tbuckley/cabot-search huggingface dataset:
Abstract 13902: Gender Differences in Lipoprotein Parameters in Cardiovascular Disease Risk; The Framingham Offspring Study
Authors: Hiroaki Ikezaki, Elise Lim, Ching-Ti Liu, L Adrienne Cupples, Bela F Asztalos, Masayuki Murata, Norihiro Furusyo, Ernst J Schaefer
Journal: Circulation (2020)

Introduction: Elevated serum lipoprotein cholesterol levels have been considered as atherosclerosis cardiovascular disease (ASCVD) risk factors. However, gender differences among these lipoproteins have not become clear. Hypothesis: Our hypothesis was that gender differences exist with regard to serum lipoprotein cholesterol levels and the risk of ASCVD risk in the prospective Framingham Offspring Study. Methods: A total of 1300 men and 1676 women, none of whom had ASCVD at baseline, were followed for a median time of 16 years for new onset fatal or non fatal myocardial infarction or stroke, coronary angioplasty or bypass, or carotid or peripheral vascular surgery (302 of 1300 or 23.2% of men and 226 of 1676 or 13.5% of women developed). At baseline, standard risk factors including fasting total and high density lipoprotein (HDL) cholesterol, and triglycerides were assessed, as were direct, small dense, and large low density lipoprotein (LDL) cholesterol and LDL triglyceride (LDL-TG), remnant lipoprotein cholesterol and lipoprotein(a) were measured. Univariate and multivariate analyses were carried out to assess relationships to disease risk. Results: All parameters were associated with ASCVD risk on univariate analysis. On multivariate analysis after controlling for all standard risk factors (age, hypertension, use of anti-hypertensive medication, diabetes, smoking, total cholesterol, HDL cholesterol, and use of cholesterol lowering medication), only lipoprotein(a) was significant in men with a 1.26 hazard ratio (P = 0.009), while small dense LDL cholesterol and LDL-TG, but not lipoprotein(a), were significant risk factors in women (hazard ratios 1.65 and 1.35, P = 0.007 and 0.015, respectively). Using the pooled cohort equation, only lipoprotein(a) added significant risk information in men and only small dense LDL cholesterol and LDL-TG added significant risk information in women. Conclusions: Our data indicate that men are at significantly higher disease risk then women, and that elevated lipoprotein(a) is a significant independent ASCVD risk factor in men, while small dense LDL cholesterol and LDL-TG are significant independent ASCVD risk factors in women after controlling for all other standard cardiovascular disease risk factors.
Abstract 14884: Invasive Hemodynamic Remote Monitoring for Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Alexander G Hajduczok, Samer N Muallem, Matthew S Nudy, Ami L DeWaters, John P Boehmer
Journal: Circulation (2020)

Background: In heart failure (HF) patients, remote monitoring of hemodynamics using implantable devices may be used to predict and reduce HF exacerbations. Methods: A meta-analysis of randomized controlled trials (RCTs) testing remote monitoring versus standard of care for management of HF patients was performed. Endpoints included all-cause mortality and Cardiovascular (CV)/HF hospitalizations. Risk Ratios (RR) and 95% confidence intervals (CI) were calculated for each endpoint. A secondary analysis tested for heterogeneity of treatment effect (HTE) using Chi 2 and I 2 tests comparing implanted right ventricular/pulmonary pressure monitoring versus impedance-based monitoring on HF hospitalization. Results: 10 RCTs (n=6,020) were identified with a mean follow-up of 1.74 years. The mean age and reported ejection fraction were 64.1 and 27.1%, respectively. Remote monitoring did not reduce mortality (RR 0.88, [95% CI 0.76, 1.03]) or CV/HF hospitalizations (RR 0.99, [0.81, 1.20]) (Figure 1). When performing the test of subgroup differences, there was significant HTE for HF hospitalization between those studies that used implanted right ventricular/pulmonary pressure monitoring versus impedance-based monitoring (Chi 2 = 7.92, p = 0.005, I 2 = 87.4%). Conclusions: Compared to standard of care, remote monitoring of physiologic markers of HF did not reduce mortality and CV or HF hospitalization. However, right ventricular/pulmonary pressure monitoring may reduce HF hospitalization compared to impendence-based monitoring. Further studies are necessary to evaluate the role of remote monitoring in patients with heart failure.
PER2-mediated ameloblast differentiation via PPARγ/AKT1/β-catenin axis
Authors: Wushuang Huang, Xueqing Zheng, Mei Yang, Ruiqi Li, Yaling Song
Journal: International Journal of Oral Science (2021)

