bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract I003: Inhibitors of DHX9 RNA helicase as synthetic lethal cancer therapeutics
Authors: Silver Serena J 
Published: November 2024

Abstract
Over 100 modifications to RNA are known to occur in human cells, where they play critical roles in many aspects of normal cellular physiology, such as cell fate decisions and terminal differentiation, through effects on RNA biology such as protein and nucleic acid interactions. Our survey of human RNA-modifying enzymes suggests many are cancer essential enzymes with striking synthetic lethal profiles, including the DHX9 helicase. DHX9 is a multifunctional DExH-box RNA helicase which can unwind regions of double-stranded DNA and RNA helices but has a greater propensity for secondary structures such as DNA/RNA hybrids (R-loops) and DNA/RNA G-quadruplexes. DHX9 interacts with and regulates many proteins, including key members of DNA damage repair pathways. We have found that DHX9 knockdown is synthetic lethal in microsatellite high (MSI-H) or defective mismatch repair (dMMR) tumor models. A suite of assays was developed to identify and optimize potent and selective inhibitors of the DHX9 helicase, which recapitulate our findings with genetic tools. Profiling of DHX9 inhibitors across a broad panel of cancer cell lines reveals that tumor cells with mutations in the DNA damage repair genes BRCA1 and/or BRCA2 are also responsive to DHX9 inhibitor treatment in vitro and in vivo. DHX9 inhibition leads to increased RNA/DNA secondary structures such as R-loops and G-quadruplexes, resulting in subsequent DNA damage and increased replication stress, leading to cell cycle arrest and apoptosis. These results suggest that DHX9 inhibitors are a novel treatment modality for patients with defective DNA damage repair pathways such as dMMR and/or BRCA mutations.
Citation Format: Serena J Silver. Inhibitors of DHX9 RNA helicase as synthetic lethal cancer therapeutics [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr I003.
Abstract PR006: Target validation and drug discovery efforts on exoribonuclease XRN1
Authors: Lynes Maureen M. , Lockbaum Gordon J. , Sparling Brian A. , Shen Sophie A. , Nayak Sunaina P. , Knockenhauer Kevin , Grigoriu Simina , Buker Shane M. , Duncan Kenneth W. , Copeland Robert A. , Blakemore Stephen J. , Silver Serena J. , Boriack-Sjodin P. Ann 
Published: November 2024

Abstract
5′→3′ exoribonuclease 1 (XRN1) degrades single stranded mRNA and plays a key role in endogenous cellular mRNA turnover. XRN1 also degrades double-stranded RNA (dsRNA), thereby playing a role in innate immunity by preventing accumulation of dsRNA and pPKR induction in virus-infected cells. XRN1 was validated as a target with selective vulnerability in lung cancer cells with intrinsically elevated Type I interferon signaling, a cellular state that phenocopies viral infection. XRN1 knockout using CRISPR resulted in robust and selective antiproliferative effects in colony formation and proliferation assays. Analysis of Caspase 3/7 confirmed antiproliferation activity was due to apoptosis in sensitive cell lines. With genetic target validation activities completed, efforts to enable identification and characterization of XRN1 inhibitors were undertaken. Biochemical and biophysical assays and crystallography with human XRN1 were enabled. This assay suite allowed full characterization of a non-selective, nucleotide-based tool compound (pAp) as well as identification and validation of Compound 1, a selective, allosteric, RNA-competitive inhibitor of XRN1.
Citation Format: Maureen M. Lynes, Gordon J. Lockbaum, Brian A. Sparling, Sophie A. Shen, Sunaina P. Nayak, Kevin Knockenhauer, Simina Grigoriu, Shane M. Buker, Kenneth W. Duncan, Robert A. Copeland, Stephen J. Blakemore, Serena J. Silver, P. Ann Boriack-Sjodin. Target validation and drug discovery efforts on exoribonuclease XRN1 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR006.
Abstract PR008: Targeting Galectin-1 to enhance immuno-radiotherapy
Authors: Jiang Yuyan , Cao Hongbin , Deng Huaping , Guan Li , Langthasa Jimpi , Le Quynh-Thu 
Published: November 2024

