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155 results on '"Laugwitz, K"'

1. Nicht kodierende Ribonukleinsäure im kardiovaskulären System: Sonderforschungsbereich-Transregio (SFB-TRR 267)

Author

Engelhardt, S., Dimmeler, S., Heim, C., Bär, C., Böttger, T., Boon, R., Brandes, R. P., Braun, T., Dueck, A., Gagneur, J., Grote, P., Holdt, L. M., Jaé, N., Krishnan, J., Kupatt, C., Laugwitz, K.-L., Leisegang, M. S., Maegdefessel, L., Meitinger, T., Moretti, A., Müller-McNicoll, M., Sattler, M., Schnieke, A., Schulz, M., Schunkert, H., Schwalbe, H., Teupser, D., Thum, T., Weber, C., Wittig, I., and Zarnack, K.

Published
2022
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4. Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy

Author

Moretti, A., Fonteyne, L., Giesert, F., Hoppmann, P., Meier, A. B., Bozoglu, T., Baehr, A., Schneider, C. M., Sinnecker, D., Klett, K., Fröhlich, T., Rahman, F. Abdel, Haufe, T., Sun, S., Jurisch, V., Kessler, B., Hinkel, R., Dirschinger, R., Martens, E., Jilek, C., Graf, A., Krebs, S., Santamaria, G., Kurome, M., Zakhartchenko, V., Campbell, B., Voelse, K., Wolf, A., Ziegler, T., Reichert, S., Lee, S., Flenkenthaler, F., Dorn, T., Jeremias, I., Blum, H., Dendorfer, A., Schnieke, A., Krause, S., Walter, M. C., Klymiuk, N., Laugwitz, K. L., Wolf, E., Wurst, W., and Kupatt, C.

Published
2020
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7. Incidence and pattern of repeat coronary revascularizations in patients with acute coronary syndromes treated with ticagrelor or prasugrel

Author

Aytekin, A, primary, Scalamogna, M, additional, Coughlan, J J, additional, Lahu, S, additional, Ndrepepa, G, additional, Menichelli, M, additional, Mayer, K, additional, Joner, M, additional, Xhepa, E, additional, Kufner, S, additional, Laugwitz, K L, additional, Neumann, F J, additional, Schunkert, H, additional, Kastrati, A, additional, and Cassese, S, additional

Published
2023
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9. Man-machine interaction-based phenotyping identifies pathophysiologically and prognostically informative clusters among patients with mitral regurgitation undergoing transcatheter edge-to-edge repair

Author

Lachmann, M, primary, Trenkwalder, T, additional, Covarrubias, H A A, additional, Rippen, E, additional, Schuermann, F, additional, Presch, A, additional, Ruff, C, additional, Mayr, P N, additional, Schunkert, H, additional, Kastrati, A, additional, Kupatt, C, additional, Laugwitz, K L, additional, Joner, M, additional, and Xhepa, E, additional

Published
2022
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10. Ticagrelor or prasugrel in patients with acute coronary syndrome and prior myocardial infarction

Author

Scalamogna, M, primary, Lahu, S, additional, Ndrepepa, G, additional, Mayer, K, additional, Gewalt, S, additional, Menichelli, M, additional, Bernlochner, I, additional, Joner, M, additional, Xhepa, E, additional, Kufner, S, additional, Laugwitz, K L, additional, Neumann, F J, additional, Schunkert, H, additional, Kastrati, A, additional, and Cassese, S, additional

Published
2022
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11. Ticagrelor or prasugrel in patients with acute coronary syndrome and high bleeding risk

Author

Lahu, S, primary, Presch, A, additional, Ndrepepa, G, additional, Bernlochner, I, additional, Joner, M, additional, Xhepa, E, additional, Kufner, S, additional, Sager, H B, additional, Mayer, K, additional, Kessler, T, additional, Laugwitz, K L, additional, Schunkert, H, additional, Neumann, F J, additional, Kastrati, A, additional, and Cassese, S, additional

Published
2022
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13. Sequential defects in cardiac lineage commitment and maturation cause hypoplastic left heart syndrome

