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1. Short- and long-term relationships between the Yucatan Channel transport and the Loop Current System

Author

Moreles, Efraín, Martínez-López, Benjamín, Higuera-Parra, Susana, Olvera-Prado, Erick R., and Zavala-Hidalgo, Jorge

Subjects
Physics - Atmospheric and Oceanic Physics
Abstract

This work uses twin 22-year free-running simulations of the Gulf of Mexico hydrodynamics performed with the HYCOM, one considering only ocean dynamics and the other incorporating atmospheric forcing, to study the behavior of the Yucatan Channel transport (YCT), the Loop Current (LC), the Loop Current Eddies (LCEs), their relationships, and the atmospheric forcing effect on them in short (daily) and long (monthly) time scales. A more comprehensive description of the LC intrusion and LCE separations was obtained by considering the upper eastern or western YCT (whose magnitudes are determined by the longitudinal displacements of the Yucatan Current's core), a perspective not evident when considering the upper total YCT; specifically, the eastern YCT provides the most meaningful description of the studied processes. Atmospheric forcing mainly affects the extended stage of the LC by creating a higher dispersion in the YCT and LC circulation values in comparison when considering only ocean dynamics. For the long-term analysis, standardized indexes that integrate the daily values of the eastern YCT and LC circulation in time were used; their temporal propagation and persistence (the changes of their characteristics from short to long time scales) were studied. Intrinsic ocean dynamics produces a persistent YCT and LC intrusion behavior and consistent LCE separation patterns from daily to 5-month scales. The atmospheric forcing effects are more emphasized on the LC intrusion and LCE separations than on the YCT: the YCT persistence is maintained but not that of the LC intrusion. An increased occurrence of LCE separations with low or moderate LC intrusion is expected due to climate change. Using the standardized indexes of the LC metrics to construct a predictive model of the LC intrusion and LCE separations using only current and past LC information is proposed for future research., Comment: 14 pages, 5 figures

Published
2024

2. On Large Uni- and Multi-modal Models for Unsupervised Classification of Social Media Images: Nature's Contribution to People as a case study

Author

Khaldi, Rohaifa, Alcaraz-Segura, Domingo, Sánchez-Herrera, Ignacio, Martinez-Lopez, Javier, Navarro, Carlos Javier, and Tabik, Siham

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence
Abstract

Social media images have proven to be a valuable source of information for understanding human interactions with important subjects such as cultural heritage, biodiversity, and nature, among others. The task of grouping such images into a number of semantically meaningful clusters without labels is challenging due to the high diversity and complex nature of the visual content in addition to their large volume. On the other hand, recent advances in Large Visual Models (LVMs), Large Language Models (LLMs), and Large Visual Language Models (LVLMs) provide an important opportunity to explore new productive and scalable solutions. This work proposes, analyzes, and compares various approaches based on one or more state-of-the-art LVM, LLM, and LVLM, for mapping social media images into a number of predefined classes. As a case study, we consider the problem of understanding the interactions between humans and nature, also known as Nature's Contribution to People or Cultural Ecosystem Services (CES). Our experiments show that the highest-performing approaches, with accuracy above 95%, still require the creation of a small labeled dataset. These include the fine-tuned LVM DINOv2 and the LVLM LLaVA-1.5 combined with a fine-tuned LLM. The top fully unsupervised approaches, achieving accuracy above 84%, are the LVLMs, specifically the proprietary GPT-4 model and the public LLaVA-1.5 model. Additionally, the LVM DINOv2, when applied in a 10-shot learning setup, delivered competitive results with an accuracy of 83.99%, closely matching the performance of the LVLM LLaVA-1.5., Comment: 17 pages, 9 figures

Published
2024

3. Measurable residual disease (MRD) dynamics in multiple myeloma and the influence of clonal diversity analyzed by artificial intelligence.

Author

Martinez-Lopez, J, Lopez-Muñoz, N, Chari, A, Dorado, S, Barrio, S, Arora, S, Kumar, A, Chung, A, Martin, T, and Wolf, J

Subjects
Humans, Multiple Myeloma, Neoplasm, Residual, Male, Female, Middle Aged, Aged, Artificial Intelligence, Retrospective Studies, Adult, Aged, 80 and over
Abstract

Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institutions experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS. PFS curves were plotted by the Kaplan-Meier method. In the newly diagnosed group, 119 of 304, achieved MRD negativity at the level of 10-6 at least once. These patients had a prolonged PFS versus patients who were persistently MRD positive at different levels (p > 0.0001). In the relapsed disease group, 64 of 178 achieved MRD negativity at 10-6, and PFS was prolonged versus patients who remained MRD positive (p = 0.03). Three categories of MRD dynamics were defined by artificial intelligence: (A) patients with ≥3 consistently MRD negative samples, (B) patients with continuously declining but detectable clones, and (C) patients with either increasing or a stable number of clones. Groups A and B had a more prolonged PFS than group C (p

Published
2024

4. Insulin and leptin oscillations license food-entrained browning and metabolic flexibility

Author

Mattar, Pamela, Reginato, Andressa, Lavados, Christian, Das, Debajyoti, Kalyani, Manu, Martinez-Lopez, Nuria, Sharma, Mridul, Skovbjerg, Grethe, Skytte, Jacob Lercke, Roostalu, Urmas, Subbarayan, Rajasekaran, Picarda, Elodie, Zang, Xingxing, Zhang, Jinghang, Guha, Chandan, Schwartz, Gary, Rajbhandari, Prashant, and Singh, Rajat

Subjects
Biochemistry and Cell Biology, Biological Sciences, Diabetes, Obesity, Nutrition, 2.1 Biological and endogenous factors, Metabolic and endocrine, Animals, Leptin, Insulin, Adipose Tissue, Brown, Mice, Mice, Inbred C57BL, Energy Metabolism, Adipose Tissue, White, Male, Feeding Behavior, CP: Metabolism, ILC2, browning, circadian, insulin, intermittent fasting, leptin, oscillations, time-restricted feeding, Medical Physiology, Biological sciences
Abstract

Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.

Published
2024

6. Improved outcome of COVID-19 over time in patients treated with CAR T-cell therapy: Update of the European COVID-19 multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP) and the European Hematology Association (EHA) Lymphoma Group

Author

Spanjaart, Anne Mea, Ljungman, Per, Tridello, Gloria, Schwartz, Juana, Martinez-Cibrián, Nuria, Barba, Pere, Kwon, Mi, Lopez-Corral, Lucia, Martinez-Lopez, Joaquin, Ferra, Christelle, Di Blasi, Roberta, Ghesquieres, Hervé, Mutsaers, Pim, Calkoen, Friso, Jak, Margot, van Doesum, Jaap, Vermaat, Joost S. P., van der Poel, Marjolein, Maertens, Johan, Gambella, Massimiliano, Metafuni, Elisabetta, Ciceri, Fabio, Saccardi, Riccardo, Nicholson, Emma, Tholouli, Eleni, Matthew, Collin, Potter, Victoria, Bloor, Adrian, Besley, Caroline, Roddie, Claire, Wilson, Keith, Nagler, Arnon, Campos, Antonio, Petersen, Soeren Lykke, Folber, Frantisek, Bader, Peter, Finke, Jurgen, Kroger, Nicolaus, Knelange, Nina, de La Camara, Rafael, Kersten, Marie José, and Mielke, Stephan

Published
2024
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7. Multi-functional oxidase-like activity of praseodymia nanorods and nanoparticles

Author

Lei, Jiang, Han, Yaning, Fernández-García, Susana, Rivas, Miguel Tinoco, Li, Zhuang, Nan, Pengli, Sun, Jingtao, Jaén, Juan José Delgado, Pan, Huiyan, Blanco, Ginesa Francisco Martínez-López, Hungría, Ana Belén, Calvino, José Juan, and Chen, Xiaowei