Abstract
Galectin-1 is overexpressed in a wide range of malignant cancers and is strongly associated with immune suppression as well as cancer aggressiveness. However, effective therapeutics targeting Galectin-1 remain elusive in clinical practice. Herein, we report an activatable nano-system, termed Pr5S, to downregulate Galectin-1 through in vivo gene silencing. Pr5S features a bio-responsive lattice that can protect siRNA during circulation and efficiently break down for gene interference upon exposure to the elevated reductive pressure in the tumor microenvironment. When used independently, Pr5S significantly reduces Galectin-1 expression and mitigates T cell apoptosis, achieving tumor inhibition comparable to anti-Galectin-1 antibodies and superior to small molecule inhibitors. In combination with radiation, Pr5S enhances the anti-tumor immunity and results in significantly improved therapeutic outcome than clinical treatments such as chemoradiation or immune checkpoint blockade + radiation. Moreover, Pr5S strengthens the abscopal effect of radiation, efficiently abrogating unirradiated tumors. In summary, this work highlights a safe and efficient design of a gene silencing nanovector to improve personalized immuno-radiotherapy.
Citation Format: Yuyan Jiang, Hongbin Cao, Huaping Deng, Li Guan, Jimpi Langthasa, Quynh-Thu Le. Targeting Galectin-1 to enhance immuno-radiotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR008.
Abstract PR015: Decoding RNA metabolism by RNA-linked CRISPR screening in human cells
Authors: Nugent Patrick J , Park Heungwon , Subramaniam Arvind Rasi 
Published: November 2024

Abstract
RNAs undergo a complex choreography of metabolic processes in human cells that are regulated by thousands of RNA-associated proteins. While the effects of individual RNA-associated proteins on RNA metabolism have been extensively characterized, the full complement of regulators for most RNA metabolic events remain unknown. Here we present a massively parallel RNA-linked CRISPR (ReLiC) screening approach to measure the responses of diverse RNA metabolic events to knockout of 2,092 human genes encoding all known RNA-associated proteins. ReLiC screens highlight modular interactions between gene networks regulating splicing, translation, and decay of mRNAs. When combined with biochemical fractionation of polysomes, ReLiC reveals striking pathway-specific coupling between growth fitness and mRNA translation. Perturbing different components of the translation and proteostasis machineries have distinct effects on ribosome occupancy, while perturbing mRNA transcription leaves ribosome occupancy largely intact. Isoform-selective ReLiC screens capture differential regulation of intron retention and exon skipping by SF3b complex subunits. Chemogenomic screens using ReLiC decipher translational regulators upstream of mRNA decay and uncover a role for the ribosome collision sensor GCN1 during treatment with the anti-leukemic drug homoharringtonine. Our work demonstrates ReLiC as a versatile platform for discovering and dissecting regulatory principles of human RNA metabolism.
Citation Format: Patrick J Nugent, Heungwon Park, Arvind Rasi Subramaniam. Decoding RNA metabolism by RNA-linked CRISPR screening in human cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR015.
Abstract 4138715: Disparities in Aortic Dissection and Aortic Aneurysm-Related Mortality in The United States From 1999-2020
Authors: Shahzad Maryam , Irfan Mariyah Zainab , Danisha FNU , Jaiswal Vikash , Mattumpuram Jishanth 
Published: November 2024

Background:
Aortic dissection (AD) and aneurysm (AA) have a low incidence but are severe health risks associated with high mortality rates, and based on location, can have a mortality rate of over 80%. We aim to highlight disparities in mortality based on gender, race, age and demographic background.

Methods:
This retrospective study analyzed death certificate data for AD and AA (ICD-10 code I71) from 1999 to 2020 using the CDC WONDER database. Age-adjusted mortality rates (AAMR) per 100,000 were assessed for adults aged 25 and older by gender, race, year, state, and place of death, while crude mortality rates (CMR) per 100,000 were used for age groups. Joinpoint regression calculated the annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals.

Results:
From 1999 to 2020, AD and AA resulted in 400,748 deaths in the US. During this period, AAMR for men (12.19) was approximately double that for women (5.77). Overall, the AAMR decreased from 12.40 to 6.71 (AAPC: -2.93; 95% CI: -3.06 to -2.79; p-value<0.000001). NH whites had the highest AAMR at 8.93, while Hispanic and Latino populations had the lowest at 4.20. Approximately 52.3% of the deaths occurred in inpatient medical facilities, whereas 18.4% occurred at home. Vermont, West Virginia, and Wyoming had the highest AAMRs, at 11.60, 11.47, and 11.30, respectively.

