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19,528 results on '"Mouton, A."'

1. Is network fragmentation a useful complexity measure?

Author

Mouton, Coenraad, Rabe, Randle, Haasbroek, Daniël G., Theunissen, Marthinus W., Potgieter, Hermanus L., and Davel, Marelie H.

Subjects
Computer Science - Machine Learning
Abstract

It has been observed that the input space of deep neural network classifiers can exhibit `fragmentation', where the model function rapidly changes class as the input space is traversed. The severity of this fragmentation tends to follow the double descent curve, achieving a maximum at the interpolation regime. We study this phenomenon in the context of image classification and ask whether fragmentation could be predictive of generalization performance. Using a fragmentation-based complexity measure, we show this to be possible by achieving good performance on the PGDL (Predicting Generalization in Deep Learning) benchmark. In addition, we report on new observations related to fragmentation, namely (i) fragmentation is not limited to the input space but occurs in the hidden representations as well, (ii) fragmentation follows the trends in the validation error throughout training, and (iii) fragmentation is not a direct result of increased weight norms. Together, this indicates that fragmentation is a phenomenon worth investigating further when studying the generalization ability of deep neural networks.

Published
2024

2. Active Prompt Tuning Enables Gpt-40 To Do Efficient Classification Of Microscopy Images

Author

Kandiyana, Abhiram, Mouton, Peter R., Kolinko, Yaroslav, Hall, Lawrence O., and Goldgof, Dmitry

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition
Abstract

Traditional deep learning-based methods for classifying cellular features in microscopy images require time- and labor-intensive processes for training models. Among the current limitations are major time commitments from domain experts for accurate ground truth preparation; and the need for a large amount of input image data. We previously proposed a solution that overcomes these challenges using OpenAI's GPT-4(V) model on a pilot dataset (Iba-1 immuno-stained tissue sections from 11 mouse brains). Results on the pilot dataset were equivalent in accuracy and with a substantial improvement in throughput efficiency compared to the baseline using a traditional Convolutional Neural Net (CNN)-based approach. The present study builds upon this framework using a second unique and substantially larger dataset of microscopy images. Our current approach uses a newer and faster model, GPT-4o, along with improved prompts. It was evaluated on a microscopy image dataset captured at low (10x) magnification from cresyl-violet-stained sections through the cerebellum of a total of 18 mouse brains (9 Lurcher mice, 9 wild-type controls). We used our approach to classify these images either as a control group or Lurcher mutant. Using 6 mice in the prompt set the results were correct classification for 11 out of the 12 mice (92%) with 96% higher efficiency, reduced image requirements, and lower demands on time and effort of domain experts compared to the baseline method (snapshot ensemble of CNN models). These results confirm that our approach is effective across multiple datasets from different brain regions and magnifications, with minimal overhead.

Published
2024

3. Rigidity of singular de-Sitter tori with respect to their lightlike bi-foliation

Author

Mion-Mouton, Martin

Subjects
Mathematics - Differential Geometry, Mathematics - Dynamical Systems, 57M50 (Primary), 37E10, 37E35 (Secondary)
Abstract

In this paper, we introduce a natural notion of constant curvature Lorentzian surfaces with conical singularities, and provide a large class of examples of such structures. We moreover initiate the study of their global rigidity, by proving that de-Sitter tori with a single singularity of a fixed angle are determined by the topological equivalence class of their lightlike bi-foliation. While this result is reminiscent of Troyanov's work on Riemannian surfaces with conical singularities, the rigidity will come from topological dynamics in the Lorentzian case., Comment: 70 pages

Published
2024

4. Risk factors for long COVID syndrome in postmenopausal women with previously reported diagnosis of COVID-19

Author

Neuhouser, Marian L, Butt, Hamza Islam, Hu, Chengcheng, Shadyab, Aladdin H, Garcia, Lorena, Follis, Shawna, Mouton, Charles, Harris, Holly R, Wactawski-Wende, Jean, Gower, Emily, Vitolins, Mara, Von Ah, Diane, Nassir, Rami, Karanth, Shama, Ng, Ted, Paskett, Electra, Manson, JoAnn E, and Chen, Zhao

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Coronaviruses, Prevention, Aging, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, chronic disease, long COVID, machine learning, postmenopausal women, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

PurposeLong COVID-19 syndrome occurs in 10-20 % of people after a confirmed/probable SARS-COV-2 infection; new symptoms begin within three months of COVID-19 diagnosis and last > 8 weeks. Little is known about risk factors for long COVID, particularly in older people who are at greater risk of COVID complications.MethodsData are from Women's Health Initiative (WHI) postmenopausal women who completed COVID surveys that included questions on whether they had ever been diagnosed with COVID and length and nature of symptoms. Long COVID was classified using standard consensus criteria. Using WHI demographic and health data collected at study enrollment (1993-98) through the present day, machine learning identified the top 20 risk factors for long COVID. These variables were tested in logistic regression models.ResultsOf n = 37,280 survey respondents, 1237 (mean age = 83 years) reported a positive COVID-19 test and 425 (30 %) reported long COVID. Symptoms included an array of neurological, cardio-pulmonary, musculoskeletal, and general fatigue, and malaise symptoms. Long COVID risk factors included weight loss, physical and mobility limitations, and specific heath conditions (e.g., history of heart valve procedure, rheumatoid arthritis).ConclusionsKnowledge of risk factors for long COVID may be the first step in understanding the etiology of this complex disease.

Published
2024

5. Reductions of path structures and classification of homogeneous structures in dimension three

Author

Falbel, Elisha, Mion-Mouton, Martin, and Veloso, Jose M.

Subjects
Mathematics - Differential Geometry
Abstract

In this paper we show that if a path structure has non-vanishing curvature at apoint then it has a canonical reduction to a Z/2Z-structure at a neighbourhood of thatpoint (in many cases it has a canonical parallelism). A simple implication of this resultis that the automorphism group of a non-flat path structure is of maximal dimensionthree (a result by Tresse of 1896). We also classify the invariant path structures onthree-dimensional Lie groups.

Published
2024

6. Geometric surgeries of three-dimensional flag structures and non-uniformizable examples

Author

Falbel, Elisha and Mion-Mouton, Martin

Subjects
Mathematics - Differential Geometry
Abstract

In this paper, we introduce a notion of geometric surgery for flag structures, which are geometric structures locally modelled on the three-dimensional flag space under the action of ${\mathrm{PGL}}_3(\mathbb{R})$. Using such surgeries we provide examples of flag structures, of both uniformizable and non-uniformizable type.

Published
2024

7. Equity in the Early Pain Management of Long Bone Fractures in Black vs White Patients: We Have Closed the Gap

Author

Jehle, Dietrich, Paul, Krishna K., Troung, Stanley, Rogers, Jackson M., Mireles, Blake, Straub, John J., Golovko, Georgiy, Talbott, Matthew M., Lindsey, Ronald W., and Mouton, Charles P.

Subjects
Equity, Opioid analgesia, non-opioid analgesia, Long bone fracture, pain management
Abstract

Introduction: Patients with long bone fractures often present to the emergency department (ED) with severe pain and are typically treated with opioid and non-opioid analgesics. Historical data reveals racial disparities in analgesic administration, with White patients more likely to receive analgesics. With the diversifying US population, health equity is increasingly crucial. In this study we aimed to evaluate the early administration of opioid and non-opioid analgesia among Black and White patients with long bone and femur fractures in EDs over different time frames using a substantial database.Methods: We retrospectively extracted Information from 57 US healthcare organizations within the TriNetX database, encompassing 95 million patients. The ED records from 2003–2023 were subjected to propensity score matching for age and gender. We focused on four cohorts: two comprising Black and White patients diagnosed with long bone fractures, and another two with Black and White patients diagnosed solely with femur fractures. We examined analgesic administration rates over 20 years (2003–2023) at five-year intervals (2003–2008; 2008–2013; 2013–2018; 2018–2023), and further analyzed the rates for the most recent two-year period (2021–2023).Results: Disparities in analgesic administration significantly diminished over the study period. For patients with long bone fractures (1,095,052), the opioid administration gap narrowed from 6.3% to 1.1%, while non-opioid administration disparities reduced from 4.4% to 0.3%. Similar trends were noted for femur fractures (265,181). By 2021–2023, no significant differences in analgesic administration were observed between racial groups.Conclusion: Over the past 20 years, the gap in early administration of opioid and non-opioid analgesics for Black and White patients presenting with long bone fractures or femur fractures has been disappearing.

