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1,649 results on '"Pagella A"'

3. YjbH contributes to Staphylococcus aureus skin pathology and immune response through Agr-mediated α-toxin regulation

Author

Aubrey K. G. McReynolds, Emma A. Pagella, Miranda J. Ridder, Olivia Rippee, Zachary Clark, Michaella J. Rekowski, Michele T. Pritchard, and Jeffrey L. Bose

Subjects
Staphylococcus, S. aureus, alpha-toxin, YjbH, skin, regulation, Infectious and parasitic diseases, RC109-216
Abstract

Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant S. aureus (MRSA) strains being a major contributor in both community and hospital settings. S. aureus relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both in vitro and in vivo. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the ΔyjbIH mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the ΔyjbH mutant. This work continues to define the importance of YjbH in the pathogenesis of S. aureus infection as well as identify a new pathway important for Hla production.

Published
2024
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4. Multidisciplinary Decision-Making—ITAlian Consensus After Two Years of Real Practice on the Management of Severe Uncontrolled CRSwNP by Biologics (ITACA Study)

Author

De Corso, Eugenio, Pipolo, Carlotta, Caminati, Marco, Cantone, Elena, Seccia, Veronica, Cecchi, Lorenzo, Nettis, Eustachio, Garzaro, Massimiliano, Ottaviano, Giancarlo, Gelardi, Matteo, Cavaliere, Carlo, Heffler, Enrico, Pagella, Fabio, Pasquini, Ernesto, Trimarchi, Matteo, Gallo, Stefania, La Mantia, Ignazio, Torretta, Sara, Mattavelli, Davide, Caruso, Cristiano, Matucci, Andrea, Vultaggio, Alessandra, Bellocchi, Gianluca, Alicandri Ciufelli, Matteo, FM, Passali, and Senna, Gianenrico

Published
2024
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7. Assessment of in-situ stress distribution and mechanical properties of wooden foundation piles instrumented with distributed fiber optic sensors (DFOS)

Author

Maria Felicita, Giorgio Pagella, Geert Ravenshorst, Michele Mirra, and Jan-Willem van de Kuilen

Subjects
Wooden foundation piles, Distributed fibre optic sensors (DFOS), In-situ stress assessment, DFOS validation, Mechanical properties, Assessment and monitoring, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

This case study explores the utilization of distributed fiber optic sensors (DFOS) in wooden foundation piles, for assessing and monitoring the stress distribution along their length. Three spruce and three pine foundation piles instrumented with DFOS were driven into the soil in a testing field in Amsterdam and axially loaded in compression. Since DFOS provided strain information, calculating the stress distribution in the piles required knowledge of their stiffness properties, which inherently vary from the head to the tip. Consequently, the piles were extracted and their overall wet dynamic elastic modulus (Ec,0,dyn,wet) was determined through frequency response measurements. Subsequently, the piles were segmented, transported to the TU Delft Laboratory and subjected to mechanical testing. For each segment, the mechanical properties were determined and their variability along the pile was studied, in particular for the static modulus of elasticity (Ec,0,stat,wet). This enabled a comprehensive assessment of the actual in-situ stress distribution (Δσactual,stat and Δσactual,dyn) along the length of the piles, calculated with DFOS strains and the pile stiffness (Ec,0,stat,wet and Ec,0,stat,dyn). Given the novelty of the DFOS application to timber piles, a validation of the accuracy was conducted on 3 pile segments equipped with DFOS. These segments underwent laboratory compression testing, allowing for a direct comparison between DFOS strain readings and strains measured with linear potentiometers attached to the pile segments. The results revealed good accuracy of DFOS in controlled lab conditions, with a maximum stress deviation of 0.65 MPa. Since the testing field featured a 6-meter-deep predrilled layer, where negligible shaft friction was mobilized, the no-friction stress (Δσno-friction) approximately aligned with Δσactual,stat on the piles. At pile tips, the maximum applied 300–350 kN compressive load (i.e. Δσno-friction = 20–26 MPa), resulted in Δσactual,stat = 4–7 MPa, highlighting shaft friction effect. The calculated Δσactual,dyn with a single Ec,0,stat,dyn for the whole pile, led to 3 MPa stress overestimation at pile tip. Although this calculation is conservative, the detailed knowledge of the variation of stiffness properties along the pile would result in a more efficient structural use.

Published
2024
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8. Serine 937 phosphorylation enhances KCC2 activity and strengthens synaptic inhibition

Author

Tamara Radulovic, Ezhilarasan Rajaram, Lena Ebbers, Sara Pagella, Michael Winklhofer, Conny Kopp-Scheinpflug, Hans Gerd Nothwang, Ivan Milenkovic, and Anna-Maria Hartmann

Subjects
Medicine, Science
Abstract

Abstract The potassium chloride cotransporter KCC2 is crucial for Cl- extrusion from mature neurons and thus key to hyperpolarizing inhibition. Auditory brainstem circuits contain well-understood inhibitory projections and provide a potent model to study the regulation of synaptic inhibition. Two peculiarities of the auditory brainstem are (i) posttranslational activation of KCC2 during development and (ii) extremely negative reversal potentials in specific circuits. To investigate the role of the potent phospho-site serine 937 therein, we generated a KCC2 Thr934Ala/Ser937Asp double mutation, in which Ser937 is replaced by aspartate mimicking the phosphorylated state, and the neighbouring Thr934 arrested in the dephosphorylated state. This double mutant showed a twofold increased transport activity in HEK293 cells, raising the hypothesis that auditory brainstem neurons show lower [Cl−]i. and increased glycinergic inhibition. This was tested in a mouse model carrying the same KCC2 Thr934Ala/Ser937Asp mutation by the use of the CRISPR/Cas9 technology. Homozygous KCC2 Thr934Ala/Ser937Asp mice showed an earlier developmental onset of hyperpolarisation in the auditory brainstem. Mature neurons displayed stronger glycinergic inhibition due to hyperpolarized ECl−. These data demonstrate that phospho-regulation of KCC2 Ser937 is a potent way to interfere with the excitation-inhibition balance in neural circuits.

