bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract Mo074: Overexpression of IPP2 Impairs Intracellular Calcium Handling, Leading to Arrhythmogenic Events
Authors: Eom Gwang Hyeon , Yoon Somy 
Published: October 2024

Cardiac arrhythmias, which are disruptions in the heart's electrical activities, critically affect the ventricular conduction system, impairing efficient blood circulation. These disturbances result in irregular heartbeats, contributing to patient mortality or causing harm to distant organs via embolic events. Given the severe implications, a profound understanding of the molecular mechanisms driving arrhythmia is crucial for devising specific treatments. This study unveils a pioneering link between the overexpression of IPP2 (Protein Phosphatase 1 Regulatory Inhibitor Subunit 2), driven by the Myh6 promoter (termed TgIPP2), and the onset of age-dependent cardiac arrhythmias. The electrical abnormalities observed in TgIPP2 overexpressing mice include a spectrum of dysfunctions such as axis deviations, elongated QRS and PR intervals, absence of P waves, AV dissociation, ventricular tachyarrhythmia, and heightened T waves. Investigating the pathophysiology behind these electrical anomalies, we subjected young adult mice to catecholamine challenges at low doses and conducted surface electrocardiogram (EKG) monitoring. TgIPP2 mice demonstrated a notable increase in arrhythmogenic episode frequency and duration following 0.2 mg/kg isoproterenol injection compared to their control counterparts. Through a protein phosphorylation analysis, we identified a key regulator of the ryanodine receptor, which modulates calcium release from the sarcoplasmic reticulum, correlating with the extended PR intervals and the delayed peaking of T waves. Therapeutic trials employing RyR blockers, specifically dantrolene, successfully normalized the erratic cardiac rhythms in aged TgIPP2 mice. However, beta blockers or L-type calcium channel blockers induced sudden cardiac death in this model. The study reveals that IPP2-induced aberrant phosphorylation disrupts calcium homeostasis, leading to arrhythmias.
In conclusion, our research marks a significant advancement in understanding arrhythmogenic mechanisms, demonstrating that IPP2 overexpression directly triggers arrhythmia, particularly affecting the atrioventricular (AV) node, atria, and ventricles. The discovery that aberrant phosphorylation, especially of the RyR regulator, plays a pivotal role in initiating cardiac arrhythmias opens new pathways for targeted anti-arrhythmic therapies.
Abstract Tu136: HIF-1α a novel therapeutic target to reduce Cardiac Ischemia Reperfusion Injury during AMI
Authors: Swain Lija , Reyelt Lara , Qiao Xiaoying , Bhave Shreyas , Everett Kay , Mahmoudi Elena , Kapur Navin 
Published: October 2024

Acute myocardial infarction (AMI) is a major cause of mortality worldwide. In preclinical models of AMI, using a trans-valvular pump (TVP) to reduce left ventricular (LV) workload for 30 minutes before reperfusion reduces infarct size by 50%. The mechanisms underlying the cardioprotective effect of LV unloading remain poorly understood. Hypoxia inducible factor 1-alpha (HIF-1α) is an oxygen-sensitive transcription factor that activates cardioprotective signaling pathways, improves cell survival and mitochondrial function during myocardial ischemia. We hypothesized that LV unloading limits myocardial injury by activating hypoxia inducible factor 1-a (HIF-1α).
To explore the effect of LV unloading on HIF-1α stabilization during ischemia, we performed left anterior descending artery (LAD) occlusion for a total of 120 minutes in adult swine in the presence and absence of LV unloading and further 180 minutes of reperfusion was performed following 120 minutes of LAD occlusion.
Trans-valvular unloading activation significantly decreased infarct size both during ischemia (IS/AAR: 4.78±4 % vs 1.5±3%) and post reperfusion when compared ischemia alone and IR alone groups (36.04±8.39 % vs 16.02±3.52 %, p<0.0001) respectively. Interestingly, HIF-1α stabilization is significantly reduced with LV unloading during ischemia and significantly increased post reperfusion in the infarct zone of the swine model of AMI. To test whether HIF1a is necessary for cardioprotection with LV unloading, adult swine were treated with intracoronary delivery of the HIF-1α inhibitor (2-methoxyestradiol; 2ME) before reperfusion. Compared to TVP activation for 30 minutes before reperfusion, addition of 2ME abolished the cardioprotective effect of TVP resulting in increased infarct size (16.03% vs 35.86% p<0.03) and decreased HIF-1a stabilization. Stabilizing HIF-1α post-reperfusion by using a well know HIF-1a stabilizing agent Roxadustat, immediately before reperfusion significantly decreased infarct size in both with and without TVP groups compared to IRI alone. Treatment with Roxadustat also preserved mitochondrial function and increased RISK signaling.
We report the novel finding that stabilizing HIF-1a activity before reperfusion plays a critical role in reducing Infarct size in preclinical model of AMI.
Abstract We012: Sheet like extracellular matrix secreting single cell microvesicles for reprogrammed endothelial cell therapy towards vascular regeneration
Authors: Morris Viola , Lee Sangho , He Simon , Huang Matthew , Chen Dandan , Kim Kyung Hee , Cho Seonggeon , Pencea Laura , Jain Divit , Yoon Young-sup 
Published: October 2024