Author

Krane, M, Dressen, M, Santamaria, G, My, I, Schneider, C, Dorn, T, Laue, S, Mastantuono, E, Berutti, R, Rawat, H, Gilsbach, R, Schneider, P, Lahm, H, Schwarz, S, Doppler, S, Paige, S, Puluca, N, Doll, S, Neb, I, Brade, T, Zhang, Z, Abou-Ajram, C, Northoff, B, Holdt, L, Sudhop, S, Sahara, M, Goedel, A, Dendorfer, A, Tjong, F, Rijlaarsdam, M, Cleuziou, J, Lang, N, Kupatt, C, Bezzina, C, Lange, R, Bowles, N, Mann, M, Gelb, B, Crotti, L, Hein, L, Meitinger, T, Wu, S, Sinnecker, D, Gruber, P, Laugwitz, K, Moretti, A, Krane M., Dressen M., Santamaria G., My I., Schneider C. M., Dorn T., Laue S., Mastantuono E., Berutti R., Rawat H., Gilsbach R., Schneider P., Lahm H., Schwarz S., Doppler S. A., Paige S., Puluca N., Doll S., Neb I., Brade T., Zhang Z., Abou-Ajram C., Northoff B., Holdt L. M., Sudhop S., Sahara M., Goedel A., Dendorfer A., Tjong F. V. Y., Rijlaarsdam M. E., Cleuziou J., Lang N., Kupatt C., Bezzina C., Lange R., Bowles N. E., Mann M., Gelb B. D., Crotti L., Hein L., Meitinger T., Wu S., Sinnecker D., Gruber P. J., Laugwitz K. -L., Moretti A., Krane, M, Dressen, M, Santamaria, G, My, I, Schneider, C, Dorn, T, Laue, S, Mastantuono, E, Berutti, R, Rawat, H, Gilsbach, R, Schneider, P, Lahm, H, Schwarz, S, Doppler, S, Paige, S, Puluca, N, Doll, S, Neb, I, Brade, T, Zhang, Z, Abou-Ajram, C, Northoff, B, Holdt, L, Sudhop, S, Sahara, M, Goedel, A, Dendorfer, A, Tjong, F, Rijlaarsdam, M, Cleuziou, J, Lang, N, Kupatt, C, Bezzina, C, Lange, R, Bowles, N, Mann, M, Gelb, B, Crotti, L, Hein, L, Meitinger, T, Wu, S, Sinnecker, D, Gruber, P, Laugwitz, K, Moretti, A, Krane M., Dressen M., Santamaria G., My I., Schneider C. M., Dorn T., Laue S., Mastantuono E., Berutti R., Rawat H., Gilsbach R., Schneider P., Lahm H., Schwarz S., Doppler S. A., Paige S., Puluca N., Doll S., Neb I., Brade T., Zhang Z., Abou-Ajram C., Northoff B., Holdt L. M., Sudhop S., Sahara M., Goedel A., Dendorfer A., Tjong F. V. Y., Rijlaarsdam M. E., Cleuziou J., Lang N., Kupatt C., Bezzina C., Lange R., Bowles N. E., Mann M., Gelb B. D., Crotti L., Hein L., Meitinger T., Wu S., Sinnecker D., Gruber P. J., Laugwitz K. -L., and Moretti A.

Abstract

BACKGROUND: Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis of HLHS is unknown, but hemodynamic disturbances are assumed to play a prominent role. METHODS: To identify perturbations in gene programs controlling ventricular muscle lineage development in HLHS, we performed whole-exome sequencing of 87 HLHS parent-offspring trios, nuclear transcriptomics of cardiomyocytes from ventricles of 4 patients with HLHS and 15 controls at different stages of heart development, single cell RNA sequencing, and 3D modeling in induced pluripotent stem cells from 3 patients with HLHS and 3 controls. RESULTS: Gene set enrichment and protein network analyses of damaging de novo mutations and dysregulated genes from ventricles of patients with HLHS suggested alterations in specific gene programs and cellular processes critical during fetal ventricular cardiogenesis, including cell cycle and cardiomyocyte maturation. Single-cell and 3D modeling with induced pluripotent stem cells demonstrated intrinsic defects in the cell cycle/unfolded protein response/autophagy hub resulting in disrupted differentiation of early cardiac progenitor lineages leading to defective cardiomyocyte subtype differentiation/ maturation in HLHS. Premature cell cycle exit of ventricular cardiomyocytes from patients with HLHS prevented normal tissue responses to developmental signals for growth, leading to multinucleation/polyploidy, accumulation of DNA damage, and exacerbated apoptosis, all potential drivers of left ventricular hypoplasia in absence of hemodynamic cues. CONCLUSIONS: Our results highlight that despite genetic heterogeneity in HLHS, many mutations converge on sequential cellular processes primarily driving cardiac myogenesis, suggesting n

