tbuckley/cabot-search huggingface dataset:
ANGINA IS ASSOCIATED WITH CORONARY BLOOD FLOW - RESULTS FROM THE NHLBI-SPONSORED WOMEN'S ISCHEMIA SYNDROME EVALUATION: CORONARY VASCULAR DYSFUNCTION (WISE-CVD) PROJECT
Authors: Nissi Sharon Suppogu, Janet Wei, Chrisandra Shufelt, Galen Cook-Wiens, David R. Anderson, Bruce Samuels, John W. Peterson, Carl J. Pepine, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2019)
ASSOCIATION OF LOW MYOCARDIAL BLOOD FLOW RESERVE ON LONG-TERM SURVIVAL DOES NOT VARY BY PATIENT SEX, REGARDLESS OF PRE-TEST CLINICAL RISK OR POST-TEST REVASCULARIZATION
Authors: Krishna Patel, Leslee J. Shaw, Brett Sperry, John A. Spertus, Arthur McGhie, Kevin Kennedy, Randall Thompson, Firas Al Badarin, Paul Chan, Timothy Bateman
Journal: Journal of the American College of Cardiology (2019)
THE INCREASE OF CAROTID TEMPERATURES IN PATIENTS WITH DOCUMENTED CORONARY ARTERY DISEASE UNDER OPTIMAL MEDICAL THERAPY INDEPENDENTLY PREDICTS MAJOR ADVERSE CARDIOVASCULAR AND CEREBROVASCULAR EVENTS
Authors: Konstantinos Toutouzas, George Oikonomou, George Benetos, Koutagiar Iosif, Spiros Galanakos, Maria Karmpalioti, Nikolaos Barampoutis, Periklis Davlouros, Elias Siores, Tousoulis Dimitrios
Journal: Journal of the American College of Cardiology (2019)
NOVEL 24-HOUR BLOOD PRESSURE PROFILE IN PATIENTS WITH RESISTANT HYPERTENSION
Authors: Mohammed Siddiqui, Byron C. Jaeger, Eric Judd, Tanja Dudenbostel, David M. Pollock, Jennifer Pollock, Martin Young, Lloyd J. Edwards, Suzanne Oparil, David Calhoun
Journal: Journal of the American College of Cardiology (2019)
Clare Gerada: Doctors and their defences
Authors: Clare Gerada
Journal: BMJ (2019)

Working as a doctor is draining—emotionally, intellectually, and physically. Doctors bear the burden of some of the most painful aspects of patients’ problems, they witness trauma, and they regularly deal with loss. And no one benefits if doctors break down every time they have to give bad news to a patient.

To survive a lifetime in medicine doctors must learn techniques to cope with their job. They need to stay emotionally present without becoming distant. They must prevent overidentification, remain patient centred, and maintain professional boundaries.

Some of these techniques are practical: time management, delegation, safety netting, and “housekeeping.” …
LIKELIHOOD OF SPONTANEOUS CARDIOVERSION AMONG PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT FOR ATRIAL FIBRILLATION AT SHORT-TERM FOLLOW-UP
Authors: Bryan Abadie, Benjamin Hansen, Adam Bernstein, Jennifer Walker, Rohan Pasi, Heather Tuttle, Tiffany Armbruster, Murrium Sadaf, Kevin Biese, Zachariah Deyo, Anil Gehi
Journal: Journal of the American College of Cardiology (2019)
AN OUTCOME COMPARISON OF PERCUTANEOUS CORONARY INTERVENTION VERSUS CORONARY ARTERY BYPASS GRAFTING IN ELDERLY PATIENT WITH MULTI-VESSEL CORONARY ARTERY DISEASE
Authors: Hassan Alkhawam, Preetham Reddy Muskula, Fadi Ghrair, Stephanie Windish, James Ampadu, Andrew Kichura, Joseph Lieber, Michael Lim, Tarek Helmy
Journal: Journal of the American College of Cardiology (2019)
Abstract 537: Identifying Novel Regulators of Mitochondrial Complex I Biogenesis
Authors: Christian J Garcia
Journal: Circulation Research (2018)

