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1. Reflecting, Representing, and Expanding the Narrative(s) in Early Childhood Curriculum

Author

Haeny S. Yoon and Tran Nguyen Templeton

Abstract

In this manuscript, we recognize that young children learn stories that propagate white supremacist narratives through selective traditions of early childhood curriculum. The role of early childhood teachers, therefore, is to critically examine curriculum for biases, omissions, and distortions, as well as to rewrite curriculum to tell accurate stories and disrupt what Viet Thanh Nguyen refers to as "narrative scarcity". Through a qualitative study of pre-service teachers' (PSTs) re-imaginings and revisions of early childhood structures, processes, and texts, we highlight the moves that teachers made to rectify, represent and expand narratives related to communities of Color.

Published
2024
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2. Peering inside the black box: Learning the relevance of many-body functions in Neural Network potentials

Author

Bonneau, Klara, Lederer, Jonas, Templeton, Clark, Rosenberger, David, Müller, Klaus-Robert, and Clementi, Cecilia

Subjects
Physics - Computational Physics
Abstract

Machine learned potentials are becoming a popular tool to define an effective energy model for complex systems, either incorporating electronic structure effects at the atomistic resolution, or effectively renormalizing part of the atomistic degrees of freedom at a coarse-grained resolution. One of the main criticisms to machine learned potentials is that the energy inferred by the network is not as interpretable as in more traditional approaches where a simpler functional form is used. Here we address this problem by extending tools recently proposed in the nascent field of Explainable Artificial Intelligence (XAI) to coarse-grained potentials based on graph neural networks (GNN). We demonstrate the approach on three different coarse-grained systems including two fluids (methane and water) and the protein NTL9. On these examples, we show that the neural network potentials can be in practice decomposed in relevance contributions to different orders, that can be directly interpreted and provide physical insights on the systems of interest.

Published
2024

3. ADDOPT: An Additive Manufacturing Optimal Control Framework Demonstrated in Minimizing Layer-Level Thermal Variance in Electron Beam Powder Bed Fusion

Author

Khrenov, Mikhail, Templeton, William Frieden, and Narra, Sneha Prabha

Subjects
Electrical Engineering and Systems Science - Systems and Control
Abstract

Additive manufacturing (AM) techniques hold promise but face significant challenges in process planning and optimization. The large temporal and spatial variations in temperature that can occur in layer-wise AM lead to thermal excursions, resulting in property variations and defects. These variations cannot always be fully mitigated by simple static parameter search. To address this challenge, we propose a general approach based on modeling AM processes on the part-scale in state-space and framing AM process planning as a numerical optimal control problem. We demonstrate this approach on the problem of minimizing thermal variation in a given layer in the electron beam powder bed fusion (EB-PBF) AM process, and are able to compute globally optimal dynamic process plans. These optimized process plans are then evaluated in simulation, achieving an 87% and 86% reduction in cumulative variance compared to random spot melting and a uniform power field respectively, and are further validated in experiment. This one-shot feedforward planning approach expands the capabilities of AM technology by minimizing the need for experimentation and iteration to achieve process optimization. Further, this work opens the possibility for the application of optimal control theory to part-scale optimization and control in AM.

Published
2024

4. The Jive Verification System and its Transformative Impact on Weather Forecasting Operations

Author

Loveday, Nicholas, Griffiths, Deryn, Leeuwenburg, Tennessee, Taggart, Robert, Pagano, Thomas C., Cheng, George, Plastow, Kevin, Ebert, Elizabeth, Templeton, Cassandra, Carroll, Maree, Khanarmuei, Mohammadreza, and Nagpal, Isha

Subjects
Physics - Atmospheric and Oceanic Physics
Abstract

Forecast verification is critical for continuous improvement in meteorological organizations. The Jive verification system was originally developed to assess the accuracy of public weather forecasts issued by the Australian Bureau of Meteorology. It started as a research project in 2015 and gradually evolved to be a Bureau operational verification system in 2022. The system includes daily verification dashboards for forecasters to visualize recent forecast performance and "Evidence Targeted Automation" dashboards for exploring the performance of competing forecast systems. Additionally, Jive includes a Jupyter Notebook server with the Jive Python library which supports research experiments, case studies, and the development of new verification metrics and tools. This paper describes the Jive verification system and how it helped bring verification to the forefront at the Bureau of Meteorology, leading to more accurate, streamlined forecasts. Jive has provided evidence to support forecast automation decisions and has helped to understand the evolving role of meteorologists in the forecast process. It has given operational meteorologists tools for evaluating forecast processes, including identifying when and how manual interventions lead to superior predictions. Work on Jive led to new verification science, including novel metrics that are decision-focused, including diagnostics for extreme conditions. Jive also provided the Bureau with an enterprise-wide data analysis environment and has prompted a clarification of forecast definitions. These collective impacts have resulted in more accurate forecasts, ultimately benefiting society, and building trust with forecast users. These positive outcomes highlight the importance of meteorological organizations investing in verification science and technology.

Published
2024

7. The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study

Author

Shah, Chirag, Whitworth, Pat, Vicini, Frank A., Narod, Steven, Gerber, Naamit, Jhawar, Sachin R., King, Tari A., Mittendorf, Elizabeth A., Willey, Shawna C., Rabinovich, Rachel, Gold, Linsey, Brown, Eric, Patel, Anushka, Vargo, John, Barry, Parul N., Rock, David, Friedman, Neil, Bedi, Gauri, Templeton, Sandra, Brown, Sheree, Gabordi, Robert, Riley, Lee, Lee, Lucy, Baron, Paul, Majithia, Lonika, Mirabeau-Beale, Kristina L., Reid, Vincent J., Hirsch, Arica, Hwang, Catherine, Pellicane, James, Maganini, Robert, Khan, Sadia, MacDermed, Dhara M., Small, William, Mittal, Karuna, Borgen, Patrick, Cox, Charles, Shivers, Steven C., and Bremer, Troy

Published
2024
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10. Experimenting with Large Language Models and vector embeddings in NASA SciX

Author

Blanco-Cuaresma, Sergi, Ciucă, Ioana, Accomazzi, Alberto, Kurtz, Michael J., Henneken, Edwin A., Lockhart, Kelly E., Grezes, Felix, Allen, Thomas, Shapurian, Golnaz, Grant, Carolyn S., Thompson, Donna M., Hostetler, Timothy W., Templeton, Matthew R., Chen, Shinyi, Koch, Jennifer, Jacovich, Taylor, Chivvis, Daniel, Alves, Fernanda de Macedo, Paquin, Jean-Claude, Bartlett, Jennifer, Polimera, Mugdha, and Jarmak, Stephanie

Subjects
Computer Science - Computation and Language, Astrophysics - Instrumentation and Methods for Astrophysics, Computer Science - Artificial Intelligence
Abstract

Open-source Large Language Models enable projects such as NASA SciX (i.e., NASA ADS) to think out of the box and try alternative approaches for information retrieval and data augmentation, while respecting data copyright and users' privacy. However, when large language models are directly prompted with questions without any context, they are prone to hallucination. At NASA SciX we have developed an experiment where we created semantic vectors for our large collection of abstracts and full-text content, and we designed a prompt system to ask questions using contextual chunks from our system. Based on a non-systematic human evaluation, the experiment shows a lower degree of hallucination and better responses when using Retrieval Augmented Generation. Further exploration is required to design new features and data augmentation processes at NASA SciX that leverages this technology while respecting the high level of trust and quality that the project holds., Comment: To appear in the proceedings of the 33th annual international Astronomical Data Analysis Software & Systems (ADASS XXXIII)

Published
2023

11. What Do You See in Mathematical Play?

Author

Melissa Gresalfi, Amy Noelle Parks, Anita A. Wager, Nathaniel Bryan, Naomi Jessup, and Tran Templeton

Abstract

As part of a longitudinal study focused on mathematical play, we (Melissa, Amy, and Anita) are often faced with questions about what counts as play and what mathematics (and other learning) we see in play, and whose play is most likely to be seen or dismissed. Rather than discuss our findings from classroom videos of kindergarten children engaged in mathematical play, we asked scholars who bring different lenses to research on play, young children, and teaching and learning mathematics to look at some of our data and provide their perspectives. In this session, we will share video and discuss with our panel (Nathaniel, Naomi, and Tran) various ways to interpret that video. This paper provides background on the potential of mathematical play and the details of the study that generated data for analysis. We conclude with a copy of a transcript that is associated with a video we will watch during the plenary with hopes that participants will watch prior to the session and come with their own questions/perspectives. [For the complete proceedings, see ED657822.]

