355 results on '"Nguyen KA"'
Search Results
2. A Dual Role for P2X7 Receptor during Porphyromonas gingivalis Infection
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Ramos-Junior, ES, Morandini, AC, Almeida-da-Silva, CLC, Franco, EJ, Potempa, J, Nguyen, KA, Oliveira, AC, Zamboni, DS, Ojcius, DM, Scharfstein, J, and Coutinho-Silva, R
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Biomedical and Clinical Sciences ,Dentistry ,Dental/Oral and Craniofacial Disease ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Animals ,Bacteroidaceae Infections ,Carrier Proteins ,Caspase 1 ,Interleukin-1beta ,Interleukin-6 ,Mice ,Mice ,Inbred C57BL ,NLR Family ,Pyrin Domain-Containing 3 Protein ,Porphyromonas gingivalis ,Receptors ,Purinergic P2X7 ,Tumor Necrosis Factor-alpha ,ATP ,inflammasome ,IL-1 beta ,macrophage ,cytokines ,periodontitis ,IL-1β - Abstract
Emerging evidence suggests a role for purinergic signaling in the activation of multiprotein intracellular complexes called inflammasomes, which control the release of potent inflammatory cytokines, such as interleukin (IL) -1β and -18. Porphyromonas gingivalis is intimately associated with periodontitis and is currently considered one of the pathogens that can subvert the immune system by limiting the activation of the NLRP3 inflammasome. We recently showed that P. gingivalis can dampen eATP-induced IL-1β secretion by means of its fimbriae in a purinergic P2X7 receptor-dependent manner. Here, we further explore the role of this purinergic receptor during eATP-induced IL-1β processing and secretion by P. gingivalis-infected macrophages. We found that NLRP3 was necessary for eATP-induced IL-1β secretion as well as for caspase 1 activation irrespective of P. gingivalis fimbriae. Additionally, although the secretion of IL-1β from P. gingivalis-infected macrophages was dependent on NLRP3, its adaptor protein ASC, or caspase 1, the cleavage of intracellular pro-IL-1β to the mature form was found to occur independently of NLRP3, its adaptor protein ASC, or caspase 1. Our in vitro findings revealed that P2X7 receptor has a dual role, being critical not only for eATP-induced IL-1β secretion but also for intracellular pro-IL-1β processing. These results were relevant in vivo since P2X7 receptor expression was upregulated in a P. gingivalis oral infection model, and reduced IFN-γ and IL-17 were detected in draining lymph node cells from P2rx7(-/-) mice. Furthermore, we demonstrated that P2X7 receptor and NLRP3 transcription were modulated in human chronic periodontitis. Overall, we conclude that the P2X7 receptor has a role in periodontal immunopathogenesis and suggest that targeting of the P2X7/NLRP3 pathway should be considered in future therapeutic interventions in periodontitis.
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- 2015
3. Capturing prediction uncertainty in upstream cell culture models using conformal prediction and Gaussian processes
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Papadopoulos, H, Nguyen, KA, Boström, H, Carlsson, L, Pham, TD, Aickelin, U, Bassett, R, Papadopoulos, H, Nguyen, KA, Boström, H, Carlsson, L, Pham, TD, Aickelin, U, and Bassett, R
- Abstract
This extended abstract compares the efficacy of Gaussian process and conformal XGBoost regressions in capturing prediction uncertainty in simulated and industrial cell culture data.
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- 2023
4. Heterogeneity and Gaps in Reporting Primary Outcomes From Neonatal Trials
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Baba, A, Webbe, J, Butcher, NJ, Rodrigues, C, Stallwood, E, Goren, K, Monsour, A, Chang, ASM, Trivedi, A, Manley, BJ, McCall, E, Bogossian, F, Namba, F, Schmölzer, GM, Harding, J, Nguyen, KA, Doyle, LW, Jardine, L, Rysavy, MA, Konstantinidis, M, Meyer, M, Helmi, MAM, Lai, NM, Hay, S, Onland, W, Choo, YM, Gale, C, Soll, RF, Offringa, M, Core Outcome Reporting in Neonatal Trials Study Group, Baba, A, Webbe, J, Butcher, NJ, Rodrigues, C, Stallwood, E, Goren, K, Monsour, A, Chang, ASM, Trivedi, A, Manley, BJ, McCall, E, Bogossian, F, Namba, F, Schmölzer, GM, Harding, J, Nguyen, KA, Doyle, LW, Jardine, L, Rysavy, MA, Konstantinidis, M, Meyer, M, Helmi, MAM, Lai, NM, Hay, S, Onland, W, Choo, YM, Gale, C, Soll, RF, Offringa, M, and Core Outcome Reporting in Neonatal Trials Study Group
- Abstract
OBJECTIVES: Clear outcome reporting in clinical trials facilitates accurate interpretation and application of findings and improves evidence-informed decision-making. Standardized core outcomes for reporting neonatal trials have been developed, but little is known about how primary outcomes are reported in neonatal trials. Our aim was to identify strengths and weaknesses of primary outcome reporting in recent neonatal trials. METHODS: Neonatal trials including ≥100 participants/arm published between 2015 and 2020 with at least 1 primary outcome from a neonatal core outcome set were eligible. Raters recruited from Cochrane Neonatal were trained to evaluate the trials' primary outcome reporting completeness using relevant items from Consolidated Standards of Reporting Trials 2010 and Consolidated Standards of Reporting Trials-Outcomes 2022 pertaining to the reporting of the definition, selection, measurement, analysis, and interpretation of primary trial outcomes. All trial reports were assessed by 3 raters. Assessments and discrepancies between raters were analyzed. RESULTS: Outcome-reporting evaluations were completed for 36 included neonatal trials by 39 raters. Levels of outcome reporting completeness were highly variable. All trials fully reported the primary outcome measurement domain, statistical methods used to compare treatment groups, and participant flow. Yet, only 28% of trials fully reported on minimal important difference, 24% on outcome data missingness, 66% on blinding of the outcome assessor, and 42% on handling of outcome multiplicity. CONCLUSIONS: Primary outcome reporting in neonatal trials often lacks key information needed for interpretability of results, knowledge synthesis, and evidence-informed decision-making in neonatology. Use of existing outcome-reporting guidelines by trialists, journals, and peer reviewers will enhance transparent reporting of neonatal trials.
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- 2023
5. Strengthening Reporting of Neonatal Trials.
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Webbe, J, Baba, A, Butcher, NJ, Rodrigues, C, Stallwood, E, Goren, K, Monsour, A, Chang, ASM, Trivedi, A, Manley, BJ, McCall, E, Bogossian, F, Namba, F, Schmölzer, GM, Popat, H, Nguyen, KA, Doyle, LW, Jardine, L, Rysavy, MA, Konstantinidis, M, Muhd Helmi, MA, Lai, NM, Hay, S, Onland, W, Choo, YM, Gale, C, Soll, RF, Offringa, M, CORE OUTCOME REPORTING IN NEONATAL TRIALS (CORINT) STUDY GROUP, Webbe, J, Baba, A, Butcher, NJ, Rodrigues, C, Stallwood, E, Goren, K, Monsour, A, Chang, ASM, Trivedi, A, Manley, BJ, McCall, E, Bogossian, F, Namba, F, Schmölzer, GM, Popat, H, Nguyen, KA, Doyle, LW, Jardine, L, Rysavy, MA, Konstantinidis, M, Muhd Helmi, MA, Lai, NM, Hay, S, Onland, W, Choo, YM, Gale, C, Soll, RF, Offringa, M, and CORE OUTCOME REPORTING IN NEONATAL TRIALS (CORINT) STUDY GROUP
- Abstract
BACKGROUND AND OBJECTIVES: There is variability in the selection and reporting of outcomes in neonatal trials with key information frequently omitted. This can impact applicability of trial findings to clinicians, families, and caregivers, and impair evidence synthesis. The Neonatal Core Outcomes Set describes outcomes agreed as clinically important that should be assessed in all neonatal trials, and Consolidated Standards of Reporting Trials (CONSORT)-Outcomes 2022 is a new, harmonized, evidence-based reporting guideline for trial outcomes. We reviewed published trials using CONSORT-Outcomes 2022 guidance to identify exemplars of neonatal core outcome reporting to strengthen description of outcomes in future trial publications. METHODS: Neonatal trials including >100 participants per arm published between 2015 to 2020 with a primary outcome included in the Neonatal Core Outcome Set were identified. Primary outcome reporting was reviewed using CONSORT 2010 and CONSORT-Outcomes 2022 guidelines by assessors recruited from Cochrane Neonatal. Examples of clear and complete outcome reporting were identified with verbatim text extracted from trial reports. RESULTS: Thirty-six trials were reviewed by 39 assessors. Examples of good reporting for CONSORT 2010 and CONSORT-Outcomes 2022 criteria were identified and subdivided into 3 outcome categories: "survival," "short-term neonatal complications," and "long-term developmental outcomes" depending on the core outcomes to which they relate. These examples are presented to strengthen future research reporting. CONCLUSIONS: We have identified examples of good trial outcome reporting. These illustrate how important neonatal outcomes should be reported to meet the CONSORT 2010 and CONSORT-Outcomes 2022 guidelines. Emulating these examples will improve the transmission of information relating to outcomes and reduce associated research waste.