Mitochondrial Complex I (CI) is composed of 44 distinct subunits, that are assembled together with eight Fe-S clusters and a single flavin mononucleotide, to form a functioning enzyme. Chaperone proteins referred to as assembly factors assist with the assembly process; and a dozen or so bona fide CI assembly factors (CIAFs) have been characterized. However, about half of CI disorders cannot be traced to mutations in any of the 44 CI subunits or known assembly factors, suggesting that additional regulators of CI biogenesis remain to be characterized. Studies from our lab have shown that the mechanism of CI assembly is conserved between humans and Drosophila , allowing us to exploit our system to find novel regulators of CI biogenesis. In our studies, we use a genetic and proteomic approach to identify novel regulators of CI assembly that interact with NDUFS3 (a CI subunit); and have tested these candidate regulators in both Drosophila and humans cell lines. The ease of isolating copious amounts of mitochondria from flight muscles, extensive arsenal of tools for genetic analyses, relatively short generation time, and limited gene redundancy in Drosophila are assets that should facilitate the discovery of new regulators of CI assembly.
Abstract 519: Mitochondrial-mediated Oxidative CaMKII Activation Induces Early Afterdepolarizations in Guinea Pig Cardiomyocytes: An <i>in Silico</i> Study
Authors: Ruilin Yang, Patrick Ernst, Jiajia Song, Xiaoguang M Liu, Jianyi Zhang, Lufang Zhou
Journal: Circulation Research (2018)

Background: Oxidative stress-mediated CaMKII phosphorylation of cardiac ion channels has emerged as a critical contributor to arrhythmogenesis in cardiac pathology. However, the link between mitochondrial-derived reactive oxygen species (mdROS) and increased CaMKII activity in the context of cardiac arrhythmias has not been fully elucidated and is difficult to establish experimentally. Methods: We hypothesize that pathological mdROS can cause erratic action potentials through the oxidation-dependent CaMKII activation pathway. We further propose that CaMKII dependent phosphorylation of sarcolemmal slow sodium channels alone is sufficient to elicit early afterdepolarizations. To test the hypotheses, we expanded our well-established guinea pig cardiomyocyte e xcitation- c ontraction coupling, m itochondrial e nergetics and R OS- i nduced- R OS- r elease model by incorporating oxidative CaMKII activation and CaMKII-dependent Na + channel phosphorylation in silico . Results: Simulations show that mdROS mediated-CaMKII activation elicits early afterdepolarizations (EADs) by augmenting the late Na + currents ( I Na,L ), which can be suppressed by blocking L-type Ca 2+ channels or Na + /Ca 2+ exchangers. Interestingly, we found that oxidative CaMKII activation-induced EADs sustain even after mdROS has returned to its physiological levels. Moreover, mitochondrial-targeting antioxidant treatment can suppress the EADs, but only if given in an appropriate time window. Incorporating concurrent mdROS-induced RyRs activation further exacerbates the proarrhythmogenic effect of oxidative CaMKII activation. Conclusions: We conclude that oxidative CaMKII activation-dependent Na channel phosphorylation is a critical pathway in mitochondria mediated cardiac arrhythmogenesis.
INCREASED RATES OF CARDIOVERSION AND ABLATION IN PATIENTS WITH ATRIAL FIBRILLATION AND SLEEP APNEA COMPARED TO PATIENTS WITH ATRIAL FIBRILLATION ALONE: A NATIONWIDE STUDY
Authors: Alba Munoz Estrella, Faris Haddadin, Dhrubajyoti Bandyopadhyay, Hassan Beydoun, Vivek Modi, Eyal Herzog
Journal: Journal of the American College of Cardiology (2019)
YIELD OF GENETIC TESTING IN NEONATES WITH CONGENITAL HEART DISEASE AND ASSOCIATION WITH CLINICAL OUTCOMES
Authors: Shannon Nees, Katharine Press Callahan, Sonya Besagar, Teresa Lee, Volkan Okur, Emily Griffin, Jiayao Wang, Yufeng Shen, Wendy K. Chung
Journal: Journal of the American College of Cardiology (2019)
Predictors for Recurrent 30-Day Unplanned Readmissions in Patients with Hematologic Malignancies
Authors: Girish Kunapareddy, Hina Ahmed, Sagar S. Patel, Bhumika J. Patel, Paul Elson, Alicia Bitterice, Aaron T. Gerds, Hetty E. Carraway, Anjali S. Advani, Aziz Nazha, Alberto J. Montero, Brad Pohlman, Colleen Strazalka, Joseph Hooley, Alicia Redden, Katherine Tullio, Kimberly Bell, Matt Kalaycio, Mikkael A. Sekeres, Sudipto Mukherjee
Journal: Blood (2017)
PREDICTORS OF ONE-YEAR MORTALITY IN PATIENTS SELECTED FOR PERCUTANEOUS CORONARY INTERVENTION BY A MULTIDISCIPLINARY HEART TEAM
Authors: Emily Pardington, Sheetal Maragiri, Paulina Phomvongsa, Sabina Shamayeva, Sheridan Reed, Erica Osip, DeeAnn Stickland, John Mulder, Denise Busman, Abbey Mulder, Stacie Vanoosterhout, Jessica Parker, Theodore Boeve, Richard McNamara, Ryan Madder
Journal: Journal of the American College of Cardiology (2019)
BEAT-TO-BEAT VARIABILITY OF MITRAL ANNULUS DIMENSIONS IN ATRIAL FIBRILLATION: IMPLICATIONS FOR PERCUTANEOUS INTERVENTIONS
Authors: Hilal Olgun Kucuk, Jeremy Thaden, Didem Oguz, Vuyisile Nkomo, Garvan Kane, Cristina Pislaru, Maurice Enriquez-Sarano, Charanjit Rihal, Mackram Eleid, Patricia Pellikka, Sorin Pislaru
Journal: Journal of the American College of Cardiology (2019)
Frontiers of Medical Robotics: From Concept to Systems to Clinical Translation
Authors: Jocelyne Troccaz, Giulio Dagnino, Guang-Zhong Yang
Journal: Annual Review of Biomedical Engineering (2019)