Among racial groups, both males and females experienced a decrease in AAMR except for NH black men. For this group, there was an increase in AAMR from 9.42 in 2012 to 10.43 in 2020 (APC:1.03; 95% CI: 0.15 to 2.22; p-value:0.028).
The CMR for young adults rose significantly from 0.62 in 2014 to 0.73 in 2020 (APC:2.55; 95% CI 1.11 to 6.74; p-value:0.02), and for middle-aged adults from 3.09 in 2010 to 3.61 in 2020 (APC: 1.57; 95% CI 1.04 to 2.25; p-value<0.000001). Conversely, a steep decline in CMR was observed for older adults from 27.93 in 2014 to 25.4 in 2020 (APC:-1.34; 95% CI -1.9 to -0.69; p-value:0.0004).

Conclusion:
Although AD and AA mortality rates have declined over time, significant disparities persist for NH Black men and young/middle-aged adults. This highlights the need for early screening programs and equitable healthcare provision for all populations.
Abstract 4139035: Health Literacy in Men and in Women With Type 2 Diabetes Undergoing Coronary Angiography
Authors: Neyer Magdalena , Vogel Johannes , Elsner Pascal , Plattner Thomas , Vonbank Alexander , Mader Arthur , Larcher Barbara , Leiherer Andreas , Muendlein Axel , Frick Matthias , Drexel Heinz , Saely Christoph H 
Published: November 2024

Health literacy reflects the ability to make appropriate health decisions and affects health outcomes. It therefore is an important parameter in patient care and for health care providers. Health literacy in patients undergoing coronary angiography, the standard procedure for the definite evaluation of coronary artery disease (CAD) is unclear and is addressed in the present study.
We recruited 515 consecutive patients (383 men and 132 women) undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in central Europe. Health literacy was measured using the validated HLS-EU-Q16 questionnaire.
A response rate of 80.4% was achieved. Overall, 177 patients (i.e. 34.3% of the cohort) had type 2 diabetes (T2DM); the prevalence of T2DM was 36.8% in men and in 27.3% in women (p=0.047). Comparing T2DM patients to those who did not have diabetes, overall median health literacy scores (HLS) were 13 [IQR=11-15] vs. 13 [IQR=10-15] among men (p=0.424) and 12 [IQR=10-15] vs. 13 [IQR=10.25-15] among women (p=0.517). Prevalence rates of adequate (HLS 13-16), problematic (HLS 9-12) and inadequate (HLS 0-8) health literacy did not differ significantly between patients with T2DM vs. subjects without T2DM (53.0% vs. 55.4%, 34.8% vs. 29.9% and 12.2% vs. 14.7% among men and 37.5% vs. 55.6%, 45.8% vs. 31.9% and 16.7% vs. 12.5% among women, respectively.
We conclude that among patients undergoing coronary angiography for the evaluation of established or suspected stable CAD, health literacy regardless of sex is suboptimal both in patients with T2DM and in non-diabetic subjects.
Abstract 4139380: A Report of

2000

Consecutive Patients Undergoing Imaging with Pacemakers and ICDs in the MRI Environment; the Additive Value of a Large, Prospective ~20-Year Observational Study
Authors: Biederman Robert , Shah Moneal , Boltralik Mark , Williams Ronald , Lombardi Richard , Mangini Francesco , Doyle Mark 
Published: November 2024

Background:
Imaging of conventional PM’s and ICDs are infrequently performed via MRI. While many studies, including the

MagnaSafe
Trial

have unequivocally supported MRI safety in patients with such devices, the
added
clinical value has rarely been considered. Accordingly, we performed an observational, IRB-approved, prospective study to determine the 'Additive Value'
beyond
safety for patients with conventional PM/ICD's undergoing clinical MRI.

We
hypothesize
that MRI in PM/ICD patients is critical to an existing diagnosis and often markedly alters diagnosis and subsequent downstream patient management.

Methods:
An MRI Device exam (GE 1.5T,WI) pioneered by cardiologists (>90% over 10 yrs; 100% over 20 years) was performed. Subsequently, a series of prospective defining questions using Boolean Logic Construct were answered within 1 week of MRI by both MRI technologist and MRI physicians.

