bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4137687: Rotational atherectomy combined with cutting balloon before stent implantation for patients with severely calcified coronary lesions: A meta analysis
Authors: Altobaishat Obieda , Tanashat Mohammad , Abuelazm Mohamed , Abouzid Mohamed , Amin Ahmed Mazen , Abdullah Bataineh Omar , Abdelazeem Basel
Published: November 2024

Background:
Rotational atherectomy (RA) has been proven to treat coronary artery calcification (CAC) during percutaneous coronary intervention (PCI). Cutting balloons (CBs) are modified balloons (MB).

Purpose:
We aim to assess the safety and efficacy of RA followed by CB angioplasty (ROTACUT) before stent placement in CAC.

Methods:
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies, which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through January 2024. We used Stata version 17 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI).

Results:
We included eight studies with a total of 846 patients. There was no significant difference between ROTACUT and RA + bare balloons in major adverse cardiovascular events (MACE) (RR: 0.60 with 95% CI [0.31, 1.16], P= 0.13), the incidence of cardiac death (RR: 1.32 with 95% CI [0.42, 4.14], P= 0.64), the incidence of target vessel revascularization (TVR) (RR: 1.89 with 95% CI [0.40, 8.84], P= 0.42), the incidence of target lesion revascularization (TLR) (RR: 0.83 with 95% CI [0.39, 1.79], P= 0.64), procedural duration (MD: 0.78 with 95% CI [-4.68, 6.24], P = 0.78), incidence of stent thrombosis (RR: 0.81 with 95% CI [0.22, 2.95], P= 0.75), and the incidence of any procedure-related complications (RR: 0.86 with 95% CI [0.42, 1.75], P= 0.68).

Conclusion:
ROTACUT and RA + bare balloons demonstrated similar efficacy and safety profiles in terms of MACE, cardiac death, TVR, TLR, procedural duration, stent thrombosis, and all safety outcomes.
Abstract 4137708: Implementation of a Standard Hydration Protocol Improves Compliance of Pre-procedural Hydration, Reducing the Incidence of Contrast-Induced Acute Kidney Injury (CI-AKI) After Percutaneous Coronary Intervention (PCI)
Authors: Lee Ju Hyun , Avendano Amilcar , Nutt Rebecca
Published: November 2024

Introduction:
Intravenous hydration and contrast media volume reduction are the most important preventive factors against CI-AKI after PCI. Multiple studies have demonstrated the effectiveness of intravenous hydration before PCI, however, varied hydration protocols have rather complicated standardization. Doctors’ preferences and local institutional factors further hinder protocol implementation, resulting in reduced compliance.

Hypothesis:
Standardizing hydration protocol increases the compliance rate of preprocedural hydration orders and administration, reducing the incidence of CI-AKI.

Methods:
A team at Memorial Hermann The Woodlands Medical Center, comprising a cardiovascular nurse coordinator, catheterization laboratory director, pharmacist, information technologist, and hospital administrators, was formed to improve PCI outcomes through a multi-faceted approach. This involved a standardized hydration protocol with direct education, continuous monitoring, and repeated internal feedback, reviewed monthly. The new protocol included normal saline pre- and post-procedure maintenance fluids, with a 250 ml normal saline bolus pre-operatively. Maintenance fluids were set at 75 ml/hr, and 20 ml/hr for patients with congestive heart failure and an ejection fraction ≤ 40%. The team reviewed 233 patients under the old protocol and 281 under the new protocol. Compliance rates of pre-procedural intravenous hydration were compared and CI-AKI incidence, defined as a >50% increase or a 0.3 mg/dL increase in creatinine levels within 5 days post-procedure, was assessed. Chi square tests and t-tests were used to compare cohorts on 12 parameters and CI-AKI incidence assessment, with a p-value of 0.05.

Results:
Compliance with pre-procedural hydration significantly increased under the new protocol (86.1% vs 55.4%, p<0.05). CI-AKI incidence was lower in the new protocol group (7.5% vs 9.9%, p=0.33). Although statistically insignificant in this preliminary analysis, the results were still promising due to a relative CI-AKI reduction of 24.3%. A sample size of 352 patients per group is needed to achieve a power of 0.8.

Conclusion:
The new standardized hydration protocol, coupled with education, increased compliance with pre-procedural hydration and showed a promising trend towards reducing CI-AKI among PCI patients. The final report will be presented upon study completion.
Abstract 4137726: A Deep Learning Digital Biomarker for Mitral Valve Prolapse using Echocardiogram Videos
Authors: Al-Alusi Mostafa , Lau Emily , Small Aeron , Reeder Christopher , Shnitzer Dery Tal , Andrews Carl , Kany Shinwan , Ramo Joel , Haimovich Julian , Khurshid Shaan , Sanborn Danita , Picard Michael , Ho Jennifer , Maddah Mahnaz , Ellinor Patrick
Published: November 2024

Background:
Mitral valve prolapse (MVP) has a prevalence of 2–3% and is a risk factor for heart failure and sudden death, but MVP diagnosis by transthoracic echocardiography (TTE) requires time and clinical expertise. We trained a deep learning model to classify MVP from TTE videos.

Methods:
DROID-MVP is a convolutional neural network trained to classify MVP using echocardiographer labels using 973,531 digital videos (parasternal long axis and apical views) from 45,657 studies performed in 15,728 cardiology patients at Massachusetts General Hospital. We validated DROID-MVP in 1,726 cardiology patients (4,869 studies) and 8,903 primary care patients (8,903 studies), and tested associations between predicted MVP score (range 0-1) and mitral regurgitation (MR) severity and left atrial (LA) anterior-posterior diameter in primary care patients with available measurements.