To enhance cell survival and engraftment for cell therapy, cell encapsulated injectable biomaterials have been widely used. However, the challenges were hypoxia and nutrient shortage in the core, inflammatory cell infiltration and limited distribution of cells from injection sites. Encapsulation of single cells in sub-100-micron microgels with higher surface to volume ratios provides more efficient oxygen and mass exchange. However, typical production of single-cell-laden microgels by microfluidics devices results in cell damage and compromised biological properties.
We hypothesized that stimuli responsive amphiphilic copolymer bearing RGD peptides may self-assemble around single cells induced by cell adhesion moieties would result in single cell microvesicles (MV).
A stimuli responsive amphiphilic copolymer GPM (Gelatin Poly glycerol sebacate Methacrylate) was synthesized by grafting hydrophobic synthetic polymer PGS into hydrophilic natural polymer gelatin via methacrylation followed by aza-Michael addition reaction. Single cell microvesicles of endothelial cells (EC-MVs) were fabricated by self-assembly of GPM at room temperature. For in vivo studies, sub-50-micron EC-MVs made of reprogrammed endothelial cells (rECs) were clustered into 200 micron spheres (mGPM) using sodium alginate and injected into a hindlimb ischemia model to investigate cell survival and biological function.
The mGPM microspheres functioned as a barrier from immune cell infiltration and also enhanced cellular distribution. The encapsulated rECs were released over 2-4 wks in vivo and were shown robust engraftment, migration, and survival in limb tissues, promoting blood flow recovery and sustained vascular regeneration over 6 months. Interestingly, in in vitro culture, rEC-MVs secreted sheet like extra cellular matrix (ECM) which appeared to make an important role for vessel formation (neovascularization) in vivo (Figure 1).
The current study clearly demonstrated the favorable biological applicability of GPM single cell MVs toward vascular regeneration by reprogrammed ECs.
Abstract We045: Development of SA Node Organoids: A Multicellular Approach to Biological Pacemaking
Authors: Won Jihee , Son Young Hoon , Cho Hee Cheol , Park Sung 
Published: October 2024