Published
2023

14. Navigating protein landscapes with a machine-learned transferable coarse-grained model

Author

Charron, Nicholas E., Musil, Felix, Guljas, Andrea, Chen, Yaoyi, Bonneau, Klara, Pasos-Trejo, Aldo S., Venturin, Jacopo, Gusew, Daria, Zaporozhets, Iryna, Krämer, Andreas, Templeton, Clark, Kelkar, Atharva, Durumeric, Aleksander E. P., Olsson, Simon, Pérez, Adrià, Majewski, Maciej, Husic, Brooke E., Patel, Ankit, De Fabritiis, Gianni, Noé, Frank, and Clementi, Cecilia

Subjects
Quantitative Biology - Biomolecules, Physics - Biological Physics, Physics - Chemical Physics, Statistics - Machine Learning
Abstract

The most popular and universally predictive protein simulation models employ all-atom molecular dynamics (MD), but they come at extreme computational cost. The development of a universal, computationally efficient coarse-grained (CG) model with similar prediction performance has been a long-standing challenge. By combining recent deep learning methods with a large and diverse training set of all-atom protein simulations, we here develop a bottom-up CG force field with chemical transferability, which can be used for extrapolative molecular dynamics on new sequences not used during model parametrization. We demonstrate that the model successfully predicts folded structures, intermediates, metastable folded and unfolded basins, and the fluctuations of intrinsically disordered proteins while it is several orders of magnitude faster than an all-atom model. This showcases the feasibility of a universal and computationally efficient machine-learned CG model for proteins.

Published
2023

15. Agent-based models of social behaviour and communication in evacuations: A systematic review

Author

Templeton, Anne, Xie, Hui, Gwynne, Steve, Hunt, Aoife, Thompson, Pete, and Köster, Gerta

Subjects
Computer Science - Multiagent Systems
Abstract

Most modern agent-based evacuation models involve interactions between evacuees. However, the assumed reasons for interactions and portrayal of them may be overly simple. Research from social psychology suggests that people interact and communicate with one another when evacuating and evacuee response is impacted by the way information is communicated. Thus, we conducted a systematic review of agent-based evacuation models to identify 1) how social interactions and communication approaches between agents are simulated, and 2) what key variables related to evacuation are addressed in these models. We searched Web of Science and ScienceDirect to identify articles that simulated information exchange between agents during evacuations, and social behaviour during evacuations. From the final 70 included articles, we categorised eight types of social interaction that increased in social complexity from collision avoidance to social influence based on strength of social connections with other agents. In the 17 models which simulated communication, we categorised four ways that agents communicate information: spatially through information trails or radii around agents, via social networks and via external communication. Finally, the variables either manipulated or measured in the models were categorised into the following groups: environmental condition, personal attributes of the agents, procedure, and source of information. We discuss promising directions for agent-based evacuation models to capture the effects of communication and group dynamics on evacuee behaviour. Moreover, we demonstrate how communication and group dynamics may impact the variables commonly used in agent-based evacuation models., Comment: Pre-print submitted to Safety Science special issue following the 2023 Pedestrian and Evacuation Dynamics conference

Published
2023
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16. A dynamic state-based model of crowds

Author

Amos, Martyn, Gwynne, Steve, and Templeton, Anne

Subjects
Computer Science - Multiagent Systems
Abstract

We consider the problem of categorizing and describing the dynamic properties and behaviours of crowds over time. Previous work has tended to focus on a relatively static "typology"-based approach, which does not account for the fact that crowds can change, often quite rapidly. Moreover, the labels attached to crowd behaviours are often subjective and/or value-laden. Here, we present an alternative approach, loosely based on the statechart formalism from computer science. This uses relatively "agnostic" labels, which means that we do not prescribe the behaviour of an individual, but provide a context within which an individual might behave. This naturally describes the time-series evolution of a crowd as "threads" of states, and allows for the dynamic handling of an arbitrary number of "sub-crowds"., Comment: Presented at the 2023 Pedestrian and Evacuation Dynamics Conference, Eindhoven, The Netherlands, June 28-30 2023

Published
2023
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17. Conversational launch pads: Strangers start their conversations with topics that lead to many other topics

Author

Templeton, Emma, Chang, Luke, and Wheatley, Thalia

Subjects
Psychology, Interactive behavior, Natural Language Processing, Corpus studies
Abstract

How do people start conversations with someone they have never met before? In this project, we investigate the hypothesis that good starting topics facilitate transitions to many different topics. To test this, we leverage a dataset of unstructured, 10-minute conversations between pairs of strangers. Using natural language processing (NLP) and network approaches, we show that strangers begin their conversations with topics that are centrally located in a network of topic transitions. These “launch pad” topics are useful starting points because they are well-connected to other topics, potentially increasing the likelihood of finding common ground. These findings underscore the fact that it is not the semantic meaning of a topic that makes it an effective starting point, but rather its transition properties. This insight paves the way for future research to identify conversational launch pads in different populations, where common starting topics may differ widely but nonetheless hold similar network positions. When people start conversations, they begin the process of trying to understand and connect with another person's mind. Here, we examine how this important process unfolds.

Published
2024

19. High-volume hybridoma sequencing on the NeuroMabSeq platform enables efficient generation of recombinant monoclonal antibodies and scFvs for neuroscience research

Author

Mitchell, KG, Gong, B, Hunter, SS, Burkart-Waco, D, Gavira-O’Neill, CE, Templeton, KM, Goethel, ME, Bzymek, M, MacNiven, LM, Murray, KD, Settles, ML, Froenicke, L, and Trimmer, JS

Abstract

The Neuroscience Monoclonal Antibody Sequencing Initiative (NeuroMabSeq) is a concerted effort to determine and make publicly available hybridoma-derived sequences of monoclonal antibodies (mAbs) valuable to neuroscience research. Over 30 years of research and development efforts including those at the UC Davis/NIH NeuroMab Facility have resulted in the generation of a large collection of mouse mAbs validated for neuroscience research. To enhance dissemination and increase the utility of this valuable resource, we applied a high-throughput DNA sequencing approach to determine immunoglobulin heavy and light chain variable domain sequences from source hybridoma cells. The resultant set of sequences was made publicly available as a searchable DNA sequence database (neuromabseq.ucdavis.edu) for sharing, analysis and use in downstream applications. We enhanced the utility, transparency, and reproducibility of the existing mAb collection by using these sequences to develop recombinant mAbs. This enabled their subsequent engineering into alternate forms with distinct utility, including alternate modes of detection in multiplexed labeling, and as miniaturized single chain variable fragments or scFvs. The NeuroMabSeq website and database and the corresponding recombinant antibody collection together serve as a public DNA sequence repository of mouse mAb heavy and light chain variable domain sequences and as an open resource for enhancing dissemination and utility of this valuable collection of validated mAbs.

Published
2023

20. A microphysiological system for studying barrier health of live tissues in real time

Author

Ryan Way, Hayley Templeton, Daniel Ball, Ming-Hao Cheng, Stuart A. Tobet, and Thomas Chen

Subjects
Engineering (General). Civil engineering (General), TA1-2040
Abstract

Abstract Epithelial cells create barriers that protect many different components in the body from their external environment. Increased gut barrier permeability (leaky gut) has been linked to several chronic inflammatory diseases. Understanding the cause of leaky gut and effective interventions are elusive due to the lack of tools that maintain tissue’s physiological environment while elucidating cellular functions under various stimuli ex vivo. Here we present a microphysiological system that records real-time barrier permeability of mouse colon in a physiological environment over extended durations. The system includes a microfluidic chamber; media composition that preserves microbiome and creates necessary oxygen gradients across the barrier; and integrated sensor electrodes for acquiring transepithelial electrical resistance (TEER). Our results demonstrate that the system can maintain tissue viability for up to 72 h. The TEER sensors can distinguish levels of barrier permeability when treated with collagenase and low pH media and detect different thickness in the tissue explant.

Published
2024
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21. First Indicator of Relapse in Testicular Cancer and Implications for Follow-up: Analysis of the Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS)

Author

Stefanie Fischer, Silke Gillessen, Odile Stalder, Angelika Terbuch, Richard Cathomas, Florian A. Schmid, Deborah Zihler, Beat Müller, Christian D. Fankhauser, Anita Hirschi-Blickenstorfer, Luis Alex Kluth, Bettina Seifert, Arnoud J. Templeton, Walter Mingrone, Mark-Peter Ufe, Natalie Fischer, Jörg Beyer, Regina Woelky, Aurelius Omlin, Ursula Vogl, Katharina Hoppe, Jörn Kamradt, Sacha I. Rothschild, and Christian Rothermundt

Subjects
Testicular cancer, Follow-up, Germ cell tumours, Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background and objective: Follow-up for patients with testicular cancer should ensure early detection of relapses. Optimal schedules and minimum requirements for cross-sectional imaging are not clearly defined, and guideline recommendations differ. Our aim was to analyse the clinical impact of different imaging modalities for detection of relapse in a large prospective cohort (Swiss Austrian German Testicular Cancer Cohort Study, SAG TCCS). Methods: Patients with seminoma or nonseminoma were prospectively enrolled between January 2014 and February 2023 after initial treatment (n = 1175). Follow-up according to the study schedule was individualised for histology and disease stage. Only patients who had received primary treatment were considered. We analysed the total number of imaging modalities and scans identifying relapse and the timing of relapse. Key findings and limitations: We analysed data for 1006 patients (64% seminoma, 36% nonseminoma); 76% had stage I disease. Active surveillance was the most frequent management strategy (65%). Recurrence occurred in 82 patients, corresponding to a 5-yr relapse-free survival rate of 90.1% (95% confidence interval 87.7–92.1%). Median follow-up for patients without relapse was 38.4 mo (interquartile range 21.6–61.0). Cross-sectional imaging of the abdomen was the most important indicator of relapse 57%, abdominal CT accounting for 46% and MRI for 11%. Marker elevation indicated relapse in 24% of cases. Chest X-ray was the least useful modality, indicating relapse in just 2% of cases. Conclusions and clinical implications: On the basis of findings from our prospective register, we have adapted follow-up schedules with an emphasis on abdominal imaging and a reduction in chest X-rays. These schedules might provide additional guidance for clinicians and will be prospectively evaluated as SAG TCCS continues to enrol patients. Patient summary: We analysed the value of different types of imaging scans for detection of relapse of testicular cancer. We used our findings to propose an optimum follow-up schedule for patients with testicular cancer.

