bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurohormonal response patterns to hunger, satiation, and postprandial fullness in normal weight, anorexia nervosa, and obesity
Authors: Campos Alejandro , Marek Tomas , Calderon Gerardo , Ghusn Wissam , Cifuentes Lizeth , Sim Leslie A. , Camilleri Michael , Dayyeh Barham Abu , Port John D. , Acosta Andres
Published: November 2023

Background

Food intake is regulated by homeostatic and hedonic systems that interact in a complex neuro‐hormonal network. Dysregulation in energy intake can lead to obesity (OB) or anorexia nervosa (AN). However, little is known about the neurohormonal response patterns to food intake in normal weight (NW), OB, and AN.

Material & Methods

During an ad libitum nutrient drink (Ensure®) test (NDT), participants underwent three pseudo‐continuous arterial spin labeling (pCASL) MRI scans. The first scan was performed before starting the NDT after a > 12 h overnight fast (Hunger), the second after reaching maximal fullness (Satiation), and the third 30‐min after satiation (postprandial fullness). We measured blood levels of ghrelin, cholecystokinin (CCK), glucagon‐like peptide (GLP‐1), and peptide YY (PYY) with every pCASL‐MRI scan. Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated and normalized (nCBF) with the CBF in the frontoparietal white matter. The hypothalamus (HT), nucleus accumbens [NAc] and dorsal striatum [DS] were selected as regions of interest (ROIs).

Results

A total of 53 participants, 7 with AN, 17 with NW (body‐mass index [BMI] 18.5–24.9 kg/m2), and 29 with OB (BMI ≥30 kg/m2) completed the study. The NW group had a progressive decrease in all five ROIs during the three stages of food intake (hunger, satiation, and post‐prandial fullness). In contrast, participants with OB showed a minimal change from hunger to postprandial fullness in all five ROIs. The AN group had a sustained nCBF in the HT and DS, from hunger to satiation, with a subsequent decrease in nCBF from satiation to postprandial fullness. All three groups had similar hormonal response patterns with a decrease in ghrelin, an increase in GLP‐1 and PYY, and no change in CCK.

Conclusion

Conditions of regulated (NW) and dysregulated (OB and AN) energy intake are associated with distinctive neurohormonal activity patterns in response to hunger, satiation, and postprandial fullness.
Time‐dependent regulation of respiration is widespread across plant evolution
Authors: Qin Haiyan , Sun Mengqi , Guo Weizhou , He Yingpeng , Yao Yinan , Resco de Dios Víctor
Published: November 2023

Establishing the temperature dependence of respiration is critical for accurate predictions of the global carbon cycle under climate change. Diurnal temperature fluctuations, or changes in substrate availability, lead to variations in leaf respiration. Additionally, recent studies hint that the thermal sensitivity of respiration could be time‐dependent. However, the role for endogenous processes, independent from substrate availability, as drivers of temporal changes in the sensitivity of respiration to temperature across phylogenies has not yet been addressed. Here, we examined the diurnal variation in the response of respiration to temperatures (R–T relationship) for different lycophyte, fern, gymnosperm and angiosperm species. We tested whether time‐dependent changes in the R–T relationship would impact leaf level respiration modelling. We hypothesized that interactions between endogenous processes, like the circadian clock, and leaf respiration would be independent from changes in substrate availability. Overall, we observed a time‐dependent sensitivity in the R–T relationship across phylogenies, independent of temperature, that affected modelling parameters. These results are compatible with circadian gating of respiration, but further studies should analyse the possible involvement of the clock. Our results indicate time‐dependent regulation of respiration might be widespread across phylogenies, and that endogenous regulation of respiration is likely affecting leaf‐level respiration fluxes.
Towards transparency: adoption of WHO best practices in clinical trial registration and reporting among top medical research funders in the USA
Authors: Gamertsfelder Elise , Delgado Figueroa Netzahualpilli , Keestra Sarai , Silva Alan Rossi , Borana Ronak , Siebert Maximilian , Bruckner Till
Published: November 2023

Objective

To assess to what extent the clinical trial policies of the largest public and philanthropic funders of clinical research in the United States meet WHO best practices in trial registration and reporting.

Methods

Public and philanthropic funders of clinical trials in the USA with >US$50 million annual spend were selected. The funders were assessed using an 11-item scoring tool based on WHO Joint Statement benchmarks. These 11 items fell into 4 categories, namely: trial registration, academic publication, monitoring and sanctions. An additional item captured whether and how funders referred to Consolidated Standards of Reporting Trials (CONSORT) within their trial policies. Each funder was independently assessed by two or three researchers. Funders were contacted to flag possible errors and omissions. Ambiguous or difficult-to-score items were settled by an independent adjudicator.

Results

Fourteen funders were assessed. Our cross-sectional study found that, on average, funders have only implemented 4.1/11 (37%) of WHO best practices in clinical trial transparency. The most frequently adopted requirement was open access publishing (14/14 funders). The least frequently adopted were (1) requiring trial ID to appear in all publications (2/14 funders, 14%) and (2) making compliance reports public (2/14 funders, 14%). Public funders, on average, adopted more policy elements (5.2/11 items, 47%) than philanthropic funders (2.8/11 items, 25%). Only one funder’s policy documents mentioned the CONSORT statement.

