tbuckley/cabot-search huggingface dataset:
Abstract 15559: In-hospital versus Out-of-hospital Cardiac Arrest in Patients Presenting to Cardiac Intensive Care Units: From the Critical Care Cardiology Trials Network (CCCTN) Registry
Authors: Anthony P CARNICELLI, Kelly Brown, Jianping Guo, Payton Kendsersky, Kelly E Arps, Jeffrey A Dixson, Ryan Keane, David D Berg, Erin A Bohula, Robert W Harrison, Christopher B Granger, Sean Van Diepen, David A Morrow, Jason N Katz, L. Kristin Newby
Journal: Circulation (2020)

Background: Cardiac arrest (CA) is a common reason for cardiac intensive care unit (CICU) admission and is associated with considerable morbidity, mortality, and resource use. Aim: To describe characteristics and outcomes of pts presenting to contemporary CICUs with in-hospital (IH) or out-of-hospital (OH) CA. Methods: The Critical Care Cardiology Trials Network (CCCTN) is a multicenter network of tertiary CICUs in North America (n=25). Participating centers contributed data from consecutive admissions during 2-month annual snapshots between 9/2017 and 8/2019 (n=8240). We analyzed characteristics and outcomes of pts with CA by IHCA vs OHCA. Results: Of 975 admissions with CA (48.9% OHCA), most were male (64.7%), Caucasian (63.4%) and smokers (60.6%). Acute coronary syndrome (ACS) was present in 30.6% and cardiomyopathy in 21.8%. Shockable rhythm was present in 54.1%, more commonly among those with reduced ejection fraction, ischemic cardiomyopathy, or ACS (p&lt;0.01 for all). Compared with IHCA, patients with OHCA were younger (median age 62 vs 66 years) and had fewer comorbidities including heart failure, atrial fibrillation, valvular disease, pulmonary HTN, and CKD (p&lt;0.01 for all). Pts with OHCA more commonly had shockable rhythms (58.3% vs 50.0%) and were more likely to be comatose at initial assessment (75.7% vs 40.4%); p&lt;0.01 for both. Resource use varied significantly between OHCA and IHCA [ Fig ] and CICU length of stay was longer for pts with OHCA (median 3.4 vs 3.1 days; p=0.049). In-hospital mortality was 41.2% and was higher in OHCA (44.7%) compared with IHCA (38.0%), p=0.03 [ Fig ]. Eventual discharge home or to rehab was more common among pts with IHCA (51.6% vs 49.1% for OHCA; p&lt;0.01). Conclusion: Despite advances in pre- and in-hospital care, pts presenting to contemporary CICUs with CA have high in-hospital mortality, with IHCA mortality only modestly lower than in OHCA. A better understanding of patterns may guide new approaches to improve patient outcomes.
MBRS-65. FBXW7 ACTS A TUMOR SUPPRESSOR IN MYC-DRIVEN MEDULLOBLASTOMA BY CONTROLLING A FEED-FORWARD REGULATORY LOOP OF PLK1 AND MYC
Authors: Dong Wang, Angela Pierce, Bethany Veo, Susan Fosmire, Krishna Madhavan, Ilango Balakrishnan, Sujatha Venkataraman, Rajeev Vibhakar
Journal: Neuro-Oncology (2020)

Abstract Group 3 medulloblastoma (MB) is often accompanied by MYC amplification and has a higher rate of metastatic disease. So, it is critical to have more effective therapies for high MYC expressing sub-groups. Here we report that FBXW7, a substrate recognition component of the SKP1-CUL1-Fbox (SCF) E3 ligase, interacts with and targets c-MYC for polyubiquitination and proteasomal degradation. FBXW7 shows lower expression level in MYC-driven MB compared with other MB subgroups suggesting activity as a tumor suppressor. Genomic deletion or mutation of Fbxw7 has frequently been identified in many human cancers but not in MB. We demonstrate that overexpression of Fbxw7 in MB cells induces apoptosis and suppresses proliferation in vitro and in vivo. Both phospho-deficient (T205A) and phosphomimetic aspartic acid (T205D) mutants deactivate its tumor suppressor function suggesting a conformational change of its protein structure. Mechanistically, PLK1 kinase specifically phosphorylates FBXW7 and promotes its auto-polyubiquitination and proteasomal degradation, counteracting FBXW7-mediated degradation of oncogene substrates, including c-MYC and PLK1. Chip-Seq results show stabilized c-MYC in turn directly activates PLK1 and FBXW7 transcription, constituting a feedforward regulatory loop. Co-immunoprecipitation demonstrates that FBXW7 directly binds to PLK1 and c-MYC, facilitating their protein degradation by promoting the ubiquitination of both proteins. Furthermore, we show that FBXW7 protein can be stabilized by various kinase inhibitors, proposing a mechanism of kinase-targeted agents to treat MYC-driven MB. These results collectively demonstrate how kinase inhibition stabilizes the tumor suppressor FBXW7 in MYC-driven MB, thus revealing an important function of FBXW7 in suppressing MB progression.