Medical robotics is poised to transform all aspects of medicine-from surgical intervention to targeted therapy, rehabilitation, and hospital automation. A key area is the development of robots for minimally invasive interventions. This review provides a detailed analysis of the evolution of interventional robots and discusses how the integration of imaging, sensing, and robotics can influence the patient care pathway toward precision intervention and patient-specific treatment. It outlines how closer coupling of perception, decision, and action can lead to enhanced dexterity, greater precision, and reduced invasiveness. It provides a critical analysis of some of the key interventional robot platforms developed over the years and their relative merit and intrinsic limitations. The review also presents a future outlook for robotic interventions and emerging trends in making them easier to use, lightweight, ergonomic, and intelligent, and thus smarter, safer, and more accessible for clinical use.
INFERIOR VENA CAVA DIAMETER MEASUREMENT PROVIDES DISTINCT AND COMPLEMENTARY INFORMATION TO RIGHT ATRIAL PRESSURE IN ACUTE DECOMPENSATED HEART FAILURE
Authors: Matthew Griffin, Veena Rao, Devin Mahoney, Brendan Stewart, Griffin Struyk, Peri Shamlian, Megan Pattoli, Nicole Gomez, Parinita Raghavendra, Joslyn Barnett, Anvin Thomas, Emily Wycallis, James Fleming, Jeffrey M. Testani
Journal: Journal of the American College of Cardiology (2019)
Recent therapeutic trends and promising targets in triple negative breast cancer
Authors: Soo-Yeon Hwang, Seojeong Park, Youngjoo Kwon
Journal: Pharmacology & Therapeutics (2019)

Breast cancer accounts for 25% of all types of cancer in women, and triple negative breast cancer (TNBC) comprises around 15~20% of breast cancers. Conventional chemotherapy and radiation are the primary systemic therapeutic strategies; no other FDA-approved targeted therapies are yet available as for TNBC. TNBC is generally characterized by a poor prognosis and high rates of proliferation and metastases. Due to these aggressive features and lack of targeted therapies, numerous attempts have been made to discover viable molecular targets for TNBC. Massive cohort studies, clinical trials, and in-depth analyses have revealed diverse molecular alterations in TNBC; however, controversy exists as to whether many of these changes are beneficial or detrimental in caner progression. Here we review the complicated tumorigenic processes and discuss critical findings and therapeutic trends in TNBC with a focus on promising therapeutic approaches, the clinical trials currently underway, and potent experimental compounds under preclinical and evaluation.
Abstract 477: Using Computational Models to Predict Stem Cell Function
Authors: Farnaz Shoja-Taheri, Alex George, Manu O Platt, Michael E Davis
Journal: Circulation Research (2018)

