tbuckley/cabot-search huggingface dataset:
Abstract 16217: Culturally-tailored Team-based Preventive Cardiology Program Improves Cardiovascular Risk for South Asian Patients
Authors: Keon Pearson, Vijaya Parameswaran, Destini Gibbs-Curtis, Austin Johnson, Kiranbir Josan, Fatima Rodriguez, Rajesh DASH
Journal: Circulation (2020)

Introduction: South Asians (SA) have a two times greater prevalence of CAD and metabolic syndrome (MetS) than matched Europeans. Diet and physical activity may be best addressed through culturally-tailored interventions. The Stanford South Asian Translational Heart Initiative (SSATHI) was designed to help SA better understand and improve their risk factors. We tested the hypothesis that a team-based and culturally-tailored clinical intervention for SA would result in a reduction in MetS risk factors. Methods: Patients underwent an initial assessment consisting of fasting lipid profile, advanced lipid studies (lipid fractionation, lp (a), apoA1, apoB), inflammatory markers (high sensitivity CRP, homocysteine), and A1c. All non-diabetics underwent two-hour OGTT. Following initial assessment by a cardiologist, a registered dietician developed a personalized nutrition plan based on SA cuisine. Results: A total of 395 patients were seen between July, 2011 and July, 2019. Of these, 198 (50%) completed at least two cardiologist visits with baseline and follow up labs. Patients had an average age of 45.5 years and 86% were male. At baseline, SSATHI patients had a mean BMI of 26.4 (IQR = 23.9-28.8), 52% of patients had total cholesterol greater than 190 mg/dl, 21% had systolic BP &gt; 140 mmHg, and 13% had diastolic BP &gt; 90 mmHg. During an average follow-up of 11.8 ± 9.2 months, diastolic BP declined from 80.9 ± 9.32 to 78.9 ± 7.6 mmHg (p = 0.028), total cholesterol decreased from 190.4 ± 46.4 to 153.4 ± 63.7 mg/dl (p &lt; 0.001), total triglycerides declined from 137.1 ± 87.1 to 100.2 ± 67.5 mg/dl (p &lt; 0.001), and LDL declined from 120.4 ± 40.0 to 92.3 ± 46.4 mg/dl (p &lt;0.001). HDL declined from 49.0 ± 15.4 to 44.5 ± 19.8 mg/dl (p = 0.022). ASCVD and A1c were not significantly different. Conclusion: A team-based and culturally-informed program targeted to South Asian populations may help improve cardiometabolic risk factors but may be limited by program attrition and generalizability.
Abstract 066: Association Between Nocturnal Blood Pressure Dipping Magnitude And Chronic Kidney Disease Risk Among Patients With Controlled Office Blood Pressure
Authors: So Mi J Cho, Hokyou Lee, Tae-Hyun Yoo, Jong Hyun Jhee, Sungha Park, Hyeon Chang Kim
Journal: Circulation (2021)

Although abnormal diurnal blood pressure (BP) patterns are associated with adverse cardiorenal outcomes, their risks are yet unquantified by BP dipping magnitude. We assessed chronic kidney disease risk across nocturnal BP dipping spectrum among patients with controlled hypertension without prior advanced kidney disease. Ambulatory BP measurements were collected from 995 middle-aged patients with controlled office BP (&lt;140/90 mmHg). The magnitude of dipping was defined as the difference between daytime and nighttime systolic BP divided by daytime systolic BP. Accordingly, patients were categorized as extreme-dipper (≥20%) dipper (10-&lt;20%), non-dipper (0-&lt;10%), or reverse-dipper (&lt;0%). We cross-sectionally analyzed continuous and categorical associations of dipping with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) and decreased estimated glomerular filtration rate (&lt;60 ml/min/1.73m 2 ), adjusting for office/ambulatory BP, antihypertensive class, body mass index, total cholesterol, fasting glucose, socioeconomic status, and health behavior. The participants (mean age 60.2 years; 52.9% male) consisted of 13.5% (134 of 995) extreme-dippers, 43.1% (429 of 995) dippers, 34.7% (345 of 995) non-dippers, and 8.7% (87 of 995) reverse-dippers. In reference to dippers, odds ratios (95% confidence interval) for albuminuria were 1.73 (1.04-2.60) in reverse-dippers, 1.67 (1.20-2.32) in non-dippers, and 0.62 (0.38-1.04) in extreme-dippers; this reflects significantly lower risk (0.77, 0.55-0.95) per 10% dipping. Likewise, persons presenting reduced and reverse-directional dipping were at higher risk for decreased estimated glomerular filtration rate: reverse-dippers 2.02 (1.06-3.84); non-dippers 1.98 (1.07-3.08); extreme-dippers 0.69 (0.20-1.17), with lower risk (0.74, 0.22-1.02) per every 10%. In short, monitoring nocturnal BP patterns may identify chronic kidney disease risk otherwise overlooked based on office BP.
Abstract 15127: Isorhamnetin Reverses Angiotensin Ii-induced Atrial Fibrillation Vulnerability Through Electrophysiological and Structural Reverse Remodeling in Mice
Authors: Kazuhiro Aonuma, Dong-Zhu Xu, Nobuyuki MURAKOSHI, Kazuko Tajiri, Kenichi Tominaga, Masaki Ieda, Hiroko Isoda
Journal: Circulation (2020)

