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1. Safety, Pharmacokinetics, and Pharmacodynamics of the ADAMTS‐5 Inhibitor GLPG1972/S201086 in Healthy Volunteers and Participants With Osteoarthritis of the Knee or Hip

Author: Stephane Delage, Paul Passier, Agnes Lalande, Emilie Leroux, Staffan Larsson, H. Deckx, André Struglics, Ann Fieuw, David Amantini, Ellen van der Aar, Sonia Dupont, and L. Stefan Lohmander
Subjects: Male, medicine.medical_specialty, Administration, Oral, Pharmaceutical Science, Osteoarthritis, Placebo, Double-Blind Method, Pharmacokinetics, Internal medicine, Healthy volunteers, Humans, Medicine, Pharmacology (medical), Dosing, Randomized Controlled Trials as Topic, Clinical Trials, Phase I as Topic, business.industry, ADAMTS, Osteoarthritis, Knee, medicine.disease, Healthy Volunteers, Endocrinology, Tolerability, Area Under Curve, Pharmacodynamics, Female, ADAMTS5 Protein, business
Abstract: GLPG1972/S201086 is a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5) inhibitor in development as an osteoarthritis disease-modifying therapy. We report the safety, tolerability, pharmacokinetics, and pharmacodynamics (turnover of plasma/serum ARGS-aggrecan neoepitope fragments [ARGS]) of GLPG1972 in 3 randomized, double-blind, placebo-controlled phase 1 trials. Study A, a first-in-human trial of single (≤2100 mg [fasted] and 300 mg [fed]) and multiple (≤1050 mg once daily [fed]; 14 days) ascending oral (solution) doses, investigated GLPG1972 in healthy men (N = 41; NCT02612246). Study B investigated multiple ascending oral (tablet) doses of GLPG1972 (≤300 mg once daily [fed]; 4 weeks) in male and female participants with osteoarthritis (N = 30; NCT03311009). Study C investigated single (Japanese: ≤1500 mg; White: 300 mg [fasted]) and multiple (Japanese, ≤1050 mg once daily; White, 300 mg once daily [fed]; 14 days) ascending oral (tablet) doses of GLPG1972 in healthy Japanese and White men (N = 88). The pharmacokinetic profile of GLPG1972 was similar between healthy participants and participants with osteoarthritis, with low to moderate interindividual variability. GLPG1972 was rapidly absorbed (median time to maximum concentration, 4 hours), and eliminated with a mean apparent terminal elimination half-life of ≈10 hours. Steady state was achieved within 2 days of dosing, with minimal accumulation. Steady-state plasma exposure after 300 mg of GLPG1972 showed no or minor differences between populations. Area under the plasma concentration-time curve (56.8-67.6 μg · h/mL) and time to maximum concentration (4 hours) were similar between studies. Urinary excretion of GLPG1972 (24 hours) was low (
Published: 2021
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2. OXIDATIVE STRESS AND SERUM S100B LEVELS IN ADOLESCENTS WITH FIRST-EPISODE DRUG-NAIVE UNIPOLAR DEPRESSION

Author: Sara Bianchi, Eleonora Valentini, Patrizia Moretti, Luigi Maria Pandolfi, Kety Amantini, Giulia Menculini, Mattia Gatto, and Alfonso Tortorella
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Depression scale, unipolar depression, adolescent, S100B, oxidative stress, gender, S100 Calcium Binding Protein beta Subunit, medicine.disease_cause, Antioxidants, chemistry.chemical_compound, Internal medicine, Humans, Medicine, Child, Depression (differential diagnoses), First episode, Depressive Disorder, business.industry, General Medicine, Oxidants, Malondialdehyde, Oxidative Stress, Psychiatry and Mental health, Drug-naïve, Pharmaceutical Preparations, chemistry, Etiology, Anxiety, Female, medicine.symptom, business, Oxidative stress, medicine.drug
Abstract: Background Unipolar depression is common among adolescents and has high recurrence rates. Studies conducted with adults show that oxidative stress plays a role in etiology of depression but studies with adolescent patients are limited. In addition, baseline S100B level in adult patients with depression is considered as a marker of response to treatment. The purpose of this study was to measure the levels of serum S100B, Malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS), which have not been previously investigated in adolescent patients with first-episode, drug-naive unipolar depression, and to investigate the relationship of these parameters with disease severity and patient-specific variables. Subjects and methods This study was conducted with 37 adolescents diagnosed with unipolar depression and 37 healthy peers. Participants were asked to fill out the Beck Depression Scale, Screen for Child Anxiety Related Disorders, and suicide probability questionnaires. After this procedure, 5 cc blood was collected from the adolescents and serum S100B, MDA, TOS, and OSI levels measured. Results Serum S100B, MDA, TOS, and OSI levels were higher and TAS level was lower in patients than their healthy peers. There was no relationship between the patients' severity of depression or suicide probability and these parameters. The serum S100B, MDA, TOS, and OSI levels of female patients were higher than their healthy peers, but the TAS level was not different. Male patients had higher TOS and OSI levels and lower TAS levels than their healthy peers. Conclusions The results show that increased serum S100B, MDA, TOS and OSI levels may contribute to etiology of depression regardless of gender. The gender-specific increase in S100B and MDA levels, which were significantly increased in female adolescent patients but not in males, should be supported by further follow-up studies.
Published: 2021
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3. Are neurophysiologic tests reliable, ultra-early prognostic indices after cardiac arrest?

Author: Antonello Grippo, Manuela Bonizzoli, Giovanni Lanzo, Francesco Lolli, M. Spalletti, Maenia Scarpino, Riccardo Carrai, Aldo Amantini, C. Cossu, Filippo Socci, and Chiara Lazzeri
Subjects: medicine.medical_specialty, Neurophysiology, Electroencephalography, 050105 experimental psychology, Eeg patterns, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, 0501 psychology and cognitive sciences, Pupillary light reflex, Coma, Good outcome, Retrospective Studies, High probability, medicine.diagnostic_test, business.industry, 05 social sciences, General Medicine, Prognosis, Predictive value, Heart Arrest, Neurology, Somatosensory evoked potential, Cardiology, Neurology (clinical), business, Clinical evaluation, 030217 neurology & neurosurgery
Abstract: Objectives Determining early and reliable prognosis in comatose subjects after cardiac arrest is a central component of post–cardiac arrest care both for developing realistic prognostic expectations for families, and for better determining which resources are mobilized or withheld for individual patients. The aim of the study was to evaluate the prognostic accuracy of EEG and SEP patterns during the very early period (within the first 6 h) after cardiac arrest. Methods We retrospectively analysed comatose patients after CA, either inside or outside the hospital, in which prognostic evaluation was made during the first 6 h from CA. Prognostic evaluation comprised clinical evaluation (GCS and pupillary light reflex) and neurophysiological (electroencephalography (EEG) and somatosensory evoked potentials (SEP)) studies. Prognosis was evaluated with regards to likelihood of recovery of consciousness and also likelihood of failure to regain consciousness. Results Forty-one comatose patients after cardiac arrest were included. All patients with continuous and nearly continuous EEG recovered consciousness. Isoelectric EEG was always associated with poor outcome. Burst-suppression, suppression and discontinuous patterns were usually associated with poor outcome although some consciousness recovery was observed. Bilaterally absent SEP responses were always associated with poor outcome. Continuous and nearly continuous EEG patterns were never associated with bilaterally absent SEP. Conclusions During the very early period following cardiac arrest (first 6 h), EEG and SEP maintain their high predictive value to predict respectively recovery and failure of recovery of consciousness. A very early EEG exam allows identification of patients with very high probability of a good outcome, allowing rapid use of the most appropriate therapeutic procedures.
Published: 2021
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4. The Italian technical/administrative recommendations for telemedicine in clinical neurophysiology

Author: Antonello Grippo, V. Di Lazzaro, C. Rabbito, R. Pasqui, Aldo Amantini, S. Lori, F. Gabbrielli, D. Olivi, D. Barloscio, Riccardo Carrai, and G. Stipa
Subjects: medicine.medical_specialty, Telemedicine, Neurophysiology, Globe, Dermatology, Telemedicine guidelines, 03 medical and health sciences, 0302 clinical medicine, Remote control, Teleneurophysiology, medicine, Humans, 030212 general & internal medicine, Public health, business.industry, Consensus conference, Information technology, General Medicine, Psychiatry and Mental health, Engineering management, medicine.anatomical_structure, Italy, General Data Protection Regulation, Telemedicine recommendations, The Internet, Original Article, Neurology (clinical), Business, Developed country, 030217 neurology & neurosurgery
Abstract: Recent advances in technology, information technology, Internet networks, and, more recently, fiber optics in industrialized countries allow the exchange of a huge amount of data, in real time, across the globe. The acquisition of increasingly sophisticated technologies has made it possible to develop telemedicine, by which the specialist's evaluation can be carried out on the patient even remotely. In Italy, this very useful tool, although possible from a technological and information technology point of view, has not been developed because of the lack of clear and univocal rules and of major administrative obstacles related to the Italian Public Health System. To promote telemedicine implementation in Italy, the Italian Society of Clinical Neurophysiology and the Italian Society of Telemedicine together with the National Centre for Telemedicine and New Assistive Technologies of the Italian Higher Institute of Health prepared these inter-society recommendations. Because of potential forensic value of these recommendations, they were prepared considering the current regulations and the General Data Protection Regulation and will provide the basis for a Consensus Conference planned to discuss and prepare National Telemedicine Guidelines.
Published: 2020

5. A multimodal diagnostic approach for lateralised rhythmic delta activity in the ictal-interictal continuum

Author: Aldo Amantini, Maenia Scarpino, Francesca Pescini, Riccardo Carrai, Cristina Boccardi, M. Spalletti, Davide Gadda, Antonello Grippo, and Benedetta Piccardi
Subjects: Male, Computed Tomography Angiography, Perfusion scanning, Electroencephalography, Status Epilepticus, Rhythm, Neuroimaging, Aphasia, Humans, Medicine, Ictal, Clinical significance, Aged, 80 and over, medicine.diagnostic_test, business.industry, Multimodal therapy, General Medicine, nervous system diseases, Delta Rhythm, nervous system, Neurology, Neurology (clinical), medicine.symptom, business, Neuroscience
Abstract: The ictal-interictal continuum represents a diagnostic challenge even for expert neurrophysiologists, often requiring an additional multimodal diagnostic workup to understand its clinical significance. Lateralised rhythmic delta activity (LRDA) is an ictal-interictal continuum pattern that has only recently been investigated and recognised as potentially ictogenic or sometimes even ictal. We describe a patient who presented with acute-onset aphasia, initially suspected of having a stroke; advanced brain imaging with CT-perfusion showed features suggesting regional left temporo-parietal hyperperfusion and an EEG revealed LRDA with fluctuations and intermixed sharp waves in the same areas. Treatment with lacosamide caused both clinical and EEG improvement after a few hours, supporting the hypothesis that the EEG pattern represented an ictal/interictal phenomenon. In the literature, a correlation between metabolic/perfusion imaging and ictal-interictal continuum patterns is described regarding lateralised periodic discharges but less studied for LRDA. In this case, we adopted a multimodal approach, integrating advanced imaging, EEG, clinical features, and response to therapy, to consider the overall clinical presentation as focal NCSE.
Published: 2020
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6. Serum C-reactive protein is a useful marker to exclude anastomotic leakage after colorectal surgery

Author: Ricardo Vieira Botelho, Sarhan Sydney Saad, Bruno Amantini Messias, Jaques Waisberg, Karine Corcione Turke, and Érica Rossi Mocchetti
Subjects: Adult, Male, medicine.medical_specialty, Science, Anastomotic Leak, 030230 surgery, Gastroenterology, Article, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, medicine, Humans, In patient, Postoperative Period, Colonic diseases, Digestive System Surgical Procedures, Aged, Retrospective Studies, Multidisciplinary, biology, Receiver operating characteristic, business.industry, Mortality rate, Anastomosis, Surgical, C-reactive protein, Area under the curve, Middle Aged, Colorectal cancer, Colorectal surgery, C-Reactive Protein, ROC Curve, Anastomotic leakage, 030220 oncology & carcinogenesis, biology.protein, Medicine, Female, business, Complication, Colorectal Surgery, Biomarkers
Abstract: Anastomotic leakage is a complication of colorectal surgery. C-reactive protein (CRP) is an acute-phase marker that can indicate surgical complications. We determined whether serum CRP levels in patients who had undergone colorectal surgery can be used to exclude the presence of anastomotic leakage and allow safe early discharge. We included 90 patients who underwent colorectal surgery with primary anastomosis. Serum CRP levels were measured retrospectively on postoperative days (PODs) 1 – 7. Patients with anastomotic leakage (n = 11) were compared to those without leakage (n = 79). We statistically analysed data and plotted receiver operating characteristic curves. The incidence of anastomotic leakage was 12.2%. Diagnoses were made on PODs 3 – 24. The overall mortality rate was 3.3% (18.2% in the leakage group, 1.3% in the non-leakage group; P
Published: 2020

7. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1

Author: Klionsky, Daniel, Abdel-Aziz, Amal Kamal, Abdelfatah, Sara, Abdellatif, Mahmoud, Abdoli, Asghar, Abel, Steffen, Abeliovich, Hagai, Abildgaard, Marie, Abudu, Yakubu Princely, Acevedo-Arozena, Abraham, Adamopoulos, Iannis, Adeli, Khosrow, Adolph, Timon, Adornetto, Annagrazia, Aflaki, Elma, Agam, Galila, Agarwal, Anupam, Aggarwal, Bharat, Agnello, Maria, Agostinis, Patrizia, Agrewala, Javed, Agrotis, Alexander, Aguilar, Patricia, Ahmad, S Tariq, Ahmed, Zubair, Ahumada-Castro, Ulises, Aits, Sonja, Aizawa, Shu, Akkoc, Yunus, Akoumianaki, Tonia, Akpinar, Hafize Aysin, Al-Abd, Ahmed, Al-Akra, Lina, Al-Gharaibeh, Abeer, Alaoui-Jamali, Moulay, Alberti, Simon, Alcocer-Gómez, Elísabet, Alessandri, Cristiano, Ali, Muhammad, Alim Al-Bari, M Abdul, Aliwaini, Saeb, Alizadeh, Javad, Almacellas, Eugènia, Almasan, Alexandru, Alonso, Alicia, Alonso, Guillermo, Altan-Bonnet, Nihal, Altieri, Dario, Álvarez, Élida, Alves, Sara, Alves Da Costa, Cristine, Alzaharna, Mazen, Amadio, Marialaura, Amantini, Consuelo, Amaral, Cristina, Ambrosio, Susanna, Amer, Amal, Ammanathan, Veena, An, Zhenyi, Andersen, Stig, Andrabi, Shaida, Andrade-Silva, Magaiver, Andres, Allen, Angelini, Sabrina, Ann, David, Anozie, Uche, Ansari, Mohammad, Antas, Pedro, Antebi, Adam, Antón, Zuriñe, Anwar, Tahira, Apetoh, Lionel, Apostolova, Nadezda, Araki, Toshiyuki, Araki, Yasuhiro, Arasaki, Kohei, Araújo, Wagner, Araya, Jun, Arden, Catherine, Arévalo, Maria-Angeles, Arguelles, Sandro, Arias, Esperanza, Arikkath, Jyothi, Arimoto, Hirokazu, Ariosa, Aileen, Armstrong-James, Darius, Arnauné-Pelloquin, Laetitia, Aroca, Angeles, Arroyo, Daniela, Arsov, Ivica, Artero, Rubén, Asaro, Dalia Maria Lucia, Aschner, Michael, Ashrafizadeh, Milad, Ashur-Fabian, Osnat, Atanasov, Atanas, Au, Alicia, Auberger, Patrick, Auner, Holger, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Ávalos, Yenniffer, Aveic, Sanja, Aveleira, Célia Alexandra, Avin-Wittenberg, Tamar, Aydin, Yucel, Ayton, Scott, Ayyadevara, Srinivas, Azzopardi, Maria, Baba, Misuzu, Backer, Jonathan, Backues, Steven, Bae, Dong-Hun, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric, Baek, Ahruem, Baek, Seung-Hoon, Baek, Sung Hee, Bagetta, Giacinto, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xiyuan, Bai, Yidong, Bairagi, Nandadulal, Baksi, Shounak, Balbi, Teresa, Baldari, Cosima, Balduini, Walter, Ballabio, Andrea, Ballester, Maria, Balazadeh, Salma, Balzan, Rena, Bandopadhyay, Rina, Banerjee, Sreeparna, Banerjee, Sulagna, Bánréti, Ágnes, Bao, Yan, Baptista, Mauricio, Baracca, Alessandra, Barbati, Cristiana, Bargiela, Ariadna, Barilà, Daniela, Barlow, Peter, Barmada, Sami, Barreiro, Esther, Barreto, George, Bartek, Jiri, Bartel, Bonnie, Bartolome, Alberto, Barve, Gaurav, Basagoudanavar, Suresh, Bassham, Diane, Bast, Robert, Basu, Alakananda, Batoko, Henri, Batten, Isabella, Baulieu, Etienne, Baumgarner, Bradley, Bayry, Jagadeesh, Beale, Rupert, Beau, Isabelle, Beaumatin, Florian, Bechara, Luiz, Beck, George, Beers, Michael, Begun, Jakob, Behrends, Christian, Behrens, Georg, Bei, Roberto, Bejarano, Eloy, Bel, Shai, Behl, Christian, Belaid, Amine, Belgareh-Touzé, Naïma, Bellarosa, Cristina, Belleudi, Francesca, Belló Pérez, Melissa, Bello-Morales, Raquel, Beltran, Jackeline Soares de Oliveira, Beltran, Sebastián, Benbrook, Doris Mangiaracina, Bendorius, Mykolas, Benitez, Bruno, Benito-Cuesta, Irene, Bensalem, Julien, Berchtold, Martin, Berezowska, Sabina, Bergamaschi, Daniele, Bergami, Matteo, Bergmann, Andreas, Berliocchi, Laura, Berlioz-Torrent, Clarisse, Bernard, Amélie, Berthoux, Lionel, Besirli, Cagri, Besteiro, Sebastien, Betin, Virginie, Beyaert, Rudi, Bezbradica, Jelena, Bhaskar, Kiran, Bhatia-Kissova, Ingrid, Bhattacharya, Resham, Bhattacharya, Sujoy, Bhattacharyya, Shalmoli, Bhuiyan, Md Shenuarin, Bhutia, Sujit Kumar, Bi, Lanrong, Bi, Xiaolin, Biden, Trevor, Bijian, Krikor, Billes, Viktor, Binart, Nadine, Bincoletto, Claudia, Birgisdottir, Asa, Bjorkoy, Geir, Blanco, Gonzalo, Blas-Garcia, Ana, Blasiak, Janusz, Blomgran, Robert, Blomgren, Klas, Blum, Janice, Boada-Romero, Emilio, Boban, Mirta, Boesze-Battaglia, Kathleen, Boeuf, Philippe, Boland, Barry, Bomont, Pascale, Bonaldo, Paolo, Bonam, Srinivasa Reddy, Bonfili, Laura, Bonifacino, Juan, Boone, Brian, Bootman, Martin, Bordi, Matteo, Borner, Christoph, Bornhauser, Beat, Borthakur, Gautam, Bosch, Jürgen, Bose, Santanu, botana, luis, Botas, Juan, Boulanger, Chantal, Boulton, Michael, Bourdenx, Mathieu, Bourgeois, Benjamin, Bourke, Nollaig, Bousquet, Guilhem, Boya, Patricia, Bozhkov, Peter, Bozi, Luiz, Bozkurt, Tolga, Brackney, Doug, Brandts, Christian, Braun, Ralf, Braus, Gerhard, Bravo-Sagua, Roberto, Bravo-San Pedro, José, Brest, Patrick, Bringer, Marie-Agnès, Briones-Herrera, Alfredo, Broaddus, V Courtney, Brodersen, Peter, Brodsky, Jeffrey, Brody, Steven, Bronson, Paola, Bronstein, Jeff, Brown, Carolyn, Brown, Rhoderick, Brum, Patricia, Brumell, John, Brunetti-Pierri, Nicola, Bruno, Daniele, Bryson-Richardson, Robert, Bucci, Cecilia, Buchrieser, Carmen, Bueno, Marta, Buitrago-Molina, Laura Elisa, Buraschi, Simone, Buch, Shilpa, Buchan, J Ross, Buckingham, Erin, Budak, Hikmet, Budini, Mauricio, Bultynck, Geert, Burada, Florin, Burgoyne, Joseph, Burón, M Isabel, Bustos, Victor, Büttner, Sabrina, Butturini, Elena, Byrd, Aaron, Cabas, Isabel, Cabrera-Benitez, Sandra, Cadwell, Ken, Cai, Jingjing, Cai, Lu, Cai, Qian, Cairó, Montserrat, Calbet, Jose, Caldwell, Guy, Caldwell, Kim, Call, Jarrod, Calvani, Riccardo, Calvo, Ana, Calvo-Rubio Barrera, Miguel, Camara, Niels OS, Camonis, Jacques, Camougrand, Nadine, Campanella, Michelangelo, Campbell, Edward, Campbell-Valois, François-Xavier, Campello, Silvia, Campesi, Ilaria, Campos, Juliane, Camuzard, Olivier, Cancino, Jorge, Candido de Almeida, Danilo, Canesi, Laura, Caniggia, Isabella, Canonico, Barbara, Cantí, Carles, Cao, Bin, Caraglia, Michele, Caramés, Beatriz, Carchman, Evie, Cardenal-Muñoz, Elena, Cardenas, Cesar, Cardenas, Luis, Cardoso, Sandra, Carew, Jennifer, Carle, Georges, Carleton, Gillian, Carloni, Silvia, Carmona-Gutierrez, Didac, Carneiro, Leticia, Carnevali, Oliana, Carosi, Julian, Carra, Serena, Carrier, Alice, Carrier, Lucie, Carroll, Bernadette, Carter, A Brent, Carvalho, Andreia Neves, Casanova, Magali, Casas, Caty, Casas, Josefina, Cassioli, Chiara, Castillo, Eliseo, Castillo, Karen, Castillo-Lluva, Sonia, Castoldi, Francesca, Castori, Marco, Castro, Ariel, Castro-Caldas, Margarida, Castro-Hernandez, Javier, Castro-Obregon, Susana, Catz, Sergio, Cavadas, Claudia, Cavaliere, Federica, Cavallini, Gabriella, Cavinato, Maria, Cayuela, Maria, Cebollada Rica, Paula, Cecarini, Valentina, Cecconi, Francesco, Cechowska-Pasko, Marzanna, Cenci, Simone, Ceperuelo-Mallafré, Victòria, Cerqueira, João, Cerutti, Janete, Cervia, Davide, Cetintas, Vildan Bozok, Cetrullo, Silvia, Chae, Han-Jung, Chagin, Andrei, Chai, Chee-Yin, Chakrabarti, Gopal, Chakrabarti, Oishee, Chakraborty, Tapas, Chakraborty, Trinad, Chami, mounia, Chamilos, Georgios, Chan, David, Chan, Edmond, Chan, Edward, Chan, H.Y. Edwin, Chan, Helen, Chan, Hung, Chan, Matthew, Chan, Yau Sang, Chandra, Partha, Chang, Chih-Peng, Chang, Chunmei, Chang, Hao-Chun, Chang, Kai, Chao, Jie, Chapman, Tracey, Charlet-Berguerand, Nicolas, Chatterjee, Samrat, Chaube, Shail, Chaudhary, Anu, Chauhan, Santosh, Chaum, Edward, Checler, Frédéric, Cheetham, Michael, Chen, Chang-Shi, Chen, Guang-Chao, Chen, Jian-Fu, Chen, Liam, Chen, Leilei, Chen, Lin, Chen, Mingliang, Chen, Mu-Kuan, Chen, Ning, Chen, Quan, Chen, Ruey-Hwa, Chen, Shi, Chen, Wei, Chen, Weiqiang, Chen, Xin-Ming, Chen, Xiong-Wen, Chen, Xu, Chen, Yan, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Zhefan Stephen, Chen, Zhi, Chen, Zhi-Hua, Chen, Zhijian, Chen, Zhixiang, Cheng, Hanhua, Cheng, Jun, Cheng, Shi-Yuan, Cheng, Wei, Cheng, Xiaodong, Cheng, Xiu-Tang, Cheng, Yiyun, Cheng, Zhiyong, Chen, Zhong, Cheong, Heesun, Cheong, Jit Kong, Chernyak, Boris, Cherry, Sara, Cheung, Chi Fai Randy, Cheung, Chun Hei Antonio, Cheung, King-Ho, Chevet, Eric, Chi, Richard, Chiang, Alan Kwok Shing, Chiaradonna, Ferdinando, Chiarelli, Roberto, Chiariello, Mario, Chica, Nathalia, Chiocca, Susanna, Chiong, Mario, Chiou, Shih-Hwa, Chiramel, Abhilash, Chiurchiù, Valerio, Cho, Dong-Hyung, Choe, Seong-Kyu, Choi, Augustine, Choi, Mary, Choudhury, Kamalika Roy, Chow, Norman, Chu, Charleen, Chua, Jason, Chua, John Jia En, Chung, Hyewon, Chung, Kin Pan, Chung, Seockhoon, Chung, So-Hyang, Chung, Yuen-Li, Cianfanelli, Valentina, Ciechomska, Iwona, Cifuentes, Mariana, Cinque, Laura, Cirak, Sebahattin, Cirone, Mara, Clague, Michael, Clarke, Robert, Clementi, Emilio, Coccia, Eliana, Codogno, Patrice, Cohen, Ehud, Cohen, Mickael, Colasanti, Tania, Colasuonno, Fiorella, Colbert, Robert, Colell, Anna, Čolić, Miodrag, Coll, Nuria, Collins, Mark, Colombo, María, Colón-Ramos, Daniel, Combaret, Lydie, Comincini, Sergio, Cominetti, Márcia, Consiglio, Antonella, Conte, Andrea, Conti, Fabrizio, Contu, Viorica Raluca, Cookson, Mark, Coombs, Kevin, Coppens, Isabelle, Corasaniti, Maria Tiziana, Corkery, Dale, Cordes, Nils, Cortese, Katia, Costa, Maria do Carmo, Costantino, Sarah, Costelli, Paola, Coto-Montes, Ana, Crack, Peter, Crespo, Jose, Criollo, Alfredo, Crippa, Valeria, Cristofani, Riccardo, Csizmadia, Tamas, Cuadrado, Antonio, Cui, Bing, Cui, Jun, Cui, Yixian, Cui, Yong, Culetto, Emmanuel, Cumino, Andrea, Cybulsky, Andrey, Czaja, Mark, Czuczwar, Stanislaw, D'Adamo, Stefania, D'Amelio, Marcello, D'Arcangelo, Daniela, D'Lugos, Andrew, D'Orazi, Gabriella, da Silva, James, Dafsari, Hormos Salimi, Dagda, Ruben, Dagdas, Yasin, Daglia, Maria, Dai, Xiaoxia, Dai, Yun, Dai, Yuyuan, Dal Col, Jessica, Dalhaimer, Paul, Dalla Valle, Luisa, Dallenga, Tobias, Dalmasso, Guillaume, Damme, Markus, Dando, Ilaria, Dantuma, Nico, Darling, April, Das, Hiranmoy, Dasarathy, Srinivasan, Dasari, Santosh, Dash, Srikanta, Daumke, Oliver, Dauphinee, Adrian, Davies, Jeffrey, Dávila, Valeria, Davis, Roger, Davis, Tanja, Dayalan Naidu, Sharadha, De Amicis, Francesca, De Bosscher, Karolien, De Felice, Francesca, De Franceschi, Lucia, De Leonibus, Chiara, de Mattos Barbosa, Mayara, De Meyer, Guido, De Milito, Angelo, De Nunzio, Cosimo, De Palma, Clara, De Santi, Mauro, De Virgilio, Claudio, De Zio, Daniela, Debnath, Jayanta, DeBosch, Brian, Decuypere, Jean-Paul, Deehan, Mark, Deflorian, Gianluca, DeGregori, James, Dehay, Benjamin, Del Rio, Gabriel, Delaney, Joe, Delbridge, Lea, Delorme-Axford, Elizabeth, Delpino, M Victoria, Demarchi, Francesca, Dembitz, Vilma, Demers, Nicholas, Deng, Hongbin, Deng, Zhiqiang, Dengjel, Joern, Dent, Paul, Denton, Donna, DePamphilis, Melvin, Der, Channing, Deretic, Vojo, Descoteaux, Albert, Devis, Laura, Devkota, Sushil, Devuyst, Olivier, Dewson, Grant, Dharmasivam, Mahendiran, Dhiman, Rohan, di Bernardo, Diego, Di Cristina, Manlio, Di Domenico, Fabio, Di Fazio, Pietro, Di Fonzo, Alessio, Di Guardo, Giovanni, Di Guglielmo, Gianni, Di Leo, Luca, Di Malta, Chiara, Di Nardo, Alessia, Di Rienzo, Martina, Di Sano, Federica, Diallinas, George, Diao, Jiajie, Diaz-Araya, Guillermo, Díaz-Laviada, Inés, Dickinson, Jared, Diederich, Marc, Dieudé, Mélanie, Dikic, Ivan, Ding, Shiping, Ding, Wen-Xing, Dini, Luciana, Dinić, Jelena, Dinic, Miroslav, Dinkova-Kostova, Albena, Dionne, Marc, Distler, Jörg, Diwan, Abhinav, Dixon, Ian, Djavaheri-Mergny, Mojgan, Dobrinski, Ina, Dobrovinskaya, Oxana, Dobrowolski, Radek, Dobson, Renwick, Đokić, Jelena, Dokmeci Emre, Serap, Donadelli, Massimo, Dong, Bo, Dong, Xiaonan, Dong, Zhiwu, Dorn Ii, Gerald, Dotsch, Volker, Dou, Huan, Dou, Juan, Dowaidar, Moataz, Dridi, Sami, Drucker, Liat, Du, Ailian, Du, Caigan, Du, Guangwei, Du, Hai-Ning, Du, Li-Lin, du Toit, André, Duan, Shao-Bin, Duan, Xiaoqiong, Duarte, Sónia, Dubrovska, Anna, Dunlop, Elaine, Dupont, Nicolas, Durán, Raúl, Dwarakanath, Bilikere, Dyshlovoy, Sergey, Ebrahimi-Fakhari, Darius, Eckhart, Leopold, Edelstein, Charles, Efferth, Thomas, Eftekharpour, Eftekhar, Eichinger, Ludwig, Eid, Nabil, Eisenberg, Tobias, Eissa, N Tony, Eissa, Sanaa, Ejarque, Miriam, El Andaloussi, Abdeljabar, El-Hage, Nazira, El-Naggar, Shahenda, Eleuteri, Anna Maria, El-Shafey, Eman, Elgendy, Mohamed, Eliopoulos, Aristides, Elizalde, María, Elks, Philip, Elsasser, Hans-Peter, Elsherbiny, Eslam, Emerling, Brooke, Emre, N., Eng, Christina, Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelsen, Agnete, Enserink, Jorrit, Escalante, Ricardo, Esclatine, Audrey, Escobar-Henriques, Mafalda, Eskelinen, Eeva-Liisa, Espert, Lucile, Eusebio, Makandjou-Ola, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Facchiano, Francesco, Fadeel, Bengt, Fader, Claudio, Faesen, Alex, Fairlie, W Douglas, Falcó, Alberto, Falkenburger, Bjorn, Fan, Daping, Fan, Jie, Fan, Yanbo, Fang, Evandro, Fang, Yanshan, Fang, Yognqi, Fanto, Manolis, Farfel-Becker, Tamar, Faure, Mathias, Fazeli, Gholamreza, Fedele, Anthony, Feldman, Arthur, Feng, Du, Feng, Jiachun, Feng, Lifeng, Feng, Yibin, Feng, Yuchen, Feng, Wei, Fenz Araujo, Thais, Ferguson, Thomas, Fernández, Álvaro, Fernandez-Checa, Jose, Fernández-Veledo, Sonia, Fernie, Alisdair, Ferrante, Anthony, Ferraresi, Alessandra, Ferrari, Merari, Ferreira, Julio, Ferro-Novick, Susan, Figueras, Antonio, Filadi, Riccardo, Filigheddu, Nicoletta, Filippi-Chiela, Eduardo, Filomeni, Giuseppe, Fimia, Gian Maria, Fineschi, Vittorio, Finetti, Francesca, Finkbeiner, Steven, Fisher, Edward, Fisher, Paul, Flamigni, Flavio, Fliesler, Steven, Flo, Trude, Florance, Ida, Florey, Oliver, Florio, Tullio, Fodor, Erika, Follo, Carlo, Fon, Edward, Forlino, Antonella, Fornai, Francesco, Fortini, Paola, Fracassi, Anna, Fraldi, Alessandro, Franco, Brunella, Franco, Rodrigo, Franconi, Flavia, Frankel, Lisa, Friedman, Scott, Fröhlich, Leopold, Frühbeck, Gema, Fuentes, Jose, Fujiki, Yukio, Fujita, Naonobu, Fujiwara, Yuuki, Fukuda, Mitsunori, Fulda, Simone, Furic, Luc, Furuya, Norihiko, Fusco, Carmela, Gack, Michaela, Gaffke, Lidia, Galadari, Sehamuddin, Galasso, Alessia, Galindo, Maria, Gallolu Kankanamalage, Sachith, Galluzzi, Lorenzo, Galy, Vincent, Gammoh, Noor, Gan, Boyi, Ganley, Ian, Gao, Feng, Gao, Hui, Gao, Minghui, Gao, Ping, Gao, Shou-Jiang, Gao, Wentao, Gao, Xiaobo, Garcera, Ana, Garcia, Maria Noé, Garcia, Verónica, García-del Portillo, Francisco, Garcia-Escudero, Vega, Garcia-Garcia, Aracely, Garcia-Macia, Marina, García-Moreno, Diana, Garcia-Ruiz, Carmen, García-Sanz, Patricia, Garg, Abhishek, Gargini, Ricardo, Garofalo, Tina, Garry, Robert, Gassen, Nils, Gatica, Damian, Ge, Liang, Ge, Wanzhong, Geiss-Friedlander, Ruth, Gelfi, Cecilia, Genschik, Pascal, Gentle, Ian, Gerbino, Valeria, Gerhardt, Christoph, Germain, Kyla, Germain, Marc, Gewirtz, David, Ghasemipour Afshar, Elham, Ghavami, Saeid, Ghigo, Alessandra, Ghosh, Manosij, Giamas, Georgios, Giampietri, Claudia, Giatromanolaki, Alexandra, Gibson, Gary, Gibson, Spencer, Ginet, Vanessa, Giniger, Edward, Giorgi, Carlotta, Girao, Henrique, Girardin, Stephen, Giridharan, Mridhula, Giuliano, Sandy, Giulivi, Cecilia, Giuriato, Sylvie, Giustiniani, Julien, Gluschko, Alexander, Goder, Veit, Goginashvili, Alexander, Golab, Jakub, Goldstone, David, Golebiewska, Anna, Gomes, Luciana, Gomez, Rodrigo, Gómez-Sánchez, Rubén, Gomez-Puerto, Maria Catalina, Gomez-Sintes, Raquel, Gong, Qingqiu, Goni, Felix, González-Gallego, Javier, Gonzalez-Hernandez, Tomas, Gonzalez-Polo, Rosa, Gonzalez-Reyes, Jose, González-Rodríguez, Patricia, Goping, Ing Swie, Gorbatyuk, Marina, Gorbunov, Nikolai, Görgülü, Kıvanç, Gorojod, Roxana, Gorski, Sharon, Goruppi, Sandro, Gotor, Cecilia, Gottlieb, Roberta, Gozes, Illana, Gozuacik, Devrim, Graef, Martin, Gräler, Markus, Granatiero, Veronica, Grasso, Daniel, Gray, Joshua, Green, Douglas, Greenhough, Alexander, Gregory, Stephen, Griffin, Edward, Grinstaff, Mark, Gros, Frederic, Grose, Charles, Gross, Angelina, Gruber, Florian, Grumati, Paolo, Grune, Tilman, Gu, Xueyan, Guan, Jun-Lin, Guardia, Carlos, Guda, Kishore, Guerra, Flora, Guerri, Consuelo, Guha, Prasun, Guillén, Carlos, Gujar, Shashi, Gukovskaya, Anna, Gukovsky, Ilya, Gunst, Jan, Günther, Andreas, Guntur, Anyonya, Guo, Chuanyong, Guo, Chun, Guo, Hongqing, Guo, Lian-Wang, Guo, Ming, Gupta, Pawan, Gupta, Shashi Kumar, Gupta, Swapnil, Gupta, Veer Bala, Gupta, Vivek, Gustafsson, Asa, Gutterman, David, H B, Ranjitha, Haapasalo, Annakaisa, Haber, James, Hać, Aleksandra, Hadano, Shinji, Hafrén, Anders, Haidar, Mansour, Hall, Belinda, Halldén, Gunnel, Hamacher-Brady, Anne, Hamann, Andrea, Hamasaki, Maho, Han, Weidong, Hansen, Malene, Hanson, Phyllis, Hao, Zijian, Harada, Masaru, Harhaji-Trajkovic, Ljubica, Hariharan, Nirmala, Haroon, Nigil, Harris, James, Hasegawa, Takafumi, Hasima Nagoor, Noor, Haspel, Jeffrey, Haucke, Volker, Hawkins, Wayne, Hay, Bruce, Haynes, Cole, Hayrabedyan, Soren, Hays, Thomas, He, Congcong, He, Qin, He, Rong-Rong, He, You-Wen, He, Yu-Ying, Heakal, Yasser, Heberle, Alexander, Hejtmancik, J Fielding, Helgason, Gudmundur Vignir, Henkel, Vanessa, Herb, Marc, Hergovich, Alexander, Herman-Antosiewicz, Anna, Hernández, Agustín, Hernandez, Carlos, Hernandez-Diaz, Sergio, Hernandez-Gea, Virginia, Herpin, Amaury, Herreros, Judit, Hervás, Javier, Hesselson, Daniel, Hetz, Claudio, Heussler, Volker, Higuchi, Yujiro, Hilfiker, Sabine, Hill, Joseph, Hlavacek, William, Ho, Emmanuel, Ho, Idy, Ho, Philip Wing-Lok, Ho, Shu-Leong, Ho, Wan Yun, Hobbs, G Aaron, Hochstrasser, Mark, Hoet, Peter, Hofius, Daniel, Hofman, Paul, Höhn, Annika, Holmberg, Carina, Hombrebueno, Jose, Yi-Ren Hong, Chang-Won Hong, Hooper, Lora, Hoppe, Thorsten, Horos, Rastislav, Hoshida, Yujin, Hsin, I-Lun, Hsu, Hsin-Yun, Hu, Bing, Hu, Dong, Hu, Li-Fang, Hu, Ming Chang, Hu, Ronggui, Hu, Wei, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Jinlian, Hua, Yingqi, Huan, Chongmin, Huang, Canhua, Huang, Chuanshu, Huang, Chuanxin, Huang, Chunling, Huang, Haishan, Huang, Kun, Huang, Michael, Huang, Rui, Huang, Shan, Huang, Tianzhi, Huang, Xing, Huang, Yuxiang Jack, Huber, Tobias, Hubert, Virginie, Hubner, Christian, Hughes, Stephanie, Hughes, William, Humbert, Magali, Hummer, Gerhard, Hurley, James, Hussain, Sabah, Hussain, Salik, Hussey, Patrick, Hutabarat, Martina, Hwang, Hui-Yun, Hwang, Seungmin, Ieni, Antonio, Ikeda, Fumiyo, Imagawa, Yusuke, Imai, Yuzuru, Imbriano, Carol, Imoto, Masaya, Inman, Denise, Inoki, Ken, Iovanna, Juan, Iozzo, Renato, Ippolito, Giuseppe, Irazoqui, Javier, Iribarren, Pablo, Ishaq, Mohd, ISHIKAWA, Makoto, Ishimwe, Nestor, Isidoro, Ciro, Ismail, Nahed, Issazadeh-Navikas, Shohreh, Itakura, Eisuke, Ito, Daisuke, Ivankovic, Davor, Ivanova, Saška, Iyer, Anand Krishnan V, Izquierdo, José, Izumi, Masanori, Jäättelä, Marja, Jabir, Majid Sakhi, Jackson, William, Jacobo-Herrera, Nadia, Jacomin, Anne-Claire, Jacquin, Elise, Jadiya, Pooja, Jaeschke, Hartmut, Jagannath, Chinnaswamy, Jakobi, Arjen, Jakobsson, Johan, Janji, Bassam, Jansen-Dürr, Pidder, Jansson, Patric, Jantsch, Jonathan, Januszewski, Sławomir, Jassey, Alagie, Jean, Steve, Jeltsch-David, Hélène, Jendelova, Pavla, Jenny, Andreas, Jensen, Thomas, Jessen, Niels, Jewell, Jenna, Ji, Jing, Jia, Lijun, Jia, Rui, Jiang, Liwen, Jiang, Qing, Jiang, Richeng, Jiang, Teng, Jiang, Xuejun, Jiang, Yu, Jimenez-Sanchez, Maria, Jin, Eun-Jung, Jin, Fengyan, Jin, Hongchuan, Jin, Li, Jin, Luqi, Jin, Meiyan, Jin, Si, Jo, Eun-Kyeong, Joffre, Carine, Johansen, Terje, Johnson, Gail, Johnston, Simon, Jokitalo, Eija, Jolly, Mohit Kumar, Joosten, Leo, Jordan, Joaquin, Joseph, Bertrand, Ju, Dianwen, Ju, Jeong-Sun, Ju, Jingfang, Juárez, Esmeralda, Judith, Delphine, Juhász, Gábor, Jun, Youngsoo, Jung, Chang Hwa, Jung, Sung-Chul, Jung, Yong Keun, Jungbluth, Heinz, Jungverdorben, Johannes, Just, Steffen, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kaganovich, Daniel, Kahana, Alon, Kain, Renate, Kajimura, Shinjo, Kalamvoki, Maria, Kalia, Manjula, Kalinowski, Danuta, Kaludercic, Nina, Kalvari, Ioanna, Kaminska, Joanna, Kaminskyy, Vitaliy, Kanamori, Hiromitsu, Kanasaki, Keizo, Kang, Chanhee, Kang, Rui, Kang, Sang Sun, Kaniyappan, Senthilvelrajan, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanthasamy, Anumantha, Kanthasamy, Arthi, Kantorow, Marc, Kapuy, Orsolya, Karamouzis, Michalis, Karim, Md Razaul, Karmakar, Parimal, Katare, Rajesh, Kato, Masaru, Kaufmann, Stefan, Kauppinen, Anu, Kaushal, Gur, Kaushik, Susmita, Kawasaki, Kiyoshi, Kazan, Kemal, Ke, Po-Yuan, Keating, Damien, Keber, Ursula, Kehrl, John, Keller, Kate, Keller, Christian, Kemper, Jongsook Kim, Kenific, Candia, Kepp, Oliver, Kermorgant, Stephanie, Kern, Andreas, Ketteler, Robin, Keulers, Tom, Khalfin, Boris, Khalil, Hany, Khambu, Bilon, Khan, Shahid, Khandelwal, Vinoth Kumar Megraj, Khandia, Rekha, Kho, Widuri, Khobrekar, Noopur, Khuansuwan, Sataree, Khundadze, Mukhran, Killackey, Samuel, Kim, Dasol, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Eun, Kim, Eun Young, Kim, Eun-Kyoung, Kim, Hak-Rim, Kim, Hee-Sik, Kim, Hyung Ryong, Kim, Jeong Hun, Kim, Jin Kyung, Kim, Jin-Hoi, Kim, Joungmok, Kim, Ju Hwan, Kim, Keun Il, Kim, Peter, Kim, Seong-Jun, Kimball, Scot, Kimchi, Adi, Kimmelman, Alec, Kimura, Tomonori, King, Matthew, Kinghorn, Kerri, Kinsey, Conan, Kirkin, Vladimir, Kirshenbaum, Lorrie, Kiselev, Sergey, Kishi, Shuji, Kitamoto, Katsuhiko, Kitaoka, Yasushi, Kitazato, Kaio, Kitsis, Richard, Kittler, Josef, Kjaerulff, Ole, Klein, Peter, Klopstock, Thomas, Klucken, Jochen, Knævelsrud, Helene, Knorr, Roland, Ko, Ben, Ko, Fred, Ko, Jiunn-Liang, Kobayashi, Hotaka, Kobayashi, Satoru, Koch, Ina, Koch, Jan, Koenig, Ulrich, Kögel, Donat, Koh, Young Ho, Koike, Masato, Kohlwein, Sepp, Kocaturk, Nur, Komatsu, Masaaki, König, Jeannette, Kono, Toru, Kopp, Benjamin, Korcsmaros, Tamas, Korkmaz, Gözde, Korolchuk, Viktor, Korsnes, Mónica Suárez, Koskela, Ali, Kota, Janaiah, Kotake, Yaichiro, Kotler, Monica, Kou, Yanjun, Koukourakis, Michael, Koustas, Evangelos, Kovacs, Attila, Kovács, Tibor, Koya, Daisuke, Kozako, Tomohiro, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Krasnodembskaya, Anna, Kretz-Remy, Carole, Kroemer, Guido, Ktistakis, Nicholas, Kuchitsu, Kazuyuki, Kuenen, Sabine, Kuerschner, Lars, Kukar, Thomas, Kumar, Ajay, Kumar, Ashok, Kumar, Deepak, Kumar, Dhiraj, Kumar, Sharad, Kume, Shinji, Kumsta, Caroline, Kundu, Chanakya, Kundu, Mondira, Kunnumakkara, Ajaikumar, Kurgan, Lukasz, Kutateladze, Tatiana, Kutlu, Ozlem, Kwak, SeongAe, Kwon, Ho Jeong, Kwon, Taeg Kyu, Kwon, Yong Tae, Kyrmizi, Irene, La Spada, Albert, Labonté, Patrick, Ladoire, Sylvain, Laface, Ilaria, Lafont, Frank, Lagace, Diane, Lahiri, Vikramjit, Lai, Zhibing, Laird, Angela, Lakkaraju, Aparna, Lamark, Trond, Lan, Sheng-Hui, Landajuela, Ane, Lane, Darius, Lane, Jon, Lang, Charles, Lange, Carsten, Langel, Ülo, Langer, Rupert, Lapaquette, Pierre, Laporte, Jocelyn, LaRusso, Nicholas, Lastres-Becker, Isabel, Lau, Wilson Chun Yu, Laurie, Gordon, Lavandero, Sergio, Law, Betty Yuen Kwan, Law, Helen Ka-wai, Layfield, Rob, Le, Weidong, Le Stunff, Herve, Leary, Alexandre, Lebrun, Jean-Jacques, Leck, Lionel, Leduc-Gaudet, Jean-Philippe, Lee, Changwook, Lee, Chung-Pei, Lee, Da-Hye, Lee, Edward, Lee, Erinna, Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu, Lee, Jae Man, Lee, Jason, Lee, Jin-A, Lee, Joo-Yong, Lee, Jun Hee, Lee, Michael, Lee, Min Goo, Lee, Min Jae, Lee, Myung-Shik, Lee, Sang Yoon, Lee, Seung-Jae, Lee, Stella, Lee, Sung Bae, Lee, Won Hee, Lee, Ying-Ray, Lee, Yong-ho, Lee, Youngil, Lefebvre, Christophe, Legouis, Renaud, Lei, Yu, Lei, Yuchen, Leikin, Sergey, Leitinger, Gerd, Lemus, Leticia, Leng, Shuilong, Lenoir, Olivia, Lenz, Guido, Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda, Leopoldino, Andréia, Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth, Leung, Chi-Ting, Leung, Po Sing, Leventhal, Jeremy, Levine, Beth, Lewis, Patrick, Ley, Klaus, Li, Bin, Li, Da-Qiang, Li, Jianming, Li, Jing, Li, Jiong, Li, Ke, Li, Liwu, Li, Mei, Li, Min, Li, Ming, Li, Mingchuan, Li, Pin-Lan, Li, Ming-Qing, Li, Qing, Li, Sheng, Li, Tiangang, Li, Wei, Li, Wenming, Li, Xue, Li, Yi-Ping, Li, Yuan, Li, Zhiqiang, Li, Zhiyong, Li, Zhiyuan, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl, Lilly, Mary, Lim, Hyunjung, Lima, Thania, Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie, Lin, Kurt, Lin, Kwang-Huei, Lin, Liang-Tzung, LIN, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia, Liou, Yih-Cherng, Lipinski, Marta, Lipovšek, Saška, Lira, Vitor, Lisiak, Natalia, Liton, Paloma, Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yueyang, Liu, Yule, Livingston, J Andrew, Lizard, Gerard, Lizcano, Jose, Ljubojevic-Holzer, Senka, LLeonart, Matilde, Llobet-Navàs, David, Llorente, Alicia, Lo, Chih Hung, Lobato-Márquez, Damián, Long, Qi, Long, Yun Chau, Loos, Ben, Loos, Julia, López, Manuela, López-Doménech, Guillermo, López-Guerrero, José Antonio, López-Jiménez, Ana, López-Pérez, Óscar, López-Valero, Israel, Lorenowicz, Magdalena, Lorente, Mar, Lorincz, Peter, Lossi, Laura, Lotersztajn, Sophie, Lovat, Penny, Lovell, Jonathan, Lovy, Alenka, Lőw, Péter, Lu, Guang, Lu, Haocheng, Lu, Jia-Hong, Lu, Jin-Jian, Lu, Mengji, Lu, Shuyan, Luciani, Alessandro, Lucocq, John, Ludovico, Paula, Luftig, Micah, Luhr, Morten, Luis-Ravelo, Diego, Lum, Julian, Luna-Dulcey, Liany, Lund, Anders, Lund, Viktor, Lünemann, Jan, Lüningschrör, Patrick, Luo, Honglin, Luo, Rongcan, Luo, Shouqing, Luo, Zhi, Luparello, Claudio, Lüscher, Bernhard, Luu, Luan, Lyakhovich, Alex, Lyamzaev, Konstantin, Lystad, Alf Håkon, Lytvynchuk, Lyubomyr, Ma, Alvin, Ma, Changle, Ma, Mengxiao, Ma, Ning-Fang, Ma, Quan-Hong, Ma, Xinliang, Ma, Yueyun, Ma, Zhenyi, MacDougald, Ormond, Macian, Fernando, MacIntosh, Gustavo, MacKeigan, Jeffrey, Macleod, Kay, Maday, Sandra, Madeo, Frank, Madesh, Muniswamy, Madl, Tobias, Madrigal-Matute, Julio, Maeda, Akiko, Maejima, Yasuhiro, Magarinos, Marta, Mahavadi, Poornima, Maiani, Emiliano, Maiese, Kenneth, Maiti, Panchanan, Maiuri, Maria Chiara, Majello, Barbara, Major, Michael, Makareeva, Elena, Malik, Fayaz, Mallilankaraman, Karthik, Malorni, Walter, Maloyan, Alina, Mammadova, Najiba, Man, Gene Chi Wai, Manai, Federico, Mancias, Joseph, Mandelkow, Eva-Maria, Mandell, Michael, Manfredi, Angelo, Manjili, Masoud, Manjithaya, Ravi, Manque, Patricio, Manshian, Bella, Manzano, Raquel, Manzoni, Claudia, Mao, Kai, Marchese, Cinzia, Marchetti, Sandrine, Marconi, Anna Maria, Marcucci, Fabrizio, Mardente, Stefania, Mareninova, Olga, Margeta, Marta, Mari, Muriel, Marinelli, Sara, Marinelli, Oliviero, Mariño, Guillermo, Mariotto, Sofia, Marshall, Richard, Marten, Mark, Martens, Sascha, Martin, Alexandre, Martin, Katie, Martin, Sara, Martin, Shaun, Martín-Segura, Adrián, Martín-Acebes, Miguel, Martin-Burriel, Inmaculada, Martin-Rincon, Marcos, Martin-Sanz, Paloma, Martina, José, Martinet, Wim, Martinez, Aitor, Martinez, Ana, Martinez, Jennifer, Martinez Velazquez, Moises, Martinez-Lopez, Nuria, Martinez-Vicente, Marta, Martins, Daniel, Martins, Joilson, Martins, Waleska, Martins-Marques, Tania, Marzetti, Emanuele, Masaldan, Shashank, Masclaux-Daubresse, Celine, Mashek, Douglas, Massa, Valentina, Massieu, Lourdes, Masson, Glenn, Masuelli, Laura, Masyuk, Anatoliy, Masyuk, Tetyana, Matarrese, Paola, Matheu, Ander, Matoba, Satoaki, Matsuzaki, Sachiko, Mattar, Pamela, Matte, Alessandro, Mattoscio, Domenico, Mauriz, José, Mauthe, Mario, Mauvezin, Caroline, Maverakis, Emanual, Maycotte, Paola, Mayer, Johanna, Mazzoccoli, Gianluigi, Mazzoni, Cristina, Mazzulli, Joseph, McCarty, Nami, Mcdonald, Christine, McGill, Mitchell, 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Yang, Jingyu, Yang, Ling, Yang, Liu, Yang, Ming, Yang, Pei-Ming, Yang, Qian, Yang, Seungwon, Yang, Shu, Yang, Shun-Fa, Yang, Wannian, Yang, Wei Yuan, Yang, Xiaoyong, Yang, Xuesong, Yang, Yi, Yang, Ying, Yao, Honghong, Yao, Shenggen, Yao, Xiaoqiang, Yao, Yong-Gang, Yao, Yong-Ming, Yasui, Takahiro, Yazdankhah, Meysam, Yen, Paul, Yi, Cong, Yin, Xiao-Ming, Yin, Yanhai, Yin, Zhangyuan, Yin, Ziyi, Ying, Meidan, Ying, Zheng, Yip, Calvin, Yiu, Stephanie Pei Tung, Yoo, Young, Yoshida, Kiyotsugu, Yoshii, Saori, Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan, Yu, Haiyang, Yu, Jun, Yu, Li, Yu, Ming-Lung, Yu, Seong-Woon, Yu, Victor, Yu, W Haung, Yu, Zhengping, Yu, Zhou, Yuan, Junying, Yuan, Ling-Qing, Yuan, Shilin, Yuan, Shyng-Shiou, Yuan, Yanggang, Yuan, Zengqiang, Yue, Jianbo, Yue, Zhenyu, Yun, Jeanho, Yung, Raymond, Zacks, David, Zaffagnini, Gabriele, Zambelli, Vanessa, Zanella, Isabella, Zang, Qun, Zanivan, Sara, Zappavigna, Silvia, Zaragoza, Pilar, Zarbalis, Konstantinos, Zarebkohan, Amir, Zarrouk, Amira, Zeitlin, Scott, Zeng, Jialiu, Zeng, Ju-deng, Žerovnik, Eva, Zhan, Lixuan, Zhang, Bin, Zhang, Donna, Zhang, Hanlin, Zhang, Hong, Zhang, Honghe, Zhang, Huafeng, Zhang, Huaye, Zhang, Hui, Zhang, Hui-Ling, Zhang, Jianbin, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Kalin, Zhang, Leshuai, Zhang, Lin, Zhang, Lisheng, Zhang, Lu, Zhang, Luoying, Zhang, Menghuan, Zhang, Peng, Zhang, Sheng, Zhang, Wei, Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei, Zhang, Xiaoyan, Zhang, Xin, Zhang, Xinxin, Zhang, Xu Dong, Zhang, Yang, Zhang, Yanjin, Zhang, Yi, Zhang, Ying-Dong, Zhang, Yingmei, Zhang, Yuan-Yuan, Zhang, Yuchen, Zhang, Zhe, Zhang, Zhengguang, Zhang, Zhibing, Zhang, Zhihai, Zhang, Zhiyong, Zhang, Zili, Zhao, Haobin, Zhao, Lei, Zhao, Shuang, Zhao, Tongbiao, Zhao, Xiao-Fan, Zhao, Ying, Zhao, Yongchao, Zhao, Yongliang, Zhao, Yuting, Zheng, Guoping, Zheng, Kai, Zheng, Ling, Zheng, Shizhong, Zheng, Xi-Long, Zheng, Yi, Zheng, Zu-Guo, Zhivotovsky, Boris, Zhong, Qing, Zhou, Ao, Zhou, Ben, Zhou, Cefan, ZHOU, Gang, Zhou, Hao, Zhou, Hong, Zhou, Hongbo, Zhou, Jie, Zhou, Jing, Zhou, Jiyong, Zhou, Kailiang, Zhou, Rongjia, Zhou, Xu-jie, Zhou, Yanshuang, Zhou, Yinghong, Zhou, Yubin, Zhou, Zheng-Yu, Zhou, Zhou, Zhu, Binglin, Zhu, Changlian, Zhu, Guo-Qing, Zhu, Haining, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Yanping, Zhu, Yushan, Zhuang, Haixia, Zhuang, Xiaohong, Zientara-Rytter, Katarzyna, Zimmermann, Christine, Ziviani, Elena, Zoladek, Teresa, Zong, Wei-Xing, Zorov, Dmitry, Zorzano, Antonio, Zou, Weiping, Zou, Zhen, Zou, Zhengzhi, Zuryn, Steven, Zwerschke, Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith, Stallings, Christina, Tong, Chun-Kit, Ahmad, S. Tariq, Alim Al-Bari, M. Abdul, Bechara, Luiz R.G., Behrens, Georg