Questions
:

1) Did the primary diagnosis change?
2) Did the MRI provide additional information to existing diagnosis?
3) Was the pre-MRI (tentative) diagnosis confirmed?
4) Did subsequent patient management change?
If 'Yes' was answered to any of the above questions, it was considered that MRI was of value to pt diagnosis and/or impending therapy.

Results:
Average MRI: 25±14min for 2,008 consecutive patients of which 1,526 (76%) were neuro/neurosurgery, 141 (7%) were musculoskeletal and 341(17%) were CV cases. Upon review: of the N
euro/neurosurgery
MRIs, 1,376 (89%) provided additional information.

The diagnosis changed in 1018 (74%), while medical therapy changed in 977 (71%). In only 124 (9%) did MRI simply confirm original diagnosis. For
Cardiac
patients, MRI changed the original diagnosis in 235 (69%). MRI did not contribute in 42 (12%) as it was uninterpretable (ICD artifact), while in 64 pts, the diagnosis did not change. Finally, in 146
Orthopedic
pts, MRI provided additional information in 143 (98%) and in 130 (89%), changed pt care, and in 4 pts (3%), simply confirmed the diagnosis. Importantly, with careful attention to device reprogramming and scanner sequences, no safety or device issues were encountered in any patient all with tracking for >1 year.

Conclusion:
Via a dedicated program of MRI in PM/ICD patients adds substantial clinical value to diagnosis and subsequent management justifying ant inherent risk(s). Herein, we propose that yet another impediment to the advancement of CMR-PM/ICD strategies can become routine and often life-changing.
Abstract 4139654: Effects of Exercising Sports on Cardiovascular Health among Youth Athletes: Basketball, Baseball, Football and Soccer
Authors: Qiu Grace , Kim Seong Kyu , Corsi Douglas , Masood Imran , Hajduczok Alexander , Osler Brian , Johnson Drew , Langstaff Renee , Shipon David 
Published: November 2024

Introduction:
The impact of exercise on the adult heart has been well studied and associated with better cardiovascular health. However, the exercise-induced physiological adaptations of the youth athlete's heart are not well understood.

Research Questions/Hypothesis:
Cardiac screening data will differ significantly based on which sport a youth athlete plays.

Goals/Aims:
To assess the impacts of different sports on youth athletes' cardiovascular health.

Methods:
The HeartBytes National Youth Database produced by Simon’s Heart was used for this study. The database contains demographics, exercise-related symptoms, ECG data obtained during Simon’s Heart PPEs, and data on various types of sports that athletes participate in. To investigate the effects of each specific sport, we excluded those playing multiple sports from the data set, and employed a propensity score match method to control the confounding influences of race, sex, and exercise intensity. This study used an odds ratio statistic and p-value of 5% criterion to evaluate associations between specific sports and cardiovascular risk factors.

Results:
Of the 7425 athletes in the HeartBytes database, the majority were male (60.6%) and White (83.1%). The mean BMI was 21.4 with SD 4.6. The median age was 15.0 years old with an interquartile range 13.5-16.5. There were 279, 120, 179, 552 athletes playing basketball, baseball, football, and soccer only respectively.

Athletes playing basketball had higher odds of exertional symptoms of feeling easily tired (p=0.017), ECG abnormalities (p=0.032), and T wave inversion (p=0.017), but lower odds of ADHD (p=0.03).
Athletes playing baseball had higher odds of asthma (p=0.02) and T wave inversion (p=0.046) if exercising less than 5 hours/week, and higher odds of murmurs (p=0.023) and exertional syncope (p=0.04) if exercising more than 10 hours/week.
Athletes playing football had higher odds of obesity (p<0.0001), hypercholesterolemia (p=0.048), and diabetes (p=0.037) if exercising more than 10 hours/week.
Athletes playing soccer had higher odds of voltage ECG left and right ventricle hypertrophy respectively (p<0.01), but lower odds of obesity (p<0.001).

