bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Technique for Crack Propagation Simulation in Viscoelastic Solid Propellant
Authors: Jiang Qiangqiang , Lv Xuan , Cui Huiru , Ma Teng
Published: June 2023

To further investigate the fracture response in propellant grain, numerical methodology is proposed to cope with crack propagation simulation especially for the mixed mode condition. The numerical discrete scheme of the propellant linear viscoelastic constitutive model is proposed, which provides a key means for the simulation of crack propagation. In order to simulate the cohesive traction distribution on the new crack surface, the extrinsic Park-Paulino-Roesler (PPR) cohesive zone model (CZM) is introduced. To let the crack propagate along any direction determined, element splitting technique and its corresponding topological operations are proposed step by step. Then, computational simulation implementation process is explained in greater detail. Typical fracture problem, single edge-notched tension test (SENT) is solved to demonstrate the efficiency and accuracy of the proposed method. In addition, double edge-notched tension test (DENT) as well as plate tension test with a slant crack is conducted to show the special fracture characters in viscoelastic solid propellant, like time dependence. Computational results reveal that the method proposed can be utilized in further fracture investigation in solid propellant combined with the experimental findings.
Behind Jarratt’s Steps: Is Jarratt’s Scheme the Best Version of Itself?
Authors: Cordero Alicia , Segura Elaine , Torregrosa Juan R.
Published: June 2023

In this paper, we analyze the stability of the family of iterative methods designed by Jarratt using complex dynamics tools. This allows us to conclude whether the scheme known as Jarratt’s method is the most stable among all the elements of the family. We deduce that classical Jarratt’s scheme is not the only stable element of the family. We also obtain information about the members of the class with chaotical behavior. Some numerical results are presented for confirming the convergence and stability results.
Supplementary Table 2 from Chi3l1 Is a Modulator of Glioma Stem Cell States and a Therapeutic Target in Glioblastoma
Authors: Guetta-Terrier Charlotte , Karambizi David , Akosman Bedia , Zepecki John P. , Chen Jia-Shu , Kamle Suchitra , Fajardo J. Eduardo , Fiser Andras , Singh Ritambhara , Toms Steven A. , Lee Chun Geun , Elias Jack A. , Tapinos Nikos
Published: June 2023

Supplementary Table 2
Data from Genomic profiling of radiation-induced sarcomas reveals the immunological characteristics and its response to immune checkpoint blockade
Authors: Hong Dong-Chun , Yang Jing , Sun Cong , Liu Yuan-Tao , Shen Lu-Jun , Xu Bu-Shu , Que Yi , Xia Xiaojun , Zhang Xing
Published: June 2023

Abstract
Purpose: Radiation-induced sarcomas (RISs) have poor prognosis and lack effective treatments. Its genome and tumor microenvironment are not well characterized and need further exploration. Experimental Design: Here, we perform whole exome (WES) and mRNA sequencing (mRNA-seq) on patient with RISs and primary sarcomas (WES samples 46 vs 48, mRNA-seq samples 16 vs 8, mainly in head and neck), investigate the anti-tumor effect of PD-1 blockade in RIS-PDX models, and analyze clinical data of RIS patients treated with chemotherapy alone or combined with an anti-PD-1 antibody. Results: Compared to primary sarcomas, RISs manifested different pattern of copy number variations, significantly higher number of predicted strong MHC-binding neoantigens, and significantly increased immune cell infiltration. Clinical data showed that the combinatorial use of chemotherapy and PD-1 blockade achieved a higher overall response rate (ORR) (36.67% vs 8.00%, p = 0.003), longer overall survival (31.9 months vs 14.8 months, p = 0.014) and longer progression free survival (4.7 months vs 9.5 months, p = 0.032) in RIS patients compared to single chemotherapy. Conclusion: Elevated genomic instability and higher immune cell infiltrations was found in RISs than primary sarcomas. Moreover, higher efficacy of chemotherapy plus PD-1 blockade was observed in animal experiment and clinical practice. These evidence indicated the promising application of immune checkpoint inhibitors in the treatment of RISs.
Data from Genomic Profiling of Radiation-Induced Sarcomas Reveals the Immunologic Characteristics and Its Response to Immune Checkpoint Blockade
Authors: Hong Dong-Chun , Yang Jing , Sun Cong , Liu Yuan-Tao , Shen Lu-Jun , Xu Bu-Shu , Que Yi , Xia Xiaojun , Zhang Xing
Published: June 2023

AbstractPurpose:
Radiation-induced sarcomas (RIS) have a poor prognosis and lack effective treatments. Its genome and tumor microenvironment are not well characterized and need further exploration.
Experimental Design:
Here, we performed whole-exome sequencing (WES) and mRNA sequencing (mRNA-seq) on patients with RIS and primary sarcomas (WES samples 46 vs. 48, mRNA-seq samples 16 vs. 8, mainly in head and neck), investigated the antitumor effect of programmed cell death protein 1 (PD-1) blockade in RIS patient-derived xenograft models, and analyzed clinical data of patients with RIS treated with chemotherapy alone or combined with an anti–PD-1 antibody.
Results:
Compared with primary sarcomas, RIS manifested different patterns of copy-number variations, a significantly higher number of predicted strong MHC-binding neoantigens, and significantly increased immune cell infiltration. Clinical data showed that the combinatorial use of chemotherapy and PD-1 blockade achieved a higher objective response rate (36.67% vs. 8.00%; P = 0.003), longer overall survival (31.9 months vs. 14.8 months; P = 0.014), and longer progression-free survival (4.7 months vs. 9.5 months; P = 0.032) in patients with RIS compared with single chemotherapy.
Conclusion:
Elevated genomic instability and higher immune cell infiltrations were found in RIS than in primary sarcomas. Moreover, higher efficacy of chemotherapy plus PD-1 blockade was observed in animal experiments and clinical practice. This evidence indicated the promising application of immune checkpoint inhibitors in the treatment of RIS.
Data from Patient Specific Targeting of the T-cell Receptor Variable Region as a Therapeutic Strategy in Clonal T-Cell Diseases
Authors: Lucero Olivia M. , Lee Ji-Ann , Bowman Jenna , Johnson Kara , Sapparapu Gopal , Thomas John K. , Fan Guang , Chang Bill H. , Thiel-Klare Karina , Eide Christopher A. , Okada Craig , Palazzolo Mike , Lind Evan , Kosaka Yoko , Druker Brian J. , Lydon Nicholas , Bowers Peter M.
Published: June 2023