Subjects
Physics - Chemical Physics
Abstract

The ability to mimic protein-based oxidase with multi-functional inorganic nanozymes would greatly advance biomedical and clinical practices. Praseodymia (PrOx) nanorods (NRs) and nanoparticles (NPs) have been synthesized using hydrothermal and precipitation methods. Both PrOx catalysts with different morphologies exhibit significantly higher oxidase-like activities (Michaelis-Menten constant Km < 0.026 mM) than commercial PrOx and most so-far-reported artificial enzymes. One of the substrates, dopamine, can be oxidized and further polymerized to generate polydopamine in acidic conditions. Akin to CeO2, which is a well-studied nanozyme, a different mechanism involving holes+, oxygen vacancies and oxygen mobility over PrOx catalysts has been proposed in this work. However, fluoride ions were found to impose opposite effects on the oxidase-mimicking activity of PrOx and CeO2, implying a promising path for the exploration of new nanozymes. In support of this, PrOx was further applied in colorimetric sensing of L-cysteine and fluoride with high sensitivity., Comment: 13 pages, 12 figures

Published
2024
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9. Health-related quality of life and symptoms of chronic myeloid leukemia patients after discontinuation of tyrosine kinase inhibitors: results from the EURO-SKI Trial

Author

Efficace, Fabio, Mahon, Francois-Xavier, Richter, Johan, Piciocchi, Alfonso, Cipriani, Marta, Nicolini, Franck E., Mayer, Jiri, Zackova, Daniela, Janssen, Jeroen J. W. M., Panayiotidis, Panayiotis, Vestergaard, Hanne, Koskenvesa, Perttu, Almeida, Antonio, Hjorth-Hansen, Henrik, Martinez-Lopez, Joaquin, Olsson-Strömberg, Ulla, Hochhaus, Andreas, Berger, Marc G., Etienne, Gabriel, Klamova, Hana, Faber, Edgar, Rousselot, Philippe, Pfirrmann, Markus, and Saussele, Susanne

Published
2024
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11. H3K9me3 demethylation by JMJD2B is regulated by pirfenidone resulting in improved NASH

Author

J. Samael Rodriguez-Sanabria, Rebeca Rosas-Campos, Ángel Vázquez-Esqueda, Ivonne Palacios-Marín, Josep Jiménez-Chillaron, Rebeca Escutia-Gutiérrez, Luis Felipe Jave-Suarez, Marina Galicia-Moreno, Hugo Christian Monroy-Ramirez, Eira Cerda-Reyes, Mónica Almeida-López, Erika Martinez-Lopez, Luis Alonso Herrera, Juan Armendáriz-Borunda, and Ana Sandoval-Rodriguez

Subjects
MASLD, H3K9, JMJD2B, Pirfenidone, Medicine, Science
Abstract

Abstract NASH is characterized by hepatic lipid accumulation and inflammation; and JMJD2B—a histone demethylase—upregulation has been linked to its progression. Pirfenidone (PFD) is an antifibrotic agent with anti-inflammatory and antioxidant effects recognized to decrease NASH symptoms. Herein, our aim was to investigate PFD-induced epigenetics mechanisms involving JMJD2B and histone modifications in experimental NASH. Male C57BL/6J mice were fed with normo-diet, or high fat/carbohydrate diet (HF) for 16 weeks. A HF-subgroup was treated with PFD 300 mg/kg/d from week 8th to the end of protocol. Insulin tolerance test and liver and fat histological and biochemical analyses were carried out. Hepatic transcriptome was examined. Liver proteins were studied by western blot (WB) and Chromatin immunoprecipitation. In vitro, lipotoxicity was induced in HepG2 cells and proteins were evaluated using WB. Molecular docking was used to explore binding of PFD to JMJD2B. Mice treated with PFD reduced weight gain, epididymal fat and inflammatory nodules, and steatosis in liver tissue, as well as, improved biochemical test. PFD modified the expression of Jmjd2b, Pparg, Fasn and Srebp1, and restored JMJD2B protein and H3K9me3 repressive mark, both in animal and cell models. PFD increased hepatic enrichment of H3K9me2 and H3K9me3 at the promoter region of Fasn and Srebp1, and Pparg. In HepG2 cells, PFD reduced lipid vacuole accumulation. In silico, PFD interacted with JMJD2B catalytic site. PFD is an epigenetic regulator modifying JMJD2B activity, resulting in reduced NASH traits.

Published
2024
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14. H3K9me3 demethylation by JMJD2B is regulated by pirfenidone resulting in improved NASH

Author

Rodriguez-Sanabria, J. Samael, Rosas-Campos, Rebeca, Vázquez-Esqueda, Ángel, Palacios-Marín, Ivonne, Jiménez-Chillaron, Josep, Escutia-Gutiérrez, Rebeca, Jave-Suarez, Luis Felipe, Galicia-Moreno, Marina, Monroy-Ramirez, Hugo Christian, Cerda-Reyes, Eira, Almeida-López, Mónica, Martinez-Lopez, Erika, Herrera, Luis Alonso, Armendáriz-Borunda, Juan, and Sandoval-Rodriguez, Ana

Published
2024
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15. The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression

Author

Medina-Herrera, A., Vazquez, I., Cuenca, I., Rosa-Rosa, J. M., Ariceta, B., Jimenez, C., Fernandez-Mercado, M., Larrayoz, M. J., Gutierrez, N. C., Fernandez-Guijarro, M., Gonzalez-Calle, V., Rodriguez-Otero, P., Oriol, A., Rosiñol, L., Alegre, A., Escalante, F., De La Rubia, J., Teruel, A. I., De Arriba, F., Hernandez, M. T., Lopez-Jimenez, J., Ocio, E. M., Puig, N., Paiva, B., Lahuerta, J. J., Bladé, J., San Miguel, J. F., Mateos, M. V., Martinez-Lopez, J., Calasanz, M. J., and Garcia-Sanz, R.

Published
2024
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16. Herbivore effects increase with latitude across the extent of a foundational seagrass

Author

Campbell, Justin E., Kennedy Rhoades, O., Munson, Calvin J., Altieri, Andrew H., Douglass, James G., Heck, Kenneth L., Paul, Valerie J., Armitage, Anna R., Barry, Savanna C., Bethel, Enrique, Christ, Lindsey, Christianen, Marjolijn J. A., Dodillet, Grace, Dutton, Katrina, Fourqurean, James W., Frazer, Thomas K., Gaffey, Bethany M., Glazner, Rachael, Goeke, Janelle A., Grana-Valdes, Rancel, Jenkins, Victoria J., Kramer, Olivier A. A., Linhardt, Samantha T., Martin, Charles W., Martinez Lopez, Isis G., McDonald, Ashley M., Main, Vivienne A., Manuel, Sarah A., Marco-Méndez, Candela, O’Brien, Duncan A., O’Shea, Owen R., Patrick, Christopher J., Peabody, Clare, Reynolds, Laura K., Rodriguez, Alex, Rodriguez Bravo, Lucia M., Sang, Amanda, Sawall, Yvonne, Smith, Khalil, Smulders, Fee O. H., Sun, Uriah, Thompson, Jamie E., van Tussenbroek, Brigitta, and Wied, William L.

Published
2024
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17. Comparative Efficacy of Talquetamab vs. Current Treatments in the LocoMMotion and MoMMent Studies in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma

Author

Einsele, Hermann, Moreau, Philippe, Bahlis, Nizar, Bhutani, Manisha, Vincent, Laure, Karlin, Lionel, Perrot, Aurore, Goldschmidt, Hartmut, van de Donk, Niels W. C. J., Ocio, Enrique M., Martinez-Lopez, Joaquin, Rodríguez-Otero, Paula, Dytfeld, Dominik, Diels, Joris, Strulev, Vadim, Haddad, Imene, Renaud, Thomas, Ammann, Eric, Cabrieto, Jedelyn, Perualila, Nolen, Gan, Ryan, Zhang, Youyi, Parekh, Trilok, Albrecht, Claire, Weisel, Katja, and Mateos, Maria-Victoria

Published
2024
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18. Measurable residual disease (MRD) dynamics in multiple myeloma and the influence of clonal diversity analyzed by artificial intelligence

Author

J. Martinez-Lopez, N. Lopez-Muñoz, A. Chari, S. Dorado, S. Barrio, S. Arora, A. Kumar, A. Chung, T. Martin, and J. Wolf

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institution’s experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS. PFS curves were plotted by the Kaplan–Meier method. In the newly diagnosed group, 119 of 304, achieved MRD negativity at the level of 10−6 at least once. These patients had a prolonged PFS versus patients who were persistently MRD positive at different levels (p > 0.0001). In the relapsed disease group, 64 of 178 achieved MRD negativity at 10−6, and PFS was prolonged versus patients who remained MRD positive (p = 0.03). Three categories of MRD dynamics were defined by artificial intelligence: (A) patients with ≥3 consistently MRD negative samples, (B) patients with continuously declining but detectable clones, and (C) patients with either increasing or a stable number of clones. Groups A and B had a more prolonged PFS than group C (p

Published
2024
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21. mTORC2-NDRG1-CDC42 axis couples fasting to mitochondrial fission.