Conclusions

There is a significant variation between the number of best practice policy items adopted by medical research funders in the USA. Many funders fell significantly short of WHO Joint Statement benchmarks. Each funder could benefit from policy revision and strengthening.
In Situ Ellipsometry and EIS Study of Potentiostatic Synthesis of Pseudocapacitive MnOx
Authors: Sampaio R. S. , Silva T. M. , Montemor M. F.
Published: November 2023

This work discusses the one-step potentiostatic growth of manganese oxide on stainless steel for pseudocapacitor electrodes. The electrode material was studied through in situ ellipsometry and electrochemical impedance spectroscopy, in order to correlate its microstructure with the capacitive response. Ellipsometry results show the formation of three layers during the potentiostatic synthesis of manganese oxide on stainless steel: the thickening of the native oxide of the substrate, and the growth of two distinct layers of manganese oxide. The inner layer is slightly more compact (>n) and more resistive (<k) than the outer one. The electrochemical characterization of modified electrodes showed that the increase in the growth potential (from 0.7 to 1.0 VSCE) leads to the formation of manganese oxide films with higher specific capacitance (from 64 to 330 F g−1 at 2 A g−1). This effect is due to an increase in the area of the active material and to a decrease in the thickness of the inner layer of the manganese oxide film. However, higher growth potentials also lead to an increase in film resistivity due to the increase in the density and thickness of the outer layer, which hinders the diffusion of ions through the film as evidenced by EIS.
Analysis of Electrochemical Degradation Phenomena of SOC Stacks Operated in Reversible SOFC/SOEC Cycling Mode
Authors: Lang M. , Lee Y. S. , Lee I. S. , Szabo P. , Hong J. , Cho J. , Costa R.
Published: November 2023

In recent years the degradation rates of high temperature stacks with solid oxide cells (SOC) during steady-state long-term operation in fuel cell (SOFC) and electrolysis (SOEC) mode have been steadily decreased. In contrast, the quantification and understanding of degradation mechanisms of SOC stacks during reversible SOFC/SOEC cycling operation still remains a challenging issue. Therefore, the present paper focusses on the detailed analysis and discussion of degradation phenomena of two SOC stacks during galvanostatic steady-state SOFC and reversible SOFC/SOEC cycling operation. The stacks with fuel electrode supported cells of Elcogen (Estonia) were fabricated by the industrial project partner E&KOA (Daejeon, Korea) within the Korean-German project “Solid Oxide Reversible Fuel Cell/Electrolysis Stack” (SORFES). The first 10-cell stack was tested at DLR during 1400 h and the results were used to improve the second 6-cell stack, which was operated at E&KOA during 2800 h. For electrochemical characterization jV-curves and electrochemical impedance spectroscopy were measured. The results between galvanostatic steady-state SOFC operation and reversible SOFC/SOEC cycling are compared. The degradation of the open circuit voltages, the performances and the resistances of the individual repeat units are presented and discussed. Moreover, possible degradation mechanisms are outlined.
Effect of Fe–N–Cs as Catalytic Active Support for Platinum towards ORR in Acidic Environment
Authors: Schonvogel Dana , Nagappan Nambi Krishnan , Müller-Hülstede Julia , Bengen Nina , Wagner Peter
Published: November 2023

Metal-nitrogen-carbon (M–N–C) compounds such as Fe–N–Cs are currently the most promising platinum group metal free catalysts for oxygen reduction in acidic environment. Regarding the overriding goal of reducing PEMFC production costs by reducing the platinum content, the use of Fe–N–Cs as catalytic active support for low Pt amounts is investigated in this study. Activity and stability of Pt in different contents on a commercial Fe–N–C is compared to Pt on a typical carbon black. Pt nanoparticles are well-distributed on both support substrate classes. Although the electrochemical surface and mass activity of Pt is lower on Fe–N–C compared to carbon black, the Fe–N–C has a contribution to total ORR activity depending on the Pt/Fe–N–C ratio, which is quantified. In the low Pt content case of 1 wt%, the ORR activity is increased by factor of two in presence of Fe–N–C. This boosting effect on ORR activity is important for future strategies to lower the Pt content in PEMFCs.
A Three-Dimensional, Thermodynamically and Variationally Consistent, Fully Coupled, Electro-Chemo-Thermo-Mechanical Model of Solid-State Batteries
Authors: Hu Tianchen , Messner Mark C. , Barai Pallab , Barua Bipul
Published: November 2023

We present a theoretical framework for high fidelity modeling of three-dimensional electro-chemo-thermo-mechanical coupled systems such as solid-state batteries. The framework provides a useful means of utilizing molecular level information to predict the overall performance of the system at the continuum level. The central statement of the theoretical framework is a thermodynamically consistent inf-sup problem. The total potential of the coupled system consists of the Helmholtz free energy, the electrical kinetic potential, the chemical potential, the Fourier potential, the chemical reaction potential, and the external power expenditure. All governing equations derive from variational principles. We also show that the resulting initial-boundary-value problem (IBVP) is consistent with existing, widely adopted equations for modeling batteries. Moreover, the IBVP can be naturally discretized using the (variational) finite element method to simulate practical solid-state batteries with arbitrary geometries. Several examples illustrate multiphysics coupling between pairs of the physical field equations, culminating in a comprehensive three-dimensional model of charge-discharge in a solid state battery.
Trimer Quinoxalines as Organic Cathode Materials for Lithium-Ion Batteries
Authors: Gao Lihong , Wang Bingning , Doan Hieu A. , Du Yachu , Shkrob Ilya A. , Liao Chen
Published: November 2023