Abstract
Purpose: Targeted therapeutics are a goal of medicine. Methods for targeting T-cell lymphoma lack specificity for the malignant cell, leading to elimination of healthy cells. The T-cell receptor (TCR) is designed for antigen recognition. T-cell malignancies expand from a single clone which expresses one of 48 TCR variable beta (Vβ) genes, providing a distinct therapeutic target. We hypothesized that a monoclonal antibody that is exclusive to a specific Vβ would eliminate the malignant clone while having minimal effects on healthy T-cells. Experimental Design: We identified a patient with large granular T-cell leukemia, and sequenced his circulating T-cell population, 95% of which expressed Vβ13.3. We developed a panel of anti-Vβ13.3 antibodies to test for binding and elimination of the malignant T-cell clone. Results: Therapeutic antibody candidates bound the malignant clone with high affinity. Antibodies killed engineered cell lines expressing the patient TCR Vβ13.3 by antibody-dependent cellular cytotoxicity, TCR-mediated activation-induced cell death, and exhibited specific killing of patient malignant T-cells in combination with exogenous NK cells. EL4 cells expressing the patient’s TCR Vβ13.3 were also killed by antibody administration in an in vivo murine model. Conclusions: This approach serves as an outline for development of therapeutics that can treat clonal T-cell based malignancies and potentially other T-cell-mediated diseases.
Integrative Single-Cell and Bulk Transcriptomes Analyses Identify Intrinsic HNSCC Subtypes with Distinct Prognoses and Therapeutic Vulnerabilities
Authors: Dai Yibin , Wang Ziyu , Xia Yingchao , Li Jin , Wu Yaping , Wang Yanling , Jiang Hongbing , Cheng Jie
Published: June 2023

Purpose:

Tumor heterogeneity in head and neck squamous cell carcinoma (HNSCC) profoundly compromises patient stratification, personalized treatment planning, and prognostic prediction, which underscores the urgent need for more effective molecular subtyping for this malignancy. Here, we sought to define the intrinsic epithelial subtypes for HNSCC by integrative analyses of single-cell and bulk RNA sequencing datasets from multiple cohorts and assess their molecular features and clinical significance.

Experimental Design:

Malignant epithelial cells were identified from single-cell RNA sequencing (scRNA-seq) datasets and subtyped on the basis of differentially expressed genes. Subtype-specific genomic/epigenetic abnormalities, molecular signaling, genetic regulatory network, immune landscape, and patient survival were characterized. Therapeutic vulnerabilities were further predicted on the basis of drug sensitivity datasets from cell lines, patient-derived xenograft models, and real-world clinical outcomes. Novel signatures for prognostication and therapeutic prediction were developed by machine learning and independently validated.

Results:

Three intrinsic consensus molecular subtypes (iCMS1–3) for HNSCC were proposed from scRNA-seq analyses and recapitulated in 1,325 patients from independent cohorts using bulk-sequencing datasets. iCMS1 was characterized by EGFR amplification/activation, stromal-enriched environment, epithelial-to-mesenchymal transition, worst survival, and sensitivities to EGFR inhibitor. iCMS2 was featured by human papillomavirus–positive oropharyngeal predilection, immune-hot, susceptibilities to anti–PD-1, and best prognosis. Moreover, iCMS3 displayed immune-desert and sensitivities to 5-FU and MEK, STAT3 inhibitors. Three novel, robust signatures derived from iCMS subtype-specific transcriptomics features were developed by machine learning for patient prognostication and cetuximab and anti–PD-1 response predictions.

Conclusions:

These findings reiterate molecular heterogeneity of HNSCC and advantages of scRNA-seq in pinpointing cellular diversities in complex cancer ecosystems. Our HNSCC iCMS regime might facilitate accurate patient stratification and individualized precise treatment.
Figure S6 from Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-Institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N.
Published: June 2023

Figure S6 shows Kaplan-Meier curves for clinical PFS from first-line therapy in patients with PEComas, and specifically effect of TFE3 positivity, TSC1/TSC2 mutational status, and uterine versus extra-uterine location on clinical PFS.
The Albumin-Bilirubin Score as a Predictor of Liver-Related Mortality in Primary Biliary Cholangitis with Compensated Cirrhosis
Authors: Chen Qingling , Zhong Rui , Wang Yao , Kui Yiwen , Wen Xiaoyu , Huang Jianjie , Jin Qinglong
Published: June 2023

Background: Although several prognostic scores have been reported to correlate with the prognosis of primary biliary cholangitis (PBC) patients, there are limited tools to predict the prognosis of PBC with compensated cirrhosis. This study aimed to evaluate the prognostic performance of the albumin-bilirubin (ALBI) score in PBC patients with compensated cirrhosis. Methods: We conducted a retrospective longitudinal study of 219 patients with compensated PBC cirrhosis to evaluate the prognostic performance of the ALBI using Cox regression model, receiver operating characteristic (ROC) curve, and Kaplan-Meier method. Results: During follow-up, a total of 19 subjects (8.7%) met the primary endpoint of liver-related death or liver transplantation (LT). Patients who died/underwent LT have higher ALBI score (−1.06 vs. −2.06, p < 0.001) at baseline than those who survived. ALBI score (hazard ratio: 15.011, 95% confidence interval [CI]: 5.045–44.665, p < 0.001) was associated with an increase in liver-related mortality or LT. ALBI score had the best discriminative capacity to predict the 5-year liver-related mortality (area under the ROC curve: 0.871, 95% CI [0.820, 0.913]) compared with other prognostic scores. The ROC curve showed that the best cut-off value of ALBI score was −1.47, with 90.0% sensitivity and 76.6% specificity. Also, the probability of transplant-free survival decreased with increasing ALBI grade (log-rank p = 0.003). The 5-year transplant-free survival rates of patients in grade 1, grade 2, and grade 3 were 100.0%, 96.4%, and 89.4%, respectively. Conclusion: ALBI score is a simple and effective predictive factor estimating the clinical outcome of patients with compensated PBC cirrhosis and provides better prognostic performance compared with other prognostic scores.
Assessment of Spin in the Abstracts of Randomized Controlled Trials in Dental Caries with Statistically Nonsignificant Results for Primary Outcomes: A Methodological Study
Authors: Su Naichuan , van der Linden Michiel W. , Faggion Jr. Clovis M. , van der Heijden Geert J.M.G.
Published: June 2023