Results:
Of 15,728 patients (6,029 [38%] women; mean age at first TTE 61 ± 17 years) in the training set, 729 (4.6%) had at least 1 study with MVP. DROID-MVP identified MVP in both the cardiology (area under the receiver operating characteristic curve [AUC] 0.955 [95% confidence interval: 0.939-0.970]; average precision [AP] 0.716 [0.649-0.776]; prevalence 0.035) and primary care (AUC 0.966 [0.955-0.978]; AP 0.668 [0.601-0.730]; prevalence 0.022) test sets (
Figure 1
). Discrimination persisted across strata of MR severity (AUC range 0.877-0.987). High (>0.67) vs low (<0.33) MVP score was associated with higher odds of moderate/severe MR (odds ratio 20.1 [12.2-33.4], p<0.001) and higher LA diameter (2.7 [0.9-4.4] mm, p<0.001;
Figure 2
), after adjusting for age, sex, height, and weight.

Conclusions:
A deep learning model identifies MVP from TTE videos with excellent discrimination and higher model predictions are associated with greater MR severity and LA size. Our work demonstrates how deep learning can automate MVP diagnosis and may serve as a digital biomarker of MVP-associated structural abnormalities.
Abstract 4137782: Fibrinogen-to-Albumin Ratio Does Not Correlate with Comprehensively Assessed Coronary Artery Disease Severity or High-Risk Plaque Features on Coronary Computed Tomographic Angiography
Authors: Nguyen Joseph , Hosadurg Nisha , Flora Christine , Patel Toral , McNamara Coleen , Villines Todd
Published: November 2024

Background:
Fibrinogen-to-albumin ratio (FAR) has been proposed as a readily available inflammatory biomarker associated with coronary artery disease (CAD). However, its association with CAD severity and prognosis has predominantly been assessed in patients with acute coronary syndromes (ACS). The Leiden score is a validated comprehensive measure of CAD incorporating stenosis proximity, severity, and plaque type that independently predicts cardiovascular events. Whether FAR is associated with Leiden score or high-risk plaque features on coronary computed tomographic angiography (CCTA) in stable outpatients is unknown.

Methods:
Adult outpatients undergoing clinically indicated CCTA were enrolled (5/2021-9/2023) in a prospective study assessing the relationship of plaque to immune markers and provided same-day pre-scan peripheral venous blood samples. CCTAs were post-processed and analyzed by the consensus of two expert readers blinded to clinical data using a 17-segment model to determine coronary artery calcium (CAC), Leiden score, and high-risk plaque features. Patients were grouped by FAR (quartiles), Leiden score (<5, 5-20, >20), and CAC score (0, >0-100, >100-300, >300-1000, >1000). Numerical variables were compared via Wilcoxon and Kruskal-Willis tests. Spearman correlation was calculated between FAR and Leiden score.

Results:
Of 284 patients, 53.8% were male, 86.7% were white, and 58.8% were on a statin (Table 1). Median FAR was 70.3 mg/g, 64.0% had a non-zero CAC score, and 25.0% had at least one segment with one high-risk plaque feature. Across quartiles of FAR, there was no difference in Leiden score (5.8 (IQR: 0.0-18.5), 12.4 (3.1-20.7), 8.0 (0.0-19.9), 6.8 (0.0-21.1), p=0.50) or probability of having at least one segment with at least one (29.6%, 23.9%, 23.9%, 22.5%, p=0.69) or two (18.3%, 14.1%, 12.7%, 15.5%, p=0.66) high-risk plaque features. There was no correlation between FAR and Leiden score (R=0.03, p=0.66). There was no difference in FAR when stratified by Leiden score (Table 1, p=0.53), CAC score (Table 2, p=0.50), or number of segments with at least one high-risk plaque feature (Table 3, p=0.18).

Conclusion:
In a prospective cohort of adult outpatients across a wide spectrum of CAD burden with high rates of baseline statin use, FAR was not associated with CAD or presence of high-risk plaque features on CCTA. Further evaluation of its role as an inflammatory biomarker in larger populations, particularly patients without ACS, is required.
Abstract 4137913: Role of serial evaluation of myocardial inflammatory activity and oxidative stress in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis
Authors: Nakashima Yusuke , Kobayashi Shigeki , ISHIKAWA MAHO , Nawata Junya , Nakamura Yoshihide , Fujimura Tatsuhiro , Sano Motoaki
Published: November 2024

Background:
Cardiac sarcoidosis (CS) was characterized by formation of granulomas in the heart. Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of major cardiovascular adverse events (MACE). Although immunosuppressive therapy is recommended for active CS, there is no established markers for treatment and prognosis.

Hypothesis:
We hypothesized that the inflammation and oxidative stress in heart were associated with MACE after steroid therapy.

Aims:
We identified prognostic markers for MACE in patients with CS after steroid therapy.

Methods:
This study was a prospective observational cohort study. Patients with CS diagnosed according to Japanese criteria were enrolled in this study. Patients with abnormal accumulation of
18
F-FDG in heart were treated with steroids with standard guideline-recommended protocol.
18
F-FDG PET were performed after more than 6 months of induction. Urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, and indices of cardiac and renal function were measured. The major outcome was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and radiological relapse with exacerbation of clinical manifestation.