Congenital heart defects (CHD) are among the most common reasons of mortality in newborns and despite advanced surgical treatments, many patients experience heart failure. Currently, transplantation is the most effective cure for heart defects which has its own limitations such as the possibility of organ rejection. Stem cell/progenitor cell therapy is a novel method in treating heart failure in congenital heart patients. However, choosing stem cells with highest regenerative effects has been a challenge and there is tremendous patient-to-patient variability. We previously showed the age-dependent regenerative effects of human cardiac progenitor cells (hCPCs) in a rat model of juvenile heart failure. In the same study, using a small subset of patients, computational modeling analysis showed that regression models could be made linking sequencing data to phenotypic outcomes. In the current study, we used that quantitative model to determine whether predictions can be made in a larger population of patients regarding cell function in neonatal hCPCs. The goal of this study was to validate the functional responses in each neonatal hCPC line and confirm our model. We performed RNAseq from CPCs isolated from 8 different neonatal patients. We tested 2 functional parameters of our model, proliferation and chemotactic potential of conditioned media using Click-it Edu and Boyden chamber assays, respectively. Interestingly, the observed proliferation and migration responses in each of the selected neonatal hCPC lines matched their predicted counterparts. Furthermore, in vitro analysis verified our model in that one of the neonate hCPCs performed far worse than other patients as predicted. Altogether, these data show that cell behavior may be predicted using large data like RNAseq, and that we may be able to identify patients that may exceed or underperform expectations. With systems biology approaches, interventions can be tailored to improve cell therapy, or mimic the qualities of reparative cells.
Abstract P333: Characteristics Associated With Lower Blood Pressure When Using a Sit-Stand Desk
Authors: John M Taormina, Robert J Kowalsky, Sophy J Perdomo, Melissa A Jones, Bethany Barone Gibbs
Journal: Circulation (2018)

Introduction: In a recent randomized crossover trial, using a sit-stand desk to alternate postures resulted in small but statistically significant decreases in average blood pressure (BP) across a simulated workday. Hypothesis: We tested the hypothesis that certain baseline characteristics are associated with a greater acute BP-lowering response to use of a sit-stand desk. Methods: This secondary analysis used data from all subjects (n=25; 36% female; mean (SD) age 42 (12) years, screening baseline SBP 132 (9) mmHg and DBP 83 (8) mmHg, BMI 32 (5) kg/m 2 ) completing a randomized crossover study with two simulated workday conditions: 1) continuous sitting (SIT) and 2) alternating sitting and standing every 30 minutes (SS). Oscillometric BP was measured hourly. Average time spent sitting and in moderate-to-vigorous intensity physical activity (MVPA) were reported using the Global Physical Activity Questionnaire. Linear regression models identified whether participant characteristics (morning BP per 10 mmHg; age &gt; 50 years; sex (female); MVPA ≥ 150 mins/week; sedentary time ≥ 10 hours/day; BMI ≥ 30 kg/m 2 ) were associated with a greater BP-lowering effect of using a sit-stand desk with a backward selection stepwise approach removing independent variables with P ≥ 0.2. Results: Lower morning baseline SBP (β = 2.8 mmHg per 10 mmHg, P = 0.012) and higher MVPA (β = -4.4 mmHg, P = 0.025) were associated with a greater SBP-lowering effect; higher age (β = -3.8 mmHg, P = 0.170) and higher BMI (β = 4.2 mmHg, P = 0.067) were retained in the model but were not statistically significant. Higher MVPA (β = -3.0 mmHg, P = 0.040) and lower BMI (β = 4.1 mmHg, P = 0.002) were associated with a greater DBP-lowering effect; female sex (β = -1.7 mmHg, P = 0.172) was retained in the model but was not statistically significant ( Figure 1 ). Conclusions: In conclusion, physically active, non-obese adults with lower SBP experienced the most beneficial BP response to intermittent standing. Future studies should investigate the mechanisms explaining this acute BP response.
CREATININE VERSUS CYSTATIN C TO ESTIMATE GLOMERULAR FILTRATION RATE IN ADULTS WITH CONGENITAL HEART DISEASE
Authors: Saurabh Rajpal, Matthew Carazo, Michael Singh, Konstantinos Dimopoulos, David Alejandro Cardona Estrada, Sushrut Waikar, Finnian McCausland, Ahmed Elantably, Gruschen Veldtman, Jasmine Grewal, Brittani Loukas, Catherine Gray, Alexander Opotowsky
Journal: Journal of the American College of Cardiology (2019)
Abstract 243: Modeling of Diastolic Dysfunction in Induced Pluripotent Stem Cell-derived Cardiomyocytes From Hypertrophic Cardiomyopathy Patients
Authors: Haodi Wu, Huaxiao Yang, June-Wha Rhee, Joe Zhang, Chi Keung Lam, Karim Sallam, Alex C Chang, Ning Ma, Helen Blau, Donald Bers, Joseph Wu
Journal: Circulation Research (2018)