The study aimed to assess the prevalence of spin in the titles and abstracts of randomized controlled trials (RCTs) in dental caries with statistically nonsignificant primary outcomes and to assess the risk indicators which may be associated with spin. Any original publication reporting a two-arm RCT in dental caries with clearly identified statistically nonsignificant primary outcomes published from January 1, 2015, until October 28, 2022, were included. PubMed was searched electronically to identify the eligible publications. The prevalence of spin in titles and abstracts were assessed and categorized into spin patterns based on a predetermined classification scheme. The association between spin and the potential risk indicators at study, author, journal, institutional, and national levels was assessed. A total of 234 eligible RCT publications were included. The prevalence of spin in the titles and abstracts was 3% (95% confidence interval [CI]: 2–6%) and 79% (95% CI: 74–84%), respectively. The most common spin patterns in the results and conclusion sections, respectively, were results focusing on statistically significant within-group comparisons (23%), and conclusions focusing only on statistically significant results without acknowledgment of statistically nonsignificant results for the primary outcomes (26%). The spin was significantly associated with number of study centers (single-center vs. multicenter) (OR = 2.131; 95% CI: 1.092–4.158; p = 0.03), trial designs (nonparallel designs vs. parallel designs) (OR = 0.395; 95% CI: 0.193–0.810; p = 0.01), and overall H index of institutions for last authors (OR = 0.998; 95% CI: 0.996–0.999; p < 0.01), while it was not significantly associated with the other indicators. In the RCT publications with statistically nonsignificant results for primary outcomes in dental caries, the prevalence of spin may be low in the titles but high in the abstracts. Single-center studies with parallel designs and a lower overall H index of institutions for last authors may be more likely to have spin in the abstracts.
Formação de professores e educação inclusiva: a démarche clínica centrada na transferência
Authors: Voltolini Rinaldo
Published: June 2023

Este artigo se propõe a discutir a pertinência e a dinâmica do funcionamento do dispositivo de démarche clínica na formação de professores. Partindo da constatação dos limites da abordagem hegemônica na formação docente — aqui denominada abordagem cientificizante com método dedutivo —, levanta-se como hipótese que um trabalho de escuta de professores em grupos de discussão de casos — abordagem clínica com método indutivo —, nos quais se parte dos impasses que surgem no trabalho docente, permite levantar elementos que promovem um modo particular de implicação do professor na teorização de seu trabalho. Para tanto, discutiremos a posição da démarche clínica no interior do campo da formação docente, bem como analisaremos, através de fragmentos de trabalho nos grupos de escuta de professores, o funcionamento e a eficácia destes grupos na formação docente.
O Procedimento de Desenhos-Estórias com Tema em pesquisas qualitativas sobre imaginários coletivos
Authors: Visintin Carlos Del Negro , Ambrosio Fabiana Follador e , Aiello-Vaisberg Tânia Maria José
Published: June 2023

O Procedimento de Desenhos-Estórias com Tema é um mediador que vem sendo utilizado em várias pesquisas sobre imaginários coletivos que tomam a psicologia psicanalítica concreta como referencial teórico-metodológico. Assim, justifica-se o objetivo do presente texto de apresentar os fundamentos teórico-metodológicos desse tipo de recurso. Para tanto, o artigo está organizado em três seções. Na primeira, discorre sobre as diversas possibilidades por meio das quais a psicanálise vem sendo vinculada à pesquisa qualitativa, com vistas a situar o trabalho com o Procedimento de Desenhos-Estórias com Tema nesse leque de alternativas. Na segunda, apresenta, detalha e fundamenta o próprio procedimento, dedicando atenção ao processo de definição do tema a ser solicitado. Na terceira, apresenta material de pesquisa para ilustrar as questões que compõem a segunda parte do artigo. Finaliza considerando que o uso do Procedimento de Desenhos-Estórias com Tema, quando fundamentado e articulado com referencial teórico devidamente explicitado, revela-se um mediador dialógico fecundo na produção de material investigativo em pesquisas sobre imaginários coletivos.
Abstract 100: Multi-drug Cocktail Approach After Asphyxial Cardiac Arrest And Cardiopulmonary Bypass Resuscitation In Rats
Authors: Choudhary Rishabh C , Shoaib Muhammad , Yin Tai , Hayashida Kei , He Mingzhu , Al-Abed Yousef , Kim Junhwan , Becker Lance B
Published: June 2023

Background:
Cardiac arrest (CA) is a leading cause of death in the US. There are limited therapies that substantially improve survival with good neurologic outcomes. The lack of neuroprotective drugs has been cited as a major roadblock to improved outcomes. There have been many failed human trials of potentially neuroprotective drugs. However, most of the failed prior studies have focused on a single drug or single pathological pathway. By contrast, our metabolomic data suggests that after CA multiple pathways are severely dysregulated.