Background: Isorhamnetin (ISO), a natural flavonoid compound, has been shown to have strong antioxidant and antifibrotic effects in vivo and in vitro; however, no report has been shown on the effect of ISO on arrhythmic disorders. This study aimed to investigate the effect of ISO on angiotensin-II (Ag-II) induced atrial fibrillation (AF) in mice. Methods: Wild-type male mice (C57BL/6J, 8 weeks old) were assigned in 3 groups as follows: control group (Cont), Ag-II group treated with Ag-II and Ag-II &amp; ISO group treated with Ag-II and ISO. Ag-II (1000 ng/kg/min) was continuously administered using an implantable osmotic pump for 2 weeks, and ISO (5 mg/kg) was administered intraperitoneally one week before starting Ag-II administration. We performed AF induction and electrophysiologic study via transvenous electrode catheter and Ca 2+ imaging with isolated cardiomyocyte. We also assessed the gene expression levels of AF-related molecules, and histological examination of atrial fibrosis. Results: Compared with Cont, AF inducibility was dramatically increased by Ag-II and significantly decreased by ISO. AF duration was also remarkably prolonged by Ag-II and significantly reduced by ISO. Atrial effective refractory period (A-ERP) (BCL=150msec) was reduced by Ag-II and recovered by ISO. Incidences of diastolic intracellular Ca 2+ abnormal activities (sarcoplasmic reticulum [SR] Ca 2+ leakage) was observed in Ag-II group; however, ISO treatment eliminated these abnormalities. Ag-II induced elevated expression of fibrosis-related molecules (Col1a1, Tgfb1 and Tgfb2) and Ca 2+ -handling related molecules (Camk2 and Ryr2), those were partially normalized by ISO. Histological examination revealed that cell size and the fibrosis ratio were increased by Ag-II, and significantly attenuated by ISO. Conclusion: These results suggest that ISO prevented against Ag-II induced AF vulnerability through both electrophysiological and structural reverse remodeling.
Abstract 15215: Pro-pace: Prospective Randomized Trial of Skin Closure for Pacemaker Implant
Authors: Jaber Abboud, Celine Guenther, Andreas Boehmer, Bernhard M Kaess, Joachim R Ehrlich
Journal: Circulation (2020)

Introduction: Pacemaker implantation is a standard technique with largely traditional knowledge and has been performed for over 50 years. Despite its huge distribution, there are hardly any randomized trials regarding technical aspects such as material of skin closure. Hypothesis: The aim was to compare if resorbable subcuticular suture skin is superior in terms of clinical or cosmetic endpoints vs. non-resorbable suture. Methods: We performed a prospective randomized comparison of non-resorbable subcuticular suture to suture with resorbable material for pacemaker implantation with indications according to current guidelines. All consecutive patients undergoing placement of pacemakers were eligible. Follow-up was 1 year. Scars were observed at day 1, week 6 and 1 year after surgery. Clinically relevant primary endpoints were: bleeding, infection or revision. Secondary endpoints recorded at day 1 were: local hematoma formation &gt; 10cm diameter, wound width, insufficient skin closure. Secondary endpoints at 6 weeks and 1 year: scar width, pathological scarring with kelloid, insufficient skin closure. Cosmetic results were assessed using “ P atient and O bserver S car A ssessment score (POSA)“. Results: We included 115 pts. (77 male) and performed non-resorbable skin closure in 50 cases. There were no differences in clinical characteristics between patient groups. At 1 day after implantation was no difference between regarding clinical or cosmetic endpoints (Scar width P=0.43, POSA P=0.44). At 6 weeks and 1 year post implantation, there were similarly no differences in clinical or cosmetic endpoints between both groups (Scar width P=0.54, POSA P=0.45, figure). No relevant clinical endpoints (bleeding, infection, revision) were associated to either technique of skin closure. Conclusions: Based on the present prospective randomized study, suture material does not influence clinical or cosmetic results of pacemaker implantation.
Abstract 14804: Complications and Mortality Following CRT-D versus ICD Implants in Older Medicare Beneficiaries
Authors: Emily P Zeitler, Andrea Austin, Daniel J Friedman, Christopher G Leggett, Lauren Gilstrap, Jonathan Skinner, Sana M Al-khatib
Journal: Circulation (2020)

