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1. On Second Thought

Author

Moss, Joshua Louis, Morris, Linda, Prados-Torreira, Teresa, Scully, Richard, Soper, Kerry, and Kneubuhl, Victoria Nalani

Published
2022

4. Pulsed Field vs Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation: Recurrent Atrial Arrhythmia Burden

Author

Whang, William, Reddy, Vivek, Koruth, Jacob, Dukkipati, Srinivas, DeLurgio, David, Patel, Anshul, Osorio, Jose, Rajendra, Anil, Morales, Gustavo, D'Souza, Benjamin, Bullinga, John, Cuoco, Frank, Sidney, Darren, Daccarett, Marcos, Harding, John, Sangrigoli, Robert, Pickett, Robert, Kaiser, Daniel, Natale, Andrea, Gallinghouse, Joseph, Gupta, Sanjaya, Steinhaus, Daniel, Mansour, Moussa, Heist, Kevin, Van Houzen, Nathan, Winterfield, Jeffrey, Field, Michael, McElderry, Tom, Maddox, William, Chinitz, Larry, Holmes, Douglas, Calkins, Hugh, Spragg, David, Eldadah, Zayd, Lee, Sung, Thomaides, Athanasios, Mangrum, Michael, Gibson, Douglas, Olson, Nicholas, Woods, Christopher, Schricker, Amir, Ellis, Christopher, Michaud, Gregory, Gerstenfeld, Edward, Moss, Joshua David, Dewland, Thomas, Mountantonakis, Stavros, Skipitaris, Nicholas, Bhasin, Kabir, Su, Wilber, Zawaneh, Michael, Weiss, Jonathan P., Santangeli, Pasquale, Lin, David, Kim, Jamie, Haugh, Connor, Latacha, Matthew, Patel, Chinmay, Link, Michael, Ellenbogen, Kenneth, Koneru, Jayanthi, Halperin, Blair, Jones, D. Randolph, D'Avila, Andre, Waks, Jonathan, Kumar, Kapil, Reddy, Vivek Y., d'Avila, Andre, Gupta, Sanjaya K., Eldadah, Zayd A., Pickett, Robert A., Su, Wilber W., Waks, Jonathan W., Schneider, Christopher W., Richards, Elizabeth, Albrecht, Elizabeth M., Sutton, Brad S., and Gerstenfeld, Edward P.

Published
2024
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8. Chronic graft-versus-host disease detected by tissue-specific cell-free DNA methylation biomarkers

Author

Avni, Batia, Neiman, Daniel, Shaked, Elior, Gal-Rosenberg, Ofer, Grisariu, Sigal, Kuzli, Mona, Avni, Ilai, Fracchia, Andrea, Stepensky, Polina, Zuckerman, Tsila, Lev-Sagie, Ahinoam, Fox-Fisher, Ilana, Piyanzin, Sheina, Moss, Joshua, Salpeter, Seth J., Glaser, Benjamin, Shemer, Ruth, and Dor, Yuval

Subjects
Immunological research, Methylation -- Research, Graft versus host reaction -- Diagnosis, Hematopoietic stem cells -- Transplantation, Extrachromosomal DNA -- Measurement -- Health aspects, Biological markers -- Research, Health care industry
Abstract

BACKGROUND. Accurate detection of graft-versus-host disease (GVHD) is a major challenge in the management of patients undergoing hematopoietic stem cell transplantation (HCT). Here, we demonstrated the use of circulating cell-free DNA (cfDNA) for detection of tissue turnover and chronic GVHD (cGVHD) in specific organs. METHODS. We established a cocktail of tissue-specific DNA methylation markers and used it to determine the concentration of cfDNA molecules derived from the liver, skin, lungs, colon, and specific immune cells in 101 patients undergoing HCT. RESULTS. Patients with active cGVHD showed elevated concentrations of cfDNA, as well as tissue-specific methylation markers that agreed with clinical scores. Strikingly, transplanted patients with no clinical symptoms had abnormally high levels of tissue-specific markers, suggesting hidden tissue turnover even in the absence of evident clinical pathology. An integrative model taking into account total cfDNA concentration, monocyte/macrophage cfDNA levels and alanine transaminase was able to correctly identify GVHD with a specificity of 86% and precision of 89% (AUC of 0.8). CONCLUSION. cfDNA markers can be used for the detection of cGVHD, opening a window into underlying tissue dynamics in patients that receive allogeneic stem cell transplants. FUNDING. This work was supported by grants from the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, The Israel Science Foundation, the Waldholtz/Pakula family, the Robert M. and Marilyn Sternberg Family Charitable Foundation and the Helmsley Charitable Trust (to YD)., Introduction Hematopoietic stem cell transplantation (HCT) is an essential and often the sole curative treatment strategy for high risk hematologic malignancies (1). Graft-versus-host disease (GVHD), the foremost complication of allogeneic [...]