Author

Mattar, Pamela, Toledo, Miriam, Bains, Henrietta, Kalyani, Manu, Aoun, Marie, Sharma, Mridul, McIntire, Laura, Gunther-Cummins, Leslie, Macaluso, Frank, Aguilan, Jennifer, Sidoli, Simone, Bourdenx, Mathieu, Singh, Rajat, and Martinez-Lopez, Nuria

Subjects
Mechanistic Target of Rapamycin Complex 2, TOR Serine-Threonine Kinases, Mitochondrial Dynamics, Carrier Proteins, Phosphorylation, Fasting
Abstract

Fasting triggers diverse physiological adaptations including increases in circulating fatty acids and mitochondrial respiration to facilitate organismal survival. The mechanisms driving mitochondrial adaptations and respiratory sufficiency during fasting remain incompletely understood. Here we show that fasting or lipid availability stimulates mTORC2 activity. Activation of mTORC2 and phosphorylation of its downstream target NDRG1 at serine 336 sustains mitochondrial fission and respiratory sufficiency. Time-lapse imaging shows that NDRG1, but not the phosphorylation-deficient NDRG1Ser336Ala mutant, engages with mitochondria to facilitate fission in control cells, as well as in those lacking DRP1. Using proteomics, a small interfering RNA screen, and epistasis experiments, we show that mTORC2-phosphorylated NDRG1 cooperates with small GTPase CDC42 and effectors and regulators of CDC42 to orchestrate fission. Accordingly, RictorKO, NDRG1Ser336Ala mutants and Cdc42-deficient cells each display mitochondrial phenotypes reminiscent of fission failure. During nutrient surplus, mTOR complexes perform anabolic functions; however, paradoxical reactivation of mTORC2 during fasting unexpectedly drives mitochondrial fission and respiration.

Published
2023

22. INTERPRETER -- Tool for non-technical losses detection

Author

Bludszuweit, Hans, Yurusen, Nurseda Yildirim, Pérez, Pablo López, and Martínez-López, Diego

Subjects
Electrical Engineering and Systems Science - Systems and Control
Abstract

This article presents a tool for the detection of non-technical losses, which is being developed within the European INTERPRETER project. The tool employs a hybrid method based on feature detection from smart meter data and grid model analysis. This paper focuses on the grid model analysis, where voltage deviations between the grid model (digital twin) and real-world measurements at a low-voltage pilot site have been evaluated. Energy measurements from smart meters represent hourly mean power, while voltage measurements are instantaneous with uneven time intervals. Thus, measurements are not synchronous, which poses a major challenge for grid analysis. The proposed method focuses on daily mean, minimum, and maximum voltage and results show that deviations in daily minimum voltage are the most useful ones. A heatmap is developed, which helps the DSO expert to have a quick overview of all deviations of all meters in a certain time interval (1-day time step). A total of 6 locations have been identified where field inspections will be done., Comment: 7 pages, 6 figures, 2 tables, conference paper

Published
2022
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23. LONG-TERM FOLLOW-UP FROM THE PHASE 1/2 MAJESTEC-1 TRIAL OF TECLISTAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: SUBGROUP ANALYSIS BY LINES OF THERAPIES

Author

LJ Costa, NWCJV Donk, L Rosinol, R Popat, Be semer, J Martinez-Lopez, D Trancucci, T Stephenson, K Chastain, and N Bahlis

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background: Teclistamab is the first approved B-cell maturation antigen × CD3 bispecific antibody (BsAb) for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM), with weight-based dosing and the longest study follow-up of any BsAb in MM. In the pivotal phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098), teclistamab demonstrated rapid, deep, and durable responses (overall response rate [ORR], 63.0%; complete response or better [≥CR] rate, 46.1%; median duration of response [mDOR], 24 mo) and a low rate of discontinuations due to adverse events (AEs; 4.8%). This subgroup analysis of MajesTEC-1 reports the overall safety and efficacy of RRMM patients (pts) who received 2-3 prior lines of therapy vs. pts with 4 or more prior lines of therapies, with extended follow-up of 30 months. Methods: Pts received the recommended phase 2 dose (RP2D) of teclistamab (1.5 mg/kg QW) and could switch to Q2W dosing if in partial response or better after ≥4 cycles of therapy (phase 1) or in ≥CR for ≥6 mo (phase 2). The primary endpoint was ORR (assessed per IMWG 2016 criteria). AEs were graded per CTCAE v4.03. CRS and ICANS were graded per ASTCT. Safety was reported in the overall population and efficacy was evaluated in pts who received 2-3 prior lines of therapy (≤3 LoT) vs. pts who received more than 3 prior lines of therapies (> 3 LoT). Results: Of 165 pts who had received teclistamab as of Aug 2023, 26% (43/165) pts received ≤ 3 prior LoT and 74% (122/165) patients received > 3 prior LoT. Pts characteristics were similar between the groups, especially in terms of high-risk features. At 30.4 mo mFU, pts that received ≤3 prior LoT achieved an ORR of 74.4% with 60.5% of pts achieving ≥ CR [sCR 46.5% and CR 14%]. mPFS was 21.7 mo (95% CI, 13.8–NR), mDOR was 24.0 mo (95% CI, 14.0–NE) and median overall survival was not reached (95% CI, 18.3–NE). Pts who had > 3 prior LoT had an ORR of 59%, with 41% of pts achieving ≥CR [sCR 36.1% and CR 4.9%], mPFS was 9.7 mo (95% CI, 6.4–13.1), mDOR was 22.4 mo (95% CI, 14.9–NE) and median overall survival was 17.7 mo (95% CI, 12.2–29.7). In the overall population, hematologic AEs (any grade/grade 3/4) included neutropenia (72%/65%), anemia (55%/38%), thrombocytopenia (42%/23%), and lymphopenia (36%/35%). Infections occurred in 79% of pts (55% grade 3/4). Of grade 5 infections, 18/22 were due to COVID-19, reflecting study conduct during the COVID-19 pandemic. Onset of new grade ≥3 infections generally decreased over time, which aligned approximately with the median time of switch to Q2W dosing; other factors, such as increasing use of IVIG, may also contribute to this trend. AEs leading to dose reduction (n = 1) or discontinuation (n = 8; 5 due to infection) were infrequent. No new safety signals were reported. Conclusion: With the longest follow-up of any BsAb in MM, teclistamab continues to demonstrate deep and durable responses, especially in the subgroup of less heavily treated patients (≤3 prior LoT), which demonstrates even better PFS and complete response rates results than those patients in later lines of treatment (> 3 prior LOT). The safety profile of teclistamab remains consistent with that of BCMA-targeted bispecific therapies, with an important decrease in new onset of severe infections with time. Acknowledgments: This study was funded by Johnson & Johnson Innovative Medicine.