Abstract Circadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has not been fully elucidated. The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation. Circadian disruption models were constructed in mice for in vivo experiments. An ameloblast-lineage cell (ALC) line was used for in vitro studies. As essential molecules of the circadian system, Bmal1 and Per2 exhibited circadian expression in ALCs. Circadian disruption mice showed reduced amelogenin (AMELX) expression and enamel matrix secretion and downregulated expression of BMAL1, PER2, PPARγ, phosphorylated AKT1 and β-catenin, cytokeratin-14 and F-actin in ameloblasts. According to previous findings and our study, BMAL1 positively regulated PER2. Therefore, the present study focused on PER2-mediated ameloblast differentiation and enamel formation. Per2 knockdown decreased the expression of AMELX, PPARγ, phosphorylated AKT1 and β-catenin, promoted nuclear β-catenin accumulation, inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs. Overexpression of PPARγ partially reversed the above results in Per2 -knockdown ALCs. Furthermore, in in vivo experiments, the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group, which was rescued by using a PPARγ agonist in circadian disturbance mice. In conclusion, through regulation of the PPARγ/AKT1/β-catenin signalling axis, PER2 played roles in amelogenin expression, cell junctions and arrangement, enamel matrix secretion and mineralization during ameloblast differentiation, which exert effects on enamel formation.
Abstract 16187: Incidence, Risk Factors, and Outcomes of Atrial Fibrillation After Blood and/or Marrow Transplant
Authors: Daniel Pinkhas, John Ning, Hyun Kim, Matthew Subramani, Anita D'Souza, Jason Rubenstein
Journal: Circulation (2020)

Introduction: Atrial fibrillation (AF) is known to occur after blood and/or marrow transplant (BMT) and has been shown to increase morbidity and mortality. Our objective was to characterize the incidence, risk factors, and clinical impact of AF in patients within the first 90 days after BMT. Methods: Patients with active malignancy undergoing BMT from 2012-2016 at the Medical College of Wisconsin were included (n=1159). Medical records were reviewed for baseline patient characteristics, AF risk factors, and clinical outcomes. Patients were categorized based on development of AF within 90 days post-BMT. Baseline characteristics and risk factors were analyzed to determine predictors for AF and all-cause mortality at 90 days. Results: Amongst the entire cohort, 5.3% of patients developed AF within the first 90 days after BMT. Significant baseline differences between those with or without AF post-BMT are outlined in Table 1. Multivariable analysis showed that a history of AF (OR: 6.7; 95% CI: 3.3-13.6; P = &lt;0.001) and prior XRT (OR: 2.3; 95% CI: 1.2-4.6; P = 0.018) were independent predictors of developing AF. Univariate analysis demonstrated that AF was associated with 90-day mortality (HR: 7.6; 95% CI: 3.5-16.5; log rank P &lt; 0.001). Multivariable analysis (adjusted for age, gender, race, history of XRT, BMT type, and malignancy type) revealed that female gender (HR: 2.6; 95% CI: 1.2-5.5; P = 0.016), non-Caucasian race (HR: 2.7; 95% CI: 1.1-6.4; P = 0.024) and development of AF (HR: 9.2; 95% CI: 3.7-21.5; P &lt; 0.001) were significant independent predictors of early mortality. Conclusions: This analysis demonstrated that a prior history of AF and prior XRT were independent predictors for the development of AF in the early period post-BMT and AF is a significant independent predictor of early mortality after BMT. Further studies assessing the potential benefits of AF prevention in patients after BMT is warranted.
Abstract P115: Older Age And Health Status Are Associated With Smartwatch Use Over 12 Months In The Electronic Framingham Heart Study
Authors: Chathurangi H Pathiravasan, Ludovic Trinquart, Yuankai Zhang, Emelia J Benjamin, Belinda Borrelli, David D McManus, Vik Kheterpal, Honghuang Lin, Mayank Sardana, Michael M Hammond, Nicole L Spartano, Amy L Dunn, Eric Schramm, Christopher Nowak, Emily S Manders, Hongshan Liu, Jelena Kornej, Chunyu Liu, Joanne Murabito
Journal: Circulation (2021)