Published
2024
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9. A DNA methylation atlas of normal human cell types

Author

Loyfer, Netanel, Magenheim, Judith, Peretz, Ayelet, Cann, Gordon, Bredno, Joerg, Klochendler, Agnes, Fox-Fisher, Ilana, Shabi-Porat, Sapir, Hecht, Merav, Pelet, Tsuria, Moss, Joshua, Drawshy, Zeina, Amini, Hamed, Moradi, Patriss, Nagaraju, Sudharani, Bauman, Dvora, Shveiky, David, Porat, Shay, Dior, Uri, Rivkin, Gurion, Or, Omer, Hirshoren, Nir, Carmon, Einat, Pikarsky, Alon, Khalaileh, Abed, Zamir, Gideon, Grinbaum, Ronit, Abu Gazala, Machmud, Mizrahi, Ido, Shussman, Noam, Korach, Amit, Wald, Ori, Izhar, Uzi, Erez, Eldad, Yutkin, Vladimir, Samet, Yaacov, Rotnemer Golinkin, Devorah, Spalding, Kirsty L., Druid, Henrik, Arner, Peter, Shapiro, A. M. James, Grompe, Markus, Aravanis, Alex, Venn, Oliver, Jamshidi, Arash, Shemer, Ruth, Dor, Yuval, Glaser, Benjamin, and Kaplan, Tommy

Published
2023
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11. Elevated cfDNA after exercise is derived primarily from mature polymorphonuclear neutrophils, with a minor contribution of cardiomyocytes

Author

Fridlich, Ori, Peretz, Ayelet, Fox-Fisher, Ilana, Pyanzin, Sheina, Dadon, Ziv, Shcolnik, Eilon, Sadeh, Ronen, Fialkoff, Gavriel, Sharkia, Israa, Moss, Joshua, Arpinati, Ludovica, Nice, Shachar, Nogiec, Christopher D., Ahuno, Samuel Terkper, Li, Rui, Taborda, Eddie, Dunkelbarger, Sonia, Fridlender, Zvi G., Polak, Paz, Kaplan, Tommy, Friedman, Nir, Glaser, Benjamin, Shemer, Ruth, Constantini, Naama, and Dor, Yuval

Published
2023
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13. The DNA methylome of human vascular endothelium and its use in liquid biopsies

Author

Peretz, Ayelet, Loyfer, Netanel, Piyanzin, Sheina, Ochana, Bracha Lea, Neiman, Daniel, Magenheim, Judith, Klochendler, Agnes, Drawshy, Zeina, Fox-Fisher, Ilana, Fridlich, Ori, Moss, Joshua, Cohen, Daniel, Zemmour, Hai, Cann, Gordon, Bredno, Joerg, Venn, Oliver, Avni, Batia, Alekberli, Tural, Samet, Yaacov, Korach, Amit, Wald, Ori, Yutkin, Vladimir, Izhar, Uzi, Pillar, Nir, Grompe, Markus, Fridlender, Zvi, Rokach, Ariel, Planer, David, Landesberg, Giora, Glaser, Benjamin, Shemer, Ruth, Kaplan, Tommy, and Dor, Yuval

Published
2023
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14. The Value of Programmed Ventricular Extrastimuli From the Right Ventricular Basal Septum During Supraventricular Tachycardia

Author

Higuchi, Satoshi, Ito, Hiroyuki, Gerstenfeld, Edward P., Lee, Adam C., Lee, Byron K., Marcus, Gregory M., Hsia, Henry H., Moss, Joshua D., Lee, Randall J., Dewland, Thomas A., Vedantham, Vasanth, Tseng, Zian H., Patel, Akash R., Tanel, Ronn E., Badhwar, Nitish, Pellegrini, Cara N., Kawamura, Mitsuharu, Shoda, Morio, Hwang, Chun, Refaat, Marwan M., and Scheinman, Melvin M.