Safety and immunogenicity of the adjunct therapeutic vaccine ID93 + GLA-SE in adults who have completed treatment for tuberculosis: a randomised, double-blind, placebo-controlled, phase 2a trial
Authors: Tracey A Day, Adam Penn-Nicholson, Angelique Kany Kany Luabeya, Andrew Fiore-Gartland, Nelita Du Plessis, Andre G Loxton, Julie Vergara, Tom A Rolf, Tim D Reid, Asma Toefy, Justin Shenje, Hendrik Geldenhuys, Michele Tameris, Simbarashe Mabwe, Nicole Bilek, Linda-Gail Bekker, Andreas Diacon, Gerhard Walzl, Jill Ashman, Aude Frevol, Zachary K Sagawa, Cecilia Lindestam Arlehamn, Alessandro Sette, Steven G Reed, Rhea N Coler, Thomas J Scriba, Mark Hatherill, Anna Marie Beckmann, Fan-Chi Hsu, Sarah Albertson, Ashley Veldsman, Constance Schreuder, Erica Smit, Yolundi Cloete, Cynthia Ontong, Elisabeth Filander, Gail Jacobs, Alana Keyser, Hadn Africa, Humphrey Mulenga, Julia Noble, Lebohang Makhethe, Marcia Steyn, Marwou de Kock, Nambitha Quaqua, Yiwen Lu, Andrea Gutschmidt, Friedrich Thienemann, Stuart Kahn, Angelique Mouton, Elma Van Rooyen, Fajwa Opperman, Ann Swarts, Amaryl Van Schalkwyk, Yolandi Herselman, Devona Hofmeester, Julia Amsterdam, Leya Hassanally, Linda van der Merwe, Alessandro Companie, Susan Rossouw, Carolyn Jones, Natasja Botes, Elize van der Riet, Sandra Goliath, Sandra Kruger, Eunice Sinandile
Journal: The Lancet Respiratory Medicine (2020)
RADT-45. EFFECT OF DIFFERENT RADIOTHERAPY TECHNIQUES ON HEMATOLOGICAL TOXICITY OF CRANIOSPINAL IRRADIATION
Authors: Yangqiong Zhang, Huajun Yang, Guanhua Deng, Rishun Luo, Ping Zhang, Linbo Cai
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE To investigate the effect of different radiotherapy techniques on hematological toxicity of craniospinal irradiation. METHODS A retrospective study involving changes in hematology during craniospinal irradiation were conducted. 79 patients were divided into observation group and control group. 36 patients in observation group received intensity modulated radiation therapy and 43 patients in control group received three-dimensional conformal radiotherapy. The prescribed dose of PTV in the two groups are 28.8-36 Gy, and the single dose are 1.6-2.0 Gy. The hematological toxicity changes and bone marrow suppression stage of the two groups of patients before, during and after radiotherapy were recorded and analyzed. RESULTS 90% of patients showed different bone marrow suppression stage during and after radiotherapy. During radiotherapy, the toxicity of hemoglobin in the observation group was more serious than that in the control group (z=-2.272, p=0.023). After radiotherapy, the toxicity of hemoglobin and white blood cells in the observation group was more serious than that in the control group (z=-3.053, p=0.002; z=-3.163, p=0.002). CONCLUSION We should closely observe the changes of hematological toxicity for craniospinal irradiation patient treated with IMRT and take corresponding preventive measures to avoid serious bone marrow suppression stage.