M.N., Bhuiyan, Md. Shenuarin, Broaddus, V. Courtney, Buchan, J. Ross, Burón, M. Isabel, Carter, A. Brent, Chan, Matthew T.V., Choi, Augustine M.K., D’Adamo, Stefania, D’Amelio, Marcello, D’Arcangelo, Daniela, D’Lugos, Andrew, D’Orazi, Gabriella, De Meyer, Guido R.Y., Delpino, M. Victoria, Distler, Jörg H.W., Dixon, Ian M.C., Dobson, Renwick C.J., 2nd Dorn, Gerald, Eissa, N. Tony, Engelsen, Agnete S.T., Fairlie, W. Douglas, Ferreira, Julio C.B., H.B., Ranjitha, Hanson, Phyllis I., Hejtmancik, J. Fielding, Ho, Idy H.T., Hobbs, G. Aaron, Hoet, Peter H.M., Huang, Michael L.H., Iyer, Anand Krishnan V., Johnson, Gail V.W., Joosten, Leo A.B., Karim, Md. Razaul, Kaufmann, Stefan H.E., Ko, Ben C.B., Leck, Lionel Y.W., Lima, Thania R.R., Livingston, J. Andrew, Martin, Alexandre P.J., Montes, L. Ruth, Murphy, J. Patrick, Ng, Charlene C.W., Nicolao, M. Celeste, O’Donovan, Tracey, O’Leary, Seónadh, O’Rourke, Eyleen, O’Sullivan, Mary, O’Sullivan, Timothy, Omary, M. Bishr, Pereira, Gustavo J.S., Ratnayaka, J. Arjuna, Riazuddin, S. Amer, Rouschop, Kasper M.A., Sanderson, J. Thomas, Scaglione, K. Matthew, Schapira, Anthony H.V., Scovassi, A. Ivana, St. Clair, Daret, Sunahara, Karen K.S., Symons, J. David, Triola, Gemma, van Wijk, Sjoerd J.L., Vanrell, M. Cristina, Vasconcelos, M. Helena, Whitton, J. Lindsay, Williams, Robin S.B., Wong, W. Wei-Lynn, Wu, William K.K., Yakhine-Diop, Sokhna M.S., Yu, W. Haung, Zhang, Kalin Y.B., Dong, X. Charlie, Ain Shams University [ASU], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University [JGU], Medical University Graz, Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Institut Pasteur d'Iran, Leibniz Institute of Plant Biochemistry [IPB], The University of Texas M.D. Anderson Cancer Center [Houston], Institut de pharmacologie moléculaire et cellulaire [IPMC], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre méditerranéen de médecine moléculaire [C3M], Institut de Biologie Valrose [IBV], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Institut NeuroMyoGène [INMG], Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)], Marqueurs cardiovasculaires en situation de stress [MASCOT (UMR_S_942 / U942)], Institut de Recherche sur le Cancer et le Vieillissement [IRCAN], Centre de Recherche en Cancérologie de Marseille [CRCM], Centre for Integrative Biology - CBI [Inserm U964 - CNRS UMR7104 - IGBMC], Oncogenesis, Stress, Signaling [OSS], Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)], Institut de Biologie Intégrative de la Cellule [I2BC], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH], Centre de Recherches en Cancérologie de Toulouse [CRCT], Physiopathologie et traitement des maladies du foie, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC], Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] [BIO-PEROXIL], Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)], Unité de génétique et biologie des cancers [U830], Laboratoire d'Optique et Biosciences [LOB], Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC], Différenciation et communication neuronale et neuroendocrine [DC2N], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Centre d'Immunologie de Marseille - Luminy [CIML], Physiopathologie et imagerie des troubles neurologiques [PhIND], Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée [LBFA], Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163], Institut Mondor de Recherche Biomédicale [IMRB], Franco-czech Laboratory for clinical research on obesity, University of Michigan [Ann Arbor], University of Michigan System, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Nutrition, Métabolisme, Aquaculture (NuMéA), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institute of genetics and molecular and cellular biology-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epithelial biology and disease - Liliane Bettencourt Chair of Developmental Biology (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the National Institute of General Medical Sciences [GM131919]., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Department of Women's and Children's Health [Stockholm, Sweden], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École polytechnique (X), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Life Sciences Institute [Ann Arbor, MI, USA], University of Michigan System-University of Michigan System, European Institute of Oncology IRCCS [Milan, Italy] (EIO), Ain Shams University (ASU), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Réseau International des Instituts Pasteur (RIIP), Leibniz Institute of Plant Biochemistry (IPB), Hebrew University of Jerusalem, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis, Stress, Signaling (OSS), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., Agrewala, J. N., Agrotis, A., Aguilar, P. V., Ahmad, S. T., Ahmed, Z. M., Ahumada-Castro, U., Aits, S., Aizawa, S., Akkoc, Y., Akoumianaki, T., Akpinar, H. A., Al-Abd, A. M., Al-Akra, L., Al-Gharaibeh, A., Alaoui-Jamali, M. A., Alberti, S., Alcocer-Gomez, E., Alessandri, C., Ali, M., Alim Al-Bari, M. A., Aliwaini, S., Alizadeh, J., Almacellas, E., Almasan, A., Alonso, A., Alonso, G. D., Altan-Bonnet, N., Altieri, D. C., Alvarez, E. M. C., Alves, S., Alves da Costa, C., Alzaharna, M. M., Amadio, M., Amantini, C., Amaral, C., Ambrosio, S., Amer, A. O., Ammanathan, V., An, Z., Andersen, S. U., Andrabi, S. A., Andrade-Silva, M., Andres, A. M., Angelini, S., Ann, D., Anozie, U. C., Ansari, M. Y., Antas, P., Antebi, A., Anton, Z., Anwar, T., Apetoh, L., Apostolova, N., Araki, T., Araki, Y., Arasaki, K., Araujo, W. L., Araya, J., Arden, C., Arevalo, M. -A., Arguelles, S., Arias, E., Arikkath, J., Arimoto, H., Ariosa, A. R., Armstrong-James, D., Arnaune-Pelloquin, L., Aroca, A., Arroyo, D. S., Arsov, I., Artero, R., Asaro, D. M. L., Aschner, M., Ashrafizadeh, M., Ashur-Fabian, O., Atanasov, A. G., Au, A. K., Auberger, P., Auner, H. W., Aurelian, L., Autelli, R., Avagliano, L., Avalos, Y., Aveic, S., Aveleira, C. A., Avin-Wittenberg, T., Aydin, Y., Ayton, S., Ayyadevara, S., Azzopardi, M., Baba, M., Backer, J. M., Backues, S. K., Bae, D. -H., Bae, O. -N., Bae, S. H., Baehrecke, E. H., Baek, A., Baek, S. -H., Baek, S. H., Bagetta, G., Bagniewska-Zadworna, A., Bai, H., Bai, J., Bai, X., Bai, Y., Bairagi, N., Baksi, S., Balbi, T., Baldari, C. T., Balduini, W., Ballabio, A., Ballester, M., Balazadeh, S., Balzan, R., Bandopadhyay, R., Banerjee, S., Banreti, A., Bao, Y., Baptista, M. S., Baracca, A., Barbati, C., Bargiela, A., Barila, D., Barlow, P. G., Barmada, S. J., Barreiro, E., Barreto, G. E., Bartek, J., Bartel, B., Bartolome, A., Barve, G. R., Basagoudanavar, S. H., Bassham, D. C., Bast, R. C., Basu, A., Batoko, H., Batten, I., Baulieu, E. E., Baumgarner, B. L., Bayry, J., Beale, R., Beau, I., Beaumatin, F., Bechara, L. R. G., Beck, G. R., Beers, M. F., Begun, J., Behrends, C., Behrens, G. M. N., Bei, R., Bejarano, E., Bel, S., Behl, C., Belaid, A., Belgareh-Touze, N., Bellarosa, C., Belleudi, F., Bello Perez, M., Bello-Morales, R., Beltran, J. S. D. O., Beltran, S., Benbrook, D. M., Bendorius, M., Benitez, B. A., Benito-Cuesta, I., Bensalem, J., Berchtold, M. W., Berezowska, S., Bergamaschi, D., Bergami, M., Bergmann, A., Berliocchi, L., Berlioz-Torrent, C., Bernard, A., Berthoux, L., Besirli, C. G., Besteiro, S., Betin, V. M., Beyaert, R., Bezbradica, J. S., Bhaskar, K., Bhatia-Kissova, I., Bhattacharya, R., Bhattacharya, S., Bhattacharyya, S., Bhuiyan, M. S., Bhutia, S. K., Bi, L., Bi, X., Biden, T. J., Bijian, K., Billes, V. A., Binart, N., Bincoletto, C., Birgisdottir, A. B., Bjorkoy, G., Blanco, G., Blas-Garcia, A., Blasiak, J., Blomgran, R., Blomgren, K., Blum, J. S., Boada-Romero, E., Boban, M., Boesze-Battaglia, K., Boeuf, P., Boland, B., Bomont, P., Bonaldo, P., Bonam, S. R., Bonfili, L., Bonifacino, J. S., Boone, B. A., Bootman, M. D., Bordi, M., Borner, C., Bornhauser, B. C., Borthakur, G., Bosch, J., Bose, S., Botana, L. M., Botas, J., Boulanger, C. M., Boulton, M. E., Bourdenx, M., Bourgeois, B., Bourke, N. M., Bousquet, G., Boya, P., Bozhkov, P. V., Bozi, L. H. M., Bozkurt, T. O., Brackney, D. E., Brandts, C. H., Braun, R. J., Braus, G. H., Bravo-Sagua, R., Bravo-San Pedro, J. M., Brest, P., Bringer, M. -A., Briones-Herrera, A., Broaddus, V. C., Brodersen, P., Brodsky, J. L., Brody, S. L., Bronson, P. G., Bronstein, J. M., Brown, C. N., Brown, R. E., Brum, P. C., Brumell, J. H., Brunetti-Pierri, N., Bruno, D., Bryson-Richardson, R. J., Bucci, C., Buchrieser, C., Bueno, M., Buitrago-Molina, L. E., Buraschi, S., Buch, S., Buchan, J. R., Buckingham, E. M., Budak, H., Budini, M., Bultynck, G., Burada, F., Burgoyne, J. R., Buron, M. I., Bustos, V., Buttner, S., Butturini, E., Byrd, A., Cabas, I., Cabrera-Benitez, S., Cadwell, K., Cai, J., Cai, L., Cai, Q., Cairo, M., Calbet, J. A., Caldwell, G. A., Caldwell, K. A., Call, J. A., Calvani, R., Calvo, A. C., Calvo-Rubio Barrera, M., Camara, N. O. S., Camonis, J. H., Camougrand, N., Campanella, M., Campbell, E. M., Campbell-Valois, F. -X., Campello, S., Campesi, I., Campos, J. C., Camuzard, O., Cancino, J., Candido de Almeida, D., Canesi, L., Caniggia, I., Canonico, B., Canti, C., Cao, B., Caraglia, M., Carames, B., Carchman, E. H., Cardenal-Munoz, E., Cardenas, C., Cardenas, L., Cardoso, S. M., Carew, J. S., Carle, G. F., Carleton, G., Carloni, S., Carmona-Gutierrez, D., Carneiro, L. A., Carnevali, O., Carosi, J. M., Carra, S., Carrier, A., Carrier, L., Carroll, B., Carter, A. B., Carvalho, A. N., Casanova, M., Casas, C., Casas, J., Cassioli, C., Castillo, E. F., Castillo, K., Castillo-Lluva, S., Castoldi, F., Castori, M., Castro, A. F., Castro-Caldas, M., Castro-Hernandez, J., Castro-Obregon, S., Catz, S. D., Cavadas, C., Cavaliere, F., Cavallini, G., Cavinato, M., Cayuela, M. L., Cebollada Rica, P., Cecarini, V., Cecconi, F., Cechowska-Pasko, M., Cenci, S., Ceperuelo-Mallafre, V., Cerqueira, J. J., Cerutti, J. M., Cervia, D., Cetintas, V. B., Cetrullo, S., Chae, H. -J., Chagin, A. S., Chai, C. -Y., Chakrabarti, G., Chakrabarti, O., Chakraborty, T., Chami, M., Chamilos, G., Chan, D. W., Chan, E. Y. W., Chan, E. D., Chan, H. Y. E., Chan, H. H., Chan, H., Chan, M. T. V., Chan, Y. S., Chandra, P. K., Chang, C. -P., Chang, C., Chang, H. -C., Chang, K., Chao, J., Chapman, T., Charlet-Berguerand, N., Chatterjee, S., Chaube, S. K., Chaudhary, A., Chauhan, S., Chaum, E., Checler, F., Cheetham, M. E., Chen, C. -S., Chen, G. -C., Chen, J. -F., Chen, L. L., Chen, L., Chen, M., Chen, M. -K., Chen, N., Chen, Q., Chen, R. -H., Chen, S., Chen, W., Chen, X. -M., Chen, X. -W., Chen, X., Chen, Y., Chen, Y. -G., Chen, Y. -J., Chen, Y. -Q., Chen, Z. S., Chen, Z., Chen, Z. -H., Chen, Z. J., Cheng, H., Cheng, J., Cheng, S. -Y., Cheng, W., Cheng, X., Cheng, X. -T., Cheng, Y., Cheng, Z., Cheong, H., Cheong, J. K., Chernyak, B. V., Cherry, S., Cheung, C. F. R., Cheung, C. H. A., Cheung, K. -H., Chevet, E., Chi, R. J., Chiang, A. K. S., Chiaradonna, F., Chiarelli, R., Chiariello, M., Chica, N., Chiocca, S., Chiong, M., Chiou, S. -H., Chiramel, A. I., Chiurchiu, V., Cho, D. -H., Choe, S. -K., Choi, A. M. K., Choi, M. E., Choudhury, K. R., Chow, N. S., Chu, C. T., Chua, J. P., Chua, J. J. E., Chung, H., Chung, K. P., Chung, S., Chung, S. -H., Chung, Y. -L., Cianfanelli, V., Ciechomska, I. A., Cifuentes, M., Cinque, L., Cirak, S., Cirone, M., Clague, M. J., Clarke, R., Clementi, E., Coccia, E. M., Codogno, P., Cohen, E., Cohen, M. M., Colasanti, T., Colasuonno, F., Colbert, R. A., Colell, A., Colic, M., Coll, N. S., Collins, M. O., Colombo, M. I., Colon-Ramos, D. A., Combaret, L., Comincini, S., Cominetti, M. R., Consiglio, A., Conte, A., Conti, F., Contu, V. R., Cookson, M. R., Coombs, K. M., Coppens, I., Corasaniti, M. T., Corkery, D. P., Cordes, N., Cortese, K., Costa, M. D. C., Costantino, S., Costelli, P., Coto-Montes, A., Crack, P. J., Crespo, J. L., Criollo, A., Crippa, V., Cristofani, R., Csizmadia, T., Cuadrado, A., Cui, B., Cui, J., Cui, Y., Culetto, E., Cumino, A. C., Cybulsky, A. V., Czaja, M. J., Czuczwar, S. J., D'Adamo, S., D'Amelio, M., D'Arcangelo, D., D'Lugos, A. C., D'Orazi, G., da Silva, J. A., Dafsari, H. S., Dagda, R. K., Dagdas, Y., Daglia, M., Dai, X., Dai, Y., Dal Col, J., Dalhaimer, P., Dalla Valle, L., Dallenga, T., Dalmasso, G., Damme, M., Dando, I., Dantuma, N. P., Darling, A. L., Das, H., Dasarathy, S., Dasari, S. K., Dash, S., Daumke, O., Dauphinee, A. N., Davies, J. S., Davila, V. A., Davis, R. J., Davis, T., Dayalan Naidu, S., De Amicis, F., De Bosscher, K., De Felice, F., De Franceschi, L., De Leonibus, C., de Mattos Barbosa, M. G., De Meyer, G. R. Y., De Milito, A., De Nunzio, C., De Palma, C., De Santi, M., De Virgilio, C., De Zio, D., Debnath, J., Debosch, B. J., Decuypere, J. -P., Deehan, M. A., Deflorian, G., Degregori, J., Dehay, B., Del Rio, G., Delaney, J. R., Delbridge, L. M. D., Delorme-Axford, E., Delpino, M. V., Demarchi, F., Dembitz, V., Demers, N. D., Deng, H., Deng, Z., Dengjel, J., Dent, P., Denton, D., Depamphilis, M. L., Der, C. J., Deretic, V., Descoteaux, A., Devis, L., Devkota, S., Devuyst, O., Dewson, G., Dharmasivam, M., Dhiman, R., di Bernardo, D., Di Cristina, M., Di Domenico, F., Di Fazio, P., Di Fonzo, A., Di Guardo, G., Di Guglielmo, G. M., Di Leo, L., Di Malta, C., Di Nardo, A., Di Rienzo, M., Di Sano, F., Diallinas, G., Diao, J., Diaz-Araya, G., Diaz-Laviada, I., Dickinson, J. M., Diederich, M., Dieude, M., Dikic, I., Ding, S., Ding, W. -X., Dini, L., Dinic, J., Dinic, M., Dinkova-Kostova, A. T., Dionne, M. S., Distler, J. H. W., Diwan, A., Dixon, I. M. C., Djavaheri-Mergny, M., Dobrinski, I., Dobrovinskaya, O., Dobrowolski, R., Dobson, R. C. J., Dokic, J., Dokmeci Emre, S., Donadelli, M., Dong, B., Dong, X., Dong, Z., Dorn II, G. W., Dotsch, V., Dou, H., Dou, J., Dowaidar, M., Dridi, S., Drucker, L., Du, A., Du, C., Du, G., Du, H. -N., Du, L. -L., du Toit, A., Duan, S. -B., Duan, X., Duarte, S. P., Dubrovska, A., Dunlop, E. A., Dupont, N., Duran, R. V., Dwarakanath, B. S., Dyshlovoy, S. A., Ebrahimi-Fakhari, D., Eckhart, L., Edelstein, C. L., Efferth, T., Eftekharpour, E., Eichinger, L., Eid, N., Eisenberg, T., Eissa, N. T., Eissa, S., Ejarque, M., El Andaloussi, A., El-Hage, N., El-Naggar, S., Eleuteri, A. M., El-Shafey, E. S., Elgendy, M., Eliopoulos, A. G., Elizalde, M. M., Elks, P. M., Elsasser, H. -P., Elsherbiny, E. S., Emerling, B. M., Emre, N. C. T., Eng, C. H., Engedal, N., Engelbrecht, A. -M., Engelsen, A. S. T., Enserink, J. M., Escalante, R., Esclatine, A., Escobar-Henriques, M., Eskelinen, E. -L., Espert, L., Eusebio, M. -O., Fabrias, G., Fabrizi, C., Facchiano, A., Facchiano, F., Fadeel, B., Fader, C., Faesen, A. C., Fairlie, W. D., Falco, A., Falkenburger, B. H., Fan, D., Fan, J., Fan, Y., Fang, E. F., Fang, Y., Fanto, M., Farfel-Becker, T., Faure, M., Fazeli, G., Fedele, A. O., Feldman, A. M., Feng, D., Feng, J., Feng, L., Feng, Y., Feng, W., Fenz Araujo, T., Ferguson, T. A., Fernandez, A. F., Fernandez-Checa, J. C., Fernandez-Veledo, S., Fernie, A. R., Ferrante, A. W., Ferraresi, A., Ferrari, M. F., Ferreira, J. C. B., Ferro-Novick, S., Figueras, A., Filadi, R., Filigheddu, N., Filippi-Chiela, E., Filomeni, G., Fimia, G. M., Fineschi, V., Finetti, F., Finkbeiner, S., Fisher, E. A., Fisher, P. B., Flamigni, F., Fliesler, S. J., Flo, T. H., Florance, I., Florey, O., Florio, T., Fodor, E., Follo, C., Fon, E. A., Forlino, A., Fornai, F., Fortini, P., Fracassi, A., Fraldi, A., Franco, B., Franco, R., Franconi, F., Frankel, L. B., Friedman, S. L., Frohlich, L. F., Fruhbeck, G., Fuentes, J. M., Fujiki, Y., Fujita, N., Fujiwara, Y., Fukuda, M., Fulda, S., Furic, L., Furuya, N., Fusco, C., Gack, M. U., Gaffke, L., Galadari, S., Galasso, A., Galindo, M. F., Gallolu Kankanamalage, S., Galluzzi, L., Galy, V., Gammoh, N., Gan, B., Ganley, I. G., Gao, F., Gao, H., Gao, M., Gao, P., Gao, S. -J., Gao, W., Gao, X., Garcera, A., Garcia, M. N., Garcia, V. E., Garcia-Del Portillo, F., Garcia-Escudero, V., Garcia-Garcia, A., Garcia-Macia, M., Garcia-Moreno, D., Garcia-Ruiz, C., Garcia-Sanz, P., Garg, A. D., Gargini, R., Garofalo, T., Garry, R. F., Gassen, N. C., Gatica, D., Ge, L., Ge, W., Geiss-Friedlander, R., Gelfi, C., Genschik, P., Gentle, I. E., Gerbino, V., Gerhardt, C., Germain, K., Germain, M., Gewirtz, D. A., Ghasemipour Afshar, E., Ghavami, S., Ghigo, A., Ghosh, M., Giamas, G., Giampietri, C., Giatromanolaki, A., Gibson, G. E., Gibson, S. B., Ginet, V., Giniger, E., Giorgi, C., Girao, H., Girardin, S. E., Giridharan, M., Giuliano, S., Giulivi, C., Giuriato, S., Giustiniani, J., Gluschko, A., Goder, V., Goginashvili, A., Golab, J., Goldstone, D. C., Golebiewska, A., Gomes, L. R., Gomez, R., Gomez-Sanchez, R., Gomez-Puerto, M. C., Gomez-Sintes, R., Gong, Q., Goni, F. M., Gonzalez-Gallego, J., Gonzalez-Hernandez, T., Gonzalez-Polo, R. A., Gonzalez-Reyes, J. A., Gonzalez-Rodriguez, P., Goping, I. S., Gorbatyuk, M. S., Gorbunov, N. V., Gorgulu, K., Gorojod, R. M., Gorski, S. M., Goruppi, S., Gotor, C., Gottlieb, R. A., Gozes, I., Gozuacik, D., Graef, M., Graler, M. H., Granatiero, V., Grasso, D., Gray, J. P., Green, D. R., Greenhough, A., Gregory, S. L., Griffin, E. F., Grinstaff, M. W., Gros, F., Grose, C., Gross, A. S., Gruber, F., Grumati, P., Grune, T., Gu, X., Guan, J. -L., Guardia, C. M., Guda, K., Guerra, F., Guerri, C., Guha, P., Guillen, C., Gujar, S., Gukovskaya, A., Gukovsky, I., Gunst, J., Gunther, A., Guntur, A. R., Guo, C., Guo, H., Guo, L. -W., Guo, M., Gupta, P., Gupta, S. K., Gupta, S., Gupta, V. B., Gupta, V., Gustafsson, A. B., Gutterman, D. D., H. B, R., Haapasalo, A., Haber, J. E., Hac, A., Hadano, S., Hafren, A. J., Haidar, M., Hall, B. S., Hallden, G., Hamacher-Brady, A., Hamann, A., Hamasaki, M., Han, W., Hansen, M., Hanson, P. I., Hao, Z., Harada, M., Harhaji-Trajkovic, L., Hariharan, N., Haroon, N., Harris, J., Hasegawa, T., Hasima Nagoor, N., Haspel, J. A., Haucke, V., Hawkins, W. D., Hay, B. A., Haynes, C. M., Hayrabedyan, S. B., Hays, T. S., He, C., He, Q., He, R. -R., He, Y. -W., He, Y. -Y., Heakal, Y., Heberle, A. M., Hejtmancik, J. F., Helgason, G. V., Henkel, V., Herb, M., Hergovich, A., Herman-Antosiewicz, A., Hernandez, A., Hernandez, C., Hernandez-Diaz, S., Hernandez-Gea, V., Herpin, A., Herreros, J., Hervas, J. H., Hesselson, D., Hetz, C., Heussler, V. T., Higuchi, Y., Hilfiker, S., Hill, J. A., Hlavacek, W. S., Ho, E. A., Ho, I. H. T., Ho, P. W. -L., Ho, S. -L., Ho, W. Y., Hobbs, G. A., Hochstrasser, M., Hoet, P. H. M., Hofius, D., Hofman, P., Hohn, A., Holmberg, C. I., Hombrebueno, J. R., Yi-Ren Hong, C. -W. H., Hooper, L. V., Hoppe, T., Horos, R., Hoshida, Y., Hsin, I. -L., Hsu, H. -Y., Hu, B., Hu, D., Hu, L. -F., Hu, M. C., Hu, R., Hu, W., Hu, Y. -C., Hu, Z. -W., Hua, F., Hua, J., Hua, Y., Huan, C., Huang, C., Huang, H., Huang, K., Huang, M. L. H., Huang, R., Huang, S., Huang, T., Huang, X., Huang, Y. J., Huber, T. B., Hubert, V., Hubner, C. A., Hughes, S. M., Hughes, W. E., Humbert, M., Hummer, G., Hurley, J. H., Hussain, S., Hussey, P. J., Hutabarat, M., Hwang, H. -Y., Hwang, S., Ieni, A., Ikeda, F., Imagawa, Y., Imai, Y., Imbriano, C., Imoto, M., Inman, D. M., Inoki, K., Iovanna, J., Iozzo, R. V., Ippolito, G., Irazoqui, J. E., Iribarren, P., Ishaq, M., Ishikawa, M., Ishimwe, N., Isidoro, C., Ismail, N., Issazadeh-Navikas, S., Itakura, E., Ito, D., Ivankovic, D., Ivanova, S., Iyer, A. K. V., Izquierdo, J. M., Izumi, M., Jaattela, M., Jabir, M. S., Jackson, W. T., Jacobo-Herrera, N., Jacomin, A. -C., Jacquin, E., Jadiya, P., Jaeschke, H., Jagannath, C., Jakobi, A. J., Jakobsson, J., Janji, B., Jansen-Durr, P., Jansson, P. J., Jantsch, J., Januszewski, S., Jassey, A., Jean, S., Jeltsch-David, H., Jendelova, P., Jenny, A., Jensen, T. E., Jessen, N., Jewell, J. 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J., Roccheri, M. C., Rocchi, S., Rodney, G. G., Rodrigues, T., Rodrigues Silva, V. R., Rodriguez, A., Rodriguez-Barrueco, R., Rodriguez-Henche, N., Rodriguez-Rocha, H., Roelofs, J., Rogers, R. S., Rogov, V. V., Rojo, A. I., Rolka, K., Romanello, V., Romani, L., Romano, A., Romano, P. S., Romeo-Guitart, D., Romero, L. C., Romero, M., Roney, J. C., Rongo, C., Roperto, S., Rosenfeldt, M. T., Rosenstiel, P., Rosenwald, A. G., Roth, K. A., Roth, L., Roth, S., Rouschop, K. M. A., Roussel, B. D., Roux, S., Rovere-Querini, P., Roy, A., Rozieres, A., Ruano, D., Rubinsztein, D. C., Rubtsova, M. P., Ruckdeschel, K., Ruckenstuhl, C., Rudolf, E., Rudolf, R., Ruggieri, A., Ruparelia, A. A., Rusmini, P., Russell, R. R., Russo, G. L., Russo, M., Russo, R., Ryabaya, O. O., Ryan, K. M., Ryu, K. -Y., Sabater-Arcis, M., Sachdev, U., Sacher, M., Sachse, C., Sadhu, A., Sadoshima, J., Safren, N., Saftig, P., Sagona, A. P., Sahay, G., Sahebkar, A., Sahin, M., Sahin, O., Sahni, S., Saito, N., Saito, S., Saito, T., Sakai, R., Sakai, Y., Sakamaki, J. -I., Saksela, K., Salazar, G., Salazar-Degracia, A., Salekdeh, G. H., Saluja, A. K., Sampaio-Marques, B., Sanchez, M. C., Sanchez-Alcazar, J. A., Sanchez-Vera, V., Sancho-Shimizu, V., Sanderson, J. T., Sandri, M., Santaguida, S., Santambrogio, L., Santana, M. M., Santoni, G., Sanz, A., Sanz, P., Saran, S., Sardiello, M., Sargeant, T. J., Sarin, A., Sarkar, C., Sarkar, S., Sarrias, M. -R., Sarmah, D. T., Sarparanta, J., Sathyanarayan, A., Sathyanarayanan, R., Scaglione, K. M., Scatozza, F., Schaefer, L., Schafer, Z. T., Schaible, U. E., Schapira, A. H. V., Scharl, M., Schatzl, H. M., Schein, C. H., Scheper, W., Scheuring, D., Schiaffino, M. V., Schiappacassi, M., Schindl, R., Schlattner, U., Schmidt, O., Schmitt, R., Schmidt, S. D., Schmitz, I., Schmukler, E., Schneider, A., Schneider, B. E., Schober, R., Schoijet, A. C., Schott, M. B., Schramm, M., Schroder, B., Schuh, K., Schuller, C., Schulze, R. J., Schurmanns, L., Schwamborn, J. C., Schwarten, M., Scialo, F., Sciarretta, S., Scott, M. J., Scotto, K. W., Scovassi, A. I., Scrima, A., Scrivo, A., Sebastian, D., Sebti, S., Sedej, S., Segatori, L., Segev, N., Seglen, P. O., Seiliez, I., Seki, E., Selleck, S. B., Sellke, F. W., Selsby, J. T., Sendtner, M., Senturk, S., Seranova, E., Sergi, C., Serra-Moreno, R., Sesaki, H., Settembre, C., Setty, S. R. G., Sgarbi, G., Sha, O., Shacka, J. J., Shah, J. A., Shang, D., Shao, C., Shao, F., Sharbati, S., Sharkey, L. M., Sharma, D., Sharma, G., Sharma, K., Sharma, P., Sharma, S., Shen, H. -M., Shen, H., Shen, J., Shen, M., Shen, W., Shen, Z., Sheng, R., Sheng, Z., Sheng, Z. -H., Shi, J., Shi, X., Shi, Y. -H., Shiba-Fukushima, K., Shieh, J. -J., Shimada, Y., Shimizu, S., Shimozawa, M., Shintani, T., Shoemaker, C. J., Shojaei, S., Shoji, I., Shravage, B. V., Shridhar, V., Shu, C. -W., Shu, H. -B., Shui, K., Shukla, A. 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S., Steinkasserer, A., Stenmark, H., Sterneckert, J., Stevens, C., Stoka, V., Storch, S., Stork, B., Strappazzon, F., Strohecker, A. M., Stupack, D. G., Su, H., Su, L. -Y., Su, L., Suarez-Fontes, A. M., Subauste, C. S., Subbian, S., Subirada, P. V., Sudhandiran, G., Sue, C. M., Sui, X., Summers, C., Sun, G., Sun, J., Sun, K., Sun, M. -X., Sun, Q., Sun, Y., Sun, Z., Sunahara, K. K. S., Sundberg, E., Susztak, K., Sutovsky, P., Suzuki, H., Sweeney, G., Symons, J. D., Sze, S. C. W., Szewczyk, N. J., Tabecka-Lonczynska, A., Tabolacci, C., Tacke, F., Taegtmeyer, H., Tafani, M., Tagaya, M., Tai, H., Tait, S. W. G., Takahashi, Y., Takats, S., Talwar, P., Tam, C., Tam, S. Y., Tampellini, D., Tamura, A., Tan, C. T., Tan, E. -K., Tan, Y. -Q., Tanaka, M., Tang, D., Tang, J., Tang, T. -S., Tanida, I., Tao, Z., Taouis, M., Tatenhorst, L., Tavernarakis, N., Taylor, A., Taylor, G. A., Taylor, J. M., Tchetina, E., Tee, A. R., Tegeder, I., Teis, D., Teixeira, N., Teixeira-Clerc, F., Tekirdag, K. A., Tencomnao, T., Tenreiro, S., Tepikin, A. V., Testillano, P. S., Tettamanti, G., Tharaux, P. -L., Thedieck, K., Thekkinghat, A. A., Thellung, S., Thinwa, J. W., Thirumalaikumar, V. P., Thomas, S. M., Thomes, P. G., Thorburn, A., Thukral, L., Thum, T., Thumm, M., Tian, L., Tichy, A., Till, A., Timmerman, V., Titorenko, V. I., Todi, S. V., Todorova, K., Toivonen, J. M., Tomaipitinca, L., Tomar, D., Tomas-Zapico, C., Tomic, S., Tong, B. C. -K., Tong, C., Tong, X., Tooze, S. A., Torgersen, M. L., Torii, S., Torres-Lopez, L., Torriglia, A., Towers, C. G., Towns, R., Toyokuni, S., Trajkovic, V., Tramontano, D., Tran, Q. -G., Travassos, L. H., Trelford, C. B., Tremel, S., Trougakos, I. P., Tsao, B. P., Tschan, M. P., Tse, H. -F., Tse, T. F., Tsugawa, H., Tsvetkov, A. S., Tumbarello, D. A., Tumtas, Y., Tunon, M. J., Turcotte, S., Turk, B., Turk, V., Turner, B. J., Tuxworth, R. I., Tyler, J. K., Tyutereva, E. V., Uchiyama, Y., Ugun-Klusek, A., Uhlig, H. H., Ulamek-Koziol, M., Ulasov, I. V., Umekawa, M., Ungermann, C., Unno, R., Urbe, S., Uribe-Carretero, E., Ustun, S., Uversky, V. N., Vaccari, T., Vaccaro, M. I., Vahsen, B. F., Vakifahmetoglu-Norberg, H., Valdor, R., Valente, M. J., Valko, A., Vallee, R. B., Valverde, A. M., Van den Berghe, G., van der Veen, S., Van Kaer, L., van Loosdregt, J., van Wijk, S. J. L., Vandenberghe, W., Vanhorebeek, I., Vannier-Santos, M. A., Vannini, N., Vanrell, M. C., Vantaggiato, C., Varano, G., Varela-Nieto, I., Varga, M., Vasconcelos, M. H., Vats, S., Vavvas, D. G., Vega-Naredo, I., Vega-Rubin-de-Celis, S., Velasco, G., Velazquez, A. P., Vellai, T., Vellenga, E., Velotti, F., Verdier, M., Verginis, P., Vergne, I., Verkade, P., Verma, M., Verstreken, P., Vervliet, T., Vervoorts, J., Vessoni, A. T., Victor, V. M., Vidal, M., Vidoni, C., Vieira, O. V., Vierstra, R. D., Vigano, S., Vihinen, H., Vijayan, V., Vila, M., Vilar, M., Villalba, J. M., Villalobo, A., Villarejo-Zori, B., Villarroya, F., Villarroya, J., Vincent, O., Vindis, C., Viret, C., Viscomi, M. T., Visnjic, D., Vitale, I., Vocadlo, D. J., Voitsekhovskaja, O. V., Volonte, C., Volta, M., Vomero, M., Von Haefen, C., Vooijs, M. A., Voos, W., Vucicevic, L., Wade-Martins, R., Waguri, S., Waite, K. A., Wakatsuki, S., Walker, D. W., Walker, M. J., Walker, S. A., Walter, J., Wandosell, F. G., Wang, B., Wang, C. -Y., Wang, C., Wang, D., Wang, F., Wang, G., Wang, H., Wang, H. -G., Wang, J., Wang, K., Wang, L., Wang, M. H., Wang, M., Wang, N., Wang, P., Wang, Q. J., Wang, Q., Wang, Q. K., Wang, Q. A., Wang, W. -T., Wang, W., Wang, X., Wang, Y., Wang, Y. -Y., Wang, Z., Warnes, G., Warnsmann, V., Watada, H., Watanabe, E., Watchon, M., Wawrzynska, A., Weaver, T. E., Wegrzyn, G., Wehman, A. M., Wei, H., Wei, L., Wei, T., Wei, Y., Weiergraber, O. H., Weihl, C. C., Weindl, G., Weiskirchen, R., Wells, A., Wen, R. H., Wen, X., Werner, A., Weykopf, B., Wheatley, S. P., Whitton, J. L., Whitworth, A. J., Wiktorska, K., Wildenberg, M. E., Wileman, T., Wilkinson, S., Willbold, D., Williams, B., Williams, R. S. B., Williams, R. L., Williamson, P. R., Wilson, R. A., Winner, B., Winsor, N. J., Witkin, S. S., Wodrich, H., Woehlbier, U., Wollert, T., Wong, E., Wong, J. H., Wong, R. W., Wong, V. K. W., Wong, W. W. -L., Wu, A. -G., Wu, C., Wu, J., Wu, K. K., Wu, M., Wu, S. -Y., Wu, S., Wu, W. K. K., Wu, X., Wu, Y. -W., Wu, Y., Xavier, R. J., Xia, H., Xia, L., Xia, Z., Xiang, G., Xiang, J., Xiang, M., Xiang, W., Xiao, B., Xiao, G., Xiao, H., Xiao, H. -T., Xiao, J., Xiao, L., Xiao, S., Xiao, Y., Xie, B., Xie, C. -M., Xie, M., Xie, Y., Xie, Z., Xilouri, M., Xu, C., Xu, E., Xu, H., Xu, J., Xu, L., Xu, W. W., Xu, X., Xue, Y., Yakhine-Diop, S. M. S., Yamaguchi, M., Yamaguchi, O., Yamamoto, A., Yamashina, S., Yan, S., Yan, S. -J., Yan, Z., Yanagi, Y., Yang, C., Yang, D. -S., Yang, H., Yang, H. -T., Yang, J. -M., Yang, J., Yang, L., Yang, M., Yang, P. -M., Yang, Q., Yang, S., Yang, S. -F., Yang, W., Yang, W. Y., Yang, X., Yang, Y., Yao, H., Yao, S., Yao, X., Yao, Y. -G., Yao, Y. -M., Yasui, T., Yazdankhah, M., Yen, P. M., Yi, C., Yin, X. -M., Yin, Y., Yin, Z., Ying, M., Ying, Z., Yip, C. K., Yiu, S. P. T., Yoo, Y. H., Yoshida, K., Yoshii, S. R., Yoshimori, T., Yousefi, B., Yu, B., Yu, H., Yu, J., Yu, L., Yu, M. -L., Yu, S. -W., Yu, V. C., Yu, W. H., Yu, Z., Yuan, J., Yuan, L. -Q., Yuan, S., Yuan, S. -S. F., Yuan, Y., Yuan, Z., Yue, J., Yue, Z., Yun, J., Yung, R. L., Zacks, D. N., Zaffagnini, G., Zambelli, V. O., Zanella, I., Zang, Q. S., Zanivan, S., Zappavigna, S., Zaragoza, P., Zarbalis, K. S., Zarebkohan, A., Zarrouk, A., Zeitlin, S. O., Zeng, J., Zeng, J. -D., Zerovnik, E., Zhan, L., Zhang, B., Zhang, D. D., Zhang, H., Zhang, H. -L., Zhang, J., Zhang, J. -P., Zhang, K. Y. B., Zhang, L. W., Zhang, L., Zhang, M., Zhang, P., Zhang, S., Zhang, W., Zhang, X., Zhang, X. -W., Zhang, X. D., Zhang, Y., Zhang, Y. -D., Zhang, Y. -Y., Zhang, Z., Zhao, H., Zhao, L., Zhao, S., Zhao, T., Zhao, X. -F., Zhao, Y., Zheng, G., Zheng, K., Zheng, L., Zheng, S., Zheng, X. -L., Zheng, Y., Zheng, Z. -G., Zhivotovsky, B., Zhong, Q., Zhou, A., Zhou, B., Zhou, C., Zhou, G., Zhou, H., Zhou, J., Zhou, K., Zhou, R., Zhou, X. -J., Zhou, Y., Zhou, Z. -Y., Zhou, Z., Zhu, B., Zhu, C., Zhu, G. -Q., Zhu, H., Zhu, W. -G., Zhu, Y., Zhuang, H., Zhuang, X., Zientara-Rytter, K., Zimmermann, C. M., Ziviani, E., Zoladek, T., Zong, W. -X., Zorov, D. B., Zorzano, A., Zou, W., Zou, Z., Zuryn, S., Zwerschke, W., Brand-Saberi, B., Dong, X. C., Kenchappa, C. S., Lin, Y., Oshima, S., Rong, Y., Sluimer, J. C., Stallings, C. L., Tong, C. -K., and Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Programmed cell death, Settore BIO/06, Autophagosome, Autolysosome, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Autophagy-Related Proteins, Review, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Settore MED/04, 03 medical and health sciences, stress, Chaperone-mediated autophagy, ddc:570, Autophagy, LC3, Animals, Humans, cancer, Settore BIO/10, flux, lysosome, macroautophagy, neurodegeneration, phagophore, vacuole, Set (psychology), Molecular Biology, 030102 biochemistry & molecular biology, business.industry, Interpretation (philosophy), Autophagosomes, Cell Biology, Multicellular organism, 030104 developmental biology, Knowledge base, Biological Assay, Lysosomes, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Published: 2021
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8. Correlation between High PD-L1 and EMT/Invasive Genes Expression and Reduced Recurrence-Free Survival in Blood-Circulating Tumor Cells from Patients with Non-Muscle-Invasive Bladder Cancer

