Pub Date : 2025-02-19DOI: 10.1016/j.jacbts.2025.02.003
Douglas L Mann
{"title":"When Facts Become Forbidden: The Past and Present History of Scientific Censorship.","authors":"Douglas L Mann","doi":"10.1016/j.jacbts.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.jacbts.2025.02.003","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jacbts.2024.09.011
Kenneth C. Bilchick MD, MS , Jesse D. Cochran BS , Chantel McSkimming BS, Hema Kothari PhD, Zhaoxia Ma MS, Derek J. Bivona PhD, Stefan Bekiranov PhD, Coleen McNamara MD
{"title":"CXC-Chemokine-Receptor-Type-5 Expression on Circulating Naive B Cells Predicts Improvement After Cardiac Resynchronization Therapy","authors":"Kenneth C. Bilchick MD, MS , Jesse D. Cochran BS , Chantel McSkimming BS, Hema Kothari PhD, Zhaoxia Ma MS, Derek J. Bivona PhD, Stefan Bekiranov PhD, Coleen McNamara MD","doi":"10.1016/j.jacbts.2024.09.011","DOIUrl":"10.1016/j.jacbts.2024.09.011","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 2","pages":"Pages 221-223"},"PeriodicalIF":8.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jacbts.2025.01.002
Douglas L. Mann MD (Editor-in-Chief: JACC: Basic to Translational Science)
{"title":"Recognizing Early Career Translational Investigators","authors":"Douglas L. Mann MD (Editor-in-Chief: JACC: Basic to Translational Science)","doi":"10.1016/j.jacbts.2025.01.002","DOIUrl":"10.1016/j.jacbts.2025.01.002","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 2","pages":"Page 241"},"PeriodicalIF":8.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jacbts.2024.10.006
Mohammad Majharul Islam MSc , Max Tamlander MD , Iryna Hlushchenko PhD , Samuli Ripatti PhD , Simon G. Pfisterer PhD
Limited access to functional information of genetic variants reduces the applicability of genetic tools for precision medicine applications in cardiovascular disease. We established an automated analysis platform based on multiplexed high-content imaging and derived in-depth functional data for several hundred LDLR gene variants. Residual low-density lipoprotein receptor activity of genetic variants impacted the risk for cardiovascular disease and elevated low-density lipoprotein cholesterol as well as the utilization of lipid-lowering and combination therapy. This enables increased risk stratification for carriers of LDLR gene variants and opens up new opportunities for improved diagnosis, risk assessment, and treatment selection in familial hypercholesterolemia.
{"title":"Large-Scale Functional Characterization of Low-Density Lipoprotein Receptor Gene Variants Improves Risk Assessment in Cardiovascular Disease","authors":"Mohammad Majharul Islam MSc , Max Tamlander MD , Iryna Hlushchenko PhD , Samuli Ripatti PhD , Simon G. Pfisterer PhD","doi":"10.1016/j.jacbts.2024.10.006","DOIUrl":"10.1016/j.jacbts.2024.10.006","url":null,"abstract":"<div><div>Limited access to functional information of genetic variants reduces the applicability of genetic tools for precision medicine applications in cardiovascular disease. We established an automated analysis platform based on multiplexed high-content imaging and derived in-depth functional data for several hundred <em>LDLR</em> gene variants. Residual low-density lipoprotein receptor activity of genetic variants impacted the risk for cardiovascular disease and elevated low-density lipoprotein cholesterol as well as the utilization of lipid-lowering and combination therapy. This enables increased risk stratification for carriers of <em>LDLR</em> gene variants and opens up new opportunities for improved diagnosis, risk assessment, and treatment selection in familial hypercholesterolemia.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 2","pages":"Pages 170-183"},"PeriodicalIF":8.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jacbts.2024.10.002
Cordula M. Wolf MD , Martin Zenker MD , Olga Boleti MD , Gabrielle Norrish MD , Mark Russell MD , Joshua K. Meisner MD, PhD , David M. Peng MD , Terence Prendiville MBDchBAO, MD , Jake Kleinmahon MD , Paul F. Kantor MBBCh , Danielle Gottlieb Sen MS, MD, MPH , Derek G. Human BMBCh , Peter Ewert MD , Marcus Krueger MD , Daniela Reber MD , Birgit Donner MD , Christopher Hart MD , Irena Odri Komazec MD, PhD , Stefan Rupp MD , Andreas Hahn MD , Gregor Andelfinger MD
There is an unmet medical need to treat patients with severe hypertrophic cardiomyopathy leading to heart failure and death in children carrying pathogenic activating variants in the RAS/mitogen-activated protein kinase pathway. A retrospective analysis of 61 patients provides evidence for decreased mortality and morbidity with improved cardiac status in patients with RASopathy with severe hypertrophic cardiomyopathy receiving mitogen-activated protein kinase kinase inhibition (n = 30) vs those with standard-of-care treatment (n = 31). Side effects were not life threatening and were manageable. The data presented suggest that personalized therapies targeting underlying signaling pathway abnormalities might be effective in critically ill patients with RASopathy warranting clinical investigation.