Published
2024

8. On margin-based generalization prediction in deep neural networks

Author

Mouton, Coenraad

Subjects
Computer Science - Machine Learning, Computer Science - Computer Vision and Pattern Recognition
Abstract

Understanding generalization in deep neural networks is an active area of research. A promising avenue of exploration has been that of margin measurements: the shortest distance to the decision boundary for a given sample or that sample's representation internal to the network. Margin-based complexity measures have been shown to be correlated with the generalization ability of deep neural networks in some circumstances but not others. The reasons behind the success or failure of these metrics are currently unclear. In this study, we examine margin-based generalization prediction methods in different settings. We motivate why these metrics sometimes fail to accurately predict generalization and how they can be improved. First, we analyze the relationship between margins measured in the input space and sample noise. We find that different types of sample noise can have a very different effect on the overall margin of a network that has modeled noisy data. Following this, we empirically evaluate how robust margins measured at different representational spaces are at predicting generalization. We find that these metrics have several limitations and that a large margin does not exhibit a strong correlation with empirical risk in many cases. Finally, we introduce a new margin-based measure that incorporates an approximation of the underlying data manifold. It is empirically demonstrated that this measure is generally more predictive of generalization than all other margin-based measures. Furthermore, we find that this measurement also outperforms other contemporary complexity measures on a well-known generalization prediction benchmark. In addition, we analyze the utility and limitations of this approach and find that this metric is well aligned with intuitions expressed in prior work., Comment: PhD Thesis

Published
2024

9. RobotCycle: Assessing Cycling Safety in Urban Environments

Author

Panagiotaki, Efimia, Reinmund, Tyler, Mouton, Stephan, Pitt, Luke, Shanthini, Arundathi Shaji, Tubby, Wayne, Towlson, Matthew, Sze, Samuel, Liu, Brian, Prahacs, Chris, De Martini, Daniele, and Kunze, Lars

Subjects
Computer Science - Robotics
Abstract

This paper introduces RobotCycle, a novel ongoing project that leverages Autonomous Vehicle (AV) research to investigate how road infrastructure influences cyclist behaviour and safety during real-world journeys. The project's requirements were defined in collaboration with key stakeholders, including city planners, cyclists, and policymakers, informing the design of risk and safety metrics and the data collection criteria. We propose a data-driven approach relying on a novel, rich dataset of diverse traffic scenes and scenarios captured using a custom-designed wearable sensing unit. By analysing road-user trajectories, we identify normal path deviations indicating potential risks or hazardous interactions related to infrastructure elements in the environment. Our analysis correlates driving profiles and trajectory patterns with local road segments, driving conditions, and road-user interactions to predict traffic behaviours and identify critical scenarios. Moreover, by leveraging advancements in AV research, the project generates detailed 3D High-Definition Maps (HD Maps), traffic flow patterns, and trajectory models to provide a comprehensive assessment and analysis of the behaviour of all traffic agents. These data can then inform the design of cyclist-friendly road infrastructure, ultimately enhancing road safety and cyclability. The project provides valuable insights for enhancing cyclist protection and advancing sustainable urban mobility., Comment: IEEE Intelligent Vehicles Symposium (IV 2024)

Published
2024

10. Exploring the Challenges of Curriculum Advisors in Schools in the Vhembe-West District, Limpopo Province, South Africa

Author

Mouton, Nelda and Malumbete, Phamela

Abstract

Monitoring and supporting teachers in the classroom, as well as the implementation of curriculum changes, pose problems in South Africa. This is due to an array of challenges such as a lack of resources, communication barriers within the Department of Basic Education (DBE) as well as a lack of proper infrastructure. In the research reported on here we investigated the challenges that curriculum advisors in the Vhembe-West district face and provides insight into some of their daily challenges. This could assist the international platform, especially as developing countries and other Third World Countries can benefit from the outcomes of this research. A qualitative research approach was used where 12 interviews were conducted with curriculum advisors in the Vhembe-West district. The interview questions were e-mailed to them beforehand so that they could familiarise themselves with the questions to be answered. Within a period of 2 weeks thereafter, interviews were conducted and recorded for analysis on Zoom or Microsoft Teams. The data were grouped and are presented in 5 different themes with the aim of highlighting the challenges as well as providing recommendations to deal with the challenges that curriculum advisors experience. The data reveal that curriculum advisors experience that they receive minimal support from their superiors and that the resources at their disposal also prove to be minimal. This study highlights the lack of resources, insufficient infrastructure, and lack of effective communication from management needed for proper curriculum implementation at schools.

Published
2023

11. A methylation risk score for chronic kidney disease: a HyperGEN study

Author

Jones, Alana C, Patki, Amit, Srinivasasainagendra, Vinodh, Hidalgo, Bertha A, Tiwari, Hemant K, Limdi, Nita A, Armstrong, Nicole D, Chaudhary, Ninad S, Minniefield, Bré, Absher, Devin, Arnett, Donna K, Lange, Leslie A, Lange, Ethan M, Young, Bessie A, Diamantidis, Clarissa J, Rich, Stephen S, Mychaleckyj, Josyf C, Rotter, Jerome I, Taylor, Kent D, Kramer, Holly J, Tracy, Russell P, Durda, Peter, Kasela, Silva, Lappalinen, Tuuli, Liu, Yongmei, Johnson, W Craig, Van Den Berg, David J, Franceschini, Nora, Liu, Simin, Mouton, Charles P, Bhatti, Parveen, Horvath, Steve, Whitsel, Eric A, and Irvin, Marguerite R

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Prevention, Clinical Research, Human Genome, Health Disparities, Kidney Disease, Minority Health, Women's Health, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Renal and urogenital, Humans, Renal Insufficiency, Chronic, DNA Methylation, Male, Female, Middle Aged, Glomerular Filtration Rate, CpG Islands, Risk Factors, Black or African American, Aged, Genome-Wide Association Study, Epigenesis, Genetic, Adult, Genetic Predisposition to Disease, Chronic kidney disease, eGFR, Methylation risk score, Epigenetics
Abstract

Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

Published
2024

13. The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics

Author

Ann M. Mc Cartney, Giulio Formenti, Alice Mouton, Diego De Panis, Luísa S. Marins, Henrique G. Leitão, Genevieve Diedericks, Joseph Kirangwa, Marco Morselli, Judit Salces-Ortiz, Nuria Escudero, Alessio Iannucci, Chiara Natali, Hannes Svardal, Rosa Fernández, Tim De Pooter, Geert Joris, Mojca Strazisar, Jonathan M. D. Wood, Katie E. Herron, Ole Seehausen, Phillip C. Watts, Felix Shaw, Robert P. Davey, Alice Minotto, José M. Fernández, Astrid Böhne, Carla Alegria, Tyler Alioto, Paulo C. Alves, Isabel R. Amorim, Jean-Marc Aury, Niclas Backstrom, Petr Baldrian, Laima Baltrunaite, Endre Barta, Bertrand BedHom, Caroline Belser, Johannes Bergsten, Laurie Bertrand, Helena Bilandija, Mahesh Binzer-Panchal, Iliana Bista, Mark Blaxter, Paulo A. V. Borges, Guilherme Borges Dias, Mirte Bosse, Tom Brown, Rémy Bruggmann, Elena Buena-Atienza, Josephine Burgin, Elena Buzan, Alessia Cariani, Nicolas Casadei, Matteo Chiara, Sergio Chozas, Fedor Čiampor, Angelica Crottini, Corinne Cruaud, Fernando Cruz, Love Dalen, Alessio De Biase, Javier del Campo, Teo Delic, Alice B. Dennis, Martijn F. L. Derks, Maria Angela Diroma, Mihajla Djan, Simone Duprat, Klara Eleftheriadi, Philine G. D. Feulner, Jean-François Flot, Giobbe Forni, Bruno Fosso, Pascal Fournier, Christine Fournier-Chambrillon, Toni Gabaldon, Shilpa Garg, Carmela Gissi, Luca Giupponi, Jessica Gomez-Garrido, Josefa González, Miguel L. Grilo, Björn Grüning, Thomas Guerin, Nadege Guiglielmoni, Marta Gut, Marcel P. Haesler, Christoph Hahn, Balint Halpern, Peter W. Harrison, Julia Heintz, Maris Hindrikson, Jacob Höglund, Kerstin Howe, Graham M. Hughes, Benjamin Istace, Mark J. Cock, Franc Janžekovič, Zophonias O. Jonsson, Sagane Joye-Dind, Janne J. Koskimäki, Boris Krystufek, Justyna Kubacka, Heiner Kuhl, Szilvia Kusza, Karine Labadie, Meri Lähteenaro, Henrik Lantz, Anton Lavrinienko, Lucas Leclère, Ricardo Jorge Lopes, Ole Madsen, Ghislaine Magdelenat, Giulia Magoga, Tereza Manousaki, Tapio Mappes, Joao Pedro Marques, Gemma I. Martinez Redondo, Florian Maumus, Shane A. McCarthy, Hendrik-Jan Megens, Jose Melo-Ferreira, Sofia L. Mendes, Matteo Montagna, Joao Moreno, Mai-Britt Mosbech, Mónica Moura, Zuzana Musilova, Eugene Myers, Will J. Nash, Alexander Nater, Pamela Nicholson, Manuel Niell, Reindert Nijland, Benjamin Noel, Karin Noren, Pedro H. Oliveira, Remi-Andre Olsen, Lino Ometto, Rebekah A. Oomen, Stephan Ossowski, Vaidas Palinauskas, Snaebjorn Palsson, Jerome P. Panibe, Joana Pauperio, Martina Pavlek, Emilie Payen, Julia Pawlowska, Jaume Pellicer, Graziano Pesole, Joao Pimenta, Martin Pippel, Anna Maria Pirttilä, Nikos Poulakakis, Jeena Rajan, Rúben M.C. Rego, Roberto Resendes, Philipp Resl, Ana Riesgo, Patrik Rodin-Morch, Andre E. R. Soares, Carlos Rodriguez Fernandes, Maria M. Romeiras, Guilherme Roxo, Lukas Rüber, Maria Jose Ruiz-Lopez, Urmas Saarma, Luis P. da Silva, Manuela Sim-Sim, Lucile Soler, Vitor C. Sousa, Carla Sousa Santos, Alberto Spada, Milomir Stefanovic, Viktor Steger, Josefin Stiller, Matthias Stöck, Torsten H. Struck, Hiranya Sudasinghe, Riikka Tapanainen, Christian Tellgren-Roth, Helena Trindade, Yevhen Tukalenko, Ilenia Urso, Benoit Vacherie, Steven M. Van Belleghem, Kees Van Oers, Carlos Vargas-Chavez, Nevena Velickovic, Noel Vella, Adriana Vella, Cristiano Vernesi, Sara Vicente, Sara Villa, Olga Vinnere Pettersson, Filip A. M. Volckaert, Judit Voros, Patrick Wincker, Sylke Winkler, Claudio Ciofi, Robert M. Waterhouse, and Camila J. Mazzoni

Subjects
General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

Abstract A genomic database of all Earth’s eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.