Aims: Diastolic dysfunction (DD) is common among hypertrophic cardiomyopathy (HCM) patients, causing major morbidity and mortality. Yet its cellular mechanisms are not fully understood, and presently, there is no effective treatment. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold great potential for investigating the mechanisms underlying DD and as a platform for drug discovery. Methods and results: In the present study, beating iPSC-CMs were generated from healthy recruits and HCM patients with evident DD. Micropatterned iPSC-CMs from HCM patients showed impaired diastolic function, as evidenced by prolonged relaxation time, retarded relaxation rate, and shortened diastolic sarcomere length. Ratiometric Ca 2+ imaging indicated elevated diastolic [Ca 2+ ] i and abnormal Ca 2+ handling in HCM iPSC-CMs, which were exacerbated by β-adrenergic challenge. Combining Ca 2+ imaging and traction force microscopy (TFM), we observed enhanced myofilament Ca 2+ sensitivity (measured as dF/Δ[Ca 2+ ] i ) in HCM iPSC-CMs. These results indicated that cytosolic diastolic Ca 2+ overload, slowed [Ca 2+ ] i decline and increased myofilament Ca 2+ sensitivity, collectively impair the relaxation of HCM cells. Treating HCM iPSC-CMs with partial blockade of Ca 2+ or late Na + current reset diastolic Ca 2+ homeostasis, restored diastolic function and improved long-term survival, suggesting disturbed Ca 2+ signaling is an important cellular pathological mechanism of DD. Further investigation showed increased expression of L-type calcium channel (LTCC) and transient receptor potential channels (TRPCs) in HCM iPSC-CMs, which likely contribute to diastolic [Ca 2+ ] i overload. Conclusion: In summary, this study recapitulated DD at the single cell level, and revealed novel mechanisms and potential therapeutic targets of DD using HCM iPSC-CMs.
Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies
Authors: Janice M. Bonsu, Avirup Guha, Lawrence Charles, Vedat O. Yildiz, Lai Wei, Brandee Baker, Jonathan E. Brammer, Farrukh Awan, Maryam Lustberg, Raquel Reinbolt, Eric D. Miller, Hani Jneid, Patrick Ruz, Rebecca R. Carter, Michael W. Milks, Electra D. Paskett, Daniel Addison
Journal: Journal of the American College of Cardiology (2020)
Abstract 275: Activating Transcription Factor 3 Protects Against Obesity and Metabolic Dysfunction Through Promoting Lipolysis and Adipocytes Browning
Authors: Ching-Feng Cheng, Hui-Chen Ku, Pei-Fang Lai, Heng Lin
Journal: Circulation Research (2017)