Introduction: Long-term use is critical for successful clinical or research applications of digital devices, but digital health studies are challenged by significant early discontinuation of use. Hypothesis: We sought to identify factors associated with long-term use of a smartwatch among participants enrolled in the electronic Framingham Heart Study (eFHS). We hypothesized that sociodemographic and health variables are associated with watch use. Methods: Participants were provided with a study smartwatch and were asked to wear the watch daily. We examined watch use over 12 months. Weekly watch use was defined as a binary response (yes=watch wear for ≥1 days for ≥ 5 hours per day, vs. no). We considered 19 different predictors including sociodemographic, health behaviors, and family relationship. We selected an individual predictor for watch use ( P &lt;0.05) using generalized linear mixed models (GLMM) adjusted for age, sex, and weeks of watch use. We further built a model with all predictors selected from initial testing adjusted for age, sex, and weeks. We report odds ratios (OR) and 95% confidence interval (95%CI). Results: Among 1243 participants (mean age 53 years, 59% women), watch use was highest in the age-group ≥65 years, and decreased linearly over time in all participants (Figure). In GLMM adjusted for age, sex, and weeks, we found that self-reported health status (excellent vs good, fair or poor) (OR=2.7; 95%CI, 1.6-4.8), BMI (OR=0.9; 95%CI, 0.9-1.0) per 1 kg/m 2 increase, and depressive symptoms (OR=0.5; 95%CI, 0.3-0.8) were associated with watch use. In the model with all selected predictors, age-group &gt; 65 (OR=4.0; 95%CI, 1.4 -11.6), excellent health (OR=2.3; 95%CI, 1.3-4.1), and depressive symptoms (OR=0.5; 95%CI, 0.3-0.9) remained significant. Conclusions: Older age, lack of depressive symptoms, and self-reported excellent health were associated with greater use of the smartwatch over the 12-month follow-up. Consideration of these factors in planning future digital studies may improve participation.
45P Long-term efficacy of neratinib in HER2-positive early-stage breast cancer: Overall survival and central nervous system outcomes from the phase III ExteNET trial
Authors: A. Chan, B. Moy, J.L. Mansi, M.I. Gnant, C.H. Barrios, R. Separovic, A. Guerrero-Zotano, I. Gore, J. Smith, R.P. Bryce, F. Xu, A. Wong, M. Martin, F.A. Holmes
Journal: Annals of Oncology (2021)
Abstract 12118: Saphenous Vein Harvesting Techniques for Coronary Artery Bypass Grafting: A Systematic Review and Network Meta-Analysis
Authors: Mohamed A Mokhtar, Nguyen Lam Vuong, Muhammed K Elfaituri, Peter Samuel Eid, Mohammed Fathi Eldoadoa, Mostafa Reda Mostafa, Ahmed Hesham Bendary, Ibrahim Radwan, Mostafa Mohamed Aboelhossen, Doaa Alaa Ibrahim, Nirmeen Atef Abdallah, Heba Abo El-Ghar, Marwa Mostafa Mohamed Zaki, Abdelrahman Elshafay, Nguyen Tien Huy
Journal: Circulation (2018)

Introduction: The great saphenous vein (GSV) graft remains the most frequent used conduit for coronary artery bypass graft (CABG) surgery. A lot of debates about technique of GSV harvesting have oc...
Abstract 17388: Loss of Bone Morphogenetic Protein 9 (BMP9) Limits Survival and Paradoxically Increases Collagen Abundance, but Limits Collagen Cross-Linking in a Murine Model of Acute Myocardial Infarction
Authors: Shreyas Bhave, Michele Esposito, Lija Swain, Xiaoying QIAO, Gregory Martin, Queeny Dasgupta, Lauren D Black, Yang Zhang, Irene Georgakoudi, Navin K Kapur
Journal: Circulation (2020)