Introduction: Despite growing numbers of older HF patients, clinical trials of implantable defibrillators (ICDs) and cardiac resynchronization therapy (CRT) rarely include older patients (≥75 yrs). Hypotheses: (1) Among Medicare beneficiaries, older CRT-D patients have a higher risk of procedure-related complications than older ICD patients. (2) Compared with older ICD patients, older CRT-D patients have lower risk of death. Methods: We identified Medicare beneficiaries with HF and reduced LVEF who underwent ICD or CRT-D implant based on CPT codes (1/2008-8/2015) by age group (65-74, 75-84, and 85+). After matching device groups with inverse probability weighting (IPW), we estimated the comparative hazard ratio (HR) of death by age group and device type using a Cox proportional hazards model. Results: Compared with the ICD group, the CRT-D group was older and more likely to be white and female and have atrial fibrillation; CRT-D patients were less likely to have ischemic heart disease. Use of guideline directed medical therapy was similar between groups. In all age groups, complications were more common in the CRT-D group. IPW was successful, and after matching, the HR for death was lower in the CRT-D versus the ICD group; this finding was most pronounced in the 85+ age group in which the HR for death in the CRT-D versus ICD group was 0.76 (95% CI 0.64-0.88). (Table) Conclusions: Procedure-related complications in older HF patients were higher in CRT-D versus ICD patients and generally increased with age. Overall high post-implant mortality in ICD patients (± CRT) highlights the difficulty in assessing competing mortality risk when considering patients for an ICD especially in the oldest patients in whom clinical trial data are absent. However, in matched Medicare beneficiaries, CRT-D was associated with a lower risk of mortality in all age groups compared with ICD alone. These findings support the use of CRT in eligible older patients undergoing ICD implantation.
User Engagement With the CamAPS FX Hybrid Closed-Loop App According to Age and User Characteristics
Authors: Natalie S. Chen, Charlotte K. Boughton, Sara Hartnell, Julia Fuchs, Janet M. Allen, Malgorzata E. Willinska, Ajay Thankamony, Carine de Beaufort, Fiona M. Campbell, Elke Fröhlich-Reiterer, Sabine E. Hofer, Thomas M. Kapellen, Birgit Rami-Merhar, Atrayee Ghatak, Tabitha L. Randell, Rachel E. J. Besser, Daniela Elleri, Nicola Trevelyan, Louise Denvir, Nikki Davis, Eleanor Gurnell, Robert Lindsay, Damian Morris, Eleanor M. Scott, Lia Bally, Hood Thabit, Lalantha Leelarathna, Mark L. Evans, Helen R. Murphy, Julia K. Mader, Roman Hovorka
Journal: Diabetes Care (2021)

CamAPS FX (CamDiab, Cambridge, U.K.) is a hybrid closed-loop app hosting the Cambridge closed-loop algorithm on an Android smartphone, and it is approved in the European Union for use in children ≥1 year and adults (including during pregnancy) with type 1 diabetes (T1D). The interoperable CamAPS FX app receives glucose data from a compatible continuous glucose monitoring system (Dexcom G6; Dexcom, San Diego, CA), connects to a compatible insulin pump (Dana Diabecare RS and DANA-i; Sooil, Seoul, South Korea) to direct glucose-responsive insulin delivery every 8–12 min, includes a bolus calculator allowing discrete bolusing via the app, and streams data in real time to cloud-based diabetes data repositories (Diasend/Glooko, Gothenburg, Sweden).

It is currently unknown how much time different user cohorts spend interacting with hybrid closed-loop systems. We aimed to investigate usage patterns of the CamAPS FX app across different populations by considering the amount of time a person spends using the app over a 24-h period.

