4,490 results on '"K. Chung"'
Search Results
2. Vaccine effectiveness of BNT162b2 and CoronaVac against SARS-CoV-2 omicron infection and related hospital admission among people with substance use disorder in Hong Kong: a matched case-control study
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Caige Huang, Yue Wei, Vincent K C Yan, Xuxiao Ye, Wei Kang, Hei Hang Edmund Yiu, Jessica J P Shami, Benjamin J Cowling, Man Li Tse, David J Castle, Celine S L Chui, Francisco T T Lai, Xue Li, Eric Y F Wan, Carlos K H Wong, Joseph F Hayes, Wing Chung Chang, Albert K K Chung, Chak Sing Lau, Ian C K Wong, and Esther W Chan
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Psychiatry and Mental health ,Biological Psychiatry - Published
- 2023
3. Critical Care of the Burn Patient
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Garrett W. Britton, Amanda R. Wiggins, Barret J. Halgas, Leopoldo C. Cancio, and Kevin K. Chung
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Surgery - Published
- 2023
4. COVID-19 and the Cardiovascular System: Requiem for a Medical Minotaur
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Milka Koupenova, Mina K. Chung, and Michael R. Bristow
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Physiology ,Cardiology and Cardiovascular Medicine - Published
- 2023
5. A Post-Pandemic Enigma: The Cardiovascular Impact of Post-Acute Sequelae of SARS-CoV-2
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Tamanna K. Singh, David A. Zidar, Keith McCrae, Kristin B. Highland, Kristin Englund, Scott J. Cameron, and Mina K. Chung
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Physiology ,Cardiology and Cardiovascular Medicine - Abstract
COVID-19 has become the first modern-day pandemic of historic proportion, affecting >600 million individuals worldwide and causing >6.5 million deaths. While acute infection has had devastating consequences, postacute sequelae of SARS-CoV-2 infection appears to be a pandemic of its own, impacting up to one-third of survivors and often causing symptoms suggestive of cardiovascular phenomena. This review will highlight the suspected pathophysiology of postacute sequelae of SARS-CoV-2, its influence on the cardiovascular system, and potential treatment strategies.
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- 2023
6. Cases in Precision Medicine: Is There an Obligation to Return Reinterpreted Genetic Results to Former Patients?
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Paul S. Appelbaum, Wylie Burke, Erik Parens, Jessica Roberts, Sara M. Berger, and Wendy K. Chung
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Internal Medicine ,General Medicine - Published
- 2023
7. Molecular Function and Contribution of TBX4 in Development and Disease
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Justyna A. Karolak, Carrie L. Welch, Christian Mosimann, Katarzyna Bzdęga, James D. West, David Montani, Mélanie Eyries, Mary P. Mullen, Steven H. Abman, Matina Prapa, Stefan Gräf, Nicholas W. Morrell, Anna R. Hemnes, Frédéric Perros, Rizwan Hamid, Malcolm P. O. Logan, Jeffrey Whitsett, Csaba Galambos, Paweł Stankiewicz, Wendy K. Chung, and Eric D. Austin
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Pulmonary and Respiratory Medicine ,Critical Care and Intensive Care Medicine - Published
- 2023
8. Integrating Process Development and Safety Analysis for Scale-Up of a Diborane-Generating Reduction Reaction
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Brittany M. Armstrong, Taylor Behre, Ben W. H. Turnbull, Daniel Bishara, Clara Hartmanshenn, Erin McCarthy, Michael Whittington, Yining Ji, Anna Jenks, Richard Desmond, Daniel J. Muzzio, James Corry, Ralph Zhao, Nadine Kuhl, and Cheol K. Chung
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Organic Chemistry ,Physical and Theoretical Chemistry - Published
- 2023
9. Addressing Class Imbalances in Software Defect Detection
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Dae-Kyoo Kim and Yeasun K. Chung
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Computer Networks and Communications ,Education ,Information Systems - Published
- 2023
10. Leveraging Synergistic Solubility in the Development of a Direct Isolation Process for Nemtabrutinib
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Yonggang Chen, Luca Iuzzolino, Samantha A. Burgess, Cheol K. Chung, James Corry, Morgan Crawford, Richard Desmond, Erik Guetschow, Clara Hartmanshenn, Nadine Kuhl, Zhu Liu, Hanlin Luo, Alison C. McQuilken, Justin A. Newman, Hong Ren, David A. Thaisrivongs, Zhixun Wang, and Eric Sirota
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Organic Chemistry ,Physical and Theoretical Chemistry - Published
- 2023
11. Development of a Kilogram-Scale Synthesis of a Key Ulevostinag Subunit Part I: Accessing a Keto-Nucleoside Intermediate from Guanosine
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Ben W. H. Turnbull, Feng Peng, Andrew J. Neel, Tamas Benkovics, Zhuqing Liu, Cheol K. Chung, Zhiguo Jake Song, Lushi Tan, Khateeta M. Emerson, Chengqian Xiao, Yi Zhang, and Benjamin D. Sherry
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Organic Chemistry ,Physical and Theoretical Chemistry - Published
- 2023
12. Development of a Kilogram-Scale Synthesis of a Key Ulevostinag Subunit Part II: An Electrophilic Approach to Fluorinated Nucleosides
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Andrew J. Neel, Zhuqing Liu, Tamas Benkovics, Lu Wang, Stephan M. Rummelt, Heather C. Johnson, Kevin M. Belyk, Feng Xu, Cheol K. Chung, David J. Lamberto, Ryan D. Cohen, Stephanus Axnanda, and Zachary E. X. Dance
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Organic Chemistry ,Physical and Theoretical Chemistry - Published
- 2023
13. Admission and Care Practices in United States Well Newborn Nurseries
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Neha S. Joshi, Valerie J. Flaherman, Bonnie Halpern-Felsher, Esther K. Chung, Jayme L. Congdon, and Henry C. Lee
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Pediatrics, Perinatology and Child Health ,General Medicine ,Pediatrics - Abstract
OBJECTIVESLate preterm and term infants comprise 97.3% of annual births in the United States. Admission criteria and the availability of medical interventions in well newborn nurseries are key determinants of these infants remaining within a mother–infant dyad or requiring a NICU admission and resultant separation of the dyad. The objective of this study was to identify national patterns for well newborn nursery care practices.METHODSWe surveyed a physician representative from each nursery in the Better Outcomes through Research for Newborns Network. We described the admission criteria and clinical management of common newborn morbidities and analyzed associations with nursery demographics.RESULTSOf 96 eligible nursery representatives, 69 (72%) completed surveys. Among respondents, 59 (86%) used a minimal birth weight criterion for admission to their well newborn nursery. The most commonly used criteria were 2000 g (n = 29, 49%) and 1800 g (n = 19, 32%), with a range between 1750 and 2500 g. All nurseries used a minimal gestational age criterion for admission; the most commonly used criterion was 35 weeks (n = 55, 80%). Eleven percent of sites required transfer to the NICU for phototherapy. Common interventions in the mother’s room included dextrose gel (n = 56, 81%), intravenous antibiotics (n = 35, 51%), opiates for neonatal abstinence syndrome (n = 15, 22%), and an incubator for thermoregulation (n = 14, 20%).CONCLUSIONSWide variation in admission criteria and medical interventions exists in well newborn nurseries. Further studies may help identify evidence-based optimal admission criteria to maximize care within the mother–infant dyad.
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- 2023
14. Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis
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Z. Oaks, A. Patel, N. Huang, G. Choudhary, T. Winans, T. Faludi, D. Krakko, M. Duarte, J. Lewis, M. Beckford, S. Blair, R. Kelly, S. K. Landas, F. A. Middleton, J. M. Asara, S. K. Chung, D. R. Fernandez, K. Banki, and A. Perl
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Physiology (medical) ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Cell Biology - Published
- 2023
15. Thrombotic outcomes in patients in a large clinical enterprise following COVID-19 vaccination
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William M. Patterson, Brady D. Greene, Leben Tefera, James Bena, Alex Milinovich, Neil Mehta, Mina K. Chung, Samir Kapadia, Lars G Svensson, and Scott J. Cameron
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Hematology ,Cardiology and Cardiovascular Medicine - Published
- 2023
16. Development of Competency-based Online Genomic Medicine Training (COGENT)
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Susanne B Haga, Wendy K Chung, Luis A Cubano, Timothy B Curry, Philip E Empey, Geoffrey S Ginsburg, Kara Mangold, Christina Y Miyake, Siddharth K Prakash, Laura B Ramsey, Robb Rowley, Carolyn R Rohrer Vitek, Todd C Skaar, Julia Wynn, and Teri A Manolio
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Pharmacology ,Molecular Medicine ,General Medicine - Abstract
The fields of genetics and genomics have greatly expanded across medicine through the development of new technologies that have revealed genetic contributions to a wide array of traits and diseases. Thus, the development of widely available educational resources for all healthcare providers is essential to ensure the timely and appropriate utilization of genetics and genomics patient care. In 2020, the National Human Genome Research Institute released a call for new proposals to develop accessible, sustainable online education for health providers. This paper describes the efforts of the six teams awarded to reach the goal of providing genetic and genomic training modules that are broadly available for busy clinicians.
