Debora Basile, Gianmarco Vannini, Carlotta Ottanelli, Salvatore Corallo, Eufemia Stefania Lutrino, Daniele Rossini, Federica Morano, Luigia Stefania Stucci, Costanza Winchler, Martina Catalano, Andrea Marini, Giuseppe Brisinda, Enrico Sammarco, Martina Carullo, Giandomenico Roviello, Mirko Barone, Maria Grazia Rodriquenz, Giuseppe Tirino, Alessia Amoruso, Anna Russo, Veronica Conca, Laura Orgiano, Sveva Macrini, Giulia Nazzicone, Maria Bensi, Martina Montesano, Emanuela Dell’Aquila, Andrea Sbrana, Beatrice Borelli, Lorenzo Fornaro, Lucrezia Raimondi, Valeria Zurlo, Mattia Garutti, Elena Ongaro, Arianna Pellegrino, Andrea lanese, Laura Bernardini, Alessandra Boccaccino, Patrizia Farina, Federica Buzzacchino, Angelica Petrillo, Ada Taravella, Vittorio Studiale, Paolo Ciracì, Giovanna Lovino, Dora Di Cosmo, Sabrina Montrone, Fabiana Gregucci, Luca Dominici, Alba Fiorentino, Filippo Carannante, Giambattista Siepe, Giampaolo Montesi, Manuele Roghi, Michele Aquilano, Andrea Romei, Ilaria Bonaparte, Roberta Grassi, Emma D’Ippolito, Giulio Frosini, Giuseppina De Marco, Gennaro Giovine, Chiara Mattioli, Ilaria Morelli, Victoria Lorenzetti, Matteo Mariotti, Carolina Orsatti, Vincenzo Troncone, Lorenzo Livi, Antonio Angrisani, Marco Banini, Teresa Di Pietro, Giuseppe Carlo Iorio, Iacopo Cavallo, Cecilia Cerbai, Valerio Nardone, Francesca De Felice, Consuelo Rosa, Giulia Stocchi, Sara Lucidi, Michele Ganovelli, Damiano Dei, Chiara Cascone, Anna Peru, Luisa Caprara, Lucia Angelini, Luca Visani, Giulio Francolini, Beatrice Bettazzi, Francesco Belia, Virginia Boccardi, Simone Serafini, Vincenzo Bottino, Luca Ferrario, Giuseppe Frazzetta, Felice Pirozzi, Gennaro Martines, Francesco Antonio Ciarleglio, Daniele Indiani, Giuliano Barugola, Luca Mazza, and Chiara Guarini

Subjects
clinical nutrition, cancer, malnutrition, nutritional assessment, survey, Nutrition. Foods and food supply, TX341-641
Abstract

Malnutrition is a common condition in cancer patients which is usually associated with functional limitations, as well as increased morbidity and mortality. Based on the support of the young sections of Italian Association of Medical Oncology (AIOM), Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Society of Surgical Oncology (SICO) merged into the NutriOnc Research Group, we performed a multidisciplinary national survey with the aim to define the awareness of nutritional issues among healthcare professionals delivering anticancer care. The questionnaire was organized in four sections, as follows: Knowledge and practices regarding Nutritional Management of cancer patients; Timing of screening and assessment of Nutritional Status; Nutritional Treatment and prescription criteria; Immunonutrition and educational topics. The modules focused on esophagogastric, hepato-bilio-pancreatic and colorectal malignancies. Overall, 215 physicians completed the survey. As regards the management of Nutritional Status of cancer patients, many responders adopted the ERAS program (49.3%), while a consistent number of professionals did not follow a specific validated nutritional care protocol (41.8%), mainly due to lack of educational courses (14.5%) and financial support (15.3%). Nearly all the included institutions had a multidisciplinary team (92%) to finalize the treatment decision-making. Cancer patients routinely underwent nutritional screening according to 57.2% of interviewed physicians. The timing of nutritional assessment was at diagnosis (37.8%), before surgery (25.9%), after surgery (16.7%), before radiochemotherapy (13.5%) and after radiochemotherapy (7%). Most of the responders reported that nutritional status was assessed throughout the duration of cancer treatments (55.6%). An important gap between current delivery and need of nutritional assessment persists. The development of specific and defined care protocols and the adherence to these tools may be the key to improving nutritional support management in clinical practice.

