bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of atrial fibrillation type on outcomes following aerobic exercise training: analysis from the ACTIVE-AF Trial
Authors: Elliott A , Verdicchio C V , Mahajan R , Gallagher C , Lau D H , Middeldorp M E , Sanders P 
Published: November 2023

Abstract

Background
The ACTIVE-AF study demonstrated that aerobic exercise prescription promotes the maintenance of sinus rhythm in patients with atrial fibrillation (AF). However, it is unclear whether these benefits are observed in patients with both paroxysmal and persistent AF.

Purpose
Compare efficacy of exercise intervention on arrhythmia recurrence between paroxysmal (ParAF) and persistent (PerAF) patients.

Methods
This study was a prospective, randomized, controlled trial of patients with symptomatic paroxysmal or persistent AF, referred for consideration of AF ablation. Randomization was 1:1 to either aerobic exercise intervention or usual medical care for a period of 6 months with a further 6 months follow-up. The exercise intervention was delivered in a hybrid format of weekly supervised exercise sessions coupled with prescribed home exercise, up to a total of 210 minutes per week. The intervention was led by a clinical exercise physiologist. Management of arrhythmia was at the discretion of a cardiologist blinded to patient randomisation. The primary endpoint reported here is recurrent AF without rhythm control strategies.

Results
Of the 120 patients enrolled in the study, 74 (62%) had a history of ParAF. Patients with PerAF typically had higher body mass index (32.0±6.6 versus 29.5±5.2 Kg/m2, p=0.02) and left atrial volume (38.0±9.4 versus 28.1±6.5 mL/m2, p&lt;0.001) but similar prevalence of hypertension, diabetes mellitus, coronary artery disease and obstructive sleep apnea. Baseline peak oxygen consumption (VO2peak) was similar between ParAF and PerAF groups (20.0±6.0 versus 19.6±5.4mL/kg/min). Over the 12-month follow-up, AF recurrence in the ParAF patients was lower in the exercise group compared to control group (Hazard Ratio 0.42, 95% CI: 0.23-0.77, p=0.005). However, we did not find evidence of any between-group difference amongst patients with PerAF (HR 0.65, 95% CI: 0.34-1.23).

Conclusions
In this post-hoc analysis of a randomised controlled trial comparing the efficacy of exercise intervention versus standard medical care amongst patients with symptomatic AF, we observed a reduction in AF recurrence for patients with ParAF, but not amongst those with PerAF. These findings support the need for early lifestyle modification amongst patients with AF, before progression to PerAF occurs. Future studies should explore whether the exercise prescription can be modified to improve outcomes for patients with more advanced AF.
HDLc levels have a protective effect for in-hospital mortality in Non-STEMI but not in STEMI patients
Authors: Cordero A , Badimon L , Alvarez-Alvarez B , Rodriguez-Manero M , Seijas-Amigo J , Escribano D , Lopez-Ayala J M , Vilahur G , Garcia-Acuna J M , Gonzalez-Juanatey J R 
Published: November 2023

Abstract

Background
High-density lipoprotein cholesterol (HDLc) has been associated to lower myocardial infarction size although it is not considered a primary target in cardiovascular prevention or as treatment target in patients with cardiovascular disease. The role of HDLc on in-hospital mortality in acute coronary syndrome (ACS) patients could be influenced by many variables.

Methods
We performed and observational and cross-sectional analysis of all patients admitted for an ACS in 2 tertiary hospitals in Spain between 2006 and 2016. HDL was measured in the first 24 of the admission in the first overnight fasting state.

Results
We included 8,684 patients, mean (standard deviation) age 66.88 (12.90), 27.5% women, mean GRACE score 143.13 (40.27), and 35.09% admitted for ST-elevation myocardial infarction (STEMI). Mean HDLc levels were 35.90 (13.64) mg/dL in whole cohort and were significantly lower in patients presenting as non-STEMI (35.53±13.62 vs. 36.55± 13.65 mg/dL), those with GRACE score &lt;140 (35.09±13.00 vs. 36.78±14.24 mg/dL) and women (34.28±12.81 vs. 40.21±14.80 mg/dL) but not in patients who died or not (p=0.43). From these variables, we observed a significant interaction of HDLc levels and STEMI presentation (p=0.03) for in-hospital mortality risk and, thus, results were analyzed separately.
After natural logarithm transformation, in-hospital mortality risk had a "U-shaped" distribution in STEMI patients compared to the linear trend in Non-STEMI patients (figure 1). Multivariate analysis, adjusted by age, gender, risk factors, hemoglobin, revascularization and GRACE score, verified the interaction and the protective effect of HDLc in Non-STEMI patients (OR: 0.48 95% CI 0.28-0.80; p=0.005) but not in STEMI patients (OR: 0.96 95% CI 0.55-1.67; p=0.887) (figure 2).