Author: Consuelo Amantini, Ettore Mearini, Marilena Gubbiotti, Matteo Santoni, Rodolfo Montironi, Maria Beatrice Morelli, Giorgio Santoni, Jacopo Adolfo Rossi de Vermandois, Oliviero Marinelli, Alessia Cimadamore, Federica Maggi, Massimo Nabissi, and Antonella Giannantoni
Subjects: Oncology, PD-L1, Cancer Research, medicine.medical_specialty, TIMP2, medicine.medical_treatment, CTC, EMT, immunotherapy, NMIBC, RFS, TWIST1, Vimentin, Article, Circulating tumor cell, Cancer immunotherapy, Internal medicine, medicine, RC254-282, Tumor microenvironment, Bladder cancer, biology, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunotherapy, medicine.disease, Immune checkpoint, biology.protein, business
Abstract: Simple Summary The correlation between immune checkpoint-programmed death-ligand 1 (PD-L1) marker and epithelial–mesenchymal transition (EMT) status may help to identify potential biomarkers for the use of immune checkpoint blockades and other immunotherapy approaches in non-muscle invasive bladder cancer (NMIBC) recurrent patients. The aim of our study was to assess to potential use of PD-L1, TWIST1, ZEB1, VIMENTIN and TIMP2 mRNA expression as prognostic biomarkers. Abstract Background: PD-L1 represents a crucial immune checkpoint molecule in the tumor microenvironment, identified as a key target for cancer immunotherapy. A correlation between PD-L1 and EMT-related genes expression in various human cancers has been suggested. Methods: By ScreenCell filtration, digital droplet PCR and confocal microscopy analysis, we aimed to investigate the expression of PD-L1 and EMT/invasive genes (TWIST1, ZEB1, VIMENTIN, TIMP2) in circulating tumor cells (CTCs) collected from the blood of non-muscle-invasive bladder cancer (NMIBC) patients, assessing the prognostic value of these biomarkers in the disease. Welchs’ test and Mann–Whitney U test, correlation index, Kaplan–Meier, Univariate and Multivariate Cox hazard proportional analysis were used. Results: Higher PD-L1, TIMP2 and VIM mRNA levels were found in pT1 compared to pTa NMIBC. As evaluated by Kaplan–Meier and Univariate and Multivariate Cox analysis, enhancement of PD-L1, TWIST1 and TIMP2 expression reduces the recurrent free survival in NMIBC patients. Conclusions: High PD-L1, TWIST1 and TIMP2 mRNAs mark the recurrent-NMIBC patients and by reducing the RFS represent negative prognostic biomarkers in these patients.
Published: 2021
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9. Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update