Published
2024
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14. Building a Portuguese coalition for biodiversity genomics

Author

João P. Marques, Paulo C. Alves, Isabel R. Amorim, Ricardo J. Lopes, Monica Moura, Eugene Myers, Manuela Sim-sim, Carla Sousa-Santos, M. Judite Alves, Paulo A. V. Borges, Thomas Brown, Miguel Carneiro, Carlos Carrapato, Luís M. P. Ceríaco, Claúdio Ciofi, Luís P. da Silva, Genevieve Diedericks, Maria Angela Diroma, Liliana Farelo, Giulio Formenti, Fátima Gil, Miguel Grilo, Alessio Iannucci, Henrique G. Leitão, Cristina Máguas, Ann M. Mc Cartney, Sofia L. Mendes, João M. Moreno, Marco Morselli, Alice Mouton, Chiara Natali, Fernando Pereira, Rúben M. C. Rego, Roberto Resendes, Guilherme Roxo, Hannes Svardal, Helena Trindade, Sara Vicente, Sylke Winkler, Marcela Alvarenga, Andreia J. Amaral, Agostinho Antunes, Paula F. Campos, Adelino V. M. Canário, Rita Castilho, L. Filipe C. Castro, Angelica Crottini, Mónica V. Cunha, Gonçalo Espregueira Themudo, Pedro J. Esteves, Rui Faria, Carlos Rodríguez Fernandes, Jean-Baptiste Ledoux, Bruno Louro, Sara Magalhaes, Octávio S. Paulo, Gareth Pearson, João Pimenta, Francisco Pina-Martins, Teresa L. Santos, Ester Serrão, José Melo-Ferreira, and Vítor C. Sousa

Subjects
General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

The diverse physiography of the Portuguese land and marine territory, spanning from continental Europe to the Atlantic archipelagos, has made it an important repository of biodiversity throughout the Pleistocene glacial cycles, leading to a remarkable diversity of species and ecosystems. This rich biodiversity is under threat from anthropogenic drivers, such as climate change, invasive species, land use changes, overexploitation, or pathogen (re)emergence. The inventory, characterisation, and study of biodiversity at inter- and intra-specific levels using genomics is crucial to promote its preservation and recovery by informing biodiversity conservation policies, management measures, and research. The participation of researchers from Portuguese institutions in the European Reference Genome Atlas (ERGA) initiative and its pilot effort to generate reference genomes for European biodiversity has reinforced the establishment of Biogenome Portugal. This nascent institutional network will connect the national community of researchers in genomics. Here, we describe the Portuguese contribution to ERGA’s pilot effort, which will generate high-quality reference genomes of six species from Portugal that are endemic, iconic, and/or endangered and include plants, insects, and vertebrates (fish, birds, and mammals) from mainland Portugal or the Azores islands. In addition, we outline the objectives of Biogenome Portugal, which aims to (i) promote scientific collaboration, (ii) contribute to advanced training, (iii) stimulate the participation of institutions and researchers based in Portugal in international biodiversity genomics initiatives, and (iv) contribute to the transfer of knowledge to stakeholders and engaging the public to preserve biodiversity. This initiative will strengthen biodiversity genomics research in Portugal and fuel the genomic inventory of Portuguese eukaryotic species. Such efforts will be critical to the conservation of the country’s rich biodiversity and will contribute to ERGA’s goal of generating reference genomes for European species.

Published
2024
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15. A new patient-reported outcome measure for the evaluation of ankle instability: description of the development process and validation protocol

Author

Pietro Spennacchio, Eric Hamrin Senorski, Caroline Mouton, Jan Cabri, Romain Seil, and Jon Karlsson

Subjects
Chronic ankle instability, Patient-reported outcomes, Surgical treatment, Scale development, Validity, Reliability, Orthopedic surgery, RD701-811, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Acute ankle sprains represent one of the most common traumatic injuries to the musculoskeletal system. Many individuals with these injuries experience unresolved symptoms such as instability and recurrent sprains, leading to chronic ankle instability (CAI), which affects their ability to maintain an active lifestyle. While rehabilitation programs focusing on sensorimotor, neuromuscular, strength and balance training are primary treatments, some patients require surgery when rehabilitation fails. A critical analysis of the patient-reported outcome tools (PROs) used to assess CAI surgical outcomes raises some concerns about their measurement properties in CAI patients, which may ultimately affect the quality of evidence supporting current surgical practice. The aim of this research is to develop and validate a new PRO for the assessment of ankle instability and CAI treatment outcomes, following recent methodological guidelines, with the implicit aim of contributing to the generation of scientifically meaningful evidence for clinical practice in patients with ankle instability. Methods Following the COnsensus-based Standards for the selection of Health Measurement Instruments (COSMIN), an Ankle Instability Treatment Index (AITI) will be developed and validated. The process begins with qualitative research based on face‒to‒face interviews with CAI individuals to explore the subjective experience of living with ankle instability. The data from the interviews will be coded following an inductive approach and used to develop the AITI content. The preliminary version of the scale will be refined through an additional round of face‒to‒face interviews with a new set of CAI subjects to define the AITI content coverage, relevance and clarity. Once content validity has been examined, the AITI will be subjected to quantitative analysis of different measurement properties: construct validity, reliability and responsiveness. Discussion The development of AITI aims to address the limitations of existing instruments for evaluating surgical outcomes in patients with CAI. By incorporating patient input and adhering to contemporary standards for validity and reliability, this tool seeks to provide a reliable and meaningful assessment of treatment effects. Trial registration Not applicable.

Published
2024
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16. Elementary Administrators' Perceptions of the Response to Intervention Framework for Addressing COVID-19 Learning Loss

Author

Kayla Mouton

Abstract

This qualitative phenomenological study examines elementary administrators' perceptions of the Response to Intervention (RtI) framework in response to the COVID-19 pandemic learning disruption. Ten elementary campus administrators were interviewed to gain insights into their perspectives and lived experiences regarding the use of RtI at the campus level. Interviews were analyzed and coded using the "theming the data" method by Saldana (2021). Findings from this study indicate that there is a need for campus procedural consistency and fidelity of tiered instruction. Additionally, campus resources have become strained in response to the heightened volume of students experiencing academic challenges after the pandemic. Lastly, participants expressed a need for further staff training on effective RtI practices, procedures, interventions, and tiers of support. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Published
2024

17. Input margins can predict generalization too

Author

Mouton, Coenraad, Theunissen, Marthinus W., and Davel, Marelie H.

Subjects
Computer Science - Machine Learning, Computer Science - Computer Vision and Pattern Recognition
Abstract

Understanding generalization in deep neural networks is an active area of research. A promising avenue of exploration has been that of margin measurements: the shortest distance to the decision boundary for a given sample or its representation internal to the network. While margins have been shown to be correlated with the generalization ability of a model when measured at its hidden representations (hidden margins), no such link between large margins and generalization has been established for input margins. We show that while input margins are not generally predictive of generalization, they can be if the search space is appropriately constrained. We develop such a measure based on input margins, which we refer to as `constrained margins'. The predictive power of this new measure is demonstrated on the 'Predicting Generalization in Deep Learning' (PGDL) dataset and contrasted with hidden representation margins. We find that constrained margins achieve highly competitive scores and outperform other margin measurements in general. This provides a novel insight on the relationship between generalization and classification margins, and highlights the importance of considering the data manifold for investigations of generalization in DNNs.

Published
2023

20. Menopausal hormone therapy and change in physical activity in the Womens Health Initiative hormone therapy clinical trials.

Author

Peila, Rita, Xue, Xiaonan, LaMonte, Michael, Shadyab, Aladdin, Wactawski-Wende, Jean, Jung, Su Yon, Johnson, Karen, Coday, Mace, Richey, Phyllis, Mouton, Charles, Saquib, Nazums, Chlebowski, Rowan, Pan, Kathy, Michael, Yvonne, LeBoff, Meryl, Manson, JoAnn, and Rohan, Thomas

Subjects
Female, Humans, Estrogens, Conjugated (USP), Estrogens, Womens Health, Menopause, Exercise, Estrogen Replacement Therapy, Medroxyprogesterone Acetate
Abstract

OBJECTIVE: The menopausal transition results in a progressive decrease in circulating estrogen levels. Experimental evidence in rodents has indicated that estrogen depletion leads to a reduction of energy expenditure and physical activity. It is unclear whether treatment with estrogen therapy increases physical activity level in postmenopausal women. METHODS: A total of 27,327 postmenopausal women aged 50-79 years enrolled in the Womens Health Initiative randomized double-blind trials of menopausal hormone therapy. Self-reported leisure-time physical activity at baseline, and years 1, 3, and 6 was quantified as metabolic equivalents (MET)-h/wk. In each trial, comparison between intervention and placebo groups of changes in physical activity levels from baseline to follow-up assessment was examined using linear regression models. RESULTS: In the CEE-alone trial, the increase in MET-h/wk was greater in the placebo group compared with the intervention group at years 3 ( P = 0.002) and 6 ( P < 0.001). Similar results were observed when analyses were restricted to women who maintained an adherence rate ≥80% during the trial or who were physically active at baseline. In the CEE + MPA trial, the primary analyses did not show significant differences between groups, but the increase of MET-h/wk was greater in the placebo group compared with the intervention group at year 3 ( P = 0.004) among women with an adherence rate ≥80%. CONCLUSIONS: The results from this clinical trial do not support the hypothesis that estrogen treatment increases physical activity among postmenopausal women.