Published
2023
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11. Impact of SARS-CoV-2 infection in patients with hereditary hemorrhagic telangiectasia: epidemiological and clinical data from the comprehensive Italian retrospective multicenter study

Author

Suppressa, Patrizia, Maiorano, Eugenia, Gaetani, Eleonora, Matti, Elina, Lenato, Gennaro Mariano, Serio, Ilaria, Masala, Maristella Salvatora, Passali, Giulio Cesare, Aguglia, Maria, Crocione, Claudia, Lopalco, Pietro Luigi, Caneschi, Francesca, Musella, Valeria, De Silvestri, Annalisa, Gambini, Giulia, Spinozzi, Giuseppe, Sabbà, Carlo, and Pagella, Fabio

Published
2023
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12. Extracellular matrix remodelling in dental pulp tissue of carious human teeth through the prism of single-cell RNA sequencing

Author

Anamaria Balic, Dilara Perver, Pierfrancesco Pagella, Hubert Rehrauer, Bernd Stadlinger, Andreas E. Moor, Viola Vogel, and Thimios A. Mitsiadis

Subjects
Dentistry, RK1-715
Abstract

Abstract Carious lesions are bacteria-caused destructions of the mineralised dental tissues, marked by the simultaneous activation of immune responses and regenerative events within the soft dental pulp tissue. While major molecular players in tooth decay have been uncovered during the past years, a detailed map of the molecular and cellular landscape of the diseased pulp is still missing. In this study we used single-cell RNA sequencing analysis, supplemented with immunostaining, to generate a comprehensive single-cell atlas of the pulp of carious human teeth. Our data demonstrated modifications in the various cell clusters within the pulp of carious teeth, such as immune cells, mesenchymal stem cells (MSC) and fibroblasts, when compared to the pulp of healthy human teeth. Active immune response in the carious pulp tissue is accompanied by specific changes in the fibroblast and MSC clusters. These changes include the upregulation of genes encoding extracellular matrix (ECM) components, including COL1A1 and Fibronectin (FN1), and the enrichment of the fibroblast cluster with myofibroblasts. The incremental changes in the ECM composition of carious pulp tissues were further confirmed by immunostaining analyses. Assessment of the Fibronectin fibres under mechanical strain conditions showed a significant tension reduction in carious pulp tissues, compared to the healthy ones. The present data demonstrate molecular, cellular and biomechanical alterations in the pulp of human carious teeth, indicative of extensive ECM remodelling, reminiscent of fibrosis observed in other organs. This comprehensive atlas of carious human teeth can facilitate future studies of dental pathologies and enable comparative analyses across diseased organs.

Published
2023
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13. Extremely Rare Pathologies of the Craniovertebral Junction Region: A Case Series and Review of the Literature

Author

Eugenia Maiorano, Giannantonio Spena, Fabio Sovardi, Puya Dehgani-Mobaraki, Fabio Pagella, Andrea Montalbetti, Elisabetta Peppucci, Christian Grasso, and Cesare Zoia

Subjects
craniovertebral junction, osteoradionecrosis, ecchordosis physaliphora, hepatocellular carcinoma metastasis, capillary hemangioma, embryonal rhabdomyosarcoma, Surgery, RD1-811
Abstract

Background: The craniovertebral junction is a complex region, connecting the occiput, the atlas, the axis, and the containing vital neural and vascular structures. There is a great variability in diseases involving the craniovertebral junction, of different nature, each rare in frequency. Methods: We conducted a retrospective chart review of the patients diagnosed with extremely rare pathologies of the craniovertebral junction that we have operated in the last 5 years. Results: After excluding the relatively more frequent pathologies, we identified nine cases of rare craniovertebral junction pathologies. Six were operated using an endoscopic endonasal approach, two using a far lateral transcranial approach, and one underwent a C1 hemilaminectomy. Conclusions: Diagnosis and management of the rare pathologies of the craniovertebral junction are challenging. A multidisciplinary approach is recommended for the proper management of these patients.

Published
2023
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14. The CUT&RUN suspect list of problematic regions of the genome

Author

Anna Nordin, Gianluca Zambanini, Pierfrancesco Pagella, and Claudio Cantù

Subjects
CUT&RUN, Chromatin, Bioinformatics, Peak calling, Blacklist, Suspect list, Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background Cleavage Under Targets and Release Using Nuclease (CUT&RUN) is an increasingly popular technique to map genome-wide binding profiles of histone modifications, transcription factors, and co-factors. The ENCODE project and others have compiled blacklists for ChIP-seq which have been widely adopted: these lists contain regions of high and unstructured signal, regardless of cell type or protein target, indicating that these are false positives. While CUT&RUN obtains similar results to ChIP-seq, its biochemistry and subsequent data analyses are different. We found that this results in a CUT&RUN-specific set of undesired high-signal regions. Results We compile suspect lists based on CUT&RUN data for the human and mouse genomes, identifying regions consistently called as peaks in negative controls. Using published CUT&RUN data from our and other labs, we show that the CUT&RUN suspect regions can persist even when peak calling is performed with SEACR or MACS2 against a negative control and after ENCODE blacklist removal. Moreover, we experimentally validate the CUT&RUN suspect lists by performing reiterative negative control experiments in which no specific protein is targeted, showing that they capture more than 80% of the peaks identified. Conclusions We propose that removing these problematic regions can substantially improve peak calling in CUT&RUN experiments, resulting in more reliable datasets.