Results:
Fifty consecutive patients with CS underwent steroid therapy and followed up (median follow-up period of 58 months). 39 of 50 patients underwent 18F-FDG PET/CT more than 6 months after steroid therapy. During the follow-up period, 17 of 39 patients showed MACE, consisting of sVT/SCD (N= 11), hospitalization (N= 2) and radiological relapse (N= 4). A Cox proportional-hazard model showed that the U-8-OHdG and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis revealed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 11.6 ng/mg Cr (AUC 0.913, sensitivity 86.7%, specificity 90.0%) and 4.64 (AUC 0.878, sensitivity 76.5%, specificity 91.0%), respectively (Fig.1). Patients with a U-8-OHdG ≧11.6 ng/mg Cr or SUV max ≧4.64 had a significantly higher MACE risk (P values for U-8-OHdG and SUV max were both 0.001 by Log Rank analysis) (Fig.2). It is noted that U-8-OHdG <11.6 ng/mg Cr and SUV max <4.64 after steroid therapy indicate the good responses to the immunosuppressive therapy and better prognosis (Fig.3).

Conclusion:
U-8-OHdG and SUV max may be useful markers in determining the therapeutic efficacy and clinical outcome in patients with CS.
Abstract 4137935: Adipogenesis in Bone Marrow Niche under Cardiac Stress Worsens Cardiac Function
Authors: GOTO KOHSAKU , Nakayama Yukiteru , Manabe Ichiro , Komuro Issei , Takeda Norihiko , Fujiu Katsuhito
Published: November 2024

Background:
We have recently reported that repetitive cardiac decompensation with multimorbidity often experienced by patients with heart failure (HF) is attributed to epigenetic modifications of hematopoietic stem cells (HSCs) in the bone marrow (BM). HF reprogrammed HSCs differentiation and altered tissue macrophage homeostasis. These findings demonstrate that the BM can carry an innate immune memory of cardiac stress that may exacerbate HF and predispose other organs to pathology.

Aims:
Because the stemness of HSCs is mainly regulated by mesenchymal stromal cells (MSCs) in the BM niche, we investigated phenotypic alterations of MSCs under cardiac stress.

Methods&Results:
Transcriptome analysis of MSCs showed preferential differentiation toward adipocytes in murine pressure overload models.
In vitro
assays and histological BM sections also support this finding. Furthermore, single-cell RNA sequencing of MSCs demonstrated that the percentage of adipocyte-primed MSCs increased in proportion to the severity of cardiac dysfunction, and also correlated with the frequency of myeloid-lineage progenitor cells. To investigate the influence of adipo-lineage MSCs on HSCs, we conducted BM transplantation supplemented with MSCs from control or HF mice. Recipient mice transplanted with HF-MSCs showed significant increases in myeloid-biased multipotent progenitors in BM and myeloid cells in peripheral blood. Additionally, the number of proinflammatory cardiac macrophages was significantly increased in the HF-MSCs group, promoting cardiac fibrosis and dysfunction.

Conclusions:
Our results demonstrated that the BM niche could perceive cardiac stress in the form of adipocytic skewing of MSCs in the setting of HF, which changed the differentiation behavior in HSCs and ultimately led to further deterioration of cardiac function through the impaired differentiation of circulating monocytes into cardiac macrophages. Therefore, suppressing the adipocytic differentiation of MSCs could have a novel therapeutic potential to avoid repeated HF events.
Abstract 4137939: Mosaic loss of Y chromosome is associated with increased all-cause mortality in patients with ST-segment elevation myocardial infarction
Authors: Li Nan , Yan Hongbing
Published: November 2024

Introduction:
Mosaic loss of Y chromosome (LOY), a common subtype of somatic mosaicism, is characterized as loss of the entire Y chromosome in a mosaic manner and increases with age. Accumulating evidence has manifested the positive link between LOY and shorter life expectations in elderly men as well as common age-associated diseases, such as cancer and cardiovascular diseases. Experimental studies also demonstrated that hematopoietic LOY in mice induced cardiac fibrosis and led to increased mortality. However, little is known about LOY and prognosis of ST-segment elevation myocardial infarction (STEMI).

Hypothesis:
We hypothesized that LOY may be associated with lower survival rate of patients with STEMI.

Aims:
Investigating the impact of LOY in peripheral blood cells on prognosis of patients with STEMI.

Methods:
This study prospectively enrolled 928 males and 272 females undergoing primary percutaneous coronary intervention for STEMI. LOY was measured in 928 males using droplet digital polymerase chain reaction technique.

Results:
During a median follow-up of 3.99 years, 93 males (10.0%) and 45 females (16.5%) died. After adjusting for traditional cardiovascular risk factors, the risk of all-cause mortality in males with LOY ≥ 18% (the 90th percentile of LOY) increased to 2.45 (95% confidence intervals [CI]: 1.16–5.15,
P
= 0.018), 2.11 (95% CI: 1.11–4.01,
P
= 0.024), and 1.88 (95% CI: 1.02–3.45,
P
= 0.043) times during 1-, 2-, and 3-year follow-up, respectively, compared to males with LOY < 18%. Among males without prior MI, those with LOY ≥ 18% had an increased risk of all-cause mortality compared to those with LOY < 18% (adjusted hazard ratio 1.93, 95% CI: 1.01–3.67;
P
= 0.045); this was not observed for males with prior MI. Female patients had a 1.71-fold (95%CI: 1.04–2.81;
P
= 0.035) increased risk of all-cause mortality than males with LOY < 18%, whereas the risk was similar to males with LOY ≥ 18%.