Published
2023

22. Author Correction: The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics

Author

Mc Cartney, Ann M., Formenti, Giulio, Mouton, Alice, De Panis, Diego, Marins, Luísa S., Leitão, Henrique G., Diedericks, Genevieve, Kirangwa, Joseph, Morselli, Marco, Salces-Ortiz, Judit, Escudero, Nuria, Iannucci, Alessio, Natali, Chiara, Svardal, Hannes, Fernández, Rosa, De Pooter, Tim, Joris, Geert, Strazisar, Mojca, Wood, Jonathan M. D., Herron, Katie E., Seehausen, Ole, Watts, Phillip C., Shaw, Felix, Davey, Robert P., Minotto, Alice, Fernández, José M., Böhne, Astrid, Alegria, Carla, Alioto, Tyler, Alves, Paulo C., Amorim, Isabel R., Aury, Jean-Marc, Backstrom, Niclas, Baldrian, Petr, Baltrunaite, Laima, Barta, Endre, BedHom, Bertrand, Belser, Caroline, Bergsten, Johannes, Bertrand, Laurie, Bilandija, Helena, Binzer-Panchal, Mahesh, Bista, Iliana, Blaxter, Mark, Borges, Paulo A. V., Dias, Guilherme Borges, Bosse, Mirte, Brown, Tom, Bruggmann, Rémy, Buena-Atienza, Elena, Burgin, Josephine, Buzan, Elena, Cariani, Alessia, Casadei, Nicolas, Chiara, Matteo, Chozas, Sergio, Čiampor, Jr., Fedor, Crottini, Angelica, Cruaud, Corinne, Cruz, Fernando, Dalen, Love, De Biase, Alessio, del Campo, Javier, Delic, Teo, Dennis, Alice B., Derks, Martijn F. L., Diroma, Maria Angela, Djan, Mihajla, Duprat, Simone, Eleftheriadi, Klara, Feulner, Philine G. D., Flot, Jean-François, Forni, Giobbe, Fosso, Bruno, Fournier, Pascal, Fournier-Chambrillon, Christine, Gabaldon, Toni, Garg, Shilpa, Gissi, Carmela, Giupponi, Luca, Gomez-Garrido, Jessica, González, Josefa, Grilo, Miguel L., Grüning, Björn, Guerin, Thomas, Guiglielmoni, Nadege, Gut, Marta, Haesler, Marcel P., Hahn, Christoph, Halpern, Balint, Harrison, Peter W., Heintz, Julia, Hindrikson, Maris, Höglund, Jacob, Howe, Kerstin, Hughes, Graham M., Istace, Benjamin, Cock, Mark J., Janžekovič, Franc, Jonsson, Zophonias O., Joye-Dind, Sagane, Koskimäki, Janne J., Krystufek, Boris, Kubacka, Justyna, Kuhl, Heiner, Kusza, Szilvia, Labadie, Karine, Lähteenaro, Meri, Lantz, Henrik, Lavrinienko, Anton, Leclère, Lucas, Lopes, Ricardo Jorge, Madsen, Ole, Magdelenat, Ghislaine, Magoga, Giulia, Manousaki, Tereza, Mappes, Tapio, Marques, Joao Pedro, Redondo, Gemma I. Martinez, Maumus, Florian, McCarthy, Shane A., Megens, Hendrik-Jan, Melo-Ferreira, Jose, Mendes, Sofia L., Montagna, Matteo, Moreno, Joao, Mosbech, Mai-Britt, Moura, Mónica, Musilova, Zuzana, Myers, Eugene, Nash, Will J., Nater, Alexander, Nicholson, Pamela, Niell, Manuel, Nijland, Reindert, Noel, Benjamin, Noren, Karin, Oliveira, Pedro H., Olsen, Remi-Andre, Ometto, Lino, Oomen, Rebekah A., Ossowski, Stephan, Palinauskas, Vaidas, Palsson, Snaebjorn, Panibe, Jerome P., Pauperio, Joana, Pavlek, Martina, Payen, Emilie, Pawlowska, Julia, Pellicer, Jaume, Pesole, Graziano, Pimenta, Joao, Pippel, Martin, Pirttilä, Anna Maria, Poulakakis, Nikos, Rajan, Jeena, M.C. Rego, Rúben, Resendes, Roberto, Resl, Philipp, Riesgo, Ana, Rodin-Morch, Patrik, Soares, Andre E. R., Fernandes, Carlos Rodriguez, Romeiras, Maria M., Roxo, Guilherme, Rüber, Lukas, Ruiz-Lopez, Maria Jose, Saarma, Urmas, da Silva, Luis P., Sim-Sim, Manuela, Soler, Lucile, Sousa, Vitor C., Santos, Carla Sousa, Spada, Alberto, Stefanovic, Milomir, Steger, Viktor, Stiller, Josefin, Stöck, Matthias, Struck, Torsten H., Sudasinghe, Hiranya, Tapanainen, Riikka, Tellgren-Roth, Christian, Trindade, Helena, Tukalenko, Yevhen, Urso, Ilenia, Vacherie, Benoit, Van Belleghem, Steven M., Van Oers, Kees, Vargas-Chavez, Carlos, Velickovic, Nevena, Vella, Noel, Vella, Adriana, Vernesi, Cristiano, Vicente, Sara, Villa, Sara, Pettersson, Olga Vinnere, Volckaert, Filip A. M., Voros, Judit, Wincker, Patrick, Winkler, Sylke, Ciofi, Claudio, Waterhouse, Robert M., and Mazzoni, Camila J.

Published
2024
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23. Building a Portuguese coalition for biodiversity genomics

Author

Marques, João P., Alves, Paulo C., Amorim, Isabel R., Lopes, Ricardo J., Moura, Monica, Myers, Eugene, Sim-sim, Manuela, Sousa-Santos, Carla, Alves, M. Judite, Borges, Paulo A. V., Brown, Thomas, Carneiro, Miguel, Carrapato, Carlos, Ceríaco, Luís M. P., Ciofi, Claúdio, da Silva, Luís P., Diedericks, Genevieve, Diroma, Maria Angela, Farelo, Liliana, Formenti, Giulio, Gil, Fátima, Grilo, Miguel, Iannucci, Alessio, Leitão, Henrique G., Máguas, Cristina, Mc Cartney, Ann M., Mendes, Sofia L., Moreno, João M., Morselli, Marco, Mouton, Alice, Natali, Chiara, Pereira, Fernando, Rego, Rúben M. C., Resendes, Roberto, Roxo, Guilherme, Svardal, Hannes, Trindade, Helena, Vicente, Sara, Winkler, Sylke, Alvarenga, Marcela, Amaral, Andreia J., Antunes, Agostinho, Campos, Paula F., Canário, Adelino V. M., Castilho, Rita, Castro, L. Filipe C., Crottini, Angelica, Cunha, Mónica V., Espregueira Themudo, Gonçalo, Esteves, Pedro J., Faria, Rui, Rodríguez Fernandes, Carlos, Ledoux, Jean-Baptiste, Louro, Bruno, Magalhaes, Sara, Paulo, Octávio S., Pearson, Gareth, Pimenta, João, Pina-Martins, Francisco, Santos, Teresa L., Serrão, Ester, Melo-Ferreira, José, and Sousa, Vítor C.

Published
2024
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24. The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics

Author

Mc Cartney, Ann M., Formenti, Giulio, Mouton, Alice, De Panis, Diego, Marins, Luísa S., Leitão, Henrique G., Diedericks, Genevieve, Kirangwa, Joseph, Morselli, Marco, Salces-Ortiz, Judit, Escudero, Nuria, Iannucci, Alessio, Natali, Chiara, Svardal, Hannes, Fernández, Rosa, De Pooter, Tim, Joris, Geert, Strazisar, Mojca, Wood, Jonathan M. D., Herron, Katie E., Seehausen, Ole, Watts, Phillip C., Shaw, Felix, Davey, Robert P., Minotto, Alice, Fernández, José M., Böhne, Astrid, Alegria, Carla, Alioto, Tyler, Alves, Paulo C., Amorim, Isabel R., Aury, Jean-Marc, Backstrom, Niclas, Baldrian, Petr, Baltrunaite, Laima, Barta, Endre, BedHom, Bertrand, Belser, Caroline, Bergsten, Johannes, Bertrand, Laurie, Bilandija, Helena, Binzer-Panchal, Mahesh, Bista, Iliana, Blaxter, Mark, Borges, Paulo A. V., Dias, Guilherme Borges, Bosse, Mirte, Brown, Tom, Bruggmann, Rémy, Buena-Atienza, Elena, Burgin, Josephine, Buzan, Elena, Cariani, Alessia, Casadei, Nicolas, Chiara, Matteo, Chozas, Sergio, Čiampor, Jr., Fedor, Crottini, Angelica, Cruaud, Corinne, Cruz, Fernando, Dalen, Love, De Biase, Alessio, del Campo, Javier, Delic, Teo, Dennis, Alice B., Derks, Martijn F. L., Diroma, Maria Angela, Djan, Mihajla, Duprat, Simone, Eleftheriadi, Klara, Feulner, Philine G. D., Flot, Jean-François, Forni, Giobbe, Fosso, Bruno, Fournier, Pascal, Fournier-Chambrillon, Christine, Gabaldon, Toni, Garg, Shilpa, Gissi, Carmela, Giupponi, Luca, Gomez-Garrido, Jessica, González, Josefa, Grilo, Miguel L., Grüning, Björn, Guerin, Thomas, Guiglielmoni, Nadege, Gut, Marta, Haesler, Marcel P., Hahn, Christoph, Halpern, Balint, Harrison, Peter W., Heintz, Julia, Hindrikson, Maris, Höglund, Jacob, Howe, Kerstin, Hughes, Graham M., Istace, Benjamin, Cock, Mark J., Janžekovič, Franc, Jonsson, Zophonias O., Joye-Dind, Sagane, Koskimäki, Janne J., Krystufek, Boris, Kubacka, Justyna, Kuhl, Heiner, Kusza, Szilvia, Labadie, Karine, Lähteenaro, Meri, Lantz, Henrik, Lavrinienko, Anton, Leclère, Lucas, Lopes, Ricardo Jorge, Madsen, Ole, Magdelenat, Ghislaine, Magoga, Giulia, Manousaki, Tereza, Mappes, Tapio, Marques, Joao Pedro, Redondo, Gemma I. Martinez, Maumus, Florian, McCarthy, Shane A., Megens, Hendrik-Jan, Melo-Ferreira, Jose, Mendes, Sofia L., Montagna, Matteo, Moreno, Joao, Mosbech, Mai-Britt, Moura, Mónica, Musilova, Zuzana, Myers, Eugene, Nash, Will J., Nater, Alexander, Nicholson, Pamela, Niell, Manuel, Nijland, Reindert, Noel, Benjamin, Noren, Karin, Oliveira, Pedro H., Olsen, Remi-Andre, Ometto, Lino, Oomen, Rebekah A., Ossowski, Stephan, Palinauskas, Vaidas, Palsson, Snaebjorn, Panibe, Jerome P., Pauperio, Joana, Pavlek, Martina, Payen, Emilie, Pawlowska, Julia, Pellicer, Jaume, Pesole, Graziano, Pimenta, Joao, Pippel, Martin, Pirttilä, Anna Maria, Poulakakis, Nikos, Rajan, Jeena, M.C. Rego, Rúben, Resendes, Roberto, Resl, Philipp, Riesgo, Ana, Rodin-Morch, Patrik, Soares, Andre E. R., Fernandes, Carlos Rodriguez, Romeiras, Maria M., Roxo, Guilherme, Rüber, Lukas, Ruiz-Lopez, Maria Jose, Saarma, Urmas, da Silva, Luis P., Sim-Sim, Manuela, Soler, Lucile, Sousa, Vitor C., Santos, Carla Sousa, Spada, Alberto, Stefanovic, Milomir, Steger, Viktor, Stiller, Josefin, Stöck, Matthias, Struck, Torsten H., Sudasinghe, Hiranya, Tapanainen, Riikka, Tellgren-Roth, Christian, Trindade, Helena, Tukalenko, Yevhen, Urso, Ilenia, Vacherie, Benoit, Van Belleghem, Steven M., Van Oers, Kees, Vargas-Chavez, Carlos, Velickovic, Nevena, Vella, Noel, Vella, Adriana, Vernesi, Cristiano, Vicente, Sara, Villa, Sara, Pettersson, Olga Vinnere, Volckaert, Filip A. M., Voros, Judit, Wincker, Patrick, Winkler, Sylke, Ciofi, Claudio, Waterhouse, Robert M., and Mazzoni, Camila J.

Published
2024
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26. Teaching transposon classification as a means to crowd source the curation of repeat annotation – a tardigrade perspective

Author

Peona, Valentina, Martelossi, Jacopo, Almojil, Dareen, Bocharkina, Julia, Brännström, Ioana, Brown, Max, Cang, Alice, Carrasco-Valenzuela, Tomàs, DeVries, Jon, Doellman, Meredith, Elsner, Daniel, Espíndola-Hernández, Pamela, Montoya, Guillermo Friis, Gaspar, Bence, Zagorski, Danijela, Hałakuc, Paweł, Ivanovska, Beti, Laumer, Christopher, Lehmann, Robert, Boštjančić, Ljudevit Luka, Mashoodh, Rahia, Mazzoleni, Sofia, Mouton, Alice, Nilsson, Maria Anna, Pei, Yifan, Potente, Giacomo, Provataris, Panagiotis, Pardos-Blas, José Ramón, Raut, Ravindra, Sbaffi, Tomasa, Schwarz, Florian, Stapley, Jessica, Stevens, Lewis, Sultana, Nusrat, Symonova, Radka, Tahami, Mohadeseh S., Urzì, Alice, Yang, Heidi, Yusuf, Abdullah, Pecoraro, Carlo, and Suh, Alexander

Published
2024
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29. Systems Development of a Two-Axis Stabilised Platform to Facilitate Astronomical Observations from a Moving Base

Author

Hepworth, James H and Mouton, Hendrik D

Subjects
Electrical Engineering and Systems Science - Systems and Control, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

This project aimed to design, simulate, and implement a two-axis inertially stabilised platform (ISP) for use in astronomical applications. It aimed to approximate the stabilisation of a Meade ETX-90 3.5" compound telescope at low-cost using a mechanical assembly designed to geometrically and inertially model the telescope. A set of system specifications was developed to guide design decisions and to provide an analysis framework against which the performance of the implemented system was compared. The electro-mechanical structure of the ISP was designed and manufactured, the associated electrical systems were specified and configured, an image processing script capable of detecting and locating the centre of the Moon in a camera field-of-view was written, a complete simulation model for the system was developed and used to design various classical controllers for the ISP control system. These controllers were implemented on a STM32F051 microcontroller and a user interface was written in LabVIEW to facilitate intuitive user control of the system and perform datalogging of the system runtime data., Comment: 2019 Southern African Universities Power Engineering Conference/Robotics and Mechatronics/Pattern Recognition Association of South Africa (SAUPEC/RobMech/PRASA)

Published
2023
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30. Deep learning-based quantum algorithms for solving nonlinear partial differential equations

Author

Mouton, Lukas, Reiter, Florentin, Chen, Ying, and Rebentrost, Patrick

Subjects
Quantum Physics
Abstract

Partial differential equations frequently appear in the natural sciences and related disciplines. Solving them is often challenging, particularly in high dimensions, due to the "curse of dimensionality". In this work, we explore the potential for enhancing a classical deep learning-based method for solving high-dimensional nonlinear partial differential equations with suitable quantum subroutines. First, with near-term noisy intermediate-scale quantum computers in mind, we construct architectures employing variational quantum circuits and classical neural networks in conjunction. While the hybrid architectures show equal or worse performance than their fully classical counterparts in simulations, they may still be of use in very high-dimensional cases or if the problem is of a quantum mechanical nature. Next, we identify the bottlenecks imposed by Monte Carlo sampling and the training of the neural networks. We find that quantum-accelerated Monte Carlo methods offer the potential to speed up the estimation of the loss function. In addition, we identify and analyse the trade-offs when using quantum-accelerated Monte Carlo methods to estimate the gradients with different methods, including a recently developed backpropagation-free forward gradient method. Finally, we discuss the usage of a suitable quantum algorithm for accelerating the training of feed-forward neural networks. Hence, this work provides different avenues with the potential for polynomial speedups for deep learning-based methods for nonlinear partial differential equations., Comment: 48 pages, 17 figures

Published
2023

31. Equity in the Early Pain Management of Long Bone Fractures in Black vs White Patients: We Have Closed the Gap

Author

Dietrich Jehle, Krishna K. Paul, Stanley Troung, Jackson M. Rogers, Blake Mireles, John J. Straub, Georgiy Golovko, Matthew M. Talbott, Ronald W. Lindsey, and Charles P. Mouton

Subjects
Medicine, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Introduction: Patients with long bone fractures often present to the emergency department (ED) with severe pain and are typically treated with opioid and non-opioid analgesics. Historical data reveals racial disparities in analgesic administration, with White patients more likely to receive analgesics. With the diversifying US population, health equity is increasingly crucial. In this study we aimed to evaluate the early administration of opioid and non-opioid analgesia among Black and White patients with long bone and femur fractures in EDs over different time frames using a substantial database. Methods: We retrospectively extracted Information from 57 US healthcare organizations within the TriNetX database, encompassing 95 million patients. The ED records from 2003–2023 were subjected to propensity score matching for age and gender. We focused on four cohorts: two comprising Black and White patients diagnosed with long bone fractures, and another two with Black and White patients diagnosed solely with femur fractures. We examined analgesic administration rates over 20 years (2003–2023) at five-year intervals (2003–2008; 2008–2013; 2013–2018; 2018–2023), and further analyzed the rates for the most recent two-year period (2021–2023). Results: Disparities in analgesic administration significantly diminished over the study period. For patients with long bone fractures (1,095,052), the opioid administration gap narrowed from 6.3% to 1.1%, while non-opioid administration disparities reduced from 4.4% to 0.3%. Similar trends were noted for femur fractures (265,181). By 2021–2023, no significant differences in analgesic administration were observed between racial groups. Conclusion: Over the past 20 years, the gap in early administration of opioid and non-opioid analgesics for Black and White patients presenting with long bone fractures or femur fractures has been disappearing.