Published
2024
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24. CILTACABTAGENE AUTOLEUCEL VS STANDARD OF CARE IN LENALIDOMIDE-REFRACTORY MULTIPLE MYELOMA: PHASE 3 CARTITUDE-4 SUBGROUP ANALYSIS BY CYTOGENETIC RISK

Author

R Mina, B Dhakal, J San-Miguel, N Lendvai, M Vogel, K Li, D Chen, N Patel, H Einsele, and J Martinez-Lopez

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background: The prognosis for patients (pts) with multiple myeloma (MM) who have high-risk (HR) cytogenetics is poor. In the phase 3 CARTITUDE-4 trial, ciltacabtagene autoleucel (cilta-cel) vs standard of care (SOC) significantly improved progression-free survival (PFS; p < 0.0001) in pts with relapsed and lenalidomide-refractory MM after 1–3 prior lines of therapy. Additionally, the proportion of pts with an overall response (OR) (85% vs 67%), complete response or better (≥CR; 73% vs 22%), and minimal residual disease (MRD) negativity rate (10–5; 61% vs 16%) was higher with cilta-cel vs SOC. Aims: To report the efficacy of cilta-cel vs SOC in pts with HR and standard-risk (SR) cytogenetics, including by type of cytogenetic abnormality from a post hoc subgroup analysis of CARTITUDE-4. Methods: Eligibility criteria for CARTITUDE-4 have been previously described. Pts in the cilta-cel arm underwent apheresis, received bridging therapy (pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]), and then a single cilta-cel infusion (target dose, 0.75 × 106 CAR+ viable T cells/kg) 5–7 days after the start of lymphodepletion. The SOC arm received PVd or DPd until progressive disease. HR cytogenetics was defined as pts with ≥1 of the following cytogenetic abnormalities at baseline determined by fluorescence in situ hybridization: del(17p), t(4;14), t(14;16), or gain/amp(1q). SR cytogenetics was defined as pts without del(17p), t(4;14), t(14;16), or gain/amp(1q) at baseline. Efficacy analyses were assessed in the intent-to-treat population (all randomized pts) and are summarized descriptively. Results: In CARTITUDE-4, 394/419 pts were evaluable for cytogenetics and had non-missing data; of these, 255 pts had HR cytogenetics (cilta-cel, n = 123; SOC, n = 132) and 139 had SR cytogenetics (cilta-cel, n = 69; SOC, n = 70). At the data cutoff (Nov 1, 2022), median follow-up was 15.9 mo (range, 0.1–27.3). In pts with HR cytogenetics, median PFS was not reached (NR; 95% CI, 18.4–not estimable [NE]) with cilta-cel vs 10.3 mo (95% CI, 7.6–12.5) with SOC; 12-mo PFS rates were 76% vs 43%, respectively. Among pts with SR cytogenetics, median PFS was NR (95% CI, NE–NE) with cilta-cel vs 20.6 mo (95% CI, 11.2–NE) with SOC; 12-mo PFS rates were 77% vs 59%, respectively. In pts with HR cytogenetics, a greater proportion had an OR (85% vs 66%), ≥CR (73% vs 20%), and MRD negativity (105; 70% vs 14%) with cilta-cel vs SOC. Similarly, in pts with SR cytogenetics a greater proportion had an OR (86% vs 71%), ≥CR (74% vs 26%), and MRD negativity (105; 49% vs 19%) with cilta-cel vs SOC. [YfA[1] Efficacy in pts with t(14;16) was excluded because the small number of pts in the cilta-cel (n = 3) and SOC (n = 7) arms precludes meaningful analyses. Summary/Conclusions: A single infusion of cilta-cel demonstrated favorable efficacy outcomes vs SOC in lenalidomide-refractory MM pts who had HR and standard-risk disease, with generally consistent results across different cytogenetic abnormalities although sample sizes for some individual types were small. Of note, cilta-cel induced comparable OR, ≥CR, and MRD-negativity rates in pts with HR and standard-risk disease, supporting the role of cilta-cel as a potential new SOC in pts with lenalidomide-refractory MM after 1–3 prior lines of therapy. Acknowledgments: This study was funded by Janssen Research & Development, LLC and Legend Biotech USA Inc.

Published
2024
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25. Novel risk loci for COVID-19 hospitalization among admixed American populations

Author

Silvia Diz-de Almeida, Raquel Cruz, Andre D Luchessi, José M Lorenzo-Salazar, Miguel López de Heredia, Inés Quintela, Rafaela González-Montelongo, Vivian Nogueira Silbiger, Marta Sevilla Porras, Jair Antonio Tenorio Castaño, Julian Nevado, Jose María Aguado, Carlos Aguilar, Sergio Aguilera-Albesa, Virginia Almadana, Berta Almoguera, Nuria Alvarez, Álvaro Andreu-Bernabeu, Eunate Arana-Arri, Celso Arango, María J Arranz, Maria-Jesus Artiga, Raúl C Baptista-Rosas, María Barreda- Sánchez, Moncef Belhassen-Garcia, Joao F Bezerra, Marcos AC Bezerra, Lucía Boix-Palop, María Brion, Ramón Brugada, Matilde Bustos, Enrique J Calderón, Cristina Carbonell, Luis Castano, Jose E Castelao, Rosa Conde-Vicente, M Lourdes Cordero-Lorenzana, Jose L Cortes-Sanchez, Marta Corton, M Teresa Darnaude, Alba De Martino-Rodríguez, Victor del Campo-Pérez, Aranzazu Diaz de Bustamante, Elena Domínguez-Garrido, Rocío Eirós, María Carmen Fariñas, María J Fernandez-Nestosa, Uxía Fernández-Robelo, Amanda Fernández-Rodríguez, Tania Fernández-Villa, Manuela Gago-Dominguez, Belén Gil-Fournier, Javier Gómez-Arrue, Beatriz González Álvarez, Fernan Gonzalez Bernaldo de Quirós, Anna González-Neira, Javier González-Peñas, Juan F Gutiérrez-Bautista, María José Herrero, Antonio Herrero-Gonzalez, María A Jimenez-Sousa, María Claudia Lattig, Anabel Liger Borja, Rosario Lopez-Rodriguez, Esther Mancebo, Caridad Martín-López, Vicente Martín, Oscar Martinez-Nieto, Iciar Martinez-Lopez, Michel F Martinez-Resendez, Angel Martinez-Perez, Juliana F Mazzeu, Eleuterio Merayo Macías, Pablo Minguez, Victor Moreno Cuerda, Silviene F Oliveira, Eva Ortega-Paino, Mara Parellada, Estela Paz-Artal, Ney PC Santos, Patricia Pérez-Matute, Patricia Perez, M Elena Pérez-Tomás, Teresa Perucho, Mellina Pinsach-Abuin, Guillermo Pita, Ericka N Pompa-Mera, Gloria L Porras-Hurtado, Aurora Pujol, Soraya Ramiro León, Salvador Resino, Marianne R Fernandes, Emilio Rodríguez-Ruiz, Fernando Rodriguez-Artalejo, José A Rodriguez-Garcia, Francisco Ruiz-Cabello, Javier Ruiz-Hornillos, Pablo Ryan, José Manuel Soria, Juan Carlos Souto, Eduardo Tamayo, Alvaro Tamayo-Velasco, Juan Carlos Taracido-Fernandez, Alejandro Teper, Lilian Torres-Tobar, Miguel Urioste, Juan Valencia-Ramos, Zuleima Yáñez, Ruth Zarate, Itziar de Rojas, Agustín Ruiz, Pascual Sánchez, Luis Miguel Real, SCOURGE Cohort Group, Encarna Guillen-Navarro, Carmen Ayuso, Esteban Parra, José A Riancho, Augusto Rojas-Martinez, Carlos Flores, Pablo Lapunzina, and Ángel Carracedo

Subjects
GWAS, COVID-19, SNP, Medicine, Science, Biology (General), QH301-705.5
Abstract

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Published
2024
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29. Phase Equilibrium in Solid Solutions of BaTiO3 Doped with Eu3+ and Gd3+

Author

Martínez López, R., Pérez Labra, M., Barrientos Hernández, F. R., Valenzuela Carrillo, M. I., Reyes Pérez, M., Romero Serrano, J. A., Hernández Ramírez, A., Hernández Lara, J. P., Peng, Zhiwei, editor, Zhang, Mingming, editor, Li, Jian, editor, Li, Bowen, editor, Monteiro, Sergio Neves, editor, Soman, Rajiv, editor, Hwang, Jiann-Yang, editor, Kalay, Yunus Eren, editor, Escobedo-Diaz, Juan P., editor, Carpenter, John S., editor, Brown, Andrew D., editor, and Ikhmayies, Shadia, editor

Published
2024
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30. Formation of Solid Solutions of BaTiO3 Doped with Eu3+ by Solid-State Reaction