Due to synthetic ease, high redox potentials, low solubility in polar electrolytes, and good electric conductivity of their semiconducting crystals, discotic quinoxaline trimers (3Q) have been considered as possible candidates for 4 V organic cathodes in lithium-ion batteries. To assess their feasibility as such materials, several 3Q derivatives have been synthesized and tested in half-cells. In voltage limited cycling tests at 1.2–3.9 V vs Li/Li+, the specific discharge capacities of 40–180 mAh g−1 were obtained at a rate of 1 C, and multiple lithiation of 3Q and its derivatives was observed during discharge. However, the obtained discharge capacity was only a fraction of the theoretical capacity expected for reversible six-electron reduction; there was also rapid capacity fade. Our spectroscopic studies indicate the reversible three-electron lithiation at 2 V vs Li/Li+, but suggest instability of more highly discharged states. Our conclusion is that while the 3Q derivatives combine several traits that are desirable in an organic cathode material (including negligible solubility, capacity for multiple charging, and near-100% coulombic efficiency), these materials are still impractical to use.
Validating Electrochemical Active Surface Area Determination of Nanostructured Electrodes: Surface Oxide Reduction on AuPd Nanoparticles
Authors: Cignoni Paolo , Hosseini Pouya , Kaiser Christoph , Trost Oliver , Nettler Dean-Robin , Trzebiatowski Lisa , Tschulik Kristina
Published: November 2023

Accurate normalization of electrochemical active surface area (ECSA) of nanostructured catalysts and nanoparticles is of utmost importance for catalyst activity determination and comparability. AuxPdy nanoparticles are a highly interesting example, as electrocatalysts for selective oxygen reduction reaction and alcohol oxidation. Most techniques used today for ECSA determination lack accurate validation for nanostructured electrodes and instead rely on reference values determined for macroelectrodes. This includes ECSA determination for AuxPdy nanoparticles, most commonly done by potentiodynamic surface oxide reduction. Here we suggest a versatile approach to validate different ECSA determination techniques for nanoparticle-modified or nanostructured electrodes, using surface oxide reduction of AuxPdy as an illustrative example. Combining this with volume determination by anodic stripping, we electrochemically estimate the NP diameter, which serves as an indication of the accuracy of the obtained ECSA values. Showcasing this for different nanoparticle compositions, we provide experimental conditions for determining AuxPdy nanoparticle ECSA using surface oxide reduction and compare those to parameters reported for macroelectrodes. The approach we introduce herein can be readily applied to a number of different alloy systems, thus, providing a widely applicable approach to determine electrochemical surface areas and validate the transferability of existing macroelectrode characterization techniques to nanostructured or nanoparticle-modified electrodes.
Relative-Humidity Dependence of Electrochemically Active Surface Area in Porous Carbon Catalyst Layers
Authors: Chowdhury Anamika , Radke Clayton J. , Weber Adam Z.
Published: November 2023

Polymer-electrolyte fuel cells (PEFCs) utilize porous catalyst layers (CLs) formed of carbon supports on which Pt particles are deposited and ionomer films are distributed. Carbon supports themselves have varying degrees of porosity, where high-surface-area carbon (HSC) supports possess nanometer-sized interior pores that are suitable for Pt nanoparticle deposition but prevent deleterious ionomer penetration. However, this requires protons to transport through water pathways inside the pores. To understand the generation of such pathways, we examine the various mechanisms of water uptake by PEFC CLs, and the subsequent impact of water uptake on Pt utilization through developing a multiphysics model of the water wetting phenomena as a function of relative humidity. The model details water uptake via ionomer absorption, capillary condensation in the hydrophilic pores, and surface adsorption using molecular potential that account for various water and surface dipole interactions. The results quantify how mesoporous carbons with highly hydrophilic pores increase Pt utilization through the development of wetted layers, which at the same time enable optimized gas-transport pathways. It also demonstrates the impact of pore-size distribution (PSD) and physical and chemical parameters on the water uptake phenomena, allowing for future CL particle and structure optimization.
Effect of Fluorohydroxyapatite on Biological and Physical Properties of MTA Angelus
Authors: Bolhari Behnam , Chitsaz Nazanin , Nazari Sara , Behroozibakhsh Marjan , Sooratgar Aidin , Hashemian Atieh
Published: November 2023

Objectives. This study aimed to assess the effect of addition of fluorohydroxyapatite (FHI) on biological and physical properties of mineral trioxide aggregate (MTA) Angelus. Materials and Methods. In this in vitro, experimental study, nano-FHI powder was first synthesized, and the morphology and chemical structure of particles were evaluated by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Three groups were evaluated in this study: MTA Angelus, MTA modified with 10% FHA, and MTA modified with 15% FHA. After mixing, the materials were applied to ring molds (10 mm diameter, 1 mm height), and the setting time of the three groups was evaluated according to ISO6876 and ASTMC266-03 with a Gillmore needle. The pH was measured using a pH meter at 24 and 48 hours and 7 days after mixing. The cytotoxicity of the materials was assessed in freshly mixed form and after 1 and 7 days using the methyl thiazolyl tetrazolium (MTT) assay according to ISO10993-5. Data were analyzed by one-way and repeated measures ANOVA and Tukey’s test (alpha = 0.05). Results. The addition of FHA to MTA significantly decreased the initial setting time (

P

 < 0.05) and had no significant effect on cell viability (compared with pure MTA Angelus) at 1 and 7 days. However, modified MTA groups in freshly mixed form showed significantly lower cell viability (

P

 < 0.05). The pH remained alkaline at all time points. Conclusion. Addition of 15% FHA to MTA Angelus decreased its setting time with no adverse effect on cell viability (except for fresh form) or pH.
Análisis comparado de la normativa nacional con la normativa internacional asociada con los estados financieros y definición de una estrategia de implementación
Authors: Carvajal Pérez Herminia , Téllez Mellad Luis
Published: November 2023