Conclusion:
LOY was associated with an increased risk of all-cause mortality in male STEMI patients, particularly in those without prior MI. Detecting LOY in STEMI patients could help further refine sex differences in prognosis and assist in identifying male patients with better prognoses.
Abstract 4137945: A Tuscany regional screening program for juvenile sudden cardiac death in high schools: the JUST project
Authors: Giannoni Alberto , Bonanni Francesca , Gentile Francesco , Moschetti Francesca , Durante Angela , Pennucci Francesca , Mariani Pier Romano , Di Paolo Marco , Passino Claudio , Nuti Sabina , Emdin Michele
Published: November 2024

Background:
Juvenile sudden cardiac death (SCD) has high impact on the family and society of the victim. While SCD screening programmes are effective in athletes, most (70-80%) young non-athletes individuals are not routinely screened.

Research question:
We hypothesized that a low-cost screening program may early identify subjects at risk of juvenile SCD, even in non-athletes.

Goals:
To evaluate the prevalence of SCD-related abnormal findings and, ultimately, to test the effectiveness of a screening programme in high schools.

Methods:
Between April 2023 and June 2024, high school individuals were enrolled in a screening programme in Tuscany (Pisa, Lucca and Livorno), based on a questionnaire investigating family history of juvenile SCD or diseases predisposing to SCD and symptoms (syncope, palpitations, chest pain), and digitally recorded electrocardiograms (ECGs). In case of abnormal findings, second-line investigations locally (echocardiography, Holter ECG monitoring and/or exercise testing) or third-line investigations at Fondazione Monasterio, Pisa, Italy (cardiac MRI, genetics or electrophysiological testing) were planned. Only preliminary results of the first-line screening are hereby reported.

Results:
We have currently enrolled 872 individuals (age 17.1±1.8 years, 481 [55%] males, 288 [33%] smokers, 102 [11.7%] recreational drugs users, and 645 [74%] non-competitive athletes). At questionnaires, 56 individuals (6.4%) had a family history of SCD, 32 (3.7%) a first-degree relative with cardiomyopathy, and 13 (1.5%) with channelopathy. As for symptoms, 21 participants (2.4%) reported chest pain or 26 (3%) syncope during exertion, while 90 (10.3%) paroxysmal palpitations. At ECG, we found 2 cases (0.2%) with a type-2 Brugada pattern, 1 female case (0.1%) with prolonged QTc interval (QTc 480 ms), 20 cases (2.3%) with V1-V3 T wave inversion (age > 16 years), 18 cases (2%) of left ventricular hypertrophy (non-athletes), and 4 cases (0.5%) with atypical ventricular ectopy. After the first-line screening, 61 (7%) and 10 (1.2%) individuals were referred to second and third-line investigations, which are currently ongoing.

Conclusions:
We hereby propose a screening model in high schools that includes specific health questionnaires and digitally recorded ECGs. From preliminary analyses, this approach seems sensitive enough to be tested as a model to favour the early diagnosis of diseased conditions associated with juvenile SCD in the general population.
Abstract 4137958: Transthoracic Echocardiography-based Differentiation of Hypertrophic Cardiomyopathy and Cardiac Amyloidosis
Authors: Akingbade Ololade , Chiou Tommy , Kotlo Srisha , Cotella Juan , Kanelidis Anthony , Beaser Andrew , Lang Roberto , Slivnick Jeremy
Published: November 2024

Introduction:
Hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA) have similar features on transthoracic echocardiography (TTE) which may make the two difficult to distinguish. However, it is recognized that CA presents at an older age compared to HCM. Our aim was to determine optimal TTE parameters for differentiating HCM from CA and the incremental value of age at the time of diagnosis for differentiation of these two disorders.

Methods:
Patients with CA (N=121) and HCM (N=227)—diagnosed in accordance with guidelines—who underwent TTE were retrospectively identified. TTE parameters—including left ventricular global longitudinal strain (LVGLS), apical sparing ratio (ASR), AMYLoidosis Index (AMYLI), relative wall thickness (RWT) and ejection fraction to strain ratio (EFSR)—were calculated using artificial intelligence software (US2.AI) and validated by a level III echocardiography reader. Univariate and multivariable logistic regressions were used to compare TTE parameters between CA and HCM patients. Receiver operating characteristic curve (ROC) analysis was conducted to determine performance of echo parameters in distinguishing CA and HCM.

Findings:
CA patients were older compared to HCM (
Figure 1A
). With respect to TTE parameters, CA was associated with lower magnitude of LVGLS and higher value of ASR, AMYLI, and EFSR. LVGLS (AUC 0.865, 95% CI 0.81-0.91) outperformed AMYLI, RWT, and EFSR for differentiation of HCM from CA (
Figure 1B
). For all five TTE parameters, age provided incremental predictive value for LVGLS (p<0.001), ASR (p<0.001), AMYLI (p=0.007), RWT (p<0.001), and EFSR (p<0.001),
Figure 2A-C
). LVGLS <-15.8% was 85% sensitive and 79% specific for CA.

Conclusion:
LVGLS is an optimal echo parameter for differentiating CA from HCM, outperforming all other traditional CA diagnostic markers. Age provides incremental diagnostic value in the differentiation of these two groups with TTE.
Abstract 4137986: Evaluation of an AI-Based Clinical Trial Screening Method Through a Randomized Controlled Implementation Study
Authors: Unlu Ozan , Varugheese Matthew , Subramaniam Samantha , McPartlin Marian , Shin Jiyeon , Wagholikar Kavishwar , Oates Michael , Wang Fei , Mailly Charlotte , Scirica Benjamin , Aronson Samuel , Blood Alexander
Published: November 2024

Background:
Clinical trial screening is labor-intensive, time-consuming, and error prone. We have developed RECTIFIER, an AI-based clinical trial screening tool, to enhance the efficiency and accuracy of patient recruitment. This study aims to evaluate RECTIFIER's effectiveness compared to manual screening in a randomized implementation study.