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- 2023
17. Utilizing biocatalysis and a sulfolane-mediated reductive acetal opening to access nemtabrutinib from cyrene
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Nadine Kuhl, Ben W. H. Turnbull, Yining Ji, Reed T. Larson, Michael Shevlin, Christopher K. Prier, Cheol K. Chung, Richard Desmond, Erik Guetschow, Cyndi Qixin He, Tetsuji Itoh, Jeffrey T. Kuethe, Justin A. Newman, Mikhail Reibarkh, Nelo R. Rivera, Gao Shang, Zhixun Wang, Daniel Zewge, and David A. Thaisrivongs
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Environmental Chemistry ,Pollution - Abstract
The development of a protecting group-free, 2-step synthesis of 5-amino-2-hydroxymethyltetrahydropyran 1a from biorenewable Cyrene™ is described which renders access to BTK-inhibitor nemtabrutinib (2) more efficient and sustainable.
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- 2023
18. Assessing and Validating a Model of Study Completion for a Prospective Cohort of Healthy Newborns
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Zachary H, Fusfeld, Neera K, Goyal, Neal D, Goldstein, and Esther K, Chung
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Pediatrics, Perinatology and Child Health ,General Medicine ,Pediatrics - Abstract
OBJECTIVES: To identify potentially modifiable or actionable factors related to study completion among healthy mother-infant dyads participating in prospective research. PATIENTS/METHODS: We conducted a secondary analysis of completion data from a prospective study on newborn jaundice in the first week of life at a tertiary-care hospital in Philadelphia, PA, from 2015 to 2019. Participation in the original study involved enrollment before newborn discharge and subsequent follow-up for a jaundice assessment between 2 and 6 days of life. For this study, our primary outcome was completion of all study procedures. Associations between predictor variables and the outcome were assessed using bivariate and multivariable analyses. We fit a predictive model of study completion using logistic regression and validated the model using 5-fold cross-validation. RESULTS: Of 501 mother-infant dyads enrolled in the original study, 304 completed the study. Median maternal age was 28 years and 81.8% of mothers delivered via vaginal birth. Study completion was associated with colocation of the study visit with the initial well-child visit (adjusted odds ratio [aOR], 2.99, 95% confidence interval [CI], 2.01–4.46) and provision of an alternate phone number by the participant (aOR, 1.99; 95% CI, 1.34–2.96). The cross-validated model performed similarly to our final predictive model and had an average area under the receiver operating characteristic curve of 0.67 (range, 0.59-0.72), with a sensitivity of 68% and specificity of 60%. CONCLUSIONS: Findings demonstrate the importance of communication and patient-centric approaches for recruitment and retention in newborn research. Future work should incorporate these approaches while continuing to evaluate study retention strategies.
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- 2022
19. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period
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Andrea M, Haqq, Wendy K, Chung, Hélène, Dollfus, Robert M, Haws, Gabriel Á, Martos-Moreno, Christine, Poitou, Jack A, Yanovski, Robert S, Mittleman, Guojun, Yuan, Elizabeth, Forsythe, Karine, Clément, and Jesús, Argente
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Treatment Outcome ,Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Humans ,Receptor, Melanocortin, Type 4 ,Obesity ,Bardet-Biedl Syndrome ,Alstrom Syndrome - Abstract
Impaired cilial signalling in the melanocortin-4 receptor (MC4R) pathway might contribute to obesity in patients with Bardet-Biedl syndrome and Alström syndrome, rare genetic diseases associated with hyperphagia and early-onset severe obesity. We aimed to evaluate the effect of setmelanotide on bodyweight in these patients.This multicentre, randomised, 14-week double-blind, placebo-controlled, phase 3 trial followed by a 52-week open-label period, was performed at 12 sites (hospitals, clinics, and universities) in the USA, Canada, the UK, France, and Spain. Patients aged 6 years or older were included if they had a clinical diagnosis of Bardet-Biedl syndrome or Alström syndrome and obesity (defined as BMI97th percentile for age and sex for those aged 6-15 years and ≥30 kg/mBetween Dec 10, 2018, and Nov 25, 2019, 38 patients were enrolled and randomly assigned to receive setmelanotide (n=19) or placebo (n=19; 16 with Bardet-Biedl syndrome and three with Alström syndrome in each group). In terms of the primary endpoint, 32·3% (95% CI 16·7 to 51·4; p=0·0006) of patients aged 12 years or older with Bardet-Biedl syndrome reached at least a 10% reduction in bodyweight after 52 weeks of setmelanotide. The most commonly reported treatment-emergent adverse events were skin hyperpigmentation (23 [61%] of 38) and injection site erythema (18 [48%]). Two patients had four serious adverse events (blindness, anaphylactic reaction, and suicidal ideation); none were considered related to setmelanotide treatment.Setmelanotide resulted in significant bodyweight reductions in patients with Bardet-Biedl syndrome; however, these results were inconclusive in patients with Alström syndrome. These results support the use of setmelanotide and provided the necessary evidence for approval of this drug as the first treatment for obesity in patients with Bardet-Biedl syndrome.Rhythm Pharmaceuticals.
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- 2022
20. Effect of Compressibility on the Trapped Vortex in the Gap between the Coaxial Disk and Cylinder and the Drag of Their Arrangement for Axisymmetric Sub-, Trans-, and Supersonic Flow
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S. A. Isaev, A. G. Sudakov, D. V. Nikushchenko, and K. Chung
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Fluid Flow and Transfer Processes ,Mechanical Engineering ,General Physics and Astronomy - Published
- 2022
21. Tensile properties of cement-stabilised clays and their contribution to seawall design
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Anthony L. Wong, Philip W. K. Chung, Florence L. F. Chu, Sunny T. C. So, and Louis N. Y. Wong
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Mechanics of Materials ,Soil Science ,Building and Construction ,Geotechnical Engineering and Engineering Geology - Abstract
Deep cement mixing is a typical ground improvement technique, and has recently been introduced in some large-scale reclamation projects in Hong Kong. There is a lack of internationally recognised testing standard for determining the tensile strength of cement-stabilised soil. In this study, tensile properties of cement-stabilised clays have been investigated using direct tension test and Brazilian test. The interpretation of tensile strength in Brazilian test is not straightforward due to the formation of multiple cracks during loading. As such, focus is placed on the validation of the fundamental assumption on crack initiation mechanism. A consolidated database of tensile strengths of cement-stabilised soils is compiled. A constitutive model in the finite-element program Plaxis, namely concrete model, has been studied. This model, originally aiming to simulate the behaviour of concrete and shotcrete, duly considers the cracking and the strain-softening characteristics, and is able to reasonably simulate the fundamental tensile behaviour of cement-stabilised soil. Numerical simulations have been carried out using the concrete model to assess the stability of seawall founded on cement-stabilised clay. Tensile properties are found to have an important bearing in maintaining the stability of the seawall when column-pattern stabilisation is adopted.