Author

Hernández-Lara, J. P., Hernández-Ramírez, A., Romero-Serrano, J. A., Pérez-Labra, M., Barrientos-Hernández, F. R., Martinez-Lopez, R., Valenzuela-Carrillo, M. I., Peng, Zhiwei, editor, Zhang, Mingming, editor, Li, Jian, editor, Li, Bowen, editor, Monteiro, Sergio Neves, editor, Soman, Rajiv, editor, Hwang, Jiann-Yang, editor, Kalay, Yunus Eren, editor, Escobedo-Diaz, Juan P., editor, Carpenter, John S., editor, Brown, Andrew D., editor, and Ikhmayies, Shadia, editor

Published
2024
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33. Comparative Effectiveness of Teclistamab Versus Real-World Physician’s Choice of Therapy in LocoMMotion and MoMMent in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma

Author

Moreau, Philippe, Mateos, María-Victoria, Gonzalez Garcia, Maria Esther, Einsele, Hermann, De Stefano, Valerio, Karlin, Lionel, Lindsey-Hill, Joanne, Besemer, Britta, Vincent, Laure, Kirkpatrick, Suriya, Delforge, Michel, Perrot, Aurore, van de Donk, Niels W. C. J., Pawlyn, Charlotte, Manier, Salomon, Leleu, Xavier, Martinez-Lopez, Joaquin, Ghilotti, Francesca, Diels, Joris, Morano, Raúl, Albrecht, Claire, Strulev, Vadim, Haddad, Imène, Pei, Lixia, Kobos, Rachel, Smit, Jennifer, Slavcev, Mary, Marshall, Alexander, and Weisel, Katja

Published
2023
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34. The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression

Author

A. Medina-Herrera, I. Vazquez, I. Cuenca, J. M. Rosa-Rosa, B. Ariceta, C. Jimenez, M. Fernandez-Mercado, M. J. Larrayoz, N. C. Gutierrez, M. Fernandez-Guijarro, V. Gonzalez-Calle, P. Rodriguez-Otero, A. Oriol, L. Rosiñol, A. Alegre, F. Escalante, J. De La Rubia, A. I. Teruel, F. De Arriba, M. T. Hernandez, J. Lopez-Jimenez, E. M. Ocio, N. Puig, B. Paiva, J. J. Lahuerta, J. Bladé, J. F. San Miguel, M. V. Mateos, J. Martinez-Lopez, M. J. Calasanz, R. Garcia-Sanz, and GEM/PETHEMA (Grupo Español de Mieloma/Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

Published
2024
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35. Biallelic TET2 mutation sensitizes to 5’-azacitidine in acute myeloid leukemia

Author

Stölzel, Friedrich, Fordham, Sarah E, Nandana, Devi, Lin, Wei-Yu, Blair, Helen J, Elstob, Claire J, Bell, Hayden L, Mohr, Brigitte, Ruhnke, Leo, Kunadt, Desiree, Dill, Claudia, Allsop, Daniel A, Piddock, Rachel E, Soura, Emmanouela-Niki, Park, Catherine Vida, Fadly, Mohd, Rahman, Thahira, Alharbi, Abrar A, Wobus, Manja, Altmann, Heidi, Röllig, Christoph, Wagenführ, Lisa, Jones, Gail L, Menne, Tobias, Jackson, Graham H, Marr, Helen J, Fitzgibbon, Jude, Onel, Kenan, Meggendorfer, Manja, Robinson, Amber, Bziuk, Zuzanna, Bowes, Emily, Heidenreich, Olaf, Haferlach, Torsten, Villar, Sara, Ariceta, Beñat, Diaz, Rosa Ayala, Altschuler, Steven J, Wu, Lani, Prosper, Felipe, Montesinos, Pau, Martinez-Lopez, Joaquin, Bornhäuser, Martin, and Allan, James M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Hematology, Genetics, Pediatric, Pediatric Cancer, Rare Diseases, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Humans, Mice, Animals, Azacitidine, Leukemia, Myeloid, Acute, Kaplan-Meier Estimate, Mutation, DNA-Binding Proteins, Dioxygenases, Leukemias, Molecular genetics, Biomedical and clinical sciences, Health sciences
Abstract

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.

Published
2023

36. Multiple Internalization Pathways of Polyelectrolyte Multilayer Capsules into Mammalian Cells

Author

Kastl, Lena, primary, Sasse, Daniel, additional, Wulf, Verena, additional, Hartmann, Raimo, additional, Mircheski, Josif, additional, Ranke, Christiane, additional, Carregal-Romero, Susana, additional, Martinez-Lopez, Jose Antonio, additional, Fernandez-Chacon, Rafael, additional, Parak, Wolfgang J., additional, Elsasser, Hans-Peter, additional, and Rivera-Gil, Pilar, additional

Published
2024
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37. Ancestral Computing for Sustainability: Centering Indigenous Epistemologies in Researching Computer Science Education

Author

López-Quiñones, Alyssa, Martinez-Lopez, Marlen, Moreno Sandoval, Cueponcaxochitl D., Carroll-Miranda, Joseph, Lindala, April E., Chatman, Michelle C., Fleming, Jeffery, Shockley, Ebony Terrell, Cadeau, Denise, and Flores-Reyes, Elizabeth

Abstract

This article offers Ancestral Computing for Sustainability (ACS) to dismantle the logics of settler colonialism that affect accessibility, identities, and epistemologies of computer science education (CSE). ACS centers Indigenous epistemologies in researching CSE across four public universities in the United States. This paper describes Ancestral Computing for Sustainability and explores reflections of two students engaging as researchers in ACS inquiry. Drawing on Indigenous methodologies and Participatory Action Research, they share their reflections as co-researchers in ACS through storywork. These critical reflections include their relationship to computing, observations of the interdependent work within ACS, ethics and sustainability, and their experiences within the focus groups. The article ends with recommendations for furthering ACS as a decolonial approach that centers Indigenous epistemologies in CSE. Recommendations for CSE education include Ancestral Knowledge Systems and adding sustainability as a topic within computing education pathways and building student-faculty relationships based on trust is recommended to foster students' academic and personal growth within CSE education and research.

Published
2023
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38. Clonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma

Author

Larissa Haertle, Umair Munawar, Hipólito N. C. Hernández, Andres Arroyo‐Barea, Tobias Heckel, Isabel Cuenca, Lucia Martin, Carlotta Höschle, Nicole Müller, Cornelia Vogt, Thorsten Bischler, Paula L. delCampo, Seungbin Han, Natalia Buenache, Xiang Zhou, Florian Bassermann, Johannes Waldschmidt, Torsten Steinbrunn, Leo Rasche, Thorsten Stühmer, Joaquin Martinez‐Lopez, K. Martin Kortüm, and Santiago Barrio

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses is one of the biggest clinical challenges. TP53 alterations are established high‐risk markers and are included in the current disease staging criteria. KRAS is the most frequently mutated gene affecting around 20% of MM patients. Applying Clonal Competition Assays (CCA) by co‐culturing color‐labeled genetically modified cell models, we recently showed that mono‐ and biallelic alterations in TP53 transmit a fitness advantage to the cells. Here, we report a similar dynamic for two mutations in KRAS (G12A and A146T), providing a biological rationale for the high frequency of KRAS and TP53 alterations at MM relapse. Resistance mutations, on the other hand, did not endow MM cells with a general fitness advantage but rather presented a disadvantage compared to the wild‐type. CUL4B KO and IKZF1 A152T transmit resistance against immunomodulatory agents, PSMB5 A20T to proteasome inhibition. However, MM cells harboring such lesions only outcompete the culture in the presence of the respective drug. To better prevent the selection of clones with the potential of inducing relapse, these results argue in favor of treatment‐free breaks or a switch of the drug class given as maintenance therapy. In summary, the fitness benefit of TP53 and KRAS mutations was not treatment‐related, unlike patient‐derived drug resistance alterations that may only induce an advantage under treatment. CCAs are suitable models for the study of clonal evolution and competitive (dis)advantages conveyed by a specific genetic lesion of interest, and their dependence on external factors such as the treatment.