Objective:
The aim of this study was to develop and test the therapeutic effectiveness of a multi-drug cocktail targeting multiple dysfunctional pathways observed during brain ischemia-reperfusion. We sought to increase survival with good neurological outcomes in a highly lethal rat model of 20 min CA followed by cardiopulmonary bypass (CPB) resuscitation.

Methods:
A multi-drug cocktail formulation was developed comprised of ten drugs (Metformin, poloxamer 188, N- acetylcysteine, Sulbutiamine, Zoniporide, SS-31, Cyclosporin A, CoQ10, Vitamin C, and Edaravone) focusing on distinct metabolic pathways of ischemia-reperfusion injury. Male Sprague-Dawley rats (400-500 g) underwent 20 min of asphyxial-CA and 30 min of CPB resuscitation. After the resumption of spontaneous circulation (ROSC), rats received either cocktail or a vehicle (n=6) through a femoral vein for over a 20-minute. Animals were extubated after 4 h of mechanical ventilation. Body temperature was maintained at 37.0 ± 0.5°C. Outcomes assessed include a 4 h survival time and retention of corneal reflex.

Results:
Cocktail treatment resulted in 4/6 rats surpassing the 4 h survival window, while only 2/6 rats after vehicle treatment. The median survival time was 240.53 min vs 120.62 min for a cocktail vs vehicle, respectively (p=0.067). Furthermore, 4/6 rats treatment with a cocktail demonstrated retention of corneal reflex after 4 h compared with 2/6 rats after vehicle treatment.

Conclusion:
This pilot study is the first to use a multi-drug cocktail in a severe CA rodent model that demonstrates a trend for better survival and corneal reflex retention. Future studies of cocktails seem warranted if neuroprotective therapies are contemplated in the setting of CA.
Abstract 10001: Relationship Between Coronary HIPs on Non-Contrast T1-WI by CMR and Vulnerable Plaque Features by NIRS-IVUS
Authors: Fukase Tatsuya , Tomotaka Dohi , Fujimoto Shinichiro , Nozaki Yui , nishio ryota , Kudo Ayako , Takeuchi Mitsuhiro , Takahashi Norihito , Chikata Yuichi , Hirohisa Endo , Kawaguchi Yuko , Doi Shinichiro , Nishiyama Hiroki , Hiki Makoto , Okai Iwao , Iwata Hiroshi , Yokoyama Takayuki , Okazaki Shinya , MIYAUCHI Katsumi , Daida Hiroyuki , Minamino Tohru
Published: June 2023

Introduction:
Although high-intensity plaques (HIPs) on cardiac magnetic resonance (CMR) have been reported to be associated with vulnerable plaque features, there is little evidence in comparison with near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) findings, which have recently been shown to positively identify vulnerable plaques and predict peri-procedural myocardial infarction (pMI).

Hypothesis:
We assumed that the coronary plaque characterization of CMR and NIRS-IVUS may have a significant relationship, and determined whether pre-percutaneous coronary intervention (PCI) evaluation using CMR identifies HIPs at risk of pMI.

Methods:
In total, 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥1.4. We evaluated the association between the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI
4mm
) and plaque morphology on IVUS, and assessed the incidence of pMI.

Results:
Of 62 lesions, HIPs were observed in 30 lesions (48%). HIPs had a significantly higher maxLCBI
4mm
(500±170 versus [vs.] 288±218,
p
<0.001) and plaque burden (69±8% vs. 63±10%,
p
=0.011) than the non-HIPs. The correlation between the maxLCBI
4mm
and PMR was significantly positive (r=0.51). In multivariable analysis, HIP independently predicted a maxLCBI
4mm
≥400 (odds ratio [OR]=3.93; 95% confidence intervals [CIs]: 1.21-13.6,
p
=0.023). Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to 5 of 32 lesions (16%) without HIP (
p
=0.005).

Conclusions:
We found an important relationship between coronary HIPs on CMR and NIRS-derived maxLCBI
4mm
. We also confirmed that non-contrast T1-weighted imaging in CMR can be useful not only for the characterization of vulnerable plaque features, but also for pre-PCI risk stratification.
Abstract 10015: Predictors of Primary Non-Adherence in Patients With Nonvalvular Atrial Fibrillation Prescribed Oral Anticoagulants in the US
Authors: Hines Dionne M , Divino Victoria , Xie Lin , Hood David W , DeKoven Mitch , Kariuki Wanjiku , Bell Griffith , Russ Cristina , Cheng Dong , Cato Matthew , Atreja Nipun , Hernandez Inmaculada
Published: June 2023

Introduction:
Primary non-adherence (PMN) is defined as the failure to fill an initial prescription for a medication or an appropriate alternative. This study assessed the rates and predictors of PMN among patients with non-valvular atrial fibrillation (NVAF) who were newly prescribed an oral anticoagulant (OAC).

Methods:
A retrospective database analysis of linked claims and electronic health record data was conducted using the Optum
®
Market Clarity Dataset. Adult NVAF patients with a first written prescription for an OAC (apixaban, rivaroxaban, dabigatran, or warfarin) from 1/2016-6/2019 were identified (date of first prescription = index date). Patients had a 1-year pre-index period to describe baseline characteristics and a 6-month post-index period to assess rates of PMN, defined as having a written OAC prescription but not having a paid claim for any OAC within 30 days following the index date. Sensitivity analyses explored 60-, 90- and 180-day PMN thresholds. Logistic regression models were used to examine predictors of PMN.

Results:
The study sample comprised 20,393 patients (mean [SD] age 70.5 [11.3], 59.3% male, 90.0% Caucasian, 53.9% with Medicare only, 30.9% Commercial only, 54.5% in the Midwest). Apixaban (55.4%) was the most commonly prescribed OAC. The overall OAC 30-day PMN rate was 28.4%. Compared to warfarin, direct oral anticoagulants were associated with significantly higher odds of PMN (Figure 1). A CHA2DS2-VASc score of ≥3, Commercial insurance, and African American race were also associated with higher odds of PMN. Sensitivity analyses revealed decreasing PMN over time with a 180-day PMN rate of 17.0%.