Published
2023
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18. Maxillary Postsurgical Ciliated Cysts (PSCCs): A Series of Three Cases

Author

Domenico Sfondrini, Fabio Pagella, Matteo Pellegrini, Martina Ghizzoni, Andrea Scribante, Chiara Tore, and Stefano Marelli

Subjects
Dentistry, RK1-715
Abstract

Introduction. A postsurgical ciliated cyst (PSCC) is an epithelial cyst that usually develops in the maxilla, although in rare cases, it can affect the mandible or other facial bones. The typical age of diagnosis is 40-50 years, with no gender prevalence, and the mean cyst development occurs approximately 10-15 years following a surgical or traumatic event. Some epithelial respiratory cells can be trapped into the bone tissue during maxillary surgical procedures or maxillary fractures. The pathogenetic mechanism can be attributed to an inflammatory process that stimulates epithelial proliferation, leading to cyst expansion caused by osmotic pressure difference. Methods. This study presents case series involving three surgical ciliated cysts located in the left maxilla, affecting two female patients (aged 49 and 55 years) and one male patient (aged 39 years). In all three cases, symptoms such as pain or swelling were mild and not consistently present. Two cases showed cyst development 10 and 15 years after implant placement, while one case was not associated with any surgical or traumatic event. CT scan identified well-defined unilocular lesions in the maxillary bone in each patient. Results. Histopathological examination of the surgical specimens confirmed the suspected diagnosis of a PSCC of maxilla. The cystic walls consisted of fibrous connective tissue with chronic inflammatory infiltrate, lined exclusively by a thin layer of ciliated pseudostratified columnar epithelium. In the third patient, it was not possible to rule out an unusual radicular cyst. Conclusions. Although PSCCs are not commonly encountered in daily practice, clinicians should consider this possibility including it in the differential diagnosis of odontogenic jaw cysts and benign jaw tumors, particularly in patients who have undergone previous surgeries in the maxillary area.

Published
2024
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22. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Author

