Search

Your search keyword '"Elaine Lui"' showing total 15 results
Start Over Author "Elaine Lui" Publication Year Range Last 3 years
15 results on '"Elaine Lui"'

1. An osteoinductive and biodegradable intramedullary implant accelerates bone healing and mitigates complications of bone transport in male rats

Author

Sien Lin, Hirotsugu Maekawa, Seyedsina Moeinzadeh, Elaine Lui, Hossein Vahid Alizadeh, Jiannan Li, Sungwoo Kim, Michael Poland, Benjamin C. Gadomski, Jeremiah T. Easley, Jeffrey Young, Michael Gardner, David Mohler, William J. Maloney, and Yunzhi Peter Yang

Subjects
Science
Abstract

Abstract Bone transport is a surgery-driven procedure for the treatment of large bone defects. However, challenging complications include prolonged consolidation, docking site nonunion and pin tract infection. Here, we develop an osteoinductive and biodegradable intramedullary implant by a hybrid tissue engineering construct technique to enable sustained delivery of bone morphogenetic protein-2 as an adjunctive therapy. In a male rat bone transport model, the eluting bone morphogenetic protein-2 from the implants accelerates bone formation and remodeling, leading to early bony fusion as shown by imaging, mechanical testing, histological analysis, and microarray assays. Moreover, no pin tract infection but tight osseointegration are observed. In contrast, conventional treatments show higher proportion of docking site nonunion and pin tract infection. The findings of this study demonstrate that the novel intramedullary implant holds great promise for advancing bone transport techniques by promoting bone regeneration and reducing complications in the treatment of bone defects.

Published
2023
Full Text
View/download PDF

2. Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

Author

Sara Larivière, Jessica Royer, Raúl Rodríguez-Cruces, Casey Paquola, Maria Eugenia Caligiuri, Antonio Gambardella, Luis Concha, Simon S. Keller, Fernando Cendes, Clarissa L. Yasuda, Leonardo Bonilha, Ezequiel Gleichgerrcht, Niels K. Focke, Martin Domin, Felix von Podewills, Soenke Langner, Christian Rummel, Roland Wiest, Pascal Martin, Raviteja Kotikalapudi, Terence J. O’Brien, Benjamin Sinclair, Lucy Vivash, Patricia M. Desmond, Elaine Lui, Anna Elisabetta Vaudano, Stefano Meletti, Manuela Tondelli, Saud Alhusaini, Colin P. Doherty, Gianpiero L. Cavalleri, Norman Delanty, Reetta Kälviäinen, Graeme D. Jackson, Magdalena Kowalczyk, Mario Mascalchi, Mira Semmelroch, Rhys H. Thomas, Hamid Soltanian-Zadeh, Esmaeil Davoodi-Bojd, Junsong Zhang, Gavin P. Winston, Aoife Griffin, Aditi Singh, Vijay K. Tiwari, Barbara A. K. Kreilkamp, Matteo Lenge, Renzo Guerrini, Khalid Hamandi, Sonya Foley, Theodor Rüber, Bernd Weber, Chantal Depondt, Julie Absil, Sarah J. A. Carr, Eugenio Abela, Mark P. Richardson, Orrin Devinsky, Mariasavina Severino, Pasquale Striano, Domenico Tortora, Erik Kaestner, Sean N. Hatton, Sjoerd B. Vos, Lorenzo Caciagli, John S. Duncan, Christopher D. Whelan, Paul M. Thompson, Sanjay M. Sisodiya, Andrea Bernasconi, Angelo Labate, Carrie R. McDonald, Neda Bernasconi, and Boris C. Bernhardt

Subjects
Science
Abstract

Epilepsy is a brain network disorder with associated genetic risk factors. Here, the authors show that spatial patterns of transcriptomic vulnerability co-vary with structural brain network alterations in focal and generalized epilepsy.

Published
2022
Full Text
View/download PDF

3. Hybprinting for musculoskeletal tissue engineering

Author

Jiannan Li, Carolyn Kim, Chi-Chun Pan, Aaron Babian, Elaine Lui, Jeffrey L. Young, Seyedsina Moeinzadeh, Sungwoo Kim, and Yunzhi Peter Yang

Subjects
tissue engineering, Biotechnology, materials science, biomaterials, Science
Abstract

Summary: This review presents bioprinting methods, biomaterials, and printing strategies that may be used for composite tissue constructs for musculoskeletal applications. The printing methods discussed include those that are suitable for acellular and cellular components, and the biomaterials include soft and rigid components that are suitable for soft and/or hard tissues. We also present strategies that focus on the integration of cell-laden soft and acellular rigid components under a single printing platform. Given the structural and functional complexity of native musculoskeletal tissue, we envision that hybrid bioprinting, referred to as hybprinting, could provide unprecedented potential by combining different materials and bioprinting techniques to engineer and assemble modular tissues.

Published
2022
Full Text
View/download PDF

4. Event‐based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross‐sectional data

Author

Seymour M, Lopez, Leon M, Aksman, Neil P, Oxtoby, Sjoerd B, Vos, Jun, Rao, Erik, Kaestner, Saud, Alhusaini, Marina, Alvim, Benjamin, Bender, Andrea, Bernasconi, Neda, Bernasconi, Boris, Bernhardt, Leonardo, Bonilha, Lorenzo, Caciagli, Benoit, Caldairou, Maria Eugenia, Caligiuri, Angels, Calvet, Fernando, Cendes, Luis, Concha, Estefania, Conde-Blanco, Esmaeil, Davoodi-Bojd, Christophe, de Bézenac, Norman, Delanty, Patricia M, Desmond, Orrin, Devinsky, Martin, Domin, John S, Duncan, Niels K, Focke, Sonya, Foley, Francesco, Fortunato, Marian, Galovic, Antonio, Gambardella, Ezequiel, Gleichgerrcht, Renzo, Guerrini, Khalid, Hamandi, Victoria, Ives-Deliperi, Graeme D, Jackson, Neda, Jahanshad, Simon S, Keller, Peter, Kochunov, Raviteja, Kotikalapudi, Barbara A K, Kreilkamp, Angelo, Labate, Sara, Larivière, Matteo, Lenge, Elaine, Lui, Charles, Malpas, Pascal, Martin, Mario, Mascalchi, Sarah E, Medland, Stefano, Meletti, Marcia E, Morita-Sherman, Thomas W, Owen, Mark, Richardson, Antonella, Riva, Theodor, Rüber, Ben, Sinclair, Hamid, Soltanian-Zadeh, Dan J, Stein, Pasquale, Striano, Peter N, Taylor, Sophia I, Thomopoulos, Paul M, Thompson, Manuela, Tondelli, Anna Elisabetta, Vaudano, Lucy, Vivash, Yujiang, Wang, Bernd, Weber, Christopher D, Whelan, Roland, Wiest, Gavin P, Winston, Clarissa Lin, Yasuda, Carrie R, McDonald, Daniel C, Alexander, Sanjay M, Sisodiya, Andre, Altmann, and Rhys H, Thomas

Subjects
Epilepsy, Sclerosis, 3,979, disease progression, duration of illness, event-based model, patient staging [Key Points, MTLE, Word Count], 3 [Word Count], 610 Medicine & health, Key Points, Hippocampus, Magnetic Resonance Imaging, Cross-Sectional Studies, Epilepsy, Temporal Lobe, Neurology, Humans, Neurology (clinical), Atrophy, patient staging, Biomarkers
Abstract

Objective: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross‐sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE‐HS) correlate with clinical features. Methods: We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1‐weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA‐Epilepsy consortium, comprising 804 people with MTLE‐HS and 1625 healthy controls from 25 centers. Features with a moderate case–control effect size (Cohen d ≥ .5) were used to train an event‐based model (EBM), which estimates a sequence of disease‐specific biomarker changes from cross‐sectional data and assigns a biomarker‐based fine‐grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance. Results: In MTLE‐HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10−16), age at onset (ρ = −.18, p = 9.82 × 10−7), and ASM resistance (area under the curve = .59, p = .043, Mann–Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE‐HS with mild or nondetectable abnormality on T1W MRI. Significance: From cross‐sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE‐HS subjects in other cohorts and help establish connections between imaging‐based progression staging and clinical features.