We noted time spent within the CamAPS FX app over an 11-week period from February to May 2020 in 134 individuals from six ongoing clinical studies. Each study involved a different demo graphic cohort: very young children (1–7 years) in which caregivers use the app (NCT03784027, ClinicalTrials.gov), children and adolescents (6–19 years) (NCT02925299), adolescents (10–17 years) using the closed-loop system from diagnosis of T1D (NCT02871089), adults (≥18 years) (NCT04055480), pregnant women (≥18 years) (ISRCTN56898625, www.isrctn.org), and older adults (≥60 years) (NCT04025762). All studies received regulatory and ethical approval; participants/guardians signed informed consent.

User engagement is the duration of time that users have the application active and in the foreground, as calculated by an analytics cloud platform (Firebase; …
Nuclear FGFR1 Regulates Gene Transcription and Promotes Antiestrogen Resistance in ER+ Breast Cancer
Authors: Alberto Servetto, Rahul Kollipara, Luigi Formisano, Chang-Ching Lin, Kyung-Min Lee, Dhivya R. Sudhan, Paula I. Gonzalez-Ericsson, Sumanta Chatterjee, Angel Guerrero-Zotano, Saurabh Mendiratta, Hiroaki Akamatsu, Nicholas James, Roberto Bianco, Ariella B. Hanker, Ralf Kittler, Carlos L. Arteaga
Journal: Clinical Cancer Research (2021)

Abstract Purpose: FGFR1 overexpression has been associated with endocrine resistance in ER+ breast cancer. We found FGFR1 localized in the nucleus of breast cancer cells in primary tumors resistant to estrogen suppression. We investigated a role of nuclear FGFR1 on gene transcription and antiestrogen resistance. Experimental Design: Tumors from patients treated with letrozole were subjected to Ki67 and FGFR1 IHC. MCF7 cells were transduced with FGFR1(SP-)(NLS) to promote nuclear FGFR1 overexpression. FGFR1 genomic activity in ER+/FGFR1-amplified breast cancer cells ± FOXA1 siRNA or ± the FGFR tyrosine kinase inhibitor (TKI) erdafitinib was examined by chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq). The nuclear and chromatin-bound FGFR1 interactome was investigated by mass spectrometry (MS). Results: High nuclear FGFR1 expression in ER+ primary tumors positively correlated with post-letrozole Ki67 values. Nuclear FGFR1 overexpression influenced gene transcription and promoted resistance to estrogen suppression and to fulvestrant in vivo. A gene expression signature induced by nuclear FGFR1 correlated with shorter survival in the METABRIC cohort of patients treated with antiestrogens. ChIP-Seq revealed FGFR1 occupancy at transcription start sites, overlapping with active transcription histone marks. MS analysis of the nuclear FGFR1 interactome identified phosphorylated RNA-Polymerase II and FOXA1, with FOXA1 RNAi impairing FGFR1 recruitment to chromatin. Treatment with erdafitinib did not impair nuclear FGFR1 translocation and genomic activity. Conclusions: These data suggest nuclear FGFR1 contributes to endocrine resistance by modulating gene transcription in ER+ breast cancer. Nuclear FGFR1 activity was unaffected by FGFR TKIs, thus supporting the development of treatment strategies to inhibit nuclear FGFR1 in ER+/FGFR1 overexpressing breast cancer.
Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19
Authors: Brian J. Ward, Philipe Gobeil, Annie Séguin, Judith Atkins, Iohann Boulay, Pierre-Yves Charbonneau, Manon Couture, Marc-André D’Aoust, Jiwanjeet Dhaliwall, Carolyn Finkle, Karen Hager, Asif Mahmood, Alexander Makarkov, Matthew P. Cheng, Stéphane Pillet, Patricia Schimke, Sylvie St-Martin, Sonia Trépanier, Nathalie Landry
Journal: Nature Medicine (2021)

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds the supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP: NCT04450004 ). The co-primary outcomes were the short-term tolerability/safety and immunogenicity of CoVLP formulations assessed by neutralizing antibody (NAb) and cellular responses. Secondary outcomes in this ongoing study include safety and immunogenicity assessments up to 12 months after vaccination. Adults (18-55 years, n = 180) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 μg, 7.5 μg, and 15 μg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced. This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate.
Body checking in non-elite adolescent ice hockey leagues: it is never too late for policy change aiming to protect the health of adolescents
Authors: Carolyn A Emery, Paul Eliason, Vineetha Warriyar, Luz Palacios-Derflingher, Amanda Marie Black, Maciek Krolikowski, Nicole Spencer, Stacy Sick, Stacy Kozak, Kathryn J Schneider, Shelina Babul, Martin Mrazik, Constance Lebrun, Claude Goulet, Alison Macpherson, Brent E Hagel
Journal: British Journal of Sports Medicine (2021)