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- 2023
6. PTBP1 controls intestinal epithelial regeneration through post-transcriptional regulation of gene expression
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Chembazhi, Ullas Valiya, primary, Tung, Wesley S, additional, Hwang, Hyojeong, additional, Wang, Yuexi, additional, Lalwani, Aryan, additional, Nguyen, Ka Lam, additional, Bangru, Sushant, additional, Yee, Danielle, additional, Chin, Kristy, additional, Yang, Jing, additional, Kalsotra, Auinash, additional, and Mei, Wenyan, additional
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- 2023
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7. Conformal Multistep-Ahead Multivariate Time-Series Forecasting
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Schlembach, Filip, Smirnov, Evgueni, Koprinska, Irena, Johansson, U, Bostrom, H, Nguyen, KA, Luo, Z, Carlsson, L, Schlembach, Filip, Smirnov, Evgueni, Koprinska, Irena, Johansson, U, Bostrom, H, Nguyen, KA, Luo, Z, and Carlsson, L
- Abstract
This paper proposes a method for conformal multistep-ahead multivariate time-series forecasting. The method minimizes the coverage loss when the data exchangeability assumption does not properly hold. This is done by weighting residual quantiles while computing prediction intervals. Preliminary experiments on real data demonstrate the method's utility.
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- 2022
8. EP1297: PTBP1 PLAYS A CRITICAL ROLE IN MEDIATING HOST-MICROBE INTERACTIONS AND PREVENTING COLITIS AND COLORECTAL CANCER
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Nguyen, Ka Lam, primary, Tung, Emily, additional, Yee, Danielle, additional, Wang, Shulei, additional, and Mei, Wenyan, additional
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- 2022
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9. 114: PTBP1/HNRNP I CONTROLS INTESTINAL EPITHELIAL CELL REGENERATION BY MAINTAINING STEM CELL SURVIVAL AND STEMNESS
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Tung, Wesley, primary, Chembazhi, Ullas, additional, Yang, Jing, additional, Nguyen, Ka Lam, additional, Lalwani, Aryan, additional, Bangru, Sushant, additional, Yee, Danielle, additional, Chin, Kristy, additional, Kalsotra, Auinash, additional, and Mei, Wenyan, additional
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- 2022
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10. 1161 CHARACTERIZING AND IDENTIFYING ANTI-INFLAMMATORY WHEAT ARABINOXYLAN-DERIVED BACTEROIDES INTESTINALIS METABOLITES TO TREAT INFLAMMATORY DISEASES
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Nguyen, Ka Lam, Zhou, Ziyu, Gharieb, Salwa A., Wang, Yuexi, Tung, Emily, Abdel-Hamid, Ahmed M., Kuo, Shanny H., Cann, Isaac, and Mei, Wenyan
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- 2024
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11. PTBP1/HNRNP I controls intestinal epithelial cell regeneration by maintaining stem cell survival and stemness
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Tung, Wesley, primary, Chembazhi, Ullas Valiya, additional, Yang, Jing, additional, Nguyen, Ka Lam, additional, Lalwani, Aryan, additional, Bangru, Sushant, additional, Yee, Danielle, additional, Chin, Kristy, additional, Kalsotra, Auinash, additional, and Mei, Wenyan, additional
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- 2021
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12. Shapley-Value based Inductive Conformal Prediction
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Jaramillo, William Lopez, Smirnov, Evgueni, Carlsson, L, Luo, Z, Cherubin, G, Nguyen, KA, Jaramillo, William Lopez, Smirnov, Evgueni, Carlsson, L, Luo, Z, Cherubin, G, and Nguyen, KA
- Abstract
Shapley values of individual instances were recently proposed for the problem of data valuation. They were defined as the average marginal instance contributions to the performance of a given predictor. In this paper we propose to use Shapley values of individual instances as conformity scores. To compute these values efficiently and exactly we employ a standard algorithm based on nearest neighbor classification and propose a variant of this algorithm for clustered data. Both variants are used for computing Shapley conformity scores for inductive conformal predictors. The experiments show that the Shapley-value conformity scores result in smaller prediction sets for significance level epsilon <= 0:1 compared with those produced by standard conformity scores (i.e. similarity between true and predicted output values).
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- 2021
13. A clustering solution for analyzing residential water consumption patterns
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Rahim, MS, Nguyen, KA, Stewart, RA, Ahmed, T, Giurco, D, Blumenstein, M, Rahim, MS, Nguyen, KA, Stewart, RA, Ahmed, T, Giurco, D, and Blumenstein, M
- Abstract
Water utility companies in urban areas face two major challenges: ensuring there is enough water for everyone during prolonged drought and maintaining adequate water pressure during the hours of peak demand. These issues can be overcome by applying data analytics and machine learning to the data gathered from digital water meters. For water conservation and demand management strategies to be effective, utility companies need to gain a better understanding of consumer behaviours, habits and routines. To accomplish this goal, we adapted a clustering approach to reveal residential water consumption patterns within metered data. In the experiment, we used two data sets (engineered features data set as well as the times of use and weighted probabilities of use data set) based on the data collected over 10 months from 306 households in Melbourne, Australia. For the engineered features data set, first, we identified the number of optimal clusters. We then performed extensive experiments to find the best clustering approach in terms of performance evaluation and clustering quality. We chose the hierarchical agglomerative clustering technique based on the nature of the data and the objective of the study. We observed that for the engineered features data set, k-means is the best performing clustering technique after considering performance metrics. For the other data set, we found that the number of clusters varies based on the type of water-consumption event, type of day (i.e., weekday or weekend), profiling interval and probability of use. In addition, we observed that insight into tap-water usage could be used to determine the population's adaptation of hygiene practices in an unprecedented time, such as the COVID-19 pandemic. Finally, we recommend that future clustering studies also employ aligned socio-demographic data and other key features.
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- 2021
14. Advanced household profiling using digital water meters.
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Rahim, MS, Nguyen, KA, Stewart, RA, Giurco, D, Blumenstein, M, Rahim, MS, Nguyen, KA, Stewart, RA, Giurco, D, and Blumenstein, M
- Abstract
Advanced householder profiling using digital water metering data analytics has been acknowledged as a core strategy for promoting water conservation because of its ability to provide near real-time feedback to customers and instil long-term conservation behaviours. Customer profiling based on household water consumption data collected through digital water meters helps to identify the water consumption patterns and habits of customers. This study employed advanced customer profiling techniques adapted from the machine learning research domain to analyse high-resolution data collected from residential digital water meters. Data analytics techniques were applied on already disaggregated end-use water consumption data (e.g., shower and taps) for creating in-depth customer profiling at various intervals (e.g., 15, 30, and 60 min). The developed user profiling approach has some learning functionality as it can ascertain and accommodate changing behaviours of residential customers. The developed advanced user profiling technique was shown to be beneficial since it identified residential customer behaviours that were previously unseen. Furthermore, the technique can identify and address novel changes in behaviours, which is an important feature for promoting and sustaining long-term water conservation behaviours. The research has implications for researchers in data analytics and water demand management, and also for practitioners and government policy advisors seeking to conserve valuable potable-water resources.
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- 2021
15. Machine learning and data analytic techniques in digitalwater metering: A review
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Rahim MS, Nguyen KA, Stewart RA, Giurco D, and Blumenstein M
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© 2020 by the authors. Digital or intelligent water meters are being rolled out globally as a crucial component in improving urban water management. This is because of their ability to frequently send water consumption information electronically and later utilise the information to generate insights or provide feedback to consumers. Recent advances in machine learning (ML) and data analytic (DA) technologies have provided the opportunity to more effectively utilise the vast amount of data generated by these meters. Several studies have been conducted to promote water conservation by analysing the data generated by digital meters and providing feedback to consumers and water utilities. The purpose of this review was to inform scholars and practitioners about the contributions and limitations of ML and DA techniques by critically analysing the relevant literature. We categorised studies into five main themes: (1) water demand forecasting; (2) socioeconomic analysis; (3) behaviour analysis; (4) water event categorisation; and (5) water-use feedback. The review identified significant research gaps in terms of the adoption of advancedMLandDAtechniques, which could potentially lead to water savings and more efficient demand management. We concluded that further investigations are required into highly personalised feedback systems, such as recommender systems, to promote water-conscious behaviour. In addition, advanced data management solutions, effective user profiles, and the clustering of consumers based on their profiles require more attention to promote water-conscious behaviours.