Published
2022

5. Impact of Different Artificial Intelligence User Interfaces on Lung Nodule and Mass Detection on Chest Radiographs

Author

Jennifer S. N. Tang, Jeffrey K. C. Lai, John Bui, Wayland Wang, Paul Simkin, Dayu Gai, Jenny Chan, Diane M. Pascoe, Stefan B. Heinze, Frank Gaillard, and Elaine Lui

Subjects
Radiological and Ultrasound Technology, Artificial Intelligence, Radiology, Nuclear Medicine and imaging, Original Research
Abstract

PURPOSE: To explore the impact of different user interfaces (UIs) for artificial intelligence (AI) outputs on radiologist performance and user preference in detecting lung nodules and masses on chest radiographs. MATERIALS AND METHODS: A retrospective paired-reader study with a 4-week washout period was used to evaluate three different AI UIs compared with no AI output. Ten radiologists (eight radiology attending physicians and two trainees) evaluated 140 chest radiographs (81 with histologically confirmed nodules and 59 confirmed as normal with CT), with either no AI or one of three UI outputs: (a) text-only, (b) combined AI confidence score and text, or (c) combined text, AI confidence score, and image overlay. Areas under the receiver operating characteristic curve were calculated to compare radiologist diagnostic performance with each UI with their diagnostic performance without AI. Radiologists reported their UI preference. RESULTS: The area under the receiver operating characteristic curve improved when radiologists used the text-only output compared with no AI (0.87 vs 0.82; P < .001). There was no difference in performance for the combined text and AI confidence score output compared with no AI (0.77 vs 0.82; P = .46) and for the combined text, AI confidence score, and image overlay output compared with no AI (0.80 vs 0.82; P = .66). Eight of the 10 radiologists (80%) preferred the combined text, AI confidence score, and image overlay output over the other two interfaces. CONCLUSION: Text-only UI output significantly improved radiologist performance compared with no AI in the detection of lung nodules and masses on chest radiographs, but user preference did not correspond with user performance. Keywords: Artificial Intelligence, Chest Radiograph, Conventional Radiography, Lung Nodule, Mass Detection © RSNA, 2023

Published
2023

6. A bioactive synthetic membrane improves bone healing in a preclinical nonunion model

Author

Malcolm R. DeBaun, Brett P. Salazar, Yan Bai, Michael J. Gardner, Yunzhi Peter Yang, Chi-chun Pan, Alex Martin Stahl, Seydesina Moeinzadeh, Sungwoo Kim, Elaine Lui, Carolyn Kim, Sien Lin, L. Henry Goodnough, and Harsh Wadhwa

Subjects
Calcium Phosphates, Animals, Humans, Polymethyl Methacrylate, General Earth and Planetary Sciences, Femur, Article, Fracture Fixation, Intramedullary, Rats, General Environmental Science
Abstract

OBJECTIVES: High energy long bone fractures with critical bone loss are at risk for nonunion without strategic intervention. We hypothesize that a synthetic membrane implanted at a single stage improves bone healing in a preclinical nonunion model. METHODS: Using standard laboratory techniques, microspheres encapsulating bone morphogenic protein-2 (BMP2) or platelet derived growth factor (PDGF) were designed and coupled to a type 1 collagen sheet. Critical femoral defects were created in rats and stabilized by locked retrograde intramedullary nailing. The negative control group had an empty defect. The induced membrane group (positive control) had a polymethylmethacrylate spacer inserted into the defect for four weeks and replaced with a bare polycaprolactone/beta-tricalcium phosphate (PCL/β-TCP) scaffold at a second stage. For the experimental groups, a bioactive synthetic membrane embedded with BMP2, PDGF or both enveloped a PCL/β-TCP scaffold was implanted in a single stage. Serial radiographs were taken at 1, 4, 8, and 12 weeks postoperatively from the definitive procedure and evaluated by two blinded observers using a previously described scoring system to judge union as primary outcome. RESULTS: All experimental groups demonstrated better union than the negative control (p=0.01). The groups with BMP2 incorporated into the membrane demonstrated higher average union Mehta scores than the other groups (p=0.01). The induced membrane group performed similarly to the PDGF group. Complete union was only demonstrated in groups with BMP2-eluting membranes. CONCLUSIONS: A synthetic membrane comprised of type 1 collagen embedded with controlled release BMP2 improved union of critical bone defects in a preclinical nonunion model.

Published
2022

7. The efficiency of genetically modified mesenchymal stromal cells combined with a functionally graded scaffold for bone regeneration in corticosteroid-induced osteonecrosis of the femoral head in rabbits

Author

Masanori Tsubosaka, Masahiro Maruyama, Elaine Lui, Seyedsina Moeinzadeh, Elijah Ejun Huang, Junichi Kushioka, Hirohito Hirata, Charu Jain, Hunter W. Storaci, Calvin Chan, Masakazu Toya, Qi Gao, Victoria Teissier, Huaishuang Shen, Xueping Li, Ning Zhang, Tomoyuki Matsumoto, Ryosuke Kuroda, Stuart B. Goodman, and Yunzhi Peter Yang

Subjects
Biomaterials, Metals and Alloys, Biomedical Engineering, Ceramics and Composites
Abstract

Core decompression (CD) with mesenchymal stromal cells (MSCs) is an effective therapy for early-stage osteonecrosis of the femoral head (ONFH). Preconditioning of MSCs, using inflammatory mediators, is widely used in immunology and various cell therapies. We developed a three-dimensional printed functionally graded scaffold (FGS), made of β-TCP and PCL, for cell delivery at a specific location. The present study examined the efficacy of CD treatments with genetically modified (GM) MSCs over-expressing PDGF-BB (PDGF-MSCs) or GM MSCs co-over-expressing IL-4 and PDGF-BB and preconditioned for three days of exposure to lipopolysaccharide and tumor necrosis factor-alpha (IL-4-PDGF-pMSCs) using the FGS for treating steroid-induced ONFH in rabbits. We compared CD without cell-therapy, with IL-4-PDGF-pMSCs alone, and with FGS loaded with PDGF-MSCs or IL-4-PDGF-pMSCs. For the area inside the CD, the bone volume in the CD alone was higher than in both FGS groups. The IL-4-PDGF-pMSCs alone and FGS + PDGF-MSCs reduced the occurrence of empty lacunae and improved osteoclastogenesis. There was no significant difference in angiogenesis among the four groups. The combined effect of GM MSCs or pMSCs and the FGS was not superior to the effect of each alone. To establish an important adjunctive therapy for CD for early ONFH in the future, it is necessary and essential to develop an FGS that delivers biologics appropriately and provides structural and mechanical support.

Published
2022

8. Bioprinting for Bone Tissue Engineering

Author

Chi Chun Pan, Carolyn Kim, Jiannan Li, Elaine Lui, Brett Salazar, Stuart B. Goodman, and Yunzhi P. Yang

Abstract

Due to its layer-by-layer process, 3D printing enables the formation of complex geometries using multiple materials. Three-dimensional printing for bone tissue engineering is called bioprinting and refers to the use of material-transfer processes for patterning and assembling biologically relevant materials, molecules, cells, tissues, and biodegradable biomaterials with a prescribed organization to accomplish one or more biological functions. Currently, 3D bioprinting constructs can be classified into two categories: acellular and cellular. This article introduces and discusses these two approaches based on the suitable materials for these constructs and the fabrication processes used to manufacture them. The materials are grouped into polymers, metals, and hydrogels. The article also summarizes the commonly used 3D printing techniques for these materials, as well as cell types used for various applications. Lastly, current challenges in tissue engineering are discussed.

Published
2022

9. Three Zone Scanning Protocol For Lung Ultrasound: An Anatomical Basis

Author

Alistair G. Royse, Elaine Lui, Dayu Gai, Ximena Cid, David Canty, Andrew Wang, Lindsay Bridgford, and Colin F. Royse

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine
Abstract

Lung ultrasound is rapidly gaining popularity based on point of care ease of use, diagnostic fidelity and lack of ionizing radiation. This was particularly notable at the beginning of the COVID-19 pandemic, where concerns of contamination of the x-ray department led to a reluctance to order frequent chest x-rays. Early COVID-19 lung involvement is of a bronchopneumonia, and patches of consolidation adjacent to the chest wall were easily detectable by ultrasound. A large number of proposed scanning protocols were advocated and are often complex and largely based on traditional stethoscope examination or access points on the chest wall rather than the underlying lung anatomy. A surgical understanding of lung anatomy and related surface anatomy has led us to develop a simplified three zone scanning protocol in 2013. The anterior zone corresponds to the upper lobe, and the posterior zone is divided between upper lobe and lower lobe. The relationship between lung lobes and the surface of the chest wall provides the anatomical basis for a simple three scanning zone lung ultrasound protocol.