Published
2024
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32. A methylation risk score for chronic kidney disease: a HyperGEN study

Author

Alana C. Jones, Amit Patki, Vinodh Srinivasasainagendra, Bertha A. Hidalgo, Hemant K. Tiwari, Nita A. Limdi, Nicole D. Armstrong, Ninad S. Chaudhary, Bré Minniefield, Devin Absher, Donna K. Arnett, Leslie A. Lange, Ethan M. Lange, Bessie A. Young, Clarissa J. Diamantidis, Stephen S. Rich, Josyf C. Mychaleckyj, Jerome I. Rotter, Kent D. Taylor, Holly J. Kramer, Russell P. Tracy, Peter Durda, Silva Kasela, Tuuli Lappalinen, Yongmei Liu, W. Craig Johnson, David J. Van Den Berg, Nora Franceschini, Simin Liu, Charles P. Mouton, Parveen Bhatti, Steve Horvath, Eric A. Whitsel, and Marguerite R. Irvin

Subjects
Chronic kidney disease, eGFR, Methylation risk score, Epigenetics, Medicine, Science
Abstract

Abstract Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

Published
2024
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33. An Open Label, Randomized, Multicenter Study of Elafibranor in Children With Nonalcoholic Steatohepatitis

Author

Goyal, Nidhi P, Mencin, Ali, Newton, Kimberly P, Durelle, Janis, Carrier, Carissa, Ugalde‐Nicalo, Patricia, Noel, Benoit, Mouton, Julie, Vargas, Dawn, Magrez, David, Tadde, Bachirou, Birman, Pascal, Best, Brookie M, Addy, Carol, and Schwimmer, Jeffrey B

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Trials and Supportive Activities, Chronic Liver Disease and Cirrhosis, Clinical Research, Liver Disease, Digestive Diseases, Hepatitis, 6.1 Pharmaceuticals, Propionates, Chalcones, Non-alcoholic Fatty Liver Disease, Humans, Male, Child, Adolescent, Drug Administration Schedule, Administration, Oral, fatty liver, NAFLD, pediatric, Medical and Health Sciences, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics, Paediatrics
Abstract

ObjectivesNonalcoholic fatty liver disease is the most common chronic liver disease in children. Elafibranor, a dual peroxisome proliferator-activated receptor α/δ agonist, has been proposed as a treatment for nonalcoholic steatohepatitis (NASH). The aims were to (1) describe pharmacokinetics (PK), safety, and tolerability of oral elafibranor at 2 doses (80 and 120 mg) in children 8-17 years and (2) assess changes in aminotransferases.MethodsChildren with NASH were randomized to open-label elafibranor 80 mg or 120 mg daily for 12 weeks. The intent-to-treat analysis included all participants who received at least 1 dose. Standard descriptive statistics and PK analyses were performed.ResultsTen males [mean 15.1 years, standard deviation (SD) 2.2] with NASH were randomized to 80 mg (n = 5) or 120 mg (n = 5). Baseline mean alanine aminotransferase (ALT) was 82 U/L (SD 13) and 87 U/L (SD 20) for 80 mg and 120 mg groups, respectively. Elafibranor was rapidly absorbed and well tolerated. Elafibranor plasma exposure increased between the 80 mg and 120 mg dose with a 1.9- and 1.3-fold increase in median Cmax and AUC 0-24 , respectively. End of treatment mean ALT was 52 U/L (SD 20) for the 120 mg group, with a relative mean ALT change from baseline of -37.4% (SD 23.8%) at 12 weeks.ConclusionsOnce daily dosing of elafibranor was well tolerated in children with NASH. There was a 37.4% relative reduction from mean baseline ALT in the 120 mg group. Decreasing ALT may be associated with improvement in liver histology, thus could be considered a surrogate for histology in early phase trials. These results may support further exploration of elafibranor in children with NASH.

Published
2023

34. Racial and Ethnic Differences in Self-Reported COVID-19 Exposure Risks, Concerns, and Behaviors Among Diverse Participants in the Women's Health Initiative Study.

Author

Bennett, Serenity J, Hunt, Rebecca P, Breathett, Khadijah, Eaton, Charles B, Garcia, Lorena, Jiménez, Monik, Johns, Tanya S, Mouton, Charles P, Nassir, Rami, Nuño, Tomas, Urrutia, Rachel P, Wactawski-Wende, Jean, and Cené, Crystal W

Subjects
COVID-19, older adults, racial and ethnic disparities, structural racism, women, Clinical Research, Basic Behavioral and Social Science, Prevention, Aging, Behavioral and Social Science, Good Health and Well Being, Clinical Sciences, Gerontology
Abstract

BackgroundRacial and ethnic disparities in COVID-19 risk are well-documented; however, few studies in older adults have examined multiple factors related to COVID-19 exposure, concerns, and behaviors or conducted race- and ethnicity- stratified analyses. The Women's Health Initiative (WHI) provides a unique opportunity to address those gaps.MethodsWe conducted a secondary analysis of WHI data from a supplemental survey of 48,492 older adults (mean age 84 years). In multivariable-adjusted modified Poisson regression analyses, we examined predisposing factors and COVID-19 exposure risk, concerns, and behaviors. We hypothesized that women from minoritized racial or ethnic groups, compared to Non-Hispanic White women, would be more likely to report: exposure to COVID-19, a family or friend dying from COVID-19, difficulty getting routine medical care or deciding to forego care to avoid COVID-19 exposure, and having concerns about the COVID-19 pandemic.ResultsAsian women and Non-Hispanic Black/African American women had a higher risk of being somewhat/very concerned about risk of getting COVID 19 compared to Non-Hispanic White women and each were significantly more likely than Non-Hispanic White women to report forgoing medical care to avoid COVID-19 exposure. However, Asian women were 35% less likely than Non-Hispanic White women to report difficulty getting routine medical care since March 2020 (aRR 0.65; 95% CI 0.57, 0.75).ConclusionsWe documented COVID-related racial and ethnic disparities in COVID-19 exposure risk, concerns, and care-related behaviors that disfavored minoritized racial and ethnic groups, particularly Non-Hispanic Black/African American women.

Published
2023

35. The Missing Margin: How Sample Corruption Affects Distance to the Boundary in ANNs

Author

Theunissen, Marthinus W., Mouton, Coenraad, and Davel, Marelie H.

Subjects
Computer Science - Machine Learning
Abstract

Classification margins are commonly used to estimate the generalization ability of machine learning models. We present an empirical study of these margins in artificial neural networks. A global estimate of margin size is usually used in the literature. In this work, we point out seldom considered nuances regarding classification margins. Notably, we demonstrate that some types of training samples are modelled with consistently small margins while affecting generalization in different ways. By showing a link with the minimum distance to a different-target sample and the remoteness of samples from one another, we provide a plausible explanation for this observation. We support our findings with an analysis of fully-connected networks trained on noise-corrupted MNIST data, as well as convolutional networks trained on noise-corrupted CIFAR10 data., Comment: This work is a preprint of a published paper by the same name, which it subsumes. This preprint is an extended version: it contains additional empirical evidence and discussion

Published
2023
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37. Sestrin2 Attenuates Myocardial Endoplasmic Reticulum Stress and Cardiac Dysfunction During Ischemia/Reperfusion Injury

Author

Xuan Li, Zhen Wang, Alan J. Mouton, Ana C. M. Omoto, Alexandre A. da Silva, Jussara M. do Carmo, Ji Li, and John E. Hall

Subjects
cardiac injury, heart, mTOR signaling, unfolded protein response, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Sesn2 (Sestrin2) is a stress‐induced protein that provides protective effects during myocardial ischemia and reperfusion (I/R) injury, while endoplasmic reticulum (ER) stress may be a pivotal mediator of I/R injury. The goal of this study was to determine whether Sesn2‐mTOR (mammalian target of rapamycin) signaling regulates ER stress during myocardial I/R. Methods and Results In vivo cardiac I/R was induced by ligation and subsequent release of the left anterior descending coronary artery in wild‐type (WT) and cardiac‐specific Sesn2 knockout (Sesn2cKO) mice. At 6 hours and 24 hours after reperfusion, cardiac function was evaluated, and heart samples were collected for analysis. I/R induced cardiac ER stress and upregulated Sesn2 mRNA and protein levels. Inhibiting ER stress with 4‐phenylbutyric acid reduced infarct size by 37.5%, improved cardiac systolic function, and mitigated myocardial cell apoptosis post‐I/R. Hearts from Sesn2cKO mice displayed increased susceptibility to ER stress during I/R compared with WT. Notably, cardiac mTOR signaling was further increased in Sesn2cKO hearts compared with WT hearts during I/R. In mice with cardiac Sesn2 deficiency, compared with WT, ER lumen was significantly expanded after tunicamycin‐induced ER stress, as assessed by transmission electron microscopy. Additionally, pharmacological inhibition of mTOR signaling with rapamycin improved cardiac function after tunicamycin treatment and significantly attenuated the unfolded protein response and apoptosis in WT and Sesn2cKO mice. Conclusions Sesn2 attenuates cardiac ER stress post‐I/R injury via regulation of mTOR signaling. Thus, modulation of the mTOR pathway by Sesn2 could be a critical factor for maintaining cardiac ER homeostasis control during myocardial I/R injury.