Conclusion:
All sports showed significant impact on youth athletes' health. Further studies are required to understand the physiological adaptations of youth athlete heart.
Abstract 4139677: A rare case of ventriculobronchial fistula caused by an epicardial defibrillator patch
Authors: Alampoondi Venkataramanan Sai Vikram , Windle John 
Published: November 2024

Background:
Epicardial patch defibrillators (EPDs) were commonly implanted in the 1990s for secondary prevention of sudden cardiac death. Despite being largely obsolete, some EPDs remain in patients and can cause late complications. This case highlights such a scenario.

Case:
A 75-year-old female with a history of cardiac arrest 30 years ago presented with shortness of breath and left leg swelling. She had idiopathic ventricular fibrillation in 1992, treated with an EPD (Picture 1A), later replaced by a transvenous ICD.

She was diagnosed with left femoral deep venous thrombosis and bilateral pulmonary embolism and started on therapeutic anticoagulation. She experienced massive hemoptysis, leading to respiratory and cardiac arrest, but was resuscitated. A CT angiogram showed no active bleeding but noted the EPD was close to the lower lobe of the left lung. Upper gastrointestinal endoscopy showed no active bleeding. Bronchoscopy revealed clots in the left lower lobe. Despite empiric bronchial artery embolization, hemoptysis persisted. A repeat bronchoscopy showed reaccumulation of clots. A repeat CT angiogram indicated contrast extension into the ventricular myocardium near the EPD but no lung spillage suggestive of pseudoaneurysm (Picture 1B).
She was transferred to our institution for further evaluation. A coronary angiogram revealed normal arteries, while a left ventriculogram revealed contrast extravasation through the lateral wall (Picture 1C). An urgent surgery revealed two EPDs: anterior and lateral. The lateral EPD had eroded into the ventricle, creating a ventriculo bronchial fistula (Picture 1D). The lateral EPD was removed (Picture 1E); the anterior EPD was left in place (Picture 1F). The ventricular defect was debrided and repaired. Postoperative recovery was successful, with no further hemoptysis, and the patient was discharged to a rehabilitation facility.

Discussion:
EPDs are no longer used due to high failure rates and complications like scar formation and constrictive pericarditis. However, patients with EPDs from the 1990s may present with delayed complications. Accurate diagnosis using multimodality imaging and early management is crucial to reduce morbidity and mortality.
Abstract 4139704: Coronary Artery Air Embolism During Left Heart Catheterization: A Rare Yet Potentially Fatal Complication
Authors: Siddiqui Arsalan , Yee Brianna , DiCaro Michael , Lee Ki , Lei KaChon , Ahsan Chowdhury 
Published: November 2024

Coronary artery air embolism is a rare yet potentially fatal complication of interventional cardiac procedures, presenting from asymptomatic to cardiac arrest. There are no established guidelines for its management, and the focus is on primary prevention. Here, we present a case of iatrogenic coronary artery air embolism during an elective left heart catheterization (LHC).
A 61-year-old male with mitral valve prolapse underwent preoperative LHC which showed a stenotic left anterior descending artery and normal right coronary artery (RCA). On the following left ventriculogram, significant inferior wall hypokinesis was observed, and the patient developed acute chest pain, ST elevations, and complete heart block (Figure 1a). Suspecting new RCA pathology, reevaluation revealed multiple air emboli and Thrombolysis In Myocardial Infarction (TIMI) grade 1 flow (Figure 1b). The RCA was flushed multiple times with heparinized saline, resolving the air emboli and restoring TIMI grade 3 flow (Figure 1c). At the procedure's end, the patient was pain-free and in sinus rhythm. A repeat transthoracic echocardiogram showed normal ventricular function without regional wall motion abnormalities. The patient was discharged without further complications.
Coronary air embolism can occur iatrogenically and is inversely correlated with operator experience. Prevention through proper technique is crucial: catheters should be adequately aspirated, all connections tightened, and the catheter should be tested distal to the aortic cusp to prevent emboli occurrence. Although there are no established guidelines, management includes administering 100% oxygen, intracoronary saline boluses, or breaking down emboli with a guidewire.
In our case, the sudden onset hypokinesis of the inferior wall with complete heart block in a confirmed normal RCA raised suspicion for new RCA pathology. Immediate heparinized saline allowed for air emboli dissociation as a more immediate intervention than 100% oxygen and did not involve intravascular manipulation which could result in dissection. Our case highlights the importance of early detection of rapidly changing pathology and stresses meticulous technique for testing equipment as a prevention method.