Published
2024
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39. Long‐term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: Update from the MagnetisMM‐3 study

Author

Michael H. Tomasson, Shinsuke Iida, Ruben Niesvizky, Mohamad Mohty, Nizar J. Bahlis, Joaquin Martinez‐Lopez, Guenther Koehne, Paula Rodriguez‐Otero, H. Miles Prince, Andrea Viqueira, Eric Leip, Umberto Conte, Sharon T. Sullivan, and Alexander M. Lesokhin

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2024
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40. Insulin and leptin oscillations license food-entrained browning and metabolic flexibility

Author

Pamela Mattar, Andressa Reginato, Christian Lavados, Debajyoti Das, Manu Kalyani, Nuria Martinez-Lopez, Mridul Sharma, Grethe Skovbjerg, Jacob Lercke Skytte, Urmas Roostalu, Rajasekaran Subbarayan, Elodie Picarda, Xingxing Zang, Jinghang Zhang, Chandan Guha, Gary Schwartz, Prashant Rajbhandari, and Rajat Singh

Subjects
CP: Metabolism, Biology (General), QH301-705.5
Abstract

Summary: Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.

Published
2024
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41. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Author

Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure Choupeaux, Benjamin Chousterman, Dragosmarius Ciocan, Ada Clarke, Gaëlle Clavere, Florian Clavier, Karine Clement, Sebastien Clerc, Yves Cohen, Fleur Cohen, Adrien Cohen, Audrey Coilly, Hester Colboc, Pauline Colin, Magalie Collet, Chloé Comarmond, Emeline Combacon, Alain Combes, Celine Comparon, Jean-Michel Constantin, Hugues Cordel, Anne-Gael Cordier, Adrien Costantini, Nathalie Costedoat Chalumeau, Camille Couffignal, Doriane Coupeau, Alain Creange, Yannie Cuvillier Lamarre, Charlène Da Silveira, Sandrine Dautheville Guibal El Kayani, Nathalie De Castro, Yann De Rycke, Lucie Del Pozo, Quentin Delannoy, Mathieu Delay, Robin Deleris, Juliette Delforge, Laëtitia Delphine, Noemie Demare, Sophie Demeret, Alexandre Demoule, Aurore Deniau, François Depret, Sophie Derolez, Ouda Derradji, Nawal Derridj, Vincent Descamps, Lydia Deschamps, Celine Desconclois, Cyrielle Desnos, Karine Desongins, Robin Dhote, Benjamin Diallo, Morgane Didier, Myriam Diemer, Stephane Diez, Juliette Djadi-Prat, Fatima-Zohra Djamouri Monnory, Siham Djebara, Naoual Djebra, Minette Djietcheu, Hadjer Djillali, Nouara Djouadi, Severine Donneger, Catarina Dos Santos, Nathalie Dournon, Martin Dres, Laura Droctove, Marie Drogrey, Margot Dropy, Elodie Drouet, Valérie Dubosq, Evelyne Dubreucq, Estelle Dubus, Boris Duchemann, Thibault Duchenoy, Emmanuel Dudoignon, Romain Dufau, Florence Dumas, Clara Duran, Emmanuelle Duron, Antoine Durrbach, Claudine Duvivier, Nathan Ebstein, Jihane El Khalifa, Alexandre Elabbadi, Caroline Elie, Gabriel Ernotte, Anne Esling, Martin Etienne, Xavier Eyer, Muriel Sarah Fartoukh, Takoua Fayali, Marion Fermaut, Arianna Fiorentino, Souha Fliss, Marie-Céline Fournier, Benjamin Fournier, Hélène Francois, Olivia Freynet, Yvann Frigout, Isaure Fromont, Axelle Fuentes, Thomas Furet, Joris Galand, Marc Garnier, Agnes Gaubert, Stéphane Gaudry, Samuel Gaugain, Damien Gauthier, Maxime Gautier, Sophie Georgin-Lavialle, Daniela Geromin, Mohamed Ghalayini, Bijan Ghaleh, Myriam Ghezal, Aude Gibelin, Linda Gimeno, Benoit Girard, Bénédicte Giroux Leprieur, Doryan Gomes, Elisabete Gomes-Pires, Anne Gouge, Amel Gouja, Helene Goulet, Sylvain Goupil, Jeanne Goupil De Bouille, Julien Gras, Segolene Greffe, Lamiae Grimaldi, Paul Guedeney, Bertrand Guidet, Matthias Guillo, Mariechristelle Gulczynski, Tassadit Hadjam, Didier Haguenauer, Soumeya Hammal, Nadjib Hammoudi, Olivier Hanon, Anarole Harrois, Coraline Hautem, Guillaume Hekimian, Nicholas Heming, Olivier Hermine, Sylvie Ho, Marie Houllier, Benjamin Huot, Tessa Huscenot, Wafa Ibn Saied, Ghilas Ikherbane, Meriem Imarazene, Patrick Ingiliz, Lina Iratni, Stephane Jaureguiberry, Jean-Francois Jean-Marc, Deleena Jeyarajasingham, Pauline Jouany, Veronique Jouis, Clement Jourdaine, Ouifiya Kafif, Rim Kallala, Sandrine Katsahian, Lilit Kelesyan, Vixra Keo, Flora Ketz, Warda Khamis, Enfel Khelili, Mehdi Khellaf, Christy Gaëlla Kotokpo Youkou, Ilias Kounis, Gaelle Kpalma, Jessica Krause, Vincent Labbe, Karine Lacombe, Jean-Marc Lacorte, Anne Gaelle Lafont, Emmanuel Lafont, Lynda Lagha, Lionel Lamhaut, Aymeric Lancelot, Cecilia Landman, Fanny Lanternier, Cecile Larcheveque, Caroline Lascoux Combe, Ludovic Lassel, Benjamin Laverdant, Christophe Lavergne, Jean-Rémi Lavillegrand, Pompilia Lazureanu, Loïc Le Guennec, Lamia Leberre, Claire Leblanc, Marion Leboyer, Francois Lecomte, Marine Lecorre, Romain Leenhardt, Marylou Lefebvre, Bénédicte Lefebvre, Paul Legendre, Anne Leger, Laurence Legros, Justyna Legrosse, Sébastien Lehuunghia, Julien Lemarec, Jeremie Leporrier-Ext, Manon Lesein, Hubert Lesur, Vincent Levy, Albert Levy, Edwige Lopes, Amanda Lopes, Vanessa Lopez, Julien Lopinto, Olivier Lortholary, Badr Louadah, Bénédicte Loze, Marie-Laure Lucas, Axelle Lucasamichi, Liem Binh Luong, Arouna Magazimama-Ext, David Maingret, Lakhdar Mameri, Philippe Manivet, Cylia Mansouri, Estelle Marcault, Jonathan Marey, Nathalie Marin, Clémence Marois, Olivier Martin, Lou Martineau, Cannelle Martinez-Lopez, Pierre Martyniuck, Pauline Mary De Farcy, Nessrine Marzouk, Rafik Masmoudi, Alexandre Mebazaa, Frédéric Mechai, Fabio Mecozzi, Chamseddine Mediouni, Bruno Megarbane, Mohamed Meghadecha, Élodie Mejean, Arsene Mekinian, Nour Mekki Abdelhadi, Rania Mekni, Thinhinan Sabrina Meliti, Breno Melo Lima, Paris Meng, Soraya Merbah, Fadhila Messani, Yasmine Messaoudi, Baboo-Irwinsingh Mewasing, Lydia Meziane, Carole Michelot-Burger, Françoise Mignot, Fadi Hillary Minka, Makoto Miyara, Pierre Moine, Jean-Michel Molina, Anaïs Montegnies-Boulet, Alexandra Monti, Claire Montlahuc, Anne-Lise Montout, Alexandre Moores, Caroline Morbieu, Helene Mortelette, Stéphane Mouly, Rosita Muzaffar, Cherifa Iness Nacerddine, Marine Nadal, Hajer Nadif, Kladoum Nassarmadji, Pierre Natella, Sandrine Ndingamondze, Stefan Neraal, Caroline Nguyen, Bao N'Guyen, Isabelle Nion Larmurier, Luc Nlomenyengue, Nicolas Noel, Hilario Nunes, Edris Omar, Zineb Ouazene, Elise Ouedraogo, Wassila Ouelaa, Anissa Oukhedouma, Yasmina Ould Amara, Herve Oya, Johanna Oziel, Thomas Padilla, Elena Paillaud, Solenne Paiva, Beatrice Parfait, Perrine Parize, Christophe Parizot, Antoine Parrot, Arthur Pavot, Laetitia Peaudecerf, Frédéric Pene, Marion Pepin, Julie Pernet, Claire Pernin, Mylène Petit, Olivier Peyrony, Marie-Pierre Pietri, Olivia Pietri, Marc Pineton De Chambrun, Michelle Pinson, Claire Pintado, Valentine Piquard, Christine Pires, Benjamin Planquette, Sandrine Poirier, Anne-Laure Pomel, Stéphanie Pons, Diane Ponscarme, Annegaelle Pourcelot, Valérie Pourcher, Anne Pouvaret, Florian Prever, Miresta Previlon, Margot Prevost, Marie-Julie Provoost, Cyril Quemeneur, Cédric Rafat, Agathe Rami, Brigitte Ranque, Maurice Raphael, Jean Herle Raphalen, Anna Rastoin, Mathieu Raux, Amani Rebai, Michael Reby, Alexis Regent, Asma Regrag, Matthieu Resche-Rigon, Quentin Ressaire, Christian Richard, Mariecaroline Richard, Maxence Robert, Benjamin Rohaut, Camille Rolland-Debord, Jacques Ropers, Anne-Marie Roque-Afonso, Charlotte Rosso, Mélanie Rousseaux, Nabila Rousseaux, Swasti Roux, Lorène Roux, Claire Rouzaud, Antoine Rozes, Emma Rubenstein, Jean-Marc Sabate, Sheila Sabet, Sophie-Caroline Sacleux, Nathalie Saidenberg Kermanach, Faouzi Saliba, Dominique Salmon, Laurent Savale, Guillaume Savary, Rebecca Sberro, Anne Scemla, Frederic Schlemmer, Mathieu Schwartz, Saïd Sedfi, Samia Sefir-Kribel, Philippe Seksik, Pierre Sellier, Agathe Selves, Nicole Sembach, Luca Semerano, Marie-Victoire Senat, Damien Sene, Alexandra Serris, Lucile Sese, Naima Sghiouar, Johanna Sigaux, Martin Siguier, Johanne Silvain, Noémie Simon, Tabassome Simon, Lina Innes Skandri, Miassa Slimani, Aurélie Snauwaert, Harry Sokol, Heithem Soliman, Nisrine Soltani, Benjamin Soyer, Gabriel Steg, Lydia Suarez, Tali-Anne Szwebel, Kossi Taffame, Yacine Tandjaoui-Lambiotte, Claire Tantet, Mariagrazia Tateo, Igor Theodose, Pierre clement Thiebaud, Caroline Thomas, Kelly Tiercelet, Julie Tisserand, Carole Tomczak, Krystel Torelino, Fatima Touam-Ext, Lilia Toumi, Gustave Toury, Mireille Toy-Miou, Olivia Tran Dinh Thanh Lien, Alexy Trandinh, Jean-Marc Treluyer, Baptiste Trinque, Jennifer Truchot, Sarah Tubiana, Simone Tunesi, Matthieu Turpin, Agathe Turpin, Tomas Urbina, Rafael Usubillaga Narvaez, Yurdagul Uzunhan, Prabakar Vaittinadaayar, Arnaud Valent, Maelle Valentian, Nadia Valin, Hélène Vallet, Marina Vaz, Miguel-Alejandro Vazquezibarra, Benoit Vedie, Laetitia Velly, Celine Verstuyft, Cedric Viallette, Eric Vicaut, Dorothee Vignes, Damien