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- 2022
22. Design Space Exploration of K-Demo Using Novel Method for the Minimum Build Determination
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G. Jo, J. -M. Kwon, A. Cho, H. -K. Chung, and B. G. Hong
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Nuclear and High Energy Physics ,Condensed Matter Physics - Published
- 2022
23. Opportunities and challenges in heart rhythm research: Rationale and development of an electrophysiology collaboratory
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Duy T. Nguyen, Kenneth C. Bilchick, Sanjiv M. Narayan, Mina K. Chung, Kevin L. Thomas, Kenneth R. Laurita, Marmar Vaseghi, Roopinder Sandhu, Mihail G. Chelu, Prince J. Kannankeril, Douglas L. Packer, David D. McManus, Atul Verma, Matthew Singleton, Khaldoun Tarakji, Sana M. Al-Khatib, Jonathan R. Kaltman, Ravi C. Balijepalli, George F. Van Hare, Jodie L. Hurwitz, Andrea M. Russo, Fred M. Kusumoto, and Christine M. Albert
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Published
- 2022
24. Cardiac Pericytes
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Mitali Das and Mina K. Chung
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Cardiology and Cardiovascular Medicine - Published
- 2023
25. A Unified Strategy to Fluorinated Nucleoside Analogues Via an Electrophilic Manifold
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Andrew J. Neel, Ben W. H. Turnbull, William P. Carson, Tamas Benkovics, Cheol K. Chung, Heather C. Johnson, Zhuqing Liu, Feng Peng, Stephan M. Rummelt, Zhiguo Jake Song, Lushi Tan, Lu Wang, and Feng Xu
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Organic Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Published
- 2022
26. Racial and ethnic disparities in arrhythmia care: A call for action
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Kevin L. Thomas, Jalaj Garg, Poonam Velagapudi, Rakesh Gopinathannair, Mina K. Chung, Fred Kusumoto, Olujimi Ajijola, Larry R. Jackson, Mohit K. Turagam, Jose A. Joglar, Felix O. Sogade, John M. Fontaine, Andrew D. Krahn, Andrea M. Russo, Christine Albert, and Dhanunjaya R. Lakkireddy
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Published
- 2022
27. Pretargeting: A Path Forward for Radioimmunotherapy
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Sarah M, Cheal, Sebastian K, Chung, Brett A, Vaughn, Nai-Kong V, Cheung, and Steven M, Larson
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Radioisotopes ,Immunoconjugates ,Neoplasms ,Antibodies, Bispecific ,Humans ,Radiology, Nuclear Medicine and imaging ,Radioimmunotherapy ,Haptens - Abstract
Pretargeted radioimmunodiagnosis and radioimmunotherapy aim to efficiently combine antitumor antibodies and medicinal radioisotopes for high-contrast imaging and high-therapeutic-index (TI) tumor targeting, respectively. As opposed to conventional radioimmunoconjugates, pretargeted approaches separate the tumor-targeting step from the payload step, thereby amplifying tumor uptake while reducing normal-tissue exposure. Alongside contrast and TI, critical parameters include antibody immunogenicity and specificity, availability of radioisotopes, and ease of use in the clinic. Each of the steps can be optimized separately; as modular systems, they can find broad applications irrespective of tumor target, tumor type, or radioisotopes. Although this versatility presents enormous opportunity, pretargeting is complex and presents unique challenges for clinical translation and optimal use in patients. The purpose of this article is to provide a brief historical perspective on the origins and development of pretargeting strategies in nuclear medicine, emphasizing 2 protein delivery systems that have been extensively evaluated (i.e., biotin-streptavidin and hapten-bispecific monoclonal antibodies), as well as radiohaptens and radioisotopes. We also highlight recent innovations, including pretargeting with bioorthogonal chemistry and novel protein vectors (such as self-assembling and disassembling proteins and Affibody molecules). We caution the reader that this is by no means a comprehensive review of the past 3 decades of pretargeted radioimmunodiagnosis and pretargeted radioimmunotherapy. But we do aim to highlight major developmental milestones and to identify benchmarks for success with regard to TI and toxicity in preclinical models and clinically. We believe this approach will lead to the identification of key obstacles to clinical success, revive interest in the utility of radiotheranostics applications, and guide development of the next generation of pretargeted theranostics.
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- 2022
28. Challenges of variant reinterpretation: Opinions of stakeholders and need for guidelines
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Sara M. Berger, Paul S. Appelbaum, Karolynn Siegel, Julia Wynn, Akilan M. Saami, Elly Brokamp, Bridget C. O’Connor, Rizwan Hamid, Donna M. Martin, and Wendy K. Chung
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Counselors ,Surveys and Questionnaires ,Humans ,Genetic Testing ,Focus Groups ,Laboratories ,Genetics (clinical) - Abstract
The knowledge used to classify genetic variants is continually evolving, and the classification can change on the basis of newly available data. Although up-to-date variant classification is essential for clinical management, reproductive planning, and identifying at-risk family members, there is no consistent practice across laboratories or clinicians on how or under what circumstances to perform variant reinterpretation.We conducted exploratory focus groups (N = 142) and surveys (N = 1753) with stakeholders involved in the process of variant reinterpretation (laboratory directors, clinical geneticists, genetic counselors, nongenetic providers, and patients/parents) to assess opinions on key issues, including initiation of reinterpretation, variants to report, termination of the responsibility to reinterpret, and concerns about consent, cost, and liability.Stakeholders widely agreed that there should be no fixed termination point to the responsibility to reinterpret a previously reported genetic variant. There were significant concerns about liability and lack of agreement about many logistical aspects of variant reinterpretation.Our findings suggest a need to (1) develop consensus and (2) create transparency and awareness about the roles and responsibilities of parties involved in variant reinterpretation. These data provide a foundation for developing guidelines on variant reinterpretation that can aid in the development of a low-cost, scalable, and accessible approach.
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- 2022
29. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial
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Cameron R Wolfe, Kay M Tomashek, Thomas F Patterson, Carlos A Gomez, Vincent C Marconi, Mamta K Jain, Otto O Yang, Catharine I Paules, Guillermo M Ruiz Palacios, Robert Grossberg, Michelle S Harkins, Richard A Mularski, Nathaniel Erdmann, Uriel Sandkovsky, Eyad Almasri, Justino Regalado Pineda, Alexandra W Dretler, Diego Lopez de Castilla, Angela R Branche, Pauline K Park, Aneesh K Mehta, William R Short, Susan L F McLellan, Susan Kline, Nicole M Iovine, Hana M El Sahly, Sarah B Doernberg, Myoung-don Oh, Nikhil Huprikar, Elizabeth Hohmann, Colleen F Kelley, Mark Holodniy, Eu Suk Kim, Daniel A Sweeney, Robert W Finberg, Kevin A Grimes, Ryan C Maves, Emily R Ko, John J Engemann, Barbara S Taylor, Philip O Ponce, LuAnn Larson, Dante Paolo Melendez, Allan M Seibert, Nadine G Rouphael, Joslyn Strebe, Jesse L Clark, Kathleen G Julian, Alfredo Ponce de Leon, Anabela Cardoso, Stephanie de Bono, Robert L Atmar, Anuradha Ganesan, Jennifer L Ferreira, Michelle Green, Mat Makowski, Tyler Bonnett, Tatiana Beresnev, Varduhi Ghazaryan, Walla Dempsey, Seema U Nayak, Lori E Dodd, John H Beigel, Andre C Kalil, Lana Wahid, Emmanuel B. Walter, Akhila G. Belur, Grace Dreyer, Jan E. Patterson, Jason E. Bowling, Danielle O. Dixon, Angela Hewlett, Robert Odrobina, Jakrapun Pupaibool, Satish Mocherla, Suzana Lazarte, Meilani Cayabyab, Rezhan H. Hussein, Reshma R. Golamari, Kaleigh L. Krill, Sandra Rajme, Paul F. Riska, Barry S. Zingman, Gregory Mertz, Nestor Sosa, Paul A. Goepfert, Mezgebe Berhe, Emma Dishner, Mohamed Fayed, Kinsley Hubel, José Arturo Martinez-Orozco, Nora Bautista Felix, Sammy T. Elmor, Amer Ryan Bechnak, Youssef Saklawi, Jason W. Van Winkle, Diego F. Zea, Maryrose Laguio-Vila, Edward E. Walsh, Ann R. Falsey, Karen Carvajal, Robert C. Hyzy, Sinan Hanna, Norman Olbrich, Jessica J. Traenkner, Colleen S. Kraft, Pablo Tebas, Jillian T Baron, Corri Levine, Joy Nock, Joanne Billings, Hyun Kim, Marie-Carmelle Elie-Turenne, Jennifer A. Whitaker, Anne F. Luetkemeyer, Jay Dwyer, Emma Bainbridge, Pyoeng Gyun Choe, Chang Kyung Kang, Nikolaus Jilg, Valeria D Cantos, Divya R. Bhamidipati, Srinivasa Nithin Gopalsamy, Aarthi Chary, Jongtak Jung, Kyoung-Ho Song, Hong Bin Kim, Constance A. Benson, Kimberly McConnell, Jennifer P. Wang, Mireya Wessolossky, Katherine Perez, Taryn A Eubank, Catherine Berjohn, Gregory C. Utz, Patrick E.H. Jackson, Taison D. Bell, Heather M. Haughey, Abeer Moanna, Sushma Cribbs, Telisha Harrison, Christopher J. Colombo, Christina Schofield, Rhonda E. Colombo, Victor F. Tapson, Jonathan Grein, Fayyaz Sutterwala, Dilek Ince, Patricia L. Winokur, Monica Fung, Hannah Jang, David Wyles, Maria G. Frank, Ellen Sarcone, Henry Neumann, Anand Viswanathan, Sarah Hochman, Mark Mulligan, Benjamin Eckhardt, Ellie Carmody, Neera Ahuja, Kari Nadeau, David Svec, Jeffrey C. Macaraeg, Lee Morrow, Dave Quimby, Mary Bessesen, Lindsay Nicholson, Jill Adams, Princy Kumar, Allison A. Lambert, Henry Arguinchona, Radica Z. Alicic, Sho Saito, Norio Ohmagari, Ayako Mikami, David Chien Lye, Tau Hong Lee, Po Ying Chia, Lanny Hsieh, Alpesh N. Amin, Miki Watanabe, Keith A. Candiotti, Jose G. Castro, Maria A. Antor, Tida Lee, Tahaniyat Lalani, Richard M. Novak, Andrea Wendrow, Scott A. Borgetti, Sarah L. George, Daniel F. Hoft, James D. Brien, Stuart H. Cohen, George R. Thompson, Melony Chakrabarty, Faheem Guirgis, Richard T. Davey, Jocelyn Voell, Jeffrey R. Strich, David A. Lindholm, Katrin Mende, Trevor R. Wellington, Rekha R. Rapaka, Jennifer S. Husson, Andrea R. Levine, Seow Yen Tan, Humaira Shafi, Jaime M F Chien, David C. Hostler, Jordanna M. Hostler, Brian T. Shahan, David H. Adams, Anu Osinusi, Huyen Cao, Timothy H. Burgess, Julia Rozman, Kevin K. Chung, Christina Nieuwoudt, Jill A. El-Khorazaty, Heather Hill, Stephanie Pettibone, Nikki Gettinger, Theresa Engel, Teri Lewis, Jing Wang, Gregory A. Deye, Effie Nomicos, Rhonda Pikaart-Tautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Tammy Yokum, Janice Arega, and Ruth Florese
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Adult ,Male ,Pulmonary and Respiratory Medicine ,ACTT-4 Study Group ,Adolescent ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Dexamethasone ,Double-Blind Method ,Clinical Research ,Humans ,Lung ,Sulfonamides ,Other Medical and Health Sciences ,SARS-CoV-2 ,Prevention ,Evaluation of treatments and therapeutic interventions ,Middle Aged ,COVID-19 Drug Treatment ,Oxygen ,Good Health and Well Being ,Treatment Outcome ,Purines ,6.1 Pharmaceuticals ,Public Health and Health Services ,Azetidines ,Pyrazoles ,Female - Abstract
BackgroundBaricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.MethodsIn this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168.FindingsBetween Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012).InterpretationIn hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered.FundingNational Institute of Allergy and Infectious Diseases.
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- 2022
30. Rare pathogenic variants in WNK3 cause X-linked intellectual disability
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Sébastien Küry, Jinwei Zhang, Thomas Besnard, Alfonso Caro-Llopis, Xue Zeng, Stephanie M. Robert, Sunday S. Josiah, Emre Kiziltug, Anne-Sophie Denommé-Pichon, Benjamin Cogné, Adam J. Kundishora, Le T. Hao, Hong Li, Roger E. Stevenson, Raymond J. Louie, Wallid Deb, Erin Torti, Virginie Vignard, Kirsty McWalter, F. Lucy Raymond, Farrah Rajabi, Emmanuelle Ranza, Detelina Grozeva, Stephanie A. Coury, Xavier Blanc, Elise Brischoux-Boucher, Boris Keren, Katrin Õunap, Karit Reinson, Pilvi Ilves, Ingrid M. Wentzensen, Eileen E. Barr, Solveig Heide Guihard, Perrine Charles, Eleanor G. Seaby, Kristin G. Monaghan, Marlène Rio, Yolande van Bever, Marjon van Slegtenhorst, Wendy K. Chung, Ashley Wilson, Delphine Quinquis, Flora Bréhéret, Kyle Retterer, Pierre Lindenbaum, Emmanuel Scalais, Lindsay Rhodes, Katrien Stouffs, Elaine M. Pereira, Sara M. Berger, Sarah S. Milla, Ankita B. Jaykumar, Melanie H. Cobb, Shreyas Panchagnula, Phan Q. Duy, Marie Vincent, Sandra Mercier, Brigitte Gilbert-Dussardier, Xavier Le Guillou, Séverine Audebert-Bellanger, Sylvie Odent, Sébastien Schmitt, Pierre Boisseau, Dominique Bonneau, Annick Toutain, Estelle Colin, Laurent Pasquier, Richard Redon, Arjan Bouman, Jill. A. Rosenfeld, Michael J. Friez, Helena Pérez-Peña, Syed Raza Akhtar Rizvi, Shozeb Haider, Stylianos E. Antonarakis, Charles E. Schwartz, Francisco Martínez, Stéphane Bézieau, Kristopher T. Kahle, Bertrand Isidor, Clinical Genetics, Clinical sciences, Medical Genetics, Reproduction and Genetics, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), University of Exeter, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Greenwood Genetic Center, GeneDx [Gaithersburg, MD, USA], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Genève = University of Geneva (UNIGE), Yale School of Medicine [New Haven, Connecticut] (YSM), This work was granted by the French network of University Hospitals HUGO ('Hôpitaux Universitaires du Grand Ouest'), the French Ministry of Health, and and the Health Regional Agencies from Poitou-Charentes (represented by Frédérique Allaire), Bretagne, Pays de la Loire, and Centre-Val de Loire (HUGODIMS, 2013, RC14_0107). W.K.C. was supported by grants from Simons Foundation Autism Research Initiative, United
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MESH: Symporters ,Exome sequencing ,Male ,KCC2 ,Mutation, Missense ,MESH: Catalytic Domain ,Neurodevelopmental disease ,Protein Serine-Threonine Kinases ,X-linked intellectual disability ,MESH: Brain ,WNK3 ,SDG 3 - Good Health and Well-being ,Loss of Function Mutation ,Catalytic Domain ,MESH: Mental Retardation, X-Linked ,Humans ,Phosphorylation ,MESH: Hemizygote ,Genetics (clinical) ,Hemizygote ,MESH: Mutation, Missense ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,MESH: Phosphorylation ,Symporters ,Brain ,MESH: Loss of Function Mutation ,MESH: Protein Serine-Threonine Kinases ,MESH: Male ,Mental Retardation, X-Linked ,Maternal Inheritance ,MESH: Maternal Inheritance - Abstract
PURPOSE: WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown. METHOD: We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID). RESULTS: We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.Pro204Arg, p.Leu300Ser, p.Glu607Val) in WNK3 in 14 male individuals from 6 unrelated families. Affected individuals had identifier with variable presence of epilepsy and structural brain defects. WNK3 variants cosegregated with the disease in 3 different families with multiple affected individuals. This included 1 large family previously diagnosed with X-linked Prieto syndrome. WNK3 pathogenic missense variants localize to the catalytic domain and impede the inhibitory phosphorylation of the neuronal-specific chloride cotransporter KCC2 at threonine 1007, a site critically regulated during the development of synaptic inhibition. CONCLUSION: Pathogenic WNK3 variants cause a rare form of human X-linked identifier with variable epilepsy and structural brain abnormalities and implicate impaired phospho-regulation of KCC2 as a pathogenic mechanism.