Abrough, Fekri, Acharya, Subhash P, Amin, Pravin, Arabi, Yaseen, Aragao, Irene, Bauer, Philippe, Beduneau, Gaëtan, Beitler, Jeremy, Berkius, Johan, Bugedo, Guillermo, Camporota, Luigi, Cerny, Vladimir, Cho, Young-Jae, Clarkson, Kevin, Estenssoro, Elisa, Goligher, Ewan, Grasselli, Giacomo, Gritsan, Alexey, Hashemian, Seyed Mohammadreza, Hermans, Greet, Heunks, Leo M, Jovanovic, Bojan, Kurahashi, Kiyoyasu, Laake, Jon Henrik, Matamis, Dimitrios, Moerer, Onnen, Molnar, Zsolt, Ozyilmaz, Ezgi, Panka, Bernardo, Papali, Alfred, Peñuelas, Óscar, Perbet, Sébastien, Piquilloud, Lise, Qiu, Haibo, Razek, Assem Abdel, Rittayamai, Nuttapol, Roldan, Rollin, Serpa Neto, Ary, Szuldrzynski, Konstanty, Talmor, Daniel, Tomescu, Dana, Van Haren, Frank, Villagomez, Asisclo, Zeggwagh, Amine Ali, Abe, Toshikazu, Aboshady, Abdelrhman, Acampo-de Jong, Melanie, Acharya, Subhash, Adderley, Jane, Adiguzel, Nalan, Agrawal, Vijay Kumar, Aguilar, Gerardo, Aguirre, Gaston, Aguirre-Bermeo, Hernan, Ahlström, Björn, Akbas, Türkay, Akker, Mustafa, Al Sadeh, Ghamdan, Alamri, Sultan, Algaba, Angela, Ali, Muneeb, Aliberti, Anna, Allegue, Jose Manuel, Alvarez, Diana, Amador, Joaquin, Andersen, Finn H, Ansari, Sharique, Apichatbutr, Yutthana, Apostolopoulou, Olympia, Arellano, Daniel, Arica, Mestanza, Arikan, Huseyin, Arinaga, Koichi, Arnal, Jean-Michel, Asano, Kengo, Asín-Corrochano, Marta, Avalos Cabrera, Jesus Milagrito, Avila Fuentes, Silvia, Aydemir, Semih, Aygencel, Gulbin, Azevedo, Luciano, Bacakoglu, Feza, Badie, Julio, Baedorf Kassis, Elias, Bai, Gabriela, Balaraj, Govindan, Ballico, Bruno, Banner-Goodspeed, Valerie, Banwarie, Preveen, Barbieri, Rosella, Baronia, Arvind, Barrett, Jonathan, Barrot, Loïc, Barrueco-Francioni, Jesus Emilio, Barry, Jeffrey, Bawangade, Harshal, Beavis, Sarah, Beck, Eduardo, Beehre, Nina, Belenguer Muncharaz, Alberto, Bellani, Giacomo, Belliato, Mirko, Bellissima, Agrippino, Beltramelli, Rodrigo, Ben Souissi, Asma, Benitez-Cano, Adela, Benlamin, Mohamed, Benslama, Abdellatif, Bento, Luis, Benvenuti, Daniela, Bernabe, Laura, Bersten, Andrew, Berta, Giacomo, Bertini, Pietro, Bertram-Ralph, Elliot, Besbes, Mohamed, Bettini, Lisandro Roberto, Beuret, Pascal, Bewley, Jeremy, Bezzi, Marco, Bhakhtiani, Lakshay, Bhandary, Rakesh, Bhowmick, Kaushik, Bihari, Shailesh, Bissett, Bernie, Blythe, David, Bocher, Simon, Boedjawan, Narain, Bojanowski, Christine M, Boni, Elisa, Boraso, Sabrina, Borelli, Massimo, Borello, Silvina, Borislavova, Margarita, Bosma, Karen J, Bottiroli, Maurizio, Boyd, Owen, Bozbay, Suha, Briva, Arturo, Brochard, Laurent, Bruel, Cédric, Bruni, Andrea, Buehner, Ulrike, Bulpa, Pierre, Burt, Karen, Buscot, Mathieu, Buttera, Stefania, Cabrera, Jorge, Caccese, Roberta, Caironi, Pietro, Canchos Gutierrez, Ivan, Canedo, Nancy, Cani, Alma, Cappellini, Iacopo, Carazo, Jesus, Cardonnet, Luis Pablo, Carpio, David, Carriedo, Demetrio, Carrillo, Ramón, Carvalho, João, Caser, Eliana, Castelli, Antonio, Castillo Quintero, Manuel, Castro, Heloisa, Catorze, Nuno, Cengiz, Melike, Cereijo, Enrique, Ceunen, Helga, Chaintoutis, Christos, Chang, Youjin, Chaparro, Gustavogcha, Chapman, Carmel, Chau, Simon, Chavez, Cecilia Eugenia, Chelazzi, Cosimo, Chelly, Jonathan, Chemouni, Frank, Chen, Kai, Chena, Ariel, Chiarandini, Paolo, Chilton, Phil, Chiumello, Davide, Chou-Lie, Yvette, Chudeau, Nicolas, Cinel, Ismail, Cinnella, Gilda, Clark, Michele, Clark, Thomas, Clementi, Stefano, Coaguila, Luis, Codecido, Alexis Jaspe, Collins, Amy, Colombo, Riccardo, Conde, Juan, Consales, Guglielmo, Cook, Tim, Coppadoro, Andrea, Cornejo, Rodrigo, Cortegiani, Andrea, Coxo, Cristina, Cracchiolo, Andrea Neville, Crespo Ramirez, Mónica, Crova, Philippe, Cruz, José, Cubattoli, Lucia, Çukurova, Zafer, Curto, Francesco, Czempik, Piotr, D'Andrea, Rocco, da Silva Ramos, Fernando, Dangers, Laurence, Danguy des Déserts, Marc, Danin, Pierre-Eric, Dantas, Fabianne, Daubin, Cédric, Dawei, Wu, de Haro, Candelaria, de Jesus Montelongo, Felipe, De Mendoza, Diego, de Pablo, Raúl, De Pascale, Gennaro, De Rosa, Silvia, Decavèle, Maxens, Declercq, Pierre-Louis, Deicas, Alberto, del Carmen Campos Moreno, María, Dellamonica, Jean, Delmas, Benjamin, Demirkiran, Oktay, Demirkiran, Hilmi, Dendane, Tarek, di Mussi, Rossella, Diakaki, Chrysi, Diaz, Anatilde, Diaz, Willy, Dikmen, Yalim, Dimoula, Aikaterini, Doble, Patricia, Doha, Nagwa, Domingos, Guilherme, Dres, Martin, Dries, David, Duggal, Abhijit, Duke, Graeme, Dunts, Pavel, Dybwik, Knut, Dykyy, Maksym, Eckert, Philippe, Efe, Serdar, Elatrous, Souheil, Elay, Gülseren, Elmaryul, Abubaker S, Elsaadany, Mohamed, Elsayed, Hany, Elsayed, Samar, Emery, Malo, Ena, Sébastien, Eng, Kevin, Englert, Joshua A, Erdogan, Elif, Ergin Ozcan, Perihan, Eroglu, Ege, Escobar, Miguel, Esen, Figen, Esen Tekeli, Arzu, Esquivel, Alejandro, Esquivel Gallegos, Helbert, Ezzouine, Hanane, Facchini, Alberto, Faheem, Mohammad, Fanelli, Vito, Farina, Maria Fernanda, Fartoukh, Muriel, Fehrle, Lutz, Feng, Feng, Feng, Yufeng, Fernandez, Irene, Fernandez, Borja, Fernandez-Rodriguez, Maria Lorena, Ferrando, Carlos, Ferreira da Silva, Maria João, Ferreruela, Mireia, Ferrier, Janet, Flamm Zamorano, Matias Jesús, Flood, Laura, Floris, Leda, Fluckiger, Martin, Forteza, Catalina, Fortunato, Antonella, Frans, Eric, Frattari, Antonella, Fredes, Sebastian, Frenzel, Tim, Fumagalli, Roberto, Furche, Mariano Andres, Fusari, Maurizio, Fysh, Edward, Galeas-Lopez, Juan Luis, Galerneau, Louis-Marie, Garcia, Analía, Garcia, María Fernanda, Garcia, Elisabet, Garcia