Author: Cristina Aguzzi, Massimo Nabissi, Maria Beatrice Morelli, Laura Zeppa, Consuelo Amantini, Federica Maggi, Giorgio Santoni, and Oliviero Marinelli
Subjects: 0301 basic medicine, TRP, leukaemia, lymphoma, Review, Biochemistry, Microbiology, Blood cancer, 03 medical and health sciences, Transient receptor potential channel, 0302 clinical medicine, Transient Receptor Potential Channels, medicine, Overall survival, Humans, Precision Medicine, Molecular Biology, business.industry, Cancer, medicine.disease, Precision medicine, Survival Analysis, QR1-502, Lymphoma, Gene Expression Regulation, Neoplastic, 030104 developmental biology, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Cancer research, Calcium, business, Haematological malignancy
Abstract: Transient receptor potential (TRP) channels are improving their importance in different cancers, becoming suitable as promising candidates for precision medicine. Their important contribution in calcium trafficking inside and outside cells is coming to light from many papers published so far. Encouraging results on the correlation between TRP and overall survival (OS) and progression-free survival (PFS) in cancer patients are available, and there are as many promising data from in vitro studies. For what concerns haematological malignancy, the role of TRPs is still not elucidated, and data regarding TRP channel expression have demonstrated great variability throughout blood cancer so far. Thus, the aim of this review is to highlight the most recent findings on TRP channels in leukaemia and lymphoma, demonstrating their important contribution in the perspective of personalised therapies.
Published: 2021

10. SSEP amplitude accurately predicts both good and poor neurological outcome early after cardiac arrest; a post-hoc analysis of the ProNeCA multicentre study

Author: Maenia Scarpino, Francesco Lolli, Giovanni Lanzo, Riccardo Carrai, Maddalena Spalletti, Franco Valzania, Maria Lombardi, Daniela Audenino, Sara Contardi, Maria Grazia Celani, Alfonso Marrelli, Oriano Mecarelli, Chiara Minardi, Fabio Minicucci, Lucia Politini, Eugenio Vitelli, Adriano Peris, Aldo Amantini, Antonello Grippo, Claudio Sandroni, Chiara Bandinelli, Pasquale Bernardo, Teresa Anna Cantisani, Roberta Ciuffini, Andrea Marudi, Cesarina Cossu, Giuseppe Olivo, Klaudio Rikani, and Rossella Sabadini
Subjects: medicine.medical_specialty, 030204 cardiovascular system & hematology, Emergency Nursing, Electroencephalography, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Intensive care, Post-hoc analysis, Settore MED/41 - ANESTESIOLOGIA, medicine, Pupillary light reflex, Coma, medicine.diagnostic_test, business.industry, 030208 emergency & critical care medicine, Cardiac arrest, Prognosis, Electroencephalogram, Somatosensory evoked potential, Pupillary reflex, Emergency Medicine, Cardiology, False positive rate, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Short-latency somatosensory evoked poitentials (SSEPs)
Abstract: Aim To assess if, in comatose resuscitated patients, the amplitude of the N20 wave (N20amp) of somatosensory evoked potentials (SSEP) can predict 6-months neurological outcome. Setting Multicentre study in 13 Italian intensive care units. Methods The N20amp in microvolts (μV) was measured at 12 h, 24 h, and 72 h from cardiac arrest, along with pupillary reflex (PLR) and a 30-min EEG classified according to the ACNS terminology. Sensitivity and false positive rate (FPR) of N20amp alone or in combination were calculated. Results 403 patients (age 69[58–68] years) were included. At 12 h, an N20amp >3 μV predicted good neurological outcome (Cerebral Performance Categories [CPC] 1–2) with 61[50−72]% sensitivity and 11[6–18]% FPR. Combining it with a benign (continuous or nearly continuous) EEG increased sensitivity to 91[82−96]%. For poor outcome (CPC 3–5), an N20Amp ≤0.38 μV, ≤0.73 μV and ≤1.01 μV at 12 h, 24 h, and 72 h, respectively, had 0% FPR with sensitivity ranging from 61[51−69]% and 82[76−88]%. Sensitivity was higher than that of a bilaterally absent N20 at all time points. At 12 h and 24 h, a highly malignant (suppression or burst-suppression) EEG and bilaterally absent PLR achieved 0% FPR only when combined with SSEP. A combination of all three predictors yielded a 0[0−4]% FPR, with maximum sensitivity of 44[36−53]%. Conclusion At 12 h from arrest, a high N20Amp predicts good outcome with high sensitivity, especially when combined with benign EEG. At 12 h and 24 h from arrest a low-voltage N20amp has a high sensitivity and is more specific than EEG or PLR for predicting poor outcome.
Published: 2021

11. Clinical impact of different exosomes’ protein expression in pancreatic ductal carcinoma patients treated with standard first line palliative chemotherapy

Author: Giulia Ricci, Alessandra Righetti, Alberto Murrone, Francesca Bianchi, Francesco Piva, Consuelo Amantini, Riccardo Giampieri, Giulia Occhipinti, Silvia Pagliaretta, Alessandro Bittoni, Rossana Berardi, Stefano Cascinu, Giovanni Principato, Matteo Giulietti, Giorgio Santoni, Giampieri, R., Piva, F., Occhipinti, G., Bittoni, A., Righetti, A., Pagliaretta, S., Murrone, A., Bianchi, F., Amantini, C., Giulietti, M., Ricci, G., Principato, G., Santoni, G., Berardi, R., and Cascinu, S.
Subjects: 0301 basic medicine, Oncology, Male, Integrins, Colorectal cancer, medicine.medical_treatment, Cancer Treatment, Gene Expression, Kaplan-Meier Estimate, Exosomes, Biochemistry, Metastasis, 0302 clinical medicine, Medicine and Health Sciences, Medicine, Enzyme-Linked Immunoassays, Multidisciplinary, Pharmaceutics, Liver Diseases, Middle Aged, Prognosis, Epithelial Cell Adhesion Molecule, Extracellular Matrix, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Disease Progression, Female, Sample collection, Cellular Structures and Organelles, Research Article, Carcinoma, Pancreatic Ductal, Clinical Oncology, Adult, medicine.medical_specialty, Science, Gastroenterology and Hepatology, Adenocarcinoma, Research and Analysis Methods, Disease-Free Survival, 03 medical and health sciences, Cancer Chemotherapy, Drug Therapy, Diagnostic Medicine, Internal medicine, Pancreatic cancer, Carcinoma, Cell Adhesion, Biomarkers, Tumor, Chemotherapy, Humans, Progression-free survival, Vesicles, Immunoassays, Aged, business.industry, Cancer, Biology and Life Sciences, Cell Biology, medicine.disease, Pancreatic Neoplasms, 030104 developmental biology, Immunologic Techniques, Clinical Medicine, business, Transcriptome, Biomarkers
Abstract: IntroductionPancreatic ductal adenocarcinoma is associated to dismal prognosis despite the use of palliative chemotherapy, partly due to the lack of knowledge of biological processes underlying disease progression. Exosomes have been identified as biomarkers sources in different cancer types. Aim of the study was to analyse the contents of circulating exosomes in patients with pancreatic cancer who received palliative chemotherapy.Patients and methodsPatients were submitted to blood sample collection before chemotherapy (T0) and after 3 months (T3). We quantified by an ELISA-based technique specific proteins of cancer-derived exosomes (CD44,CD44v6,EpCAM,CD9,CD81,Tspan8,Integrin α6,Integrin β4,CD24,CXCR4). We correlated the baseline levels of these factors and changes between T3 and T0 and survival outcomes. Survival analyses were performed by Kaplan-Meier method. Correlation was assessed by log-rank test and level of statistical significance was set at 0.05. Multivariate analysis was performed by logistic regression analysis.ResultsNineteen patients were enrolled. EpCAM T0 levels and increased EpCAM levels from T0 to T3 were those mostly associated with differences in survival. Patients having higher EpCAM had median progression free survival (PFS) of 3.18vs7.31 months (HR:2.82,95%CI:1.03-7.73,p = 0.01). Overall survival (OS) was shorter for patients having higher EpCAM (5.83vs16.45 months,HR:6.16,95%CI:1.93-19.58,p = 0.0001) and also response rates (RR) were worse (20%vs87%,p = 0.015). EpCAM increase during treatment was associated with better median PFS (2.88vs7.31 months,HR:0.24,95%CI:0.04-1.22,p = 0.003). OS was also better (8.75vs11.04 months, HR:0.77,95%CI:0.21-2.73,p = 0.66) and RR were 60%vs20% (p = 0.28). Among clinical factors that might determine changes on PFS and OS, only ECOG PS was associated to significantly worse PFS and OS (p = 0.0137andConclusionsPancreatic cancer patients exosomes express EpCAM, whose levels change during treatment. This represents a useful prognostic factor and also suggests that future treatment modalities who target EpCAM should be tested in pancreatic cancer patients selected by exosome EpCAM expression.
Published: 2019

12. Neurophysiology and neuroimaging accurately predict poor neurological outcome within 24 hours after cardiac arrest: The ProNeCA prospective multicentre prognostication study

Author: Scarpino, Maenia, Lolli, Francesco, Lanzo, Giovanni, Carrai, Riccardo, Spalletti, Maddalena, Valzania, Franco, Lombardi, Maria, Audenino, Daniela, Celani, Maria Grazia, Marrelli, Alfonso, Contardi, Sara, Peris, Adriano, Amantini, Aldo, Sandroni, Claudio, Grippo, Antonello, Amantini, A12, Carrai, R12, Grippo, A12, Lanzo, G12, Lolli, F12, Masi, G12, Moretti, M12, Peris, A12, Scarpino, M12, Spalletti, M12, Bandinelli, C5, Lombardi, M5, Contardi, S13, Marudi, A13, Audenino, D14, Rikani, K14, Ospedale Galliera EO14, Marrelli, A15, Splendiani, Alessandra, Cantisani, Ta15, Celani, Mg15, Fiacca, A17, Sabadini, R4, and Valzania, F4.
Subjects: Male, medicine.medical_specialty, Neuroimaging, 030204 cardiovascular system & hematology, Emergency Nursing, Electroencephalography, Clinical neurophysiology, White matter, 03 medical and health sciences, 0302 clinical medicine, Hypothermia, Induced, Anoxia-ischemia, Internal medicine, Evoked Potentials, Somatosensory, Settore MED/41 - ANESTESIOLOGIA, medicine, Humans, Prospective Studies, Brain, Cardiac arrest, Coma, Computed tomography, Electroencephalogram, Prognosis, Somatosensory evoked potentials, Aged, medicine.diagnostic_test, business.industry, 030208 emergency & critical care medicine, Multimodal therapy, Neurophysiology, Middle Aged, Heart Arrest, medicine.anatomical_structure, Somatosensory evoked potential, Emergency Medicine, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: To investigate the ability of 30-min electroencephalogram (EEG), short-latency somatosensory evoked potentials (SEPs) and brain computed tomography (CT) to predict poor neurological outcome (persistent vegetative state or death) at 6 months in comatose survivors of cardiac arrest within 24 h from the event.Prospective multicentre prognostication study in seven hospitals. SEPs were graded according to the presence and amplitude of their cortical responses, EEG patterns were classified according to the American Clinical Neurophysiology Society terminology and brain oedema on brain CT was measured as grey/white matter (GM/WM) density ratio. Sensitivity for poor outcome prediction at 100% specificity was calculated for the three tests individually and in combination. None of the patients underwent withdrawal of life-sustaining treatments before the index event occurred.A total of 346/396 patients were included in the analysis. At 6 months, 223(64%) had poor neurological outcome; of these, 68 were alive in PVS. Bilaterally absent/absent-pathological amplitude cortical SEP patterns, a GM/WM ratio1.21 on brain CT and isoelectric/burst-suppression EEG patterns predicted poor outcome with 100% specificity and sensitivities of 57.4%, 48.8% and 34.5%, respectively. At least one of these unfavourable patterns was present in 166/223 patients (74.4% sensitivity). Two unfavourable patterns were simultaneously present in 111/223 patients (49.7% sensitivity), and three patterns in 38/223 patients (17% sensitivity).In comatose resuscitated patients, a multimodal approach based on results of SEPs, EEG and brain CT accurately predicts poor neurological outcome at 6 months within the first 24 h after cardiac arrest.
Published: 2019

13. Does a combination of ≥2 abnormal tests vs. the ERC-ESICM stepwise algorithm improve prediction of poor neurological outcome after cardiac arrest? A post-hoc analysis of the ProNeCA multicentre study

Author: Maria Lombardi, Franco Valzania, Adriano Peris, Maenia Scarpino, Riccardo Carrai, Claudio Sandroni, Aldo Amantini, Maria Grazia Celani, Alfonso Marrelli, Francesco Lolli, M. Spalletti, Antonello Grippo, Sara Contardi, Giovanni Lanzo, and Daniela Audenino
Subjects: Adult, Test sensitivity, Status epilepticus, Emergency Nursing, Electroencephalography, Hypothermia, Induced, Settore MED/41 - ANESTESIOLOGIA, Post-hoc analysis, medicine, Humans, Coma, medicine.diagnostic_test, business.industry, Cardiac arrest, Prognosis, Heart Arrest, Somatosensory evoked potential, Emergency Medicine, medicine.symptom, Abnormal results, Cardiology and Cardiovascular Medicine, business, Myoclonus, Algorithm, Algorithms
Abstract: BACKGROUND Bilaterally absent pupillary light reflexes (PLR) or N20 waves of short-latency evoked potentials (SSEPs) are recommended by the 2015 ERC-ESICM guidelines as robust, first-line predictors of poor neurological outcome after cardiac arrest. However, recent evidence shows that the false positive rates (FPRs) of these tests may be higher than previously reported. We investigated if testing accuracy is improved when combining PLR/SSEPs with malignant electroencephalogram (EEG), oedema on brain computed tomography (CT), or early status myoclonus (SM). METHODS Post-hoc analysis of ProNeCA multicentre prognostication study. We compared the prognostic accuracy of the ERC-ESICM prognostication strategy vs. that of a new strategy combining ≥2 abnormal results from any of PLR, SSEPs, EEG, CT and SM. We also investigated if using alternative classifications for abnormal SSEPs (absent-pathological vs. bilaterally-absent N20) or malignant EEG (ACNS-defined suppression or burst-suppression vs. unreactive burst-suppression or status epilepticus) improved test sensitivity. RESULTS We assessed 210 adult comatose resuscitated patients of whom 164 (78%) had poor neurological outcome (CPC 3-5) at six months. FPRs and sensitivities of the ≥2 abnormal test strategy vs. the ERC-ESICM algorithm were 0[0-8]% vs. 7 [1-18]% and 49[41-57]% vs. 63[56-71]%, respectively (p
Published: 2020

14. Is there inter-observer variation in the interpretation of SSEPs in comatose cardiac arrest survivors? Further considerations following the Italian multicenter ProNeCa study

Author: Maria Grazia Celani, Riccardo Carrai, Teresa Anna Cantisani, Maenia Scarpino, Maria Vittoria Ercolani, Francesco Lolli, Giovanni Lanzo, Paolo Costa, Paola Lanteri, Angelo Antonio Bignamini, Aldo Amantini, Antonello Grippo, Daniela Audenino, Chiara Bandinelli, Pasquale Bernardo, Roberta Ciuffini, Sara Contardi, Leonardo Davì, Maria Lombardi, Alfonso Marrelli, Andrea Marudi, Oriano Mecarelli, Chiara Minardi, Fabio Minicucci, Marco Moretti, Giuseppe Olivo, Adriano Peris, Lucia Politini, Klaudio Rikani, Rossella Sabadini, Claudio Sandroni, Maddalena Spalletti, Franco Valzania, Eugenio Vitelli, and Angelo Zilioli
Subjects: medicine.medical_specialty, medicine.medical_treatment, 030204 cardiovascular system & hematology, Emergency Nursing, Audiology, 03 medical and health sciences, 0302 clinical medicine, Evoked Potentials, Somatosensory, Medicine, Humans, Cardiopulmonary resuscitation, Survivors, Noise level, Coma, Reference standards, Observer Variation, Health professionals, business.industry, Reproducibility of Results, 030208 emergency & critical care medicine, Heart Arrest, Inter-rater reliability, Italy, Somatosensory evoked potential, Emergency Medicine, Cardiology and Cardiovascular Medicine, business, Observer variation, Kappa
Abstract: Bilateral absence of N20 peak in median nerve Somatosensory Evoked Potentials (SSEPs) is considered the most valid predictor of poor outcome in comatose survivors after cardiopulmonary resuscitation. We investigated the consistency in interpreting SSEP recordings in a multicentre study.44 SSEP recordings randomly extracted from 600 recordings of 392 patients included in the "Prognostication of Neurological outcome after Cardiac Arrest (ProNeCa) study" were blindly read by three expert neurophysiologists. Agreement between raters, and individual agreement of each rater vs. reference standard (RS), were calculated using Kappa Coefficients. Inter-rater reliability was calculated with Intra-class Correlation Coefficient (ICC).When raters had to evaluate the presence of N20 with normal amplitude, the inter-rater agreement was very high (Kappa = 0.84). In the case of N20 absence the agreement was good (Kappa = 0.66), but when N20 amplitude was low, the agreement decreased to moderate (Kappa = 0.579) becoming even weaker when it was "Non Assessable" (Kappa = 0.107). The agreement of each rater with the RS had a range from moderate to very good; rater1 Kappa = 0.589 (95%CI 0.397-0.781; p 0.001), rater2 Kappa = 0.644 (95%CI 0.460-0.828; p 0.001), rater3 Kappa = 0.859 (95%CI 0.698-1.000; p 0.001). The ICC was barely good, 0.682 (95%CI 0.539-0.798; p = 0.0075).Different health professionals, using different equipment in a multicentre study, had very good inter-rater agreement in interpreting SSEP records. The interpretation of "Non Assessable" SEPPs, mainly in relation to noise level, is still a crucial issue because it increases rater uncertainty. For this reason, it is important to focus on improving recording quality and interpretation of records.
Published: 2020

15. What is new about somatosensory evoked potentials as neurological predictors of comatose survivors after cardiac arrest?

Author: Aldo Amantini, Giovanni Lanzo, Antonello Grippo, and Maenia Scarpino
Subjects: medicine.medical_specialty, Neurology, business.industry, Somatosensory evoked potential, Internal medicine, Pupillary reflex, medicine, Cardiology, Multimodal therapy, Neurology (clinical), business, Hypoxic Ischemic Encephalopathy
Published: 2020
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16. Neurophysiology for predicting good and poor neurological outcome at 12 and 72 h after cardiac arrest: The ProNeCA multicentre prospective study

Author: Maenia Scarpino, Riccardo Carrai, Francesco Lolli, Giovanni Lanzo, Maddalena Spalletti, Franco Valzania, Maria Lombardi, Daniela Audenino, Sara Contardi, Maria Grazia Celani, Alfonso Marrelli, Oriano Mecarelli, Chiara Minardi, Fabio Minicucci, Lucia Politini, Eugenio Vitelli, Adriano Peris, Aldo Amantini, Claudio Sandroni, Antonello Grippo, Angelo Zilioli, Chiara Bandinelli, Pasquale Bernardo, Teresa Anna Cantisani, Roberta Ciuffini, Leonardo Davì, Andrea Marudi, Marco Moretti, Giuseppe Olivo, Klaudio Rikani, and Rossella Sabadini
Subjects: medicine.medical_specialty, Resuscitation, Neurophysiology, Emergency Nursing, Electroencephalography, Clinical neurophysiology, Anoxia-ischemia, Brain, Cardiac arrest, Coma, Electroencephalogram, Prognosis, Somatosensory evoked potentials, Hypothermia, Induced, Internal medicine, Settore MED/41 - ANESTESIOLOGIA, medicine, Humans, In patient, Prospective Studies, Prospective cohort study, medicine.diagnostic_test, business.industry, Heart Arrest, Somatosensory evoked potential, Emergency Medicine, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Aims To assess the accuracy of electroencephalogram (EEG) and somatosensory evoked potentials (SEPs) recorded at 12 and 72 h from resuscitation for predicting six-months neurological outcome in patients who are comatose after cardiac arrest. Methods Prospective multicentre prognostication study. EEG was classified according to the American Clinical Neurophysiology Society terminology. SEPs were graded according to the presence and amplitude of their cortical responses. Neurological outcome was defined as good (cerebral performance categories [CPC] 1–3) vs. poor (CPC 4–5). None of the patients underwent withdrawal of life-sustaining treatment. Results A total of 351 patients were included, of whom 134 (38%) had good neurological outcome. At 12 h, a continuous, nearly continuous and low-voltage EEG pattern predicted good neurological outcome with 71[61–80]% sensitivity, while an isoelectric EEG and a bilaterally absent/absent-pathological amplitude (AA/AP) cortical SEP pattern predicted poor neurological outcome with 14[8–21]% and 59[50–68]% sensitivity, respectively. Specificity was 100[97–100]% for all predictors. At 72 h, both an isoelectric, suppression or burst-suppression pattern on EEG and an AA/AP SEP pattern predicted poor outcome with 100[97–100]% specificity. Their sensitivities were 63[55–70]% and 66[58–74]%, respectively. When EEG and SEPs were combined, sensitivity for poor outcome prediction increased to 79%. Conclusions In comatose resuscitated patients, EEG and SEPs predicted good and poor neurological outcome respectively, with 100% specificity as early as 12 h after cardiac arrest. At 72 h after arrest, unfavourable EEG and SEP patterns predicted poor neurological outcome with 100% specificity and high sensitivity, which further increased after their combination.
Published: 2020

17. Discovery and development of ASK1 inhibitors

Author: Tanja Poljak, David Amantini, Karl Richard Gibson, Reginald Brys, and Steven Emiel Van Der Plas
Subjects: Programmed cell death, MAP kinase kinase kinase, Kinase, Drug discovery, business.industry, p38 mitogen-activated protein kinases, Inflammation, 01 natural sciences, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Human disease, medicine, ASK1, medicine.symptom, business, Neuroscience
Abstract: Aberrant activation of mitogen-activated protein kinases (MAPKs) like c-Jun N-terminal kinase (JNK) and p38 is an event involved in the pathophysiology of numerous human diseases. The apoptosis signal-regulating kinase 1 (ASK1) is an upstream target that gets activated only under pathological conditions and as such is a promising target for therapeutic intervention. In the first part of this review the molecular mechanisms leading to ASK1 activation and regulation will be described as well as the evidences supporting a pathogenic role for ASK1 in human disease. In the second part, an update on drug discovery efforts towards the discovery and development of ASK1-targeting therapies will be provided.
Published: 2020
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18. Perda auditiva unilateral e assimétrica na infância