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- 2022
31. Dominantly acting KIF5B variants with pleiotropic cellular consequences cause variable clinical phenotypes
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Elisabetta Flex, Shahad Albadri, Francesca Clementina Radio, Serena Cecchetti, Antonella Lauri, Manuela Priolo, Marta Kissopoulos, Giovanna Carpentieri, Giulia Fasano, Martina Venditti, Valentina Magliocca, Emanuele Bellacchio, Carrie L Welch, Paolo C Colombo, Stephanie M Kochav, Richard Chang, Rebekah Barrick, Marina Trivisano, Alessia Micalizzi, Rossella Borghi, Elena Messina, Cecilia Mancini, Simone Pizzi, Flavia De Santis, Marion Rosello, Nicola Specchio, Claudia Compagnucci, Kirsty McWalter, Wendy K Chung, Filippo Del Bene, and Marco Tartaglia
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Genetics ,General Medicine ,Molecular Biology ,Genetics (clinical) - Abstract
Kinesins are motor proteins involved in microtubule (MT)-mediated intracellular transport. They contribute to key cellular processes, including intracellular trafficking, organelle dynamics and cell division. Pathogenic variants in kinesin-encoding genes underlie several human diseases characterized by an extremely variable clinical phenotype, ranging from isolated neurodevelopmental/neurodegenerative disorders to syndromic phenotypes belonging to a family of conditions collectively termed as ‘ciliopathies.’ Among kinesins, kinesin-1 is the most abundant MT motor for transport of cargoes towards the plus end of MTs. Three kinesin-1 heavy chain isoforms exist in mammals. Different from KIF5A and KIF5C, which are specifically expressed in neurons and established to cause neurological diseases when mutated, KIF5B is an ubiquitous protein. Three de novo missense KIF5B variants were recently described in four subjects with a syndromic skeletal disorder characterized by kyphomelic dysplasia, hypotonia and DD/ID. Here, we report three dominantly acting KIF5B variants (p.Asn255del, p.Leu498Pro and p.Leu537Pro) resulting in a clinically wide phenotypic spectrum, ranging from dilated cardiomyopathy with adult-onset ophthalmoplegia and progressive skeletal myopathy to a neurodevelopmental condition characterized by severe hypotonia with or without seizures. In vitro and in vivo analyses provide evidence that the identified disease-associated KIF5B variants disrupt lysosomal, autophagosome and mitochondrial organization, and impact cilium biogenesis. All variants, and one of the previously reported missense changes, were shown to affect multiple developmental processes in zebrafish. These findings document pleiotropic consequences of aberrant KIF5B function on development and cell homeostasis, and expand the phenotypic spectrum resulting from altered kinesin-mediated processes.
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- 2022
32. Expanding the phenotypic spectrum of <scp> COLEC10 ‐Related 3MC </scp> syndrome: A glimpse into <scp> COLEC10 ‐Related 3MC </scp> syndrome in the Ashkenazi Jewish population
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Rachel Rabin, Yoel Hirsch, Wendy K. Chung, Josef Ekstein, Ephrat Levy‐Lahad, Shachar Zuckerman, Hagar Mor‐Shaked, Vardiella Meiner, Kevin T. Booth, and John Pappas
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Genetics ,Genetics (clinical) - Published
- 2022
33. A Case Series on Hypertrophic Cardiomyopathy with Midventricular Obstruction and Apical Aneurysm
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Philippe Ryan K. Chung, Emma Y. Gaspar-Trinidad, Tamara Louise J. Razon-Cuenza, and Lucky R. Cuenza
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General Medicine - Abstract
Midventricular obstruction (MVO) is a rare phenotypic subvariant of hypertrophic cardiomyopathy (HCM). It occurs in 1-10% of patients and due to its rarity, its clinical progression and natural history has not yet been extensively studied. However, the available data has shown it to have worse clinical outcomes and prognosis. While reports on hypertrophic cardiomyopathy has been published in the Philippines, there has been no data on this particular variant in the local literature. We identified 3 cases of hypertrophic cardiomyopathy with midventricular obstruction. 2 cases were initially managed as a case of ischemic heart disease who were ruled out after undergoing cardiac magnetic resonance. One case was initially admitted due to a stroke however, an incidental finding on 2D Echo noted the presence of HCM. He also underwent cardiac magnetic resonance which revealed the full extent of his disease. All 3 patients were also found to have apical aneurysms due to ischemia from the pressure coming from the obstruction. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disease but its subvariants are rare and difficult to diagnose. Apical aneurysms are also often missed on 2D Echo. However, cardiac magnetic resonance provides increased detection of the disease with better detailing of the extent and severity. It could also provide information regarding prognostication with regards to arrhythmias and sudden cardiac death. More data however is needed so new avenues for research are open on its application.
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- 2022
34. High sweet foods and low life satisfaction can act as risk factors for acute coronary syndrome through synergistic interaction
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J So, K Chung, J Seo, B Kim, H Chun, S Han, and I Chung
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Epidemiology ,Cardiology and Cardiovascular Medicine - Abstract
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health & Welfare, Republic of Korea. Background Dietary and psychological factors contribute to development of coronary artery disease (CAD). However, contributing components of these lifestyle factors may vary depending on ethnic and cultural background, and secondary prevention programs dealing with these factors in specific population are not well established. Aims We aimed to analyze dietary and psychological characteristics and independent risk factors in Korean patients with acute coronary syndrome (ACS). Methods Ninety-two patients with ACS (29 acute myocardial infarction, 63 unstable angina) and 69 controls were subject to analysis of lifestyle factors focused on dietary and psychological status. Dietary intake was assessed by a food frequency questionnaire (FFQ) using the KoGES software and Can-Pro 4.0. Psychological depression and perceived stress were measured with the Patient Health Questionnaire 9 (PHQ-9) and the Korean version of Perceived Stress Scale (K-PSS), respectively. In additions, eight domains of life satisfaction was assessed with the Domain Satisfaction Questionnaire (DSQ). Results ACS group had more men (79% vs 61%) and was older (53 yr vs. 49 yr), less physically active, and higher waist circumference and BMI than controls. Dietary analyses showed that ACS group had more intakes of sweets and fish/seafood in both men and women compared to controls. Psychological analyses showed that ACS group had higher depressive symptom (5.4 vs. 4.2, p Conclusions High sweet food intake and low life satisfaction can act as independent risk factors for ACS through interactive mechanism. These data also highlight the importance of the role of positive psychological factor in cardiovascular health.
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- 2023
35. 2023 <scp>HRS</scp> / <scp>APHRS</scp> / <scp>LAHRS</scp> guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure
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Mina K. Chung, Kristen K. Patton, Chu‐Pak Lau, Alexander R. J. Dal Forno, Sana M. Al‐Khatib, Vanita Arora, Ulrika Maria Birgersdotter‐Green, Yong‐Mei Cha, Eugene H. Chung, Edmond M. Cronin, Anne B. Curtis, Iwona Cygankiewicz, Gopi Dandamudi, Anne M. Dubin, Douglas P. Ensch, Taya V. Glotzer, Michael R. Gold, Zachary D. Goldberger, Rakesh Gopinathannair, Eiran Z. Gorodeski, Alejandra Gutierrez, Juan C. Guzman, Weijian Huang, Peter B. Imrey, Julia H. Indik, Saima Karim, Peter P. Karpawich, Yaariv Khaykin, Erich L. Kiehl, Jordana Kron, Valentina Kutyifa, Mark S. Link, Joseph E. Marine, Wilfried Mullens, Seung‐Jung Park, Ratika Parkash, Manuel F. Patete, Rajeev Kumar Pathak, Carlos A. Perona, John Rickard, Mark H. Schoenfeld, Swee‐Chong Seow, Win‐Kuang Shen, Morio Shoda, Jagmeet P. Singh, David J. Slotwiner, Arun Raghav M. Sridhar, Uma N. Srivatsa, Eric C. Stecker, Tanyanan Tanawuttiwat, W. H. Wilson Tang, Carlos Andres Tapias, Cynthia M. Tracy, Gaurav A. Upadhyay, Niraj Varma, Kevin Vernooy, Pugazhendhi Vijayaraman, Sarah Ann Worsnick, Wojciech Zareba, and Emily P. Zeitler
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Cardiology and Cardiovascular Medicine - Published
- 2023
36. A diminutive snake species can maintain regional heterothermy in both homogenous and heterogenous thermal environments
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Christian L. Cox, Albert K. Chung, Myles E. Davoll, Steph A. DeHart, Samuel T. Gerardi, Tony K. Ly, Kyle Moxley, Preston T. Nipper, Delaney R. Novak, Phillip F. Reeves, Becky J. Williams, and Michael L. Logan
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Physiology ,Insect Science ,Animal Science and Zoology ,Aquatic Science ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
Regional heterothermy is a pattern whereby different body regions are maintained at different temperatures, often to prioritize function of certain body parts over others, or to maximize function of organs and tissues that vary in thermal sensitivity. Regional heterothermy is relatively well understood in endotherms, where physiological mechanisms maintain heterogeneity. However, less is known about regional heterothermy in ectotherms, where behavioral mechanisms are more important for generating thermal variation. In particular, whether small and elongate ectotherms with high surface area to volume ratios such as diminutive snakes can maintain regional heterothermy, despite rapid thermal equilibration, is not yet known. We measured regional variation in body temperature and tested whether environmental heterogeneity is used to generate regional heterothermy in the ring-necked snake (Diadophis punctatus) using both field and laboratory studies. We found that ring-necked snakes have robust regional heterothermy in a variety of contexts, despite their small body size and elongate body shape. Temperature variation along the length of their bodies was not detectable when measured externally. However, snakes had higher mouth than cloacal temperatures both in the field and in laboratory thermal gradients. Further, this regional heterothermy was maintained even in ambient laboratory conditions, where the thermal environment was relatively homogeneous. Our results indicate that regional heterothermy in ring-necked snakes is not solely driven by environmental variation, but is instead linked to physiological or morphological mechanisms that maintain regional variation in body temperature irrespective of environmental context.