Olivares, Pablo, Garlicki, Jaroslaw, Garnero, Aude, Garofalo, Eugenio, Gautam, Prabha, Gazenkampf, Andrey, Gelinotte, Stéphanie, Gelormini, Domenico, Ghrenassia, Etienne, Giacomucci, Angelo, Giannoni, Robert, Gigante, Andrea, Glober, Nancy, Gnesin, Paolo, Gollo, Yari, Gomaa, Dina, Gomero Paredes, Rosita, Gomes, Rui, Gomez, Raúl Alejandro, Gomez, Oscar, Gomez, Aroa, Gondim, Louise, Gonzalez, Manuel, Gonzalez, Isabel, Gonzalez-Castro, Alejandro, Gordillo Romero, Orlando, Gordo, Federico, Gouin, Philippe, Graf Santos, Jerónimo, Grainne, Rooney, Grando, Matilde, Granov Grabovica, Sanja, Grasso, Salvatore, Grasso, Rinaldo, Grimmer, Lisa, Grissom, Colin, Gu, Qing, Guan, Xiang-Dong, Guarracino, Fabio, Guasch, Neus, Guatteri, Luca, Gueret, Renaud, Guérin, Claude, Guerot, Emmanuel, Guitard, Pierre-Gildas, Gül, Fethi, Gumus, Ayca, Gurjar, Mohan, Gutierrez, Patricia, Hachimi, Abdelhamid, Hadzibegovic, Adi, Hagan, Samantha, Hammel, Clare, Han Song, Joo, Hanlon, Gabrielle, Heines, Serge, Henriksson, Johanna, Herbrecht, Jean-Etienne, Heredia Orbegoso, Gabriel Omar, Hermon, Andrew, Hernandez, Rosana, Hernandez, Carmen, Herrera, Luis, Herrera-Gutierrez, Manuel, Heunks, Leo, Hidalgo, Juan, Hill, Dianne, Holmquist, Dagmar, Homez, Marcela, Hongtao, Xia, Hormis, Anil, Horner, Daniel, Hornos, M Carmen, Hou, Meihong, House, Stacy, Housni, Brahim, Hugill, Keith, Humphreys, Sally, Humbert, Louis, Hunter, Stephanie, Hwa Young, Lee, Iezzi, Nicolas, Ilutovich, Santiago, Inal, Volkan, Innes, Richard, Ioannides, Panagiotis, Iotti, Giorgio Antonio, Ippolito, Mariachiara, Irie, Hiromasa, Iriyama, Hiroki, Itagaki, Taiga, Izura, Javier, Izza, Santiago, Jabeen, Rakhshanda, Jamaati, Hamidreza, Jamadarkhana, Sunil, Jamoussi, Amira, Jankowski, Milosz, Jaramillo, Luis Alberto, Jeon, Kyeongman, Jeong Lee, Seok, Jeswani, Deepak, Jha, Simant, Jiang, Liangyan, Jing, Chen, Jochmans, Sébastien, Johnstad, Bror Anders, Jongmin, Lee, Joret, Aurélie, Junhasavasdikul, Detajin, Jurado, Maria Teresa, Kam, Elisa, Kamohara, Hidenobu, Kane, Caroline, Kara, Iskender, Karakurt, Sait, Karnjanarachata, Cherdkiat, Kataoka, Jun, Katayama, Shinshu, Kaushik, Shuchi, Kelebek Girgin, Nermin, Kerr, Kathryn, Kerslake, Ian, Khairnar, Prakash, Khalid, Abidi, Khan, Akram, Khanna, Ashish K, Khorasanee, Reza, Kienhorst, Dieneke, Kirakli, Cenk, Knafelj, Rihard, Kol, Mark Kol, Kongpolprom, Napplika, Kopitko, Csaba, Korkmaz Ekren, Pervin, Kubisz-Pudelko, Agnieszka, Kulcsar, Zoltan, Kumasawa, Junji, Kuriyama, Akira, Kutchak, Fernanda, Labarca, Eduardo, Labat, Françoise, Laborda, César, Laca Barrera, Manuel Alberto, Lagache, Laurie, Landaverde Lopez, Antonio, Lanspa, Michael, Lascari, Valeria, Le Meur, Matthieu, Lee, Su Hwan, Lee, Young Ju, Lee, Jinwoo, Lee, Won-Yeon, Lee, Jarone, Legernaes, Terje, Leiner, Tamaas, Lemiale, Virginie, Leonor, Tiago, Lepper, Philipp M, Li, Dahuan, Li, Hongbin, Li, Oleg, Lima, Ana Raquel, Lind, Dan, Litton, Edward, Liu, Ning, Liu, Ling, Liu, Jialin, Llitjos, Jean-François, Llorente, Beatriz, Lopez, Rodolfo, Lopez, Claudia Elizabeth, Lopez Nava, Claudia, Lovazzano, Pablo, Lu, Min, Lucchese, Francesca, Lugano, Manuela, Lugo Goytia, Gustavo, Luo, Hua, Lynch, Ceri, Macheda, Sebastiano, Madrigal Robles, Victor Hugo, Maggiore, Salvatore Maurizio, Magret Iglesias, Mònica, Malaga, Peter, Mallapura Maheswarappa, Harish, Malpartida, Guillermo, Malyarchikov, Andrey, Mansson, Helena, Manzano, Anaid, Marey, Ismael, Marin, Nathalie, Marin, Maria del Carmen, Markman, Eliana, Martin, Felix, Martin, Alex, Martin Dal Gesso, Cristina, Martinez, Felipe, Martínez-Fidalgo, Conchita, Martin-Loeches, Ignacio, Mas, Arantxa, Masaaki, Sakuraya, Maseda, Emilio, Massa, Eleni, Mattsson, Anna, Maugeri, Jessica, McCredie, Victoria, McCullough, James, McGuinness, Shay, McKown, Andrew, Medve, László, Mei, Chengqing, Mellado Artigas, Ricard, Mendes, Vitor, Mervat, Mohamed Khalaf Ebraheim, Michaux, Isabelle, Mikhaeil, Michael, Milagros, Olga, Milet, Igor, Millan, Maria Teresa, Minwei, Zhang, Mirabella, Lucia, Mishra, Sanghamitra, Mistraletti, Giovanni, Mochizuki, Katsunori, Moghal, Arif, Mojoli, Francesco, Molin, Alexandre, Montiel, Raquel, Montini, Luca, Monza, Gianmario, Mora Aznar, Maria, Morakul, Sunthiti, Morales, Maria, Moreno Torres, Daniel, Morocho Tutillo, Diego Rolando, Motherway, Catherine, Mouhssine, Doumiri, Mouloudi, Eleni, Muñoz, Tapia, Munoz de Cabo, Carlos, Mustafa, Mohamed, Muthuchellappan, Radhakrishnan, Muthukrishnan, Muraleekrishnan, Muttini, Stefano, Nagata, Isao, Nahar, Dick, Nakanishi, Misuzu, Nakayama, Izumi, Namendys-Silva, Silvio Antonio, Nanchal, Rahul, Nandakumar, Sivakumar, Nasi, Alessandra, Nasir, Kamal, Navalesi, Paolo, Naz Aslam, Tayyba, Nga Phan, Thuy, Nichol, Alistair, Niiyama, Shuhei, Nikolakopoulou, Sofia, Nikolic, Elena, Nitta, Kenichi, Noc, Marko, Nonas, Stephanie, Nseir, Saad, Nur Soyturk, Ayse, Obata, Yukako, Oeckler, Richard, Oguchi, Moe, Ohshimo, Shinichiro, Oikonomou, Marina, Ojados, Agueda, Oliveira, Maria Teresa, Oliveira Filho, Wilson, Oliveri, Carlo, Olmos, Aitor, Omura, Kazuya, Orlandi, Maria Cristina, Orsenigo, Francesca, Ortiz-Ruiz De Gordoa, Laura, Ota, Kei, Ovalle Olmos, Rainier, Öveges, Nándo, Oziemski, Peter, Ozkan Kuscu, Ozlem, Pachas Alvarado, Fernando, Pagella, Gonzalo, Palaniswamy, Vijayanand, Palazon Sanchez, Eugenio Luis, Palmese, Salvatore, Pan, Guojun, Pan, Wensen, Papanikolaou, Metaxia, Papavasilopoulou, Theonymfi, Parekh, Ameet, Parke, Rachael, Parrilla, Francisco J, Parrilla, Dácil, Pasha, Taha, Pasin, Laura, Patão, Luis, Patel, Mayur, Patel, Grisma, Pati, Basanta Kumar, Patil, Jayaprakash, Pattnaik, Saroj, Paul, Daniel, Pavesi, Maurizio, Pavlotsky, Vanesa Alejandra, Paz, Graciela, Paz, Enrique, Pecci, Elisabetta, Pellegrini, Carlos, Peña Padilla, Andrea