Conclusions
Clinical presentation of STEMI vs. non-STEMI modifies the effect of HDLc on in-hospital mortality. HDLc might have a protective effect in patients presenting with non-STEMI only.
Longitudinal trajectories of lipid parameters and their associations with mid-life carotid intima-media thickness
Authors: Kohansal K , Abdi A M I R , Afaghi S I A M A K , Hadaegh F A R Z A D , Khalili D A V O O D 
Published: November 2023

Abstract

Background/Introduction
Studies showed positive associations between previous dyslipidemia and subsequent subclinical atherosclerosis.

Purpose
To examine the longitudinal association of cumulative burden of different lipid parameters and subsequent carotid intima-media thickness (CIMT).

Methods
Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study from year 0 (Y0) to year 20 (Y20), young adulthood, midlife, and also longitudinal cumulative burdens (estimated by the area under the curve (AUC) using nonlinear mixed-effects methods) values of different lipid parameters including TC, LDL-C, non-HDL-C, HDL-C, Remnant-C, and Ln TG were considered as exposures. Linear regression models were used to estimate the effect of each 1-SD change in exposure variables on mean CIMT by sex-race group.

Results
In 2991 black and white women and men participants, young adulthood, midlife, and cumulative burden of TC, LDL, and non-HDL were associated with the increased mean of CIMT in black and white and also men and women populations; higher impacts were founded in whites compared to blacks and men compared to women for young adulthood and cumulative burden values (all p for interactions &lt;0.05). In terms of other lipid parameters, in women and whites, longitudinal increases in Remnant-C and Ln-TG cumulative burdens were associated with increased mean CIMT, whereas increases in HDL-C cumulative burdens were associated with decreased mean CIMT.

Conclusions
Midlife to later-life cumulative burdens of different lipid parameters are associated with mean CIMT which these associations are different between races and genders.12
Strike Cover, Consultation and Quashing: An Analysis of R. (Associated Society of Locomotive Engineers and Firemen) v Secretary of State
Authors: Bell Joanna 
Published: November 2023

Abstract
In June 2022, the UK Government enacted Regulations purporting to remove the offence of introducing or supplying workers to cover those on strike. In R. (Associated Society of Locomotive Engineers and Firemen) v Secretary of State the High Court held that the decision-making process preceding the enactment of the Regulations was unlawful and quashed them. This analysis outlines the case, with a particular focus on the central role played by the existence of a statutory duty to consult in the court's reasoning and the extent to which third party interests were considered in the course of determining the proper remedy.
Role of the integrin-linked kinase/TGF-β/SMAD pathway in sitagliptin-mediated cardioprotective effects in a rat model of diabetic cardiomyopathy
Authors: Bin Dayel Anfal F , Alonazi Asma S , Alrasheed Nawal M , Alamin Maha A , Sarawi Wedad S , Alharbi Abeer O , Alabbad Nahla’a A , Albuaijan Danah A , Alassiri Dareen N , Aljarbua Alanoud F , Almusaytir Fatimah K , Alrasheed Nouf M 
Published: November 2023

Abstract

Objectives
Diabetic cardiomyopathy is a known complication of diabetes mellitus. Herein, we aimed to determine whether glycemic control mediated by sitagliptin, a dipeptidyl peptidase-4 inhibitor, can ameliorate diabetic myocardial abnormalities by modulating TGF-β signaling via the SMAD and integrin-linked kinase (ILK) pathways.

Methods
Four groups of male Wistar albino rats were used, with six rats in each group. Two nondiabetic and two diabetic (produced by a single intraperitoneal dose of streptozotocin (55 mg/kg)) groups were administered either normal saline or sitagliptin (100 mg/kg) orally for 6 weeks. Subsequently, HW/BW ratios and cardiac enzymes were assessed, along with a histological examination of cardiac tissues. Levels of TGF-β, collagen I, p-SMAD2/3, TNF-α, MMP-9, and ILK were detected.