Methods:
This study was designed as an implementation study as part of an active heart failure trial named COPILOT-HF (NCT05734690). Potential eligible patients were identified via a structured electronic medical record query and randomized to be screened for clinical trial eligibility either by RECTIFIER or manually by clinical staff. The outcome measures included the number of patients contacted, and the number of patients reached for clinical trial enrollment. Data was collected over a period of 3 months.

Results:
A total of 3834 patients were included in the study, with 1919 patients randomized to the RECTIFIER group and 1915 patients to the manual screening group (Figure). Study staff could manually screen only 1367 patients at the end of the 3-month period. RECTIFIER identified more eligible patients compared to manual screening (833[43.4%] vs. 284[14.8%], p<0.001). The most common reason for exclusion was absence of symptomatic heart failure in both groups (287 in RECTIFIER 304 in manual screening). Screening via RECTIFIER also led to a higher contact rate, with 455 patients being contacted compared to 216 in the manual group (23.7% vs. 11.3%, p<0.001). The percentage of patients who could be reached for an enrollment call was also higher in the RECTIFIER group, with 330 patients responding versus 164 in the manual group (17.2% vs. 8.6%, p<0.001).

Conclusion:
Screening via RECTIFIER significantly outperformed manual screening in identifying eligible patients, contacting them, and eliciting responses. These results suggest that integrating AI into clinical trial recruitment processes can enhance efficiency and effectiveness, potentially leading to increased patient participation in clinical trials. Future studies with sufficient power should assess recruitment endpoints and explore scalability.
Abstract 4138019: eQTL Analysis of the PAH Biomarker CCN2 Identifies a Novel SNP that Associates with Survival
Authors: Byrd Carly , Benza Raymond , Webb Amy , Schramm Jennifer , Yang Jun , Griffiths Megan , Brandal Stephanie , Damico Rachel , Vaidya Dhananjay , Simpson Catherine , Kolb Todd , Pauciulo Michael , Nichols William , Ivy Dunbar , Hassoun Paul , Everett Allen , Austin Eric , Martin Lisa
Published: November 2024

Background:
We recently determined that cellular communication network factor 2 (CCN2) (also known as IGFBP8) levels associate with metrics of severity, and survival, in pulmonary arterial hypertension (PAH). While genetic variants that modify CCN2 gene expression have been described, the variants across the genome that associate with CCN2 protein levels in human circulation remain unknown.

Research Question:
We sought to identify genetic variants associated with circulating levels of CCN2 and to determine those variants’ relationship with clinical severity and survival.

Methods:
Serum CCN2 was measured by ELISA in subjects from a national sample repository, the PAH Biobank. A genome wide association study (GWAS) for CCN2 (natural log transformed) was performed in White idiopathic PAH (IPAH) PAH Biobank participants (n = 768) using Illumina OMNI5 genotypes in plink after standard quality control. Subsequent exploration of the SNP of interest was conducted in a separate dataset of 687 White PAH participants (n=360 IPAH, n=313 APAH) linked to genetic and clinical data, including REVEAL 2.0 risk score assessment (divided into low, medium, and high-risk levels) and outcomes (the STRIDE (Sitaxsentan To Relieve Impaired Exercise) trials cohort).

Results:
In the PAH Biobank, using GWAS, we found CCN2 levels were significantly associated with rs9493157 (p = 2.8 x10
-12
) (
Figure A
). rs9493157 is reported in the Genotype-Tissue Expression (GTEx) portal to be an eQTL for CCN2 expression in the left ventricle. In the STRIDE cohort, the hazard ratio (HR) for death was 1.33 (99% CI 1.03 to 1.72) for participants with one or more T alleles (p=0.027; (
Figure B
)). On multivariate analysis, the HR for death was 1.28 (95% CI 0.99 to 1.66; p=0.060). Among subjects with the highest REVEAL2.0 risk, those with a T allele had worse survival than those no T allele, with best survival among those with low a REVEAL2.0 score and no T allele.

Conclusions:
In White PAH subjects, rs9493157 associates with human levels of serum CCN2, a known biomarker for PAH. While additional studies are warranted, the T allele associates with worse survival and may enhance the prognostic value of the REVEAL2.0 risk score.
Abstract 4138035: Inclisiran in Routine Clinical Practice: Results from a Nationwide Study of >5,000 Patients
Authors: Lusk Jay , Li Fan , Mac Grory Brian
Published: November 2024

Introduction:
Inclisiran is a small interfering RNA drug which inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Inclisiran was recently approved for the treatment of hypercholesterolemia and durably lowers LDL levels by around 50% with injections once every six months based on the results of large, randomized controlled trials. However, no nationwide studies have evaluated the use or effectiveness of Inclisiran in routine clinical practice.

Goals/Aims:
To characterize the use and effectiveness of Inclisiran in routine clinical practice in a large nationwide cohort.

Methods/Approach:
We used the Truveta healthcare database, a large nationwide database of electronic health records, to study patients who were administered Inclisiran up to September 2023. Patient demographic characteristics and lipid levels before and after treatment were summarized. Means and 95% confidence intervals were estimated using t-tests.