Recent studies implying that promoting lipolysis or enhancing brown remodeling of white adipose tissue is a potential strategy to treat obesity and metabolic syndrome. Activating transcription factor 3 (ATF3) is a member of the ATF/cAMP-response element binding protein family of transcriptional factors. It is upregulated under stress condition in a variety of tissues, including the adipocytes. However, the mechanism of ATF3 in adipocytes and obesity regulation are not clear. We gave high-fat-diet (HFD) to both ATF3-/- (KO) and their wild type littermates (WT) for 16 weeks. KO showed obvious obesity as compared to WT. The obese KO mice then received AAV8-mediated gene transfer of ATF3 (AAV8-ATF3) at 16 weeks, in which decrease body weights were observed as compared to KO receiving AAV8-GFP. Histology demonstrated increased adipocyte cell diameter in KO, in which such enlargement of adipocytes can be reversed by AAV8-ATF3 therapy. We then used ATF3-overexpressing 3T3-L1 preadipocytes for in vitro studies. These cells demonstrated decreased lipid accumulation with diminished adipogenic markers (C/EBPα, PPARγ2, FABP4, and perilipin 1) and lipogenic markers (ACC1, ACC2, FAS, ChREBP, and SREBP1) as compared to the control cells. To our surprise, ATF3 overexpressed 3T3-L1 cells also demonstrated increased lipolysis (ATGL, HSL, and MGL), upregulated mitochondrial protein UCP1 and PCG1α expression, and enhanced brown/beige genes expression (Prdm16, Dio2, CIDEA, Tbx1, and Elovl3) as compared to control cells. Mechanistically, our ChIP assay found that ATF3 can directly repress ChREBP activity and ATF3 enhanced adipocyte browning via inhibition of SCD1. Lastly, we established a screening platform for ATF3 inducer, and found compound 5 could induce ATF3 expression. Our results demonstrated that compound 5 could induce UCP1 and promote lipolysis and white adipocyte browning in vitro and inhibit HFD induced obesity and increase insulin sensitivity in vivo. In summary, our findings confirmed ATF3 and its inducer, can promote lipolysis, increase UCP1 expression, and enhance adipocytes white-to-brown trans-differentiation through ChREBP and SCD1 pathways, thus represent an attractive drug candidate to protect against obesity and metabolic dysfunction.
Implantable Cardiac Alert System for Early Recognition of ST-Segment Elevation Myocardial Infarction
Authors: C. Michael Gibson, David Holmes, Ghiath Mikdadi, Dale Presser, David Wohns, Megan K. Yee, Andrew Kaplan, Allen Ciuffo, Arthur L. Eberly, Bruce Iteld, Mitchell W. Krucoff
Journal: Journal of the American College of Cardiology (2019)
Changes in airway inflammation, remodelling and PD20 following inhaled corticosteroid treatment are not temporally concordant
Authors: C. Ward, R. Bish, D. Reid, S. Gollant, M. Pais, G. Westall, E. H. Walters
Journal: Thorax (2000)

Introduction. There have been direct calls for studies evaluating the relationship of airway inflammation to airway remodelling, lung function and BHR (Pedersen S. AJRCCM. 2000; 161 : pp S182-185). Current asthma guidelines rely on lung function and symptoms in management decisions. Methods. In a prospective, double blind study 33 steroid naive, symptomatic asthmatics were randomised to receive FP 750μg bd or identical placebo. We obtained airway biopsies and 3x60 mL BAL at time zero, 3 and 12 months. 2μm glycol methacrylate embedded sections were stained for collagen I for assessment of reticular basement membrane thickness (rbm) using image analysis (Image Pro Plus). In addition BAL differential cell counts and PD20 FEV1.0 to methacholine (BHR) were assessed at each time point. Results. Mean (s.d) rbm was increased in asthmatics vs normals (9.1±2.2 vs 7.7±1.μm,p=0.003), as were % BAL eosinophils (2.9±4.1 vs 1.0±1.62, p=0.011) and mast cells (0.13±0.13 vs 0.03±0.04, p 6.4)**,∧ 1.3±1.7**,# 0.06±.06**# **p<0.01 vsbaseline, *p<0.05 vs3 months, ∧p<0.001 vs3 months, #p<0.05vsplacebo. Summary. Increased rbm thickness is related both to airway inflammation and BHR. ICS can modulate airway wall remodelling but this begins later than changes in spirometry, PD20 and airway inflammation. PD20 continues to improve as modulation of airway remodelling occurs. Conclusions: Changes in airway inflammation, spirometry, PD20 and airway remodelling are not temporally concordant. Maximal benefit of ICS on spirometry and inflammation are manifest before changes in airway remodelling or maximal benefits in BHR. Prolonged ICS treatment is necessary if maximal improvement in PD20 and airway remodelling are desired. Current asthma guidelines, based on lung function and symptoms, do not provide an index of disease progression reflecting these long-term effects of ICS.