Enhanced IL-36R signaling promotes barrier impairment and inflammation in skin and intestine
Authors: Zaruhi Hovhannisyan, Nengyin Liu, Sara Khalil-Aguero, Casandra Panea, Jeffrey VanValkenburgh, Ruoyu Zhang, Wei Keat Lim, Yu Bai, Wen Fury, Tammy Huang, Elena Garnova, Jeanette Fairhurst, Jee Kim, Smita Aryal, Dharani Ajithdoss, Adelekan Oyejide, Maria del Pilar Molina-Portela, Hock E, William Poueymirou, Nicole Stokes Oristian, Susannah Brydges, Xia Liu, William Olson, George Yancopoulos, Andrew J. Murphy, Matthew A. Sleeman, Sokol Haxhinasto
Journal: Science Immunology (2020)

Unrestrained IL-36R signaling in a humanized mouse model causes barrier impairment and increased cutaneous and intestinal inflammation.
DDRE-28. EGFR INHIBITION DOWNREGULATES MGMT AND SENSITIZES GBM CELLS TO TMZ
Authors: Gao Guo, Ke Gong, Jann Sarkaria, Amyn Habib
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) is a highly malignant type of adult brain tumor with a poor prognosis. Temozolomide (TMZ), a DNA alkylating agent, has been widely used as an effective first-line chemotherapeutic agent for the treatment of GBM patients. The efficacy of TMZ in GBM depends on the absence of the DNA repair protein MGMT which reverses the DNA damage induced by TMZ. The MGMT promoter is hypermethylated in about 45% of GBMs, resulting in lack of MGMT expression and increased responsiveness to TMZ. TMZ is less effective in MGMT unmethylated GBMs. We propose that EGFR inhibition downregulates MGMT and sensitizes glioma cells to TMZ and a combination of pretreatment with erlotinib followed by TMZ could be a useful therapeutic approach in MGMT expressing GBMs. As our experimental model we used multiple MGMT unmethylated lines from the Mayo Clinic patient derived xenografts (PDXs) panel. Our data demonstrate that exposure of cells to EGFR tyrosine kinase inhibitor erlotinib for 48h results in downregulation of MGMT at the mRNA and protein level. Additionally, EGFR inhibition activates the AP-1 transcription factor and overexpression of AP-1 components Fos and Jun results in decreased MGMT expression in TMZ resistant PDXs, suggesting that AP-1 acts as a transcriptional repressor of MGMT. We further identified that the mice implanted with TMZ resistant PDXs pretreated with afatinib followed by TMZ treatment survived longer compared to those treated with TMZ alone. Thus, the use of EGFR inhibition may enhance the sensitivity of MGMT unmethylated GBMs to TMZ.
Host miRNA-21 promotes liver dysfunction by targeting small intestinal <i>Lactobacillus</i> in mice
Authors: André A. Santos, Marta B. Afonso, Ricardo S. Ramiro, David Pires, Madalena Pimentel, Rui E. Castro, Cecília M.P. Rodrigues
Journal: Gut Microbes (2020)

New evidence shows that host-microbiota crosstalk can be modulated via endogenous miRNAs. We have previously reported that miR-21 ablation protects against liver injury in cholestasis. In this study, we investigated the role of miR-21 in modulating the gut microbiota during cholestasis and its effects in liver dysfunction. Mice lacking miR-21 had reduced liver damage and were protected against small intestinal injury as well as from gut microbiota dysbiosis when subjected to bile duct ligation surgery. The unique microbiota profile of miR-21KO mice was characterized by an increase in
High-resolution 3D abdominal segmentation with random patch network fusion
Authors: Yucheng Tang, Riqiang Gao, Ho Hin Lee, Shizhong Han, Yunqiang Chen, Dashan Gao, Vishwesh Nath, Camilo Bermudez, Michael R. Savona, Richard G. Abramson, Shunxing Bao, Ilwoo Lyu, Yuankai Huo, Bennett A. Landman
Journal: Medical Image Analysis (2020)
High-Dose Statins Prior to Percutaneous Coronary Intervention: A Paradigm Shift to Influence Clinical Outcomes in the Cardiac Catheterization Laboratory⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2009)
EXTH-60. CHARACTERIZATION OF THE ONCOLYTIC ADENOVIRUS DELTA-24-RGD AS THERAPEUTIC AGENT FOR THE TREATMENT OF THE PEDIATRIC EMBRYONAL BRAIN TUMORS AT/RT AND CNS-PNET
Authors: Marc Garcia-Moure, Marisol González-Huarriz, Virginia Laspidea, Lucía Marrodán, Candelaria Gomez-Manzano, Juan Fueyo, Ana Patiño-García, Marta M Alonso
Journal: Neuro-Oncology (2020)