Published
2023
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47. Illuminating cellular and extracellular vesicle-mediated communication via a split-Nanoluc reporter in vitro and in vivo

Author

Thomas S. van Solinge, Shadi Mahjoum, Stefano Ughetto, Alessandro Sammarco, Marike L.D. Broekman, Xandra O. Breakefield, and Killian P. O’Brien

Subjects
CP: Cell biology, Biotechnology, TP248.13-248.65, Biochemistry, QD415-436, Science
Abstract

Summary: Tools to effectively demonstrate and quantify functional delivery in cellular communication have been lacking. This study reports the use of a fluorescently labeled split Nanoluc reporter system to demonstrate and quantify functional transfer between cells in vitro and in a subcutaneous tumor mouse model. Our construct allows monitoring of direct, indirect, and specifically extracellular vesicle-mediated functional communication. Motivation: In tracking protein-mediated cellular communication, few tools distinguish between proteins that escape the endosome and are functional within the cytosol and proteins that are degraded by the lysosome or released back into the extracellular space. We designed a tool that signals functional protein delivery and can be used to study cell-to-cell and extracellular vesicle-mediated communication in vitro and in vivo.

Published
2023
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48. Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization

Author

Josue Jaramillo, Caroline Taylor, Rachel McCarley, Melissa Berger, Emily Busse, and Mimi C. Sammarco

Subjects
bone, oxaloacetate, limb regeneration, cell metabolism, digit regeneration, Biology (General), QH301-705.5
Abstract

Cell metabolism coordinates the biochemical reactions that produce carbon and ATP in order for the cell to proliferate, differentiate, and respond to environmental changes. Cell type determines metabolic demand, so proliferating skeletal progenitors and differentiated osteoblasts exhibit different levels of cell metabolism. Limb regeneration is an energetically demanding process that involves multiple types of tissues and cell functions over time. Dysregulation of cell metabolism in aged mice results in impaired regeneration, a defect that can be rescued in part by the administration of oxaloacetate (OAA). A better understanding of how cell metabolism regulates regeneration in general, and how these changes can be modulated to benefit potential regenerative strategies in the future is needed. Here we sought to better understand the effects of OAA on young mice and determine whether the same mechanism could be tapped to improve regeneration without an aged-defect. We also asked which dosing time periods were most impactful for promoting regenerative outcomes, and whether these effects were sustained after dosing was stopped. Consistent with our findings in aged mice we found that OAA enhanced regeneration by accelerating bone growth, even beyond control measures, by increasing trabecular thickness, decreasing trabecular spacing, and improving the patterning by decreasing the taper, making the regenerated bone more like an unamputated digit. Our data suggests that the decrease in spacing, an improvement over aged mice, may be due to a decrease in hypoxia-driven vasculature. Our findings suggest that OAA, and similar metabolites, may be a strong tool to promote regenerative strategies and investigate the mechanisms that link cell metabolism and regeneration.

Published
2023
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50. Multidisciplinary ocular and periocular cancers meetings: implementation in a tertiary referral center and analysis over a 12-months period

Author

Savino, Gustavo, Piccinni, Fabrizio, Pagliara, Monica Maria, Sammarco, Maria Grazia, Caputo, Carmela Grazia, Moro, Alessandro, Barbera, Giorgio, Tagliaferri, Luca, Fionda, Bruno, Schinzari, Giovanni, Rossi, Ernesto, Zagaria, Luca, Peris, Ketty, Di Stefani, Alessandro, Musarra, Teresa, Ausili Cefaro, Luca, Martucci, Matia, and Blasi, Maria Antonietta

Published
2022
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