Published
2022

10. Worldwide Disparities in Recovery of Cardiac Testing 1 Year Into COVID-19

Author

Andrew J. Einstein, Cole Hirschfeld, Michelle C. Williams, Joao V. Vitola, Nathan Better, Todd C. Villines, Rodrigo Cerci, Leslee J. Shaw, Andrew D. Choi, Sharmila Dorbala, Ganesan Karthikeyan, Bin Lu, Valentin Sinitsyn, Alexey A. Ansheles, Takashi Kudo, Chiara Bucciarelli-Ducci, Bjarne Linde Nørgaard, Pál Maurovich-Horvat, Roxana Campisi, Elisa Milan, Lizette Louw, Adel H. Allam, Mona Bhatia, Lorenzo Sewanan, Eli Malkovskiy, Yosef Cohen, Michael Randazzo, Jagat Narula, Olga Morozova, Thomas N.B. Pascual, Yaroslav Pynda, Maurizio Dondi, Diana Paez, Gerd Hinterleitner, Yao Lu, Zhuoran Xu, Cole B. Hirschfeld, Ikenna Erinne, Mrinali Shetty, Andrew Choi, Juan Lopez-Mattei, Purvi Parwani, Artan Goda, Ervina Shirka, Salah Bouyoucef, Lydia Chelghoum, Farouk Mansouri, Abdelkader Medjahedi, Qais Naili, Mokhtar Ridouh, Diego Alasia, Lucia Alberghina, Natalia Aramayo, Diego Buchara, Franco Gabriel Busso, Jose Javier Bustos Rivadero, Jorge Camilletti, Hugo Campanelli, Ricardo Belisario Castro, Mariana Daicz, Horacio del Riego, Laura Dragonetti, Diego Echazarreta, Juan Erriest, Fernando Faccio, Adolfo Facello, Hugo Gallegos, Ricardo Geronazzo, Horacio Glait, Victor Hasbani, Victor Jäger, Julio Manuel Lewkowicz, Jose Lotti, Neiva Maciel, Osvaldo Masoli, Edgardo Mastrovito, Maria Medus, Maria Fernanda Merani, Susana Molteni, Marcos Montecinos, Gustavo Parisi, Claudio Pereyra Sueldo, Diego Perez de Arenaza, Luis Quintana, Alejandro Radzinschi, Marcela Redruello, Marina Rodríguez, Horacio Rojas, Arturo Romero Acuña, Daniel Schere, Sonia Traverso, Gustavo Vazquez, Susana Zeffiro, Mari Sakanyan, Scott Beuzeville, Raef Boktor, Michael Crowley, D'Arne Downie, Girish Dwivedi, Barry Elison, Omar Farouque, Kim Jasper, Subodh Joshi, Joseph Lee, Kenneth Lee, Elaine Lui, Peter Mcconachie, Joanne Meaker, Dee Nandurkar, Johanne Neill, Edward O'Rourke, Patricia O'Sullivan, George Pandos, Manuja Premaratne, David Prior, Natalie Rutherford, Connor Saunders, Kim Taubman, Andrew Tauro, Andrew Taylor, James Theuerle, Paul Thomas, Jonathan Tow, Anthony Upton, Shankar Vamadevan, Victor Wayne, Eva Alina Wegner, David Wong, John Younger, Dietrich Beitzke, Gudrun Feuchtner, Oliver Sommer, Konrad Weiss, Natallia Maroz-Vadalazhskaya, Uladzimir Tserakhau, Filip Homans, Caroline M. Van De Heyning, Raúl Araujo, Valentina Soldat-Stankovic, Sinisa Stankovic, Augusto Almeida, Carlos Anselmi, Guilherme S.A. Azevedo, Marcio Sommer Bittencourt, Diego Bromfman Pianta, Estevan Cabeda, Lara Carreira, Igor Coelho, Fernando de Amorim Fernandes, Andrea de Lorenzo, Roberta Delgado, Fernanda Erthal, Fabio Fernandes, Juliano Fernandes, Thiago Ferreira de Souza, Murilo Foppa, Wilson Furlan Matos Alves, Cibele Gontijo, Ilan Gottlieb, Gabriel Grossman, Maria Helena Albernaz Siqueira, Cesar Higa Nomura, Katia Hiromoto Koga, Ronaldo Lima, Rafael Lopes, Hugo Humberto Marçal Filho, Paulo Masiero, Luiz Mastrocola, Maria Eduarda Menezes de Siqueira, Claudio Mesquita, Danilo Naves, Filipe Penna, Ibraim Pinto, Thércio Rocha, Juliana Leal Rocha, Alfredo Rodrigues, Leila Salioni, Adelina Sanches, Marcelo Santos, Leonardo Sara Da Silva, Paulo Schvartzman, Cristina Sebastião Matushita, Tiago Senra, Marcelo Silva, Carlos Eduardo Soares, Bernardo Spiro, Carlos Eduardo Suaide Silva, Rafael Torres, Guilherme Urpia Monte, Andrea Vilela, Alexandre Volney Villa, Joao Vitola, Themissa Voss, Roberto Waltrick, Marcello Zapparoli, Hamid Naseer, Marina Garcheva-Tsacheva, Tiémégna Florence Ouattara, Sarameth Thou, Soley Varoeun, Gad Abikhzer, Rob Beanlands, Michael Chetrit, Dominique Dabreo, Carole Dennie, Matthias Friedrich, Mohmmed Nassoh Hafez, Kate Hanneman, Robert Miller, Anastasia Oikonomou, Idan Roifman, Gary Small, Vikas Tandon, Adwait Trivedi, James White, Katherine Zukotynski, Rita Alay, Carmen Concha, Teresa Massardo, Pedro Abad, Kelly Anzola, Harold Arturo, Luis Benitez, Alberto Cadena, Carlos Caicedo Zamudio, Antonio Calderón, Claudia T. Gutierrez Villamil, Claudia Jaimes, Juan L. Londono, Nelson Lopez, Sonia Merlano-Gaitan, Ramon Murgieitio-Cabrera, Manuel Valencia, Damiana Vergel, Alejandro Zuluaga Santamaria, Felix Solis, Tonci Batinic, Maja Franceschi, Maja Hrabak Paar, Marina Prpic, Cuba: Juan Felipe Batista, Lazaro Omar Cabrera, Amalia Peix, Yamilé Peña, Luis Manuel Rochela Vázquez, Ioannis Ntalas, Milan Kaminek, Vladimir Kincl, Otto Lang, Jawdat Abdulla, Morten Bøttcher, Martin Busk, Uka Geisler, Lars C. Gormsen, Nicolaj Hansson, Søren Hess, Jens Hove, Lars Thorbjoern Jensen, Magnus T. Jensen, Kristian Hay Kragholm, Bjarne L. Nørgaard, Kristian Øvrehus, Jan Rasmussen, Niels Peter Rønnow Sand, Hanne Sondergaard, Tomas Zaremba, Herwin Speckter, Nelson Amores, Mayra Sanchez Velez, Taghreed Abd Alrahman, Sherif Abd Elsamad, Alia Abdelfattah, Adel Allam, Sameh Elkaffas, Mona Hassan, Elshaymaa Hussein, Ahmed Ibrahim, Ahmed Kandeel, Mohamed Mandour Ali, Mahmoud Shaaban, Camila Flores, Verónica Vanesa Gómez Leiva, Anita Liiver, Martti Larikka, Valtteri Uusitalo, Denis Agostini, Clothilde Berger, Matthieu Dietz, Fabien Hyafil, Mickaël Ohana, Kevin Prigent, Hamza Regaieg, Laure Sarda-Mantel, Darach O. H-Ici, Harold Ayetey, George Angelidis, Christina Fragkaki, Chrysoula Fragkiadaki, Panagiotis Georgoulias, Maria Koutelou, Elena Kyrozi, Niki Lama, Vassilis Prassopoulos, Michael Spartalis, Theodora Zaglavara, Carla Gonzalez, Goleat Gutierrez, Alejandro Maldonado, Yassine Martinez, Attila Kovács, Bálint Szilveszter, Nilesh Banthia, Vivek Bhat, Partha Choudhury, Vijay Sai Chowdekar, Johann Christopher, Tushar Garg, Naresh Kumar Goyal, Ripen Kumar Gupta, Abhishek Gupta, Julie Hephzibah, Shashank Jain, Jesu Krupa, Parveen Kumar, Sukriti Kumar, Arati Lalchandani, Animesh Mishra, Vivaswan Dutt Mishra, Parul Mohan, Ahmad Ozair, Shivani Pandey, Ramanathapuram Parameswaran, Chetan Patel, Tapan Patel, Shivani Patel, Leena Robinson Vimala, Dr Pradosh Kumar Sarangi, Shantanu Sengupta, Arvind Sethi, Amit Sharma, Awadhesh Kumar Sharma, Punit Sharma, Apurva Shrigiriwar, Santosh Singh, Harpreet Singh, Ashwani Sood, Atul Verma, Ajay Vyas, Erwin Affandi Soeriadi, Edison Bun, Febby Hutomo, Hilman Syawaluddin, Ryan Yudistiro, Amjed Albadr, Majid Assadi, Farshad Emami, Alireza Emami-Ardekani, Saeed Farzanehfar, Ramezan Jafari, Reyhaneh Manafi-Farid, Maryam Tajik, Yoav Arnson, Shmuel Fuchs, Ronen Goldkorn, John Kennedy, Marina Leitman, Aryeh Shalev, Wanda Acampa, Domenico Albano, Pierpaolo Alongi, Gaspare Arnone, Roberta Assante, Anna Baritussio, Matteo Bauckneht, Francesco Bianco, Rachele Bonfiglioli, Francesco Bovenzi, Isabella Bruno, Andrea Bruno, Elena Busnardo, Elena Califaretti, Roberta Casoni, Vittorio Censullo, Franca Chierichetti, Marcello Chiocchi, Corrado Cittanti, Alberto Clemente, Alberto