Author: Fernanda Navarro Gouveia, Lilian Cássia Bórnia Jacob-Corteletti, Bárbara Cristiane Sordi Silva, Eliene Silva Araújo, Regina Célia Bortoleto Amantini, Eduardo Boaventura Oliveira, and Kátia de Freitas Alvarenga
Subjects: Gynecology, medicine.medical_specialty, Perda Auditiva Neurossensorial, business.industry, Perda Auditiva, INFÂNCIA, Características da População, P1-1091, Criança, Language and Linguistics, 03 medical and health sciences, Speech and Hearing, 0302 clinical medicine, RF1-547, Otorhinolaryngology, Sex factors, 030220 oncology & carcinogenesis, Medicine, Perda Auditiva Unilateral, 030223 otorhinolaryngology, business, Philology. Linguistics
Abstract: RESUMO Objetivo Descrever a perda auditiva sensorioneural unilateral e bilateral assimétrica em crianças quanto às características etiológicas, audiológicas e demográficas. Método Estudo retrospectivo transversal, desenvolvido na Seção de Implante Coclear do Hospital de Reabilitação de Anomalias Craniofaciais, por meio da análise de prontuários. Resultados Foram analisados os dados de 1152 pacientes, sendo 424 (37%) adolescentes, adultos ou idosos e 728 (63%) crianças, dentre as quais, 691 (95%) apresentavam perda auditiva bilateral simétrica e 37 (5%) perda auditiva sensorioneural unilateral (n=10) ou bilateral assimétrica (n=27). A idade média ao diagnóstico na perda auditiva sensorioneural unilateral foi de 33,58±21,69 meses e na bilateral assimétrica de 33,12±21,69 meses, com prevalência de 1,4% e 3,7%, respectivamente. O indicador de risco para a deficiência auditiva de maior ocorrência para ambos os grupos foi o de antecedente familiar. A maioria dos familiares das crianças com perda auditiva sensorioneural unilateral apresentaram a classificação socioeconômica baixa superior (50%), enquanto que as crianças com perda auditiva sensorioneural bilateral assimétrica se subdividiram igualmente em baixa superior (37%) e média inferior (37%). Conclusão Houve uma maior prevalência da perda auditiva sensorioneural bilateral assimétrica em relação à unilateral, bem como do indicador de risco de hereditariedade, com predomínio do grau profundo na pior orelha e preponderância do sexo feminino, em ambos os grupos. Apesar de a triagem auditiva neonatal propiciar a identificação precoce da perda auditiva sensorioneural unilateral, a idade no diagnóstico audiológico ainda se encontra acima do recomendado. Adicionalmente, a maioria dos familiares das crianças apresentou nível de rendimento baixo.
Published: 2020

19. The Effects of Cannabidiol and Prognostic Role of TRPV2 in Human Endometrial Cancer

Author: Laura Zeppa, Cristina Aguzzi, Consuelo Amantini, Massimo Nabissi, Benedetta Ferretti, Maria Beatrice Morelli, Giorgio Santoni, Daniela Annibali, Sandra Tuyaerts, Oliviero Marinelli, Federica Maggi, Frédéric Amant, ARD - Amsterdam Reproduction and Development, CCA - Cancer biology and immunology, Obstetrics and Gynaecology, Clinical sciences, and Medical Oncology
Subjects: Chemistry, Multidisciplinary, Apoptosis, CELL-MIGRATION, migration, Receptor, Cannabinoid, CB2, lcsh:Chemistry, cannabidiol, CHANNEL, Receptor, Cannabinoid, CB1, Cell Movement, PROSTATE, lcsh:QH301-705.5, Spectroscopy, INDUCED APOPTOSIS, Drug Synergism, General Medicine, Middle Aged, Computer Science Applications, CANNABINOIDS, Gene Expression Regulation, Neoplastic, Chemistry, Physical Sciences, endometrial cancer, Female, Life Sciences & Biomedicine, Carcinoma, Endometrioid, medicine.drug, EXPRESSION, Biochemistry & Molecular Biology, CARCINOMA, Cell Survival, chemo-resistance, progression-free survival, TRPV2, TRPV Cation Channels, Antineoplastic Agents, BREAST, Catalysis, Article, Inorganic Chemistry, In vivo, Cell Line, Tumor, Adjuvant therapy, medicine, Autophagy, Humans, Viability assay, Progression-free survival, Physical and Theoretical Chemistry, Molecular Biology, Aged, Cell Proliferation, Cisplatin, Science & Technology, RECEPTOR, Cell growth, business.industry, Endometrial cancer, Organic Chemistry, Cancer, IN-VITRO, medicine.disease, Cystadenocarcinoma, Serous, Endometrial Neoplasms, lcsh:Biology (General), lcsh:QD1-999, Cancer research, business
Abstract: Several studies support, both in vitro and in vivo, the anti-cancer effects of cannabidiol (CBD), a transient receptor potential vanilloid 2 (TRPV2) ligand. TRPV2, often dysregulated in tumors, is associated with altered cell proliferation and aggressiveness. Endometrial cancer (EC) is historically divided in type I endometrioid EC and type II non-endometrioid EC, associated with poor prognosis. Treatment options with chemotherapy and combinations with radiation showed only limited efficacy. Since no data are reported concerning TRPV2 expression as well as CBD potential effects in EC, the aim of this study was to evaluate the expression of TRPV2 in biopsies and cell lines as well as the effects of CBD in in vitro models. Overall survival (OS), progression-free survival (PFS), cell viability, migration, and chemo-resistance have been evaluated. Results show that TRPV2 expression increased with the malignancy of the cancer tissue and correlated with shorter PFS (p = 0.0224). Moreover, in vitro TRPV2 over-expression in Ishikawa cell line increased migratory ability and response to cisplatin. CBD reduced cell viability, activating predominantly apoptosis in type I cells and autophagy in mixed type EC cells. The CBD improved chemotherapeutic drugs cytotoxic effects, enhanced by TRPV2 over-expression. Hence, TRPV2 could be considered as a marker for optimizing the therapy and CBD might be a useful therapeutic option as adjuvant therapy. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:21 issue:15 ispartof: location:Switzerland status: published
Published: 2020

20. Data on multimodal approach for early poor outcome (Cerebral Performance Categories 3-5) prediction after cardiac arrest

Author: Francesco Lolli, Maenia Scarpino, Marco Moretti, Riccardo Carrai, Aldo Amantini, Antonello Grippo, Adriano Peris, Giovanni Lanzo, Morena Cozzolino, and M. Spalletti
Subjects: medicine.medical_specialty, Grey matter, Electroencephalography, lcsh:Computer applications to medicine. Medical informatics, White matter, 03 medical and health sciences, 0302 clinical medicine, Text mining, Internal medicine, medicine, Severe disability, lcsh:Science (General), Multidisciplinary, medicine.diagnostic_test, business.industry, 030208 emergency & critical care medicine, Multimodal therapy, Medicine and Dentistry, medicine.anatomical_structure, Somatosensory evoked potential, Cardiology, lcsh:R858-859.7, Wakefulness, business, 030217 neurology & neurosurgery, lcsh:Q1-390
Abstract: The data presented in this article are related to our research article entitled ‘Neurophysiological and neuroradiological multimodal approach for early poor outcome prediction after cardiac arrest’ (Scarpino et al., 2018) [1]. We reported two additional analyses, including results gathered from somatosensory evoked potentials(SEPs), brain computed tomography(CT) and electroencephalography(EEG) performed on 183 subjects within the first 24 h after cardiac arrest(CA). In the first analysis, we considered the Cerebral Performance Categories(CPC) 3, 4 and 5a,b (severe disability, unresponsive wakefulness state, neurological death and non-neurological death, respectively) as poor outcomes. In the second analysis, patients that died from non-neurological causes (CPC 5b) were excluded from the analysis. Concerning the first analysis, bilateral absent/absent-pathologic(AA/AP) cortical SEPs predicted poor outcome with a sensitivity of 49.3%. A Grey Matter/White Matter(GM/WM) ratio
Published: 2018

21. Why we prefer levetiracetam over phenytoin for treatment of status epilepticus

Author: Fabio Giovannelli, Filippo Sean Giorgi, A Amantini, P Nazerian, Gaetano Zaccara, G Giannasi, R. Campostrini, and M. Paganini
Subjects: Phenytoin, fosphenytoin, lacosamide, Infusions, Levetiracetam, Lacosamide, convulsive status epilepticus, macromolecular substances, Status epilepticus, Administration, Cutaneous, Loading dose, antiepileptic drugs, focal status epilepticus, valproate, Administration, Intravenous, Anticonvulsants, Exanthema, Humans, Infusions, Intravenous, Piracetam, Status Epilepticus, Treatment Outcome, 03 medical and health sciences, 0302 clinical medicine, Fosphenytoin, medicine, 030212 general & internal medicine, business.industry, Purple glove syndrome, General Medicine, medicine.disease, Cutaneous, Neurology, Anesthesia, Administration, Neurology (clinical), medicine.symptom, Intravenous, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine-resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time-consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine-resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment.
Published: 2018
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22. High CTLA-4 expression correlates with poor prognosis in thymoma patients

Author: Oliviero Marinelli, Massimo Nabissi, Maria Beatrice Morelli, Silvia Rinaldi, Daniele Tomassoni, Consuelo Amantini, Claudio Cardinali, Vittorio Paolucci, Giovanni Bernardini, Matteo Santoni, Giorgio Santoni, Francesca Morgese, Mariangela Torniai, and Rossana Berardi
Subjects: 0301 basic medicine, Poor prognosis, Pathology, medicine.medical_specialty, Thymoma, chemical and pharmacologic phenomena, tumor-infiltrating leukocytes (TILs), Anterior mediastinum, cytotoxic T lymphocyte antigen 4 (CTLA-4), 03 medical and health sciences, 0302 clinical medicine, Cytotoxic T lymphocyte antigen 4 (CTLA-4), Overall survival (OS), Tumor-infiltrating leukocytes (TILs), Oncology, Atypical Thymoma, hemic and lymphatic diseases, Medicine, Pathological, Messenger RNA, business.industry, Cancer, overall survival (OS), thymoma, medicine.disease, 030104 developmental biology, CTLA-4, 030220 oncology & carcinogenesis, business, Research Paper
Abstract: Thymomas, tumors that arise from epithelial cells of the thymus gland, are the most common neoplasms of the anterior mediastinum, with an incidence rate of approximately 2.5 per million/year. Cytotoxic T Lymphocyte Antigen 4 (CTLA-4 or CD152) exerts inhibitory activity on T cells, and since its oncogenic role in the progression of different types of tumors, it has emerged as a potential therapeutic target in cancer patients. In this study, we assessed the expression of CTLA-4 both at mRNA and protein levels in paraffin embedded-tissues from patients with thymomas. Furthermore, we evaluated the relationship between CTLA-4 expression and the clinical-pathologic characteristics and prognosis in patients with thymomas. Sixty-eight patients with median age corresponding to 62 years were included in this analysis. Thymomas were classified accordingly to the WHO and Masaoka-Koga for histochemical analysis and for prognostic significance. A statistical difference was found between CTLA-4 mRNA levels in human normal thymus compared with thymoma specimens. CTLA-4 expression was statistically found to progressively increase in A, B1, B2, AB and it was maximal in B3 thymomas. According to Masaoka-Koga pathological classification, CTLA-4 expression was lower in I, IIA and IIB, and higher in invasive III and IV stages. By confocal microscopy analysis we identified the expression of CTLA-4 both in tumor cells and in CD45+ tumor-infiltrating leukocytes, mainly in B3 and AB thymomas. Finally, CTLA-4 overexpression significantly correlates with reduced overall survival in thymoma patients and in atypical thymoma subgroup, suggesting that it represents a negative prognostic factor.
Published: 2018

23. Delayed cerebral fat embolism occurring after off-pump coronary artery bypass grafting

Author: Giuseppe Olivo, Aldo Amantini, Antonello Grippo, Giovanni Lanzo, Marco Moretti, and Maenia Scarpino
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Grafting (decision trees), General Medicine, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Cardiology, Fat embolism, Cardiology and Cardiovascular Medicine, business, Off-pump coronary artery bypass
Published: 2018
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24. EEG and Coma Recovery Scale-Revised prediction of neurological outcome in Disorder of Consciousness patients

Author: Tiziana Atzori, Antonello Grippo, Emilio Portaccio, Francesco Lolli, Francesca Draghi, Maenia Scarpino, Bahia Hakiki, Giovanni Lanzo, Aldo Amantini, and Raisa Sterpu
Subjects: Male, medicine.medical_specialty, media_common.quotation_subject, Electroencephalography, Clinical neurophysiology, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, medicine, Humans, In patient, 030212 general & internal medicine, Coma, media_common, Persistent vegetative state, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Persistent Vegetative State, Area under the curve, Rehabilitation unit, General Medicine, Recovery of Function, Middle Aged, medicine.disease, Prognosis, Treatment Outcome, Neurology, Brain Injuries, Consciousness Disorders, Female, Neurology (clinical), Consciousness, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Objective According to electroencephalogram (EEG) descriptors included in the American Clinical Neurophysiology Society (ACNS) terminology, we generated a score, and we compared it to the EEG scores previously proposed in order to identify the one with the best prognostic power for neurological outcome at post-acute stages in patients with severe disorders of consciousness (DoC). Materials and methods Patients included in the analysis were clinically evaluated with the Coma Recovery Scale-Revised (CRS-R). An EEG was performed within the first week after admission to Intensive Rehabilitation Unit (IRU). EEGs were classified according to the ACNS terminology and to the scores of Bagnato and Estraneo. Results A total of 260 patients admitted to the IRU were analysed. A total of 160 patients (61%) improved their consciousness level during IRU stay. EEG score based on the ANCS terminology showed higher overall performance (receiver-operating area under the curve = 0.79) and greater sensitivity (65%), at comparable specificities (80%), for clinical improvement as compared to both CRS-R admission score and other EEG scores. Combining our EEG score with CRS-R score at admission, the cumulative sensitivity increased to 76% when at least one good prognostic index test was present in the same patient, whereas specificity increased up to 93% if both the good prognostic patterns of clinical and instrumental parameters were simultaneously present. Conclusion The EEG scored according to the ACNS terminology is the best among those looked at for the prediction of short-term clinical improvement in patients with DoC and represents a useful instrumental test, complementary to clinical evaluation at admission, to be added in post-acute neurological prognostication methods.
Published: 2019

25. Neurophysiological and neuroradiological test for early poor outcome (Cerebral Performance Categories 3-5) prediction after cardiac arrest: Prospective multicentre prognostication data

Author: Sara Contardi, Antonello Grippo, Claudio Sandroni, Daniela Audenino, Maria Lombardi, Aldo Amantini, Maenia Scarpino, Riccardo Carrai, Franco Valzania, Adriano Peris, Francesco Lolli, Maria Grazia Celani, Giovanni Lanzo, Alfonso Marrelli, and M. Spalletti
Subjects: medicine.medical_specialty, Computed tomography, Grey matter, Electroencephalography, lcsh:Computer applications to medicine. Medical informatics, White matter, Neuroimaging, Anoxia-ischemia, Internal medicine, Settore MED/41 - ANESTESIOLOGIA, Medicine, Brain, Cardiac arrest, Coma, Electroencephalogram, Prognosis, Somatosensory evoked potentials, lcsh:Science (General), Multidisciplinary, medicine.diagnostic_test, business.industry, Medicine and Dentistry, Neurophysiology, medicine.anatomical_structure, Somatosensory evoked potential, Cardiology, lcsh:R858-859.7, medicine.symptom, business, lcsh:Q1-390
Abstract: The data presented here are related to our research article entitled “Neurophysiology and neuroimaging accurately predict poor neurological outcome within 24 hours after cardiac arrest: a prospective multicentre prognostication study (ProNeCA)” [1].We report a secondary analysis on the ability of somatosensory evoked potentials (SEPs), brain computed tomography (CT) and electroencephalography (EEG) to predict poor neurological outcome at 6 months in 346 patients who were comatose after cardiac arrest. Differently from the related research article, here we included cerebral performance category (CPC) 3 among poor outcomes, so that the outcomes are dichotomised as CPC 1–2 (absent to mild neurological disability: good outcome) vs. CPC 3–5 (severe neurological disability, persistent vegetative state, or death: poor outcome). The accuracy of the index tests was recalculated accordingly. A bilaterally absent/absent-pathological amplitude (AA/AP) N20 SEPs wave, a Grey Matter/White Matter (GM/WM) ratio
Published: 2019

26. The TRPV2 cation channels: from urothelial cancer invasiveness to glioblastoma multiforme interactome signature

Author: Maria Beatrice Morelli, Consuelo Amantini, Massimo Nabissi, Matteo Santoni, Giorgio Santoni, Federica Maggi, and Oliviero Marinelli
Subjects: 0301 basic medicine, Urologic Neoplasms, Angiogenesis, TRPV Cation Channels, transient Rreceptor potential, glioblastoma, cancer progression, Pathology and Forensic Medicine, 03 medical and health sciences, Prostate cancer, Mice, 0302 clinical medicine, Cancer stem cell, medicine, Animals, Humans, Neoplasm Invasiveness, Protein Interaction Maps, Molecular Biology, business.industry, Cancer, Myeloid leukemia, Cell Biology, medicine.disease, Fas receptor, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Signal transduction, Stem cell, business, Glioblastoma
Abstract: Changes in transient receptor potential (TRP) Ca2+ permeable channels are associated with development and progression of different types of cancer. Herein, we report data relative to the expression and function of TRP vanilloid 2 (TRPV2) channels in cancer. Overexpression of TRPV2 is observed in high-grade urothelial cancers and treatment with the TRPV2 agonist cannabidiol induces apoptosis. In prostate cancer, TRPV2 promotes migration and invasion, and TRPV2 overexpression characterizes the castration-resistant phenotype. In breast cancer cells, inhibition of TRPV2 by tranilast reduces the insulin-like growth factor-1 stimulated proliferation. TRPV2 overexpression in triple-negative breast cancer cells is associated with high recurrence-free survival. Increased TRPV2 overexpression is present in patients with esophageal squamous cell carcinoma associated with advanced disease, lymph node metastasis, and poor prognosis. Increased TRPV2 transcripts have been found both in benign hepatoma and in hepatocarcinomas, where TRPV2 expression is associated with portal vein invasion and reduction of cancer stem cell expression. TRPV2 expression and function has been also evaluated in gliomagenesis. This receptor negatively controls survival, proliferation, and resistance to CD95- or BCNU-induced apoptosis. In glioblastoma stem cells, TRPV2 activation promotes differentiation and inhibits the proliferation in vitro and in vivo. In glioblastoma, the TRPV2 is part of an interactome-based signature complex, which is negatively associated with survival, and it is expressed in high risk of recurrence and temozolomide-resistant patients. Finally, also in hematological malignancies, such as myeloma or acute myeloid leukemia, TRPV2 might represent a target for novel therapeutic approaches. Overall, these findings demonstrate that TRPV2 exhibits an oncogenic activity in different types of cancers, controlling survival, proliferation, migration, angiogenesis, and invasion signaling pathways. Thus, it prompts the pharmacological use of TRPV2 targeting in the control of cancer progression.
Published: 2019

27. Anti-MAG IgM: differences in antibody tests and correlation with clinical findings

Author: Monica Del Mastio, Lucia Toscani, Tiziana Biagioli, Alessandro Barilaro, Fabio Giannini, Marinella Carpo, Sandro Sorbi, Giacomo P. Comi, Aldo Amantini, Stefano Ambrosini, Sabrina Matà, and Domenica Saccomanno
Subjects: Male, Pathology, medicine.medical_specialty, Adolescent, Autoimmune diseases, HNK-1, Chronic inflammatory demyelinating polyneuropathy, Dermatology, Immunofluorescence, EMG, Myelin-associated glycoprotein, Animals, Autoantibodies, Child, Child, Preschool, Female, Humans, Immunoglobulin M, Myelin Sheath, Myelin-Associated Glycoprotein, Peripheral Nervous System Diseases, Polyneuropathies, Rats, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Western blot, Medicine, 030212 general & internal medicine, Preschool, medicine.diagnostic_test, biology, business.industry, Autoantibody, General Medicine, medicine.disease, Psychiatry and Mental health, nervous system, biology.protein, Neurology (clinical), Antibody, business, Polyneuropathy, 030217 neurology & neurosurgery
Abstract: Anti-myelin-associated glycoprotein (MAG) antibody is associated with clinically heterogeneous polyneuropathies. Our purpose was to compare neuropathy phenotypes identified by different anti-MAG tests’ results. Cohort study: Sera from 40 neuropathy anti-MAG EIA positive patients were tested for anti-MAG by Western blot (WB), for anti-peripheral nerve myelin (PNM) on monkey nerve by immunofluorescence assay (IFA), and for anti-HNK1 on rat CNS slices by IFA. Anti-sulfatide antibodies, for comparison, were also tested by EIA. Among 40 anti-MAG EIA positive sera, 85% also had anti-PNM IFA reactivity and 67.5% bind HNK1 on rat CNS. Anti-HNK1 positive patients had the classical predominantly distal acquired demyelinating symmetric (DADS) neuropathy with a benign course, while anti-PNM positive but anti-HNK1 negative patients had predominantly axonal neuropathy with a high frequency of anti-sulfatide reactivity and the worst long-term prognosis. Anti-MAG EIA positive patients without anti-PNM or anti-HNK1 IFA reactivity had a CIDP-like polyneuropathy. Different methods to test for anti-MAG antibodies identify different clinical and electrophysiological findings, as well as long-term outcome. HNK1 reactivity is the strongest marker of DADS.
Published: 2019

28. Expression Profiling of Circulating Tumor Cells in Pancreatic Ductal Adenocarcinoma Patients: Biomarkers Predicting Overall Survival

Author: Consuelo Amantini, Maria Beatrice Morelli, Massimo Nabissi, Francesco Piva, Oliviero Marinelli, Federica Maggi, Francesca Bianchi, Alessandro Bittoni, Rossana Berardi, Riccardo Giampieri, and Giorgio Santoni
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, overall survival, pancreatic cancer, circulating tumor cells, lcsh:RC254-282, gene signature, 03 medical and health sciences, 0302 clinical medicine, Circulating tumor cell, Internal medicine, Pancreatic cancer, medicine, Progression-free survival, Liquid biopsy, ALCAM, Original Research, biology, business.industry, atypical CTC, digital droplet PCR, CD44, Gene signature, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, digestive system diseases, Gene expression profiling, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, business
Abstract: The interest in liquid biopsy is growing because it could represent a non-invasive prognostic or predictive tool for clinical outcome in patients with pancreatic ductal adenocarcinoma (PDAC), an aggressive and lethal disease. In this pilot study, circulating tumor cells (CTCs), CD16 positive atypical CTCs, and CTC clusters were captured and characterized in the blood of patients with PDAC before and after palliative first line chemotherapy by ScreenCell device, immunohistochemistry, and confocal microscopy analysis. Gene profiles were performed by digital droplet PCR in isolated CTCs, five primary PDAC tissues, and three different batches of RNA from normal human pancreatic tissue. Welsh's t-test, Kaplan-Meier survival, and Univariate Cox regression analyses have been performed. Statistical analysis revealed that the presence of high CTC number in blood is a prognostic factor for poor overall survival and progression free survival in advanced PDAC patients, before and after first line chemotherapy. Furthermore, untreated PDAC patients with CTCs, characterized by high ALCAM, POU5F1B, and SMO mRNAs expression, have shorter progression free survival and overall survival compared with patients expressing the same biomarkers at low levels. Finally, high SHH mRNA levels are negatively associated to progression free survival, whereas high vimentin mRNA levels are correlated with the most favorable prognosis. By hierarchical clustering and correlation index analysis, two cluster gene signatures were identified in CTCs: the first, with high expression of VEGFA, NOTCH1, EPCAM, IHH, is the signature of PDAC patients before chemotherapy, whereas the second, with an enrichment in the expression of CD44, ALCAM, and POU5F1B stemness and pluripotency genes, is reported after palliative chemotherapy. Overall our data support the clinic value of the identification of CTC's specific biomarkers to improve the prognosis and the therapy in advanced PDAC patients.
Published: 2019

29. Prognostic value of post-acute EEG in severe disorders of consciousness, using American Clinical Neurophysiology Society terminology

Author: Anna Maria Romoli, Emilio Portaccio, Maenia Scarpino, Tiziana Atzori, Giovanni Lanzo, Antonello Grippo, Claudio Macchi, Bahia Hakiki, Azzurra Morrocchesi, Francesco Lolli, Aldo Amantini, and Raisa Sterpu
Subjects: Male, medicine.medical_specialty, Electroencephalography, Clinical neurophysiology, Logistic regression, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, 0501 psychology and cognitive sciences, Stage (cooking), Societies, Medical, Persistent vegetative state, Retrospective Studies, Coma, Trauma Severity Indices, medicine.diagnostic_test, business.industry, Persistent Vegetative State, 05 social sciences, Minimally conscious state, General Medicine, medicine.disease, Prognosis, Neurology, Brain Injuries, Consciousness Disorders, Wakefulness, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Summary Objective To evaluate whether electroencephalographic (EEG) features recorded during the post-acute stage in patients with severe disorders of consciousness (DoC) after acute brain injury (ABI), contribute to neurological outcome prediction of these patients at discharge from the intensive rehabilitation unit (IRU). Methods We retrospectively evaluated all patients consecutively admitted to the IRU from August 2012 to December 2016. Inclusion criteria were: 1) age > 18years, 2) patients with unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS), and 3) EEG and a coma recovery scale-revised (CRS-R) score available within the first week after admission. Clinical evaluation was performed using the Italian version of the CRS-R score. EEGs were classified according to American Clinical Neurophysiology Society (ACNS) terminology. Clinical state at final discharge was evaluated using the CRS-R score. Results In total, 102 patients were included in the analysis. After a mean of five months of IRU stay, among the 61 UWS subjects, 19 transitioned to MCS and 11 recovered to exit-MCS (E-MCS); twenty-three of the 41 subjects in MCS progressed to E-MCS. Using logistic regression, consciousness level (UWS/MCS-OR = 13.4), CRS-R score at admission (OR = 1.33) and use of activating drugs (OR = 4.7) were significant predictors of clinical improvement. Multivariable analysis showed that specific EEG patterns were independent predictors of improved consciousness at discharge in UWS patients. Discussion EEG performed within the first week after IRU admission, classified according to ACNS-terminology in patients with UWS at admission, can provide useful prognostic contribution.
Published: 2019