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- 2020
16. Changes in mechanics of septal and lateral walls in patients with left bundle-branch block are related to extent of systolic dysfunction
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Kupczynska, K, primary, Nguyen, KA, additional, Surkova, E, additional, Palermo, CH, additional, Sambugaro, F, additional, Previtero, M, additional, Muraru, D, additional, and Badano, L, additional
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- 2021
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17. Su1254 DISSECT THE FUNCTION OF PTBP1 IN INTESTINAL EPITHELIAL REGENERATION THROUGH THE CONTROL OF PANETH CELL
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Zhou, Ziyu, Tung, Wesley, Chembazhi, Ullas Valiya, Hwang, Hyojeong, Wang, Yuexi, Lalwani, Aryan, Nguyen, Ka Lam, Yang, Jing, Kalsotra, Auinash, and Mei, Wenyan
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- 2023
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18. Maternal- and Fetal-Encoded Perforin-2 Limits Placental Infection by a Bloodborne Pathogen
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Gayle, Petoria, primary, McGaughey, Vanessa, additional, Hernandez, Rosmely, additional, Wylie, Marina, additional, Colletti, Rachel C., additional, Nguyen, Ka Lam, additional, Arons, Marshall, additional, Padula, Laura, additional, Strbo, Natasa, additional, and Schesser, Kurt, additional
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- 2020
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19. Perforin-2 limits pathogen proliferation at the maternal-fetal interface
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Gayle, Petoria, primary, McGaughey, Vanessa, additional, Hernandez, Rosmely, additional, Wylie, Marina, additional, Colletti, Rachel C., additional, Nguyen, Ka Lam, additional, Arons, Marshall, additional, Padula, Laura, additional, Strbo, Natasa, additional, and Schesser, Kurt, additional
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- 2020
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20. Production of high cellulase yields from polypore fungi in solid-state fermentation using green tea waste
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Nguyen, KA, primary, Penkhrue, W, additional, and Lumyong, S, additional
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- 2019
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21. Opportunities and challenges to improving antibiotic prescribing practices through a One Health approach: Results of a comparative survey of doctors, dentists and veterinarians in Australia
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Zhuo, A, Labbate, M, Norris, JM, Gilbert, GL, Ward, MP, Bajorek, BV, Degeling, C, Rowbotham, SJ, Dawson, A, Nguyen, KA, Hill-Cawthorne, GA, Sorrell, TC, Govendir, M, Kesson, AM, Iredell, JR, Dominey-Howes, D, Zhuo, A, Labbate, M, Norris, JM, Gilbert, GL, Ward, MP, Bajorek, BV, Degeling, C, Rowbotham, SJ, Dawson, A, Nguyen, KA, Hill-Cawthorne, GA, Sorrell, TC, Govendir, M, Kesson, AM, Iredell, JR, and Dominey-Howes, D
- Abstract
© 2018 Article author(s). Objectives To explore and compare the knowledge, attitudes and experiences of doctors, dentists and veterinarians (as prescribers) in relation to antibiotic use and antibiotic resistance (AbR), and to consider the implications of these for policy-making that support a One Health approach. Design A cross-sectional survey conducted online. Setting Doctors, dentists and veterinarians practising in primary, secondary or tertiary care in Australia. Participants 547 doctors, 380 dentists and 403 veterinarians completed the survey. Main outcome measures Prescribers' knowledge, attitudes and perceptions of AbR, the extent to which a range of factors are perceived as barriers to appropriate prescribing practices, and perceived helpfulness of potential strategies to improve antibiotic prescribing in practice. Results There was substantial agreement across prescriber groups that action on AbR is required by multiple sectors and stakeholders. However, prescribers externalised responsibility to some extent by seeing the roles of others as more important than their own in relation to AbR. There were common and context-specific barriers to optimal prescribing across the prescriber groups. Prescriber groups generally perceived restrictive policies as unhelpful to supporting appropriate prescribing in their practice. Conclusions The results have implications for implementing a One Health approach that involves doctors, dentists and veterinarians as key players to tackling the crisis of AbR. The findings are that (1) prescribers understand and are likely receptive to a One Health policy approach to AbR, (2) policy development should be sensitive to barriers that are specific to individual prescriber groups and (3) the development and introduction of interventions that might be perceived as reducing prescriber autonomy will need to be carefully designed and implemented.
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- 2018
22. Assessing the public acceptability of proposed policy interventions to reduce the misuse of antibiotics in Australia: A report on two community juries
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Degeling, C, Johnson, J, Iredell, J, Nguyen, KA, Norris, J, Turnidge, J, Dawson, A, Carter, SM, and Gilbert, GL
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(mis)use of antibiotics ,antibiotic resistance ,accountability ,Australia ,public consultation ,Antimicrobial resistance ,health care economics and organizations ,policy interventions ,community juries - Abstract
Objective To elicit the views of well-informed community members on the acceptability of proposed policy interventions designed to improve community use of antibiotics in Australia. Design Two community juries held in 2016. Setting and participants Western Sydney and Dubbo communities in NSW, Australia. Twenty-nine participants of diverse social and cultural backgrounds, mixed genders and ages recruited via public advertising: one jury was drawn from a large metropolitan setting; the other from a regional/rural setting. Main outcome measure Jury verdict and rationale in response to a prioritization task and structured questions. Results Both juries concluded that potential policy interventions to curb antibiotic misuse in the community should be directed towards: (i) ensuring that the public and prescribers were better educated about the dangers of antibiotic resistance; (ii) making community-based human and animal health-care practitioners accountable for their prescribing decisions. Patient-centred approaches such as delayed prescribing were seen as less acceptable than prescriber-centred approaches; both juries completely rejected any proposal to decrease consumer demand by increasing antibiotic prices. Conclusion These informed citizens acknowledged the importance of raising public awareness of the risks, impacts and costs of antibiotic resistance and placed a high priority on increasing social and professional accountability through restrictive measures. Their overarching aim was that policy interventions should be directed towards creating collective actions and broad social support for changing antibiotic use through establishing and explaining the need for mechanisms to control and support better prescribing by practitioners, while not transferring the burdens, costs and risks of interventions to consumers. This work was supported by a seed grant from the Marie Bashir Institute for Infectious Disease and Biosecurity and NHMRC CRE 1102962. CD, JJ and GLG received funding support from a NHMRC Project grant (#1083079). SMC is funded through NHMRC Career Development Fellowship (#1032963).
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- 2017
23. PS-049 Prospective detection of adverse drug reactions among 2263 hospitalised children over a 19 month period: Eremi intermediate report: Abstract PS-049 Table 1
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Lajoinie, A, primary, Nguyen, KA, additional, Mimouni, Y, additional, Paret, N, additional, Carcel, C, additional, Malik, S, additional, Milliat-Guittard, L, additional, Dode, X, additional, Vial, T, additional, and Kassai, B, additional
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- 2016
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24. Research Trends in Evidence-Based Medicine: A Joinpoint Regression Analysis of More than 50 Years of Publication Data
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Pietschnig, J, Bui, TH, Nguyen, PL, Le, PH, Nguyen, TL, Nguyen, HA, Tran, DN, Mai, VH, Nguyen, THT, Rafidinarivo, HF, Nguyen, KA, Hawkes, D, Nguyen, TH, Hirayama, K, Pietschnig, J, Bui, TH, Nguyen, PL, Le, PH, Nguyen, TL, Nguyen, HA, Tran, DN, Mai, VH, Nguyen, THT, Rafidinarivo, HF, Nguyen, KA, Hawkes, D, Nguyen, TH, and Hirayama, K
- Abstract
BACKGROUND: Evidence-based medicine (EBM) has developed as the dominant paradigm of assessment of evidence that is used in clinical practice. Since its development, EBM has been applied to integrate the best available research into diagnosis and treatment with the purpose of improving patient care. In the EBM era, a hierarchy of evidence has been proposed, including various types of research methods, such as meta-analysis (MA), systematic review (SRV), randomized controlled trial (RCT), case report (CR), practice guideline (PGL), and so on. Although there are numerous studies examining the impact and importance of specific cases of EBM in clinical practice, there is a lack of research quantitatively measuring publication trends in the growth and development of EBM. Therefore, a bibliometric analysis was constructed to determine the scientific productivity of EBM research over decades. METHODS: NCBI PubMed database was used to search, retrieve and classify publications according to research method and year of publication. Joinpoint regression analysis was undertaken to analyze trends in research productivity and the prevalence of individual research methods. FINDINGS: Analysis indicates that MA and SRV, which are classified as the highest ranking of evidence in the EBM, accounted for a relatively small but auspicious number of publications. For most research methods, the annual percent change (APC) indicates a consistent increase in publication frequency. MA, SRV and RCT show the highest rate of publication growth in the past twenty years. Only controlled clinical trials (CCT) shows a non-significant reduction in publications over the past ten years. CONCLUSIONS: Higher quality research methods, such as MA, SRV and RCT, are showing continuous publication growth, which suggests an acknowledgement of the value of these methods. This study provides the first quantitative assessment of research method publication trends in EBM.