Published
2023
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16. A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Alcohol to Assess Changes in Atrial Electrophysiology

Author

Marcus, Gregory M., Dukes, Jonathan W., Vittinghoff, Eric, Nah, Gregory, Badhwar, Nitish, Moss, Joshua D., Lee, Randall J., Lee, Byron K., Tseng, Zian H., Walters, Tomos E., Vedantham, Vasanth, Gladstone, Rachel, Fan, Shannon, Lee, Emily, Fang, Christina, Ogomori, Kelsey, Hue, Trisha, Olgin, Jeffrey E., Scheinman, Melvin M., Hsia, Henry, Ramchandani, Vijay A., and Gerstenfeld, Edward P.

Published
2021
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19. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus on risk assessment in cardiac arrhythmias: use the right tool for the right outcome, in the right population

Author

Nielsen, Jens Cosedis, Lin, Yenn-Jiang, de Oliveira Figueiredo, Marcio Jansen, Sepehri Shamloo, Alireza, Alfie, Alberto, Boveda, Serge, Dagres, Nikolaos, Di Toro, Dario, Eckhardt, Lee L., Ellenbogen, Kenneth, Hardy, Carina, Ikeda, Takanori, Jaswal, Aparna, Kaufman, Elizabeth, Krahn, Andrew, Kusano, Kengo, Kutyifa, Valentina, Lim, Han S., Lip, Gregory Y.H., Nava-Townsend, Santiago, Pak, Hui-Nam, Diez, Gerardo Rodríguez, Sauer, William, Saxena, Anil, Svendsen, Jesper Hastrup, Vanegas, Diego, Vaseghi, Marmar, Wilde, Arthur, Bunch, T. Jared, Buxton, Alfred E., Calvimontes, Gonzalo, Chao, Tze-Fan, Eckardt, Lars, Estner, Heidi, Gillis, Anne M., Isa, Rodrigo, Kautzner, Josef, Maury, Philippe, Moss, Joshua D., Nam, Gi-Byung, Olshansky, Brian, Pava Molano, Luis Fernando, Pimentel, Mauricio, Prabhu, Mukund, Tzou, Wendy S., Sommer, Philipp, Swampillai, Janice, Vidal, Alejandro, Deneke, Thomas, Hindricks, Gerhard, and Leclercq, Christophe

Published
2020
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24. Use of Programmed Ventricular Extrastimulus During Supraventricular Tachycardia to Differentiate Atrioventricular Nodal Re-Entrant Tachycardia From Atrioventricular Re-Entrant Tachycardia

Author

Ito, Hiroyuki, Badhwar, Nitish, Patel, Akash R., Hoffmayer, Kurt S., Moss, Joshua D., Pellegrini, Cara N., Vedantham, Vasanth, Tseng, Zian H., Tanel, Ronn E., Hsia, Henry H., Lee, Randall J., Marcus, Gregory M., Gerstenfeld, Edward P., and Scheinman, Melvin M.

Published
2018
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31. Chemical evolution of atmospheric organic carbon over multiple generations of oxidation

Author

Isaacman-VanWertz, Gabriel, Massoli, Paola, O’Brien, Rachel, Lim, Christopher, Franklin, Jonathan P., Moss, Joshua A., Hunter, James F., Nowak, John B., Canagaratna, Manjula R., Misztal, Pawel K., Arata, Caleb, Roscioli, Joseph R., Herndon, Scott T., Onasch, Timothy B., Lambe, Andrew T., Jayne, John T., Su, Luping, Knopf, Daniel A., Goldstein, Allen H., Worsnop, Douglas R., and Kroll, Jesse H.