30. Disorders of Consciousness

Author: Antonello Grippo, Marianna Brienza, Oriano Mecarelli, and Aldo Amantini
Subjects: business.industry, media_common.quotation_subject, Thalamus, Minimally conscious state, coma, medicine.disease, Alertness, coma, disorders of consciousness, ARAS, Medicine, Wakefulness, Locked-in syndrome, Consciousness, business, ARAS, Neuroscience, Reticular activating system, disorders of consciousness, Vigilance (psychology), media_common
Abstract: The concept of consciousness has fascinated philosophers, psychologists and neurophysiologists for a long time; however, it remains difficult to give its univocal and universally accepted definition. Consciousness is defined as “the state of full awareness of the self and one’s relationship to the environment”; consequently, a distinction must be made between consciousness (or awareness) and vigilance/alertness (wakefulness). In fact, it is possible for a patient to be conscious, but unresponsive to the examiner, for lack of sensory inputs or for psychiatric reasons. Conversely, a subject can be alert and awake with open eyes, but not conscious and not aware (in part or at all) of itself and of the environment. From a neurophysiological point of view, it has been demonstrated that the brainstem Reticular Activating System (RAS) is responsible for the state of alertness, through its projections to the thalamus and cortex. The integrity of the upper cortical centres, which are closely related to each other and receive the reticular activating stimuli, is also essential for the maintenance of consciousness level. Therefore, Disorders Of Consciousness (DOC) and vigilance may depend on damage to one or both of these neurofunctional systems, acute or chronic, reversible or irreversible. Serious damage to the reticular system, with or without concomitant widespread cortical damage, can produce a state of coma. Coma is then a pathological condition in which the subject lies with eyes closed and he is neither conscious nor alert, with altered - or completely absent - responsiveness to stimuli. In case of widespread damage to the cerebral cortex without involvement of the RAS, a particular condition - named Vegetative State (VS) - may occur: the consciousness of self and of the environment is impaired, but a certain level of vigilance is still preserved. Moreover, there also exist several neurological conditions that can be defined as “borderline”, such as the Minimally Conscious State. Finally, brain death is the irreversible definitive impairment of both the cortical and brainstem functions. Electroencephalography is an important diagnostic and prognostic tool, useful to better characterise the evolution of a coma state, to recognise any kind of epileptiform activity - that could be clinically hidden - and to monitor the effects of antiepileptic drugs, level of sedation, and treatment of intracranial hypertension.
Published: 2019

31. The Controversial Role of PD-1 and Its Ligands in Gynecological Malignancies

Author: Oliviero Marinelli, Daniela Annibali, Cristina Aguzzi, Sandra Tuyaerts, Frédéric Amant, Maria Beatrice Morelli, Giorgio Santoni, Consuelo Amantini, Federica Maggi, Massimo Nabissi, Clinical sciences, and Medical Oncology
Subjects: 0301 basic medicine, PD-L1, Cancer Research, PD-L2, cervical cancer, endometrial cancer, immunotherapy, ovarian cancer, PD-1, medicine.medical_treatment, Review, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Cancer immunotherapy, medicine, Tumor microenvironment, biology, business.industry, Endometrial cancer, Immunotherapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immune checkpoint, Review article, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Ovarian cancer, business
Abstract: The programmed death-1 (PD-1, CD279) receptor with its ligands, programmed death ligand 1 (PD-L1, CD274, B7-H1), and programmed death ligand 2 (PD-L2, CD273, B7-DC), are the key players of one of the immune checkpoint pathways inhibiting T-cell activation. PD-L1 and PD-L2 are expressed in different cancer cells and their microenvironment, including infiltrating immune cells. However, their prognostic value is still debated and their role in the tumor microenvironment has not been fully elucidated yet. Considering the importance that cancer immunotherapy with anti-PD-1 and anti-PD-L1 antibodies gained in several tumor types, in this review article we aim to discuss the role of the PD-1/PD-L1/PD-L2 axis in gynecological cancers. PD-1 ligands have been detected in ovarian, cervical, vulvar and uterine cancers, and correlation with prognosis seems dependent from their distribution. About PD-L2, very few reports are available so far in gynecological malignancies, and its role is still not completely understood. Clinical trials using anti-PD-1 or anti-PD-L1 antibodies, but not anti-PD-L2, are currently ongoing, in all types of gynecological cancers. They have shown good safety profiles in a certain cohort of patients, but response rates remain low and many aspects remain controversial. In this review, we propose possible solutions to enhance the clinical efficacy of PD-1 axis targeting therapies. Regarding PD-L2, it might be useful to better clarify its role in order to improve the efficiency of immunotherapy in female malignancies. ispartof: FRONTIERS IN ONCOLOGY vol:9 ispartof: location:Switzerland status: published
Published: 2019

32. Amplitude Instability of Somatosensory Evoked Potentials as an Indicator of Delayed Cerebral Ischemia in a Case of Subarachnoid Hemorrhage

Author: Maenia Scarpino, Antonello Grippo, Enrico Fainardi, L Bucciardini, Marinella Marinoni, Vanni Orzalesi, Riccardo Carrai, Aldo Amantini, C. Cossu, and M. Spalletti
Subjects: Male, medicine.medical_specialty, Subarachnoid hemorrhage, medicine.medical_treatment, Ischemia, behavioral disciplines and activities, 050105 experimental psychology, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Evoked Potentials, Somatosensory, Internal medicine, medicine, Humans, 0501 psychology and cognitive sciences, cardiovascular diseases, Intracranial pressure, business.industry, Penumbra, musculoskeletal, neural, and ocular physiology, 05 social sciences, Electroencephalography, Vasospasm, Cerebral Infarction, General Medicine, Middle Aged, Subarachnoid Hemorrhage, medicine.disease, Transcranial Doppler, nervous system diseases, body regions, Neurology, Somatosensory evoked potential, Cardiology, Decompressive craniectomy, Neurology (clinical), acute brain injury, continuous SEP monitoring, delayed cerebral ischemia, neurophysiological monitoring, subarachnoid hemorrhage, Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract: We describe a 55-year-old male patient with a subarachnoid hemorrhage (SAH) as a result of left middle cerebral artery (MCA) aneurysm rupture, who underwent continuous electroencephalogram (EEG) and somatosensory evoked potential (cEEG-SEP) monitoring that showed an unusual SEP trend pattern. EEG was continuously recorded, and SEPs following stimulation of median nerves were recorded every 50 minutes, with the amplitude and latency of the cortical components automatically trended. An increase in intracranial pressure required a left decompressive craniectomy. cEEG-SEP monitoring was started on day 7, which showed a prolonged (24 hours) instability of SEPs in the left hemisphere. During this phase, left MCA vasospasm was demonstrated by transcranial Doppler (TCD), and computed tomography perfusion (CTP) showed a temporo-parieto-occipital ischemic penumbra. Following intravascular treatment, hypoperfusion and the amplitude of cortical SEPs improved. In our case, a prolonged phase of SEP amplitude instability during vasospasm in SAH correlated with a phase of ischemic penumbra, as demonstrated by CTP. In SAH, SEP instability during continuous monitoring is a pattern of alert that can allow treatments capable of avoiding irreversible neurological deterioration.
Published: 2019

33. Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration

Author: Pietro Leoni, Claudio Cardinali, Silvia Gentili, Consuelo Amantini, Giorgio Santoni, Maria Beatrice Morelli, Massimo Nabissi, Alessandra Soriani, and Massimo Offidani
Subjects: 0301 basic medicine, Integrin beta Chains, THC, Combination therapy, Cell Survival, Antineoplastic Agents, Pharmacology, CXCR4, combination therapy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, Cell Line, Tumor, Autophagy, medicine, Humans, Viability assay, Tetrahydrocannabinol, Cell Proliferation, carfilzomib, Dose-Response Relationship, Drug, Cannabinoids, Bortezomib, business.industry, Cell Cycle Checkpoints, Carfilzomib, multiple myeloma, 030104 developmental biology, immuno-proteasome, Oncology, chemistry, 030220 oncology & carcinogenesis, Proteasome inhibitor, CBD, business, Oligopeptides, Cannabidiol, Biomarkers, Research Paper, medicine.drug
Abstract: // Massimo Nabissi 1, * , Maria Beatrice Morelli 2, * , Massimo Offidani 3 , Consuelo Amantini 4 , Silvia Gentili 3 , Alessandra Soriani 2 , Claudio Cardinali 2 , Pietro Leoni 3 , Giorgio Santoni 1 1 School of Pharmacy, Experimental Medicine Section, University of Camerino, Camerino, Italy 2 Department of Molecular Medicine, Sapienza University, Rome, Italy 3 Clinica di Ematologia, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona, Ancona, Italy 4 School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy * These authors have contributed equally to this work Correspondence to: Massimo Nabissi, email: massimo.nabissi@unicam.it Keywords: carfilzomib, THC, CBD, multiple myeloma, immuno-proteasome, combination therapy Received: September 01, 2016 Accepted: October 05, 2016 Published: October 18, 2016 ABSTRACT Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ 9 -tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy. In the current study, we evaluated the effects of THC alone and in combination with CBD in MM cell lines. We found that CBD and THC, mainly in combination, were able to reduce cell viability by inducing autophagic-dependent necrosis. Moreover, we showed that the CBD-THC combination was able to reduce MM cells migration by down-regulating expression of the chemokine receptor CXCR4 and of the CD147 plasma membrane glycoprotein. Furthermore, since the immuno-proteasome is considered a new target in MM and also since carfilzomib (CFZ) is a new promising immuno-proteasome inhibitor that creates irreversible adducts with the β5i subunit of immuno-proteasome, we evaluated the effect of CBD and THC in regulating the expression of the β5i subunit and their effect in combination with CFZ. Herein, we also found that the CBD and THC combination is able to reduce expression of the β5i subunit as well as to act in synergy with CFZ to increase MM cell death and inhibits cell migration. In summary, these results proved that this combination exerts strong anti-myeloma activities.
Published: 2016
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34. Evaluations of thyme extract effects in human normal bronchial and tracheal epithelial cell lines and in human lung cancer cell line

Author: Santoni Giorgio, Nabissi Massimo, Nicotra Giovanna, Morelli Maria Beatrice, Iannarelli Romilde, Cardinali Claudio, Maggi Filippo, Amantini Consuelo, Valisi Matteo, and Marinelli Oliviero
Subjects: 0301 basic medicine, Lung Neoplasms, medicine.drug_class, Interleukin-1beta, Anti-Inflammatory Agents, Bronchi, Inflammation, Respiratory Mucosa, Pharmacology, Toxicology, Anti-inflammatory, Cell Line, Thymus Plant, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, medicine, Humans, Interleukin 8, Lung, Thymol, Cell Death, Plant Extracts, business.industry, Interleukin-8, NF-kappa B, General Medicine, respiratory system, Antineoplastic Agents, Phytogenic, Mucus, respiratory tract diseases, Trachea, 030104 developmental biology, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Cancer cell, Immunology, medicine.symptom, business
Abstract: Thyme (Thymus vulgaris) is used traditionally to prepare herbal remedies possessing expectorant, mucolytic, antitussive and antispasmodic properties. The aim of the present study was to investigate the effects of a standardized hydroalcoholic extract of thyme on primary human airway (bronchial/tracheal) epithelial cell lines in a model of lung inflammation induced by LPS. In addition, the effects of thyme extract on human lung cancer cell line (H460) were analysed. Thyme extract showed significant anti-inflammatory properties by reducing the NF-κB p65 and NF-κB p52 transcription factors protein levels followed by the decrease of pro-inflammatory cytokines (IL-1 beta and IL-8), and Muc5ac secretion in human normal bronchial and tracheal epithelial cells. Moreover, the extract showed cytotoxic effects on H460 cancer cells, modulated the release of IL-1 beta, IL-8 and down-regulated NF-κB p65 and NF-κB p52 proteins. Taken together, these results substantiated the traditional uses of thyme in the treatment of respiratory diseases. Thyme extract might be an effective treatment of chronic diseases based on inflammatory processes when hypersecretion of mucus overwhelms the ciliary clearance and obstructs airways, causing morbidity and mortality. Moreover thyme extract, evaluated in H460 lung cancer cell line, demonstrated to induce cell cytotoxicity in addition to reduce inflammatory cell signals.
Published: 2016
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35. Using Augmented Reality to Motivate Oral Hygiene Practice in Children: Protocol for the Development of a Serious Game

Author: Alexandre Alberto Pascotto Montilha, Susy Nazaré Silva Ribeiro Amantini, Bianca Caseiro Antonelli, Daniela Rios, Natalino Lourenço Neto, Maria Aparecida de Andrade Moreira Machado, Thais Marchini de Oliveira, Kim Tanabe De Moura Leite, and Thiago Cruvinel
Subjects: Emerging technologies, Computer science, Interface (Java), computer.software_genre, Outcome (game theory), Oral hygiene, 03 medical and health sciences, 0302 clinical medicine, Protocol, computer simulation, 030212 general & internal medicine, Protocol (science), Medical education, business.industry, ComputingMilieux_PERSONALCOMPUTING, video games, education, dental, 030206 dentistry, General Medicine, pediatric dentistry, Action (philosophy), user-computer interface, Virtual machine, ODONTOPEDIATRIA, Augmented reality, business, computer
Abstract: Background New technologies create possible new ways of action, interaction, and learning which is extremely relevant in the field of oral health education. There is a lack of protocol in using an immersive interactive ludic-educational interface to motivate oral hygiene practice in children by means of augmented reality. Objective This study aims to present a protocol on the development of a serious game to motivate oral hygiene practice in children. Methods A serious game will be designed by augmented reality techniques to improve toothbrushing effectiveness of children aged 6 to 10 years. The functional structure of this interface is activated by means of movements recognized by Kinect (Microsoft Corp). The toothbrushing technique will be available in the game, enabling the children to execute the movement in the virtual environment. By identifying errors, this game will be tailored to improve the oral health of children by correcting the technique and teaching the user the adequate toothbrushing method. A template analysis will be performed to identify barriers and facilitators in each scenario. Results After the implementation of the virtual interactive and immersive panels, enrollment will begin and evaluations will be made by means of questionnaires distributed to participants who interact with the game. Thus, an analysis of the product efficacy will be conducted. The expected outcome will be to obtain a digital instrument to motivate oral hygiene practice and enhance health awareness in children. Conclusions The serious game will support the prevention of oral diseases by sharing scientific research in the school environment and community. International Registered Report Identifier (IRRID) PRR1-10.2196/10987
Published: 2020
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36. Early-SEPs' amplitude reduction is reliable for poor-outcome prediction after cardiac arrest?

Author: Maenia Scarpino, Antonello Grippo, Riccardo Carrai, Chiara Lazzeri, Francesco Lolli, Giovanni Lanzo, Adriano Peris, Aldo Amantini, and M. Spalletti
Subjects: Male, medicine.medical_specialty, Amplitude reduction, Electroencephalography, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Evoked Potentials, Somatosensory, medicine, Humans, 030212 general & internal medicine, Coma, Receiver operating characteristic, medicine.diagnostic_test, business.industry, Glasgow Outcome Scale, Area under the curve, General Medicine, Middle Aged, Heart Arrest, Amplitude, Neurology, Somatosensory evoked potential, Cardiology, Disease Progression, Female, Neurology (clinical), business, Outcome prediction, 030217 neurology & neurosurgery
Abstract: OBJECTIVE The bilateral absence of cortical Somatosensory Evoked Potentials (SEPs), after cardiac arrest (CA), is a high reliable predictor of poor outcome but it is present in no more than 40% of patients. An amplitude reduction of cortical SEPs was found in about 30% of subjects, but few papers analysed its prognostic significance. The aim of our study is to identify a value of SEP amplitude reduction below which all the CA patients had poor outcome and the relationship between SEP and Electroencephalogram (EEG) patterns. MATERIAL AND METHODS We analysed comatose patients in whom SEPs and EEG were recorded at 6-12 hours after CA. We evaluated the sensitivity at specificity of 100% of SEP amplitude in predicting the non-recovery of consciousness by plotting Receiver Operating Characteristic (ROC) curves. We also analysed the relationship between SEP amplitude and EEG patterns. Outcome was evaluated at 6 months by Glasgow Outcome Scale. RESULTS We analysed 119 subjects. According to the ROC analysis (area under the curve = 0.95/CI 0.91-0.99), all patients with a cortical SEP amplitude
Published: 2018

37. Authors' comments on two published resuscitation editorials

Author: M. Spalletti, Antonello Grippo, Aldo Amantini, Marco Moretti, Maenia Scarpino, Riccardo Carrai, Francesco Lolli, Giovanni Lanzo, Adriano Peris, and Morena Cozzolino
Subjects: medicine.medical_specialty, Resuscitation, business.industry, MEDLINE, 030208 emergency & critical care medicine, 030204 cardiovascular system & hematology, Emergency Nursing, 03 medical and health sciences, 0302 clinical medicine, Emergency Medicine, medicine, Cardiology and Cardiovascular Medicine, Intensive care medicine, business
Published: 2018

38. OP0258 Efficacy of the highly selective adamts-5 inhibitor glpg1972 in the rat meniscectomy model

Author: E. van der Aar, L. Lepescheux, I. Botez, Thierry Christophe, F. Brebion, Pierre Deprez, Roland Blanque, D. Merciris, S. Meurisse, Monica Borgonovi, R. Gosmini, F. De Ceuninck, Patrick Mollat, Philippe Clément-Lacroix, D. Comas, Nele Vandervoort, C. Cottereaux, and D. Amantini
Subjects: Fibrillation, medicine.medical_specialty, business.industry, ADAMTS, Cartilage, Arthritis, Hindlimb, Osteoarthritis, medicine.disease, medicine.anatomical_structure, Endocrinology, Internal medicine, medicine, medicine.symptom, business, Aggrecan, Aggrecanase
Abstract: Background Aggrecan cleavage is an early process in cartilage degradation observed in OA. As a result, aggrecanase inhibition is an attractive therapeutic strategy for the treatment of OA.1 2 A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) is an aggrecanase playing a key role in the catabolic events leading to OA.3 We previously described the pharmacological characterisation of GLPG1972, a potent, selective and orally bioavailable ADAMTS-5 inhibitor showing anti-catabolic activity in cartilage explants and displaying disease-modifying OA drug (DMOAD) potential in the destabilisation of the medial meniscus (DMM) model in mice.4 5 Objectives In this communication we report the activity of GLPG1972 in a second model of surgery-induced OA, the rat meniscectomy (MNX) model.6 Methods OA pathology was induced by meniscectomy in the right hind leg of each rat. On day 1 post surgery, rats were randomly assigned to a treatment group (n=20 per group) according to their body weight. GLPG1972 was administered orally over 3 weeks at dose levels of 10, 25 and 50 mg/kg b.i.d. At sacrifice, the right tibias were collected and processed for histological analysis. OA development in the tibial plateau was evaluated using the OARSI score. The following structural parameters were measured by imaging histomorphometry analysis: subchondral bone plate thickness, proteoglycan content and fibrillation index. Blood samples were collected at steady state at predose, 1, 3 and 6 hour postdose for the determination of GLPG1972 plasma concentrations. Results Three weeks post-surgery, a significant reduction in OARSI score compared to vehicle-treated rats was observed with GLPG1972 at 25 and 50 mg/kg b.i.d. (−24% and −23%, respectively). Treatment with GLPG1972 also resulted in a significant reduction in cartilage fibrillation as of 25 mg/kg b.i.d. and prevented proteoglycan loss and subchondral bone plate thickening at all doses. At 25 mg/kg b.i.d. GLPG1972 average plasma concentration over 24 hour was found to be in line with the value observed in other rat MNX experiments (385 ng/mL). GLPG1972 bio-distribution in the target tissue was also determined: the average condyle to plasma ratio was found to be 0.14. Conclusions Oral dosing with GLPG1972 in rat MNX model resulted in significant chondroprotection confirming the DMOAD potential of GLPG1972. A Phase 1 first-in-human study was successfully completed with GLPG1972 (NCT02612246), and a dose-escalation Phase 1b study in OA patients is ongoing (NCT03311009). GLPG1972 is a promising OA drug candidate and a Phase 2 program is currently under preparation. References [1] Little CB, et al. J Clin Invest2007;117:1627–1636. [2] Larsson S, et al. Arthritis Res Ther2009;11:R92. [3] Fosang AJ. Osteoarthritis Cartilage2015;23(8):1231–1232. [4] Clement-Lacroix P, et al. OARSI congress2017. [5] Clement-Lacroix P, et al. EULAR congress2017. [6] Little CB, Smith MM. Curr RheumatoloRev2008;4:175–182. Disclosure of Interest None declared
Published: 2018
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39. Transplante de microbiota fecal no tratamento da infecção por Clostridium difficile: estado da arte e revisão de literatura

Author: Bárbara Freitas Franchi, Bruno Amantini Messias, Pedro Henrique Pontes, Daniel Átila De Andrade Medeiros Barbosa, and César Augusto Sanita Viana
Subjects: medicine.medical_specialty, Transplante de Microbiota Fecal, lcsh:Surgery, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Clostridium, Internal medicine, Antibacterianos, medicine, Humans, 030212 general & internal medicine, Antibiotic use, Adverse effect, Enterocolitis, Pseudomembranous, Enterocolitis, High rate, biology, Clostridioides difficile, business.industry, Enterocolite Pseudomembranosa, lcsh:RD1-811, Clostridium difficile, Fecal bacteriotherapy, Fecal Microbiota Transplantation, biology.organism_classification, Anti-BacterialAgents, 030211 gastroenterology & hepatology, Surgery, medicine.symptom, business, Complication
Abstract: Clostridium difficile infection is a common complication following intestinal dysbiosis caused by abusive antibiotic use. It presents medical importance due to the high rates of recurrence and morbidity. Fecal microbiota transplantation is an effective alternative for the treatment of recurrent and refractory C. difficile infection and consists of introducing the intestinal microbiota from a healthy donor into a patient with this infection. The exact physiological mechanism by which fecal microbiota transplantation alters the intestinal microbiota is not well established, but it is clear that it restores the diversity and structure of the microbiota by promoting increased resistance to colonization by C. difficile. Several routes of transplant administration are being studied and used according to the advantages presented. All forms of application had a high cure rate, and the colonoscopic route was the most used. No relevant complications and adverse events have been documented, and the cost-effectiveness over conventional treatment has proven advantageous. Despite its efficacy, it is not commonly used as initial therapy, and more studies are needed to establish this therapy as the first option in case of refractory and recurrent Clostridium difficileinfection. RESUMO A infecção por Clostridium difficile é uma complicação comum após a disbiose intestinal ocasionada pelo uso abusivo de antibióticos. Apresenta elevada importância médica devido às altas taxas de recorrência e morbidade. O transplante de microbiota fecal é uma alternativa eficaz para o tratamento da infecção recorrente e refratária pelo C. difficile e consiste na introdução da microbiota intestinal de um doador saudável em um paciente portador desta infecção. O mecanismo fisiológico exato pelo qual o transplante de microbiota fecal altera a microbiota intestinal não está tão bem estabelecido, mas é evidente que restaura a diversidade e a estrutura da microbiota promovendo aumento da resistência à colonização pelo C.difficile. Diversas vias de administração do transplante estão sendo estudadas e utilizadas de acordo com as vantagens apresentadas. Todas as formas de aplicação apresentaram elevada taxa de cura, sendo a via colonoscópica a mais utilizada. Não foram documentados complicações e efeitos adversos relevantes, e seu custo benefício em relação ao tratamento convencional se mostrou vantajoso. Apesar da sua eficácia é pouco utilizado como terapia inicial, sendo necessários mais estudos para firmar essa terapêutica como primeira opção no caso de infecção por Clostridium difficile refratária e recorrente.
Published: 2018
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40. Efficacy of high-frequency (15Hz) repetitive transcranial magnetic stimulation (rTMS) of the left premotor cortex/dorsolateral prefrontal cortex in decreasing cocaine intake (the MagneTox study): A study protocol for a randomized placebo-controlled pilot trial