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- 2015
25. Estimating blood donor loss due to the variant CJD travel deferral
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Murphy, EL, Connor, JD, McEvoy, P, Hirschler, N, Busch, MP, Roberts, P, Nguyen, KA, and Reich, P
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Adult ,Male ,Travel ,Adolescent ,Clinical Sciences ,Immunology ,Age Factors ,Blood Donors ,Middle Aged ,Cardiorespiratory Medicine and Haematology ,Creutzfeldt-Jakob Syndrome ,Logistic Models ,Cross-Sectional Studies ,Sex Factors ,Cardiovascular System & Hematology ,Humans ,Female ,Aged - Abstract
BACKGROUND: The FDA recommended new travel deferrals in May 2002 to prevent the potential transmission of variant CJD (vCJD). The predicted impact of such deferrals on the blood supply was controversial. STUDY DESIGN AND METHODS: We distributed anonymous, self-administered questionnaires to donors over 2 weeks in April 2002. Two thousand surveys were allocated to each of five geographic groupings of blood centers in the western and central US. Results were analyzed with chi-squared tests and logistic regression. RESULTS: Of 9800 surveys, 7405 (76%) were returned and analyzed. Overall, 257 (3.47%; 95% CI, 3.05-3.89) donors responding to the survey met the expanded May and November 2002 FDA vCJD travel criteria for deferral. Deferral rates ranged from 1 percent or less in Northern and Southern centers, 3 to 4 percent in San Francisco, California, and Scottsdale, Arizona, to over 13 percent in El Paso, Texas (p < 0.0001). Service at a European military base was the most common reason for deferral, whereas in San Francisco most deferrals were for UK and European travel or residence. The vCJD deferral was also associated with ages 30 through 49 years and with male gender. During June through September 2002, observed deferral rates were 1.6 percent at the same centers. CONCLUSIONS: Predicted deferrals due the new vCJD travel criteria depend upon the number of military donors at a blood center, as well as on the age and gender of donors. Actual deferrals were lower than predicted by an anonymous survey.
- Published
- 2004
26. O-100 Relationship Between Adverse Drug Reactions And Off-label/unlicensed Drug Use In Hospitalised Children. Eremi Study
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Nguyen, KA, primary, Mimouni, Y, additional, Lajoinie, A, additional, Paret, N, additional, Malik, S, additional, Milliat-Guittard, L, additional, El-Amrani, L, additional, Castellan, C, additional, Schott, AM, additional, Vial, T, additional, and Kassai, B, additional
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- 2014
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27. O-115 Relationship Between Adverse Drug Reactions And Off-label/unlicensed Drug Use In Hospitalised Neonates. Remineo Study
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Nguyen, KA, primary, Paret, N, additional, Plaisant, F, additional, Giraud, C, additional, Beissel, A, additional, Millaret, A, additional, Al-Sohim, F, additional, Gaillard, S, additional, Vial, T, additional, Claris, O, additional, and Kassai, B, additional
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- 2014
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28. PO-0681 Effects Of Education Nurse Program In Improving Feeding Pattern In Premature Infants
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Beissel, A, primary, Nguyen, KA, additional, Pillet, F, additional, Doiret, F, additional, Plaisant, F, additional, Gauthier-Moulinier, H, additional, Magrou, AS, additional, Tarifa-Buisson, H, additional, Deruy, F, additional, Goyet, AS, additional, Conti, I, additional, Keita, C, additional, Duhamel, C, additional, Hommey, S, additional, Hommey, SDA, additional, Touzet, S, additional, and Claris, O, additional
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- 2014
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29. Environmental Hazards and Risk Identification in the Arctic Shelf Development as Part of China and Russia Energy Interests
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Svetlana Razmanova, Zhanna Pisarenko, Olga Nesterova, Nguyen Kahn Toan, and Leonid Ivanov
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Arctic ,environmental hazards ,energy resources ,risks ,interests ,Russia ,Technology - Abstract
China and Russia have different interests in the Arctic but are forced to look for possible ways of cooperation in energy projects in the current external conditions. This changes the priorities of both countries and, accordingly, transforms the risks. Objectives of the research: to build an algorithm for identifying anthropogenic environmental risks in the context of two major players economic activities in the Arctic region: the Russian Federation and China. In the paper, we formulated an algorithm of environmental risk identification. We identified environmental hazards from the main parameter—the type of economic activity for the extraction of energy resources, premises, and factors for the occurrence of environmental hazards and compiled criteria for risk selection. Methods used: complex analysis (mixed method research): empirical and comparative methods, methods of expert assessments, the method of inductive statistics (inferential statistics) to compare the perception of risk at the level of different groups. Results: the algorithm has been formed for determining risks in the changed external conditions. Major anthropogenic environmental risks are identified from the perspective of the main players in the Arctic—Russia and China, which can help to make the necessary decisions on time and partially prevent environmental degradation. This makes it possible to identify the risks associated with conducting economic activities for the extraction of energy resources in the Arctic region. Therefore, this study contributes to a more accurate identification of anthropogenic environmental risks in the Arctic region.
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- 2023
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30. Dichotomy of gingipains action as virulence factors: from cleaving substrates with the precision of a surgeon's knife to a meat chopper-like brutal degradation of proteins.
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Guo Y, Nguyen KA, Potempa J, Guo, Yonghua, Nguyen, Ky-Anh, and Potempa, Jan
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- 2010
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31. Two-year experience with aerobic culturing of apheresis and whole blood-derived platelets.
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Kleinman SH, Kamel HT, Harpool DR, Vanderpool SK, Custer B, Wiltbank TB, Nguyen KA, and Tomasulo PA
- Abstract
BACKGROUND: Throughout its system of regional centers, Blood Systems implemented culture based bacterial testing with a standardized protocol for both apheresis and whole blood-derived platelets (PLTs). STUDY DESIGN AND METHODS: After a 24-hour hold, 4 mL of PLT product was inoculated into an aerobic bottle (BacT/ALERT, bioMérieux). Cultures were incubated for 24 hours before routine product release to prevent distribution of infected products while minimizing consignee notification, product retrievals, and hospital PLT inventory problems. Initial-positives were further tested (and bacteria identified) by performing cultures from the original component and subcultures from the BacT/ALERT bottle. Results were categorized according to AABB recommended definitions with minor modifications. RESULTS: The rate of true-positive detections from culturing 122,971 apheresis PLTs was 0.017 percent (95% confidence interval [CI], 0.011%-0.026%). All true-positive microorganisms were Gram-positive with a predominance of coagulase-negative Staphylococcus and Bacillus species. Twenty of the 21 true-positive samples (95%) were detected by 24 hours but only 14 (68%) were detected by 18 hours. The false-positive rate due to contamination was 0.1 percent with the majority of isolates being skin or environmental organisms. Results did not differ significantly for whole blood-derived versus apheresis PLTs. CONCLUSION: These data corroborate the fact that the rate of detection of truly contaminated PLT apheresis products in the United States is approximately 1 in 5000 (0.02%); this is lower than the 0.03 to 0.05 percent rates that were generally quoted in the literature before the implementation of prospective bacterial culturing programs. [ABSTRACT FROM AUTHOR]
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- 2006
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32. Using human factors methods to mitigate bias in artificial intelligence-based clinical decision support.
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Militello LG, Diiulio J, Wilson DL, Nguyen KA, Harle CA, Gellad W, and Lo-Ciganic WH
- Abstract
Objectives: To highlight the often overlooked role of user interface (UI) design in mitigating bias in artificial intelligence (AI)-based clinical decision support (CDS)., Materials and Methods: This perspective paper discusses the interdependency between AI-based algorithm development and UI design and proposes strategies for increasing the safety and efficacy of CDS., Results: The role of design in biasing user behavior is well documented in behavioral economics and other disciplines. We offer an example of how UI designs play a role in how bias manifests in our machine learning-based CDS development., Discussion: Much discussion on bias in AI revolves around data quality and algorithm design; less attention is given to how UI design can exacerbate or mitigate limitations of AI-based applications., Conclusion: This work highlights important considerations including the role of UI design in reinforcing/mitigating bias, human factors methods for identifying issues before an application is released, and risk communication strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2024
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33. Exploring the associations of tobacco smoking and serum cotinine levels with selected inflammatory markers in adults with HIV in South Africa.