Myocardial infarction (MI) is a major cause of heart failure (HF). HF is associated with adverse cardiac remodeling that is primarily driven by Transforming growth factor beta (TGFb1) mediated fibrosis and myocyte hypertrophy. We previously reported that loss of bone morphogenetic protein 9 (BMP9) promotes cardiac fibrosis in pressure-overload induced HF. No studies have explored a role for BMP9 in post MI cardiac remodeling. We hypothesize that loss of BMP9 may promote cardiac healing by stabilizing LV scar formation. To test this hypothesis, we subjected whole body BMP9 knockout (-/-) mice to left coronary artery ligation for two weeks followed by PV loop analysis and studied indices of cardiac remodeling. Compared to wild type (WT) controls BMP9-/- mice had significantly lower survival (83% vs 61%, p&lt;0.001, respectively) with a higher rate of cardiac rupture(15% vs 90%). Compared to WT controls, surviving BMP9-/- mice had higher LVEDP, reduced LV dP/dt, and higher lung weight. Compared to WT mice, BMP9-/- mice had significantly higher levels of Type I collagen (2 fold p&lt;0.05). Compared to WT mice, BMP9-/- mice had increased matrix metalloproteinases (MMP)-2 and MMP-9 (2.5 fold p&lt;0.05) activity levels in the LV. Treatment of cultured primary human cardiac fibroblasts with recombinant BMP9 attenuated TGFb1-mediated Type I collagen and MMP-9 protein expression. To assess collagen content and cross-linking, two-photon excitation fluorescence imaging was performed and identified an increase in collagen abundance, but a trend towards lower collagen cross-linking in the LV of BMP9-/- mice compared to WT mice 2 weeks after MI. Our central finding is that loss of BMP9 is associated with reduced survival, increased propensity towards cardiac rupture, and increased LV collagen abundance, but reduced collagen integrity in a murine model of acute MI. These identify a potentially important functional role for BMP9 in post-infarct cardiac remodeling.
Hypoxia-Driven Oncometabolite L-2HG Maintains Stemness-Differentiation Balance and Facilitates Immune Evasion in Pancreatic Cancer
Authors: Vineet K. Gupta, Nikita S. Sharma, Brittany Durden, Vanessa T. Garrido, Kousik Kesh, Dujon Edwards, Dezhen Wang, Ciara Myer, Beatriz Mateo-Victoriano, Sai Sundeep Kollala, Yuguang Ban, Zhen Gao, Sanjoy K. Bhattacharya, Ashok Saluja, Pankaj K. Singh, Sulagna Banerjee
Journal: Cancer Research (2021)

Abstract In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intratumoral metabolic pathways and leading to poor survival. One metabolic enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate (L-2HG), an epigenetic modifier, that regulates the tumor transcriptome. However, the role of L-2HG in remodeling the pancreatic tumor microenvironment is not known. Here we used mass spectrometry to detect L-2HG in serum samples from patients with pancreatic cancer, comprising tumor cells as well as stromal cells. Both hypoxic pancreatic tumors as well as serum from patients with pancreatic cancer accumulated L-2HG as a result of promiscuous activity of LDHA. This abnormally accumulated L-2HG led to H3 hypermethylation and altered gene expression, which regulated a critical balance between stemness and differentiation in pancreatic tumors. Secreted L-2HG inhibited T-cell proliferation and migration, suppressing antitumor immunity. In a syngeneic orthotopic model of pancreatic cancer, inhibition of LDH with GSK2837808A decreased L-2HG, induced tumor regression, and sensitized tumors to anti-PD1 therapy. In conclusion, hypoxia-mediated promiscuous activity of LDH produces L-2HG in pancreatic tumor cells, regulating the stemness-differentiation balance and contributing to immune evasion. Targeting LDH can be developed as a potential therapy to sensitize pancreatic tumors to checkpoint inhibitor therapy. Significance: This study shows that promiscuous LDH activity produces L-2HG in pancreatic tumor and stromal cells, modulating tumor stemness and immune cell function and infiltration in the tumor microenvironment.
Brian Gerard Dooley
Authors: Mike Thirlwall
Journal: BMJ (2021)