Vimpere, Myriam Virlouvet, Guillaume Voiriot, Lena Voisot, Emmanuel Weiss, Nicolas Weiss, Anaïs Winchenne, Youri Yordanov, Lara Zafrani, Mohamad Zaidan, Wissem Zaidi, Cathia Zak, Aida Zarhrate-Ghoul, Ouassila Zatout, Suzanne Zeino, Michel Zeitouni, Naïma Zemirli, Lorene Zerah, Ounsa Zia, Marianne Ziol, Oceane Zolario, Julien Zuber, Claire Andrejak, François Angoulvant, Delphine Bachelet, Marie Bartoli, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, Lila Bouadma, Sabelline Bouchez, Maude Bouscambert, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chirouze, Alexandra Coelho, Sandrine Couffin-Cadiergues, Eric d’Ortenzio, Marie-Pierre Debray, Laurene Deconinck, Dominique Deplanque, Diane Descamps, Mathilde Desvallée, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Brigitte Elharrar, Vincent Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Eglantine Ferrand Devouge, Nathalie Gault, Alexandre Gaymard, Tristan Gigante, Morgane Gilg, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Jean-Sébastien Hulot, Salma Jaafoura, Florentia Kaguelidou, Sabrina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Sophie Letrou, Yves Levy, Bruno Lina, Guillaume Lingas, Jean-Christophe Lucet, Denis Malvy, Marina Mambert, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Duc Nguyen, Marion Noret, Saad Nseir, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Thomas Perpoint, Ventzislava Petrov-Sanchez, Gilles Peytavin, Huong Pham, Olivier Picone, Oriane Puéchal, Christian Rabaud, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Richa Su, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Christelle Tual, Sylvie Van Der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Charlotte Charpentier, Aline Dechanet, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Jonathan Lehacaut, Pauline Manchon, Mariama Nouroudine, Caroline Quintin, Michael Thy, Sylvie van der Werf, Valérie Vignali, Abir Chahine, Nawal Waucquier, Maria-Claire Migaud, Félix Djossou, Mayka Mergeay-Fabre, Aude Lucarelli, Magalie Demar, Léa Bruneau, Patrick Gérardin, Adrien Maillot, Christine Payet, Bruno Laviolle, Fabrice Laine, Christophe Paris, Mireille Desille-Dugast, Julie Fouchard, Thierry Pistone, Pauline Perreau, Valérie Gissot, Carole L.E. Goas, Samatha Montagne, Lucie Richard, Kévin Bouiller, Maxime Desmarets, Alexandre Meunier, Marilou Bourgeon, Benjamin Lefévre, Hélène Jeulin, Karine Legrand, Sandra Lomazzi, Bernard Tardy, Amandine Gagneux-Brunon, Frédérique Bertholon, Elisabeth Botelho-Nevers, Christelle Kouakam, Leturque Nicolas, Layidé Roufai, Karine Amat, Hélène Espérou, Samia Hendou, Giuseppe Foti, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Giacomo Bellani, Jorge Abad, Giulia Accordino, Micol Angelini, Sergio Aguilera-Albesa, Aina Aguiló-Cucurull, Esra Akyüz Özkan, Ilad Alavi Darazam, Jonathan Antonio Roblero Albisures, Juan C. Aldave, Miquel Alfonso Ramos, Taj Ali Khan, Anna Aliberti, Seyed Alireza Nadji, Gulsum Alkan, Suzan A. AlKhater, Jerome Allardet-Servent, Luis M. Allende, Rebeca Alonso-Arias, Mohammed S. Alshahrani, Laia Alsina, Zahir Amoura, Arnau Antolí, Romain Arrestier, Mélodie Aubart, Teresa Auguet, Iryna Avramenko, Gökhan Aytekin, Axelle Azot, Seiamak Bahram, Fanny Bajolle, Fausto Baldanti, Aurélie Baldolli, Maite Ballester, Benoit Barrou, Federica Barzaghi, Sabrina Basso, Gulsum Iclal Bayhan, Liliana Bezrodnik, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blázquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Elisabeth Botdhlo-Nevers, Aurore Bousquet, David Boutolleau, Claire Bouvattier, Oksana Boyarchuk, Juliette Bravais, M. Luisa Briones, Marie-Eve Brunner, Raffaele Bruno, Maria Rita P. Bueno, Huda Bukhari, Jacinta Bustamante, Juan José Cáceres Agra, Ruggero Capra, Raphael Carapito, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Irene Cassaniti, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Jale Bengi Celik, Alessandro Ceschi, Martin Chalumeau, Bruno Charbit, Cécile Boulanger, Père Clavé, Bonaventura Clotet, Anna Codina, Cloé Comarmond, Patrizia Comoli, Angelo G. Corsico, Taner Coşkuner, Aleksandar Cvetkovski, Cyril Cyrus, David Dalmau, François Danion, David Ross Darley, Vincent Das, Nicolas Dauby, Stéphane Dauger, Paul De Munte, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Isabelle Desguerre, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Elena Domínguez-Garrido, Clément Dubost, Olov Ekwall, Şefika Elmas Bozdemir, Marwa H. Elnagdy, Melike Emiroglu, Akifumi Endo, Emine Hafize Erdeniz, Selma Erol Aytekin, Maria Pilar Etxart Lasa, Romain Euvrard, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Ricard Ferrer, Jose Ferreres, Bruno Francois, Victoria Fumadó, Kitty S.C. Fung, Francesca Fusco, Alenka Gagro, Blanca Garcia Solis, Pierre Garçon, Pascale Gaussem, Zeynep Gayretli, Juana Gil-Herrera, Laurent Gilardin, Audrey Giraud Gatineau, Mònica Girona-Alarcón, Karen Alejandra Cifuentes Godínez, Jean-Christophe Goffard, Nacho Gonzales, Luis I. Gonzalez-Granado, Rafaela González-Montelongo, Antoine Guerder, Belgin Gülhan, Victor Daniel Gumucio, Leif Gunnar Hanitsch, Jan Gunst, Marta Gut, Jérôme Hadjadj, Selda Hancerli, Tetyana Hariyan, Nevin Hatipoglu, Deniz Heppekcan, Elisa Hernandez-Brito, Po-ki Ho, María Soledad Holanda-Peña, Juan P. Horcajada, Sami Hraiech, Linda Humbert, Ivan F.N. Hung, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Marie-Thérèse Jimeno, Iolanda Jordan, Saliha Kanık-Yüksek, Yalcin Kara, Aydın Karahan, Adem Karbuz, Kadriye Kart Yasar, Ozgur Kasapcopur, Kenichi Kashimada, Sevgi Keles, Yasemin Kendir Demirkol, Yasutoshi Kido, Can Kizil, Ahmet Osman Kılıç, Adam Klocperk, Antonia Koutsoukou, Zbigniew J. Król, Hatem Ksouri, Paul Kuentz, Arthur M.C. Kwan, Yat Wah M. Kwan, Janette S.Y. Kwok, Jean-Christophe Lagier, David S.Y. Lam, Vicky Lampropoulou, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Daniele Lilleri, Edson Jose Adrian Bolanos Lima, Agnes Linglart, Eduardo López-Collazo, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Kwok-Cheung Lung, Charles-Edouard Luyt, David C. Lye, Cinthia Magnone, Enrico Marchioni, Carola Marioli, Majid Marjani, Laura Marques, Jesus Marquez Pereira, Andrea Martín-Nalda, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Carmen Mata-Martínez, Alexis Mathian, Larissa R.B. Matos, Gail V. Matthews, Julien Mayaux, Raquel McLaughlin-Garcia, Philippe Meersseman, Jean-Louis Mège, Armand Mekontso-Dessap, Isabelle Melki, Federica Meloni, Jean-François Meritet, Paolo Merlani, Özge Metin Akcan, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Matthieu Million, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Yoko Mizoguchi, Bhavi P. Modi, Francesco Mojoli, Elsa Moncomble, Abián Montesdeoca Melián, Antonio Morales Martinez, Francisco Morandeira, Pierre-Emmanuel Morange, Clémence Mordacq, Guillaume Morelle, Stéphane J. Mouly, Adrián Muñoz-Barrera, Cyril Nafati, Shintaro Nagashima, Yu Nakagama, Bénédicte Neven, João Farela Neves, Yuk-Yung Ng, Hubert Nielly, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, Semsi Nur Karabela, J. Gonzalo Ocejo-Vinyals, Mehdi Oualha, Amani Ouedrani, Tayfun Özçelik, Aslinur Ozkaya-Parlakay, Michele Pagani, Maria Papadaki, Philippe Parola, Tiffany Pascreau, Stéphane Paul, Estela Paz-Artal, Sigifredo Pedraza, Nancy Carolina González Pellecer, Silvia Pellegrini, Rebeca Pérez de Diego, Xosé Luis Pérez-Fernández, Aurélien Philippe, Quentin Philippot, Adrien Picod, Marc Pineton de Chambrun, Antonio Piralla, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Garyphallia Poulakou, Marie S. Pouletty, Persia Pourshahnazari, Jia Li Qiu-Chen, Paul Quentric, Thomas Rambaud, Didier Raoult, Violette Raoult, Anne-Sophie Rebillat, Claire Redin, Léa Resmini, Pilar Ricart, Jean-Christophe Richard, Raúl Rigo-Bonnin, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora-Blanch, Mathieu P. Rodero, Carlos Rodrigo, Luis Antonio Rodriguez, Carlos Rodriguez-Gallego, Agustí Rodriguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Damien Roux, Nikoletta Rovina, Flore Rozenberg, Yvon Ruch, Montse Ruiz, Maria Yolanda Ruiz del Prado, Juan Carlos Ruiz-Rodriguez, Joan Sabater-Riera, Kai Saks, Maria Salagianni, Oliver Sanchez, Adrián Sánchez-Montalvá, Silvia Sánchez-Ramón, Laire Schidlowski, Agatha Schluter, Julien Schmidt, Matthieu Schmidt, Catharina Schuetz, Cyril E. Schweitzer, Francesco Scolari, Luis Seijo, Analia Gisela Seminario, Piseth Seng, Sevtap Senoglu, Mikko Seppänen, Alex Serra Llovich, Virginie Siguret, Eleni Siouti, David M. Smadja, Nikaia Smith, Ali Sobh, Xavier Solanich, Jordi Solé-Violán, Catherine Soler, Betül Sözeri, Giulia Maria Stella, Yuriy Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Jean-Luc Taupin, Simon J. Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia

Subjects
HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Published
2024
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42. Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?

Author

Macauda, Angelica, Clay-Gilmour, Alyssa, Hielscher, Thomas, Hildebrandt, Michelle, Kruszewski, Marcin, Orlowski, Robert, Kumar, Shaji, Ziv, Elad, Orciuolo, Enrico, Brown, Elizabeth, Försti, Asta, Waller, Rosalie, Machiela, Mitchell, Chanock, Stephen, Camp, Nicola, Rymko, Marcin, Raźny, Małgorzata, Cozen, Wendy, Várkonyi, Judit, Piredda, Chiara, Pelosini, Matteo, Belachew, Alem, Subocz, Edyta, Hemminki, Kari, Rybicka-Ramos, Malwina, Giles, Graham, Milne, Roger, Hofmann, Jonathan, Zaucha, Jan, Vangsted, Annette, Goldschmidt, Hartmut, Rajkumar, S, Tomczak, Waldemar, Sainz, Juan, Butrym, Aleksandra, Watek, Marzena, Iskierka-Jazdzewska, Elżbieta, Buda, Gabriele, Robinson, Dennis, Jurczyszyn, Artur, Dudziński, Marek, Martinez-Lopez, Joaquin, Sinnwell, Jason, Slager, Susan, Jamroziak, Krzysztof, Reis, Rui, Weinhold, Niels, Bhatti, Parveen, Carvajal-Carmona, Luis, Zawirska, Daria, Norman, Aaron, Mazur, Grzegorz, Berndt, Sonja, Campa, Daniele, Vachon, Celine, and Canzian, Federico

Subjects
Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multiple Myeloma, Polymorphism, Single Nucleotide, Risk Factors
Abstract

BACKGROUND: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival. METHODS: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed. RESULTS: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P < 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09-1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01-1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant. CONCLUSIONS: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS. IMPACT: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.

Published
2022

45. Monitoring drift and associated biodiversity of nearshore rafts of holopelagic Sargassum spp. in the Mexican Caribbean

Author

van Tussenbroek, Brigitta I., Monroy-Velázquez, L. Verónica, Rodríguez, Dení, Suescún-Bolívar, L. Parmenio, Thomé, Patricia E., Cerqueda-García, Daniel, García-Maldonado, José Q., Martínez-López, Isis G., López-Portillo, José Antonio, Barba-Santos, M. Guadalupe, Gómez-Reali, Miguel Angel, and Escalante-Mancera, J. Edgar

Published
2024
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