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Peer N, Nguyen KA, Peprah E, Xu H, Matsha TE, Chegou NN, and Kengne AP
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- Humans, Female, Male, South Africa epidemiology, Adult, Inflammation blood, Middle Aged, Tumor Necrosis Factor-alpha blood, Interferon-gamma blood, Interleukin-2 blood, Interleukin-10 blood, Cotinine blood, HIV Infections blood, Tobacco Smoking blood, Tobacco Smoking adverse effects, Biomarkers blood
- Abstract
This study examined the associations between tobacco smoking and serum cotinine levels, an objective biochemical measure of tobacco smoke exposure, with markers of inflammation, i.e., interferon-gamma (IFN-γ), interleukin 10 (IL-10), interleukin 2 (IL-2) and tumour necrosis factor-alpha (TNF-α) in people living with HIV (PLWH).These specific markers were selected because of their hypothesised associations with smoking, PLWH and their outcomes. In a random sample of ≥ 18-year-old PLWH receiving care at 17 public healthcare facilities across the Western Cape Province in South Africa, data collection included self-reported smoking history, and serum levels of cotinine and selected inflammatory markers. The inflammatory marker data were log transformed because of the skewedness of their distribution. Linear regression models (1) adjusted for age and gender, and (2) fully adjusted for age, gender, current alcohol use, body mass index and CD4 counts were used to examine the associations between smoking tobacco or serum cotinine and inflammatory markers. Level of significance was p < 0.05. Among 749 PLWH who were mainly women (79%), the mean age was 38.5 (8.9) years and similar when stratified by smoking status. Serum cotinine levels exhibited a striking discrepancy, with a median of 154 ng/mL among current smokers, in stark contrast to the consistent median values of 10 ng/mL observed among past and never smokers. In regression models adjusted for age and gender, current smoking and frequent smoking were associated with lower IL-2 but higher TNF-α. Log-cotinine exhibited associations with IFN-γ, IL-10, and TNF-α, while cotinine levels ≥ 10 ng/mL compared to < 10 ng/mL were associated with higher IFN-γ and TNF-α. In fully adjusted models, log-cotinine and cotinine levels ≥ 10 ng/mL displayed significant associations with higher IFN-γ and lower IL-2. This study underscores the importance of investigating the interplay between smoking tobacco or serum cotinine levels with pro-inflammatory cytokines in PLWH. It signals the need for comprehensive research to unravel the potential synergistic impacts of smoking tobacco and HIV infection on chronic inflammation and immune dysregulation, shedding light on critical avenues for intervention and management strategies., (© 2024. The Author(s).)
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- 2024
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34. Electronic Structures and Spectra of Donor-Acceptor Conjugated Oligomers.
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Nguyen KA, Pachter R, Loftus LM, Hong G, Day PN, Azoulay JD, and Grusenmeyer TA
- Abstract
Narrow band gap donor-acceptor conjugated polymers present excellent paradigms in photonics and optoelectronics due to their chemical tunability, correlated electronic structures, and tunable open-shell electronic configurations. However, rational design for enhancing the properties of these molecular systems remains challenging. In this study, we employed density functional theory (DFT) calculations to investigate prototypical narrow band gap donor-acceptor conjugated oligomers, consisting of alternating cyclopentadithiophene (CPDT) donors paired with benzothiadiazole (BT), benzoselenadiazole (BSe), benzobisthiadiazole (BBT), and thiadiazoloquinoxaline (TQ) acceptors. Analyses of structures, singlet-triplet gaps, and absorption spectra of oligomers with up to ten repeat units have shown that when incorporating the BT, BSe, and TQ acceptors, the backbone curvature resulted in spiral structures that were energetically favored over their linear counterparts, causing differences in the calculated circular dichroism spectra. Oligomers with BBT-based acceptors preferred, however, a linear geometry, consistent with an open-shell electronic structure. Calculated singlet-triplet splittings demonstrated the importance of long chains and specific structures for consistency with the experiment, while effects of the solvent were also quantified. Based on the predicted low-energy conformations, one-photon absorption spectra for the considered oligomers have shown that using the Tamm-Dancoff approximation within time-dependent DFT for the large systems offers good agreement with the first absorption maxima in measured experimental spectra, thus validating the method for large donor-acceptor oligomers. Natural transition orbital analyses provided insights into the excited-state characteristics. Two-photon absorption maxima were accurately predicted, but the cross-sections were overestimated or underestimated, as dependent on the level of theory employed, to be addressed in future work.
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- 2024
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35. Clinicians' use of Health Information Exchange technologies for medication reconciliation in the U.S. Department of Veterans Affairs: a qualitative analysis.
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Snyder ME, Nguyen KA, Patel H, Sanchez SL, Traylor M, Robinson MJ, Damush TM, Taber P, Mixon AS, Fan VS, Savoy A, Dismore RA, Porter BW, Boockvar KS, Haggstrom DA, Locke ER, Gibson BS, Byerly SH, Weiner M, and Russ-Jara AL
- Subjects
- Humans, United States, Female, Male, Middle Aged, Electronic Health Records, Interviews as Topic, Adult, Attitude of Health Personnel, Medication Reconciliation methods, United States Department of Veterans Affairs, Qualitative Research, Health Information Exchange
- Abstract
Background: Medication reconciliation is essential for optimizing medication use. In part to promote effective medication reconciliation, the Department of Veterans Affairs (VA) invested substantial resources in health information exchange (HIE) technologies. The objectives of this qualitative study were to characterize VA clinicians' use of HIE tools for medication reconciliation in their clinical practice and to identify facilitators and barriers., Methods: We recruited inpatient and outpatient prescribers (physicians, nurse practitioners, physician assistants) and pharmacists at four geographically distinct VA medical centers for observations and interviews. Participants were observed as they interacted with HIE or medication reconciliation tools during routine work. Participants were interviewed about clinical decision-making pertaining to medication reconciliation and use of HIE tools, and about barriers and facilitators to use of the tools. Qualitative data were analyzed via inductive and deductive approaches using a priori codes., Results: A total of 63 clinicians participated. Over half (58%) were female, and the mean duration of VA clinical experience was 7 (range 0-32) years. Underlying motivators for clinicians seeking data external to their VA medical center were having new patients, current patients receiving care from an external institution, and clinicians' concerns about possible medication discrepancies among institutions. Facilitators for using HIE software were clinicians' familiarity with the HIE software, clinicians' belief that medication information would be available within HIE, and their confidence in the ability to find HIE medication-related data of interest quickly. Six overarching barriers to HIE software use for medication coordination included visual clutter and information overload within the HIE display; challenges with HIE interface navigation; lack of integration between HIE and other electronic health record interfaces, necessitating multiple logins and application switching; concerns with the dependability of HIE medication information; unfamiliarity with HIE tools; and a lack of HIE data from non-VA facilities., Conclusions: This study is believed to be the first to qualitatively characterize clinicians' HIE use with respect to medication reconciliation. Results inform recommendations to optimize HIE use for medication management activities. We expect that healthcare organizations and software vendors will be able to apply the findings to develop more effective and usable HIE information displays., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2024
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36. One Trocar-Assisted Retroperitoneoscopic Ureteroureterostomy for Ureteral Duplication.
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Nguyen QT, Le DA, Nguyen KA, Nguyen TLV, Dang TT, and Nguyen LT
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- Humans, Female, Male, Child, Preschool, Infant, Retroperitoneal Space surgery, Child, Ureterostomy methods, Surgical Instruments, Treatment Outcome, Ureter surgery, Ureter abnormalities, Ureter diagnostic imaging, Laparoscopy methods
- Abstract
Aim: To describe the operative technique and outcome of one trocar-assisted retroperitoneoscopic ureteroureterostomy (OTAU) in 40 cases of complete ureteral duplication in children. Patients and Methods: From September 2016 to December 2020, 40 patients (12 male and 28 female) less than 10 years of age underwent OTAU. A transverse skin incision of 12 mm in length was created approximately 1 cm above the iliac crest. Muscle was spared and retracted with stay sutures to expose the retroperitoneal space. Subsequently, a balloon trocar was then inserted, and pneumoperitoneum was achieved. A 10 mm operating laparoscope (Stema, Germany) with a Maryland was used to dissect and isolate the ureters from surrounding tissues. The ureters were then exteriorized and end-to-side ureteroureterostomy was performed using Polydioxanone (PDS) 6/0 running sutures. Patient's demographic, operative, and follow-up data were collected prospectively. Results: The mean age of patients was 25.2 months (range: 1-105 months). The mean operating time was 81.9 ± 11.3 minutes. There were no intraoperative conversions or complications. After a median follow-up time of 47.5 months, the differential renal function of the pathological upper pole moiety (UPM) was preserved in all patients. Ultrasound revealed a significant reduction in UPM's renal pelvis anterior-posterior diameter from 19.6 ± 9.1 mm preoperatively to 11.1 ± 6.7 mm postoperatively ( p < 0.05), accompanied by a reduction in ureter's diameter from 10.8 ± 4.4 mm to 4.8 ± 1.2 mm ( p < 0.05). Overall, all 32 patients with preoperative symptoms experienced complete symptom resolution. Conclusion: OTAU is a safe and feasible approach that yields excellent outcomes for complete ureteral duplication.