Cuocolo, Maria Luisa De Rimini, Giuseppe De Vincentis, Veronica Della Tommasina, Santo Dellegrottaglie, Paola Anna Erba, Laura Evangelista, Lara Faggi, Evelina Faragasso, Luigia Florimonte, Viviana Frantellizzi, Marco Gatti, Angela Gaudiano, Fabrizia Gelardi, Alberto Gerali, Alessia Gimelli, Marco Guglielmo, Lucia Leccisotti, Riccardo Liga, Carlo Liguori, Giampiero Longo, Margherita Maffione, Claudio Marcassa, Giovanni Matassa, Donato Mele, Luca Mircoli, Andrea Paccagnella, Sara Pacella, Federica Padovano, Dario Pellegrini, Valeria Pergola, Luca Pugliese, Natale Quartuccio, Lucia Rampin, Fabrizio Ricci, Giuseppe Rubini, Vincenzo Russo, Gianmario Sambuceti, Alessandra Scatteia, Roberto Sciagrà, Gianluca Spidalieri, Antonella Stefanelli, Carlo Tedeschi, Guido Ventroni, Dainia Baugh, Ernest Madu, Tadao Aikawa, Hiroshi Asano, Shinichiro Fujimoto, Koichiro Fujise, Yoshimitsu Fukushima, Kae Fukuyama, Yasutaka Ichikawa, Reiko Ideguchi, Nobuo Iguchi, Masamichi Imai, Hayato Ishimura, Satoshi Isobe, Kimiteru Ito, Yu Izawa, Toshiaki Kadokami, Tokuo Kasai, Takao Kato, Takashi Kawamoto, Shigeru Kiryu, Shinichiro Kumita, Osamu Manabe, Hirotaka Maruno, Naoya Matsumoto, Masao Miyagawa, Masao Moroi, Shigeki Nagamachi, Kenichi Nakajima, Ryo Nakazato, Mamoru Nanasato, Masanao Naya, Takashi Norikane, Yasutoshi Ohta, Yoichi Otomi, Hideki Otsuka, Noriko Oyama-Manabe, Masaki Saito, Masayoshi Sarai, Junichi Sato, Daisuke Sato, Shinya Shiraishi, Kentaro Takanami, Kazuya Takehana, Yasuyo Taniguchi, Hiroki Teragawa, Nobuo Tomizawa, Kyoko Umeji, Yasushi Wakabayashi, Shinichiro Yamada, Shinya Yamazaki, Tatsuya Yoneyama, Mohammad Rawashdeh, Tairkhan Dautov, Khalid Makhdomi, Mostafa Abass, Masoud Garashi, Qaisar Siraj, Marika Kalnina, Mohamad Haidar, Renata Komiagiene, Giedre Kviecinskiene, Donatas Vajauskas, Noor Khairiah A. Karim, Mady Doucoure, Luise Reichmuth, Anthony Samuel, Mohamed Lemine Dieng, Ambedhkar Shantaram Naojee, Estrella Aguilera Hernandez, Cesar Rene Alducin Tellez, Erick Alexánderson-Rosas, Erika Barragan, Manuel Cabada, Daniel Calderón, Isabel Carvajal-Juarez, José Esparza, Manlio Gerardo Gama-Moreno, Virginia Garcia Quinto, Nelsy Coromoto Gonzalez, Mary Carmen Herrera-Zarza, Aloha Meave, Jesus Gregorio Medina Verdugo, Gabriela Melendez, Rafael Humberto Morales Murguia, Carlos Salvador Navarro Quiroz, Mario Ornelas, Andres Preciado-Anaya, Oscar Ulises Preciado-Gutiérrez, Adriana Puente, Aristóteles Ramírez Salazar, Sandra Graciela Rosales Uvera, Sandra Rosales-Uvera, Jose Antonio Serna Macias, Lilia Sierra-Galan, Lilia M. Sierra-Galan, Juan Carlos Tirado Alderete, Enrique Vallejo, Marc Faraggi, Erdenechimeg Sereegotov, Nouzha Ben Rais, Nadia Ismaili Alaoui, Thiri Kyiphyu, Su Thet Oo, Soe Myat Win, Htin Zar, Ram Ghimire, Madhu Neupane, Andor Glaudemans, Riemer Slart, Derk Verschure, Berry Allen, John Edmond, Clare Mckenzie, Stuart Tie, Niels Van Pelt, Kirsten Worthington, Calum Young, Idrissa Adamou Soli, Shehu Kana, Uchenna Onubogu, Mahmoud Sani, Anders Tjellaug Bråten, Arve Jørgensen, Hanne-Elin Vassbotn, Humoud Al Dhuhli, Zabah Jawa, Naima Tag, Shazia Fatima, Muhammad Babar Imran, Muhammad Numair Younis, Mohammad Saadullah, Yariela Herrera Malo, Dora Lenturut-Katal, Manuel Castillo, José Ortellado, Afroza Akhter, F. Aaysha Cader, Raihan Hussain, Saidur Rahman Khan, Tapati Mandal, Faria Nasreen, Yunqiang An, Dianbo Cao, Lianggeng Gong, Yang Hou, Chongfu Jia, Tao Li, Caiying Li, Hui Liu, Wenya Liu, Jinkang Liu, Ming-Yen Ng, Heshui Shi, Chunxiang Tang, Ximing Wang, Zhaoqian Wang, Yining Wang, Jiang Wu, Yan Yi, Li Yuan, Tong Zhang, Longjiang Zhang, Edith Chavez, Carlos Cruz, Christian Llontop, Rosanna Morales, Paz Abrihan, Asela Bustos-Barroso, Michele Duldulao-Ogbac, Christopher Eduarte, Jerry Obaldo, Alvin Quinon, Belinda San Juan, Carlo Joe San Juan, Marie Rhiamar Sauler-Gomez, Mila Uy, Magdalena Kostkiewicz, Jolanta Kunikowska, Anna Teresinska, Tomasz Urbanik, Nuno Bettencourt, Ricardo Fontes-Carvalho, Cristina Gavina, Lino Gonçalves, Filipe Macedo, Nuno Moreno, Carla Sousa, Ana Teresa Timoteo, Maria João Vidigal, Mahmoud Al Heidous, Subramaniyan Ramanathan, Samer Arnous, Said Aytani, Angela Byrne, Tadhg Gleeson, David Kerins, Julie O'Brien, Ji-In Bang, Henry Bom, Miju Cheon, Gi Jeong Cheon, Sang-Geon Cho, Chae Moon Hong, Yong Hyu Jeong, Won Jun Kang, Yeon-Koo Kang, Ji-Young Kim, So Won Oh, Young So, Ho-Chun Song, Kyoung Sook Won, Soo Woong Yoo, Irena Mitevska, Marija Vavlukis, Barbara Gužic Salobir, Monika Štalc, Theodora Benedek, Marian Pop, Claudiu Stan, Alexey Ansheles, Olga Dariy, Nina Gagarina, Irina Itskovich, Anatoliy Karalkin, Alexander Kokov, Gulya Marina, Ekaterina Migunova, Viktor Pospelov, Daria Ryzhkova, Guzaliya Sayfullina, Vladimir Sergienko, Irina Shurupova, Margarita Vakhromeeva, Nailia Valiullina, Konstantin Zavadovsky, Kirill Zhuravlev, Rami Abazid, Turki Al Garni, Mirvat Alasnag, Ahmed Aljizeeri, Hamid Amer, Ahmad Amro, Hesham Hamdy, Osama Smettei, Dragana Sobic Saranovic, Marina Vlajkovic, Felix Keng, Jason See, Zuzana Berecova, Jana Polakova Mistinova, Osayande Evbuomwan, Nerisha Govender, Jonathan Hack, Bawinile Hadebe, Khanyisile Hlongwa, Mitchell Kaplan, Hoosen Lakhi, Katarina Milos, Moshe Modiselle, Stuart More, Ntanganedzeni Muambadzi, Leonie Scholtz, Manuel Barreiro-Perez, Isabel Blanco, Jordi Broncano, Alicia Camarero, Irene Casáns-Tormo, Javier De Haro, Albert Flotats, Elia García, Ceferino Gutierrez Mendiguchia, Amelia Jimenez-Heffernan, Ruben Leta, Javier Lopez Diaz, Luis Lumbreras Vega, Ana Manovel-Sánchez, Amparo Martinez Monzonis, Bianca Patrut, Virginia Pubul, Ricardo Ruano Perez, Nahla Zeidan, Damayanthi Nanayakkara, Ahmed Suliman, Henrik Engblom, Mustafa Murtadha, Ellen Ostenfeld, Magnus Simonsson, Hatem Alkadhi, Ronny Ralf Buechel, Peter Burger, Christoph Gräni, Christel Kamani, Nadine Kawel-Böhm, Bernd Klaeser, Robert Manka, John Prior, Tawika Kaewchur, Benjapa Khiewvan, Arpakorn Kositwattanarerk, Sirianong Namwongprom, Tanyaluck Thientunyakit, Haluk Burcak Sayman, Mahmut Yüksel, Mugisha Julius Sebikali, Emmy Okello, Pavlo Korol, Iryna Noverko, Maryna Satyr, Tahir Ahmad, Khaled Alfakih, Ivo Andrade, Susan Buckingham, Anda Bularga, John-Paul Carpenter, Graham Cole, David Cusack, Sarojini David, Patrick Davis, Timothy Fairbairn, Arjun Ghosh, Prasad Guntur Ramkumar, Mark Hamilton, Faisal Haque, Benjamin Hudson, Annette Johnstone, V.J. Karthikeyan, Mike Kay, Mohammad Ali Khan, Jamie Kitt, Chen Sheng Low, Elisa Mcalindon, David Mccreavy, Brian Morrissey, Manish Motwani, Dilip Na, Edward Nicol, Dilip Patel, Jonathan Rodrigues, Chris Rofe, Rebecca Schofield, Thomas Semple, Azeem Sheikh, Apurva Sinha, Deepak Subedi, William Topping, Katherine Tweed, Stephen Richard Underwood, Jonathan Weir-Mccall, Hamed Zuhairy, Taimur Abbasi, Shady Abohashem, Sandra Abramson, Mouaz Al-Mallah, Mohan