Brian Gerard Dooley’s early years were spent in Essex, but he moved to Ireland in 1936 when his GP father took up a new post there. He and his brother were educated at boarding schools in the UK and Ireland. He won a scholarship to University College Cork, where he won the Pearson medal for outstanding performance in his finals. He did several junior house jobs in the UK including Coventry, where he met Sylvia, who became his wife in 1955. After national service in the Royal Air Force he joined a general practice in Swindon, and in 1961 he and Sylvia started …
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
Authors: Jennifer M. Mitchell, Michael Bogenschutz, Alia Lilienstein, Charlotte Harrison, Sarah Kleiman, Kelly Parker-Guilbert, Marcela Ot’alora G., Wael Garas, Casey Paleos, Ingmar Gorman, Christopher Nicholas, Michael Mithoefer, Shannon Carlin, Bruce Poulter, Ann Mithoefer, Sylvestre Quevedo, Gregory Wells, Sukhpreet S. Klaire, Bessel van der Kolk, Keren Tzarfaty, Revital Amiaz, Ray Worthy, Scott Shannon, Joshua D. Woolley, Cole Marta, Yevgeniy Gelfand, Emma Hapke, Simon Amar, Yair Wallach, Randall Brown, Scott Hamilton, Julie B. Wang, Allison Coker, Rebecca Matthews, Alberdina de Boer, Berra Yazar-Klosinski, Amy Emerson, Rick Doblin
Journal: Nature Medicine (2021)

Abstract Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants ( n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo ( P &lt; 0.0001, d = 0.91) and to significantly decrease the SDS total score ( P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.
Abstract 15277: Monitoring Progression of Aneurysms of the Ascending Aorta: Timing, Cost and Radiation Exposure
Authors: Alexander E Callow, Jordan Long, Sahar Rehman, Isna H Khaliq, Sebastian Boland, J. Ronald Mikolich
Journal: Circulation (2020)

Introduction: Current guidelines of the American Heart Association (AHA) recommend annual serial imaging for patients with aneurysm of the ascending aorta (AscAoA). However, recent data (Park K-H et al. Eur J CT Surg 2017;51:959-64) have suggested that this imaging frequency may not be necessary. This study was designed to compare the progression in growth rates of AscAoA using cardiac MRI (CMR) in 2 large cohorts of patients reassessed every 1 year and every 2 years. Methods: An institutional cardiac imaging database was queried for all patients with AscAoA, defined as a maximum ascending aorta diameter &gt; 3.5 cm measured perpendicular to flow using CMR. The study cohort was divided into two groups; patients who had a follow up CMR every 1 (Group A), and those who had a CMR every 2 years (Group B). AscAoA growth rates were computed for each group and statistically compared using a two-sample t-test. For analysis of cost to the healthcare system, Medicare reimbursement rates for 2019 were utilized. Published mean radiation dose for cardiac CT (CCT) was utilized to assess radiation exposure. Results: Of 6,210 patients in the cardiac imaging database, 1,849 had a diagnosis of AscAoA, of which 941 had serial CMR studies. Of these 941 patients, 342 had a follow up CMR every 1 year, while 206 had a follow up CMR every 2-years. The mean progression of AscAoA was 0.0247 ± 0.475 cm for Group A and 0.0598 ± 0.209 cm for Group B. The growth rate of AscAoA was not significantly different between groups (p=0.236). The Medicare reimbursement for CMR was $23,056 per 100 patients (CPT 75557) without radiation exposure. If CCT had been used for these patients, Medicare reimbursement would have been $20,174 per 100 patients (CPT 75572) with exposure to 10.5 mSv of radiation per study. Conclusions: There was no significant difference in progression of AscAoA diameter between Groups A and B. These data suggest that serial imaging of AscAoA every 2 years may be appropriate, with reduced cost to the healthcare system and cumulative radiation exposure. Although CMR is slightly more costly than CCT, it eliminates cumulative breast radiation exposure, a feature of particular importance for female patients.