Published
2021

14. Nicht kodierende Ribonukleinsäure im kardiovaskulären System:Sonderforschungsbereich-Transregio (SFB-TRR 267)

Author

Engelhardt, S., Dimmeler, S., Heim, C., Bär, C., Böttger, T., Boon, R., Brandes, R. P., Braun, T., Dueck, A., Gagneur, J., Grote, P., Holdt, L. M., Jaé, N., Krishnan, J., Kupatt, C., Laugwitz, K. L., Leisegang, M. S., Maegdefessel, L., Meitinger, T., Moretti, A., Müller-McNicoll, M., Sattler, M., Schnieke, A., Schulz, M., Schunkert, H., Schwalbe, H., Teupser, D., Thum, T., Weber, C., Wittig, I., and Zarnack, K.

Abstract

The discovery of regulatory noncoding RNA molecules (ncRNA) revolutionized our previous understanding of gene expression. As shown by extensive sequencing projects from earlier times, ncRNA occurs in the human transcriptome in a previously unforeseen number and diversity, whereas mRNA coding for proteins only makes up a small proportion of the human transcriptome. In addition to structurally important ncRNA, tens of thousands of regulatory ncRNAs were identified in humans, of which microRNAs, long noncoding RNAs and the recently discovered circular RNAs are important groups. Members of this joint project have already contributed essential knowledge on the role, the mechanisms and the target structures of ncRNAs in the cardiovascular (CV) system. Furthermore, they have shown the feasibility of treatment based on the manipulation of ncRNA in cardiovascular diseases. Although a fascinating new field of research has opened up with ncRNAs, the enormous number of RNA transcripts, their different mechanisms of action and the complex methods necessary for their investigation represent major challenges. The tasks are now 1) to determine those ncRNAs which are essential for the development and homeostasis as well as the development and progression of diseases in the cardiovascular system and 2) to mechanistically understand their mode of functioning, with the aim to derive target structures and their manipulation to develop urgently needed new therapies.

Published
2022

18. 8 Stent optimization using optical coherence tomography and its prognostic implications after percutaneous coronary intervention

Author

Rai, H, primary, Harzer, F, additional, Otsuka, T, additional, Abdelwahed, YS, additional, Antuña, P, additional, Blachutzik, F, additional, Koppara, T, additional, Räber, L, additional, Leistner, DM, additional, Alfonso, F, additional, Nef, H, additional, Seguchi, M, additional, Aytekin, A, additional, Xhepa, E, additional, Kufner, S, additional, Cassese, S, additional, Laugwitz, K-L, additional, Byrne, RA, additional, Kastrati, A, additional, and Joner, M, additional

Published
2021
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20. Reticulated platelet mass cytometry reveals unexplored therapeutic targets in patients with chronic coronary syndrome

Author

Bongiovanni, D, primary, Klug, M, additional, Lazareva, O, additional, Kirmes, K, additional, Biasi, M, additional, Okrojek, R, additional, Gosetti, R, additional, Manz, Q, additional, Arend, L, additional, Bernett, J, additional, Von Scheidt, M, additional, Condorelli, G, additional, Laugwitz, K L, additional, List, M, additional, and Bernlochner, I, additional

Published
2021
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21. Body mass index and efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes

Author

Lahu, S, primary, Behnes, M, additional, Ndrepepa, G, additional, Neumann, F J, additional, Sibbing, D, additional, Bernlochner, I, additional, Menichelli, M, additional, Mayer, K, additional, Richardt, G, additional, Angiolillo, D J, additional, Laugwitz, K L, additional, Schunkert, H, additional, Schuepke, S, additional, Kastrati, A, additional, and Akin, I, additional

Published
2021
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23. Nocturnal respiratory rate predicts ICD benefit:a prospective, controlled, multicentre cohort study

Author

Dommasch, M. (Michael), Steger, A. (Alexander), Barthel, P. (Petra), Huster, K. M. (Katharina M.), Müller, A. (Alexander), Sinnecker, D. (Daniel), Laugwitz, K.-L. (Karl-Ludwig), Penzel, T. (Thomas), Lubinski, A. (Andrzej), Flevari, P. (Panagiota), Harden, M. (Markus), Friede, T. (Tim), Kääb, S. (Stefan), Merkely, B. (Bela), Sticherling, C. (Christian), Willems, R. (Rik), Huikuri, H. V. (Heikki V.), Bauer, A. (Axel), Malik, M. (Marek), Zabel, M. (Markus), Schmidt, G. (Georg), and T. E. (The EU-CERT-ICD investigators)

Subjects
Benefit prediction, Nocturnal respiratory rate, Primary prophylactic ICD
Abstract

Background: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. ICD implantation decisions are currently based on reduced left ventricular ejection fraction (LVEF≤35%). However, in some patients, the non-arrhythmic death risk predominates thus diminishing ICD-therapy benefits. Based on previous observations, we tested the hypothesis that compared to the others, patients with nocturnal respiratory rate (NRR) ≥18 breaths per minute (brpm) benefit less from prophylactic ICD implantations. Methods: This prospective cohort study was a pre-defined sub-study of EU-CERT-ICD trial conducted at 44 centers in 15 EU countries between May 12, 2014, and September 6, 2018. Patients with ischaemic or non-ischaemic cardiomyopathy were included if meeting primary prophylactic ICD implantation criteria. The primary endpoint was all-cause mortality. NRR was assessed blindly from pre-implantation 24-hour Holters. Multivariable models and propensity stratification evaluated the interaction between NRR and the ICD mortality effect. This study is registered with ClinicalTrials.gov (NCT0206419). Findings: Of the 2,247 EU-CERT-ICD patients, this sub-study included 1,971 with complete records. In 1,363 patients (61.7 (12) years; 244 women) an ICD was implanted; 608 patients (63.2 (12) years; 108 women) were treated conservatively. During a median 2.5-year follow-up, 202 (14.8%) and 95 (15.6%) patients died in the ICD and control groups, respectively. NRR statistically significantly interacted with the ICD mortality effect (p = 0.0070). While the 1,316 patients with NRR

Published
2021

25. Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction

Author

Schulz, Stefanie, Richardt, Gert, Laugwitz, Karl-Ludwig, Morath, Tanja, Neudecker, Julia, Hoppmann, Petra, Mehran, Roxana, Gershlick, Anthony H., Tölg, Ralph, Anette Fiedler, K., Abdel-Wahab, Mohamed, Kufner, Sebastian, Schneider, Simon, Schunkert, Heribert, Ibrahim, Tareq, Mehilli, Julinda, Kastrati, Adnan, Kastrati, A., Mehilli, J., Richardt, G., Mehran, R., Gershlick, A., Mehilli, J., Burgdorf, C., Byrne, R.A., Cassese, S., Fusaro, M., Hausleiter, J., Hengstenberg, C., Joner, M., Kasel, M., Kastrati, A., Massberg, S., Ott, I., Pache, J., Schunkert, H., Seyfarth, M., Sibbing, D., Tiroch, K., Laugwitz, K.-L., Ibrahim, T., Hoppmann, P., Schneider, S., Bradaric, C., Richardt, G., Abdel-Wahab, M., Geist, V., Schwarz, B., Sulimov, D., Tölg, R., Schulz, S., Schömig, G., von Merzljak, B., Luckmann, J., Ruf, J., Morath, T., Holle, H., Paul, H., Vogel, J., Hoesl, K., Rifatov, N., Pastor, I., Maimer-Rodrigues, F., Schulz, M., Neudecker, J., Mayer, K., Hofmann, F., Mann, J., Hauschke, D., Schmitt, C., Poci, D., Barthel, P., Ndrepepa, G., Keta, D., Byrne, R.A., Kufner, S., Piniek, S., Hurt, S., Kastrati, S., and Anette Fiedler, K.