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- 2024
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37. Engineering the substrate specificity and regioselectivity of Burkholderia thailandensis lipoxygenase.
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Chrisnasari R, Hennebelle M, Nguyen KA, Vincken JP, van Berkel WJH, and Ewing TA
- Abstract
Lipoxygenases (LOXs) catalyze the regioselective dioxygenation of polyunsaturated fatty acids (PUFAs), generating fatty acid hydroperoxides (FAHPs) with diverse industrial applications. Bacterial LOXs have garnered significant attention in recent years due to their broad activity towards PUFAs, yet knowledge about the structural factors influencing their substrate preferences remains limited. Here, we characterized a bacterial LOX from Burkholderia thailandensis (Bt-LOX), and identified key residues affecting its substrate preference and regioselectivity through site-directed mutagenesis. Bt-LOX preferred ω-6 PUFAs and exhibited regioselectivity at the ω-5 position. Mutations targeting the substrate binding pocket and the oxygen access channel led to the production of three active variants with distinct catalytic properties. The A431G variant bifurcated dioxygenation between the ω-5 and ω-9 positions, while F446V showed reduced regioselectivity with longer PUFAs. Interestingly, L445A displayed altered substrate specificity, favoring ω-3 over ω-6 PUFAs. Furthermore, L445A shifted the regioselectivity of dioxygenation to the ω-2 position in ω-3 PUFAs, and, for some substrates, facilitated dioxygenation closer to the carboxylic acid terminus, suggesting an altered substrate orientation. Among these variants, L445A represents a significant milestone in LOX research, as these alterations in substrate specificity, dioxygenation regioselectivity, and substrate orientation were achieved by a single mutation only. These findings illuminate key residues governing substrate preference and regioselectivity in Bt-LOX, offering opportunities for synthesizing diverse FAHPs and highlighting the potential of bacterial LOXs as biocatalysts with widespread applications., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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38. A mechanistic kinetic model for lipid oxidation in Tween 20-stabilized O/W emulsions.
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Nguyen KA, Boerkamp VJP, van Duynhoven JPM, Dubbelboer A, Hennebelle M, and Wierenga PA
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- Kinetics, Water chemistry, Particle Size, Models, Chemical, Oils chemistry, Emulsions chemistry, Oxidation-Reduction, Polysorbates chemistry, Lipids chemistry
- Abstract
Models predicting lipid oxidation in oil-in-water (O/W) emulsions are a requirement for developing effective antioxidant solutions. Existing models do, however, not include explicit equations that account for composition and structural features of O/W emulsions. To bridge this gap, a mechanistic kinetic model for lipid oxidation in emulsions is presented, describing the emulsion as a one-dimensional three phase (headspace, water, and oil) system. Variation in oil droplet sizes, overall surface area of oil/water interface, oxidation of emulsifiers, and the presence of catalytic transition metals were accounted for. For adequate predictions, the overall surface area of oil/water interface needs to be determined from the droplet size distribution obtained by dynamic and static light scattering (DLS, SLS). The kinetic model predicted well the formation of oxidation products in both mono- and polydisperse emulsions, with and without presence of catalytic transition metals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Arend Dubbelboer and John P.M. Van Duynhoven are employed by companies that manufacture and market oil based food products., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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39. Extramammary Paget disease. Part II. Evidence-based approach to management.
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Shah RR, Shah K, Wilson BN, Leitao MM, Smogorzewski J, Nguyen KA, Crane C, Funt SA, Hosein S, Dafinone M, and Rossi A
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- Humans, Skin Neoplasms therapy, Skin Neoplasms pathology, Male, Female, Paget Disease, Extramammary therapy, Paget Disease, Extramammary pathology, Paget Disease, Extramammary diagnosis, Evidence-Based Medicine
- Abstract
Extramammary Paget disease is a rare cutaneous malignancy that most commonly affects the genitals, perianal area, and axilla of elderly patients. Delays in care often lead to high levels of disease burden for patients. Thus, evidence-based recommendations are paramount in mitigating morbidity and mortality for this unique patient population. This 2-part continuing medical education series provides a complete picture of extramammary Paget disease. Part 2 of this continuing medical education series focuses on the complex management of extramammary Paget disease including surgical and noninvasive therapies, as well as novel approaches for advanced disease., Competing Interests: Conflicts of interest Dr Rossi has no relevant conflicts of interest related to this article but has received grant funding from The Skin Cancer Foundation and the A. Ward Ford Memorial Grant, served on advisory board, as a consultant, given educational presentations for Almirall, Allergan Inc, Galderma Inc, Evolus Inc, Elekta, Biofrontera (Quantia), Merz Inc, Dynamed, Skinuvia, Perf-Action, Cutera, and LAM therapeutics, and holds equity in DAR companies. Dr Funt has received research support from AstraZenecaAstraZeneca, GenentechGenentech/RocheRoche, and Decibel Therapeutics, is a consultant/advisory board member for MerckMerck and BioNTech, and owns stock in Urogen, Allogene Therapeutics, Neogene Therapeutics, Kronos Bio, ByHeart, 76Bio, Vida Ventures, Ginkgo Bioworks, Doximity, and Inconovir. The other authors have no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
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- 2024
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40. Extramammary Paget disease. Part I. epidemiology, pathogenesis, clinical features, and diagnosis.
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Shah RR, Shah K, Wilson BN, Tchack M, Busam KJ, Moy A, Leitao MM, Cordova M, Neumann NM, Smogorzewski J, Nguyen KA, Hosein S, Dafinone M, Schwartz RA, and Rossi A
- Subjects
- Humans, Prognosis, Male, Female, Diagnosis, Differential, Paget Disease, Extramammary epidemiology, Paget Disease, Extramammary diagnosis, Paget Disease, Extramammary pathology, Skin Neoplasms epidemiology, Skin Neoplasms diagnosis, Skin Neoplasms pathology
- Abstract
Extramammary Paget disease (EMPD) is a rare skin cancer of apocrine-rich skin that mimics common inflammatory and infectious dermatoses, leading to delays in diagnosis and increased patient morbidity. Better clinical recognition of this entity, multidisciplinary patient assessment, and deeper understanding of the underlying pathophysiology are essential to improve patient care and disease outcomes. It is important to distinguish primary intraepithelial/micro-invasive EMPD from invasive EMPD or cases with adenocarcinoma arising within EMPD. This 2-part continuing medical education series provides a complete picture of EMPD. Part 1 of this continuing medical education series reviews the epidemiology, oncogenesis, clinical and histopathologic presentation, workup, and prognosis of this rare cancer., Competing Interests: Conflict of interest Anthony Rossi: Dr Rossi has no relevant conflicts of interest related to this manuscript. He also served on advisory board, as a consultant, or given educational presentations for: Almirall; Allergan, Inc; Galderma Inc; Evolus Inc; Elekta; Biofrontera, Quantia; Merz Inc; Dynamed; Skinuvia; Perf-Action; Cutera; and LAM therapeutics. Equity in DAR companies., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
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- 2024
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41. Association between Early Basal Ganglia and Thalami Perfusion Assessed by Color Doppler Ultrasonography and Brain Injury in Infants with Hypoxic-Ischemic Encephalopathy: A Prospective Cohort Study.