Abstract Atypical teratoid/rhabdoid tumors (AT/RTs) and primitive neuroectodermal tumors of the central nervous system (CNS-PNET) are rare pediatric brain tumors affecting mainly infants and young children. Current therapies for these diseases are inefficient and often cause severe side effects; thus, new therapeutic strategies are urgently needed. Here, we evaluate the anti-tumor effect of the Delta-24-RGD oncolytic adenovirus in preclinical models of CNS-PNET and AT/RT. In vitro, the virus infects and efficiently replicates in different cell culture models of AT/RT and CNS-PNET, inducing a dose-dependent cytotoxic effect (IC50 values below 1 PFU/cell) and the release of immunogenic cell death stimuli. Survival studies in mice bearing orthotopic AT/RTs (supra and infratentorial) or CNS-PNETs demonstrate the therapeutic benefit of a single Delta-24-RGD intratumoral administration (107 or 108 PFU). In virus-treated mice, median overall survival increased between 50–300% (depending on the model), obtaining up to 60% of long-term survivors. Intra-ventricular injection of Delta-24-RGD hinders the development of secondary AT/RT spinal lesions. Moreover, response to the treatment was observed even delaying viral administration up to 30 days after tumor engraftment; thus, demonstrating therapeutic benefit even in animals challenged with large well-established tumor masses. The effect of the oncolytic virus was also assessed in an immunocompetent environment using hCD34+ humanized NSG-SGM3 mice. In this model, Delta-24-RGD significantly extended overall survival (from 23 to 24 days in AT/RT model and from 28 to 55 days in CNS-PNET) with no signs of toxicity associated with inflammation. Immunophenotyping of Delta-24-RGD treated tumors by flow cytometry, RNAseq and multiplexed histology revealed that Delta-24-RGD contributes to generate a pro-inflammatory status, allowing the infiltration of immune cells and the trigger of an antitumor immune response. In conclusion, these results demonstrate that Delta-24-RGD could be a feasible therapeutic choice for AT/RT and CNS-PNET, paving the way for upcoming clinical trials.
Impact of Exercise on Chemotherapy Tolerance and Survival in Early-Stage Breast Cancer: A Nonrandomized Controlled Trial
Authors: Amy A. Kirkham, Karen A. Gelmon, Cheri L. Van Patten, Kelcey A. Bland, Holly Wollmann, Donald C. McKenzie, Taryne Landry, Kristin L. Campbell
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: Available preliminary evidence is conflicting on whether exercise can positively influence antineoplastic treatment tolerance and in turn improve survival. Patients and Methods: This study compared chemotherapy treatment tolerance and survival among women receiving adjuvant chemotherapy for early-stage breast cancer who participated in a single-arm trial of supervised aerobic and resistance exercise programming versus a historical cohort that did not receive structured exercise programming. Results: The exercise group (EX; n=73) and control group (CTR; n=85) participants were matched on age and treatment and balanced on medical history, cancer diagnosis, and body mass index. Attendance in the EX group was 64% ± 27% of 3 offered sessions per week. For all chemotherapy agents combined, the relative risk (RR) of a chemotherapy dose reduction (RR, 0.78; 95% CI, 0.54–1.11) or delay (RR, 1.05; 95% CI, 0.62–1.80) did not differ between groups. However, the EX group had reduced relative and absolute risks of a dose reduction in doxorubicin by 60% and 18%, respectively. For all agents combined, there were no differences between groups in risk of anemia, neutropenia, or weight gain. In the EX group, dose reductions due to neutropenia ( P =.027), other infections ( P =.049), and fatigue ( P =.037) were less common, whereas mucositis was more common ( P =.023), compared with the CTR group. The EX group had reduced relative and absolute risks of weight gain on the docetaxel + cyclophosphamide regimen by 38% and 30%, respectively. After a median follow-up of 70 months (range, 54–84 months), there was no difference between the EX and CTR groups in disease-free survival events (n=8 [11%] vs n=9 [11%], respectively; log-rank test, P =.78) or overall survival events (n=5 [7%] vs n=6 [7%], respectively; log-rank test, P =.974). Conclusions: Overall, exercise programming during adjuvant chemotherapy does not appear to impact treatment tolerance or survival in women receiving common modern regimens of adjuvant chemotherapy for early-stage breast cancer. However, exercise may provide selective benefits, depending on the treatment regimen received.