Published
2014
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28. 51 Neointimal tissue coverage and characterization assessment using optical coherence tomography surveillance six months after implantation of bioresorbable scaffolds versus conventional everolimus eluting stents in ISAR-absorb MI trial

Author

Rai, H, primary, Alfonso, F, additional, Maeng, M, additional, Bradaric, C, additional, Wiebe, J, additional, Cuesta, J, additional, Christiansen, E-H, additional, Harzer, F, additional, Cassese, S, additional, Hoppmann, P, additional, Colleran, R, additional, Schneider, S, additional, Laugwitz, K-L, additional, Kastrati, A, additional, and Byrne, RA, additional

Published
2020
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30. The Wnt inhibitor Dkk1 is required for maintaining the normal cardiac differentiation program in Xenopus laevis

Author

Guo, Y. (Yanchun), Dorn, T. (Tatjana), Kühl, S. J. (Susanne J.), Linnemann, A. (Alexander), Rothe, M. (Melanie), Pfister, A. S. (Astrid S.), Vainio, S. (Seppo), Laugwitz, K.-L. (Karl-Ludwig), Moretti, A. (Alessandra), Kühl, M. (Michael), Guo, Y. (Yanchun), Dorn, T. (Tatjana), Kühl, S. J. (Susanne J.), Linnemann, A. (Alexander), Rothe, M. (Melanie), Pfister, A. S. (Astrid S.), Vainio, S. (Seppo), Laugwitz, K.-L. (Karl-Ludwig), Moretti, A. (Alessandra), and Kühl, M. (Michael)

Abstract

Wnt proteins can activate different intracellular signaling pathways. These pathways need to be tightly regulated for proper cardiogenesis. The canonical Wnt/β-catenin inhibitor Dkk1 has been shown to be sufficient to trigger cardiogenesis in gain-of-function experiments performed in multiple model systems. Loss-of-function studies however did not reveal any fundamental function for Dkk1 during cardiogenesis. Using Xenopus laevis as a model we here show for the first time that Dkk1 is required for proper differentiation of cardiomyocytes, whereas specification of cardiomyocytes remains unaffected in absence of Dkk1. This effect is at least in part mediated through regulation of non-canonical Wnt signaling via Wnt11. In line with these observations we also found that Isl1, a critical regulator for specification of the common cardiac progenitor cell (CPC) population, acts upstream of Dkk1.

Published
2019

32. A new hERG allosteric modulator rescues genetic and drug-induced long-QT syndrome phenotypes in cardiomyocytes from isogenic pairs of patient induced pluripotent stem cells

Author

Sala, L, Yu, Z, Ward-van Oostwaard, D, van Veldhoven, J, Moretti, A, Laugwitz, K, Mummery, C, Ijzerman, A, Bellin, M, Sala L., Yu Z., Ward-van Oostwaard D., van Veldhoven J. P. D., Moretti A., Laugwitz K. -L., Mummery C. L., Ijzerman A. P., Bellin M., Sala, L, Yu, Z, Ward-van Oostwaard, D, van Veldhoven, J, Moretti, A, Laugwitz, K, Mummery, C, Ijzerman, A, Bellin, M, Sala L., Yu Z., Ward-van Oostwaard D., van Veldhoven J. P. D., Moretti A., Laugwitz K. -L., Mummery C. L., Ijzerman A. P., and Bellin M.