Conclusions:
More than a quarter of patients experienced PMN within 30 days of an initial written OAC prescription; however, this rate decreases over a 180-day period, suggesting a delay in fills. Understanding the factors associated with no fills or delayed fills is warranted to guide interventions for improving OAC treatment rates in NVAF.
Abstract 10028: A Predictive Model of Iliofemoral Vascular Complications Following Transfemoral Transcatheter Aortic Valve Replacement
Authors: Koren Ofir , Patel Vivek , Makkar Raj , Naami Robert , Naami Edmund , Natanzon Sharon Shalom
Published: June 2023

Objective:
Design and validate a predictive model for iliofemoral vascular complications (IVC) following transfemoral-transcatheter aortic valve replacement (TF-TAVR).

Background:
IVC following TF-TAVR are common and associated with higher adverse events. However, there is no acceptable method to predict IVC.

Methods:
We used data from 3,706 TF-TAVR patients treated at Cedars-Sinai medical center between 2013-2021. We analyzed CT images of 516 matched patients to formulate a novel score index (Cedars-Sinai Index, CSI) and a predictive model and validated it on data of 609 consecutive patients. Patients with pre-procedural alternative access were excluded.

Results:
IVC occurred in 352 (9.1%) patients. The model design cohort includes 516 matched patients (by age, sex, and year of procedure) in a 2:1 ratio of control and IVC group. Sheath size, the sum of angles, number of curves, minimal lumen diameter (MLD), and sheath-to-femoral artery diameter ratio (SFAR) were significant predictors for IVC. The CSI formula consisting of the multiplication of the sum of angles and the number of curves divided by the MLD had an 84.3% sensitivity and 96.8% specificity (C-stat 0.936, 95% CI 0.911-0.959, p<0.001) for predicting IVC. Setting CSI score > 100 and SFAR >1.0 increased overall accuracy and correctly predicted 97.7% of the complications. The validated model showed a 89.5% sensitivity, 98.9% specificity and 94.2% accuracy (C-stat 0.942, 95% CI 0.904-0.980, p<.0001).

Conclusion:
Our proposed model is simple-to-use and accurately identifies patients at high risk for IVC. The model may be useful to implement in the pre-procedural planning of TAVR.
Abstract 10060: Racial Differences in Outcomes of Hypertensive Crisis in Women With History of Preeclampsia: A National Sample Study
Authors: Ehtesham Moiz , Khan Arshan , Shabbir Muhammad Asim
Published: June 2023

Objective:
Preeclampsia has been shown to put women at an increased risk of developing hypertension later in life. We aimed to determine racial differences in in-hospital outcomes of hypertensive crisis in women with history of preeclampsia in the United States.

Methods:
The national inpatient sample was retrospectively studied from 2012-2019 to identify hospitalizations for hypertensive crisis aged >18. We further identified history of preeclampsia within each admission using ICD-10 codes. The primary outcome was hospital length of stay (LOS) and inpatient mortality rate. Secondary outcomes were chosen as a 3-point composite development of stroke, myocardial infarction (MI) or congestive heart failure (CHF). Demographic (age, sex, race) information was also recorded. Caucasian patients were chosen as baseline reference to compare other ethnicities with. Data was analyzed with STATA 16.0, and adjusted odds ratios (AOR) were calculated using multivariate logistic regression.

Results:
There were 531,432 hospitalizations for hypertensive crisis, out of which 11% (58,457) had history of preeclampsia. 65% of this subset was Caucasian, 21% were African American (AA) and 11% Hispanic. Inpatient mortality rate was higher in Hispanic patients with preeclampsia vs Caucasians [6.2% vs 4.3%; AOR: 1.56 (1.49 – 1.61, p<0.001)]. AA patients had a longer LOS vs Caucasians [5.5 vs 3.2; AOR: 1.21 (1.19 – 1.25, p<0.001)]. There was no significant difference in LOS in Hispanic patients (p=0.08). Hispanic women had increased odds of developing stroke while inpatient compared to their Caucasian counterparts (AOR: 2.31, p<0.001). There was no significant difference in development of MI amongst the races (p=0.09). However, AA women with history of preeclampsia were more likely to develop CHF compared to Caucasians (AOR: 1.92, p<0.001).

Conclusion:
Hispanic women with history of preeclampsia have higher mortality rate and incidence of stroke when admitted with hypertensive crisis. Similarly, African American women with preeclampsia have longer hospital stay when admitted with hypertensive crisis. Further research is needed to understand and alleviate these cardiovascular burdens in ethnic minorities.
Abstract 10096: Genetic Control of Lysosomal Dysfunction Reprograms Sterol Metabolism in Pulmonary Arterial Hypertension
Authors: Harvey Lloyd D , Kim Hee-Jung J , Alotaibi Mona , Tai Yi-Yin , Tang Ying , Arshad Sanya , Sun Wei , Wu Haodi , Zhao Jingsi , Kirillova Anna , Woodcock Chen-shan J , Handen Adam , Al Aaraj Yassmin , Culley Miranda K , Hafeez Neha , Watson Annie , Wallace Callen , Wu Haodi , Sullivan Mara G , St. Croix Claudette M , Stolz Donna , Li Gang , Corley Chase , McDonald Jeffrey G , Nouraie Mehdi , Schwantes-An Tae-Hwi , Desai Ankit A , Pauciulo Michael , Nichols Bill , Lafyatis Robert , Benza Raymond L , Bertero Thomas , Jain Mohit , Chan Stephen Y
Published: June 2023

Background
: Vascular inflammation critically regulates endothelial pathophenotypes, yet causative mechanisms remain incompletely defined, particularly in pulmonary arterial hypertension (PAH). Immune dysregulation and metabolic reprogramming are recognized tenets of PAH pathogenesis, but a unifying theory connecting the two has not been established.