{"title":"Impact of MEK Inhibition on Childhood RASopathy-Associated Hypertrophic Cardiomyopathy","authors":"Cordula M. Wolf MD , Martin Zenker MD , Olga Boleti MD , Gabrielle Norrish MD , Mark Russell MD , Joshua K. Meisner MD, PhD , David M. Peng MD , Terence Prendiville MBDchBAO, MD , Jake Kleinmahon MD , Paul F. Kantor MBBCh , Danielle Gottlieb Sen MS, MD, MPH , Derek G. Human BMBCh , Peter Ewert MD , Marcus Krueger MD , Daniela Reber MD , Birgit Donner MD , Christopher Hart MD , Irena Odri Komazec MD, PhD , Stefan Rupp MD , Andreas Hahn MD , Gregor Andelfinger MD","doi":"10.1016/j.jacbts.2024.10.002","DOIUrl":"10.1016/j.jacbts.2024.10.002","url":null,"abstract":"<div><div>There is an unmet medical need to treat patients with severe hypertrophic cardiomyopathy leading to heart failure and death in children carrying pathogenic activating variants in the RAS/mitogen-activated protein kinase pathway. A retrospective analysis of 61 patients provides evidence for decreased mortality and morbidity with improved cardiac status in patients with RASopathy with severe hypertrophic cardiomyopathy receiving mitogen-activated protein kinase kinase inhibition (n = 30) vs those with standard-of-care treatment (n = 31). Side effects were not life threatening and were manageable. The data presented suggest that personalized therapies targeting underlying signaling pathway abnormalities might be effective in critically ill patients with RASopathy warranting clinical investigation.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 2","pages":"Pages 152-166"},"PeriodicalIF":8.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jacbts.2024.11.014
Daphne T. Hsu MD
{"title":"Promising But Not Yet the Promised Land","authors":"Daphne T. Hsu MD","doi":"10.1016/j.jacbts.2024.11.014","DOIUrl":"10.1016/j.jacbts.2024.11.014","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 2","pages":"Pages 167-169"},"PeriodicalIF":8.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jacbts.2024.10.008
Rajika Roy PhD , Sarah M. Schumacher PhD , Haley Christine Murphy BS , Jessica Grondolsky , Thiele Osvaldt Rosales PhD , J. Kurt Chuprun PhD , Erhe Gao MD, PhD , Huaqing Zhao PhD, MS , Remus M. Berretta BS , Alexander R.H. Hobby PhD , Steven R. Houser PhD , Larisa V. Avramova PhD , John J.G. Tesmer PhD , Walter J. Koch PhD
GRK2 is the most prominent G protein-coupled receptor kinase that is upregulated in heart failure (HF), and inhibiting GRK2 has improved cardiac function in mice. CCG258208, generated from the paroxetine scaffold, which has GRK2 inhibitory properties, has a 50-fold higher selectivity for GRK2 at 100-fold lower doses. We evaluated CCG258208 in 2 mice HF models and found that CCG258208 has robust therapeutic effects. In a chronic mini-swine HF model, acute administration of CCG258208 enhanced dobutamine inotropic responses. Our results indicate that CCG258208 has robust cardioprotective and HF-reversing effects in different HF models and it stands as a promising lead for HF therapy.
{"title":"Therapeutic Efficacy of a Novel Pharmacologic GRK2 Inhibitor in Multiple Animal Models of Heart Failure","authors":"Rajika Roy PhD , Sarah M. Schumacher PhD , Haley Christine Murphy BS , Jessica Grondolsky , Thiele Osvaldt Rosales PhD , J. Kurt Chuprun PhD , Erhe Gao MD, PhD , Huaqing Zhao PhD, MS , Remus M. Berretta BS , Alexander R.H. Hobby PhD , Steven R. Houser PhD , Larisa V. Avramova PhD , John J.G. Tesmer PhD , Walter J. Koch PhD","doi":"10.1016/j.jacbts.2024.10.008","DOIUrl":"10.1016/j.jacbts.2024.10.008","url":null,"abstract":"<div><div>GRK2 is the most prominent G protein-coupled receptor kinase that is upregulated in heart failure (HF), and inhibiting GRK2 has improved cardiac function in mice. CCG258208, generated from the paroxetine scaffold, which has GRK2 inhibitory properties, has a 50-fold higher selectivity for GRK2 at 100-fold lower doses. We evaluated CCG258208 in 2 mice HF models and found that CCG258208 has robust therapeutic effects. In a chronic mini-swine HF model, acute administration of CCG258208 enhanced dobutamine inotropic responses. Our results indicate that CCG258208 has robust cardioprotective and HF-reversing effects in different HF models and it stands as a promising lead for HF therapy.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 2","pages":"Pages 202-217"},"PeriodicalIF":8.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号