Published
2024
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38. Long Covid: a global health issue – a prospective, cohort study set in four continents

Author

Synne Jenum, Renaud Tamisier, Clark D Russell, Rachel Evans, Piero Valentini, Sylvain Diamantis, Dominique Deplanque, Jordi Rello, Agnes Meybeck, Maxime Hentzien, Clotilde Allavena, André Cabié, Firouzé Bani-Sadr, Patrick Rossignol, Lionel Piroth, Mathieu Blot, Marie-Pierre Debray, François Angoulvant, Marc Leone, Ewen M Harrison, Maria Zambon, Michael Edelstein, Florentia Kaguelidou, Marc Lambert, Olivier Lairez, Tom Solomon, Carrol Gamble, Laura Marsh, Christiana Kartsonaki, Natalie Wright, Behzad Nadjm, Srinivas Murthy, Gail Carson, Jake Dunning, Laura Merson, Peter Horby, Timothy M Uyeki, Piero Olliaro, Guillermo Maestro de la Calle, Stephen R Knight, Thomas M Drake, Marlene Murris, Aurore Bousquet, Kenneth A McLean, Hugues Cordel, Marc Fabre, Laurence Bouillet, Katrina Hann, Xavier Duval, James Lee, Christian Rabaud, Paul Klenerman, Jean-Christophe Lucet, Jean-François Timsit, Jennifer Lee, David J Lowe, Nicolas Terzi, Saad Nseir, Gwenhaël Colin, Steve Webb, Kalynn Kennon, Caroline Mudara, Diana Hernández, Yazdan Yazdanpanah, Jean-François Payen, Samreen Ijaz, Joanne McPeake, Meera Chand, Catherine A Shaw, Cameron J Fairfield, Bruno Levy, Eric D'ortenzio, Pierre Delobel, Tiphaine Goulenok, Bronner P Gonçalves, Arnaud Scherpereel, Danilo Buonsenso, Mark G Pritchard, Susanne Dudman, Adrien Auvet, Caterina Caminiti, Debby Bogaert, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Merce Jourdain, Sue Smith, Jia Wei, Antoine Khalil, Clément Le Bihan, Nathalie Pansu, Vincent Le Moing, Victor Fomin, Christophe Fraser, Daniel Munblit, William Greenhalf, François-Xavier Lescure, Nicolas Carlier, Saye Khoo, Annemarie B Docherty, Christopher A Green, Riinu Pius, Louise Sigfrid, Sophie Halpin, Clare Jackson, Antonia Ho, Malcolm G Semple, Andrew Dagens, Carlo Palmieri, Lance Turtle, Zeno Bisoffi, Thomas Flament, Julie Mankikian, Romain Basmaci, Peter Openshaw, Rob Fowler, Tom Fletcher, Adrien Lemaignen, Pierre Tattevin, Christelle Delmas, Hélène Espérou, Claire Lévy-Marchal, Olivier Picone, Jeanne Sibiude, Cecile Yelnik, Michelle Girvan, Piero L Olliaro, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Graham S Cooke, Ana da Silva Filipe, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Shiranee Sriskandan, David Stuart, Charlotte Summers, Emma C Thomson, Ryan S Thwaites, Lance C W Turtle, Hayley Hardwick, Wilna Oosthuyzen, Fiona Griffiths, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Marie Connor, Gary Leeming, Ross Hendry, Victoria Shaw, Jade Ghosn, Lucille Blumberg, Nicolas Benech, Odile Launay, Yoan Lavie-Badie, Minh Le, Elise Artaud-Macari, Muge Cevik, Nicola Latronico, Mylène Maillet, Didier Laureillard, Ben Morton, Claire Hastie, Nicholas Sedillot, Anne-Sophie Boureau, Laurent Abel, Guillaume Martin-Blondel, Valérie Garrait, Isabelle Delacroix, Andrea Cortegiani, Jean-Benoît Arlet, Raphaël Borie, Kévin Bouiller, Vincent Langlois, Mélanie Roriz, Vincent Dubée, John H Amuasi, Madiha Hashmi, Edwin Jesudason, Jan Cato Holter, Anders Benjamin Kildal, Luis Felipe Reyes, Anna Beltrame, Sulaiman Lakoh, Stéphanie Fry, Lynsey Goodwin, Laurent Plantier, Anna Casey, Denis Malvy, Nina Jamieson, François Dubos, Jean-Sébastien Hulot, Paola Rodari, Frank Bloos, Cécile Tromeur, Paul Loubet, Marina Esposito-Farèse, France Mentré, Valérie Gaborieau, Cécile Goujard, Vincent Thibault, Adam Ali, Sadie Kelly, Fernando A Bozza, Bertrand Dussol, Marion Schneider, Marielle Buisson, Yves Levy, Carine Roy, Walter Picard, Olivier Sanchez, Nazir Lone, Antoine Kimmoun, Roberto Roncon-Albuquerque, Nathan Peiffer-Smadja, Julien Poissy, Lila Bouadma, Bruno Lina, Maude Bouscambert, Alexandre Gaymard, Gilles Peytavin, Jeremie Guedj, Claire Andrejak, Cedric Laouenan, Anissa Chair, Samira Laribi, Marie-Capucine Tellier, Sandrine Couffin-Cadiergues, Ventzislava Petrov-Sanchez, Alpha Diallo, Sarah Tubiana, Patrick Imbert, Emmanuelle Mercier, Waasila Jassat, Arsene Kpangon, Dominique Luton, Simone Piva, Sophie Mahy, Pierre-Adrien Bolze, Sarah Moore, Raphael Favory, Andrea Angheben, Andrea Rossanese, Matthew Hall, Johann Auchabie, Christophe Rapp, Vincent Peigne, Fredrik Müller, Christl A Donnelly, François Goehringer, Elodie Curlier, Catherine Chirouze, Vegard Skogen, Stéphane Jaureguiberry, Laurent Bitker, Hodane Yonis, Laurent Mandelbrot, Jérémie Pasquier, Bato Hammarström, Thushan de Silva, Polina Bugaeva, Julie Chas, Dario Sinatti, Arne Søraas, Murray Wham, Sara Clohisey, Seán Keating, Thibault Chiarabini, Agnes Sommet, Hugues Aumaître, Charlotte Charpentier, Sylvie LeGac, Sarah E McDonald, Jeanne Truong, Anne-Hélène Boivin, Mariachiara Ippolito, Ellen Pauley, Diane Descamps, Sérgio Gaião, Stéphane Lasry, Amanda Rojek, Charlotte Salmon Gandonniere, Sebastien Preau, Benoit Thill, Karine Faure, Denis Garot, Grégory Corvaisier, Elsa Nyamankolly, Merete Ellingjord-Dale, Eva Geraud, Barbara Wanjiru Citarella, Kévin Alexandre, Nathalie Allou, Séverine Ansart, Laurène Azemar, Cecile Azoulay, Delphine Bachelet, Claudine Badr, Valeria Balan, Marie Bartoli, Joaquín Baruch, Jules Bauer, Alexandra Bedossa, Husna Begum, Marine Beluze, Delphine Bergeaud, Giulia Bertoli, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Krishna Bhavsar, Laetitia Bodenes, Isabela Bolaños, Olivier Bouchaud, Sabelline Bouchez, Camile Bouisse, Marielle Boyer-Besseyre, Axelle Braconnier, Ingrid G Bustos, Denis Butnaru, Eder Caceres, Cyril Cadoz, Valentine Campana, Pauline Caraux-Paz, Thierry Carmoi, Marie-Christine Carret, Maire-Laure Casanova, Guylaine Castor-Alexandre, François-Xavier Catherine, Minerva Cervantes-Gonzalez, Catherine Chakveatze, Jean-Marc Chapplain, Antoine Cheret, Bernard Cholley, Marie-Charlotte Chopin, Roxane Courtois, Stéphanie Cousse, Alexa Debard, Nathalie DeCastro, Romain Decours, Eve Defous, Karen Delavigne, Elisa Demonchy, Emmanuelle Denis, Mathilde Desvallées, Kévin Didier, Jean-Luc Diehl, Vincent Dinot, Fara Diop, Alphonsine Diouf, Félix Djossou, Céline Dorival, Nathalie Dournon, Murray Dryden, Alexandre Ducancelle, Paul Dunand, Brigitte Elharrar, Philippine Eloy, Isabelle Enderle, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Manuel Etienne, Isabelle Fabre, François-Xavier Ferrand, Eglantine Ferrand Devouge, Nicolas Ferriere, Céline Ficko, Erwan Fourn, Rostane Gaci, Jean-Charles Gagnard, Esteban Garcia-Gallo, Tristan Gigante, Guillermo Giordano, Valérie Gissot, Petr Glybochko, Marie Gominet, Isabelle Gorenne, Laure Goubert, Pascal Granier, Segolène Greffe, Martin Guego, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Thomas Guimard, Ali Hachemi, Nadir Hadri, Rebecca Hamidfar, Lars Heggelund, Rupert Higgins, Hikombo Hitoto, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Margaux Isnard, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Florence Jego, Cédric Joseph, Ouifiya Kafif, Sabina Kali, Younes Kerroumi, Marie Lachatre, Marie Lacoste, Marie Lagrange, Fabrice Laine, Antonio Lalueza, Marie Langelot-Richard, Delphine Lariviere, Andy Law, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefèvre, Jean-Daniel Lelievre, Véronique Lemee, Anthony Lemeur, Quentin Lepiller, Olivier Lesens, Mathieu Lesouhaitier, Geoffrey Liegeon, Guillaume Lingas, Sylvie Lion-Daolio, Marine Livrozet, Bouchra Loufti, Guillame Louis, Liem Luong, Moïse Machado, Gabriel Macheda, Rafael Mahieu, Thomas Maitre, Victoria Manda, Aldric Manuel, Samuel Markowicz, Martin Martinot, Mathieu Mattei, Laurence Maulin, Thierry Mazzoni, Cécile Mear-Passard, Antoine Merckx, Mayka Mergeay-Fabre, Vanina Meysonnier, Mehdi Mezidi, Isabelle Michelet, Lucia Moro, Julien Moyet, Jimmy Mullaert, Nadège Neant, Nikita Nekliudov, Anthony Nghi, Duc Nguyen, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Justine Pages Maïder Pagadoy, Aurélie Papadopoulos, Bruno Pastene, Christelle Paul, Florent Peelman, Daniel Perez, Thomas Perpoint, Vincent Pestre, Ryadh Pokeerbux, Diane Ponscarme, Marie Rafiq, Blandine Rammaert, Stanislas Rebaudet, Sarah Redl, Anne-Sophie Resseguier, Matthieu Revest, Laurent Richier, Patrick Rispal, Karine Risso, Olivier Robineau, Manuel Rosa-Calatrava, Benoît Roze, Hélène Salvator, Pierre-François Sandrine, Benjamine Sarton, Eric Senneville, Albert Sotto, Sarah Stabler, Andrey Svistunov, Coralie Tardivon, François Téoulé, Olivier Terrier, Simon-Djamel Thiberville, Peter S Timashev, Noémie Tissot, Tiffany Trouillon, Christelle Tual, Noémie Vanel, Charline Vauchy, Aurélie Veislinger, Fanny Vuotto, Aurélie Wiedemann, Marion Zabbe, David Zucman, Silvio Hamacher, Ekaterina Pazukhina, Allegra Chatterjee, Kyle Gomez, Matteo Puntoni, Oksana Kruglova, Yock Ping Chow, Yash Doshi, Sara Isabel Duque Vallejo, Elsa D Ibáñez-Prada, Yuli V Fuentes, Margaret E O'Hara, Tigist Menkir, Amal Abrous, Younes Ait Tamlihat, Aliya Mohammed Alameen, Marta Alessi, Kazali Enagnon Alidjnou, Jean Baptiste Assie, Eyvind W Axelsen, John Kenneth Baillie, José Luis Bernal Sobrino, Sonja Hjellegjerde Brunvoll, Roar Bævre-Jensen, Jose Andres Calvache, Léo Chenard, Juan Luis Cruz Bermúdez, Jaime Cruz Rojo, Charlene Da Silveira, John Arne Dahl, Etienne De Montmollin, Cristina De Rose, Fernanda Dias Da Silva, Thomas Drake, Amiel A Dror, Anne Margarita Dyrhol-Riise, Linn Margrete Eggesbø, Mohammed El Sanharawi, William Finlayson, Aline-Marie Florence, Linda Gail Skeie, Noelia García Barrio, Anatoliy Gavrylov, Louis Gerbaud Morlaes, Yanay Gorelik, Mette Stausland Istre, Silje Bakken Jørgensen, Karl Trygve Kalleberg, Beathe Kiland Granerud, Eyrun Floerecke Kjetland Kjetland, Gry Kloumann Bekken, Galyna Kutsyna, Nadhem Lafhej, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Hervé Le Nagard, Sophie Letrou, Wei Shen Lim, Andreas Lind, Carlos Lumbreras Bermejo, Miles Lunn, Olga Martynenko, Roberta Meta, Lina Morales Cely, Clara Mouton Perrot, Alamin Mustafa, Karl Erik Müller, Ebrahim Ndure, Anders Benteson Nygaard, Claudia Milena Orozco-Chamorro, Paul Otiku, Miguel Pedrera Jiménez, Frank Olav Pettersen, Chiara Piubelli, Víctor Quirós González, Else Quist-Paulsen, Dag Henrik Reikvam, Antonia Ricchiuto, Aleksander Rygh Holten, Nadia Saidani, Pablo Serrano Balazote, Nassima Si Mohammed, Lene Bergendal Solberg, Edouard Soum, Elisabetta Spinuzza, Trude Steinsvik, Birgitte Stiksrud, Mathew Thorpe, Vadim Tieroshyn, Kristian Tonby, Anders Tveita, Sylvie Van Der Werf, Paul Henri Wicky, Ibrahim Richard Bangura, Leonardo Bastos, Daniel Cassaglia, Barbara Citarella, Sarah Duque, Anne Margarita Dyrhol Riise, Annelies Gillesen, Bronner P Goncalvez, Margareta O’Hara, Lars Hegelund, Aquiles Henriquez Trujillo, Elsa D Ibañez, Jane Ireson, Oksana Krugalova, Sam Lissaeur, Sinnadurai Manohan, Prasan K Panda, Daniel R Plotkin, Liliana Resende, Sergio Ruiz Saltana, Steffi Ryckaert, Girish Sindhwani Pulm, and Caroline Vika