Ashok Kumar, Mallory Balmer-Swain, Daniel Berman, Adam Bernheim, Sabha Bhatti, Robert Biederman, Erik Bieging, Scott Bingham, Stephen Bloom, Sean Blue, Andressa Borges, Kelley Branch, Paco Bravo, Sujatha Buddhe, Matthew Budoff, Renée Bullock-Palmer, Michael Cahill, Candace Candela, Jane Cao, Saurav Chatterjee, Yiannis Chatzizisis, Nita Ray Chaudhuri, Michael Cheezum, Anjali Chelliah, Tiffany Chen, Marcus Chen, Lu Chen, Aalap Chokshi, Jina Chung, Sorin Danciu, William DeSisto, Michael Dilorenzo, Rami Doukky, William Duvall, Maros Ferencik, Cameron Foster, Anthon Fuisz, Michael Gannon, David German, Myron Gerson, Jeffrey Geske, Fadi Hage, Agha Haider, Sofia Haider, Yasmin Hamirani, Karen Hassen, Robert Hendel, Jacqueline Henkel, Stephen Horgan, Mark Hyun, Rajesh Janardhanan, Scott Jerome, Dinesh Kalra, David Kassop, Mona Kinkhabwala, George Kinzfogl, Bernard Koch, Lynne Koweek, Joseph Krepp, Younghoon Kwon, Jay Layer, John Lesser, Steve Leung, Bernadette Lisske, Kathleen Magurany, Jeremy Markowitz, Brenda Mccullough, Azita Moalemi, Chanan Moffitt, Juan Montanez, Warren Moore, Shamil Morayati, Mahmud Mossa-Basha, Zorana Mrsic, Venkatesh Murthy, Prashant Nagpal, Katarina Nelson, Prabhjot Nijjar, Rupal O’Quinn, Edward Passen, Toral Patel, Pravin Patil, Amit Pursnani, Nancy Quachang, Mark Rabbat, Pragya Ranjan, Patricia Rodriguez Lozano, Mary Schemmer, Rebecca Seifried, Nishant Shah, Amee Shah, Sujata Shanbhag, Gaurav Sharma, Robert Skotnicki, Michael Sobczak, Prem Soman, Vincent Sorrell, Monvadi Srichai, Jim Streeter, Leah Strickland, Suliman Suliman, Naghmeh Tebyanian, Dustin Thomas, Randall Thompson, Seth Uretsky, Srikanth Vallurupalli, Marian Vandyck-Acquah, Vikas Verma, Todd Villines, Joseph Weinstein, David Wolinsky, Karolina Zareba, Michael Zgaljardic, Mario Beretta, Rodolfo Ferrando, Miguel Kapitan, Fernando Mut, Omoa Djuraev, Gulnora Rozikhodjaeva, Luisa Vera, Binh Duong Duc, Xuan Canh Nguyen, Phuoc Minh Hiep Nguyen, Translational Immunology Groningen (TRIGR), Cardiovascular Centre (CVC), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Molecular Pharmacology, Drug Design, Einstein, A, Hirschfeld, C, Williams, M, Vitola, J, Better, N, Villines, T, Cerci, R, Shaw, L, Choi, A, Dorbala, S, Karthikeyan, G, Lu, B, Sinitsyn, V, Ansheles, A, Kudo, T, Bucciarelli-Ducci, C, Norgaard, B, Maurovich-Horvat, P, Campisi, R, Milan, E, Louw, L, Allam, A, Bhatia, M, Sewanan, L, Malkovskiy, E, Cohen, Y, Randazzo, M, Narula, J, Morozova, O, Pascual, T, Pynda, Y, Dondi, M, Paez, D, Hinterleitner, G, Lu, Y, Xu, Z, Erinne, I, Shetty, M, Lopez-Mattei, J, Parwani, P, Goda, A, Shirka, E, Bouyoucef, S, Chelghoum, L, Mansouri, F, Medjahedi, A, Naili, Q, Ridouh, M, Alasia, D, Alberghina, L, Aramayo, N, Buchara, D, Busso, F, Bustos Rivadero, J, Camilletti, J, Campanelli, H, Castro, R, Daicz, M, del Riego, H, Dragonetti, L, Echazarreta, D, Erriest, J, Faccio, F, Facello, A, Gallegos, H, Geronazzo, R, Glait, H, Hasbani, V, Jager, V, Lewkowicz, J, Lotti, J, Maciel, N, Masoli, O, Mastrovito, E, Medus, M, Merani, M, Molteni, S, Montecinos, M, Parisi, G, Sueldo, C, Perez de Arenaza, D, Quintana, L, Radzinschi, A, Redruello, M, Rodriguez, M, Rojas, H, Acuna, A, Schere, D, Traverso, S, Vazquez, G, Zeffiro, S, Sakanyan, M, Beuzeville, S, Boktor, R, Crowley, M, Downie, D, Dwivedi, G, Elison, B, Farouque, O, Jasper, K, Joshi, S, Lee, J, Lee, K, Lui, E, Mcconachie, P, Meaker, J, Nandurkar, D, Neill, J, O'Rourke, E, O'Sullivan, P, Pandos, G, Premaratne, M, Prior, D, Rutherford, N, Saunders, C, Taubman, K, Tauro, A, Taylor, A, Theuerle, J, Thomas, P, Tow, J, Upton, A, Vamadevan, S, Wayne, V, Wegner, E, Wong, D, Younger, J, Beitzke, D, Feuchtner, G, Sommer, O, Weiss, K, Maroz-Vadalazhskaya, N, Tserakhau, U, Homans, F, Van De Heyning, C, Araujo, R, Soldat-Stankovic, V, Stankovic, S, Almeida, A, Anselmi, C, Azevedo, G, Bittencourt, M, Pianta, D, Cabeda, E, Carreira, L, Coelho, I, de Amorim Fernandes, F, de Lorenzo, A, Delgado, R, Erthal, F, Fernandes, F, Fernandes, J, Ferreira de Souza, T, Foppa, M, Matos Alves, W, Gontijo, C, Gottlieb, I, Grossman, G, Albernaz Siqueira, M, Nomura, C, Koga, K, Lima, R, Lopes, R, Marcal Filho, H, Masiero, P, Mastrocola, L, Menezes de Siqueira, M, Mesquita, C, Naves, D, Penna, F, Pinto, I, Rocha, T, Rocha, J, Rodrigues, A, Salioni, L, Sanches, A, Santos, M, Da Silva, L, Schvartzman, P, Matushita, C, Senra, T, Silva, M, Soares, C, Spiro, B, Suaide Silva, C, Torres, R, Monte, G, Vilela, A, Villa, A, Voss, T, Waltrick, R, Zapparoli, M, Naseer, H, Garcheva-Tsacheva, M, Ouattara, T, Thou, S, Varoeun, S, Abikhzer, G, Beanlands, R, Chetrit, M, Dabreo, D, Dennie, C, Friedrich, M, Hafez, M, Hanneman, K, Miller, R, Oikonomou, A, Roifman, I, Small, G, Tandon, V, Trivedi, A, White, J, Zukotynski, K, Alay, R, Concha, C, Massardo, T, Abad, P, Anzola, K, Arturo, H, Benitez, L, Cadena, A, Zamudio, C, Calderon, A, Gutierrez Villamil, C, Jaimes, C, Londono, J, Lopez, N, Merlano-Gaitan, S, Murgieitio-Cabrera, R, Valencia, M, Vergel, D, Santamaria, A, Solis, F, Batinic, T, Franceschi, M, Paar, M, Prpic, M, Felipe Batista, C, Cabrera, L, Peix, A, Pena, Y, Rochela Vazquez, L, Ntalas, I, Kaminek, M, Kincl, V, Lang, O, Abdulla, J, Bottcher, M, Busk, M, Geisler, U, Gormsen, L, Hansson, N, Hess, S, Hove, J, Jensen, L, Jensen, M, Kragholm, K, Ovrehus, K, Rasmussen, J, Ronnow Sand, N, Sondergaard, H, Zaremba, T, Speckter, H, Amores, N, Velez, M, Alrahman, T, Elsamad, S, Abdelfattah, A, Elkaffas, S, Hassan, M, Hussein, E, Ibrahim, A, Kandeel, A, Ali, M, Shaaban, M, Flores, C, Gomez Leiva, V, Liiver, A, Larikka, M, Uusitalo, V, Agostini, D, Berger, C, Dietz, M, Hyafil, F, Ohana, M, Prigent, K, Regaieg, H, Sarda-Mantel, L, H-Ici, D, Ayetey, H, Angelidis, G, Fragkaki, C, Fragkiadaki, C, Georgoulias, P, Koutelou, M, Kyrozi, E, Lama, N, Prassopoulos, V, Spartalis, M, Zaglavara, T, Gonzalez, C, Gutierrez, G, Maldonado, A, Martinez, Y, Kovacs, A, Szilveszter, B, Banthia, N, Bhat, V, Choudhury, P, Chowdekar, V, Christopher, J, Garg, T, Goyal, N, Gupta, R, Gupta, A, Hephzibah, J, Jain, S, Krupa, J, Kumar, P, Kumar, S, Lalchandani, A, Mishra, A, Mishra, V, Mohan, P, Ozair, A, Pandey, S, Parameswaran, R, Patel, C, Patel, T, Patel, S, Vimala, L, Kumar Sarangi, D, Sengupta, S, Sethi, A, Sharma, A, Sharma, P, Shrigiriwar, A, Singh, S, Singh, H, Sood, A, Verma, A, Vyas, A, Soeriadi, E, Bun, E, Hutomo, F, Syawaluddin, H, Yudistiro, R, Albadr, A, Assadi, M, Emami, F, Emami-Ardekani, A, Farzanehfar, S, Jafari, R, Manafi-Farid, R, Tajik, M, Arnson, Y, Fuchs, S, Goldkorn, R, Kennedy, J, Leitman, M, Shalev, A, Acampa, W, Albano, D, Alongi, P, Arnone, G, Assante, R, Baritussio, A, Bauckneht, M, Bianco, F, Bonfiglioli, R, Bovenzi, F, Bruno, I, Bruno, A, Busnardo, E, Califaretti, E, Casoni, R, Censullo, V, Chierichetti, F, Chiocchi, M, Cittanti, C, Clemente, A, Cuocolo, A, De