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- 2023
37. Contribution of Previously Unrecognized RNA Splice-Altering Variants to Congenital Heart Disease
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Min Young Jang, Parth N. Patel, Alexandre C. Pereira, Jon A.L. Willcox, Alireza Haghighi, Angela C. Tai, Kaoru Ito, Sarah U. Morton, Joshua M. Gorham, David M. McKean, Steven R. DePalma, Daniel Bernstein, Martina Brueckner, Wendy K. Chung, Alessandro Giardini, Elizabeth Goldmuntz, Jonathan R. Kaltman, Richard Kim, Jane W. Newburger, Yufeng Shen, Deepak Srivastava, Martin Tristani-Firouzi, Bruce D. Gelb, George A. Porter, Christine E. Seidman, and Jonathan G. Seidman
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General Medicine - Abstract
BACKGROUND: Known genetic causes of congenital heart disease (CHD) explain METHODS: We tested de novo variants from trio studies of 2649 CHD probands and their parents, as well as rare (allele frequency, − 6 ) variants from 4472 CHD probands in the Pediatric Cardiac Genetics Consortium through a combined computational and in vitro approach. RESULTS: We identified 53 de novo and 74 rare variants in CHD cases that alter splicing and thus are loss of function. Of these, 77 variants are in known dominant, recessive, and candidate CHD genes, including KMT2D and RBFOX2 . In 1 case, we confirmed the variant’s predicted impact on RNA splicing in RNA transcripts from the proband’s cardiac tissue. Two probands were found to have 2 loss-of-function variants for recessive CHD genes HECTD1 and DYNC2H1 . In addition, SpliceAI—a predictive algorithm for altered RNA splicing—has a positive predictive value of ≈93% in our cohort. CONCLUSIONS: Through assessment of RNA splicing, we identified a new loss-of-function variant within a CHD gene in 78 probands, of whom 69 (1.5%; n=4472) did not have a previously established genetic explanation for CHD. Identification of splice-altering variants improves diagnostic classification and genetic diagnoses for CHD. REGISTRATION: URL: https://clinicaltrials.gov ; Unique identifier: NCT01196182.
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- 2023
38. The relationship between liver function and neurophysiological factors in depressed individuals: a cross-sectional study using an integrated 'East meets West' medicine approach
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Jiajia Ye, Yunying Yu, Raymond C. K. Chung, Xiaowen Lian, Xin Wang, Wai Ming Cheung, and Hector W. H. Tsang
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Psychiatry and Mental health - Abstract
Introduction:Depression is a common mental disorder worldwide. The pathology of depression may involve the dysregulation of neurotransmitters and immunity and produce genetic and environmental effects. Traditional Chinese Medicine (TCM) has been practiced for several thousand years and has a different understanding of depression compared to Western medicine. However, this approach has not been widely accepted by scientific communities as TCM mainly focuses on clinical practice.Methods:In this study, we conducted a cross-sectional study among 100 participants in a rehabilitation hospital to analyze the plausible pathways linking TCM-based liver function and depression, which we hypothesized in a prior theoretical review.Results:A significant relationship between adrenocorticotropic hormone and TCM-based liver function was found (r = 0.211, p = 0.041). Cortisol was significantly associated with norepinephrine (r = 0.243, p = 0.015) and adrenocorticotropic hormone (r = 0.302, p r = 0.272, p p = 0.690).Discussion:These results suggest that TCM-based liver function can be interpreted using the hypothalamic-pituitary-adrenal axis. This is a pioneering study to examine the mechanisms of depression in relation to liver function by integrating Eastern and Western medical approaches. The findings of this study are valuable for a deeper understanding of depression and public education.
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- 2023
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39. Surviving sepsis after burn campaign
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David G. Greenhalgh, David M. Hill, David M. Burmeister, Eduardo I. Gus, Heather Cleland, Alex Padiglione, Dane Holden, Fredrik Huss, Michelle S. Chew, John C. Kubasiak, Aidan Burrell, William Manzanares, María Chacón Gómez, Yuya Yoshimura, Folke Sjöberg, Wei-Guo Xie, Paula Egipto, Athina Lavrentieva, Arpana Jain, Ariel Miranda-Altamirano, Ed Raby, Ignacio Aramendi, Soman Sen, Kevin K. Chung, Renata Jennifer Quintana Alvarez, Chunmao Han, Asako Matsushima, Moustafa Elmasry, Yan Liu, Carlos Segovia Donoso, Alberto Bolgiani, Laura S. Johnson, Luiz Philipe Molina Vana, Rosario Valdez Duval de Romero, Nikki Allorto, Gerald Abesamis, Virginia Nuñez Luna, Alfredo Gragnani, Carolina Bonilla Gonzàles, Hugo Basilico, Fiona Wood, James Jeng, Andrew Li, Mervyn Singer, Gaoxing Luo, Tina Palmieri, Steven Kahn, Victor Joe, and Robert Cartotto
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Emergency Medicine ,Surgery ,General Medicine ,Critical Care and Intensive Care Medicine - Published
- 2023
40. 2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure
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Mina K. Chung, Kristen K. Patton, Chu-Pak Lau, Alexander R.J. Dal Forno, Sana M. Al-Khatib, Vanita Arora, Ulrika Maria Birgersdotter-Green, Yong-Mei Cha, Eugene H. Chung, Edmond M. Cronin, Anne B. Curtis, Iwona Cygankiewicz, Gopi Dandamudi, Anne M. Dubin, Douglas P. Ensch, Taya V. Glotzer, Michael R. Gold, Zachary D. Goldberger, Rakesh Gopinathannair, Eiran Z. Gorodeski, Alejandra Gutierrez, Juan C. Guzman, Weijian Huang, Peter B. Imrey, Julia H. Indik, Saima Karim, Peter P. Karpawich, Yaariv Khaykin, Erich L. Kiehl, Jordana Kron, Valentina Kutyifa, Mark S. Link, Joseph E. Marine, Wilfried Mullens, Seung-Jung Park, Ratika Parkash, Manuel F. Patete, Rajeev Kumar Pathak, Carlos A. Perona, John Rickard, Mark H. Schoenfeld, Swee-Chong Seow, Win-Kuang Shen, Morio Shoda, Jagmeet P. Singh, David J. Slotwiner, Arun Raghav M. Sridhar, Uma N. Srivatsa, Eric C. Stecker, Tanyanan Tanawuttiwat, W.H. Wilson Tang, Carlos Andres Tapias, Cynthia M. Tracy, Gaurav A. Upadhyay, Niraj Varma, Kevin Vernooy, Pugazhendhi Vijayaraman, Sarah Ann Worsnick, Wojciech Zareba, and Emily P. Zeitler
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.