Published
2018
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33. Identification of tissue-specific cell death using methylation patterns of circulating DNA

Author

Lehmann-Werman, Roni, Neiman, Daniel, Zemmour, Hai, Moss, Joshua, Magenheim, Judith, Vaknin-Dembinsky, Adi, Rubertsson, Sten, Nellgård, Bengt, Blennow, Kaj, Zetterberg, Henrik, Spalding, Kirsty, Haller, Michael J., Wasserfall, Clive H., Schatz, Desmond A., Greenbaum, Carla J., Dorrell, Craig, Grompe, Markus, Zick, Aviad, Hubert, Ayala, Maoz, Myriam, Fendrich, Volker, Bartsch, Detlef K., Golan, Talia, Sasson, Shmuel A. Ben, Zamir, Gideon, Razin, Aharon, Cedar, Howard, Shapiro, A. M. James, Glaser, Benjamin, Shemer, Ruth, and Dor, Yuval

Published
2016

34. Design and characteristics of the prophylactic intra‐operative ventricular arrhythmia ablation in high‐risk LVAD candidates (PIVATAL) trial.

Author

Huang, David T., Gosev, Igor, Wood, Katherine L., Vidula, Hima, Stevenson, William, Marchlinski, Frank, Supple, Gregory, Zalawadiya, Sandip K., Weiss, J. Peter, Tung, Roderick, Tzou, Wendy S., Moss, Joshua D., Kancharla, Krishna, Chaudhry, Sunit‐Preet, Patel, Parin J., Khan, Arfaat M., Schuger, Claudio, Rozen, Guy, Kiernan, Michael S., and Couper, Gregory S.

Abstract

Background: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra‐operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. Methods: We designed a prospective, multicenter, open‐label, randomized‐controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra‐operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. Conclusion: The primary aim of this first‐ever randomized trial is to assess the efficacy of intra‐operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA. [ABSTRACT FROM AUTHOR]

Published
2023
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38. Rapid Classification of Sarcomas Using Methylation Fingerprint: A Pilot Study.

Author

Iluz, Aviel, Maoz, Myriam, Lavi, Nir, Charbit, Hanna, Or, Omer, Olshinka, Noam, Demma, Jonathan Abraham, Adileh, Mohammad, Wygoda, Marc, Blumenfeld, Philip, Gliner-Ron, Masha, Azraq, Yusef, Moss, Joshua, Peretz, Tamar, Eden, Amir, Zick, Aviad, and Lavon, Iris

Subjects
PILOT projects, SEQUENCE analysis, DNA, DNA fingerprinting, MACHINE learning, RANDOM forest algorithms, DNA methylation, GENOMES, RESEARCH funding, SARCOMA, ALGORITHMS
Abstract

Simple Summary: Sarcomas encompass a diverse range of cancers, resulting in intricate classification that contributes to treatment delays. The aim of this pilot study, conducted within a specific subset of sarcoma types, is to demonstrates the feasibility of methylation and copy-number variation data obtained from low-coverage whole-genome sequencing using Oxford Nanopore for rapid point-of-care sarcoma classification. Oxford Nanopore sequencers are relatively affordable for laboratories, unlike other technologies used in previous studies for methylation-based sarcoma classification. Our findings indicate that this method attained an overall correct classification rate of 78%. This study could serve as the foundation for a rapid point-of-care sarcoma classification test, facilitating timely and efficient care across diverse clinical settings. Sarcoma classification is challenging and can lead to treatment delays. Previous studies used DNA aberrations and machine-learning classifiers based on methylation profiles for diagnosis. We aimed to classify sarcomas by analyzing methylation signatures obtained from low-coverage whole-genome sequencing, which also identifies copy-number alterations. DNA was extracted from 23 suspected sarcoma samples and sequenced on an Oxford Nanopore sequencer. The methylation-based classifier, applied in the nanoDx pipeline, was customized using a reference set based on processed Illumina-based methylation data. Classification analysis utilized the Random Forest algorithm and t-distributed stochastic neighbor embedding, while copy-number alterations were detected using a designated R package. Out of the 23 samples encompassing a restricted range of sarcoma types, 20 were successfully sequenced, but two did not contain tumor tissue, according to the pathologist. Among the 18 tumor samples, 14 were classified as reported in the pathology results. Four classifications were discordant with the pathological report, with one compatible and three showing discrepancies. Improving tissue handling, DNA extraction methods, and detecting point mutations and translocations could enhance accuracy. We envision that rapid, accurate, point-of-care sarcoma classification using nanopore sequencing could be achieved through additional validation in a diverse tumor cohort and the integration of methylation-based classification and other DNA aberrations. [ABSTRACT FROM AUTHOR]