Una de las premisas fundamentales de los países miembros de la OCDE, dentro de los cuales se encuentra Chile, ha sido cooperar para que la gestión financiera de los Gobiernos se rija por normas internacionales comunes de contabilidad, iniciativa que el país asumió desde 2010 para estar en armonía con las normas dictadas por la Federación Internacional de Contadores para el sector público mundial-IFAC. En este artículo se presenta un examen crítico y sistemático respecto al grado de implementación del proceso de convergencia internacional relacionado específicamente con la presentación de estados financieros. Para estos efectos, se utilizó una matriz de convergencia e impacto, con la finalidad de organizar y ordenar conclusiones que permitan contribuir al fortalecimiento de la normativa nacional.
Phase Ib Trial of Phenformin in Patients with V600-mutated Melanoma Receiving Dabrafenib and Trametinib
Authors: Chapman Paul B. , Klang Mark , Postow Michael A. , Shoushtari Alexander Noor , Sullivan Ryan J. , Wolchok Jedd D. , Merghoub Taha , Budhu Sadna , Wong Phillip , Callahan Margaret K. , Zheng Bin , Zippin Jonathan
Published: November 2023

Purpose:

Preclinical studies show that activation of AMP kinase by phenformin can augment the cytotoxic effect and RAF inhibitors in BRAF V600-mutated melanoma. We conducted a phase Ib dose-escalation trial of phenformin with standard dose dabrafenib/trametinib in patients with metastatic BRAF V600-mutated melanoma.

Experimental Design:

We used a 3+3 dose-escalation design which explored phenformin doses between 50 and 200 mg twice daily. Patients also received standard dose dabrafenib/trametinib. We measured phenformin pharmacokinetics and assessed the effect of treatment on circulating myeloid-derived suppressor cells (MDSC).

Results:

A total of 18 patients were treated at dose levels ranging from 50 to 200 mg twice daily. The planned dose-escalation phase had to be cancelled because of the COVID 19 pandemic. The most common toxicities were nausea/vomiting; there were two cases of reversible lactic acidosis. Responses were seen in 10 of 18 patients overall (56%) and in 2 of 8 patients who had received prior therapy with RAF inhibitor. Pharmacokinetic data confirmed drug bioavailability. MDSCs were measured in 7 patients treated at the highest dose levels and showed MDSC levels declined on study drug in 6 of 7 patients.

Conclusions:

We identified the recommended phase II dose of phenformin as 50 mg twice daily when administered with dabrafenib/trametinib, although some patients will require short drug holidays. We observed a decrease in MDSCs, as predicted by preclinical studies, and may enhance immune recognition of melanoma cells.

Significance:

This is the first trial using phenformin in combination with RAF/MEK inhibition in patients with BRAF V600-mutated melanoma. This is a novel strategy, based on preclinical data, to increase pAMPK while blocking the MAPK pathway in melanoma. Our data provide justification and a recommended dose for a phase II trial.
O horror fáustico à linha reta: uma comparação entre Doutor Fausto e Tristram Shandy
Authors: Coquemala Luisa de Quadros
Published: November 2023

O presente artigo procura investigar as semelhanças entre A vida e as opiniões do cavalheiro Tristram Shandy (1759-1767), de Laurence Sterne, e o Doutor Fausto (1947), romance do autor alemão Thomas Mann. Para além da referência direta a Sterne dentro do romance de Mann e da clara semelhança quanto a comentários metaficcionais, procuramos demonstrar que há igualmente uma ressonância do Tristram Shandy na estrutura narrativa da obra de Mann. Isso se manifesta em dois sentidos: primeiramente, pelo tratamento do tempo, que se altera entre passado (tempo da narrativa) e presente (tempo da narração, no qual os narradores fazem seus comentários metaficcionais). Ademais, ambas as obras trazem uma representação complexa e multifacetada dos fatos narrados, além de uma discussão sobre o gênero romance dentro das próprias obras. Por fim, procuramos apontar como tais mecanismos têm na obra de Mann uma função primordialmente política, uma vez que os artifícios narrativos utilizados são a base da reflexão de Serenus Zeitblom sobre a ascensão dos ideais fascistas na Alemanha.
Dá um play aí: a importância da tecnologia para a fruição artístico-cultural e o desenvolvimento da economia da cultura
Authors: Ficheira Carolina Marques Henriques , Leão Daniel Velasco
Published: November 2023

Este artigo tem por objetivo discutir os impactos da tecnologia no campo da criação, distribuição e fruição de produtos artístico-culturais, principalmente no setor musical, bem como os impactos sociais da economia da cultura no país. Para isso, valer-se-á de uma pesquisa exploratória, que circunda o cenário da plataformização da produção cultural, tecnologia e renda dos brasileiros e da apresentação de exemplos de casos que contrapõem a lógica hegemônica no cenário digital global.
Abstract 12525: Acute Pulmonary Edema, Mid-Ventricular Stress Cardiomyopathy and Cardiogenic Shock Following Intranasal Lidocaine/Epinephrine Administration During Septorhinoplasty
Authors: Maryniak Andrii , Oleszak Filip , Anderson Lucas , Stys Adam , Stys Tom P
Published: November 2023

Case Presentation:
A 19-year-old female presented for elective septorhinoplasty for nasal septal deviation and turbinate hypertrophy. After induction of anesthesia, and orotracheal intubation, pledgets soaked in 4% topical lidocaine with 1:1,000 epinephrine were placed in bilateral nares. Next, 1% lidocaine with 1:100,000 epinephrine was locally injected in the nasal mucosa to obtain hemostasis and analgesia. This resulted in transient hypertensive emergency, followed by undifferentiated shock requiring the initiation of norepinephrine. No signs of ischemia were seen on EKG. Chest X-ray revealed acute pulmonary edema. TTE showed reduced left ventricular systolic function, EF 30%, with mid-segment akinesis, consistent with mid-ventricular stress cardiomyopathy. Coronary angiography identified normal anatomy and patent arteries, supporting the diagnosis. Surveillance TTE after extubation and empiric treatment with metoprolol and losartan, showed improvement of EF to 45-50% and resolution of regional wall motion abnormalities.