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- 2023
41. Identifying phenotypic expansions for congenital diaphragmatic hernia plus ( <scp>CDH</scp> +) using <scp>DECIPHER</scp> data
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Amy Hardcastle, Aliska M. Berry, Ian M. Campbell, Xiaonan Zhao, Pengfei Liu, Amanda E. Gerard, Jill A. Rosenfeld, Saumya D. Sisoudiya, Andres Hernandez‐Garcia, Sara Loddo, Silvia Di Tommaso, Antonio Novelli, Maria L. Dentici, Rossella Capolino, Maria C. Digilio, Ludovico Graziani, Cecilie F. Rustad, Katherine Neas, Giovanni B. Ferrero, Alfredo Brusco, Eleonora Di Gregorio, Diana Wellesley, Claire Beneteau, Madeleine Joubert, Kris Van Den Bogaert, Anneleen Boogaerts, Dominic J. McMullan, John Dean, Maria G. Giuffrida, Laura Bernardini, Vinod Varghese, Nora L. Shannon, Rachel E. Harrison, Wayne W. K. Lam, Shane McKee, Peter D. Turnpenny, Trevor Cole, Jenny Morton, Jacqueline Eason, Marilyn C. Jones, Rebecca Hall, Michael Wright, Karen Horridge, Chad A. Shaw, Wendy K. Chung, and Daryl A. Scott
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DNA Copy Number Variations ,Diaphragm ,USP9X ,CREBBP ,DECIPHER database ,SMARCA4 ,UBA2 ,congenital diaphragmatic hernia ,Mice ,Genetics ,Animals ,Hernias, Diaphragmatic, Congenital ,Genetics (clinical) - Abstract
Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are cataloged in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, UBA2, and USP9X. The role of these genes in diaphragm development was supported by their expression in the developing mouse diaphragm, their similarity to known CDH genes using data from a previously published and validated machine learning algorithm, and/or the presence of CDH in other individuals with their associated genetic disorders. Our results demonstrate how data from DECIPHER, and other public databases, can be used to identify new phenotypic expansions and suggest that CREBBP, SMARCA4, UBA2, and USP9X play a role in diaphragm development.
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- 2022
42. Reproduction and genetic causal attribution of epilepsy
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Ruth Ottman, John B. Wetmore, Itzel A. Camarillo, Sophia Rodriguez, Sylwia Misiewicz, Karolynn Siegel, Wendy K. Chung, Jo C. Phelan, Chen‐Shiun Leu, Lawrence H. Yang, and Hyunmi Choi
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Adult ,Epilepsy ,Social Perception ,Neurology ,Reproduction ,Surveys and Questionnaires ,Humans ,Genetic Testing ,Neurology (clinical) ,Child - Abstract
This study addresses the contribution of genetics-related concerns to reduced childbearing among people with epilepsy.Surveys were completed by 606 adult patients with epilepsy of unknown cause at our medical center. Poisson regression analysis was used to assess the relations of number of offspring to: (1) genetic attribution (GA: participants' belief that genetics was a cause of their epilepsy), assessed via a novel scale developed from four survey items (Cronbach's alpha = .89), (2) participants' estimates of epilepsy risk in the child of a parent with epilepsy (1%, 5%-10%, 25%, and 50%-100%), and (3) participants' reports of the influence on their reproductive decisions of "the chance of having a child with epilepsy" (none/weak/moderate, strong/very strong). Analyses were adjusted for age, education, race/ethnicity, religion, type of epilepsy (generalized, focal, and both/unclassifiable), and age at epilepsy onset (10, 10-19, and ≥20 years).Among participants 18-45 years of age, the number of offspring decreased significantly with increasing GA (highest vs lowest GA quartile rate ratio [RR] = .5, p .001), and increasing estimated epilepsy risk in offspring (with 5%-10% as referent because it is closest to the true value, RR for 25%: .7, p = .05; RR for 50%-100%: .6, p = .03). Number of offspring was not related to the reported influence of "the chance of having a child with epilepsy" on reproductive decisions. Among participants45 years of age, the number of offspring did not differ significantly according to GA quartile or estimated offspring epilepsy risk. However, those reporting a strong/very strong influence on their reproductive decisions of "the chance of having a child with epilepsy" had only 60% as many offspring as others.These findings suggest that overestimating the risk of epilepsy in offspring can have important consequences for people with epilepsy. Patient and provider education about recurrence risks and genetic testing options to clarify risks are critical, given their potential influence on reproductive decisions.
- Published
- 2022
43. A Diastereoselective Method for the Construction of syn-2′-Deoxy-2′-fluoronucleosides
- Author
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Michael T. Pirnot, Edna Mao, Yu-hong Lam, John Limanto, Ryan D. Cohen, Cheol K. Chung, and Eric M. Phillips
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Organic Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Published
- 2022
44. The Challenge of Genetic Variants of Uncertain Clinical Significance
- Author
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Wylie Burke, Erik Parens, Wendy K. Chung, Sara M. Berger, and Paul S. Appelbaum
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Uncertainty ,Internal Medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,General Medicine ,Probability - Abstract
Genomic tests expand diagnostic and screening opportunities but also identify genetic variants of uncertain clinical significance (VUSs). Only a minority of VUSs are likely to prove pathogenic when later reassessed, but resolution of the uncertainty is rarely timely. That uncertainty adds complexity to clinical decision making and can result in harms and costs to patients and the health care system, including the time-consuming analysis required to interpret a VUS and the potential for unnecessary treatment and adverse psychological effects. Current efforts to improve variant interpretation will help reduce the scope of the problem, but the high prevalence of rare and novel variants in the human genome points to VUSs as an ongoing challenge. Additional strategies can help mitigate the potential harms of VUSs, including testing protocols that limit identification or reporting of VUSs, subclassification of VUSs according to the likelihood of pathogenicity, routine family-based evaluation of variants, and enhanced counseling efforts. All involve tradeoffs, and the appropriate balance of measures is likely to vary for different test uses and clinical settings. Cross-specialty deliberation and public input could contribute to systematic and broadly supported policies for managing VUSs.
- Published
- 2022
45. Clinical and genetic characterization of <scp> CACNA1A </scp> ‐related disease
- Author
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Amy R, Lipman, Xiao, Fan, Yufeng, Shen, and Wendy K, Chung
- Subjects
Autism Spectrum Disorder ,Genetics ,Humans ,Ataxia ,Calcium Channels ,Nystagmus, Pathologic ,Genetics (clinical) - Abstract
Pathogenic variants in the CACNA1A gene have been associated with episodic ataxia type 2, familial hemiplegic migraine, and spinocerebellar ataxia 6. With increasing use of clinical genetic testing, associations have expanded to include developmental delay, epilepsy, paroxysmal dystonia, and neuropsychiatric disorders. We report 47 individuals with 33 unique likely pathogenic or pathogenic CACNA1A variants. A machine learning method, funNCion, was used to predict loss-of-function (LoF)/gain-of-function (GoF) impact of genetic variants, and a heuristic severity score was designed to analyze genotype/phenotype correlations. Commonly reported phenotypes include developmental delay/intellectual disability (96%), hemiplegic migraines (36%), episodic ataxia type 2 (32%), epilepsy (55%), autism spectrum disorder (23%), and paroxysmal tonic upward gaze (36%). Severity score was significantly higher for predicted GoF variants, variants in the S5/S6 helices, and the recurrent p.Val1392Met variant. Seizures/status epilepticus were correlated with GoF and were more frequent in those with the p.Val1392Met variant. Our findings demonstrate a breadth of disease severity in CACNA1A-related disease and suggest that the clinical phenotypic heterogeneity likely reflects diverse molecular phenotypes. A better understanding of the natural history of CACNA1A-related disease and genotype/phenotype correlations will help inform prognosis and prepare for future clinical trials.
- Published
- 2022
46. Newborn screening for neurodevelopmental diseases: Are we there yet?
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Wendy K. Chung, Jonathan S. Berg, Jeffrey R. Botkin, Steven E. Brenner, Jeffrey P. Brosco, Kyle B. Brothers, Robert J. Currier, Amy Gaviglio, Walter E. Kowtoniuk, Colleen Olson, Michele Lloyd‐Puryear, Annamarie Saarinen, Mustafa Sahin, Yufeng Shen, Elliott H. Sherr, Michael S. Watson, and Zhanzhi Hu
- Subjects
Pediatric ,Genetics & Heredity ,Parents ,Pediatric Research Initiative ,Intellectual and Developmental Disabilities (IDD) ,Prevention ,Clinical Sciences ,Infant, Newborn ,Infant ,Pilot Projects ,Reproductive health and childbirth ,Perinatal Period - Conditions Originating in Perinatal Period ,Newborn ,Brain Disorders ,Good Health and Well Being ,Neonatal Screening ,Clinical Research ,Neurodevelopmental Disorders ,Infant Mortality ,Genetics ,Humans ,Genetics (clinical) - Abstract
In the US, newborn screening (NBS) is a unique health program that supports health equity and screens virtually every baby after birth, and has brought timely treatments to babies since the 1960's. With the decreasing cost of sequencing and the improving methods to interpret genetic data, there is an opportunity to add DNA sequencing as a screening method to facilitate the identification of babies with treatable conditions that cannot be identified in any other scalable way, including highly penetrant genetic neurodevelopmental disorders (NDD). However, the lack of effective dietary or drug-based treatments has made it nearly impossible to consider NDDs in the current NBS framework, yet it is anticipated that any treatment will be maximally effective if started early. Hence there is a critical need for large scale pilot studies to assess if and how NDDs can be effectively screened at birth, if parents desire that information, and what impact early diagnosis may have. Here we attempt to provide an overview of the recent advances in NDD treatments, explore the possible framework of setting up a pilot study to genetically screen for NDDs, highlight key technical, practical, and ethical considerations and challenges, and examine the policy and health system implications.