Gabriela, Perchiazzi, Gaetano, Pereira, Tiago, Pereira, Vera, Perez, Manuel, Perez Calvo, Cesar, Perez Cheng, Meisy, Perez Maita, Ronald, Pérez-Araos, Rodrigo, Perez-Teran, Purificación, Perez-Torres, David, Perkins, Gavin, Persona, Paolo, Petnak, Tananchai, Petrova, Marina, Pham, Tai, Philippart, François, Picetti, Edoardo, Pierucci, Elisabetta, Piervincenzi, Edoardo, Pinciroli, Riccardo, Pintado, Maria-Consuelo, Piraino, Thomas, Piras, Stephanie, Piras, Claudio, Pirompanich, Pattarin, Pisani, Luigi, Platas, Enrique, Plotnikow, Gustavo, Porras, Willy, Porta, Virginia, Portilla, Mariana, Portugal, José, Povoa, Pedro, Prat, Gwenael, Pratto, Romina, Preda, Gabriel, Prieto, Isidro, Prol-Silva, Estefania, Pugh, Richard, Qi, Yupeng, Qian, Chuanyun, Qin, Tiehe, Qu, Hongping, Quintana, Teobaldo, Quispe Sierra, Rosari, Quispe Soto, Rocio, Rabbani, Raihan, Rabee, Mohamed, Rabie, Ahmed, Rahe Pereira, Maria Augusta, Rai, Ashish, Raj Ashok, Sundar, Rajab, Mostafa, Ramdhani, Navin, Ramey, Elizabeth, Ranieri, Marco, Rathod, Darshana, Ray, Banambar, Redwanul Huq, Shihan Mahmud, Regli, Adrian, Reina, Rosa, Resano Sarmiento, Natalia, Reynaud, Faustine, Rialp, Gemma, Ricart, Pilar, Rice, Todd, Richardson, Angus, Rieder, Marcelo, Rinket, Martin, Rios, Fernando, Risso Vazquez, Alejandro, Riva, Ivano, Rivette, Monaly, Roca, Oriol, Roche-Campo, Ferran, Rodriguez, Covadonga, Rodriguez, Gabriel, Rodriguez Gonzalez, Daniel, Rodriguez Tucto, Xandra Yanina, Rogers, Angela, Romano, María Elena, Rørtveit, Linda, Rose, Alastair, Roux, Damien, Rouze, Anahita, Rubatto Birri, Paolo Nahuel, Ruilan, Wang, Ruiz Robledo, Aldana, Ruiz-Aguilar, Antonio Luis, Sadahiro, Tomohito, Saez, Ignacio, Sagardia, Judith, Saha, Rajnish, Saha, Rohit, Saiphoklang, Narongkorn, Saito, Shigeki, Salem, Maie, Sales, Gabriele, Salgado, Patricia, Samavedam, Srinivas, Sami Mebazaa, Mhamed, Samuelsson, Line, San Juan Roman, Nandyelly, Sanchez, Patricia, Sanchez-Ballesteros, Jesus, Sandoval, Yazcitk, Sani, Emanuele, Santos, Martin, Santos, Carla, Sanui, Masamitsu, Saravanabavan, Lakshmikanthcharan, Sari, Sema, Sarkany, Agnes, Sauneuf, Bertrand, Savioli, Monica, Sazak, Hilal, Scano, Riccardo, Schneider, Francis, Schortgen, Frédérique, Schultz, Marcus J, Schwarz, Gabriele Leonie, Seçkin Yücesoy, Faruk, Seely, Andrew, Seiler, Frederik, Seker Tekdos, Yasemin, Seok Chan, Kim, Serano, Luca, Serednicki, Wojciech, Setten, Mariano, Shah, Asim, Shah, Bhagyesh, Shang, You, Shanmugasundaram, Pradeep, Shapovalov, Konstantin, Shebl, Eman, Shiga, Takuya, Shime, Nobuaki, Shin, Phil, Short, Jack, Shuhua, Chen, Siddiqui, Sughrat, Silesky Jimenez, Juan Ignacio, Silva, Daniel, Silva Sales, Betania, Simons, Koen, Sjøbø, Brit Ågot, Slessor, David, Smiechowicz, Jakub, Smischney, Nathan, Smith, Paul, Smith, Tim, Smith, Mark, Snape, Sarah, Snyman, Lindi, Soetens, Filiep, Sook Hong, Kyung, Sosa Medellin, Miguel Ángel, Soto, Giovanna, Souloy, Xavier, Sousa, Elsa, Sovatzis, Stefania, Sozutek, Didem, Spadaro, Savino, Spagnoli, Marco, Spångfors, Martin, Spittle, Nick, Spivey, Mike, Stapleton, Andrew, Stefanovic, Branislava, Stephenson, Lorraine, Stevenson, Elizabeth, Strand, Kristian, Strano, Maria Teresa, Straus, Slavenka, Sun, Chenliang, Sun, Rongqing, Sundaram, Venkat, SunPark, Tai, Surlemont, Elisabeth, Sutherasan, Yuda, Szabo, Zsuzsanna, Tainter, Christopher, Takaba, Akihiro, Tallott, Mandy, Tamasato, Tamasato, Tang, Zhanhong, Tangsujaritvijit, Viratch, Taniguchi, Leandro, Taniguchi, Daisuke, Tarantino, Fabio, Teerapuncharoen, Krittika, Temprano, Susana, Terragni, Pierpaolo, Terzi, Nicolas, Thakur, Anand, Theerawit, Pongdhep, Thille, Arnaud W, Thomas, Matt, Thungtitigul, Poungrat, Thyrault, Martial, Tilouch, Nejla, Timenetsky, Karina, Tirapu, Juna, Todeschini, Manuel, Tomas, Roser, Tomaszewski, Christian, Tonetti, Tommaso, Tonnelier, Alexandre, Trinder, John, Trongtrakul, Konlawij, Truwit, Jonathon, Tsuei, Betty, Tulaimat, Aiman, Turan, Sema, Turkoglu, Melda, Tyagi, Sanjeev, Ubeda, Alejandro, Vagginelli, Federica, Valenti, María Florencia, Vallverdu, Imma, Van Axel, Alisha, van den Hul, Ingrid, van der Hoeven, Hans, Van Der Meer, Nardo, Vanhoof, Marc, Vargas-Ordoñez, Mónica, Vaschetto, Rosanna, Vascotto, Ettore, Vatsik, Maria, Vaz, Ana, Vazquez-Sanchez, Antonia, Ventura, Sara, Vermeijden, Jan Wytze, Vidal, Anxela, Vieira, Jocyelle, Vilela Costa Pinto, Bruno, Villagra, Ana, Villegas Succar, Cristina, Vinorum, Ole Georg, Vitale, Giovanni, Vj, Ramesh, Vochin, Ana, Voiriot, Guillaume, Volta, Carlo Alberto, von Seth, Magnus, Wajdi, Maazouzi, Walsh, Don, Wang, Shouhong, Wardi, Gabriel, Ween-Velken, Nils Christian, Wei, Bi-Lin, Weller, Dolf, Welsh, Deborah, Welters, Ingeborg, Wert, Michael, Whiteley, Simon, Wilby, Elizabeth, Williams, Erin, Williams, Karen, Wilson, Antoinette, Wojtas, Jadwiga, Won Huh, Jin, Wrathall, David, Wright, Christopher, Wu, Jian-Feng, Xi, Guo, Xing, Zheng-Jiang, Xu, Hongyang, Yamamoto, Kotaro, Yan, Jie, Yáñez, Julio, Yang, Xiaobo, Yates, Elliot, Yazicioglu Mocin, Ozlem, Ye, Zhenglong, Yildirim, Fatma, Yoshida, Norifumi, Yoshido, Hector Higo Leon, Young Lee, Bo, Yu, Rongguo, Yu, Gong, Yu, Tao, Yuan, Boyun, Yuangtrakul, Nadwipa, Yumoto, Tetsuya, Yun, Xie, Zakalik, Graciela, Zaki, Ahmad, Zalba-Etayo, Begoña, Zambon, Massimo, Zang, Bin, Zani, Gianluca, Zarka, Jonathan, Zerbi, Simone Maria, Zerman, Avsar, Zetterquist, Harald, Zhang, Jiuzhi, Zhang, Hongwen, Zhang, Wei, Zhang, Guoxiu, Zhang, Weixin, Zhao, Hongsheng, Zheng, Jia, Zhu, Bin, Zumaran, Ronald, Pham, Tài, Madotto, Fabiana, Goligher, Ewan C, Mancebo, Jordi, Peñuelas, Oscar, Pesenti, Antonio, Wunsch, Hannah, van Haren, Frank, and Laffey, John G