The rising prevalence of sinoatrial (SA) node dysfunction, attributed to the aging population, is emerging as a critical health issue. The SA node, a natural organoid within the heart, comprises the pacemaker cells embedded within a connective tissue matrix, insulated electrically from the surrounding atrial muscle cells. This isolated architecture, along with a heterogeneous cellular composition, is crucial for the SA node's robust pacemaking and electrical conduction. Developing methods to reconstruct this crucial heterogeneous structure could offer a long-term solution for individuals with SA node dysfunction. However, the use of current biological pacemakers, which typically involve a single cell type, has often led to unstable heart rhythms during one-month in vivo integration, challenging their long-term clinical application as biological pacemakers.
To address existing SA node model limitations, we developed a SA node organoid that reproduces the human SA node's multicellular tissue structure. Initially, we developed a protocol for generating cardiac SA node organoids by employing a lentivirus to deliver dox-inducible genes for key pacemaker transcription factors, specifically TBX-18 or Shox-2. We mixed wild-type human-induced pluripotent stem cells (hiPSCs) with those modified to express TBX-18 or Shox-2. These cell mixtures were aggregated, embedded in a diluted Matrigel, and then exposed to a cardiac differentiation protocol, activating TBX-18 or Shox-2 at specific times (D1 or D7) via Dox administration. By D9, these organoids began to exhibit contraction, which lasted beyond 60 days, with notable upregulation of two transcription factors and pacemaker-specific genes following Dox treatment. Subsequently, we integrated the SA node organoid into 2D hiPSC-derived atrial muscle tissue constructs, maintaining geometric isolation within the cardiac tissue to enhance source-sink mismatch. This isolation allowed the SA node organoid to successfully trigger activity in adjacent dormant cardiomyocytes, preserving the rhythm for over 60 days.
These findings could redefine the role of tissue architecture and cell diversity in the SA node's pacemaking function, potentially leading to a high-fidelity, tissue-level biological pacemaker as a new treatment strategy for SA node dysfunctions.
Abstract We051: Chronic mavacamten treatment prevents development of contractile dysfunction in cMyBP-C null engineered heart tissue constructs, but not in constructs carrying the cMyBP-C W792R missense mutation
Authors: De Lange Willem , Gauchan Angeela , Farrell Emily , Ralphe J Carter 
Published: October 2024

Hypercontractility, caused by mutations that increase the number of myosin heads in the disordered relaxed (DRX) state, is a prevalent cause of hypertrophic cardiomyopathy (HCM). A subgroup of HCM mutations cause primary hypocontractility, by stabilizing super-relaxed crossbridges (SRX). Mavacamten (mava) directly targets hypercontractility by reducing the number of DRX heads and improves outcomes in ~70% patients with obstructive HCM.
We here assessed the efficacy of chronic mava treatment at preventing phenotype development in human iPSC engineered heart tissue (EHT) in a cMyBP-C null model (-/-), that increases the number of DRX heads, and EHT carrying the W792R (RR) HCM mutation. While the primary contractile defect caused by the W792R mutation is unknown, we postulated that it differed from the cMyBP-C -/- model, as RR mice die prior to weaning while -/- mice do not.
Twitch force (TF) measurements performed on day 7 on control (+/+), -/- and RR EHT show that -/- EHT were hypercontractile while RR EHT were hypocontractile (Fig. 1). Following measurement, EHT from each genotype were either treated with vehicle or 100nM mava and cultured for 21 days. By day 28, TF production was similar between +/+ and -/- vehicle treated EHT while RR EHT remained hypocontractile (Fig. 2). Chronic mava treatment significantly reduced TF production in +/+ EHT but not in -/- or RR EHT (Fig. 2). Consistent with diastolic dysfunction, a hallmark of HCM in humans, day 28 -/- and RR EHT displayed slow relaxation, though the effect was more pronounced in RR EHT (Fig. 3). While chronic mava treatment accelerated relaxation in -/- EHT to levels that were similar to that observed in vehicle treated +/+ EHT, it failed to do so in RR EHT (Fig. 3).
cMyBP-C -/- EHTs initially present with a hypercontractile phenotype, consistent with an increase in DRX crossbridges, while W792R RR EHT present with a hypocontractile phenotype. By 4 weeks in EHT culture, both genotypes present with impaired relaxation, that is more severe in RR EHT. While chronic mava treatment prevents development of slow relaxation in -/- EHT, it failed to do so in RR EHT. These findings suggest that the primary disease mechanism of the W792R mutation is not an increase in DRX crossbridges and that mavacamten may not be an effective treatment for patients carrying this mutation, further highlighting the need for studying the pathomechansims of HCM mutations and the development of novel therapies.
Quantum mutati! Hector, Pompey, and the Fortune of a Mut(il)ation
Authors: Pontiggia Ludovico 
Published: October 2024

Abstract
This article collects various passages of the Pharsalia in which Lucan alludes to the apparition of Hector’s mutilated shade, portrayed by Aeneas in Aeneid 2 as deeply changed from the relentless hero of the Iliad, and uses it as a model for the tragic fall from glory that republican Rome and Pompey have undergone throughout the civil war. Following up on metapoetic interpretations of Aeneas’ dream, it is then argued that in the Pharsalia, too, Hector’s ghost functions as an intertextual marker flagging up the Virgilian model, and symbolises the transition from a type of epic aimed at celebrating the winners to Lucan’s epic of the losers.
38. The Algorithmic Music of Iannis Xenakis–What’s Next?
Authors: Manaris Bill 
Published: October 2024