Methods & Results:
Guided by an unbiased, metabolome-wide association study from the multicenter PAH Biobank cohort (N=2,666) that identified a proinflammatory sterol and bile acid metabolite plasma signature significantly associated with PAH mortality (adjusted
P
values<1.1x10
-6
), we found in pulmonary arterial endothelial cells (ECs) that induction of the nuclear receptor coactivator 7 (NCOA7) tempered the generation of proinflammatory sterols by bolstering lysosomal acidification and constraining EC immunoactivation. Conversely, reduced NCOA7 promoted lysosomal dysfunction, resulting in sterol- and bile acid-driven inflammation and EC phenotypes consistent with PAH. Notably, the common variant intronic SNP rs11154337 in
NCOA7
was found to control NCOA7 levels, lysosome activity, sterol and bile acid production, and EC immunoactivation in isogenic, CRISPR-Cas9, SNP-edited, iPSC-derived ECs, indicating a potentially widespread genetic predisposition to NCOA7 deficiency. Correspondingly, SNP rs11154337 was associated with PAH severity as noted by six-minute walk distance (
P
=0.0130, β=58.15, 95% CI [14.45-119.36]) and mortality (
P
=0.0250; hazard ratio=0.4368, 95% CI [0.21-0.90]) in an independent, single-center PAH cohort (N=93).
In vivo
, mice deficient for
Ncoa7
or treated with exogenous 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA)—chosen as a representative metabolite from the sterol signature associated with mortality in the PAH Biobank—demonstrated worsened hemodynamic and histological indices of PAH.

Conclusions:
Our work establishes a genetic and metabolic paradigm that links lysosomal biology and sterol and bile acid processes with EC inflammation. This paradigm carries broad implications not only on molecular diagnostic and therapeutic development in PAH but also in other vascular disorders dependent upon acquired and innate immune regulation.
Abstract 10108: SuPAR, Galectin-3 and ST2 Are Associated With Chronic Kidney Disease Progression in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Gordon Jonathan S , Roehm Bethany , Xu Pin , McAdams Meredith , Grodin Justin L , Hedayati Susan
Published: June 2023

Introduction:
Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for both acute and progressive kidney disease. Elevated levels of the circulating soluble urokinase plasminogen activator receptor (suPAR), Galectin-3, and soluble suppression of tumorigenicity 2 (ST2) have been associated with kidney disease progression in those with CKD. However, there is little known about their predictive value for glomerular filtration rate (GFR) decline in populations with HFrEF.

Methods:
We aimed to determine whether these biomarkers were associated with decline in GFR and death in patients with HFrEF. We included 310 participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life in whom baseline suPAR, Galectin-3, and ST2 and repeated measures of GFR were obtained. The primary outcome was change in 2021 CKD-EPI creatinine-based GFR over 2 years. Secondary outcome was mortality. A joint cox regression model for mortality controlled for age, sex, race, NYHA class, and change in GFR and accounted for competing risks of ventricular assist device (VAD) implantation and heart transplantation.

Results:
Participants were followed for 2 years or until VAD, transplant, or death. Mean age was 59 years (standard error of mean 0.7) and 36% had diabetes mellitus. Median GFR was 60 ml/min/1.73m
2
with 58% NYHA Class III. Of these, 45 died, 33 received LVAD, and 25 were transplanted. Higher baseline suPAR (β coefficient -0.22 √(ml/min/1.73m
2
); 95%CI -0.29, -0.15; P<0.001), Galectin-3 (β coefficient -0.02 √(ml/min/1.73m
2
); 95%CI -0.04, -0.01; P=0.012), and ST2 (β coefficient -0.01 √(ml/min/1.73m
2
); 95%CI -0.02, -0.01, -0.19; P<0.001) plasma concentrations were associated with a decline in eGFR over time in multivariable models. Only ST2 (HR 1.02 per ng/mL increase; 95%CI 1.01, 1.03; P<0.001) was associated with mortality, after controlling for longitudinal change in GFR.

Conclusions:
Higher baseline suPAR, Galectin-3, and ST2 were associated with GFR decline over 2 years in patients with HFrEF. ST2 was associated with a greater risk of mortality, while suPAR and Galectin-3 were not. These biomarkers may be incremental tools used to predict GFR decline in patients with advanced heart failure.
Abstract 10115: Unique Imaging Morphology and Rare Location of Papillary Fibroelastoma Resulting in a Cardioembolic Stroke
Authors: Ghanie Nazeera , Maisuradze Nodari , Thirugnanasambandam Ram Prakash , Taklalsingh Nicholas , Graham-Hill Suzette
Published: June 2023

Clinical Presentation:
Afro-Caribbean female, age 59, with a comorbidity of hypertension presented with acute painless right-sided vision loss. Brain MRI revealed numerous scattered T2/FLAIR hyperintense foci throughout the periventricular, deep, and subcortical white matter, which were favored to represent chronic microvascular ischemic changes. CTA of the head and neck demonstrated mild atherosclerotic calcification of the cavernous segment of the left internal carotid artery without significant stenosis, mild noncalcified atherosclerotic plaque at the right carotid bifurcation, and mild irregularity and narrowing of the mid basilar artery.

Cardiac Imaging:
Transthoracic Echocardiography (TTE) demonstrated severe concentric left ventricular hypertrophy, left ventricle ejection fraction 60-65%, and a mobile, intracavitary mass measuring 1.60cm x 1.59cm. Repeat TTE estimated the mass to be 1.8cm x 1.2cm in the region of the posteromedial papillary muscle. Transesophageal Echocardiography (TEE) redemonstrated a mobile left ventricular mass measuring 2.0cm x 1.8cm along the inferior wall of the interventricular septum. Left heart catheterization demonstrated nonobstructive coronary artery disease with a 30% stenosis of the proximal Right Coronary and Distal Circumflex. Patient underwent surgical removal of the cardiac mass, biopsy-proven to be a Papillary Fibroelastoma (PFE).