Published
2023
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40. A universal cell‐free DNA approach for response prediction to preoperative chemoradiation in rectal cancer.

Author

Grinshpun, Albert, Kustanovich, Anatoli, Neiman, Daniel, Lehmann‐Werman, Roni, Zick, Aviad, Meir, Karen, Vainer, Elez, Granit, Roy Z., Arad, Amit, Daskal, Noa, Schwartz, Ruth, Sapir, Eli, Maoz, Myriam, Tahover, Esther, Moss, Joshua, Ben‐Dov, Iddo Z., Peretz, Tamar, Hubert, Ayala, Shemer, Ruth, and Dor, Yuval

Subjects
RECTAL cancer, CELL-free DNA, CIRCULATING tumor DNA, CHEMORADIOTHERAPY, DNA methylation, PATIENT selection, NEOADJUVANT chemotherapy
Abstract

The standard treatment approach for stage II/III rectal cancer is neoadjuvant chemoradiation therapy (nCRT) followed by surgery. In recent years, new treatment approaches have led to higher rates of complete tumor eradication combined with organ‐preservation strategies. However, better tools are still needed to personalize therapy for the individual patient. In this prospective observational study, we analyzed colon‐derived cell‐free (cf)DNA (c‐cfDNA) using a tissue‐specific DNA methylation signature, and its association with therapy outcomes. Analyzing plasma samples (n = 303) collected during nCRT from 37 patients with locally advanced rectal cancer (LARC), we identified colon‐specific methylation markers that discriminated healthy individuals from patients with untreated LARC (area under the curve, 0.81; 95% confidence interval, 0.70‐0.92; P <.0001). Baseline c‐cfDNA predicted tumor response, with increased levels linked to larger residual cancer. c‐cfDNA measured after the first week of therapy identified patients with maximal response and complete cancer eradication, who had significantly lower c‐cfDNA compared with those who had residual disease (8.6 vs 57.7 average copies/ml, respectively; P =.013). Increased c‐cfDNA after 1 week of therapy was also associated with disease recurrence. Methylation‐based liquid biopsy can predict nCRT outcomes and facilitate patient selection for escalation and de‐escalation strategies. [ABSTRACT FROM AUTHOR]

Published
2023
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50. Adding epicardial ablation for ventricular tachycardia: a 1–2 punch, or simply 3rd time's the charm?

Author

Howell, Stacey J. and Moss, Joshua D.

Abstract

Keywords: Catheter ablation; Ventricular tachycardia; Epicardial ablation EN Catheter ablation Ventricular tachycardia Epicardial ablation 95 97 3 02/17/23 20230101 NES 230101 Catheter ablation for the treatment of ventricular tachycardia (VT) has been shown to reduce arrhythmia events, electrical storm, and recurrent device therapies, and successful ablation has been associated with improved survival in patients with structural heart disease (SHD) [[1]]. Freedom from recurrent ventricular tachycardia after catheter ablation is associated with improved survival in patients with structural heart disease: an international vt ablation center collaborative group study. Of the 316 consecutive patients with drug-refractory, scar-based VT referred for ablation at two institutions, 53 (17%) underwent C-ABL, usually with separate endocardial and epicardial procedures, and 263 (83%) underwent NC-ABL, predominantly with endocardial ablation alone. Effectively then, the benefit was notable mainly in patients who underwent two endocardial ablation procedures plus an epicardial ablation procedure over months or years, compared with patients who underwent two endocardial ablation procedures alone. [Extracted from the article]

Published
2023
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