Iannis Xenakis was a pioneer in algorithmic composition of music and art. He combined architecture, mathematics, music, and performance art to create avant-garde compositions and performances that are still being analyzed, performed widely, and discussed. Xenakis’s musical contributions are deeply algorithmic in nature, inspired by his understanding and appreciation of mathematics and controlled randomness; i.e., stochastic processes. His work was made possible through his use of early computer programming languages, such as FORTRAN and BASIC, and the formalization, standardization, and replicability such languages provide. This chapter explores the intersection of science and art, Xenakis’s early computational techniques for a non-technical audience, and how algorithmic music composition has advanced since his passing. It includes the retelling of one of his early works, Concret PH; a reimagining of UPIC; and musical examples derived from blending artificial intelligence, advanced algorithms, modern technology and smartphones, and user interaction, into the body of techniques introduced by him.
48. Polytope XXI
Authors: Marandola Fabrice , Boucher Myriam , Thibault Dominic 
Published: October 2024

Polytope XXI is the title of a concert presented by Montreal-based percussion sextet Sixtrum to pay tribute to Iannis Xenakis. It is also the name that composers Myriam Boucher and Dominic Thibault have given to their monumental instrumental project that was premiered during this concert in May 2022: a sort of giant, electronically augmented, audio-luminescent harp, whose strings are put in vibration by multiple means by the percussionists of Sixtrum during the concert.
The project was inspired by the first Polytope imagined by Iannis Xenakis, an ‘electronic sculpture combining light, music, and structure’, that was presented inside the French Pavilion during Expo67—the World’s Fair that took place in Montreal in 1967. This original installation created an artistic work inscribed in space and made of multiple layers of sound and light, and was designed so that spectators could move freely within the installation itself. Polytope XXI inverts this approach and sets the installation on stage with the goal to make it mobile, so that changes in the perception of space, light and sound can still be experienced by the audience, while also taking advantage of modern technological capabilities (actuators, sensors, etc). Here, we present a live recording of the world premiere of this work.
Lightning Casualties of Vulnerable Caterpillar Fungus Collectors on the Qinghai–Tibetan Plateau
Authors: Zhang Daile , Holle Ronald L. 
Published: October 2024

Abstract
Lightning has killed and injured many people in recent years in the Qinghai–Tibetan Plateau area of China when they were collecting a rare product used for medical applications. The fungus that grows on dead caterpillars at high altitudes in this region demands a high price when sold, so it attracts collectors that unfortunately become at risk from lightning during this process. A total of 12 lightning-related events during 2004–22 resulted in 29 deaths and 53 injuries. All cases occurred at high elevations in rugged terrain with no available lightning-safe structures or vehicles. The fungus collection occurred during the daytime hours in late spring and early summer, which is also when lightning is frequent. Maps of lightning for the cases and information gained from the Chinese-language reports are summarized. It is apparent that this is a unique high-risk, high-reward occupation that is similar in terms of exposure to other situations around the world that result in lightning deaths and injuries.

Significance Statement
Lightning deaths and injuries often occur when people push the limits of safety due to occupational or recreational demands. Most of these decisions are on short time scales such as while tending agricultural fields, working on roofs, running a competitive race, or walking home from school when a thunderstorm is approaching. In the scenario presented here, groups of people with few income alternatives spend weeks or months in mountainous regions where lightning is common, but safety is elusive. This situation is an unusual version of high lightning risk occurring while pursuing a high reward.
Poster 139: A Prospective, Observational Study to Assess the Efficacy of BioEnthesis in Patients Undergoing Arthroscopic Rotator Cuff Repair
Authors: Haneberg Erik , Phillips Andrew , Danilkowicz Richard , Elias Tristan , Wang Zachary , Forsythe Brian , Garrigues Grant , Yanke Adam 
Published: October 2024