Published
2024
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24. ASO Visual Abstract: The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study

Author

Shah, Chirag, Whitworth, Pat, Vicini, Frank A., Narod, Steven, Gerber, Naamit, Jhawar, Sachin R., King, Tari A., Mittendorf, Elizabeth A., Willey, Shawna C., Rabinovich, Rachel, Gold, Linsey, Brown, Eric, Patel, Anushka, Vargo, John, Barry, Parul N., Rock, David, Friedman, Neil, Bedi, Gauri, Templeton, Sandra, Brown, Sheree, Gabordi, Robert, Riley, Lee, Lee, Lucy, Baron, Paul, Majithia, Lonika, Mirabeau-Beale, Kristina L., Reid, Vincent J., Hirsch, Arica, Hwang, Catherine, Pellicane, James, Maganini, Robert, Khan, Sadia, MacDermed, Dhara M., Small, William, Mittal, Karuna, Borgen, Patrick, Cox, Charles, Shivers, Steven C., and Bremer, Troy

Published
2024
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26. Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review

Author

Kaufmann, Ernest, Aeppli, Stefanie, Arnold, Winfried, Balermpas, Panagiotis, Beyer, Jörg, Bieri, Uwe, Cathomas, Richard, de Bari, Berardino, Dressler, Marco, Engeler, Daniel S., Erdmann, Andreas, Gallina, Andrea, Gomez, Silvia, Guckenberger, Matthias, Herrmann, Thomas R. W., Hermanns, Thomas, Ilaria, Lucca, John, Hubert, Kessler, Thomas M., Klein, Jan, Laouiti, Mohamed, Lauffer, David, Mattei, Agostino, Müntener, Michael, Nguyen, Daniel, Niederberger, Philipp, Papachristofilou, Alexandros, Prause, Lukas, Reinhardt, Karsten, Salati, Emanuela, Sèbe, Philippe, Shelan, Mohamed, Strebel, Räto, Templeton, Arnoud J., Vogl, Ursula, Wettstein, Marian S., Zihler, Deborah, Zilli, Thomas, Zwahlen, Daniel, Roth, Beat, and Fankhauser, Christian

Published
2024
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31. Transitioning from Triton X-100 to Tergitol 15-S-9: impacts on diagnostic assays using viral PCR sample solution

Author

Azul Zorzoli, Alasdair MacLean, Scott Nicholson, Alison Daniels, Stephen Hughes, Susan Bennet-Slater, Christine Tait-Burkard, Noha El Sakka, Rory Gunson, and Kate Templeton

Subjects
cycle threshold (Ct), SARS-CoV-2, Tergitol 15-S-9, Triton X-100, viral load, Biology (General), QH301-705.5
Abstract

In 2019, the European Union banned Triton X-100, a detergent widely used in laboratory diagnostics, including the Viral PCR Sample Solution (VPSS), and urged manufacturers to find environmentally sustainable alternatives. Tergitol 15-S-9 (VPSS2) has been proposed as an alternative surfactant. This multicenter study evaluated the effectiveness of VPSS2, a Tergitol-based viral solution, as a replacement for VPSS. Our results show the equivalent performance of VPSS2 to VPSS for nucleic acid extraction and viral stability over time at different temperatures. The new VPSS formulation was also tested against external quality assurance panels and clinical samples. The results of this work support adopting this modified viral PCR sample solution to replace Triton X-100-containing viral transport solutions.

Published
2024
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32. Estimating drinking water turbidity using images collected by a smartphone camera

Author

Chotiwat Jantarakasem, Laure Sioné, and Michael R. Templeton

Subjects
cnn, drinking water, protocol, smartphone camera, turbidity, Environmental technology. Sanitary engineering, TD1-1066, Environmental sciences, GE1-350
Abstract

The lack of robust water quality data in drinking water services in many low-income settings can be attributed to inadequate funding for regular monitoring using analytical equipment. Turbidity is an indicator that is relatively quick and easy to measure; however, it still requires a turbidimeter and a trained operator. This study developed an entire smartphone camera-based application to measure turbidity in drinking water, removing both the need for external equipment and skilled labour. The application was created using a convolutional neural network, able to classify water samples into eight turbidity bins ranging from 0 to 40 NTU. The turbidity of the samples was created using formazine and kaolin clay suspensions. The in-built camera of a smartphone was used to capture images of water samples with known turbidity values. This algorithm was then embedded in a smartphone application, thereby providing an easy-to-use tool for users to estimate turbidity. Specifically, the protocol for using this application was developed with the intention that it will be used in low-resource settings by laypersons. Formazine samples achieved a turbidity classification accuracy of 98.7%, while kaolin clay samples achieved 90.9% accuracy using this method, which provides an encouraging proof of concept, as justification for further testing and improvements. HIGHLIGHTS An algorithm and accompanying protocol for estimating drinking water turbidity using only a smartphone camera were developed. The protocol is designed for use in low-resource settings by laypersons.; A correct turbidity bin classification accuracy of 98.7% was obtained for formazine samples between 0 and 40 NTU in the laboratory.;

Published
2024
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33. Awake Supraglottic Airway Placement in Pediatric Patients for Airway Obstruction or Difficult Intubation: Insights From an International Airway Registry (PeDI)

Author

Longacre, Mckenna, Park, Raymond S., Staffa, Steven J., Rowland, Matthew J., Meserve, Jonathan, Lord, Charles, Templeton, T. Wesley, Garcia-Marcinkiewicz, Annery G., Peyton, James M., Fiadjoe, John E., Kovatsis, Pete G., Stein, Mary Lyn, Bruins, Benjamin B., Stricker, Paul, Laverriere, Elizabeth K., Lockman, Justin L., Struyk, Brian, Ward, Christopher, Nishisaki, Akira, Kodavatiganti, Ramesh, Guris, Rodrigo J. Daly, Sequera-Ramos, Luis, Teen, Mark S., Oke, Ayodele, Hsu, Grace, Lingappan, Arul, Egbuta, Chinyere, Flynn, Stephen, Sarmiento, Lina, Battles, Rhae, Bocanegra, Ashley D., Goldfarb, Tally, Kiss, Edgar E., Olomu, Patrick N., Szmuk, Peter, Mireles, Sam, Murray, Andrea, Whyte, Simon, Jain, Ranu, Khan, Sabina A., Matuszczak, Maria, Hunyady, Agnes, Holmes, Christopher, McCann, Alexander, Sabato, Stefano, Matava, Clyde, Dalesio, Nicholas, Greenberg, Robert, Lucero, Angela, Desai, Sapna, Tennessee, Nashville, Rosander, Sondra, Samba, Sindhu, Schrock, Charles, Nykiel-Bailey, Sydney, Marsh, Jennifer, Brooks Peterson, Melissa, Johnson Lee, Amy Colleen, Bhattacharya, Somaletha, Burjek, Nicholas E., Jagannathan, Narasimhan, Lardner, David, Crockett, Christy, Robertson, Sara, Sathyamoorthy, Madhankumar, Chiao, Franklin, Patel, Jasmine, Sharma, Aarti, Echeverry Marin, Piedad, Pérez-Pradilla, Carolina, Singh, Neeta, Taicher, Brad, von Ungern-Sternberg, Britta S., Sommerfield, David, Hauser, Neil, Hesselink, Emily, Lewkowitz-Shpuntoff, Hilana, Castro, Pilar, Riveros Perez, N. Ricardo, Leite, Fernanda, Vega, Eduardo, González, Alejandro, Ostermann, Paola, Rubin, Kasia, Lee, Angela, Valairucha, Songyos, Dalal, Priti, Tran, Thanh, Anspach, Taylor, Lee, Lisa K., Ayad, Ihab, Rehman, Mohamed, Fernandez, Allison, Zamora, Lillian, Ravula, Niroop, Shaik, Sadiq, Szolnoki, Judit, Mathew, Preethy J., Yaddanapudi, Sandhya, Sen, Indu, Gupta, Aakriti, Handlogten, Kathryn, Sroka, J. Michael, Caldeira Quintao, Vinicius, and Vieira Carlos, Ricardo

Published
2024
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35. Patient and Process Outcomes among Pediatric Patients Undergoing Appendectomy during the COVID-19 Pandemic: An International Retrospective Cohort Study