Discussion:
Stress cardiomyopathy, also known as Takotsubo (TCM), is a rare form of cardiomyopathy accounting for 2-3% of ACS. The syndrome mainly affects the LV, causing a regional, transient, systolic dysfunction visualized on TTE or left ventriculography, that occurs in the absence of obstructive epicardial coronary lesions. Pathogenesis is poorly understood. Postulated mechanisms include catecholamine excess, coronary artery spasm and microvascular dysfunction. A systematic review found elevated norepinephrine levels in 74.3% of patients diagnosed with TCM, as was the case for our patient. Rapid systemic absorption of epinephrine can cause diffuse microvascular spasm and myocardial stunning. Catecholamine surge may also afflict direct myocardial toxicity, leading to disorganized cytoskeletal structures, excess extracellular matrix proteins and dysfunctional contractile properties of the myocardium.
Abstract 16913: The Association Between Adverse Childhood Experiences and Physiologic Age as Determined by Artificial Intelligence-ECG
Authors: Medina-Inojosa Betsy J , Medina-Inojosa Jose R , chen zhuo , Clark Matthew , Mangold Kathryn , Rajai Nazanin , Lerman Amir , Attia Zachi , Friedman Paul , Lopez-Jimenez Francisco
Published: November 2023

Background:
The gap between electrocardiogram (ECG) artificial intelligence-derived age (ECG-Age) and chronological age (Age-Gap) predicts cardiovascular (CV) comorbidities and mortality reflecting physiologic age. Adverse childhood experiences (ACEs) are traumatic and harmful events that impact adulthood CV outcomes. We hypothesized that ACEs would be associated with physiologic age as determined by the Age-Gap.

Methods:
We applied a previously validated ECG-Age algorithm to the ECGs of 1,988 consecutive individuals aged ≥18, that within 2 years completed an ACEs questionnaire as part of psychological evaluations for weight management. The ACE questionnaire assesses 3 psychosocial domains (i) childhood abuse (psychological, physical or sexual), (ii) household dysfunction (substance abuse, mental illness, female figure treated violently, criminal behavior and parental separation/divorce) and (iii) neglect (emotional or physical) before age 18; results ranged 0 to 10 and were categorized as burden (0, 1-3, and ≥4) and presence (abuse, household dysfunction, neglect). Age-Gap was operationalized as (≤mean or > mean) positive values reflect physiological aging. Logistic regression analyses tested the association between ACE and Age-Gap.

Results:
Mean ± SD chronological age was 49±13 yr, ECG-Age 54±12 yr, Age-Gap 4.26±8.95 yr,75% women, average ACE 2±2, 32% experienced 0, 44% 1-3, and 24% ≥4 ACEs. Age-Gap was 1.4 years higher in those who experienced at least 1 ACE. Compared to those who didn’t experience ACE those who faced 1-3 ACE were more likely to have an Age-Gap >mean (OR 1.28 95%CI 1.57-1.04) independent of sex and the age-adjusted Charlson comorbidity index
Fig A.
Also, they were more prone to experiencing neglect and household dysfunction
Fig B.

Conclusions:
Age-gap was associated with ACEs burden and domains, underscoring the need to identify ACEs during clinical evaluations to prevent ACEs at the individual, family, and community levels.
Abstract 16922: One-Year Latent Health Status Trajectories in Patients With Symptomatic Peripheral Artery Disease
Authors: Grubman Scott , Romain Gaelle , Cleman Jacob , Scierka Lindsey , Pajarillo Carmen , Kluger Jonathan , Mena-Hurtado Carlos , Smolderen Kim G
Published: November 2023

Background:
Symptomatic peripheral artery disease (PAD) can dramatically impact health status. We aimed to characterize typical health status trajectories following initiation of PAD specialty care and to identify demographic, medical, and psychosocial predictors of suboptimal recovery.

Methods:
Adults with new or worsening PAD (Rutherford 1-3) presenting to vascular clinics in the US, Australia, and Netherlands 2011-2015 in the PORTRAIT study were included. Demographics, comorbidities, and psychosocial measures including the EQ-5D (generic health status), PHQ-8 (depression), GAD-2 (anxiety), PSS (stress), ESSI (social support) were obtained upon initial evaluation. Peripheral Artery Questionnaires (PAQ; 0-100, higher = better PAD-specific health status) were administered at 0, 3, 6, and 12 months. Latent trajectory modeling was used to identify typical PAQ score trajectories by Bayesian information criterion. Predictors of favorable vs. poor recovery trajectory (<10-point PAQ increase at 1 year) were assessed by logistic regression. Missingness was handled by multiple imputation.

Results:
The final cohort included 1,204 patients, had a mean age of 67.5 (±9.4) years, was 62.5% male, and 82.1% white. A 5-group model best fit the data (Figure). At 1 year, the High (n=401), Intermediate (n=400), and Sustained Response (n=98) groups demonstrated “favorable” mean PAQ changes of +16.8 , +24.0, and +59.4 points, respectively. The Low (n=150) and Transient Response (n=155) groups demonstrated “poor” recovery of +8.6 and +7.6 points, respectively. Significant predictors of poor recovery included age, nonwhite race, worse EQ-5D, and worse PHQ-8 (all p<0.05).