Objectives: Rotator cuff repair (RCR) remains an area needing further research to optimize patient outcomes postoperatively. This study investigates a novel allogenic, acellular, biphasic cancellous bone scaffold that lies between the tendon and bone in an RCR. The purpose of this study is to assess the efficacy of this graft in improving the integration of soft tissue to bone post RCR. Methods: Ten patients were consented to receive the BioEnthesis graft prior to undergoing arthroscopic RCR. Patients received an MRI and patient reported outcomes (PROs) preoperatively and at 6 and 12-months postoperatively. A control cohort was obtained from a previous randomized controlled trial and matched in a 2:1 ratio by sex, tear size, and number of anchors used in the repair. The control cohort had an MRI at 12-months only. Two reviewers (R.D., A.B.Y.) independently graded each MRI according to the Sugaya classification assessing post-operative rotator cuff repair as well as a binomial assessment for the presence of a retear. Results: Analysis included 10 patients (7 male, 3 female) receiving the BioEnthesis graft and 20 Control patients (14 male, 6 female). The BioEnthesis cohort was significantly older than the Control cohort (69.7 ± 5.9 vs 56.11 ± 9.4; p<0.001). At 12-months postoperatively, there was a trend in the average Sugaya score graded on MRI favoring the BioEnthesis over the Control cohort (2.28 ± 1.2 vs 3.3 ± 1.09; p=0.054). BioEnthesis patients had a lower rate of retear on 12-month MRI, but this difference was not significant (29% vs 45%; p=0.23). No significant differences were found for PRO’s at any time point. VAS was not assessed for the control group, however, BioEnthesis patients significantly improved from pre-operative to 12-months post-operative (5.0 ± 2.4 to 0.875 ± 0.8; p<0.001). BioEnthesis patients experienced significant strength increases in abduction, scapular plane abduction, and external rotation at 6 and 12-months postoperatively. Conclusions: The BioEnthesis graft is a safe graft option that may reduce the risk of retear and help the integration of tendon to bone in arthroscopic RCR.
Poster 162: Time to Achievement of Clinically Significant Outcomes Following Revision Rotator Cuff Repair
Authors: Mirle Vikranth , Gamsarian Vahram , Tashjian Michelle , Chang Joshua , Khazi-Syed Daanish , Brusalis Christopher , Yanke Adam , Cole Brian , Verma Nikhil , Nicholson Gregory , Garigues Grant , Forsythe Brian 
Published: October 2024

Objectives: To define the time required to achieve outcomes (CSOs) following revision rotator cuff repair (RCR). The main outcome was to identify an evidence-based timepoint for functional recovery, including the time needed to attain minimally clinically important difference (MCID) and patient acceptable symptomatic state (PASS) for revision RCR. Methods: Patients who underwent rotator cuff repair between 2016 and 2022 were collected. Those with completed preoperative and at least 1 post-operative (3-month, 6-month, 1 year, and 2 years) Patient-Reported Outcome Measures (PROMs), including American Shoulder and Elbow Surgeons (ASES), or Single Assessment Numeric Evaluation (SANE) were included. Exclusion criteria included patients with significant concomitant procedures, or primary rotator cuff repairs. MCID and PASS for each PROM were identified from prior literature and utilized as a threshold needed to attain functional recovery. The time needed to achieve CSO was then calculated and plotted using Kaplan-Meier survival analysis. Results: The average patient was 58.8 years old, male (66%), and white (72%). Of the 99 included patients, 48 patients had completed SANE forms, and 52 had completed ASES forms. Patients attained SANE achievement rates of 68.8% for MCID and 35.5% for PASS, and ASES achievement rates of 75% for MCID and 38.5% for PASS. Median achievement time across both surveys ranged between 4.3 – 5.01 months for MCID, and between 5.01 – 5.72 months for PASS. Averages for achievement time for MCID ranged from 5.2 – 5.6 months, and for PASS from 6.3-9.2 months, respectively. (Figure 1) Conclusions: When comparing the mean time to CSO of revision RCR to primary RCR in previously published literature, the results are not only similar, but illustrate a slightly earlier time to CSO in revision cases. However, the overall percentage of MCID and PASS attainment are significantly reduced. This can potentially inform clinicians, that while a lower percentage of the revision cases will attain clinically significant outcomes compared to primary patients, those who do attain CSO will have a similar post-operative course. The timeline for achieving improvement that was established by this study may aid in setting patient expectations and designing future outcome studies involving revision RCR.