Results
Compared with the diabetic control group, sitagliptin-treated diabetic rats exhibited considerably reduced HW/BW ratios and troponin I and creatine kinase-MB levels, with improvements in histopathological changes in cardiac tissues. TGF-β, collagen I, p-SMAD2/3, TNF-α, and MMP-9 levels were significantly decreased in the sitagliptin-treated diabetic group, whereas ILK was elevated following sitagliptin treatment.

Conclusion
Sitagliptin could afford cardioprotective effects for the first time by altering ILK-associated TGF-β/SMAD signaling pathways. Thus, sitagliptin may be a promising therapeutic target for the prevention of diabetic cardiomyopathy.
MATLAB-Based Algorithm and Software for Analysis of Wavy Collagen Fibers
Authors: Polzer Stanislav , Thompson Sarah , Vittalbabu Swathi , Ulu Arzu , Carter David , Nordgren Tara , Eskandari Mona 
Published: November 2023

Abstract
Knowledge of soft tissue fiber structure is necessary for accurate characterization and modeling of their mechanical response. Fiber configuration and structure informs both our understanding of healthy tissue physiology and of pathological processes resulting from diseased states. This study develops an automatic algorithm to simultaneously estimate fiber global orientation, abundance, and waviness in an investigated image. To our best knowledge, this is the first validated algorithm which can reliably separate fiber waviness from its global orientation for considerably wavy fibers. This is much needed feature for biological tissue characterization. The algorithm is based on incremental movement of local regions of interest (ROI) and analyzes two-dimensional images. Pixels belonging to the fiber are identified in the ROI, and ROI movement is determined according to local orientation of fiber within the ROI. The algorithm is validated with artificial images and ten images of porcine trachea containing wavy fibers. In each image, 80–120 fibers were tracked manually to serve as verification. The coefficient of determination R2 between curve lengths and histograms documenting the fiber waviness and global orientation were used as metrics for analysis. Verification-confirmed results were independent of image rotation and degree of fiber waviness, with curve length accuracy demonstrated to be below 1% of fiber curved length. Validation-confirmed median and interquartile range of R2, respectively, were 0.90 and 0.05 for curved length, 0.92 and 0.07 for waviness, and 0.96 and 0.04 for global orientation histograms. Software constructed from the proposed algorithm was able to track one fiber in about 1.1 s using a typical office computer. The proposed algorithm can reliably and accurately estimate fiber waviness, curve length, and global orientation simultaneously, moving beyond the limitations of prior methods.
Connecting core galaxy properties to the massive black hole binary population
Authors: Harris C J , Gültekin Kayhan 
Published: November 2023

ABSTRACT
We investigate how the properties of massive black hole binaries influence the observed properties of core galaxies. We compare the observed trend in stellar mass deficit as a function of total stellar mass in the core galaxy with predicted trends in IllustrisTNG. We calculate mass deficits in simulated galaxies by applying subgrid, post-processing physics based on the results of literature N-body experiments. We find that the median value of the posterior distribution for the minimum binary mass ratio capable of creating a core is 0.7. For the gas mass fraction above which a core is erased, we find a median value of 0.6. Thus, low mass ratio binaries do not contribute to core formation and gas-rich mergers must lead to star formation within the nucleus, ultimately erasing the core. Such constraints have important implications for the overall massive black hole binary population, black hole–galaxy co-evolution, and the origin of the gravitational wave background.
Black hole binary mergers in dense star clusters: the importance of primordial binaries
Authors: Barber Jordan , Chattopadhyay Debatri , Antonini Fabio 
Published: November 2023

ABSTRACT
Dense stellar clusters are expected to house the ideal conditions for binary black hole (BBH) formation, both through binary stellar evolution and through dynamical encounters. We use theoretical arguments as well as N-body simulations to make predictions for the evolution of BBHs formed through stellar evolution inside clusters from the cluster birth (which we term primordial binaries), and for the sub-population of merging BBHs. We identify three key populations: (i) BBHs that form in the cluster, and merge before experiencing any strong dynamical interaction; (ii) binaries that are ejected from the cluster after only one dynamical interaction; and (iii) BBHs that experience more than one strong interaction inside the cluster. We find that populations (i) and (ii) are the dominant source of all BBH mergers formed in clusters with escape velocity vesc ≤ 30 $\mathrm{km\, s^{-1}}$. At higher escape velocities, dynamics are predicted to play a major role both for the formation and subsequent evolution of BBHs. Finally, we argue that for sub-Solar metallicity clusters with vesc ≲ 100 $\mathrm{km\, s^{-1}}$, the dominant form of interaction experienced by primordial BBHs (BBHs formed from primordial binaries) within the cluster is with other BBHs. The complexity of these binary–binary interactions will complicate the future evolution of the BBH and influence the total number of mergers produced.
88. Fostamatinib for the Treatment of Hospitalized Patients With COVID-19 Who Required Oxygen Supplementation: Results of a Phase 3 Trial
Authors: Gotur Deepa B , Malik Anuj , Markovtsov Vadim , Yan Lucy , Dummer Wolfgang , Mallat Ziad 
Published: November 2023