- Published
- 2022
47. Is there a way to reduce the inequity in variant interpretation on the basis of ancestry?
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Paul S, Appelbaum, Wylie, Burke, Erik, Parens, David A, Zeevi, Laura, Arbour, Nanibaa' A, Garrison, Vence L, Bonham, and Wendy K, Chung
- Subjects
Canada ,Ethnicity ,Commentary ,Genetics ,Humans ,Family ,Genetic Testing ,Genomics ,Genetics (clinical) - Abstract
The underrepresentation of non-European ancestry groups in current genomic databases complicates interpretation of their genetic test results, yielding a much higher prevalence of variants of uncertain significance (VUSs). Such VUS findings can frustrate the goals of genetic testing, create anxiety in patients, and lead to unnecessary medical interventions. Approaches to addressing underrepresentation of people with genetic ancestries other than European are being undertaken by broad-based recruitment efforts. However, some underrepresented groups have concerns that might preclude participation in such efforts. We describe here two initiatives aimed at meeting the needs of underrepresented ancestry groups in genomic datasets. The two communities, the Sephardi Jewish community in New York and First Peoples of Canada, have very different concerns about contributing to genomic research and datasets. Sephardi concerns focus on the possible negative effects of genetic findings on the marriage prospects of family members. Canadian Indigenous populations seek control over the research uses to which their genetic data would be put. Both cases involve targeted efforts to respond to the groups’ concerns; these efforts include governance models aimed at ensuring that the data are used primarily to inform clinical test analyses and at achieving successful engagement and participation of community members. We suggest that these initiatives could provide models for other ancestral groups seeking to improve the accuracy and utility of clinical genetic testing while respecting the underlying preferences and values of community members with regard to the use of their genetic data.
- Published
- 2022
48. Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders
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Lauren O'Grady, Samantha A. Schrier Vergano, Trevor L. Hoffman, Dean Sarco, Sara Cherny, Emily Bryant, Laura Schultz‐Rogers, Wendy K. Chung, Stephanie Sacharow, Ladonna L. Immken, Susan Holder, Rebecca R. Blackwell, Catherine Buchanan, Roman Yusupov, François Lecoquierre, Anne‐Marie Guerrot, Lance Rodan, Bert B. A. de Vries, Erik Jan Kamsteeg, Fernando Santos Simarro, Maria Palomares‐Bralo, Natasha Brown, Lynn Pais, Alejandro Ferrer, Eric W. Klee, Dusica Babovic‐Vuksanovic, Lindsay Rhodes, Richard Person, Amber Begtrup, Jennifer Keller‐Ramey, Teresa Santiago‐Sim, Rhonda E. Schnur, David A. Sweetser, and Nina B. Gold
- Subjects
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Genetics ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,Genetics (clinical) - Abstract
Contains fulltext : 282684.pdf (Publisher’s version ) (Closed access) The pre-mRNA-processing factor 8, encoded by PRPF8, is a scaffolding component of a spliceosome complex involved in the removal of introns from mRNA precursors. Previously, heterozygous pathogenic variants in PRPF8 have been associated with autosomal dominant retinitis pigmentosa. More recently, PRPF8 was suggested as a candidate gene for autism spectrum disorder due to the enrichment of sequence variants in this gene in individuals with neurodevelopmental disorders. We report 14 individuals with various forms of neurodevelopmental conditions, found to have heterozygous, predominantly de novo, missense, and loss-of-function variants in PRPF8. These individuals have clinical features that may represent a new neurodevelopmental syndrome.
- Published
- 2022
49. Hemoperfusion with Seraph 100 Microbind Affinity Blood Filter Unlikely to Require Increased Antibiotic Dosing: A Simulations Study Using a Pharmacokinetic/Pharmacodynamic Approach
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Daniel J. Selig, Tyler Reed, Kevin K. Chung, Adrian T. Kress, Ian J. Stewart, and Jesse P. DeLuca
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Nephrology ,Hematology ,General Medicine - Abstract
Introduction: The Seraph® 100 Microbind® Affinity Blood Filter (Seraph 100) is a hemoperfusion device that can remove pathogens from central circulation. However, the effect of Seraph 100 on achieving pharmacodynamic (PD) targets is not well described. We sought to determine the impact of Seraph 100 on ability to achieve PD targets for commonly used antibiotics. Methods: Estimates of Seraph 100 antibiotic clearance were obtained via literature. For vancomycin and gentamicin, published pharmacokinetic models were used to explore the effect of Seraph 100 on ability to achieve probability of target attainment (PTA). For meropenem and imipenem, the reported effect of continuous kidney replacement therapy (CKRT) on achieving PTA was used to extrapolate decisions for Seraph 100. Results: Seraph 100 antibiotic clearance is likely less than 0.5 L/h for most antibiotics. Theoretical Seraph 100 clearance up to 0.5 L/h and 2 L/h had a negligible effect on vancomycin PTA in virtual patients with creatinine clearance (CrCl) = 14 mL/min and CrCl >14 mL/min, respectively. Theoretical Seraph 100 clearance up to 0.5 L/h and 2 L/h had a negligible effect on gentamicin PTA in virtual patients with CrCl = 120 mL/min and CrCl Conclusion: Seraph 100 clearance of vancomycin, gentamicin, meropenem, and imipenem is likely clinically insignificant. There is insufficient evidence to recommend increased doses. For aminoglycosides, we recommend extended interval dosing and initiating Seraph 100 at least 30 min to 1 h after completion of infusion to avoid the possibility of interference with maximum concentrations.
- Published
- 2022
50. The ENHANCE-AF clinical trial to evaluate an atrial fibrillation shared decision-making pathway: Rationale and study design
- Author
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Tina Baykaner, Krishna Pundi, Bryant Lin, Ying Lu, Katie DeSutter, Karma Lhamo, Gotzone Garay, Julio C. Nunes, Daniel P. Morin, Samuel F. Sears, Mina K. Chung, Michael K. Paasche-Orlow, Lee M. Sanders, Thomas Jared Bunch, Mellanie True Hills, Kenneth W. Mahaffey, Randall S. Stafford, and Paul J. Wang
- Subjects
Stroke ,Atrial Fibrillation ,Anticoagulants ,Humans ,Patient Participation ,Cardiology and Cardiovascular Medicine ,Decision Making, Shared - Abstract
Shared decision making (SDM) may result in treatment plans that best reflect the goals and wishes of patients, increasing patient satisfaction with the decision-making process. There is a knowledge gap to support the use of decision aids in SDM for anticoagulation therapy in patients with atrial fibrillation (AF). We describe the development and testing of a new decision aid, including a multicenter, randomized, controlled, 2-arm, open-label ENHANCE-AF clinical trial (Engaging Patients to Help Achieve Increased Patient Choice and Engagement for AF Stroke Prevention) to evaluate its effectiveness in 1,200 participants.Participants will be randomized to either usual care or to a SDM pathway incorporating a digital tool designed to simplify the complex concepts surrounding AF in conjunction with a clinician tool and a non-clinician navigator to guide the participants through each step of the tool. The participant-determined primary outcome for this study is the Decisional Conflict Scale, measured at 1 month after the index visit during which a decision was made regarding anticoagulation use. Secondary outcomes at both 1 and 6 months will include other decision making related scales as well as participant and clinician satisfaction, oral anticoagulation adherence, and a composite rate of major bleeding, death, stroke, or transient ischemic attack. The study will be conducted at four sites selected for their ability to enroll participants of varying racial and ethnic backgrounds, health literacy, and language skills. Participants will be followed in the study for 6 months.The results of the ENHANCE-AF trial will determine whether a decision aid facilitates high quality shared decision making in anticoagulation discussions for stroke reduction in AF. An improved shared decision-making experience may allow patients to make decisions better aligned with their personal values and preferences, while improving overall AF care.
- Published
- 2022
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