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Faingold R, Prempunpong C, Garfinkle J, St Martin C, Menegotto F, Boyle R, Aguilera JM, Nguyen KA, and Sant'Anna GM
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- Humans, Prospective Studies, Male, Female, Infant, Newborn, Infant, Brain Injuries diagnostic imaging, Basal Ganglia diagnostic imaging, Hypoxia-Ischemia, Brain diagnostic imaging, Hypoxia-Ischemia, Brain therapy, Ultrasonography, Doppler, Color methods, Magnetic Resonance Imaging methods, Thalamus diagnostic imaging, Hypothermia, Induced
- Abstract
Objective: To evaluate associations between neurologic outcomes and early measurements of basal ganglia (BG) and thalamic (Th) perfusion using color Doppler ultrasonography (CDUS) in infants with hypoxic-ischemic encephalopathy (HIE)., Study Design: Prospective study of infants with mild (n = 18), moderate (n = 17), and severe HIE (n = 14) and controls (n = 17). Infants with moderate-severe HIE received therapeutic hypothermia (TH). CDUS was performed at 24-36 hours and brain magnetic resonance imaging (MRI) at a median of 10 days. Development was followed through 2.5-5 years. The primary outcome was the association between BG and Th perfusion and brain MRI injury. Secondary analyses focused on associations between perfusion measurements and admission neurologic examinations, MRI scores in infants treated with TH, and motor and sensory disability, or death. An exploratory analysis assessed the accuracy of BG and Th perfusion to predict brain MRI injury in infants treated with TH., Results: Increased BG and Th perfusion on CDUS was observed in infants with severe MRI scores and those with significant motor and neurosensory disability or death through 2.5-5 years (P < .05). Infants with severe HIE showed increased BG and Th perfusion (P < .005) compared with infants with moderate HIE. No differences were identified between the between the control and mild HIE groups. Th perfusion ≥0.237 cm/second (Area under the curve of 0.824) correctly classified 80% of infants with severe MRI scores., Conclusions: Early dynamic CDUS of the BG and Th is a potential biomarker of severe brain injury in infants with HIE and may be a useful adjunct to currently used assessments., Competing Interests: Declaration of Competing Interest The study received support from a local grant of the Research Institute of the McGill University Health Center &Montreal Children's Hospital. The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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42. Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators.
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Skaar TC, Myers RA, Fillingim RB, Callaghan JT, Cicali E, Eadon MT, Elwood EN, Ginsburg GS, Lynch S, Nguyen KA, Obeng AO, Park H, Pratt VM, Rosenman M, Sadeghpour A, Shuman S, Singh R, Tillman EM, Volpi S, Wiisanen K, Winterstein AG, Horowitz CR, Voora D, Orlando L, Chakraborty H, Van Driest S, Peterson JF, Cavallari LA, Johnson JA, and Dexter PR
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Pain Management methods, Pain Measurement, Pharmacogenomic Testing, Precision Medicine methods, Analgesics, Opioid therapeutic use, Analgesics, Opioid adverse effects, Chronic Pain drug therapy, Cytochrome P-450 CYP2D6 genetics, Cytochrome P-450 CYP2D6 metabolism
- Abstract
Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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- 2024
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43. PKR Mediates the Mitochondrial Unfolded Protein Response through Double-Stranded RNA Accumulation under Mitochondrial Stress.
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Kusuma F, Park S, Nguyen KA, Elvira R, Lee D, and Han J
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- Animals, Mice, Stress, Physiological, Signal Transduction, bcl-2-Associated X Protein metabolism, bcl-2-Associated X Protein genetics, Fibroblasts metabolism, bcl-2 Homologous Antagonist-Killer Protein metabolism, bcl-2 Homologous Antagonist-Killer Protein genetics, Humans, eIF-2 Kinase metabolism, eIF-2 Kinase genetics, Mitochondria metabolism, Unfolded Protein Response, RNA, Double-Stranded metabolism
- Abstract
Mitochondrial stress, resulting from dysfunction and proteostasis disturbances, triggers the mitochondrial unfolded protein response (UPR
MT ), which activates gene encoding chaperones and proteases to restore mitochondrial function. Although ATFS-1 mediates mitochondrial stress UPRMT induction in C . elegans , the mechanisms relaying mitochondrial stress signals to the nucleus in mammals remain poorly defined. Here, we explored the role of protein kinase R (PKR), an eIF2α kinase activated by double-stranded RNAs (dsRNAs), in mitochondrial stress signaling. We found that UPRMT does not occur in cells lacking PKR, indicating its crucial role in this process. Mechanistically, we observed that dsRNAs accumulate within mitochondria under stress conditions, along with unprocessed mitochondrial transcripts. Furthermore, we demonstrated that accumulated mitochondrial dsRNAs in mouse embryonic fibroblasts (MEFs) deficient in the Bax/Bak channels are not released into the cytosol and do not induce the UPRMT upon mitochondrial stress, suggesting a potential role of the Bax/Bak channels in mediating the mitochondrial stress response. These discoveries enhance our understanding of how cells maintain mitochondrial integrity, respond to mitochondrial dysfunction, and communicate stress signals to the nucleus through retrograde signaling. This knowledge provides valuable insights into prospective therapeutic targets for diseases associated with mitochondrial stress.- Published
- 2024
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44. Omics analysis unveils changes in the metabolome and lipidome of Caenorhabditis elegans upon polydopamine exposure.
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Nguyen BT, Le QV, Ahn J, Nguyen KA, Nguyen HT, Kang JS, Long NP, and Kim HM
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- Animals, Lipids, Lipid Metabolism drug effects, Caenorhabditis elegans metabolism, Caenorhabditis elegans drug effects, Polymers metabolism, Indoles metabolism, Metabolomics methods, Lipidomics methods, Metabolome drug effects
- Abstract
Polydopamine (PDA) is an insoluble biopolymer with a dark brown-black color that forms through the autoxidation of dopamine. Because of its outstanding biocompatibility and durability, PDA holds enormous promise for various applications, both in the biomedical and non-medical domains. To ensure human safety, protect health, and minimize environmental impacts, the assessment of PDA toxicity is important. In this study, metabolomics and lipidomics assessed the impact of acute PDA exposure on Caenorhabditis elegans (C. elegans). The findings revealed a pronounced perturbation in the metabolome and lipidome of C. elegans at the L4 stage following 24 hours of exposure to 100 µg/mL PDA. The changes in lipid composition varied based on lipid classes. Increased lipid classes included lysophosphatidylethanolamine, triacylglycerides, and fatty acids, while decreased species involved in several sub-classes of glycerophospholipids and sphingolipids. Besides, we detected 37 significantly affected metabolites in the positive and 8 in the negative ion modes due to exposure to PDA in C. elegans. The metabolites most impacted by PDA exposure were associated with purine metabolism, biosynthesis of valine, leucine, and isoleucine; aminoacyl-tRNA biosynthesis; and cysteine and methionine metabolism, along with pantothenate and CoA biosynthesis; the citrate cycle (TCA cycle); and beta-alanine metabolism. In conclusion, PDA exposure may intricately influence the metabolome and lipidome of C. elegans. The combined application of metabolomics and lipidomics offers additional insights into the metabolic perturbations involved in PDA-induced biological effects and presents potential biomarkers for the assessment of PDA safety., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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45. Chirality-Induced Spin Selectivity: Analysis of Density Functional Theory Calculations.
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Day PN, Pachter R, Nguyen KA, and Hong G
- Abstract
Chirality-induced spin selectivity (CISS), which was demonstrated in several molecular and material systems, has drawn much interest recently. The phenomenon, described in electron transport by the difference in the transport rate of electrons of opposite spins through a chiral system, is however not fully understood. Herein, we employed density functional theory in conjunction with spin-orbit coupling to evaluate the percent spin-polarization in a device setup with finite electrodes at zero bias, using an electron transport program developed in-house. To study the interface effects and the level of theory considered, we investigated a helical oligopeptide chain, an intrinsically chiral gold cluster, and a helicene model system that was previously studied (Zöllner et al. J. Chem. Theory Comput. 2020, 16, 7357-7371). We find that the magnitude of the spin-polarization depends on the chiral system-electrode interface that is modeled by varying the interface boundary between the system's regions, on the method of calculating spin-orbit coupling, and on the exchange-correlation functional, e.g., the amount of exact exchange in the hybrid functionals. In addition, to assess the effects of bias, we employ the nonequilibrium Green's function formalism in the Quantum Atomistix Toolkit program, showing that the spin-flip terms could be important in calculating the CISS effect. Although understanding CISS in comparison to experiment is still not resolved, our study provides intrinsic responses from first-principles calculations.
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- 2024
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46. Droplet size dependency and spatial heterogeneity of lipid oxidation in whey protein isolate-stabilized emulsions.