Conclusion:
Patients with symptomatic PAD follow predictable health status trajectories after initiating care. Poor recovery trajectory is predicted by age, nonwhite race, worse generic health status, and depressive symptom burden. Further emphasis should be placed on these factors during treatment.
Abstract 16931: Network Analysis Identifies Partially Distinct Plasma Protein Associations Underlying HFpEF and HFrEF
Authors: Lamberson Victoria , De Marzio Margherita , Yang Yimin , Buckley Leo F , Dorbala Pranav , Claggett Brian , Myhre Peder L , Rasheed Humaira , Omland Torbjorn , Hoogeveen Ron C , Ballantyne Christie M , Coresh Josef , Yu Bing , Joseph Jacob , Sun Yan , Glass Kimberly , Shah Amil M
Published: November 2023

Introduction:
Underlying biological differences predisposing to heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction are unclear. We used a network analysis technique with plasma proteomics to uncover protein relationships differing between HFpEF and HFrEF.

Methods:
Among 4485 HF-free participants in the Atherosclerosis Risk in Communities study at Visit 5 (2011-2013), we used aptamer-based proteomics values (SomaScan v4; 4955 proteins) as inputs for the LIONESS network approach and reconstructed individual protein-protein interaction networks for each participant (4485 networks). Edge weights across these networks were regressed against incident HF to identify protein correlations statistically different between HFrEF vs no HF and HFpEF vs no HF. This resulted in two differential networks, one for HFpEF and one for HFrEF. Protein node pairs with an absolute difference in correlation of 0.45 were visualized. Two-sample Mendelian Randomization (MR) was used to identify potential causal associations between protein nodes and HFpEF or HFrEF using summary statistics from the Million Veterans Program.

Results:
Mean age was 75±5 years, 58% were women, and 193 HFpEF and 157 HFrEF events occurred at a median follow-up of 7 [IQR 6-8] years. The HFrEF network had 1205 protein nodes, 839 of which were in the largest connected component (LCC, Figure). In contrast, the HFpEF network had 592 proteins, 166 of which comprised the LCC. Only 257 proteins overlap between the two networks. MR identified 10 HFrEF node proteins with potential causal effects on HFrEF with 7 in the LCC, including 2 highly connected nodes (KIAA1549L, ZNF843) previously implicated in cardiac phenotypes. No causal associations were seen for HFpEF.

Conclusions:
Single-sample proteomics-based networks suggest different protein interactions characterize HFpEF and HFrEF. The HFrEF network was larger, more connected, and identified proteins with potential causal effects.
Abstract 16941: Breast Artery Calcification for Primary Prevention of Major Adverse Cardiovascular Outcomes: A New Risk Stratification Tool for Women
Authors: Ali Thara S , diFlorio-Alexander Roberta , Austin-Strohbehn Judith , Truglio Thomas S , Kulkarni Hemant , Amin Amit , Taub Cynthia C
Published: November 2023

Introduction:
Reductions in cardiovascular mortality among women lag behind men. There is a critical need for improved primary prevention of major adverse cardiovascular events (MACE) in women. We examined if breast artery calcification (BAC), detected on screening mammograms, prognosticates long-term MACE.

Methods:
In this retrospective study of consecutive women age 40-75 years without coronary disease from 2011-12, followed for 10 years at Dartmouth-Hitchcock Medical Center, we recorded baseline mammograms, clinical parameters and 10-year MACE risk was estimated via the pooled cohort equation (PCE). The association of BAC and MACE was examined by a multivariable, interactive logistic regression model with MACE as dependent variable, adjusting for confounders and an interaction of BAC with 3 strata of PCE predicted risk: low (<5%), moderate (5-7.5%) and high (>7.5%). The primary endpoint was MACE over 10 years.

Results:
Among 1216 women, 19% had BAC. Women with BAC were older, had more hypertension and diabetes, and a higher baseline PCE score. Over 10 years of follow-up, 21% of women with BAC developed MACE compared to 11% women without BAC (p<0.001). This association was independent of risk factors and statin use. Among women with low (< 5%) risk of MACE, those with BAC had an 18% incidence of MACE, compared to 7% in women without BAC (OR 2.8, 95% CI 1.5 - 5.0) (Fig 1A). The incremental increase in MACE in patients with BAC decreased with higher PCE-predicted risk. Peak interaction occurred at a PCE-predicted risk of 10% (Fig 1B). Among women with a PCE-predicted risk <10%, BAC was a strong predictor of MACE with an attributable fraction of 20% (Fig 1B).

Conclusions:
BAC is a strong, independent predictor of MACE, particularly in women at low risk by PCE. Although PCE is used widely to risk stratify women for MACE, our study suggests it severely underestimates risk in women with a low PCE score. Further prospective trials are needed to validate these findings.
Abstract 16942: Organized Thrombus (OTh) Formation Mediated by Disturbed Flow-Induced Endothelial Senescence-Associated Stemness (SAS)
Authors: Kotla Sivareddy , Samanthapudi Venkata Subrahman K , Hernandez Gonzalez Selina , Perez Kaylah Y , Lin Steven , Koutroumpakis Efstratios , Palaskas Nicolas L , Reyes-Gibby Cielito , Yeung Sai-Ching , Dantzer Robert , Morrell Craig , Krishnan Sunil , Li Shengyu , Wang Guangyu , Chini Eduardo N , Martin James F , LE NHAT TU T , Abe Junichi
Published: November 2023