Author

Matava, Clyde T, Tighe, Nathaniel TG, Baertschiger, Reto, Wilder, Robert T, Correll, Lynnie, Staffa, Steven J, Zurakowski, David, Kato, Meredith A, Meier, Petra M, Raman, Vidya, Reddy, Srijaya K, Roque, Remigio A, Peterson, Melissa Brooks, Zhong, John, Edala, Thejovathi, Greer, Timothy J, von Ungern-Sternberg, Britta S, Cravero, Joseph, Simpao, Allan F, Ali, Anita Akbar, Al-Rabbat, Mohamad F, Brzenski, Alyssa B, Casey, William F, Chhabada, Surendrasingh, Collin, Michael, Dhumak, Vipul J, D’Mello, Ajay, Echeverry, Piedad C, Ellison, Pavithra R, Fernandez, Allison M, Fisher, Jake A, Fuller, Clinton L, Glover, Chris D, Guruswamy, Velu, Hesselink, Emily B, Hunyady, Agnes I, Lorinc, Amanda N, King, Michael, Mihaila, Lavinia, Nelson, Jonathon H, Ng, Ann S, Ramjist, Joshua K, Ravula, Nirop R, Beel, Elizabeth Rossmann, Rugnathx, Rahil, Shaw, Robert E, Sheth, Michelle M, Sinha, Tripiti, Sommerfield, Aine, Soneru, Codruta, Templeton, Thomas W, and Williams, RJ

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Pediatric, Patient Safety, Prevention, Good Health and Well Being, Humans, Child, COVID-19, Retrospective Studies, Pandemics, Appendicitis, Appendectomy, COVID-19 Testing, Postoperative Complications, SARS-CoV-2, Length of Stay, PEACOC Collaborators, Anesthesiology, Clinical sciences
Abstract

BackgroundCOVID-19 forced healthcare systems to make unprecedented changes in clinical care processes. The authors hypothesized that the COVID-19 pandemic adversely impacted timely access to care, perioperative processes, and clinical outcomes for pediatric patients undergoing primary appendectomy.MethodsA retrospective, international, multicenter study was conducted using matched cohorts within participating centers of the international PEdiatric Anesthesia COVID-19 Collaborative (PEACOC). Patients younger than 18 yr old were matched using age, American Society of Anesthesiologists Physical Status, and sex. The primary outcome was the difference in hospital length of stay of patients undergoing primary appendectomy during a 2-month period early in the COVID-19 pandemic (April to May 2020) compared with prepandemic (April to May 2019). Secondary outcomes included time to appendectomy and the incidence of complicated appendicitis.ResultsA total of 3,351 cases from 28 institutions were available with 1,684 cases in the prepandemic cohort matched to 1,618 in the pandemic cohort. Hospital length of stay was statistically significantly different between the two groups: 29 h (interquartile range: 18 to 79) in the pandemic cohort versus 28 h (interquartile range: 18 to 67) in the prepandemic cohort (adjusted coefficient, 1 [95% CI, 0.39 to 1.61]; P < 0.001), but this difference was small. Eight centers demonstrated a statistically significantly longer hospital length of stay in the pandemic period than in the prepandemic period, while 13 were shorter and 7 did not observe a statistically significant difference. During the pandemic period, there was a greater occurrence of complicated appendicitis, prepandemic 313 (18.6%) versus pandemic 389 (24.1%), an absolute difference of 5.5% (adjusted odds ratio, 1.32 [95% CI, 1.1 to 1.59]; P = 0.003). Preoperative SARS-CoV-2 testing was associated with significantly longer time-to-appendectomy, 720 min (interquartile range: 430 to 1,112) with testing versus 414 min (interquartile range: 231 to 770) without testing, adjusted coefficient, 306 min (95% CI, 241 to 371; P < 0.001), and longer hospital length of stay, 31 h (interquartile range: 20 to 83) with testing versus 24 h (interquartile range: 14 to 68) without testing, adjusted coefficient, 7.0 (95% CI, 2.7 to 11.3; P = 0.002).ConclusionsFor children undergoing appendectomy, the COVID-19 pandemic did not significantly impact hospital length of stay.Editor’s perspective

Published
2023

36. Difficult or impossible facemask ventilation in children with difficult tracheal intubation: a retrospective analysis of the PeDI registry

Author

Garcia-Marcinkiewicz, Annery G, Lee, Lisa K, Haydar, Bishr, Fiadjoe, John E, Matava, Clyde T, Kovatsis, Pete G, Peyton, James, Stein, Mary L, Park, Raymond, Taicher, Brad M, Templeton, Thomas W, Collaborative, on behalf of the PeDI, Bruins, Benjamin B, Stricker, Paul, Laverriere, Elizabeth K, Lockman, Justin L, Struyk, Brian, Ward, Christopher, Nishisaki, Akira, Kodavatiganti, Ramesh, Guris, Rodrigo J Daly, Sequera-Ramos, Luis, Teen, Mark S, Oke, Ayodele, Hsu, Grace, Lingappan, Arul, Egbuta, Chinyere, Flynn, Stephen, Sarmiento, Lina, Goldfarb, Tally, Kiss, Edgar E, Olomu, Patrick N, Szmuk, Peter, Mireles, Sam, Murray, Andrea, Whyte, Simon, Jain, Ranu, Matuszczak, Maria, Hunyady, Agnes, Bosenberg, Adrian, Tham, See, Low, Daniel, Holmes, Christopher, Sabato, Stefan, Dalesio, Nicholas, Greenberg, Robert, Lucero, Angela, Reynolds, Paul, Lewis, Ian, Schrock, Charles, Nykiel-Bailey, Sydney, Starker, Elizabeth, Szolnoki, Judit, Brooks-Peterson, Melissa, Bhattacharya, Somaletha, Burjek, Nicholas E, Jagannathan, Narasimhan, Lardner, David, Watkins, Scott, Crockett, Christy, Moore, John, Robertson, Sara, Sathyamoorthy, Madhankumar, Chiao, Franklin, Patel, Jasmine, Sharma, Aarti, Marin, Piedad Echeverry, Pérez-Pradilla, Carolina, Singh, Neeta, von Ungern-Sternberg, Britta S, Sommerfield, David, Bilen-Rosas, Guelay, Lewkowitz-Shpuntoff, Hilana, Castro, Pilar, Perez, N Ricardo Riveros, de Graaff, Jurgen C, Vega, Eduardo, González, Alejandro, Ostermann, Paola, Rubin, Kasia, Lord, Charles, Lee, Angela, Heitmiller, Eugenie, Valairucha, Songyos, Dalal, Priti, Tran, Thanh, Ayad, Ihab, Rehman, Mohamed, Fernandez, Allison, Zamora, Lillian, Ravula, Niroop, and Shaik, Sadiq

Subjects
Rare Diseases, Lung, Assistive Technology, Bioengineering, Infant, Humans, Child, Masks, Intubation, Intratracheal, Retrospective Studies, Respiration, Laryngeal Masks, Airway Management, complications, difficult airway, difficult facemask ventilation, impossible facemask ventilation, paediatrics, supraglottic airway, PeDI Collaborative, Clinical Sciences, Anesthesiology
Abstract

BackgroundDifficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation.MethodsWe queried a multicentre registry for children who experienced "difficult" or "impossible" facemask ventilation. Patient and case factors known before mask ventilation attempt were included for consideration in this regularised multivariable regression analysis. Incidence of complications, and frequency and efficacy of rescue placement of a supraglottic airway device were also tabulated. Changes in quality of mask ventilation after injection of a neuromuscular blocking agent were assessed.ResultsThe incidence of difficult mask ventilation was 9% (483 of 5453 patients). Infants and patients having increased weight, being less than 5th percentile in weight for age, or having Treacher-Collins syndrome, glossoptosis, or limited mouth opening were more likely to have difficult mask ventilation. Anaesthetic induction using facemask and opioids was associated with decreased risk of difficult mask ventilation. The incidence of complications was significantly higher in patients with "difficult" mask ventilation than in patients without. Rescue placement of a supraglottic airway improved ventilation in 71% (96 of 135) of cases. Administration of neuromuscular blocking agents was more frequently associated with improvement or no change in quality of ventilation than with worsening.ConclusionsCertain abnormalities on physical examination should increase suspicion of possible difficult facemask ventilation. Rescue use of a supraglottic airway device in children with difficult or impossible mask ventilation should be strongly considered.