Author: Maenia Scarpino, C. Cossu, Brunella Occupati, Guido Mannaioni, Stefano Pallanti, Antonello Grippo, M. Bastianelli, Amedeo del Vecchio, Giovanni Lanzo, Francesco Lolli, Aldo Amantini, Maya Salimova, and Cecilia Lanzi
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Prefrontal Cortex, Stimulation, Craving, Placebo, behavioral disciplines and activities, 050105 experimental psychology, Premotor cortex, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Cocaine, Double-Blind Method, Physiology (medical), mental disorders, Medicine, Humans, 0501 psychology and cognitive sciences, Pain Measurement, business.industry, 05 social sciences, Motor Cortex, General Medicine, Middle Aged, Transcranial Magnetic Stimulation, Dorsolateral prefrontal cortex, Transcranial magnetic stimulation, medicine.anatomical_structure, Mood, Treatment Outcome, nervous system, Neurology, Quality of Life, Female, Neurology (clinical), medicine.symptom, Hypoactivity, business, psychological phenomena and processes, 030217 neurology & neurosurgery
Abstract: Summary Background Cocaine use disorder (CUD) is very common and has psychological and physical consequences. Patients with CUD present hypoactivity of the prefrontal cortical area. Thus, excitatory repetitive transcranial magnetic stimulation (rTMS) targeting the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC), given its ability to increase prefrontal area excitability and to modulate cortico-limbic activity, could result in a decrease in cocaine intake. Methods We designed a protocol for a monocentric, randomized, double-blind, placebo-controlled, parallel-group pilot trial, with the principal aim of assessing the efficacy of rTMS on the reduction of cocaine intake. Patients with CUD will be recruited according to inclusion and exclusion criteria, and then randomized to undergo active or sham rTMS. Our rTMS protocol will consist of 15 days of 15 Hz rTMS targeting the left PMC/DLPFC. Toxicological and psychiatric assessments, urine drug tests, the Cocaine Craving Questionnaire (CCQ) and the Visual Analogic Scale (VAS) will be used to assess changes from baseline in cocaine intake and craving, mood and quality of life. Discussion Only a few studies have evaluated the efficacy of rTMS for CUD treatment in humans, with limitations concerning small sample size, short treatment duration, different rTMS protocols and the absence of a placebo-controlled group. Our study will attempt to overcome these shortcomings and will provide data that can be used for future larger studies of non-invasive left PMC/DLPFC stimulation as a treatment for CUD.
Published: 2018

41. Urinary Markers in Bladder Cancer: An Update

Author: Giorgio Santoni, Maria B. Morelli, Consuelo Amantini, and Nicola Battelli
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Urinary system, exosomes, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Circulating tumor cell, Internal medicine, Biopsy, medicine, urinary biomarkers, Liquid biopsy, Survival rate, Bladder cancer, liquid biopsy, microRNA, medicine.diagnostic_test, business.industry, Cancer, Cystoscopy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, bladder cancer, business
Abstract: Bladder cancer (BC) is ones of the most common cancer worldwide. It is classified in muscle invasive (MIBC) and muscle non-invasive (NMIBC) BC. NMIBCs frequently recur and progress to MIBCs with a reduced survival rate and frequent distant metastasis. BC detection require unpleasant and expensive cystoscopy and biopsy, which are often accompanied by several adverse effects. Thus, there is an urgent need to develop novel diagnostic methods for initial detection and surveillance in both MIBCs and NMIBCs. Multiple urine-based tests approved by FDA for BC detection and surveillance are commercially available. However, at present, sensitivity, specificity and diagnostic accuracy of these urine-based assays are still suboptimal and, in the attend to improve them, novel molecular markers as well as multiple-assays must to be translated in clinic. Now there are growing evidence toward the use of minimally invasive “liquid biopsy” to identify biomarkers in urologic malignancy. DNA- and RNA-based markers in body fluids such as blood and urine are promising potential markers in diagnostic, prognostic, predictive and monitoring urological malignancies. Thus, circulating cell-free DNA, DNA methylation and mutations, circulating tumor cells, miRNA, IncRNA and mRNAs, cell-free proteins and peptides, and exosomes have been assessed in urine specimens. However, proteomic and genomic data must to be validated in well-designed multicenter clinical studies, before to be employed in clinic oncology.
Published: 2018

42. ICOS-L as a Potential Therapeutic Target for Cancer Immunotherapy

Author: Oliviero Marinelli, Giorgio Santoni, Consuelo Amantini, Luciana Torquati, Massimo Nabissi, and Maria Beatrice Morelli
Subjects: 0301 basic medicine, medicine.medical_treatment, T cell, Population, Antineoplastic Agents, Biochemistry, 03 medical and health sciences, Inducible T-Cell Co-Stimulator Ligand, 0302 clinical medicine, Immune system, Cancer immunotherapy, Neoplasms, Biomarkers, Tumor, Tumor Microenvironment, Medicine, CD278, Humans, Molecular Targeted Therapy, education, Molecular Biology, education.field_of_study, business.industry, Cancer, Cell Biology, General Medicine, Immunotherapy, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, business, CD8, Immunosuppressive Agents
Abstract: Background: The co-stimulatory B7 family members are cell-surface protein ligands, binding to receptors on lymphocytes to regulate immune responses. One of them is the inducible co-stimulatory molecule ligand (ICOS-L). This protein is expressed on professional antigen-presenting cells (APCs), including B cells, macrophages, and dendritic cells (DCs), but it can also be expressed by endothelial cells, lung epithelium and in tumour microenvironment cells. ICOS-L is important for memory and effector T cells during the specific humoral immune responses, but its role in cancer is not yet understood. Objective: To discuss the role of ICOS/ICOS-L in cancer, given importance of identifying selective targets for cancer treatment, and knowing the mechanism of immune evasion by tumour. Main findings: ICOS/ICOS-L signal has opposite effects on the T-cell response. ICOS-L is activated in several types of cancers to maintain immunosuppressive CD4+ T cell subsets, such as regulatory T cells (Tregs). ICOS-L over-expression is associated with tumour progression and poor overall survival. In colon cancer, activation of this co-stimulatory signal is associated with improved survival suggesting a dualistic effect of the ICOS/ICOs-L signal pathway. Interestingly, following anti-cancer vaccine or anti-CTLA-4 treatment, ICOS+ T cells increased significantly in both the CD4+ and CD8+ population and the ratio Teff/Treg increased in tumour microenvironment. This suggests a potential role of ICOS/ICOS-L in improving effectiveness of cancer therapy. Conclusion: ICOS/ICOS-L signal pathway has the potential to improve cancer treatment. However, studies in other models are needed to understand whether inhibition of ICOS expression or the blockage of its co-stimulation could be a potential therapeutic target or adjuvant treatment for immunotherapy.
Published: 2018

43. Thyme extract increases mucociliary-beating frequency in primary cell lines from chronic obstructive pulmonary disease patients

Author: Filippo Maggi, Consuelo Amantini, Giovanna Nicotra, Romilde Iannarelli, Massimo Nabissi, Oliviero Marinelli, Maria Beatrice Morelli, and Giorgio Santoni
Subjects: 0301 basic medicine, Interleukin-1beta, Down-Regulation, Bronchi, Pharmacology, Cell Line, Thymus Plant, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Extracellular, Cyclic AMP, Medicine, Humans, Interleukin 8, Cilia, Respiratory system, Lung, COPD, business.industry, Plant Extracts, Interleukin-8, NF-kappa B, Epithelial Cells, General Medicine, medicine.disease, Epithelium, respiratory tract diseases, 030104 developmental biology, medicine.anatomical_structure, Chronic inflammatory response, Calcium, Salmeterol, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by a progressive and irreversible airflow limitation. COPD is associated to a chronic inflammatory response with infiltration of inflammatory cells in the surface epithelium of large airways and abnormalities in structure and functions of cilia. Thyme (Thymus vulgaris L.) is a traditional medicinal plant of the Mediterranean area used to treat respiratory disorders. We previously evidenced that thyme extract reduce IL-1beta and IL-8, by downregulating the activated NF-κB levels, suggesting its potential therapeutically use in COPD. Cilia beating frequency (CBF) is dramatically impaired in COPD and different pharmacological agents can modulate cilia function. Herein we evaluated the effect of a commercial thyme extract in modulating CBF by measuring its activity in stimulating cAMP, Ca2+ levels and CBF in a MucilAir 3D human COPD airway epithelia reconstituted in vitro system using salmeterol, YM976, isoproterenol and GSK1016790 A as positive controls. Results showed that thyme extract increased cAMP levels starting from 12 h post-treatment, decreased extracellular Ca2+ levels and increased the CBF in airway epithelia from COPD donors. Overall, this work demonstrated that thyme extract is effective in stimulating CBF by inducing an increase of cAMP and Ca2+ levels, thus supporting its therapeutical use in the treatment of COPD.
Published: 2018

44. OP0180 Pharmacological characterization of the ADAMTS-5 inhibitor GLPG1972: an oral anti-catabolic agent for the treatment of osteoarthritis

Author: R. Gosmini, E. van der Aar, Pierre Deprez, Roland Blanque, Thierry Christophe, L. Lepescheux, Christopher B. Little, Philippe Clément-Lacroix, F. Brebion, C. Cottereaux, D. Amantini, I. Botez, Patrick Mollat, D. Comas, Nele Vandervoort, F. De Ceuninck, and S. Meurisse
Subjects: Metalloproteinase, business.industry, ADAMTS, Cartilage, Assay, Osteoarthritis, Matrix metalloproteinase, Pharmacology, medicine.disease, In vitro, medicine.anatomical_structure, In vivo, Medicine, business
Abstract: Background Degradation of articular cartilage and alterations of the underlying subchondral bone are hallmarks of osteoarthritis (OA) 1 . A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) is a key aggrecan-cleaving enzyme involved in this pathogenic process from the earliest stages of cartilage degradation 2 and as such, is an attractive drug target for the development of a disease-modifying OA drug (DMOAD) 3 . Objectives In this report we describe the in vitro and in vivo characterization of the small molecule GLPG1972, an inhibitor of ADAMTS-5. GLPG1972 anti-catabolic activity was evaluated in murine and human cartilage explants and DMOAD activity was investigated in the destabilization of the medial meniscus (DMM) mouse model 4 . Methods The ADAMTS-5 biochemical assay is based on the cleavage of a fluorescent substrate by recombinant ADAMTS-5. Mouse femoral head cartilage explants were stimulated by interleukin-1a (IL-1a) for 3 days and GAG release quantified 2b . Human articular cartilage explants were stimulated with IL-1β for 12 or 19 days and the NITEGE epitope quantified using the AGNx1 assay. Unilateral OA was induced in C57BL6 mice by DMM 4 . Mice were treated with vehicle or GLPG1972 at 30, 60 or 120 mg/kg, b.i.d. for 8 weeks. Medial femorotibial joint sections were scored by an evaluator blinded to treatment. Results GLPG1972 showed potent inhibition of human ADAMTS-5 (IC 50 =20 nM). Inhibition of ADAMTS-4 was moderate (IC 50 =57 nM), and selectivity over 100-fold was observed against a large panel of zinc metalloproteinases. GLPG1972 displayed potent anti-catabolic activity in cartilage explants, with IC 50 values being 2 μM and Conclusions GLPG1972 is an orally bioavailable, potent and selective ADAMTS-5 inhibitor showing significant anti-catabolic activity in cartilage explants. In the DMM model, treatment with GLPG1972 resulted in significant protective effects on both cartilage and subchondral bone pathology. Taken together these results provide support to progress GLPG1972 into the clinic as an oral treatment for OA. References Hunter, D.J., et al. Curr. Opin. Rheumatol. 2009, 21,110–117. a) Glasson, S.S., et al Nature. 2005, Vol 434: 644–8; b) Stanton, H., et al. Nature. 2005, Vol 434: 648–5; c) Little, C.B., et al. Journal of Clinical Investigation. 2007, Vol 117(6):1627–36. Larkin, J. et al. Osteoarthritis Cartilage. 2015, 23 (8): 1254–1266. Little, C.B. and Hunter, D.J. Nat. Rev. Rheumatol. 2013, 9(8):485–497. Disclosure of Interest None declared
Published: 2017
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45. Electroencephalogram and somatosensory evoked potential evaluation for good and poor neurological prognosis after cardiac arrest: a prospective multicenter cohort trial (ProNeCA)

Author: Francesco Lolli, Daniela Audenino, Oriano Mecarelli, Maria Lombardi, M. Spalletti, Maenia Scarpino, Riccardo Carrai, Franco Valzania, Alfonso Marrelli, Aldo Amantini, Eugenio Vitelli, Lucia Politini, Fabio Minicucci, Chiara Minardi, Claudio Callegarin, Adriano Peris, Maria Grazia Celani, Giovanni Lanzo, Antonello Grippo, and Luisa Motti
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Electroencephalography, Hypoxic Ischemic Encephalopathy, Neurology, Multicenter study, Somatosensory evoked potential, Internal medicine, Cohort, Cardiology, Medicine, Neurology (clinical), business, Prospective cohort study
Abstract: Aim: Hypoxic-ischemic-encephalopathy is a severe and frequent neurological complication of successful cardiopulmonary-resuscitation after cardiac arrest. Prognosticating neurological outcomes in patients with hypoxic-ischemic-encephalopathy is challenging and recent guidelines suggest a multimodal approach. Only few studies have analyzed the prognostic power of the association between instrumental tests and, in addition, most of them were monocentric, retrospective and evaluating only poor outcome. Methods/design: We designed a multicenter prospective cohort study to assessing the prognostic power of the association of electroencephalogram and somatosensory evoked potentials for the prediction of both poor and good neurological outcomes at different times after cardiac arrest. Discussion: The results of our study will provide a high level of evidence for the use of neurophysiological evaluation in the current clinical practice.
Published: 2019
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46. Efficacy of lacosamide on seizures and myoclonus in a patient with epilepsia partialis continua

Author: Antonello Grippo, L Bucciardini, Alessandro Vagaggini, M. Spalletti, Aldo Amantini, and A. Comanducci
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Neurology, Lacosamide, Epilepsia partialis continua, Epilepsia Partialis Continua, Status epilepticus, Refractory, Acetamides, mental disorders, medicine, Humans, Neuroradiology, business.industry, Neuropsychology, General Medicine, medicine.disease, nervous system diseases, Hematoma, Subdural, Anticonvulsants, Neurology (clinical), medicine.symptom, business, Myoclonus, medicine.drug
Abstract: A 39-year-old male with epilepsia partialis continua, refractory to first- and second-line antiepileptic drugs, is described. Lacosamide produced a progressive antiepileptic effect on Jacksonian motor seizures and subsequently on positive myoclonus, which developed into negative myoclonus before complete resolution. Our report confirms the efficacy of lacosamide on focal motor refractory status epilepticus and documents a unique effect of lacosamide on seizure semiology.
Published: 2013
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47. Axitinib induces senescence-associated cell death and necrosis in glioma cell lines: The proteasome inhibitor, bortezomib, potentiates axitinib-induced cytotoxicity in a p21(Waf/Cip1) dependent manner

Author: Matteo Santoni, Giorgio Santoni, Claudio Cardinali, Giovanni Bernardini, Consuelo Amantini, Maria Beatrice Morelli, Massimo Nabissi, and Angela Santoni
Subjects: 0301 basic medicine, Cyclin-Dependent Kinase Inhibitor p21, Programmed cell death, Cell cycle checkpoint, Indazoles, senescence, Axitinib, Cell Survival, axitinib, glioblastoma, bortezomib, p21, Gene Expression, Mitosis, Pharmacology, Bortezomib, 03 medical and health sciences, Necrosis, 0302 clinical medicine, Glioma, Cell Line, Tumor, medicine, Humans, U87, Mitotic catastrophe, neoplasms, Protein Kinase Inhibitors, Cellular Senescence, Cell Death, Dose-Response Relationship, Drug, business.industry, Imidazoles, Drug Synergism, medicine.disease, G2 Phase Cell Cycle Checkpoints, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Proteasome inhibitor, Cancer research, business, Reactive Oxygen Species, Proteasome Inhibitors, medicine.drug, DNA Damage, Signal Transduction, Research Paper
Abstract: // Maria Beatrice Morelli 1, 2 , Consuelo Amantini 3 , Massimo Nabissi 1 , Claudio Cardinali 1, 2 , Matteo Santoni 4 , Giovanni Bernardini 2, 5 , Angela Santoni 2, 5 , Giorgio Santoni 1 1 School of Pharmacy, University of Camerino, Camerino, Italy 2 Department of Molecular Medicine, Sapienza University, Rome, Italy 3 School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy 4 Department of Medical Oncology, Polytechnic University of Marche, Ancona, Italy 5 I.N.M. Neuromed, Pozzilli, Isernia, Italy Correspondence to: Giorgio Santoni, email: giorgio.santoni@unicam.it Keywords: axitinib, glioblastoma, bortezomib, p21, senescence Received: August 02, 2016 Accepted: November 18, 2016 Published: December 01, 2016 ABSTRACT Glioblastoma is associated with a poor overall survival despite new treatment advances. Antiangiogenic strategies targeting VEGF based on tyrosine kinase inhibitors (TKIs) are currently undergoing extensive research for the treatment of glioma. Herein we demonstrated that the TKI axitinib induces DNA damage response (DDR) characterized by γ-H2AX phosphorylation and Chk1 kinase activation leading to G2/M cell cycle arrest and mitotic catastrophe in U87, T98 and U251 glioma cell lines. Moreover, we found that p21(Waf1/Cip1) increased levels correlates with induction of ROS and senescence-associated cell death in U87 and T98 cell lines, which are reverted by N-acetyl cysteine pretreatment. Conversely, U251 cell line showed a resistant phenotype in response to axitinib treatment, as evidenced by cell cycle arrest but no sign of cell death. The combinatorial use of axitinib with other therapies, with the aim of inhibiting multiple signaling pathways involved in tumor growth, can increase the efficiency of this TKI. Thus, we addressed the combined effects of axitinib with no toxic doses of the proteasome inhibitor bortezomib on the growth of U87 and T98 axitinib-sensitive and axitinib-resistant U251 cell lines. Compared to single treatments, combined exposure was more effective in inhibiting cell viability of all glioma cell lines, although with different cell death modalities. The regulation of key DDR and cell cycle proteins, including Chk1, γ-H2AX and p21(Waf1/Cip1) was also studied in glioma cell lines. Collectively, these findings provide new perspectives for the use of axitinib in combination with Bortezomib to overcome the therapy resistance in gliomas.
Published: 2016

48. Cerebral Fat Embolism After Video-Assisted Thoracic Surgery

Author: Francesco Cappelli, Massimo Pistolesi, Antonello Grippo, Gianni Misuri, Aldo Amantini, Luca Voltolini, Maenia Scarpino, Marco Moretti, and Giovanni Lanzo
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Long bone, Embolism, Fat, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Neuroimaging, medicine, Humans, Fat embolism, medicine.diagnostic_test, business.industry, Intracranial Embolism, Thoracic Surgery, Video-Assisted, Magnetic resonance imaging, Electroencephalography, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Surgery, Pneumonia, medicine.anatomical_structure, Embolism, Cardiothoracic surgery, Female, Radiology, Cardiology and Cardiovascular Medicine, business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery
Abstract: Cerebral fat embolism (CFE) is an uncommon disease occurring mainly after traumatic lower limb long bone fractures. A 64-year-old woman with pneumonia and bilateral pleural effusion underwent video-assisted thoracic surgery (VATS). After 3 days, the patient had an acute decrease in consciousness level followed by the onset of seizures and right hemiparesis. Brain computed tomography and magnetic resonance imaging showed findings suggestive of CFE. CFE occurring after an uncommon nontraumatic cause of fat embolism, such as VATS, is a rare clinical event whose diagnosis could be challenging. Neuroimaging can hasten diagnosis and prevent other unnecessary investigations and treatments.
Published: 2016

49. Post-transcriptional regulation of 5'-untranslated regions of human Transient Receptor Potential Vanilloid type-1 (TRPV-1) channels: role in the survival of glioma patients

Author: Massimo Nabissi, Matteo Santoni, Antonietta Arcella, Claudio Cardinali, Angela Santoni, Giovanni Bernardini, Giorgio Santoni, Maria Beatrice Morelli, and Consuelo Amantini
Subjects: 0301 basic medicine, Untranslated region, survival rate, Time Factors, Five prime untranslated region, RNA Stability, TRPV1, TRPV Cation Channels, Kaplan-Meier Estimate, Transfection, TRPV, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Glioma, medicine, 5’UTR, Humans, RNA, Messenger, RNA Processing, Post-Transcriptional, Post-transcriptional regulation, Survival rate, Proportional Hazards Models, Sirolimus, Brain Neoplasms, business.industry, glioblastoma, medicine.disease, Molecular medicine, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, 5'UTR, 030220 oncology & carcinogenesis, Immunology, Neoplastic Stem Cells, Cancer research, Nucleic Acid Conformation, lipids (amino acids, peptides, and proteins), prognosis, 5' Untranslated Regions, business, Half-Life, Research Paper
Abstract: // Massimo Nabissi 1 , Maria Beatrice Morelli 2 , Antonietta Arcella 3 , Claudio Cardinali 2 , Matteo Santoni 4 , Giovanni Bernardini 2, 3 , Angela Santoni 2, 3 , Giorgio Santoni 1 , Consuelo Amantini 5 1 School of Pharmacy, Experimental Medicine Section, University of Camerino, Camerino (MC), Italy 2 Department of Molecular Medicine, Sapienza University, Rome (RM), Italy 3 I.N.M. Neuromed, Pozzilli, Isernia (IS), Italy 4 Department of Medical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona (AN), Italy 5 School of Biosciences and Veterinary Medicine, University of Camerino, Camerino (MC), Italy Correspondence to: Massimo Nabissi, email: massimo.nabissi@unicam.it Consuelo Amantini, email: consuelo.amantini@unicam.it Keywords: TRPV1, glioblastoma, 5’UTR, survival rate, prognosis Received: August 02, 2016 Accepted: October 14, 2016 Published: November 05, 2016 ABSTRACT The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel is a non-selective cation channel belonging to the Transient Receptor Potential family; variation of its expression has been correlated to glioma progression. In human, TRPV1 transcripts display a remarkable homogeneity differing only for the 5'-untranslated region (5’UTR) sequence that generates four variants encoding the same protein. Herein, we investigated the role of the 5’UTR sequences in TRPV1 transcripts stability, regulation of translation, expression in glioma cells and tissues. In addition, the expression of 5’UTR TRPV1 variants as prognostic factor in the survival of glioblastoma patients was evaluated. The expression level for each 5’UTR and their stability was evaluated by RT-PCR analysis. The effect of rapamycin and interferon-gamma in 5’UTR-regulating TRPV1 translation was determined by western blot analysis in glioma cell lines. We demonstrated that the 5’UTR influences the stability and translation efficacy of TRPV1 transcripts, and that TRPV1 variant three (TRPV1 v3 ) was the most stable and the only variant expressed in GBM samples and in glioma stem-like cells. Furthermore, we found that TRPV1 v3 expression levels correlate with patient’s survival, suggesting that it may represent a potential prognostic marker for patients with glioma.
Published: 2016

50. Diagnostic accuracy of neurophysiological criteria for early diagnosis of AIDP: a prospective study

Author: Antonello Grippo, Maenia Scarpino, Giovanni Lanzo, Riccardo Carrai, Aldo Amantini, Alessandro Barilaro, Francesco Lolli, M. Spalletti, and Francesco Fattapposta
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Pediatrics, Neurology, Adolescent, Neural Conduction, Diagnostic accuracy, acute inflammatory demyelinating polyneuropathy, Cohort study, electrodiagnosis, Guillain-Barré syndrome, Guillain-Barre Syndrome, Sensitivity and Specificity, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Physiology (medical), medicine, Humans, In patient, Prospective Studies, Young adult, Prospective cohort study, Aged, Aged, 80 and over, Guillain-Barre syndrome, business.industry, Electrodiagnosis, General Medicine, Middle Aged, medicine.disease, 030104 developmental biology, Early Diagnosis, Acute Inflammatory Demyelinating Polyneuropathy, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Summary Objective To assess the diagnostic accuracy of electrodiagnostic (EDX) criteria for the early detection and characterization of Guillain-Barre syndrome (GBS) in clinical practice. Methods We conducted a prospective study in patients referred for an EDX exam with clinical suspicion of GBS. We evaluated four sets of neurophysiological criteria and four neurophysiological tests among those recently proposed for the early diagnosis of GBS. Results We recruited 84 patients. Acute inflammatory demyelinating polyneuropathy (AIDP) was the final diagnosis in 23 patients. No axonal forms were found. The best sensitivity was obtained using Rajabally et al.’s criteria (82.1%), whereas the specificity was 90.0% for Ho et al.’s and Hadden et al.’s criteria and 100% for the Dutch GBS study group and Rajabally's criteria. Regarding the neurophysiological tests proposed for early diagnosis, the sensitivity ranged from 16.6 to 100%, whereas specificity ranged from 73.1 to 98.3%. Conclusion The Dutch GBS study group and Rajabally et al.’s criteria showed an optimal combination of sensitivity and specificity for clinical practice, although with a slightly higher sensitivity for Rajabally et al.’s criteria. None of the neurophysiological parameters recently proposed for early diagnosis have good diagnostic accuracy for clinical application. Significance In a real clinical setting with patients referred by neurologists and emergency doctors, an EDX study performed within a week of symptom onset supports the diagnosis of AIDP in 82% of cases.
Published: 2016

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