MBCL-26. FACTORS ASSOCIATED WITH LONGER SURVIVAL AFTER FIRST RECURRENCE IN MEDULLOBLASTOMA BY MOLECULAR SUBGROUP AFTER RISK-BASED INITIAL THERAPY
Authors: Murali Chintagumpala, Colton Terhune, Lin Tong, Eric Bouffet, Ute Bartels, Michael Fisher, Tim Hassall, Shridharan Gururangan, Kristin Schroeder, Jordan Hansford, Dong Anh Khuong Quang, Richard Cohn, Stewart Kellie, Geoffrey McCowage, Kyle Smith, Paul Northcott, Giles Robinson, Amar Gajjar
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE To evaluate differences in time to recurrence among molecular subgroups of medulloblastoma treated on a single protocol and to identify factors associated with survival after first recurrence. METHODS Time to recurrence following SJMB03 treatment was compared across methylation subgroups among relapsed patients. Therapies received subsequent to relapse were noted. Kaplan-Meier methods and log-rank tests were used for statistical analyses. RESULTS 74 of 330 medulloblastoma patients developed recurrence after initial therapy. (38 Standard-Risk; 36 High-Risk). The 2- and 5-year survival after first recurrence was 30.4% and 14.6% respectively. DNA methylation-based subgroups from initial diagnosis were SHH (n=14), Group 3 (n=24), Group 4 (n=26), and unclassified (n=8). None of the pts with WNT MB had recurrent disease. Median time to first recurrence was 1.23, 0.91, and 3.09 years in SHH, Group3, and Group 4 respectively. Group 4 patients had longer post-recurrence survival than others (p-value=0.0169). Clinical risk at diagnosis (p-value=0.337), anaplasia (p-value=0.4032), TP53 (p-value=0.1969), MYC (p-value=0.8967), and MYCN (p value = 0.9404) abnormalities were not associated with post progression survival. Patients who received any therapeutic modality (chemotherapy, re-radiation and second surgery) had longer survival and those who had all three (n=10) had the best outcome (p-value&amp;lt;0.0001). CONCLUSION Outcome after recurrence in medulloblastoma is dismal, however, association with subgroups is still present. Group 4 patients had a longer time to recurrence and post progression survival. No other prognostic factor at initial diagnosis was associated with outcome after recurrence. Patients who received all 3 types of conventional therapy had better survival.
Incidence of SARS-CoV-2 Infection Among Patients Undergoing Active Antitumor Treatment in Italy
Authors: Carlo Aschele, Maria Emanuela Negru, Alessandro Pastorino, Luigi Cavanna, Vittorina Zagonel, Francesco Barone-Adesi, Livio Blasi
Journal: JAMA Oncology (2020)

This cohort study examines rates of SARS-CoV-2 infection among patients with cancer receiving antitumor treatment.