Published
2023
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25. A large pool of actively cycling progenitors orchestrates self-renewal and injury repair of an ectodermal appendage

Author

Sharir, Amnon, Marangoni, Pauline, Zilionis, Rapolas, Wan, Mian, Wald, Tomas, Hu, Jimmy K, Kawaguchi, Kyogo, Castillo-Azofeifa, David, Epstein, Leo, Harrington, Kyle, Pagella, Pierfrancesco, Mitsiadis, Thimios, Siebel, Christian W, Klein, Allon M, and Klein, Ophir D

Subjects
Biological Sciences, Genetics, Stem Cell Research, Regenerative Medicine, Stem Cell Research - Nonembryonic - Non-Human, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Ameloblasts, Animals, Cell Differentiation, Cell Division, Cell Proliferation, Ectoderm, Epithelial Cells, Incisor, Mice, Transgenic, Signal Transduction, Stem Cells, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

The classical model of tissue renewal posits that small numbers of quiescent stem cells (SCs) give rise to proliferating transit-amplifying cells before terminal differentiation. However, many organs house pools of SCs with proliferative and differentiation potentials that diverge from this template. Resolving SC identity and organization is therefore central to understanding tissue renewal. Here, using a combination of single-cell RNA sequencing (scRNA-seq), mouse genetics and tissue injury approaches, we uncover cellular hierarchies and mechanisms that underlie the maintenance and repair of the continuously growing mouse incisor. Our results reveal that, during homeostasis, a group of actively cycling epithelial progenitors generates enamel-producing ameloblasts and adjacent layers of non-ameloblast cells. After injury, tissue repair was achieved through transient increases in progenitor-cell proliferation and through direct conversion of Notch1-expressing cells to ameloblasts. We elucidate epithelial SC identity, position and function, providing a mechanistic basis for the homeostasis and repair of a fast-turnover ectodermal appendage.