Published
2023

43. Is Clot Composition Associated With Cause of Stroke? A Systematic Review and Meta‐Analysis

Author

Nanthiya Sujijantarat, Kelsey A. Templeton, Joseph P. Antonios, Daniela Renedo, Andrew B. Koo, Joseph O. Haynes, Bushra Fathima, Abdelaziz Amllay, Kamil Nowicki, Anita Huttner, James A. Giles, Dhasakumar Navaratnam, Lauren H. Sansing, Ryan M. Hebert, Joseph T. King, and Charles C. Matouk

Subjects
cause of stroke, histology, stroke, thrombectomy, thrombus, Neurology. Diseases of the nervous system, RC346-429, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Prior studies have suggested an association between clot histological composition and cause of stroke. However, the results have been conflicting. Our objective is to provide an updated systematic review and meta‐analysis of the association between clot histological composition and cause of stroke for patients who underwent mechanical thrombectomy. Methods We searched Cochrane Library, Embase, and MEDLINE databases for English language articles reporting clot histology in adult patients who underwent mechanical thrombectomy for acute ischemic stroke between January 2000 and March 2024. Studies included reported on the association between causes of clots and the quantity of red blood cells and fibrin and/or platelets. Random effects meta‐analysis was used. Results A total of 448 records were identified. Of these, 25 studies were included in the qualitative synthesis, and 17 contained data in a format suitable for quantitative review. A total of 1656 patients had continuous data on clot composition and its association with cause of stroke. The pooled mean percentage difference between the cardioembolic group and the large artery atherosclerosis /noncardioembolic group was −10.3% (95% CI −16.3% to −4.4%) for red blood cells and +9.9% (95% CI +4.5% to +15.4%) for fibrin and/or platelets. Only 7 studies reported on overall white blood cells quantity. Of these, the pooled percentage difference of white blood cells between the cardioembolic group and the large artery atherosclerosis/non‐cardioembolic group was +1.1% (95% CI +0.3% to +1.9%). Conclusion Our results suggest that cardioembolic clots have higher fibrin and/or platelets and lower red blood cells compared with large artery atherosclerosis/noncardioembolic clots. However, these differences are unlikely to be of clinical utility in differentiating cause of stroke. Future studies would benefit from more rigorous analysis of clot constituents beyond cellular composition.

Published
2024
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45. Exercising educational equity using California’s physical fitness data: a call for more school physical fitness programs, data, and research

Author

Da’Shay Templeton and Ruslan Korchagin

Subjects
physical activity, physical fitness and sport, adolescence health, California schools, educational equity, educational equity (finance), Education (General), L7-991
Abstract

Childhood obesity has risen and is one of the most important global problems of our time, and school physical education programs are the key to ameliorating it. In American schools, physical fitness scores have declined; yet, global, national, state, and local concerns for the overall health, physical fitness, and wellbeing of children are at an all-time high. The lack of safe and affordable options for physical activity coupled with the significant decrease in physical activity rates among most American children underscores the need for programs, data, and research on physical fitness in schools, where children spend a significant amount of their time. The purpose of this brief research report is to call the federal government and states to mandate physical fitness programs and to increase data collection capacity on physical fitness in schools. Subsequently, this study asks researchers to study physical fitness in schools in the U.S. to increase its importance to policy makers and educational stakeholders and advance our understanding of educational inequities in school physical fitness. As an example, using descriptive analyses, we have provided policymakers, educational stakeholders, and researchers with a first look at California’s physical fitness data which shows how our findings complement prior literature as well as extend them. Implications for the research and practice are discussed.

Published
2024
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46. Incorporating functional traits with habitat maps: patterns of diversity in coastal benthic assemblages

Author

Shreya Nemani, Benjamin Misiuk, David Cote, Evan Edinger, Julia Mackin-McLaughlin, Adam Templeton, and Katleen Robert

Subjects
biological traits analysis, coastal habitats, functional diversity, geomorphometry, predictive modelling, species assemblages, Science, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

Benthic species assemblages are groups of species that co-occur on the seafloor. Linking assemblages to physical environmental features allows for understanding and predicting their spatial distribution. Species identity and abundance are commonly quantified using a taxonomic approach to assess benthic diversity, yet functional traits that describe the behavior, life history, and morphology of a species may be equally or more important. Here, we investigate the biodiversity of five benthic species assemblages in relation to their habitat and environmental conditions in an Ecologically and Biologically Significant Area (EBSA) along Canada’s east coast, using both a taxonomic approach and biological traits analysis. Random Forest regression was applied to map spatial patterns of functional and taxonomic diversity metrics, including richness, Shannon index, and Rao’s quadratic entropy. We evaluate discrepancies between related taxonomic and trait measures, and the community-weighted mean of trait data was calculated to characterize each assemblage. Taxonomic and functional richness – representing the number of species and the species community volume in the trait space, respectively – showed similar spatial patterns. However, when considering diversity, which also accounts for the relative abundance and differences among species or traits, these patterns diverged. Taxonomically different assemblages exhibited similar trait compositions for two assemblages, indicating potential trait equivalencies, while one assemblage exhibited traits potentially indicating sensitivity to human activity. The taxonomic and functional metrics of richness and diversity were low close to the coast, which could be indicative of disturbance. Consideration of functional metrics can support spatial planning and prioritization for management and conservation efforts by assessing the sensitivity of traits to different stressors.

Published
2024
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47. Syphilis testing, incidence, and reinfection among gay and bisexual men in Australia over a decade spanning HIV PrEP implementation: an analysis of surveillance data from 2012 to 2022Research in context

Author

Michael W. Traeger, Rebecca Guy, Caroline Taunton, Eric P.F. Chow, Jason Asselin, Allison Carter, Htein Linn Aung, Mark Bloch, Christopher K. Fairley, Anna McNulty, Vincent J. Cornelisse, Phillip Read, Louise Owen, Nathan Ryder, David J. Templeton, Darryl O'Donnell, Basil Donovan, Margaret E. Hellard, and Mark A. Stoové

Subjects
Syphilis, Treponema pallidum, Gay and bisexual men, Men who have sex with men, MSM, HIV, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Gay and bisexual men (GBM) remain overrepresented among syphilis diagnoses in Australia and globally. The extent to which changes in sexual networks associated with HIV pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) may have influenced syphilis transmission among GBM at the population-level is poorly understood. We describe trends in syphilis testing and incidence among GBM in Australia over eleven years spanning widespread uptake of HIV PrEP and TasP. Methods: We analysed linked clinical data from GBM aged 16 years or older across a sentinel surveillance network in Australia from January 1, 2012, to December 31, 2022. Individuals with at least two clinic visits and with at least two syphilis tests during the observations period were included in testing and incidence analyses, respectively. Annual rates of testing and infectious syphilis incidence from 2012 to 2022 were disaggregated by HIV status and PrEP use (record of PrEP prescription; retrospectively categorised as ever or never-PrEP user). Cox regression explored associations between demographics, PrEP use and history of bacterial sexually transmissible infections (STIs) and infectious syphilis diagnosis. Findings: Among 129,278 GBM (mean age, 34.6 years [SD, 12.2]) included in testing rate analyses, 7.4% were living with HIV at entry and 31.1% were prescribed PrEP at least once during the study period. Overall syphilis testing rate was 114.0/100 person-years (py) and highest among GBM with HIV (168.4/100 py). Syphilis testing increased from 72.8/100 py to 151.8/100 py; driven largely by increases among ever-PrEP users. Among 94,710 GBM included in incidence analyses, there were 14,710 syphilis infections diagnosed over 451,560 person-years (incidence rate = 3.3/100 py). Syphilis incidence was highest among GBM with HIV (6.5/100 py), followed by ever-PrEP users (3.5/100 py) and never-PrEP users (1.4/100 py). From 2012 to 2022, syphilis incidence increased among ever-PrEP users from 1.3/100 py to 5.1/100 py, and fluctuated between 5.4/100 py and 6.6/100 py among GBM with HIV. In multivariable Cox regression, previous syphilis diagnosis (adjusted hazard ratio [aHR] = 1.98, 95% CI = 1.83–2.14), living with HIV (aHR = 1.83, 95% CI = 1.12–1.25) and recent (past 12 m) prescription of PrEP (aHR = 1.78, 95% CI = 1.61–1.97) were associated with syphilis diagnosis. Interpretation: Syphilis trends between GBM with HIV and GBM with evidence of PrEP use have converged over the past decade in Australia. Our findings recommend targeting emergent syphilis control strategies (e.g. doxycycline post-exposure prophylaxis) to GBM with prior syphilis diagnoses, using HIV PrEP or who are living with HIV. Funding: Australian Department of Health and Aged Care, National Health and Medical Research Council.

Published
2024
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48. Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Author