Abstract

Background
Severe COVID-19 is linked to hyperactivation of the host immune response involving signaling through multiple spleen tyrosine kinase (SYK) pathways. Fostamatinib is an orally administered potent and selective inhibitor of SYK that has been approved in the US, Canada, Japan, and Europe for the treatment of chronic immune thrombocytopenia (ITP).

Methods
We conducted a double-blind, randomized, placebo-controlled phase 3 trial of fostamatinib in adults hospitalized for COVID-19 who required oxygen supplementation (NCT04629703). Patients (pts) were randomly assigned 1:1 to receive fostamatinib (150 mg BID administered orally) or placebo for 14 days. All pts additionally received standard of care at their hospital. The primary endpoint was days on oxygen (days 1-29).

Results
A total of 280 pts underwent randomization (with 141 assigned to fostamatinib and 139 to placebo). The primary endpoint was met; those who received fostamatinib had lower mean days on oxygen than those who received placebo (4.8 vs. 7.6 days, P=0.0136; Table 1).
Fostamatinib showed significance or trend towards significance in all secondary endpoints of reducing mortality and morbidity compared to placebo. The mean change in the 8-point ordinal score from baseline to the average of Day 5 to 15 was significantly improved in pts who received fostamatinib vs. placebo (P=0.0092,Table 1). Furthermore, 6 pts were enrolled with a baseline ordinal score of 6 (3 in each group). All patients in the fostamatinib group survived, and all in the placebo group died by Day 30. A significantly higher proportion of pts who received fostamatinib were discharged from the hospital by Day 15 compared to placebo (P=0.0029,Table 1). Significantly more patients were alive and oxygen-free by Day 29 and Day 60 with fostamatinib treatment in comparison to placebo (P=0.0213 and P=0.0271, respectively, Table 1). Treatment-emergent adverse events were consistent with previous studies and were similar between the 2 groups.

Conclusion
The addition of fostamatinib to standard of care treatment resulted in significantly fewer days on oxygen, an improved 8-point ordinal scale score, and significantly more patients alive and oxygen-free by Day 60 compared to placebo in pts with COVID-19 requiring hospitalization and supplemental oxygen.

Disclosures
Deepa B. Gotur, MD, FCCP, FCCM, GSK: Advisor/Consultant|GSK: Speaker at ATS|Moderna: Advisor/Consultant Vadim Markovtsov, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Lucy Yan, MD, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Wolfgang Dummer, MD, PhD, Rigel Pharmaceuticals, Inc.: Stocks/Bonds.
98. Resurgence of Invasive Group A Streptococcal Disease in Utah Children
Authors: McMillion Benjamin , Pershing Nicole L , Crandall Hillary , Krow Ampofo Kwabena , Hersh Adam , Olson Jared , Oakeson Kelly F , Wagner Jennifer M , Young Erin L , Nielsen Shannon , Dickey Mandy , Huynh Kelly , Pavia Andrew T , Blaschke Anne J 
Published: November 2023

Abstract

Background
Streptococcus pyogenes (GAS) is a common cause of non-invasive mucosal infections in childhood as well as life-threatening invasive infections. Since 1997, emm1 has been the most common emm type associated with invasive GAS (iGAS) in the US. Apparent increases in iGAS have been reported in several countries during the winter of 2022-23. We sought to characterize changing clinical and molecular epidemiology of iGAS disease in Utah children before and after the emergence of COVID-19.

Methods
We retrospectively identified children 0-18 years with iGAS treated at Primary Children’s Hospital (Salt Lake City, Utah) from 2018- 2023. Cases were identified through the laboratory database. Electronic health record review confirmed that cases met the CDC definition of iGAS and streptococcal toxic shock syndrome (STSS). We abstracted demographics, disease classification and outcomes (Table). Comparisons were made across years. GAS isolates underwent whole genome sequencing for emm type determination.