Results/Data:
A total of 5,256 patients (median age 71, first quartile 65, third quartile 76) were prescribed Inclisiran, of whom 2,919 (55.5%) were Female. In terms of race, most of the patients identified as White (81.0%), and a smaller proportion as African American (7.3%), Asian (2.1%), or American Indian/Alaska Native (0.5%); 7.3% of patients identified as more than one race or did not provide race data. Mean LDL and HDL levels (mg/dL) before Inclisiran were 125 (95% CI 123-127) and 51 (95% CI 51-52) respectively and after Inclisiran were 88 (95% CI 85-90) and 50 (95% CI 49-51) respectively. The mean difference in LDL after treatment was -39 (95% CI -42 to -37) mg/Dl for a mean percent change of -22% (95% CI -25% to -19%). Effects of Inclisiran on LDL levels are shown in Figure 1. At the conference, we will compare effects of Inclisiran to those of Alirocumab and Evolocumab (two older monoclonal antibodies against PCSK9) using a propensity score overlap weighting design.

Conclusions:
In a large cohort of patients administered Inclisiran in routine clinical practice, Inclisiran use was associated with substantial decreases in LDL levels, but those decreases were nonetheless smaller than the effects seen in randomized controlled trials of the drug.
Countering Radicalization in the North Caucasus
Authors: Popov Maxim
Published: November 2024

By the mid-2010s, a significant decrease in the number of jihadists in the North Caucasus, in addition to internal ideological differences, was facilitated by fundamental factors: the lack of mass support in local Muslim communities, the anti-terrorism activities of the state, its informational and ideological support, and the policy of post-conflict integration. The number of supporters of the Caucasus Emirate decreased due to the split after the 2014 Olympics in Sochi; in 2015, the Caucasus Emirate officially ceased its activities, and after 2017, the flow of radical Islamists leaving Russia and joining ISIS stopped—violent extremism has begun to de-escalate in the region. To reduce ethnoreligious extremism and strengthen the integration of Muslims into Russian society, the federal government adopted a multi-level deradicalization strategy, including anti-terrorism operations and a large-scale policy of co-optation and support for moderate Russian Muslim leaders and their traditional communities.
Expanders of the Realm
Authors: Ferrario Marco
Published: November 2024

The Bīsutūn inscription carries an Old Persian coda dedicated to Darius’ expedition against the Sakā (DBp col. V § 74). The campaign’s geography and the identity of the defeated have been often discussed. Instead, the reasons behind both the campaign and its prominence in the inscription have been neglected. This article contextualizes the episode within its Ancient Near Eastern framework of imperial discourse on universal rulership and the limits thereof. Then, it provides an anthropological reading of the inscription through the prism of sacred (divine) kingship, seeking to account for the paramount importance of Central Asian (border)lands within the mental maps—even the cosmology—of the dawning Empire. This approach puts front stage the proactive role of local élites in negotiating their own position(ality) under, and sometimes—even simultaneously—against, Persian power.
Ossetic Boar
Authors: Dzitstsoity Yuriy , Falileyev Alexander
Published: November 2024

The article deals with the Ossetic word for ‘boar’ against the backgrounds of modern Ossetic porcine terminology. The Common Iranian name of the beast has survived in Ossetic anthroponymy only. Due to taboos many descriptive names for ‘boar’ are in use, such as ‘forest pig’, etc. The standard term (Digorian) tusk’a ‘boar’ was discussed by V. Abaev on a number of occasions, and the doyen of Ossetic studies considered it among Ossetic-European isoglosses in view of Eng. tusk, etc. The paper adds Iron evidence never mentioned before in its discussion and reassesses several questions regarding its alleged borrowing from Gothic. It is shown that the currently accepted approach to the pre-history of the Ossetic word as a linguistic loan at least requires adjustments, and that the term may well be of indigenous origin.
Armeno-Avarica
Authors: Asatrian Garnik S.
Published: November 2024

The paper is dedicated to the identification of a mysterious term in Avar denoting ‘sorceress’, as well as the examination of some related issues concerning Armenian/Iranian-South Caucasian language contacts and historical lexicology of Avar.
Russian Orientalistics (Vostokovedenie)
Authors: Zelenev Evgenij
Published: November 2024

This article examines the history, current state and prospects of Oriental and African Studies (OAS) in modern Russia. It explains why there are several educational models of OAS at bachelor’s and master’s degree in Russia and describes the current situation where 22 Russian universities offering OAS programmes produce graduates with mostly only two majors, i.e., historians and philologists. The article addresses the position of OAS among modern Russian scientific disciplines. Another aim is to trace the historical logic of the development of Oriental Studies and related African Studies in Russia, placing the discourse in the context of the Eastern Question, or the political fate of the Ottoman Empire. Finally, it identifies and justifies some current alternative trends in the development of OAS in Russian education and science.
Caucasian Albania
Authors: Outtier Bernard
Published: November 2024

This review article presents the newly released international handbook on Caucasian Albania, which provides a comprehensive academic examination of the history, ethnic formation, archaeology, culture, art, language and literature of this ancient kingdom. Featuring contributions from leading scholars, the handbook offers a diverse array of perspectives, encompassing ancient literary sources and contemporary events.
Jesus and Nationalism in Republican China
Authors: Cen Esther G.
Published: November 2024