Published
2019

31. The European Rare Disease Network for HHT Frameworks for management of hereditary haemorrhagic telangiectasia in general and speciality care

Author

Shovlin, C.L., Buscarini, E., Sabbà, C., Mager, H.J., Kjeldsen, A.D., Pagella, F., Sure, U., Ugolini, S., Torring, P.M., Suppressa, P., Rennie, C., Post, M.C., Patel, M.C., Nielsen, T.H., Manfredi, G., Lenato, G.M., Lefroy, D., Kariholu, U., Jones, B., Fialla, A.D., Eker, O.F., Dupuis, O., Droege, F., Coote, N., Boccardi, E., Alsafi, A., Alicante, S., and Dupuis-Girod, S.

Published
2022
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38. Notch signaling in the dynamics of perivascular stem cells and their niches

Author

Pierfrancesco Pagella, Laura deVargas Roditi, Bernd Stadlinger, Andreas E. Moor, and Thimios A. Mitsiadis

Subjects
dental pulp stem cells, carious teeth, mesenchymal stem cells, microenvironment, Notch ligands, Notch signaling, Medicine (General), R5-920, Cytology, QH573-671
Abstract

Abstract The Notch signaling pathway is a fundamental regulator of cell fate determination in homeostasis and regeneration. In this work, we aimed to determine how Notch signaling mediates the interactions between perivascular stem cells and their niches in human dental mesenchymal tissues, both in homeostatic and regenerative conditions. By single cell RNA sequencing analysis, we showed that perivascular cells across the dental pulp and periodontal human tissues all express NOTCH3, and that these cells are important for the response to traumatic injuries in vivo in a transgenic mouse model. We further showed that the behavior of perivascular NOTCH3‐expressing stem cells could be modulated by cellular and molecular cues deriving from their microenvironments. Taken together, the present studies, reinforced by single‐cell analysis, reveal the pivotal importance of Notch signaling in the crosstalk between perivascular stem cells and their niches in tissue homeostasis and regeneration.

Published
2021
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39. Characterization of epidemiological distribution and outcome of COVID-19 in patients with hereditary hemorrhagic telangiectasia: a nationwide retrospective multi-centre study during first wave in Italy

Author

Patrizia Suppressa, Fabio Pagella, Gennaro Mariano Lenato, Eleonora Gaetani, Ilaria Serio, Maristella Salvatora Masala, Giuseppe Spinozzi, Roberta Lizzio, Elina Matti, Annalisa De Silvestri, Giulio Cesare Passali, Maria Aguglia, Claudia Crocione, and Carlo Sabbà

Subjects
Hereditary hemorrhagic telangiectasia, Rare diseases, COVID-19, PANDEMICS 2020, SARS-CoV-2 infection, Medicine
Abstract

Abstract Background Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue. Objectives The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency. Methods The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period. Results The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population. Conclusions COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population.

Published
2021
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45. Hereditary hemorrhagic telangiectasia: First demonstration of a founder effect in Italy; the ACVRL1 c.289_294del variant originated in the country of Bergamo 200 years ago

Author

Anna Sbalchiero, Yasmin Abu Hweij, Tommaso Mazza, Elisabetta Buscarini, Claudia Scotti, Fabio Pagella, Guido Manfredi, Elina Matti, Giuseppe Spinozzi, and Carla Olivieri

Subjects
ACVRL1, age estimation, common ancestor, founder effect, HHT, Rendu‐Osler‐weber syndrome, Genetics, QH426-470
Abstract

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder, affecting 1:5000 individuals worldwide. All the genes associated to the disease (ENG, ACVRL1, SMAD4, GDF2) belong to the TGF‐β/BMPs signaling pathway. We found 19 HHT unrelated families, coming from a Northern Italy region and sharing the ACVRL1 in‐frame deletion c.289_294del (p.H97_N98). Methods To test the hypothesis of a founder effect, we analyzed 88 subjects from 19 families (66 variant carriers, showing clinical signs of HHT, and 22 non‐carriers, unaffected) using eight microsatellite markers within 3.7 Mb around the ACVRL1 locus. After the haplotype reconstruction, age estimation of the variant was carried out. Results We observed a common disease haplotype in 16/19 families, while three families showed evidence of recombination around the ACVRL1 locus. The subsequent age estimation analyses suggested that the mutation occurred about 8 generations ago, corresponding to about 200 years ago. We also present novel in silico and modeling data supporting the variant pathogenicity: the deletion alters the protein stability and removes the unique extracellular glycosylation site. Conclusion We have demonstrated, for the first time, a “founder effect” for a HHT pathogenic variant in Italy.

Published
2022
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46. Bioengineered tooth emulation systems for regenerative and pharmacological purposes

Author

P Pagella, A Cordiale, GD Marconi, O Trubiani, M Rasponi, and TA Mitsiadis

Subjects
tooth, dental pulp stem cells, periodontal ligament stem cells, bioreactors, microfluidics, organ-on-a-chip, stem cells, drug discovery, regeneration, Diseases of the musculoskeletal system, RC925-935, Orthopedic surgery, RD701-811
Abstract

Genetic conditions, traumatic injuries, carious lesions and periodontal diseases are all responsible for dental pathologies. The current clinical approaches are based on the substitution of damaged dental tissues with inert materials, which, however, do not ensure full physiological recovery of the teeth. Different populations of dental mesenchymal stem cells have been isolated from dental tissues and several attempts have already been made at using these stem cells for the regeneration of human dental tissues. Despite encouraging progresses, dental regenerative therapies are very far from any clinical applications. This is tightly connected with the absence of proper platforms that would model and faithfully mimic human dental tissues in their complexity. Therefore, in the last decades, many efforts have been dedicated for the development of innovative systems capable of emulating human tooth physiology in vitro. This review focuses on the use of in vitro culture systems, such as bioreactors and “organ-on-a-chip” microfluidic devices, for the modelling of human dental tissues and their potential use for dental regeneration and drug testing.

Published
2021
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