Jannik Boos, Caspar I. van der Made, Gayatri Ramakrishnan, Eamon Coughlan, Rosanna Asselta, Britt-Sabina Löscher, Luca V.C. Valenti, Rafael de Cid, Luis Bujanda, Antonio Julià, Erola Pairo-Castineira, J. Kenneth Baillie, Sandra May, Berina Zametica, Julia Heggemann, Agustín Albillos, Jesus M. Banales, Jordi Barretina, Natalia Blay, Paolo Bonfanti, Maria Buti, Javier Fernandez, Sara Marsal, Daniele Prati, Luisa Ronzoni, Nicoletta Sacchi, Joachim L. Schultze, Olaf Riess, Andre Franke, Konrad Rawlik, David Ellinghaus, Alexander Hoischen, Axel Schmidt, Kerstin U. Ludwig, Valeria Rimoldi, Elvezia M. Paraboschi, Alessandra Bandera, Flora Peyvandi, Giacomo Grasselli, Francesco Blasi, Francesco Malvestiti, Serena Pelusi, Cristiana Bianco, Lorenzo Miano, Angela Lombardi, Pietro Invernizzi, Alessio Gerussi, Giuseppe Citerio, Andrea Biondi, Maria Grazia Valsecchi, Marina Elena Cazzaniga, Giuseppe Foti, Ilaria Beretta, Mariella D'Angiò, Laura Rachele Bettini, Xavier Farré, Susana Iraola-Guzmán, Manolis Kogevinas, Gemma Castaño-Vinyals, Koldo Garcia-Etxebarria, Beatriz Nafria, Mauro D'Amato, Adriana Palom, Colin Begg, Sara Clohisey, Charles Hinds, Peter Horby, Julian Knight, Lowell Ling, David Maslove, Danny McAuley, Johnny Millar, Hugh Montgomery, Alistair Nichol, Peter J.M. Openshaw, Alexandre C. Pereira, Chris P. Ponting, Kathy Rowan, Malcolm G. Semple, Manu Shankar-Hari, Charlotte Summers, Timothy Walsh, Latha Aravindan, Ruth Armstrong, Heather Biggs, Ceilia Boz, Adam Brown, Richard Clark, Audrey Coutts, Judy Coyle, Louise Cullum, Sukamal Das, Nicky Day, Lorna Donnelly, Esther Duncan, Angie Fawkes, Paul Fineran, Max Head Fourman, Anita Furlong, James Furniss, Bernadette Gallagher, Tammy Gilchrist, Ailsa Golightly, Fiona Griffiths, Katarzyna Hafezi, Debbie Hamilton, Ross Hendry, Andy Law, Dawn Law, Rachel Law, Sarah Law, Rebecca Lidstone-Scott, Louise Macgillivray, Alan Maclean, Hanning Mal, Sarah McCafferty, Ellie Mcmaster, Jen Meikle, Shona C. Moore, Kirstie Morrice, Lee Murphy, Sheena Murphy, Mybaya Hellen, Wilna Oosthuyzen, Chenqing Zheng, Jiantao Chen, Nick Parkinson, Trevor Paterson, Katherine Schon, Andrew Stenhouse, Mihaela Das, Maaike Swets, Helen Szoor-McElhinney, Filip Taneski, Lance Turtle, Tony Wackett, Mairi Ward, Jane Weaver, Nicola Wrobel, Marie Zechner, Gill Arbane, Aneta Bociek, Sara Campos, Neus Grau, Tim Owen Jones, Rosario Lim, Martina Marotti, Marlies Ostermann, Christopher Whitton, Zoe Alldis, Raine Astin-Chamberlain, Fatima Bibi, Jack Biddle, Sarah Blow, Matthew Bolton, Catherine Borra, Ruth Bowles, Maudrian Burton, Yasmin Choudhury, David Collier, Amber Cox, Amy Easthope, Patrizia Ebano, Stavros Fotiadis, Jana Gurasashvili, Rosslyn Halls, Pippa Hartridge, Delordson Kallon, Jamila Kassam, Ivone Lancoma-Malcolm, Maninderpal Matharu, Peter May, Oliver Mitchelmore, Tabitha Newman, Mital Patel, Jane Pheby, Irene Pinzuti, Zoe Prime, Oleksandra Prysyazhna, Julian Shiel, Melanie Taylor, Carey Tierney, Suzanne Wood, Anne Zak, Olivier Zongo, Stephen Bonner, Keith Hugill, Jessica Jones, Steven Liggett, Evie Headlam, Nageswar Bandla, Minnie Gellamucho, Michelle Davies, Christopher Thompson, Marwa Abdelrazik, Dhanalakshmi Bakthavatsalam, Munzir Elhassan, Arunkumar Ganesan, Anne Haldeos, Jeronimo Moreno-Cuesta, Dharam Purohit, Rachel Vincent, Kugan Xavier, Kumar Rohit, Frater Alasdair, Malik Saleem, Carter David, Jenkins Samuel, Zoe Lamond, Wall Alanna, Jaime Fernandez-Roman, David O. Hamilton, Emily Johnson, Brian Johnston, Maria Lopez Martinez, Suleman Mulla, David Shaw, Alicia A.C. Waite, Victoria Waugh, Ingeborg D. Welters, Karen Williams, Anna Cavazza, Maeve Cockrell, Eleanor Corcoran, Maria Depante, Clare Finney, Ellen Jerome, Mark McPhail, Monalisa Nayak, Harriet Noble, Kevin O'Reilly, Evita Pappa, Rohit Saha, Sian Saha, John Smith, Abigail Knighton, David Antcliffe, Dorota Banach, Stephen Brett, Phoebe Coghlan, Ziortza Fernandez, Anthony Gordon, Roceld Rojo, Sonia Sousa Arias, Maie Templeton, Megan Meredith, Lucy Morris, Lucy Ryan, Amy Clark, Julia Sampson, Cecilia Peters, Martin Dent, Margaret Langley, Saima Ashraf, Shuying Wei, Angela Andrew, Archana Bashyal, Neil Davidson, Paula Hutton, Stuart McKechnie, Jean Wilson, David Baptista, Rebecca Crowe, Rita Fernandes, Rosaleen Herdman-Grant, Anna Joseph, Denise O'Connor, Meryem Allen, Adam Loveridge, India McKenley, Eriko Morino, Andres Naranjo, Richard Simms, Kathryn Sollesta, Andrew Swain, Harish Venkatesh, Jacyntha Khera, Jonathan Fox, Gillian Andrew, Lucy Barclay, Marie Callaghan, Rachael Campbell, Sarah Clark, Dave Hope, Lucy Marshall, Corrienne McCulloch, Kate Briton, Jo Singleton, Sohphie Birch, Lutece Brimfield, Zoe Daly, David Pogson, Steve Rose, Ceri Battle, Elaine Brinkworth, Rachel Harford, Carl Murphy, Luke Newey, Tabitha Rees, Marie Williams, Sophie Arnold, Petra Polgarova, Katerina Stroud, Eoghan Meaney, Megan Jones, Anthony Ng, Shruti Agrawal, Nazima Pathan, Deborah White, Esther Daubney, Kay Elston, Lina Grauslyte, Musarat Hussain, Mandeep Phull, Tatiana Pogreban, Lace Rosaroso, Erika Salciute, George Franke, Joanna Wong, Aparna George, Laura Ortiz-Ruiz de Gordoa, Emily Peasgood, Claire Phillips, Michelle Bates, Jo Dasgin, Jaspret Gill, Annette Nilsson, James Scriven, Carlos Castro Delgado, Deborah Dawson, Lijun Ding, Georgia Durrant, Obiageri Ezeobu, Sarah Farnell-Ward, Abiola Harrison, Rebecca Kanu, Susannah Leaver, Elena Maccacari, Soumendu Manna, Romina Pepermans Saluzzio, Joana Queiroz, Tinashe Samakomva, Christine Sicat, Joana Texeira, Edna Fernandes Da Gloria, Ana Lisboa, John Rawlins, Jisha Mathew, Ashley Kinch, William James Hurt, Nirav Shah, Victoria Clark, Maria Thanasi, Nikki Yun, Kamal Patel, Sara Bennett, Emma Goodwin, Matthew Jackson, Alissa Kent, Clare Tibke, Wiesia Woodyatt, Ahmed Zaki, Azmerelda Abraheem, Peter Bamford, Kathryn Cawley, Charlie Dunmore, Maria Faulkner, Rumanah Girach, Helen Jeffrey, Rhianna Jones, Emily London, Imrun Nagra, Farah Nasir, Hannah Sainsbury, Clare Smedley, Tahera Patel, Matthew Smith, Srikanth Chukkambotla, Aayesha Kazi, Janice Hartley, Joseph Dykes, Muhammad Hijazi, Sarah Keith, Meherunnisa Khan, Janet Ryan-Smith, Philippa Springle, Jacqueline Thomas, Nick Truman, Samuel Saad, Dabheoc Coleman, Christopher Fine, Roseanna Matt, Bethan Gay, Jack Dalziel, Syamlan Ali, Drew Goodchild, Rhiannan Harling, Ravi Bhatterjee, Wendy Goddard, Chloe Davison, Stephen Duberly, Jeanette Hargreaves, Rachel Bolton, Miriam Davey, David Golden, Rebecca Seaman, Shiney Cherian, Sean Cutler, Anne Emma Heron, Anna Roynon-Reed, Tamas Szakmany, Gemma Williams, Owen Richards, Yusuf Cheema, Hollie Brooke, Sarah Buckley, Jose Cebrian Suarez, Ruth Charlesworth, Karen Hansson, John Norris, Alice Poole, Alastair Rose, Rajdeep Sandhu, Brendan Sloan, Elizabeth Smithson, Muthu Thirumaran, Veronica Wagstaff, Alexandra Metcalfe, Mark Brunton, Jess Caterson, Holly Coles, Matthew Frise, Sabi Gurung Rai, Nicola Jacques, Liza Keating, Emma Tilney, Shauna Bartley, Parminder Bhuie, Sian Gibson, Amanda Lyle, Fiona McNeela, Jayachandran Radhakrishnan, Alistair Hughes, Bryan Yates, Jessica Reynolds, Helen Campbell, Maria Thompsom, Steve Dodds, Stacey Duffy, Sandra Greer, Karen Shuker, Ascanio Tridente, Reena Khade, Ashok Sundar, George Tsinaslanidis, Isobel Birkinshaw, Joseph Carter, Kate Howard, Joanne Ingham, Rosie Joy, Harriet Pearson, Samantha Roche, Zoe Scott, Hollie Bancroft, Mary Bellamy, Margaret Carmody, Jacqueline Daglish, Faye Moore, Joanne Rhodes, Mirriam Sangombe, Salma Kadiri, Maria Croft, Ian White, Victoria Frost, Maia Aquino, Rajeev Jha, Vinodh Krishnamurthy, Lai Lim, Li Lim, Edward Combes, Teishel Joefield, Sonja Monnery, Valerie Beech, Sallyanne Trotman, Christine Almaden-Boyle, Pauline Austin, Louise Cabrelli, Stephen Cole, Matt Casey, Susan Chapman, Clare Whyte, Yolanda Baird, Aaron Butler, Indra Chadbourn, Linda Folkes, Heather Fox, Amy Gardner, Raquel Gomez, Gillian Hobden, Luke Hodgson, Kirsten King, Michael Margarson, Tim Martindale, Emma Meadows, Dana Raynard, Yvette Thirlwall, David Helm, Jordi Margalef, Kristine Criste, Rebecca Cusack, Kim Golder, Hannah Golding, Oliver Jones, Samantha Leggett, Michelle Male, Martyna Marani, Kirsty Prager, Toran Williams, Belinda Roberts, Karen Salmon, Peter Anderson, Katie Archer, Karen Austin, Caroline Davis, Alison Durie, Olivia Kelsall, Jessica Thrush, Charlie Vigurs, Laura Wild, Hannah-Louise Wood, Helen Tranter, Alison Harrison, Nicholas Cowley, Michael McAlindon, Andrew Burtenshaw, Stephen Digby, Emma Low, Aled Morgan, Naiara Cother, Tobias Rankin, Sarah Clayton, Alex McCurdy, Cecilia Ahmed, Balvinder Baines, Sarah Clamp, Julie Colley, Risna Haq, Anne Hayes, Jonathan Hulme, Samia Hussain, Sibet Joseph, Rita Kumar, Zahira Maqsood, Manjit Purewal, Leonie Benham, Zena Bradshaw, Joanna Brown, Melanie Caswell, Jason Cupitt, Sarah Melling, Stephen Preston, Nicola Slawson, Emma Stoddard, Scott Warden, Bethan Deacon, Ceri Lynch, Carla Pothecary, Lisa Roche, Gwenllian Sera Howe, Jayaprakash Singh, Keri Turner, Hannah Ellis, Natalie Stroud, Jodie Hunt, Joy Dearden, Emma Dobson, Andy Drummond, Michelle Mulcahy, Sheila Munt, Grainne O'Connor, Jennifer Philbin, Chloe Rishton, Redmond Tully, Sarah Winnard, Susanne