EPCT-02. PBTC-051: FIRST IN PEDIATRICS PHASE 1 STUDY OF CD40 AGONISTIC MONOCLONAL ANTIBODY APX005M IN PEDIATRIC SUBJECTS WITH RECURRENT/REFRACTORY BRAIN TUMORS
Authors: Holly Lindsay, Arzu Onar-Thomas, Mehmet Kocak, Tina Young Poussaint, Girish Dhall, Alberto Broniscer, Anna Vinitsky, Tobey MacDonald, Ovid Trifan, Jason Fangusaro, Ira Dunkel
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND CD40 is a co-stimulatory molecule expressed on antigen presenting cells (APCs). APX005M is a CD40 agonist monoclonal antibody which stimulates innate and adaptive anti-tumor immunity through activation of APCs, macrophages, and antigen-specific CD8+T-cells. Pediatric Brain Tumor Consortium study PBTC-051 is the first investigation of APX005M in pediatric patients and is evaluating the safety, recommended phase 2 dose (RP2D), pharmacokinetics, and preliminary efficacy of APX005M in children with central nervous system (CNS) tumors. RESULTS Accrual of patients with recurrent/refractory primary malignant CNS tumors (stratum 1) began in March 2018. 16 patients (2 ineligible) have enrolled on this stratum; 14 were treated. Dose escalation through 3 planned dose levels of APX005M was completed without excessive or unanticipated toxicities. The highest dose level (0.6 mg/kg q3 weeks) is the presumptive RP2D, and an expansion cohort is currently enrolling at this dose. 2 patients at dose level 3 have received &amp;gt;12 cycles of therapy. Grade 3 or higher adverse events at least possibly attributable to APX005M include 11 lymphopenia, 5 neutropenia, 5 leukopenia, 3 ALT elevations, 1 AST elevation, 1 thrombocytopenia, and 1 hypoalbuminemia. PK data will be available March 2020. Stratum 2 is now enrolling patients with post-radiation/pre-progression DIPG beginning at dose level 2, with 1 patient currently enrolled. CONCLUSION The CD40 agonistic antibody APX005M has demonstrated preliminary safety in pediatric patients with recurrent/refractory primary malignant CNS tumors and has a likely RP2D of 0.6 mg/kg q3 weeks in this population. Preliminary efficacy data are pending.
NCOG-06. A NOVEL ONLINE CALCULATOR PREDICTING SHORT-TERM POSTOPERATIVE OUTCOMES IN METASTATIC BRAIN CANCER PATIENTS
Authors: Adham Khalafallah, Adrian Jimenez, Palak Patel, Sakibul Huq, Omar Azmeh, Debraj Mukherjee
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Establishing predictors of hospital length of stay (LOS), discharge deposition, and total hospital charges is essential to providing high-quality, value-based care. Though previous research has investigated these outcomes for patients with metastatic brain tumors, there are currently no tools that synthesize such research findings and allow for prediction of these outcomes on a patient-by-patient basis. OBJECTIVE We sought to develop a prediction calculator that uses patient demographic and clinical information to predict extended hospital length of stay, nonroutine discharge disposition, and high total hospital charges for patients with metastatic brain tumors. METHODS Patients undergoing surgery for metastatic brain tumors at a single academic institution were analyzed (2017-2019). Multivariate logistic regression was used to identify independent predictors of extended LOS (&amp;gt; 8 days), nonroutine discharge, and high total hospital charges (&amp;gt; $45,660.00). p &amp;lt; 0.05 was considered statistically significant. C-statistics and the Hosmer-Lemeshow test were used to assess model discrimination and calibration, respectively. RESULTS A total of 222 patients were included in our analysis, with a mean age of 62.2 years. The majority of patients were male (52.7%) and Caucasian (76.6%). Our models predicting extended LOS, nonroutine discharge, and high hospital charges had optimism-corrected c-statistics &amp;gt; 0.7, and all three models demonstrated adequate calibration (p &amp;gt; 0.05). The final models are available as an online calculator (https://neurooncsurgery.shinyapps.io/mets_brain_cancer_calculator/). CONCLUSIONS Our models predicting postoperative outcomes allow for individualized risk-estimation for patients following surgery for metastatic brain cancer. Our results may be useful in helping clinicians to provide high-value care and to ensure optimal patient outcomes
Abstract 17451: Accumulation of Phospholamban at the Nuclear Envelope Delays Its Trafficking Along a Transverse Sarcoplasmic Reticulum (SR) Pathway Common to Serca2a and Other SR Proteins
Authors: Danning Wang, Juyi Wan, Steven Cala, Zhenhui Chen
Journal: Circulation (2017)

Introduction: Phospholamban (PLB) and cardiac Ca-pump (SERCA2a) are key to SR Ca handling. We recently showed that PLB is concentrated in the nuclear envelope (NE) of cardiomyocytes (CMs), with a r...