Discussion:
PFEs account for 7.9% of all primary benign cardiac tumors and are the most common valvular tumor. More than 80% of these tumors are attached on the aortic or mitral valve, unlike in this patient where it was attached to the left ventricular trabeculae without involvement of the mitral valve or sub-valvular apparatus. The classic appearance of PFEs on TTE is pedunculated and often compared to a sea anemone but appeared homogenous in nature with central vacuolization in this case. This made characterizing the mass as a thrombus or cardiac tumor challenging.
Abstract 10121: Hypoimmunogenic Human Induced Pluripotent Stem Cells Derived Cardiomyocytes for Cardiac Regeneration
Authors: Liu Yen-Wen , Fang I-Hsien , Wang Saprina P
Published: June 2023

Introduction:
Post-transplant rejection resulting from human leukocyte antigen (HLA) mismatch is a challenge in allogeneic cell therapy. Human amniotic fluid stem cell-derived iPSCs (hAFSC-iPSCs) are proved to have immune privilege.

Hypothesis:
hAFSC-iPSC derived cardiomyocytes (hAFSC-iPSC-CMs) are less immunogenic.

Methods and Results:
hAFSC-iPSCs and hAFSC-iPSC-CMs expressed classical HLA-Ia (HLA-A, -B and -C) and non-classical HLA-Ib but did not have HLA-II expression, indicating that these cells may not be highly immunogenic. We did T Cell Assays to confirm low immunogenicity of hAFSC-iPSC-CMs. We did ischemia-reperfusion surgery of left anterior descending coronary artery to create large transmural myocardial infarction in rats. At post-infarct 4 days, we injected human pluripotent stem cell-derived cardiomyocytes (1.0х10
7
cells/kg), including human embryonic stem cell-derived cardiomyocytes (hESC-CMs), hiPSC-CMs and hAFSC-iPSC-CMs, into the infarcted myocardium. Using very low dose of cyclosporine A (CsA, 2.5 mg/kg/day), only hAFSC-iPSC-CMs transplantation could improve post-infarct cardiac function (left ventricular ejection fraction improvement in hAFSC-iPSC-CMs, hESC-CMs and hiPSC-CMs: 13.1 ± 1.8%, 0.6 ± 1.7% and -1.9 ± 1.6%, respectively). Compared with hESC-CMs and hiPSC-CMs, hAFSC-iPSC-CM transplantation remuscularized the infarcted myocardium with infarct size reduction. Using very low dose CsA, these engrafted hAFSC-iPSC-CMs resulted in a 3-month survival in vivo. hAFSC-iPSC-CMs expressing non-classical HLA-Ib evaded detection and attack by natural killer (NK) cells and cytotoxic T cells because these hAFSC-iPSC-CMs activated the protein tyrosine phosphatase SHP-1/SHP-2 signalling pathway of NK cells and cytotoxic T cells which downregulated signal transducer and activator of transcription 1 (STAT-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression.

Conclusions:
We demonstrated the immune privilege of hAFSC-iPSC-CM for cardiac regeneration. HLA-Ib-expressing hiPSCs with reduced HLA-II expression are less immunogenic and may serve as platforms for regenerative medicine.
Abstract 10135: Mortality From Birth to Young Adulthood Among Individuals With Congenital Heart Defects: Results From the Congenital Heart Survey to Recognize Outcomes, Needs, and Well-Being
Authors: Downing Karrie F , Nembhard Wendy N , ROSE CHARLES E , Oster Matthew , Klewer Scott E , Goudie Anthony , Andrews Jennifer , Farr Sherry
Published: June 2023

Introduction:
Limited information exists on long-term mortality of individuals with congenital heart defects (CHD) in the United States. Our objective was to evaluate mortality and related factors among a population-based sample of individuals with CHD born in three U.S. locations.

Methods:
Birth defects surveillance system data on individuals with CHD born between 1980-1997 in Arkansas, Arizona, and Atlanta, Georgia, for the Congenital Heart Survey to Recognize Outcomes, Needs, and well-beinG (CH STRONG) were linked to death records through 2015. Survival probability was estimated using Kaplan-Meier survival curves. For those who survived past one year of age, associations between age at death up to 35 years and characteristics at birth were assessed by adjusted hazards ratios and 95% confidence intervals (CIs) from multivariable Cox proportional hazards models. Standardized mortality ratios (SMRs) and CIs comparing observed to expected deaths based on age-, sex-, year-, race/ethnicity-, and site-specific population mortality rates from the National Vital Statistics System (NVSS) data were calculated.

Results:
Of 11,333 included individuals from CH STRONG, 9,630 (85%) survived to one year of age; of those, probability of survival to age 35 years was 95.8%. Hazard ratios for death up to age 35 years were elevated for those with severe defects, non-cardiac congenital anomalies, and maternal race other than non-Hispanic (NH) white (Figure). The SMR comparing CH STRONG to NVSS was 4.6 (CI: 4.3, 5.0); SMRs remained elevated when limiting to NH white (SMR=4.1, CI: 3.7, 4.5), NH Black (SMR=4.6, CI: 3.9, 5.4), males (SMR=3.6, CI: 3.3, 4.1) and females (SMR=6.8, CI: 6.0, 7.6).

Conclusions:
Individuals with CHD who survived to 1 year of age had 95.8% survival to age 35 years, with their risk of mortality 4.6 times that of the general population. People with severe defects, non-cardiac congenital anomalies, and maternal race other than NH white had the greatest mortality risk.
Abstract 10215: Investigating Aortic Geometric Changes After Endovascular and Open Surgery Repair of Descending Thoracic Aortic Aneurysms
Authors: Cebull Hannah , Dong Andy , Molinari Leonardo , Veneziani Alessandro , Leshnower Bradley G , Piccinelli Marina
Published: June 2023

Introduction:
Repair of descending thoracic aortic aneurysms (DTAA) by endovascular (TEVAR) or open aortic replacement alters aortic anatomical and biomechanical characteristics, which may result in adverse cardiac remodeling. The interplay between all these factors remains mostly unknown.