Atherosclerotic and high-risk plaques are predominantly localized to vessel wall regions with non-laminar disturbed blood flow (d-flow), leading to the principle that d-flow-, but not laminar flow (l-flow)-driven endothelial cells (EC) dysfunction plays a role in this process. LATS1/2 and YAP are components of the Hippo signaling pathway that are involved in cellular responses to l-flow. The l-flow-mediated inhibition of LATS1/2 activity triggers YAP activation and maintains vascular structure. However, the role of Hippo signaling under d-flow remains unclear. Although both l- and d-flow increased YAP activity, only d-flow decreased LATS1/2 expression. Since the effects of l- and d-flow on EC differ, we studied the role of EC LATS1/2 using EC-specific
Lats1
and
2
knock-out (EKO) mice. Within 14 days after inducing
Lats1/2
deletion in tamoxifen-inducible
Lats1
homo
/
Lats2
homo
EKO mice, all the mice (27/27) died of severe systemic edema, accompanied by increased EC apoptosis and vascular permeability. We generated
Lats1

he

t
/
Lats2
homo
-EKO mice (
Lats1
het
/2
homo
-EKO) and induced hypercholesteremia with AAV8-PCSK9 injections and a high-fat diet (HFD). After HFD, we detected plaque erosion-like plaque lesions at the d-flow areas, which revealed strongly fibrin/fibrinogen-positive organized thrombus (OTh) formation without sizeable necrotic cores. In
Lats1
het
/2
homo
-EKO, we found significant increases in 1) EC proliferation, 2) EC apoptosis with senescent phenotype, 3) tissue factor (TF) expression, and 4) inflammation. Therefore, the phenotype observed in
Lats1
het
/2
homo
-EKO represents a unique senescence-associated stemness (SAS) phenotype, which allows EC to escape senescence-induced cell cycle arrest. The EC proliferation induced by depletion of LATS1/2 was YAP-dependent. In contrast, EC senescence induced by CD38-mediated NAD
+
depletion was YAP-independent. These findings indicate that downregulating LATS1/2 expression-induced SAS leads to OTh via both YAP-dependent and independent mechanisms. OTh plays a key role in human atherosclerosis but is rarely observed in the mouse atherosclerosis model.
Lats1
het
/2
homo
-EKO can provide a valuable platform for studying the mechanism and unique role of EC SAS-induced OTh formation.
Abstract 16944: Risk Stratification With Hemodynamic Gain Index and Peak Rate-Pressure Product in Patients With Chronic Heart Failure Undergoing Treadmill Exercise Testing
Authors: Chaikijurajai Thanat , Finet J. Emanuel , Wu Yuping , Van Iterson Erik H , Harb Serge C , Jaber Wael A , Tang Wai Hong W
Published: November 2023

Introduction:
We recently demonstrated the combined prognostic value of two simple non-invasive parameters obtained from treadmill exercise testing in patients with HFrEF, the hemodynamic gain index (HGI) and peak rate-pressure product (pRPP). However, their prognostic value is yet to be validated in patients with undifferentiated HF syndrome.

Hypothesis:
Both HGI and pRPP predict all-cause mortality in patients with chronic HF.

Methods:
We identified 126,356 consecutive patients undergoing treadmill exercise testing for HF symptom evaluation between 1/1991-2/2015. Patients with a confirmed diagnosis of HF were included. HGI was calculated from [(SBPpeak x HRpeak) - (SBPrest x HRrest)]/(SBPrest x HRrest), and pRPP was calculated from SBPpeak x HRpeak. Hazard ratios per doubling of HGI and pRPP for all-cause mortality were estimated using multivariable Cox regression models with adjustment for traditional cardiovascular risk factors and exercise testing parameters (chronotropic reserve index, METs, abnormal heart rate recovery, and total exercise time). Optimal cut-off for HGI and pRPP were determined by the Youden’s index. Kaplan-Meier plots with log-rank test across patients with low or high HGI and pRPP were used.

Results:
There were 5,940 patients with symptomatic HF diagnosis included in the analysis (mean age 56.2±12.4 years, 68.1% male, 46.5% with CAD, 55.8% with beta-blocker use). During the median follow up of 7.1 years, 2,222 (37.4%) patients died. Higher both HGI and pRPP were associated with a lower risk of mortality (hazard ratio 0.85 [0.81-0.90] and 0.72 [0.62-0.84], respectively, all
P
<0.001). Optimal cut-off values for HGI and peak RPP were 1.06 and 18,966, respectively.
Figure 1
shows Kaplan-Meier plots across patients with low and high HGI and pRPP (log-rank
P
<0.001).

Conclusions:
Both HGI and pRPP are predictors of mortality in patients with chronic HF and can be used for prognostication and referral for advanced HF therapy evaluation.
Abstract 19112: Hemodynamic Optimization of Left Ventricular Assist Devices During Right Heart Catheterization Ramp Studies
Authors: Hajduczok Alexander , Maucione Carly , DiChiacchio Laura , Bent Brinnae , Boehmer John
Published: November 2023

Background:
Studies have shown that hemodynamic LVAD ramp studies can be used to optimize speeds and improve clinical outcomes, yet these studies lack external validation.

Methods:
470 LVAD patients, including 3 LVAD subtypes, were retrospectively analyzed and 53 ramp studies were identified. Measurements (RA, mean PA, PCWP, and CI) were taken at speeds +/- 20% of the manufacturer recommended set speed for HM2, HM3, and HVAD devices. Primary outcomes were all-cause and heart failure (HF) hospitalizations in the 6-month period pre- and post-ramp study. Secondary outcomes included final LVAD speed and hemodynamic measurements following ramp study. Time to first hospitalization and cumulative incidence rate of all-cause and HF hospitalization were reported.

Results:
Baseline characteristics of 53 studies included: mean age of 60.1 (+/- 10.9), 84.9% male, 56.6% ischemic etiology, 71.7% destination therapy, and average NYHA class and INTERMACS of 2.5 (+/- 0.7) and 5.9 (+/- 1), respectively. 38 of 53 studies (71.7%) showed PCWP decompression >20%, with average PCWP decompression of 51.2% (+/- 21.0%), and CI increase of 22.5% (+/- 18.7%). Optimal LVAD speeds were chosen to maintain CI > 2.2, PCWP < 15 and minimize RAP, in the absence of suction events. 31 (58.5%) of studies resulted in an LVAD speed change and 16 (30.2%) of studies resulted in diuretic change. All-cause and HF hospitalizations were significantly decreased in the 6-months following ramp studies compared the 6-months pre-ramp (total days hospitalized for all causes: 12.0 vs 26.6, p=0.002; total days hospitalized for HF, 4.8 vs 22.1, p=0.0003). Speed changes were associated with a nonsignificant improvement in time to first hospitalization.