Abstract

Long-QT syndrome (LQTS) is an arrhythmogenic disorder characterised by prolongation of the QT interval in the electrocardiogram, which can lead to sudden cardiac death. Pharmacological treatments are far from optimal for congenital forms of LQTS, while the acquired form, often triggered by drugs that (sometimes inadvertently) target the cardiac hERG channel, is still a challenge in drug development because of cardiotoxicity. Current experimental models in vitro fall short in predicting proarrhythmic properties of new drugs in humans. Here, we leveraged a series of isogenically matched, diseased and genetically engineered, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients to test a novel hERG allosteric modulator for treating congenital LQTS, drug-induced LQTS or a combination of the two. By slowing IK r deactivation and positively shifting IK r inactivation, the small molecule LUF7346 effectively rescued all of these conditions, demonstrating in a human system that allosteric modulation of hERG may be useful as an approach to treat inherited and drug-induced LQTS. Furthermore, our study provides experimental support of the value of isogenic pairs of patient hiPSC-CMs as platforms for testing drug sensitivities and performing safety pharmacology.

Published
2016

34. P5630Morphometric and qualitative differences in neointimal tissue six months after implantation of bioresorbable scaffolds versus conventional everolimus eluting stents in ISAR-Absorb MI trial

Author

Rai, H, primary, Alfonso, F, additional, Maeng, M, additional, Bradaric, C, additional, Wiebe, J, additional, Cuesta, J, additional, Christiansen, E H, additional, Bohner, J, additional, Hoppmann, P, additional, Colleran, R, additional, Schneider, S, additional, Laugwitz, K L, additional, Kastrati, A, additional, and Byrne, R A, additional

Published
2019
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35. 2181The prothrombotic transcriptome of reticulated platelets

Author

Bongiovanni, D, primary, Santamaria, G, additional, Klug, M, additional, Santovito, D, additional, Felicetta, A, additional, Hristov, M, additional, Aslani, M, additional, Weber, C, additional, Peano, C, additional, Condorelli, G, additional, Laugwitz, K L, additional, and Bernlochner, I, additional

Published
2019
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43. P4559Outcome after single-layer polytetrafluoroethylene-covered stent implantation for the treatment of coronary artery perforation

Author

Kufner, S, primary, Ferenc, M, additional, Schlundt, C, additional, Hoppmann, P, additional, Abdel-Wahab, M, additional, Cassese, S, additional, Joner, M, additional, Xhepa, E, additional, Fusaro, M, additional, Schunkert, H, additional, Laugwitz, K.-L, additional, Neumann, F.-J, additional, Byrne, R A, additional, and Kastrati, A, additional

Published
2018
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44. P2632Optical coherence tomography tissue coverage and characterization at six months after implantation of bioresorbable scaffolds versus conventional everolimus eluting stents in the ISAR-Absorb MI trial

Author

Rai, H, primary, Alfonso, F, additional, Maeng, M, additional, Bradaric, C, additional, Wiebe, J, additional, Cuesta, J, additional, Christiansen, E H, additional, Bohner, J, additional, Hoppmann, P, additional, Kufner, S, additional, Colleran, R, additional, Schneider, S, additional, Laugwitz, K L, additional, Kastrati, A, additional, and Byrne, R A, additional

Published
2018
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47. Identification of Differentially Regulated Pathways in Cardiac Development and Cardiac Gene Expression during In Vitro Cardiac Differentiation of HLHS-derived Human Induced Pluripotent Stem Cells using Transcriptome Analysis

Author

Dreßen, M., additional, Northoff, B., additional, Laue, S., additional, Neb, I., additional, Zhang, Z., additional, Gödel, A., additional, Doppler, S., additional, Deutsch, M., additional, Lahm, H., additional, Teupser, D., additional, Moretti, A., additional, Laugwitz, K.-L., additional, Holdt, L., additional, Lange, R., additional, and Krane, M., additional

Published
2018
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49. 24 A non-randomized comparison of two paclitaxel-coated balloons for the treatment of coronary in-stent restenosis

Author

Colleran, R, primary, Joner, M, additional, Kufner, S, additional, Altevogt, F, additional, Neumann, F, additional, Wahab, A, additional, Richardt, G, additional, Giacoppo, D, additional, Cassese, S, additional, Ibrahim, T, additional, Laugwitz, K, additional, Schunkert, H, additional, Kastrati, A, additional, and Byrne, R, additional

Published
2017
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