Hypothesis:
A robust and objective quantification of 3D geometrical changes to the treated aorta will help investigate long-term cardiovascular consequences of DTAA repair.

Methods:
Pre- and post-operative 3D modeling from CT angiography was obtained for 6 patients undergoing OPEN (n=3) or TEVAR (n=3). An automated analysis was conducted to extract aorta centerlines, register pre/post geometries based on anatomical landmarks, calculate the following features: length (
L
), curvature (
C
), torsion (
T
), tortuosity (
TT
), cross sectional area (
A
), and volume (
V
). Pre/post repair geometric analysis was conducted on the ascending (AscAo) and descending (DesAo) aorta, and in consecutive segments based on
C
/
T
profiles; rotations between segments modeled as osculating planes were calculated; TEVAR vs OPEN differences were investigated.

Results:
The age of patients was 65±15 years and 4 were female. All centerline and geometric features were calculated from the models. Fig 1 shows one case with registered
C
profiles. Main results between pre/post were: increase in A
AscAo
(mean 43.4±20.5 mm
2
) and V
AscAo
(mean 31.3±9 cm
3
); increase in
TT
DesAo
(0.6±0.4 vs 1.4±0.5, p=0.01); TEVAR cases showed DesAo elongation (mean 17.8±4 mm); trends for increasing

C
max

(AscAo) and decreasing

C
max

(DesAo); inter-segment rotations show notable pre/post variations (Fig 1b).

Conclusions:
Our preliminary analysis automatically quantified relevant changes in aortic anatomy pre/post repair of DTAA with either open or endovascular repair. Complemented with fluid dynamics and biomechanical studies these investigations could clarify mechanisms affecting long-term consequences of DTAA repair.
Abstract 10239: Association of Lipoprotein(a) and Hypertension in Primary Prevention of Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Rikhi Rishi , Bhatia Harpreet , Schaich Christopher L , Ashburn Nicklaus , Herrington David M , Tsai Michael Y , Michos Erin D , Chevli Parag A , Tsimikas Sam , Shapiro Michael D
Published: June 2023

Introduction:
The presence of both dyslipidemia and hypertension is associated with considerable cardiovascular disease (CVD) risk, yet few studies have explored the relationship between elevated lipoprotein(a) (Lp(a)) and hypertension. This study explored the longitudinal relationship of Lp(a) and hypertension to cardiovascular outcomes in a large multiethnic cohort free of baseline CVD.

Methods:
Individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) (n- 6,674) were grouped as follows: Group 1: Lp(a) < 50 mg/dL and no hypertension; Group 2: Lp(a) ≥ 50 mg/dL and no hypertension; Group 3: Lp(a) < 50 mg/dL and hypertension; and Group 4: Lp(a) ≥ 50 mg/dL and hypertension. Kaplan Meier curves and multivariable Cox proportional hazard models were used to assess the relationship between Lp(a) and hypertension with time to CVD events.

Results:
The mean follow up time was 13.9 years and there were a total of 809 CVD events. A statistically significant interaction was found between LogLp(a) and hypertension status (p = 0.086). Compared to the reference group (Lp(a) < 50 mg/dL and no hypertension), those with Lp(a) ≥ 50 mg/dL and no hypertension (Group 2) had no increase in risk for CVD events (HR: 1.07; 95% CI: 0.78, 1.46) (Table). However, those with Lp(a) < 50 mg/dL and hypertension (Group 3) or Lp(a) ≥ 50 mg/dL and hypertension (Group 4) demonstrated a statistically significant increase in CVD risk compared to the reference group (HR: 1.66; 95% CI: 1.40, 1.98) and (HR: 2.04; 95% CI: 1.62, 2.59), respectively (Table). Among those with hypertension (Groups 3 and 4), Lp(a) was associated with a significant increase in CVD risk (HR: 1.23; 95% CI: 1.00, 1.51).

Conclusion:
The present study found a significant interaction between Lp(a) and hypertension. More research is needed to understand the mechanistic link between Lp(a), hypertension, and CVD.
Abstract 10259: A Case of Mitral Annulus Disjunction Highlighting a Disjunction in Our Knowledge
Authors: Madgula Anantha Sriharsha , Biederman Robert W
Published: June 2023

A 56-year-old female patient was brought to our hospital after she suffered a witnessed cardiac arrest while flying on an airplane. She underwent bystander (in the aisle) CPR for about 20 minutes while forcing the plane to land. Altogether, she received seven shocks via AED. At the time of our evaluation, she was alert and in no distress. She did not carry a family history of SCD but reported “she had an issue with heart valve”. Her initial ECG showed atrial fibrillation with a heart rate of 135 bpm, QTc of 515 ms and no findings suggestive of myocardial injury. Her initial workup showed a potassium level of 3.2 mmol/L and no other significant laboratory abnormalities. Her TTE revealed thickened mitral valve leaflets with bileaflet prolapse and severe (4+) central MR. In addition, mitral annular disjunction (MAD) was noted. Her LVEF was 65% with normal wall motion. A left heart catheterization demonstrated normal coronary arteries. Following, a cardiac MRI confirmed MAD at the P3 scallop only, dilated mitral annulus and with a disjunction gap of 7 mm. Furthermore, there was no intramyocardial or annular late gadolinium enhancement (LGE) noted. An ICD was implanted for secondary prevention and she was then referred for mitral valve repair. With this case, we aim at increasing awareness of MAD and SCD. Currently, clinicians rely mostly on anecdotal evidence. While there is increasing literature suggesting the arrhythmogenic nature of MAD, the pathophysiology and implications are still debated. Interestingly, a subject of recent debate, our patient did not have any LGE suggesting no scar/fibrosis that would serve as a nidus for ventricular arrhythmias. Further, a threshold disjunction gap distance of clinical significance has yet to be determined. The benefit of surgical correction remains unclear. Indeed, further prospective studies are required to delineate MAD and help guide early management and its’ ultimate impact on prognosis