Conclusion:
This externally validates previous data suggesting that LVAD hemodynamic ramp studies decrease hospitalizations. Larger studies and longer follow up may elucidate specific hemodynamic targets to improve mortality and further reduce rehospitalizations.
Abstract 19127: The Effect of Frailty on 30 Day Rate of Readmission Among Patients With N/Stemi and Spontaneous Coronary Artery Dissection
Authors: Johal Anmol S , Udongwo Ndausung , Imburgio Steven , Mararenko Anton , Pannu Viraaj , Miller Brett , Dandu Sowmya , Abe Temidayp , Akhlaq Hira , Sealove Brett , Heaton Joseph
Published: November 2023

Introduction:
Spontaneous coronary artery dissection (SCAD) can present as myocardial infarction or sudden death, particularly in young patients. SCAD is primarily diagnosed on angiography thus the majority of patients present with findings of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI).

Hypothesis:
We sought to determine the 30-Day readmission rate (30-DRr) for STEMI/NSTEMI in frail individuals with SCAD and its impact on healthcare utilization and economic burden in the United States.

Methods:
Using the 2020 National Readmission Database and International Classification of Diseases, 10th revision (ICD-10) codes, a retrospective study of patient discharges with N/STEMI as a primary diagnosis and with SCAD as a secondary diagnosis. The primary outcome was 30-DRr, while secondary outcomes were readmission mortality rate, length of stay, and resource utilization defined by hospital charge (HC). Outcomes were analyzed to compare frail and non-frail individuals.

Results:
A total of 19,277 index hospitalizations for N/STEMI with a secondary diagnosis of SCAD were identified. The mean age on index admission was 59.53 ± 12.10 years, 57.16% (11,018) were female, and the in-hospital mortality rate was 5.84% (n = 1,125.70). There were 4,068 (21.10%) frail individuals identified. The 30-DRr was 13.30% for frail patients vs 6.51% for non-frail patients (adjusted p < 0.001). There was an 18.48% in-hospital mortality for frail individuals vs 2.46% mortality for non-frail individuals (adjusted p < 0.001). There were also significant increases in length of stay for frail patients, 9.58 days, vs 3.49 days for non-frail patients (adjusted p < 0.001), and total HC for frail patients $61,068.09 when compared to non-frail, $25,248.12 (adjusted p < 0.001).

Conclusions:
Frail patients with SCAD are at higher risk for readmission when compared to non-frail individuals with SCAD. The implications of this data include the possible implementation of closer follow-up with cardiology post-discharge, and need for further studies into the clinical course, interventions, and outcomes associated with SCAD.
Abstract 19130: Is Early Hospital Discharge Safe After Adult Heart Transplantation?
Authors: Shorbaji Khaled , Kwon Jennie , Welch Brett , John Delgaizo , Kilic Arman
Published: November 2023

Introduction:
The impact of early hospital discharge (EHD) after adult heart transplantation (HT) on longitudinal outcomes is unclear. Many HT recipients are intentionally kept in the hospital for extended stays for continued clinical monitoring. However, there is growing interest in implementing EHD protocols and initiatives to improve patient throughput, optimize hospital resources and bed capacity, and reduce costs.

Hypothesis:
This study evaluated the impact of EHD on HT outcomes.

Methods:
The United Network for Organ Sharing (UNOS) database was utilized to identify adult (≥ 18 years old) HT recipients surviving to hospital discharge between January 2010 and December 2022. EHD was defined as occurring within 7 days of HT. Kaplan-Meier analysis was used to estimate survival probability of EHD recipients at 30-days, 90-days, 1-year, 1-year conditional on 30-day survival and 1-year conditional on 90-day survival. Multivariable Cox regression was used for risk adjustment.

Results:
Of the 31,638 total HTs performed in the study period, 30,720 (97.1%) survived to hospital discharge of which 1,033 (3.36%) were classified as EHD. In an unadjusted analysis, HT recipients survival rates were: [(30-days: ED 99.5% vs non-EHD 98.4%, log-rank p= 0.004), (90-days: EHD 98.8% vs non-EHD 96.4%, log-rank p< 0.001), (1-year: EHD 96.5% vs non-EHD 92.9%, log-rank p< 0.001), (1-year conditional on 30-day survival: EHD 96.9% vs non-EHD 94.5%, log-rank p< 0.001), and (1-year conditional on 90-day survival: EHD 97.6% vs non-EHD 96.4%, log-rank p= 0.036)] (Figure 1). After risk adjustment, the Hazard Ratio (HR) of mortality for EHD recipients was: [30-days HR: 0.37 (0.15-0.89, p=0.027), 90-days HR: 0.39 (0.22-0.70, p=0.001), 1-year HR: 0.57 (0.39-0.82, p=0.003), 1-year conditional on 30-day survival HR: 0.60 (0.40-0.90, p=0.013), and 1-year conditional on 90-day survival HR: 0.75 (0.47-1.18, p=0.213)].

Conclusions:
HT patients with EHD have lower complication rates than non-EHD patients. Although a minority of patients have EHD after HT, these data suggest it can be done safely with excellent longitudinal outcomes. Efforts to share best practices and protocols allowing for EHD may be prudent to broadening this practice nationwide in appropriate cases.