Results
From 1/2018 to 3/2023, we identified 141 cases of iGAS. Case numbers ranged from 6/yr (2021) to 39 (2019). The highest number of cases by quarter was seen in Q1 2023 (Figure). We observed a marked decrease in iGAS from Q1 2020 through Q3 2022 followed by a steep increase, coinciding with surges in RSV and influenza. Demographics were similar across the study period. 60% of iGAS cases were in males. Complicated pneumonia and head/neck infections predominated. iGAS associated with STSS appeared higher post-pandemic (4/73 [5%] cases in 2018-19 vs. 8/51 [16%] in 2022-23 [OR = 3.2; 95% CI 0.8-15]). The majority of STSS (7/12; 57%) was associated with complicated pneumonia. Clinical outcomes were comparable pre- and post-pandemic. emm types were available for 49/51 (96%) of isolates in 2022-23. emm1 and emm12 were associated with 67% of iGAS disease (emm1 n = 16 [33%]; emm12 n = 17 [35%]).

Conclusion
After a marked drop in iGAS infections in children during the COVID-19 pandemic in Utah there was a resurgence of iGAS starting in late 2022 and early 2023, modestly exceeding pre-pandemic levels. emm1 and emm12 predominated in the surge. Further analysis of disease severity and molecular epidemiology are in progress.

Disclosures
Kwabena Krow Ampofo, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support Andrew T. Pavia, MD, GlaxoSmith Kline: Advisor/Consultant|Sanofi: Advisor/Consultant Anne J. Blaschke, MD, PhD, BioFire Diagnostics: Grant/Research Support|BioFire Diagnostics: I have IP owned by the U. of Utah licensed to BioFire and receive royalties. I have been a consultant and received grant support as well.|Merck and Company, Inc.: Advisor/Consultant
101. Serious Adverse Event Rates for Cefazolin and Ceftriaxone Outpatient Parenteral Antimicrobial Therapy
Authors: Sunagawa Shawnalyn , Arduser Sarah , Miller Molly M , Lyden Elizabeth , Cortes-Penfield Nicolas W , Hankins Richard , Bergman Scott J , Alexander Bryan T 
Published: November 2023

Abstract

Background
Beta-lactams are thought to be well-tolerated in outpatient parenteral antimicrobial therapy (OPAT), but few studies address the utility of regularly monitoring laboratory parameters for beta-lactams in the OPAT setting. Our aim was to assess OPAT adverse event (AE) rates for cefazolin and ceftriaxone to better define appropriate laboratory monitoring for these antimicrobials.

Methods
We retrospectively evaluated patients prescribed either cefazolin or ceftriaxone via OPAT between 3/1/2019-9/30/2022. Combination intravenous antimicrobial therapies were excluded. The primary outcome was incidence of clinically significant OPAT-related AEs, defined as drug-related AE leading to treatment alterations (e.g., abnormal labs, allergic reactions, Clostridioides difficile infection) or any catheter-associated AE. Secondary outcomes included time from start of therapy to clinically significant AEs, unplanned healthcare utilization (e.g., emergency department visits, readmissions), and factors associated with increased risk of clinically significant AEs. We performed descriptive statistics for cohort characteristics, Fisher’s exact and independent sample T-tests for associations with primary and secondary outcomes, and univariate and multivariate regressions for predictors of AEs.

Results
Characteristics of the cohort are listed in Table 1. Primary and secondary outcomes are reported in Table 2. There were 3282 sets of weekly labs, 99.7% were obtained and reviewed within 72 hours from lab draw. Laboratory monitoring detected 2.7 clinically significant AEs per 1000 sets of weekly labs. Median time from start of therapy to abnormal lab drug-associated AE was 26 days (IQR 19, 34). Univariate and multivariate logistic regressions are listed in Table 3. There were no statistically significant differences in antibiotic, duration of therapy, or OPAT modality between the groups with or without clinically significant drug-related AE.

Conclusion
Cefazolin and ceftriaxone were well tolerated during OPAT, with few drug-associated AEs mainly occurring beyond 3 weeks of therapy. As we identified just 2.7 clinically significant AEs per 1000 sets of weekly labs, routine weekly laboratory monitoring for cefazolin and ceftriaxone in the OPAT setting may be excessive.

Disclosures
Scott J. Bergman, PharmD, bioMerieux, Inc.: Honoraria Bryan T. Alexander, PharmD, BCIDP, AAHIVP, Astellas Pharma: Advisor/Consultant|F2G: Advisor/Consultant|Merck: Grant/Research Support