Historians recognize the twentieth century as an age of nationalism in the Majority World. During times of foreign dominance and internal division, nationalism often united the masses and ignited social reformation. At the turn of the twentieth century, various social movements emerged in the land now known as the People’s Republic of China, motivating young people in cities such as Peking and Shanghai to seek salvation for their country. In response to China’s crisis, Chinese Christian educators and theologians offered their perspectives on saving China by developing Christlike character. This study explores two key players: T.C. Chao (赵紫宸) and Princeton S. Hsu (徐松石). By comparing their views on China’s problems, nationalism, and China’s salvation, I present two strategies for contextualizing Christianity in Republican China: preaching the Social Gospel and promoting Christianity’s indigenization. Despite their courage and ingenuity, their contextual theology ultimately tends to domesticate Jesus and adapt theology to fit their cultural and societal agendas.
Towards a Redefinition of Squatter Rights: Adverse Possession in Ghana and the United Kingdom
Authors: Faakye Solomon
Published: November 2024

A squatter may under certain circumstances extinguish the title of the registered proprietor and obtain good title. Many arguments have been made for and against these extensive rights. The broad consensus appears to be that in relation to registered land, there is less justification for it. The English Land Registration Act 2002 substantially modified the effect of adverse possession on registered land making adverse possession inapplicable to registered lands. Under Ghana’s new land law; Land Act, 2020 (Act 1036), except for public lands, a claim in adverse possession can defeat title to land whether registered or unregistered. This feature of Ghana’s land law appears unsatisfactory in light of the policy justifying land title registration. Using a comparative approach, this work evaluates adverse possession law in Ghana and England within the context of its objectives. The work established that the current regime on adverse possession does not effectively promote the objectives of land registration and requires reform.
Koima, a new genus of nemacheilid loach from the Western Ghats, India (Cypriniformes: Nemacheilidae)
Authors: ANOOP V.K. , DAHANUKAR NEELESH , RAGHAVAN RAJEEV
Published: November 2024

Koima, a new genus of nemacheilid loach, is described for Mesonoemacheilus remadevii Shaji 2002, and Nemacheilus monilis Hora 1921, both of which are endemic to the Western Ghats of southern peninsular India. Koima is distinguished from all other genera of family Nemacheilidae by its unique colour pattern comprising a yellowish-brown ground colour, single row of black spots on lateral line, all fins hyaline, and absence of a uniform banding pattern on dorsal side. Koima remadevii was initially identified as a species of Mesonoemacheilus Bănărescu & Nalbant 1982, from which it can be distinguished by the presence of a lower adipose crest, and an absence of a banding pattern on the dorsal side and on the caudal fin, while Koima monilis was initially identified as a species of Nemacheilus Bleeker 1863, from which it can be distinguished by the presence of a lower adipose crest, a narrow and deeply incised upper lip and having the fins hyaline. In the multi-gene phylogenetic analysis based on concatenated mitochondrial and nuclear gene sequences, Koima remadevii and K. monilis were recovered in a monophyletic group, sister to the endemic peninsular Indian nemacheilid, Schistura denisoni. Resolution of the identity of Koima remadevii and K. monilis contributes to our understanding of the phylogenetics of family Nemacheilidae, which is widely considered to be a polyphyletic group.
Description of Neuroandricus a new genus of gall wasp (Hym.: Cynipidae) and a new species of associated Sycophila (Hym.: Eurytomidae)
Authors: PUJADE-VILLAR JULI , SAVALL-ROIG GABRIEL , EQUIHUA-MARTÍNEZ ARMANDO , ESTRADA-VENEGAS EDITH G. , BARRERA-RUIZ URIEL M. , CIBRIÁN-TOVAR DAVID , VERA-ORTIZ ALEXIS , ROMERO-RANGEL SILVIA , CUESTA-PORTA VÍCTOR , CAZORLA-VILA JÚLIA , MELIKA GEORGE
Published: November 2024

A new genus of oak gall wasps, Neuroandricus Pujade-Villar & Melika, gen. nov., with one new species, N. pustulatus Pujade-Villar & Melika, sp. nov. is described from Mexico. The new Cynipini species is known from its asexual generation which induces galls on leaves of Quercus (section Quercus). Also, a new species of gall-associated parasitoid is described, Sycophila baldufi Savall-Roig & Pujade-Villar, sp. nov. (Eurytomidae), emerged from N. pustulatus galls. Diagnosis, distribution and biological data of the new species are given.
Exploring Police Reporting Among Victimized U.S. Nomads
Authors: Whaley Rachel Bridges , Abbott Jessica
Published: November 2024

Many people live and travel in recreational or retrofitted vehicles on a part-time and full-time basis with many living the Nomad lifestyle permanently. Research finds this population experiences high victimization prevalence. The current study finds Nomads have a high likelihood to report victimizations to the police and provides the first exploration into who among them report to the police. Hypotheses are derived from historically dominant theories and contemporary interest in the intersection of marginalizing and privileging social identities. Analyses of additive relationships and interactions are reported. Results raise questions about how the exigencies of life on the road encourage police reporting among those predicted to be less likely to report.
Clinicopathological Characteristics of Neutrophil-Rich Hepatocellular Carcinoma: An Uncommon Subtype of Primary Liver Cancer
Authors: Vij Mukul , Raju Lexmi Priya , Jothimani Dinesh , Subbiah Komalavalli , Simon Evangeline , Gowrishankar Gowripriya , Rajalingam Rajesh , Kaliamoorthy Ilankumaran , Rammohan Ashwin , Rela Mohamed
Published: November 2024