Rimini, M, De Vincentis, G, Della Tommasina, V, Dellegrottaglie, S, Erba, P, Evangelista, L, Faggi, L, Faragasso, E, Florimonte, L, Frantellizzi, V, Gatti, M, Gaudiano, A, Gelardi, F, Gerali, A, Gimelli, A, Guglielmo, M, Leccisotti, L, Liga, R, Liguori, C, Longo, G, Maffione, M, Marcassa, C, Matassa, G, Mele, D, Mircoli, L, Paccagnella, A, Pacella, S, Padovano, F, Pellegrini, D, Pergola, V, Pugliese, L, Quartuccio, N, Rampin, L, Ricci, F, Rubini, G, Russo, V, Sambuceti, G, Scatteia, A, Sciagra, R, Spidalieri, G, Stefanelli, A, Tedeschi, C, Ventroni, G, Baugh, D, Madu, E, Aikawa, T, Asano, H, Fujimoto, S, Fujise, K, Fukushima, Y, Fukuyama, K, Ichikawa, Y, Ideguchi, R, Iguchi, N, Imai, M, Ishimura, H, Isobe, S, Ito, K, Izawa, Y, Kadokami, T, Kasai, T, Kato, T, Kawamoto, T, Kiryu, S, Kumita, S, Manabe, O, Maruno, H, Matsumoto, N, Miyagawa, M, Moroi, M, Nagamachi, S, Nakajima, K, Nakazato, R, Nanasato, M, Naya, M, Norikane, T, Ohta, Y, Otomi, Y, Otsuka, H, Oyama-Manabe, N, Saito, M, Sarai, M, Sato, J, Sato, D, Shiraishi, S, Takanami, K, Takehana, K, Taniguchi, Y, Teragawa, H, Tomizawa, N, Umeji, K, Wakabayashi, Y, Yamada, S, Yamazaki, S, Yoneyama, T, Rawashdeh, M, Dautov, T, Makhdomi, K, Abass, M, Garashi, M, Siraj, Q, Kalnina, M, Haidar, M, Komiagiene, R, Kviecinskiene, G, Vajauskas, D, Karim, N, Doucoure, M, Reichmuth, L, Samuel, A, Dieng, M, Naojee, A, Hernandez, E, Alducin Tellez, C, Alexanderson-Rosas, E, Barragan, E, Cabada, M, Calderon, D, Carvajal-Juarez, I, Esparza, J, Gama-Moreno, M, Quinto, V, Gonzalez, N, Herrera-Zarza, M, Meave, A, Medina Verdugo, J, Melendez, G, Morales Murguia, R, Navarro Quiroz, C, Ornelas, M, Preciado-Anaya, A, Preciado-Gutierrez, O, Puente, A, Salazar, A, Rosales Uvera, S, Rosales-Uvera, S, Serna Macias, J, Sierra-Galan, L, Tirado Alderete, J, Vallejo, E, Faraggi, M, Sereegotov, E, Ben Rais, N, Alaoui, N, Kyiphyu, T, Oo, S, Win, S, Zar, H, Ghimire, R, Neupane, M, Glaudemans, A, Slart, R, Verschure, D, Allen, B, Edmond, J, Mckenzie, C, Tie, S, Van Pelt, N, Worthington, K, Young, C, Soli, I, Kana, S, Onubogu, U, Sani, M, Braten, A, Jorgensen, A, Vassbotn, H, Al Dhuhli, H, Jawa, Z, Tag, N, Fatima, S, Imran, M, Younis, M, Saadullah, M, Malo, Y, Lenturut-Katal, D, Castillo, M, Ortellado, J, Akhter, A, Cader, F, Hussain, R, Khan, S, Mandal, T, Nasreen, F, An, Y, Cao, D, Gong, L, Hou, Y, Jia, C, Li, T, Li, C, Liu, H, Liu, W, Liu, J, Ng, M, Shi, H, Tang, C, Wang, X, Wang, Z, Wang, Y, Wu, J, Yi, Y, Yuan, L, Zhang, T, Zhang, L, Chavez, E, Cruz, C, Llontop, C, Morales, R, Abrihan, P, Bustos-Barroso, A, Duldulao-Ogbac, M, Eduarte, C, Obaldo, J, Quinon, A, San Juan, B, San Juan, C, Sauler-Gomez, M, Uy, M, Kostkiewicz, M, Kunikowska, J, Teresinska, A, Urbanik, T, Bettencourt, N, Fontes-Carvalho, R, Gavina, C, Goncalves, L, Macedo, F, Moreno, N, Sousa, C, Timoteo, A, Vidigal, M, Al Heidous, M, Ramanathan, S, Arnous, S, Aytani, S, Byrne, A, Gleeson, T, Kerins, D, O'Brien, J, Bang, J, Bom, H, Cheon, M, Cheon, G, Cho, S, Hong, C, Jeong, Y, Kang, W, Kang, Y, Kim, J, Oh, S, So, Y, Song, H, Won, K, Yoo, S, Mitevska, I, Vavlukis, M, Salobir, B, Stalc, M, Benedek, T, Pop, M, Stan, C, Dariy, O, Gagarina, N, Itskovich, I, Karalkin, A, Kokov, A, Marina, G, Migunova, E, Pospelov, V, Ryzhkova, D, Sayfullina, G, Sergienko, V, Shurupova, I, Vakhromeeva, M, Valiullina, N, Zavadovsky, K, Zhuravlev, K, Abazid, R, Al Garni, T, Alasnag, M, Aljizeeri, A, Amer, H, Amro, A, Hamdy, H, Smettei, O, Saranovic, D, Vlajkovic, M, Keng, F, See, J, Berecova, Z, Mistinova, J, Evbuomwan, O, Govender, N, Hack, J, Hadebe, B, Hlongwa, K, Kaplan, M, Lakhi, H, Milos, K, Modiselle, M, More, S, Muambadzi, N, Scholtz, L, Barreiro-Perez, M, Blanco, I, Broncano, J, Camarero, A, Casans-Tormo, I, De Haro, J, Flotats, A, Garcia, E, Mendiguchia, C, Jimenez-Heffernan, A, Leta, R, Diaz, J, Vega, L, Manovel-Sanchez, A, Monzonis, A, Patrut, B, Pubul, V, Perez, R, Zeidan, N, Nanayakkara, D, Suliman, A, Engblom, H, Murtadha, M, Ostenfeld, E, Simonsson, M, Alkadhi, H, Buechel, R, Burger, P, Grani, C, Kamani, C, Kawel-Bohm, N, Klaeser, B, Manka, R, Prior, J, Kaewchur, T, Khiewvan, B, Kositwattanarerk, A, Namwongprom, S, Thientunyakit, T, Sayman, H, Yuksel, M, Sebikali, M, Okello, E, Korol, P, Noverko, I, Satyr, M, Ahmad, T, Alfakih, K, Andrade, I, Buckingham, S, Bularga, A, Carpenter, J, Cole, G, Cusack, D, David, S, Davis, P, Fairbairn, T, Ghosh, A, Ramkumar, P, Hamilton, M, Haque, F, Hudson, B, Johnstone, A, Karthikeyan, V, Kay, M, Khan, M, Kitt, J, Low, C, Mcalindon, E, Mccreavy, D, Morrissey, B, Motwani, M, Na, D, Nicol, E, Patel, D, Rodrigues, J, Rofe, C, Schofield, R, Semple, T, Sheikh, A, Sinha, A, Subedi, D, Topping, W, Tweed, K, Underwood, S, Weir-Mccall, J, Zuhairy, H, Abbasi, T, Abohashem, S, Abramson, S, Al-Mallah, M, Kumar, M, Balmer-Swain, M, Berman, D, Bernheim, A, Bhatti, S, Biederman, R, Bieging, E, Bingham, S, Bloom, S, Blue, S, Borges, A, Branch, K, Bravo, P, Buddhe, S, Budoff, M, Bullock-Palmer, R, Cahill, M, Candela, C, Cao, J, Chatterjee, S, Chatzizisis, Y, Chaudhuri, N, Cheezum, M, Chelliah, A, Chen, T, Chen, M, Chen, L, Chokshi, A, Chung, J, Danciu, S, Desisto, W, Dilorenzo, M, Doukky, R, Duvall, W, Ferencik, M, Foster, C, Fuisz, A, Gannon, M, German, D, Gerson, M, Geske, J, Hage, F, Haider, A, Haider, S, Hamirani, Y, Hassen, K, Hendel, R, Henkel, J, Horgan, S, Hyun, M, Janardhanan, R, Jerome, S, Kalra, D, Kassop, D, Kinkhabwala, M, Kinzfogl, G, Koch, B, Koweek, L, Krepp, J, Kwon, Y, Layer, J, Lesser, J, Leung, S, Lisske, B, Magurany, K, Markowitz, J, Mccullough, B, Moalemi, A, Moffitt, C, Montanez, J, Moore, W, Morayati, S, Mossa-Basha, M, Mrsic, Z, Murthy, V, Nagpal, P, Nelson, K, Nijjar, P, O'Quinn, R, Passen, E, Patil, P, Pursnani, A, Quachang, N, Rabbat, M, Ranjan, P, Lozano, P, Schemmer, M, Seifried, R, Shah, N, Shah, A, Shanbhag, S, Sharma, G, Skotnicki, R, Sobczak, M, Soman, P, Sorrell, V, Srichai, M, Streeter, J, Strickland, L, Suliman, S, Tebyanian, N, Thomas, D, Thompson, R, Uretsky, S, Vallurupalli, S, Vandyck-Acquah, M, Verma, V, Weinstein, J, Wolinsky, D, Zareba, K, Zgaljardic, M, Beretta, M, Ferrando, R, Kapitan, M, Mut, F, Djuraev, O, Rozikhodjaeva, G, Vera, L, Duc, B, Nguyen, X, Hiep Nguyen, P, Einstein, Andrew J, Hirschfeld, Cole, Williams, Michelle C, Vitola, Joao V, Better, Nathan, Villines, Todd C, Cerci, Rodrigo, Shaw, Leslee J, Choi, Andrew D, Dorbala, Sharmila, Karthikeyan, Ganesan, Lu, Bin, Sinitsyn, Valentin, Ansheles, Alexey A, Kudo, Takashi, Bucciarelli-Ducci, Chiara, Nørgaard, Bjarne Linde, Maurovich-Horvat, Pál, Campisi, Roxana, Milan, Elisa, Louw, Lizette, Allam, Adel H, Bhatia, Mona, Sewanan, Lorenzo, Malkovskiy, Eli, Cohen, Yosef, Randazzo, Michael, Narula, Jagat, Morozova, Olga, Pascual, Thomas N B, Pynda, Yaroslav, Dondi, Maurizio, Paez, Diana, and Cuocolo, Alberto