Cathcart, Katharine Duffy, Alex Puxty, Kathryn Puxty, Lynne Turner, Jane Ireland, Gary Semple, Kate Long, Simon Whiteley, Elizabeth Wilby, Bethan Ogg, Amanda Cowton, Andrea Kay, Melanie Kent, Kathryn Potts, Ami Wilkinson, Suzanne Campbell, Ellen Brown, Julie Melville, Jay Naisbitt, Rosane Joseph, Maria Lazo, Olivia Walton, Alan Neal, Peter Alexander, Schvearn Allen, Joanne Bradley-Potts, Craig Brantwood, Jasmine Egan, Timothy Felton, Grace Padden, Luke Ward, Stuart Moss, Susannah Glasgow, Lynn Abel, Michael Brett, Brian Digby, Lisa Gemmell, James Hornsby, Patrick MacGoey, Pauline O'Neil, Richard Price, Natalie Rodden, Kevin Rooney, Radha Sundaram, Nicola Thomson, Bridget Hopkins, Laura Thrasyvoulou, Heather Willis, Martyn Clark, Martina Coulding, Edward Jude, Jacqueline McCormick, Oliver Mercer, Darsh Potla, Hafiz Rehman, Heather Savill, Victoria Turner, Charlotte Downes, Kathleen Holding, Katie Riches, Mary Hilton, Mel Hayman, Deepak Subramanian, Priya Daniel, Oluronke Adanini, Nikhil Bhatia, Maines Msiska, Rebecca Collins, Ian Clement, Bijal Patel, A. Gulati, Carole Hays, K. Webster, Anne Hudson, Andrea Webster, Elaine Stephenson, Louise McCormack, Victoria Slater, Rachel Nixon, Helen Hanson, Maggie Fearby, Sinead Kelly, Victoria Bridgett, Philip Robinson, Julie Camsooksai, Charlotte Humphrey, Sarah Jenkins, Henrik Reschreiter, Beverley Wadams, Yasmin Death, Victoria Bastion, Daphene Clarke, Beena David, Harriet Kent, Rachel Lorusso, Gamu Lubimbi, Sophie Murdoch, Melchizedek Penacerrada, Alastair Thomas, Jennifer Valentine, Ana Vochin, Retno Wulandari, Brice Djeugam, Gillian Bell, Katy English, Amro Katary, Louise Wilcox, Michelle Bruce, Karen Connolly, Tracy Duncan, Helen T-Michael, Gabriella Lindergard, Samuel Hey, Claire Fox, Jordan Alfonso, Laura Jayne Durrans, Jacinta Guerin, Bethan Blackledge, Jade Harris, Martin Hruska, Ayaa Eltayeb, Thomas Lamb, Tracey Hodgkiss, Lisa Cooper, Joanne Rothwell, Angela Allan, Felicity Anderson, Callum Kaye, Jade Liew, Jasmine Medhora, Teresa Scott, Erin Trumper, Adriana Botello, Liana Lankester, Nikitas Nikitas, Colin Wells, Bethan Stowe, Kayleigh Spencer, Craig Brandwood, Lara Smith, Katie Birchall, Laurel Kolakaluri, Deborah Baines, Anila Sukumaran, Elena Apetri, Cathrine Basikolo, Laura Catlow, Bethan Charles, Paul Dark, Reece Doonan, Alice Harvey, Daniel Horner, Karen Knowles, Stephanie Lee, Diane Lomas, Chloe Lyons, Tracy Marsden, Danielle McLaughlan, Liam McMorrow, Jessica Pendlebury, Jane Perez, Maria Poulaka, Nicola Proudfoot, Melanie Slaughter, Kathryn Slevin, Vicky Thomas, Danielle Walker, Angiy Michael, Matthew Collis, Tracey Cosier, Gemma Millen, Neil Richardson, Natasha Schumacher, Heather Weston, James Rand, Nicola Baxter, Steven Henderson, Sophie Kennedy-Hay, Christopher McParland, Laura Rooney, Malcolm Sim, Gordan McCreath, Louise Akeroyd, Shereen Bano, Matt Bromley, Lucy Gurr, Tom Lawton, James Morgan, Kirsten Sellick, Deborah Warren, Brian Wilkinson, Janet McGowan, Camilla Ledgard, Amelia Stacey, Kate Pye, Ruth Bellwood, Michael Bentley, Jeremy Bewley, Zoe Garland, Lisa Grimmer, Bethany Gumbrill, Rebekah Johnson, Katie Sweet, Denise Webster, Georgia Efford, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Jocelyn Keshet-Price, Georgina Randell, Katie Stammers, Maria Bokhari, Vanessa Linnett, Rachael Lucas, Wendy McCormick, Jenny Ritzema, Amanda Sanderson, Helen Wild, Anthony Rostron, Alistair Roy, Lindsey Woods, Sarah Cornell, Fiona Wakinshaw, Kimberley Rogerson, Jordan Jarmain, Robert Parker, Amie Reddy, Ian Turner-Bone, Laura Wilding, Peter Harding, Caroline Abernathy, Louise Foster, Andrew Gratrix, Vicky Martinson, Priyai Parkinson, Elizabeth Stones, Llucia Carbral-Ortega, Georgia Bercades, David Brealey, Ingrid Hass, Niall MacCallum, Gladys Martir, Eamon Raith, Anna Reyes, Deborah Smyth, Letizia Zitter, Sarah Benyon, Suzie Marriott, Linda Park, Samantha Keenan, Elizabeth Gordon, Helen Quinn, Kizzy Baines, Lenka Cagova, Adama Fofano, Lucie Garner, Helen Holcombe, Sue Mepham, Alice Michael Mitchell, Lucy Mwaura, Krithivasan Praman, Alain Vuylsteke, Julie Zamikula, Bally Purewal, Vanessa Rivers, Stephanie Bell, Hayley Blakemore, Borislava Borislavova, Beverley Faulkner, Emma Gendall, Elizabeth Goff, Kati Hayes, Matt Thomas, Ruth Worner, Kerry Smith, Deanna Stephens, Louise Mew, Esther Mwaura, Richard Stewart, Felicity Williams, Lynn Wren, Sara-Beth Sutherland, Emily Bevan, Jane Martin, Dawn Trodd, Geoff Watson, Caroline Wrey Brown, Amy Collins, Waqas Khaliq, Estefania Treus Gude, Olugbenga Akinkugbe, Alasdair Bamford, Emily Beech, Holly Belfield, Michael Bell, Charlene Davies, Gareth A.L. Jones, Tara McHugh, Hamza Meghari, Lauran O'Neill, Mark J. Peters, Samiran Ray, Ana Luisa Tomas, Iona Burn, Geraldine Hambrook, Katarina Manso, Ruth Penn, Pradeep Shanmugasundaram, Julie Tebbutt, Danielle Thornton, Jade Cole, Rhys Davies, Donna Duffin, Helen Hill, Ben Player, Emma Thomas, Angharad Williams, Denise Griffin, Nycola Muchenje, Mcdonald Mupudzi, Richard Partridge, Jo-Anna Conyngham, Rachel Thomas, Mary Wright, Maria Alvarez Corral, Reni Jacob, Cathy Jones, Craig Denmade, Sarah Beavis, Katie Dale, Rachel Gascoyne, Joanne Hawes, Kelly Pritchard, Lesley Stevenson, Amanda Whileman, Patricia Doble, Joanne Hutter, Corinne Pawley, Charmaine Shovelton, Marius Vaida, Deborah Butcher, Susie O'Sullivan, Nicola Butterworth-Cowin, Norfaizan Ahmad, Joann Barker, Kris Bauchmuller, Sarah Bird, Kay Cawthron, Kate Harrington, Yvonne Jackson, Faith Kibutu, Becky Lenagh, Shamiso Masuko, Gary H. 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McGuigan, Christopher Wasson, Stephanie Finn, Jackie Green, Erin Collins, Bernadette King, Andy Campbell, Sara Smuts, Joseph Duffield, Oliver Smith, Lewis Mallon, Watkins Claire, Liam Botfield, Joanna Butler, Catherine Dexter, Jo Fletcher, Atul Garg, Aditya Kuravi, Poonam Ranga, Emma Virgilio, Zakaula Belagodu, Bridget Fuller, Anca Gherman, Olumide Olufuwa, Remi Paramsothy, Carmel Stuart, Naomi Oakley, Charlotte Kamundi, David Tyl, Katy Collins, Pedro Silva, June Taylor, Laura King, Charlotte Coates, Maria Crowley, Phillipa Wakefield, Jane Beadle, Laura Johnson, Janet Sargeant, Madeleine Anderson, Ailbhe Brady, Rebekah Chan, Jeff Little, Shane McIvor, Helena Prady, Helen Whittle, Bijoy Mathew, Ben Attwood, Penny Parsons, Geraldine Ward, Pamela Bremmer, West Joe, Baird Tracy, Ruddy Jim, Ellie Davies, Sonia Sathe, Catherine Dennis, Alastair McGregor, Victoria Parris, Sinduya Srikaran, Anisha Sukha, Noreen Clarke, Jonathan Whiteside, Mairi Mascarenhas, Avril Donaldson, Joanna Matheson, Fiona Barrett, Marianne O'Hara, Laura Okeefe, Clare Bradley, Christine Eastgate-Jackson, Helder Filipe, Daniel Martin, Amitaa Maharajh, Sara Mingo Garcia, Glykeria Pakou, Mark De Neef, Kathy Dent, Elizabeth Horsley, Muhmmad Nauman Akhtar, Sandra Pearson, Dorota Potoczna, Sue Spencer, Melanie Clapham, Rosemary Harper, Una Poultney, Polly Rice, Rachel Mutch, Lisa Armstrong, Hayley Bates, Emma Dooks, Fiona Farquhar, Brigid Hairsine, Chantal McParland, Sophie Packham, Rehana Bi, Barney Scholefield, Lydia Ashton, Linsha George, Sophie Twiss, David Wright, Manish Chablani, Amy Kirkby, Kimberley Netherton, Kim Davies, Linda O'Brien, Zohra Omar, Emma Perkins, Tracy Lewis, Isobel Sutherland, Karen Burns, Dr Ben Chandler, Kerry Elliott, Janine Mallinson, Alison Turnbull, Prisca Gondo, Bernard Hadebe, Abdul Kayani, Bridgett Masunda, Taya Anderson, Dan Hawcutt, Laura O'Malley, Laura Rad, Naomi Rogers, Paula Saunderson, Kathryn Sian Allison, Deborah Afolabi, Jennifer Whitbread, Dawn Jones, Rachael Dore, Matthew Halkes, Pauline Mercer, Lorraine Thornton, Joy Dawson, Sweyn Garrioch, Melanie Tolson, Jonathan Aldridge, Ritoo Kapoor, David Loader, Karen Castle, Sally Humphreys, Ruth Tampsett, Katherine Mackintosh, Amanda Ayers, Wendy Harrison, Julie North, Suzanne Allibone, Roman Genetu, Vidya Kasipandian, Amit Patel, Ainhi Mac, Anthony Murphy, Parisa Mahjoob, Roonak Nazari, Lucy Worsley, Andrew Fagan, Thomas Bemand, Ethel Black, Arnold Dela Rosa, Ryan Howle, Shaman Jhanji, Ravishankar Rao Baikady, Kate Colette Tatham, Benjamin Thomas, Dina Bell, Rosalind Boyle, Katie Douglas, Lynn Glass, Emma Lee, Liz Lennon, Austin Rattray, Abigail Taylor, Rachel Anne Hughes, Helen Thomas, Alun Rees, Michaela Duskova, Janet Phipps, Suzanne Brooks, Michelle Edwards, Sheena Quaid, Ekaterina Watson, Adam Brayne, Emma Fisher, Jane Hunt, Peter Jackson, Duncan Kaye, Nicholas Love, Juliet Parkin, Victoria Tuckey, Lynne Van Koutrik, Sasha Carter, Benedict Andrew, Louise Findlay, Katie Adams, Jen Service, Alison Williams, Claire Cheyne, Anne Saunderson, Sam Moultrie, Miranda Odam, Kathryn Hall, Isheunesu Mapfunde, Charlotte Willis, Alex Lyon, Chunda Sri-Chandana, Joslan Scherewode, Lorraine Stephenson, Sarah Marsh, John Hardy, Henry Houlden, Eleanor Moncur, Ambreen Tariq, Arianna Tucci, Maria Hobrok, Ronda Loosley, Heather McGuinness, Helen Tench, Rebecca Wolf-Roberts, Val Irvine, Benjamin Shelley, Claire Gorman, Abhinav Gupta, Elizabeth Timlick, Rebecca Brady, Barry Milligan, Arianna Bellini, Jade Bryant, Anton Mayer, Amy Pickard, Nicholas Roe, Jason Sowter, Alex Howlett, Katy Fidler, Emma Tagliavini, and Kevin Donnelly