Objectives The objective of this study is to evaluate the effect of policy change disallowing body checking in adolescent ice hockey leagues (ages 15–17) on reducing rates of injury and concussion. Methods This is a prospective cohort study. Players 15–17 years-old were recruited from teams in non-elite divisions of play (lower 40%–70% by division of play depending on year and city of play in leagues where policy permits or prohibit body checking in Alberta and British Columbia, Canada (2015–18). A validated injury surveillance methodology supported baseline, exposure-hours and injury data collection. Any player with a suspected concussion was referred to a study physician. Primary outcomes include game-related injuries, game-related injuries (&gt;7 days time loss), game-related concussions and game-related concussions (&gt;10 days time loss). Results 44 teams (453 player-seasons) from non-body checking and 52 teams (674 player-seasons) from body checking leagues participated. In body checking leagues there were 213 injuries (69 concussions) and in non-body checking leagues 40 injuries (18 concussions) during games. Based on multiple multilevel mixed-effects Poisson regression analyses, policy prohibiting body checking was associated with a lower rate of injury (incidence rate ratio (IRR): 0.38 (95% CI 0.24 to 0.6)) and concussion (IRR: 0.49; 95% CI 0.26 to 0.89). This translates to an absolute rate reduction of 7.82 injuries/1000 game-hours (95% CI 2.74 to 12.9) and the prevention of 7326 injuries (95% CI 2570 to 12083) in Canada annually. Conclusions The rate of injury was 62% lower (concussion 51% lower) in leagues not permitting body checking in non-elite 15–17 years old leagues highlighting the potential public health impact of policy prohibiting body checking in older adolescent ice hockey players.
Abstract 16874: Papillary Muscle Approximation Relieves Tethering Forces and Improves Systolic Mitral Valve Kinematics in an Ex-Vivo Model of Functional Mitral Regurgitation
Authors: Samantha Zhan Moodie, Kirthana Sreerangathama Suresh, Dongyang Xu, Muralidhar Padala
Journal: Circulation (2020)

Introduction: Undersizing annuloplasty (UA), which is the current standard to correct functional mitral regurgitation (FMR) is effective, but the resulting unphysiological systolic geometry causes FMR recurrence. On the other hand, papillary muscle approximation (PMA), a sub-annular technique, reduces inter-papillary separation and tethering forces, mobilizing the leaflets. Objective: To investigate the effect of PMA on mitral valve tethering forces and systolic coaptation geometry, compared to UA. Methods: A left heart model with pig mitral valves was used to create a tethered mitral valve geometry and to perform surgical repairs ( Fig. A ). Mitral valve geometry, and marginal and strut chordal forces acting on both leaflets were measured. Eight individual pig valves (n=8) were studied, with hemodynamic and mechanics data acquired at normal geometry (BASELINE) ( Fig. B) , after tethering (FMR) ( Fig. C) , undersizing annuloplasty (UA) to size 34 (Edwards Lifesciences Physio ring) ( Fig. D) , papillary muscle approximation (PMA), and combination (PMA+UA). Results: Tenting height, which increased after FMR, was least with PMA (0.46 cm± 0.21) and PMA+UA (0.50± 0.16) but remained significantly high with UA (0.73±0.21, p=0.03) ( Fig. E ). Excursion angles of anterior and posterior leaflets were restored close to baseline values after PMA and PMA+UA but remained significantly tethered after UA ( Fig. F &amp; G ). Tethering of the valve increased the strut and marginal chordae forces from 0.47 and 0.14 N to 0.89 and 0.21 N, an increase of 89% and 50% respectively. PMA reduced the forces by 47% and 34%, and PMA+UA reducing it by 43% and 34%to 0.51 while UA only reduced it by 15% and 20% ( Fig. H &amp; I ). Conclusion: PMA significantly reduced the tethering forces on both marginal and strut chordae of both leaflets. Decrease in tethering forces restored the physiologically favorable valve geometry enabling better leaflet mobility and coaptation compared to UA.