- Author
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Yang S, Ten Klooster S, Nguyen KA, Hennebelle M, Berton-Carabin C, Schroën K, van Duynhoven JPM, and Hohlbein J
- Subjects
- Boron Compounds chemistry, Kinetics, Peroxides chemistry, Lipids chemistry, Whey Proteins chemistry, Emulsions chemistry, Oxidation-Reduction, Particle Size
- Abstract
Spatiotemporal assessment of lipid and protein oxidation is key for understanding quality deterioration in emulsified food products containing polyunsaturated fatty acids. In this work, we first mechanistically validated the use of the lipid oxidation-sensitive fluorophore BODIPY 665/676 as a semi-quantitative marker for local peroxyl radical formation. Next, we assessed the impact of microfluidic and colloid mill emulsification (respectively producing mono- and polydisperse droplets) on local protein and lipid oxidation kinetics in whey protein isolate (WPI)-stabilized emulsions. We further used BODIPY 581/591 C11 and CAMPO-AFDye 647 as colocalisation markers for lipid and protein oxidation. The polydisperse emulsions showed an inverse relation between droplet size and lipid oxidation rate. Further, we observed less protein and lipid oxidation occurring in similar sized droplets in monodisperse emulsions. This observation was linked to more heterogeneous protein packing at the droplet surface during colloid mill emulsification, resulting in larger inter-droplet heterogeneity in both protein and lipid oxidation. Our findings indicate the critical roles of emulsification methods and droplet sizes in understanding and managing lipid oxidation., Competing Interests: Declaration of competing interest J.P.M.v.D. is employed by a company that manufactures and markets mayonnaise. The other authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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47. Real-Time Machine Learning Alerts to Prevent Escalation of Care: A Nonrandomized Clustered Pragmatic Clinical Trial.
- Author
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Levin MA, Kia A, Timsina P, Cheng FY, Nguyen KA, Kohli-Seth R, Lin HM, Ouyang Y, Freeman R, and Reich DL
- Subjects
- Humans, Female, Male, Prospective Studies, Middle Aged, Aged, Hospital Rapid Response Team organization & administration, Hospital Rapid Response Team statistics & numerical data, Hospital Mortality, Machine Learning, Clinical Deterioration
- Abstract
Objectives: Machine learning algorithms can outperform older methods in predicting clinical deterioration, but rigorous prospective data on their real-world efficacy are limited. We hypothesized that real-time machine learning generated alerts sent directly to front-line providers would reduce escalations., Design: Single-center prospective pragmatic nonrandomized clustered clinical trial., Setting: Academic tertiary care medical center., Patients: Adult patients admitted to four medical-surgical units. Assignment to intervention or control arms was determined by initial unit admission., Interventions: Real-time alerts stratified according to predicted likelihood of deterioration sent either to the primary team or directly to the rapid response team (RRT). Clinical care and interventions were at the providers' discretion. For the control units, alerts were generated but not sent, and standard RRT activation criteria were used., Measurements and Main Results: The primary outcome was the rate of escalation per 1000 patient bed days. Secondary outcomes included the frequency of orders for fluids, medications, and diagnostic tests, and combined in-hospital and 30-day mortality. Propensity score modeling with stabilized inverse probability of treatment weight (IPTW) was used to account for differences between groups. Data from 2740 patients enrolled between July 2019 and March 2020 were analyzed (1488 intervention, 1252 control). Average age was 66.3 years and 1428 participants (52%) were female. The rate of escalation was 12.3 vs. 11.3 per 1000 patient bed days (difference, 1.0; 95% CI, -2.8 to 4.7) and IPTW adjusted incidence rate ratio 1.43 (95% CI, 1.16-1.78; p < 0.001). Patients in the intervention group were more likely to receive cardiovascular medication orders (16.1% vs. 11.3%; 4.7%; 95% CI, 2.1-7.4%) and IPTW adjusted relative risk (RR) (1.74; 95% CI, 1.39-2.18; p < 0.001). Combined in-hospital and 30-day-mortality was lower in the intervention group (7% vs. 9.3%; -2.4%; 95% CI, -4.5% to -0.2%) and IPTW adjusted RR (0.76; 95% CI, 0.58-0.99; p = 0.045)., Conclusions: Real-time machine learning alerts do not reduce the rate of escalation but may reduce mortality., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)
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- 2024
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48. Development and Validation of a Deep Learning Classifier Using Chest Radiographs to Predict Extubation Success in Patients Undergoing Invasive Mechanical Ventilation.
- Author
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Tandon P, Nguyen KA, Edalati M, Parchure P, Raut G, Reich DL, Freeman R, Levin MA, Timsina P, Powell CA, Fayad ZA, and Kia A
- Abstract
The decision to extubate patients on invasive mechanical ventilation is critical; however, clinician performance in identifying patients to liberate from the ventilator is poor. Machine Learning-based predictors using tabular data have been developed; however, these fail to capture the wide spectrum of data available. Here, we develop and validate a deep learning-based model using routinely collected chest X-rays to predict the outcome of attempted extubation. We included 2288 serial patients admitted to the Medical ICU at an urban academic medical center, who underwent invasive mechanical ventilation, with at least one intubated CXR, and a documented extubation attempt. The last CXR before extubation for each patient was taken and split 79/21 for training/testing sets, then transfer learning with k-fold cross-validation was used on a pre-trained ResNet50 deep learning architecture. The top three models were ensembled to form a final classifier. The Grad-CAM technique was used to visualize image regions driving predictions. The model achieved an AUC of 0.66, AUPRC of 0.94, sensitivity of 0.62, and specificity of 0.60. The model performance was improved compared to the Rapid Shallow Breathing Index (AUC 0.61) and the only identified previous study in this domain (AUC 0.55), but significant room for improvement and experimentation remains.
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- 2024
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49. An oral carbon monoxide-releasing molecule protects against acute hyperhemolysis in sickle cell disease.
- Author
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Nguyen KA, Matte A, Foresti R, Federti E, Kiger L, Lefebvre C, Hocini H, Pelinski Y, Kitagishi H, Bencheikh L, Pirenne F, de Franceschi L, Motterlini R, and Bartolucci P
- Subjects
- Animals, Mice, Humans, Administration, Oral, Disease Models, Animal, Male, Mice, Inbred C57BL, Anemia, Sickle Cell drug therapy, Anemia, Sickle Cell complications, Carbon Monoxide pharmacology, Hemolysis drug effects, NF-E2-Related Factor 2 metabolism
- Abstract
Abstract: Acute hyperhemolysis is a severe life-threatening complication in patients with sickle cell disease (SCD) that may occur during delayed hemolytic transfusion reaction (DHTR), or vaso-occlusive crises associated with multiorgan failure. Here, we developed in vitro and in vivo animal models to mimic endothelial damage during the early phase of hyperhemolysis in SCD. We then used the carbon monoxide (CO)-releasing molecule CORM-401 and examined its effects against endothelial activation, damage, and inflammation inflicted by hemolysates containing red blood cell membrane-derived particles. The in vitro results revealed that CORM-401: (1) prevented the upregulation of relevant proinflammatory and proadhesion markers controlled by the NF-κB enhancer of activated B cells, and (2) abolished the expression of the nuclear factor erythroid-2-related factor 2 (Nrf2) that regulates the inducible antioxidant cell machinery. We also show in SCD mice that CORM-401 protects against hemolysate-induced acute damage of target organs such as the lung, liver, and kidney through modulation of NF-κB proinflammatory and Nrf2 antioxidant pathways. Our data demonstrate the efficacy of CORM-401 as a novel therapeutic agent to counteract hemolysate-induced organ damage during hyperhemolysis in SCD. This approach might be considered as possible preventive treatment in high-risk situations such as patients with SCD with history of DHTR., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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50. PTBP1 mediates Sertoli cell actin cytoskeleton organization by regulating alternative splicing of actin regulators.
- Author
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Wang Y, Chembazhi UV, Yee D, Chen S, Ji J, Wang Y, Nguyen KL, Lin P, Ratti A, Hess R, Qiao H, Ko C, Yang J, Kalsotra A, and Mei W
- Abstract
Spermatogenesis is a biological process within the testis that produces haploid spermatozoa for the continuity of species. Sertoli cells are somatic cells in the seminiferous epithelium that orchestrate spermatogenesis. Cyclic reorganization of Sertoli cell actin cytoskeleton is vital for spermatogenesis, but the underlying mechanism remains largely unclear. Here, we report that RNA-binding protein PTBP1 controls Sertoli cell actin cytoskeleton reorganization by programming alternative splicing of actin cytoskeleton regulators. This splicing control enables ectoplasmic specializations, the actin-based adhesion junctions, to maintain the blood-testis barrier and support spermatid transport and transformation. Particularly, we show that PTBP1 promotes actin bundle formation by repressing the inclusion of exon 14 of Tnik , a kinase present at the ectoplasmic specialization. Our results thus reveal a novel mechanism wherein Sertoli cell actin cytoskeleton dynamics is controlled post-transcriptionally by utilizing functionally distinct isoforms of actin regulatory proteins, and PTBP1 is a critical regulatory factor in generating such isoforms., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.
- Published
- 2024
- Full Text
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