Subjects
SARS-CoV-2, host genetics, toll-like receptor 7, targeted sequencing, rare variants, variant collapsing analysis, Genetics, QH426-470
Abstract

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Published
2024
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50. Harnessing the potential of the NALT and BALT as targets for immunomodulation using engineering strategies to enhance mucosal uptake

Author

Madison L. Seefeld, Erin L. Templeton, Justin M. Lehtinen, Noah Sinclair, Daman Yadav, and Brittany L. Hartwell

Subjects
nasal associated lymphoid tissue (NALT), bronchus associated lymphoid tissue (BALT), secretory IgA (SIgA), mucosal vaccine, antigen specific immunotherapy (ASIT), drug delivery, Immunologic diseases. Allergy, RC581-607
Abstract

Mucosal barrier tissues and their mucosal associated lymphoid tissues (MALT) are attractive targets for vaccines and immunotherapies due to their roles in both priming and regulating adaptive immune responses. The upper and lower respiratory mucosae, in particular, possess unique properties: a vast surface area responsible for frontline protection against inhaled pathogens but also simultaneous tight regulation of homeostasis against a continuous backdrop of non-pathogenic antigen exposure. Within the upper and lower respiratory tract, the nasal and bronchial associated lymphoid tissues (NALT and BALT, respectively) are key sites where antigen-specific immune responses are orchestrated against inhaled antigens, serving as critical training grounds for adaptive immunity. Many infectious diseases are transmitted via respiratory mucosal sites, highlighting the need for vaccines that can activate resident frontline immune protection in these tissues to block infection. While traditional parenteral vaccines that are injected tend to elicit weak immunity in mucosal tissues, mucosal vaccines (i.e., that are administered intranasally) are capable of eliciting both systemic and mucosal immunity in tandem by initiating immune responses in the MALT. In contrast, administering antigen to mucosal tissues in the absence of adjuvant or costimulatory signals can instead induce antigen-specific tolerance by exploiting regulatory mechanisms inherent to MALT, holding potential for mucosal immunotherapies to treat autoimmunity. Yet despite being well motivated by mucosal biology, development of both mucosal subunit vaccines and immunotherapies has historically been plagued by poor drug delivery across mucosal barriers, resulting in weak efficacy, short-lived responses, and to-date a lack of clinical translation. Development of engineering strategies that can overcome barriers to mucosal delivery are thus critical for translation of mucosal subunit vaccines and immunotherapies. This review covers engineering strategies to enhance mucosal uptake via active targeting and passive transport mechanisms, with a parallel focus on mechanisms of immune activation and regulation in the respiratory mucosa. By combining engineering strategies for enhanced mucosal delivery with a better understanding of immune mechanisms in the NALT and BALT, we hope to illustrate the potential of these mucosal sites as targets for immunomodulation.

Published
2024
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