Subjects
cardiac testing, Health Personnel, delivery of health care, coronavirus, COVID-19, global health, 610 Medicine & health, cardiovascular disease, health personnel, humans, pandemics, surveys and questionnaires, coronaviru, Surveys and Questionnaires, Humans, Cardiology and Cardiovascular Medicine, Delivery of Health Care, Pandemics, COVID-19/epidemiology
Abstract

BACKGROUND: The extent to which health care systems have adapted to the COVID-19 pandemic to provide necessary cardiac diagnostic services is unknown.OBJECTIVES: The aim of this study was to determine the impact of the pandemic on cardiac testing practices, volumes and types of diagnostic services, and perceived psychological stress to health care providers worldwide.METHODS: The International Atomic Energy Agency conducted a worldwide survey assessing alterations from baseline in cardiovascular diagnostic care at the pandemic's onset and 1 year later. Multivariable regression was used to determine factors associated with procedure volume recovery.RESULTS: Surveys were submitted from 669 centers in 107 countries. Worldwide reduction in cardiac procedure volumes of 64% from March 2019 to April 2020 recovered by April 2021 in high- and upper middle-income countries (recovery rates of 108% and 99%) but remained depressed in lower middle- and low-income countries (46% and 30% recovery). Although stress testing was used 12% less frequently in 2021 than in 2019, coronary computed tomographic angiography was used 14% more, a trend also seen for other advanced cardiac imaging modalities (positron emission tomography and magnetic resonance; 22%-25% increases). Pandemic-related psychological stress was estimated to have affected nearly 40% of staff, impacting patient care at 78% of sites. In multivariable regression, only lower-income status and physicians' psychological stress were significant in predicting recovery of cardiac testing.CONCLUSIONS: Cardiac diagnostic testing has yet to recover to prepandemic levels in lower-income countries. Worldwide, the decrease in standard stress testing is offset by greater use of advanced cardiac imaging modalities. Pandemic-related psychological stress among providers is widespread and associated with poor recovery of cardiac testing.

Published
2022

11. Interpretable surface-based detection of focal cortical dysplasias: a multi-centre epilepsy lesion detection study

Author

Hannah Spitzer, Mathilde Ripart, Kirstie Whitaker, Felice D’Arco, Kshitij Mankad, Andrew A Chen, Antonio Napolitano, Luca De Palma, Alessandro De Benedictis, Stephen Foldes, Zachary Humphreys, Kai Zhang, Wenhan Hu, Jiajie Mo, Marcus Likeman, Shirin Davies, Christopher Güttler, Matteo Lenge, Nathan T Cohen, Yingying Tang, Shan Wang, Aswin Chari, Martin Tisdall, Nuria Bargallo, Estefanía Conde-Blanco, Jose Carlos Pariente, Saül Pascual-Diaz, Ignacio Delgado-Martínez, Carmen Pérez-Enríquez, Ilaria Lagorio, Eugenio Abela, Nandini Mullatti, Jonathan O’Muircheartaigh, Katy Vecchiato, Yawu Liu, Maria Eugenia Caligiuri, Ben Sinclair, Lucy Vivash, Anna Willard, Jothy Kandasamy, Ailsa McLellan, Drahoslav Sokol, Mira Semmelroch, Ane G Kloster, Giske Opheim, Letícia Ribeiro, Clarissa Yasuda, Camilla Rossi-Espagnet, Khalid Hamandi, Anna Tietze, Carmen Barba, Renzo Guerrini, William Davis Gaillard, Xiaozhen You, Irene Wang, Sofía González-Ortiz, Mariasavina Severino, Pasquale Striano, Domenico Tortora, Reetta Kälviäinen, Antonio Gambardella, Angelo Labate, Patricia Desmond, Elaine Lui, Terence O’Brien, Jay Shetty, Graeme Jackson, John S Duncan, Gavin P Winston, Lars H Pinborg, Fernando Cendes, Fabian J Theis, Russell T Shinohara, J Helen Cross, Torsten Baldeweg, Sophie Adler, and Konrad Wagstyl

Subjects
Epilepsy, Magnetic Resonance Imaging, Focal cortical dysplasia, Malformations of Cortical Development, Structural MRI, machine learning, Machine learning, Humans, epilepsy, Epilepsies, Partial, Neurology (clinical), focal cortical dysplasia, structural MRI, Retrospective Studies
Abstract

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted ‘gold-standard’ subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