Subjects
Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract

Introduction A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).Methods A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to

Published
2024
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39. In silico and pharmacological evaluation of GPR65 as a cancer immunotherapy target regulating T-cell functions

Author

Shamin Li, Fabien Melchiore, Chahrazade Kantari-Mimoun, Aurore Mouton, Samantha Knockaert, Wendy Philippon, Benjamin Chanrion, Christophe Bourgeois, Céline Lefebvre, Jamila Elhmouzi-Younes, Véronique Blanc, Fernando Ramon Olayo, and Bruno Laugel

Subjects
acidosis, immunosuppression, immunotherapy, GPCRs, Gpr65, T-cells, Immunologic diseases. Allergy, RC581-607
Abstract

The success of cancer immunotherapies such as immune checkpoint inhibitors, CAR T-cells and immune cell engagers have provided clinicians with tools to bypass some of the limitations of cancer immunity. However, numerous tumour factors curtail the immune response against cancer and limit the efficiency of immuno-oncology (IO) therapies. Acidification of the extra-cellular tumour environment consecutive to aberrant cancer cell metabolism is a well-known promoter of oncogenic processes that also acts as an immune regulator. Yet, the suppressive mechanisms of low extra-cellular pH on anti-cancer immunity remain poorly understood. Recent reports have suggested that GPR65, a Gαs-coupled proton-sensing GPCR broadly expressed in the immune system, may act as an immune suppressant detrimental to anti-tumour immunity. So far, the immuno-regulatory properties of GPR65 in acidic milieux have mostly been documented in macrophages and myeloid cells. Our computational evaluation of GPR65’s transcriptomic expression profile and potential as an IO target using public datasets prompted us to further investigate its functions in human T-cells. To this end, we identified and validated GPR65 small molecule inhibitors active in in vitro cellular assays and we showed that GPR65 inhibition promoted the killing capacity of antigen-specific human T-cells. Our results broaden the scope of GPR65 as an IO target by suggesting that its inhibition may enhance T-cell anti-tumour activity and provide useful pharmacological tools to further investigate the therapeutic potential of GPR65 inhibition.

Published
2024
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40. Nucleoporin Nsp1 surveils the phase state of FG-Nups

Author

Tegan A. Otto, Tessa Bergsma, Maurice Dekker, Sara N. Mouton, Paola Gallardo, Justina C. Wolters, Anton Steen, Patrick R. Onck, and Liesbeth M. Veenhoff

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

Summary: Transport through the nuclear pore complex (NPC) relies on intrinsically disordered FG-nucleoporins (FG-Nups) forming a selective barrier. Away from the NPC, FG-Nups readily form condensates and aggregates, and we address how this behavior is surveilled in cells. FG-Nups, including Nsp1, together with the nuclear transport receptor Kap95, form a native daughter cell-specific cytosolic condensate in yeast. In aged cells, this condensate disappears as cytosolic Nsp1 levels decline. Biochemical assays and modeling show that Nsp1 is a modulator of FG-Nup condensates, promoting a liquid-like state. Nsp1’s presence in the cytosol and condensates is critical, as a reduction of cytosolic levels in young cells induces NPC defects and a general decline in protein quality control that quantitatively mimics aging phenotypes. These phenotypes can be rescued by a cytosolic form of Nsp1. We conclude that Nsp1 is a phase state regulator that surveils FG-Nups and impacts general protein homeostasis.

Published
2024
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49. Arthroscopic Meniscal Ramp Tear Repair

Author

Jacquet, Christophe, Mouton, Caroline, Kracke, Markus, Seil, Romain, Krych, Aaron J., Section editor, Faucett, Scott C., Section editor, Sherman, Seth L., editor, Chahla, Jorge, editor, LaPrade, Robert F., editor, and Rodeo, Scott A., editor

Published
2024
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50. Real-time Mapping of Physical Scene Properties with an Autonomous Robot Experimenter

Author

Haughton, Iain, Sucar, Edgar, Mouton, Andre, Johns, Edward, and Davison, Andrew J.

Subjects
Computer Science - Robotics, Computer Science - Computer Vision and Pattern Recognition
Abstract

Neural fields can be trained from scratch to represent the shape and appearance of 3D scenes efficiently. It has also been shown that they can densely map correlated properties such as semantics, via sparse interactions from a human labeller. In this work, we show that a robot can densely annotate a scene with arbitrary discrete or continuous physical properties via its own fully-autonomous experimental interactions, as it simultaneously scans and maps it with an RGB-D camera. A variety of scene interactions are possible, including poking with force sensing to determine rigidity, measuring local material type with single-pixel spectroscopy or predicting force distributions by pushing. Sparse experimental interactions are guided by entropy to enable high efficiency, with tabletop scene properties densely mapped from scratch in a few minutes from a few tens of interactions.

Published
2022

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