Introduction. Neutrophil-rich hepatocellular carcinoma (HCC) is an extremely uncommon subtype of HCC with an overall incidence of <1%. Neutrophil-rich HCC shows poor cellular differentiation and sarcomatoid transformation in most patients. There is prominent neutrophilic inflammatory cell infiltration in the tumor. These tumors are associated with poor prognosis, high rate of recurrence, and metastasis. Methods. Herein, we investigated 4 patients with neutrophil-rich HCC reported at our center. Clinical, radiological, and pathological findings were reviewed. Immunophenotypic characterization of the tumors were done. Granulocyte colony-stimulating factor (G-CSF), programmed cell death ligand 1 (PD-L1), and mismatch repair immunostains were performed in all 4 tumors. Results. We report 4 neutrophil-rich HCCs in 3 male patients and one female patient with an age range of 43 to 64 years. Three underwent living donor liver transplantation and one underwent right hepatectomy. Tumor measured 0.5 cm to 12 cm in maximum dimension. Histologically, tumors demonstrated moderate to marked cellular pleomorphism. Spindle cell transformation was noted in 3 tumors. Three tumors showed vascular invasion, and one tumor showed bile duct invasion. Immunopositivity for Hep Par-1, arginase-1, and glypican-3 was present in all tumors. Tumors also expressed stemness markers including KRT19 and EpCAM. Cytoplasmic positivity for G-CSF and immunoexpression of PD-L1 was demonstrated. We also report proficient mismatch repair by immunohistochemistry in all tumors. Conclusion. Neutrophil-rich HCC is an aggressive primary liver cancer which demonstrates stemness-related features. Programmed cell death ligand 1 expression in tumor cells suggests distinct immunogenic features and potential role of anti-PD-L1 therapies in inoperable disease.
Investigating visual perspective taking and belief reasoning in autistic adults: A pre-registered online study
Authors: Lara Green Rachel , Joanne Carrington Sarah , Shaw Daniel Joel , Kessler Klaus
Published: November 2024

As many autistic individuals report mentalizing difficulties into adulthood, the current pre-registered study investigated potential differences in belief reasoning and/or visual perspective taking between autistic and non-autistic adults. The Seeing-Believing task was administered to 121 gender-balanced participants online (57 with a self- reported diagnosis of an autism spectrum condition and 64 without), as well as Raven’s Progressive Matrices (on which the groups did not significantly differ) and the Autism Spectrum Quotient. Non-autistic adults replicated previous findings with this task, revealing slower responses to belief-reasoning than to perspective-taking trials. Autistic adults did not show significantly slower or more error-prone performance during perspective taking and/or belief reasoning. In fact, the autistic group committed significantly fewer mistakes, including fewer altercentric intrusions. The main group difference in response times was a steeper increase with increasing angular disparity between self and other in the autistic group. We discuss our findings in terms of differences in self-other control, but emphasise that our findings cannot be explained in terms of simplistic deficit-based notions of autism and suggest that autistic adults might favour slightly different strategies when judging another’s perspective or belief.

Lay abstract

Many autistic individuals report difficulties in social situations, where they are required to think about what goes on in others’ minds. These states of the mind can include how others perceive the world around them, their beliefs, or their desires. While research has shown that autistic children could be delayed in developing their full capacity in this regard, less is known about how adults process others’ experiences and beliefs. Here we used a novel task and asked adults to participate online. Participants self-reported whether they had been diagnosed with autism or not and we split them into two groups depending on their response. We also asked participants to fill in a self-report questionnaire about social preferences and habits and we also asked them to conduct a test of their nonverbal reasoning ability. Importantly, the autistic and the non-autistic groups did not differ in their nonverbal reasoning abilities, and on our task, we observed that the autistic group committed fewer mistakes than the non-autistic group. Autistic participants were particularly fast and made fewer mistakes on those responses that overlapped with their own view and belief of reality. In conclusion, our findings do not support a simple view of autism in terms of deficits in either social or more general thinking abilities. Instead, autistic adults might favour slightly different ways of thinking about other’s experiences and beliefs that is more firmly linked to their own experience and knowledge.
Fracture mode classification of UHPC based on deep learning and wavelet time–frequency spectrum derived from acoustic emission waveform
Authors: Jiao Yubo , Yang Hua , Fang Menghan , Xu Lijun
Published: November 2024

Fracture mode categorization is essential in identifying the failure stage, evaluating the damage characteristics, and providing references for structural maintenance. Acoustic emission (AE), as a passive nondestructive technique, presents great potential in damage characterization of cementitious materials and structures. In this study, a convolutional neural network (CNN) and gated recurrent unit (GRU) integrated model for tensile, shear, and mixed cracking mode classification of ultra-high-performance concrete (UHPC) was proposed and verified based on AE waveform features. First, four-point bending and direct shear tests for UHPC specimens were carried out, respectively, to generate AE waveform signals corresponding to different cracking modes (tensile, shear, and mixed ones). Subsequently, the collected one-dimensional AE signals were converted into two-dimensional time–frequency spectrum by continuous wavelet transform. And an AE dataset was constructed after manual labeling based on the corresponding relationships between cracking modes and wavelet time–frequency spectra. Then, an automatic CNN-GRU automatic classification model was established using wavelet time–frequency spectrum images as input variables, where the CNN extracts spatial image features, and the GRU screens time dependencies and realizes final classification. The proposed CNN-GRU model achieves an accuracy of 96.17% for cracking mode classification of UHPC, which is superior both in computational accuracy and efficiency to lightweight CNN and AlexNet. Classification outcomes for UHPC specimen under four-point bending and direct shear tests revealed the proportion of tensile cracks progressively decreased with the increase of damage, while shear cracks exhibited the opposite trend. The percentage of mixed mode cracks maintained relatively stable throughout the failure stages. The model proposed in this study presents favorable performance to reveal the underlying damage evolution mechanism during UHPC fracture, which can also provide references for the cracking mode classification of other cementitious materials and structures.