Published
2022

12. Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Author

Bo-yong Park, Sara Larivière, Raul Rodríguez-Cruces, Jessica Royer, Shahin Tavakol, Yezhou Wang, Lorenzo Caciagli, Maria Eugenia Caligiuri, Antonio Gambardella, Luis Concha, Simon S Keller, Fernando Cendes, Marina K M Alvim, Clarissa Yasuda, Leonardo Bonilha, Ezequiel Gleichgerrcht, Niels K Focke, Barbara A K Kreilkamp, Martin Domin, Felix von Podewils, Soenke Langner, Christian Rummel, Michael Rebsamen, Roland Wiest, Pascal Martin, Raviteja Kotikalapudi, Benjamin Bender, Terence J O’Brien, Meng Law, Benjamin Sinclair, Lucy Vivash, Patrick Kwan, Patricia M Desmond, Charles B Malpas, Elaine Lui, Saud Alhusaini, Colin P Doherty, Gianpiero L Cavalleri, Norman Delanty, Reetta Kälviäinen, Graeme D Jackson, Magdalena Kowalczyk, Mario Mascalchi, Mira Semmelroch, Rhys H Thomas, Hamid Soltanian-Zadeh, Esmaeil Davoodi-Bojd, Junsong Zhang, Matteo Lenge, Renzo Guerrini, Emanuele Bartolini, Khalid Hamandi, Sonya Foley, Bernd Weber, Chantal Depondt, Julie Absil, Sarah J A Carr, Eugenio Abela, Mark P Richardson, Orrin Devinsky, Mariasavina Severino, Pasquale Striano, Costanza Parodi, Domenico Tortora, Sean N Hatton, Sjoerd B Vos, John S Duncan, Marian Galovic, Christopher D Whelan, Núria Bargalló, Jose Pariente, Estefania Conde-Blanco, Anna Elisabetta Vaudano, Manuela Tondelli, Stefano Meletti, Xiang-Zhen Kong, Clyde Francks, Simon E Fisher, Benoit Caldairou, Mina Ryten, Angelo Labate, Sanjay M Sisodiya, Paul M Thompson, Carrie R McDonald, Andrea Bernasconi, Neda Bernasconi, and Boris C Bernhardt

Subjects
Adult, Neuroinformatics, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], 610 Medicine & health, Hippocampus, Magnetic Resonance Imaging, behavioral disciplines and activities, Epilepsy, Temporal Lobe, nervous system, Connectome, Humans, Neurology (clinical), Atrophy
Abstract

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.

Published
2022

13. Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia:A MELD study

Author

Jose Carlos Pariente, Antonio Gambardella, Fernando Cendes, Ane Kloster, Ailsa McLellan, Ben Sinclair, Terry O'Brien, Jonathan O'Muircheartaigh, Gavin P. Winston, Mira Semmelroch, Estefanía Conde-Blanco, Torsten Baldeweg, Zachary Humphreys, Xiaozhen You, Elaine Lui, Nandini Mullatti, Clarissa L. Yasuda, Domenico Tortora, Stephen T. Foldes, Jakob Seidlitz, Martin Tisdall, Yawu Liu, Carmen Barba, Petra E. Vértes, Angelo Labate, Shan Wang, Konrad Wagstyl, Lars H. Pinborg, Jothy Kandasamy, Irene Wang, Mathilde Ripart, Mariasavina Severino, Aswin Chari, Lucy Vivash, Shirin Davies, Carmen Pérez-Enríquez, Nathan T. Cohen, John S. Duncan, Ilaria Lagorio, Maria Eugenia Caligiuri, Drahoslav Sokol, Reetta Kälviäinen, Eugenio Abela, William D. Gaillard, Giske Opheim, Jiajie Mo, Anna Willard, Graeme D. Jackson, Jay Shetty, JH Cross, Marcus Likeman, Renzo Guerrini, Wenhan Hu, Katy Vecchiato, Khalid Hamandi, Sophie Adler, Kai Zhang, Saül Pascual-Diaz, Matteo Lenge, Ignacio Delgado-Martínez, Kirstie Whitaker, Núria Bargalló, Pasquale Striano, Patricia Desmond, Yingying Tang, Sofía González-Ortiz, Armin Raznahan, Wagstyl, Konrad [0000-0003-3439-5808], Cohen, Nathan T [0000-0002-1410-3487], Tang, Yingying [0000-0001-5813-0308], Wang, Shan [0000-0002-6238-2644], Chari, Aswin [0000-0003-0053-147X], Conde-Blanco, Estefanía [0000-0001-7436-987X], Pérez-Enríquez, Carmen [0000-0002-2109-0426], Opheim, Giske [0000-0002-1516-0838], Barba, Carmen [0000-0001-5445-5842], Guerrini, Renzo [0000-0002-7272-7079], Gaillard, William Davis [0000-0001-5709-0033], Wang, Irene [0000-0002-3829-5217], Striano, Pasquale [0000-0002-6065-1476], Gambardella, Antonio [0000-0001-7384-3074], Labate, Angelo [0000-0002-8827-7324], Cendes, Fernando [0000-0001-9336-9568], Baldeweg, Torsten [0000-0002-5724-1679], and Apollo - University of Cambridge Repository

Subjects
Freedom, medicine.medical_specialty, Drug Resistant Epilepsy, lesions, Lesion, Epilepsy, drug-resistant epilepsy, Neuroimaging, Seizures, medicine, Humans, neurosurgery, Child, Retrospective Studies, Errata, business.industry, Retrospective cohort study, Cortical dysplasia, medicine.disease, Magnetic Resonance Imaging, Malformations of Cortical Development, Treatment Outcome, Neurology, Frontal lobe, Neurology (clinical), Radiology, Superior frontal sulcus, medicine.symptom, business, focal cortical dysplasia, MRI
Abstract

Funder: National Institute for Health Research (NIHR) GOSH BRC, OBJECTIVE: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. METHODS: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. RESULTS: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. SIGNIFICANCE: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy.

Published
2022

14. Interpretable surface-based detection of focal cortical dysplasias: a MELD study

Author

Hannah Spitzer, Mathilde Ripart, Kirstie Whitaker, Antonio Napolitano, Luca De Palma, Alessandro De Benedictis, Stephen Foldes, Zachary Humphreys, Kai Zhang, Wenhan Hu, Jiajie Mo, Marcus Likeman, Shirin Davies, Christopher Guttler, Matteo Lenge, Nathan T. Cohen, Yingying Tang, Shan Wang, Aswin Chari, Martin Tisdall, Nuria Bargallo, Estefanía Conde-Blanco, Jose Carlos Pariente, Saül Pascual-Diaz, Ignacio Delgado-Martínez, Carmen Pérez-Enríquez, Ilaria Lagorio, Eugenio Abela, Nandini Mullatti, Jonathan O’Muircheartaigh, Katy Vecchiato, Yawu Liu, Maria Caligiuri, Ben Sinclair, Lucy Vivash, Anna Willard, Jothy Kandasamy, Ailsa McLellan, Drahoslav Sokol, Mira Semmelroch, Ane Kloster, Giske Opheim, Letícia Ribeiro, Clarissa Yasuda, Camilla Rossi-Espagnet, Khalid Hamandi, Anna Tietze, Carmen Barba, Renzo Guerrini, William Davis Gaillard, Xiaozhen You, Irene Wang, Sofía González-Ortiz, Mariasavina Severino, Pasquale Striano, Domenico Tortora, Reetta Kalviainen, Antonio Gambardella, Angelo Labate, Patricia Desmond, Elaine Lui, Terence O’Brien, Jay Shetty, Graeme Jackson, John Duncan, Gavin Winston, Lars Pinborg, Fernando Cendes, Fabian J. Theis, Russell T. Shinohara, J Helen Cross, Torsten Baldeweg, Sophie Adler, and Konrad Wagstyl

Abstract

IntroductionOne outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualise on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide.MethodsThe Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonised a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance.ResultsOur pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. Overall, after including a border-zone around lesions, the developed MELD FCD surface-based algorithm had a sensitivity of 67% and a specificity of 54% on the withheld test cohort, and a sensitivity of 85% on a restricted subcohort of seizure free patients with FCD type IIB who had T1 and FLAIR MRI data.ConclusionsThis multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions.HighlightsThis large, multi-centre, multi-scanner neuroimaging cohort captures the heterogeneity of histopathological subtypes and imaging features of patients with FCD.We developed a robust and interpretable surface-based algorithm which detects FCDs with a sensitivity of 67% and a specificity of 54%.The algorithm generates individual patient reports that “open the AI black-box” highlighting predicted lesion locations, alongside the imaging features and their relative saliency to the classifier.

Published
2021

15. Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies

Author

Elaine Luiza Santos Soares de Mendonça, Marilene Brandão Tenório Fragoso, Jerusa Maria de Oliveira, Jadriane Almeida Xavier, Marília Oliveira Fonseca Goulart, and Alane Cabral Menezes de Oliveira

Subjects
insulin resistance, pregnancy, pro-inflammatory cytokines, reactive oxygen and nitrogen species, dysbiosis, natural products, Therapeutics. Pharmacology, RM1-950
Abstract

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may contribute to the pathophysiogenesis of GDM. Recently, researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful effects on the health of the maternal-fetal binomial, in the short and long terms. In this context, alternative therapies were investigated from two perspectives: the modulation of the intestinal microbiota, with probiotics and prebiotics, and the use of natural products with antioxidant and anti-inflammatory properties, which may mitigate the endogenous processes of the GDM, favoring the health of the mother and her offspring, and in a future perspective, alleviating this critical public health problem.

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results