bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality in long-term care residents: retrospective national cohort study
Authors: MacRae Jane , Ciminata Giorgio , Geue Claudia , Lynch Ellen , Shenkin Susan D , Quinn Terence J , Burton Jennifer Kirsty
Published: October 2024

Objectives

Mortality trends among people living in long-term care settings have been poorly understood. Linking data offers the potential to provide real-world, long-term national follow-up. Our aim was to describe patterns and associations with mortality among people moving-in to care homes in Scotland.

Methods

A retrospective cohort study was undertaken using routinely collected national social care data from the Scottish Care Home Census. These data were indexed and linked to national health data and mortality records for individuals moving- in to care homes in Scotland between 1 April 2013 and 31 March 2016. Location of death, underlying causes and time to death are reported. Survival analysis was undertaken using the Gompertz model for human mortality adjusted for key variables.

Results

Of 23 892 individuals moving-in to care homes, 20 250 (84.8%) died by 31 May 2020. Most deaths occurred in the care home setting (77.5%), with a fifth (20.5%) occurring in the hospital. 0.1% died the day they moved-in, 3.2% within a month, 24.2% within a year and 85% by 7 years. Dementia codes account for more than a third of all deaths (35.1%). Median survival time was shorter (701 vs 951 days; 23 vs 32 months) for those moving-in from the hospital, compared with the community. The adjusted HR for moving-in from the hospital was 1.19 (95% CI 1.15 to 1.22).

Conclusions

Mortality is common in Scotland’s care homes but varies in timing. Dementia is the most common cause. Those moving-in from the hospital are more likely to die sooner, and this evidence provides opportunities to improve support for all involved.
Effect of packaging with versus without candy-oriented marketing themes on the appeal and sensory attributes of flavoured e-cigarettes
Authors: Jafarzadeh Nikki S , Han Dae Hee , Peraza Natalia , Anderson Marissa K , Harlow Alyssa F , Monterosso John R , Pang Raina D , Mason Tyler B , Hong Kurt , Cahn Rael , Leventhal Adam M
Published: October 2024

Significance

E-cigarettes with candy-themed marketing are implicated in decisions to first try e-cigarettes but have unknown effects on the experience of vaping. We compared adults’ perceived appeal and sensory attributes after self-administering flavoured e-cigarettes in experimentally manipulated packaging with candy-themed versus standard marketing. We also assessed effect modification by salt vs free-base nicotine formulation.

Methods

Adults who currently used e-cigarettes and/or cigarettes (N=72; age M(SD)=31.4 (12.8) years) completed single-puff self-administrations from eight individually-packaged pods containing fruit or dessert-flavoured e-liquid via staff-guided video sessions. For each e-liquid flavour, we custom-manufactured packaging with standard (eg, ‘mango’; mango fruit image) and candy (eg, ‘mango gummy bear’; gummy bear image) marketing versions, which we varied within-subject (four pods candy; four pods standard). After participants opened the package and vaped the pod inside, they rated its sensory attributes and appeal (0–100 scale). Participants were randomised between subjects to salt or free-base ~2.3% nicotine in all pods.

Results

Marketing theme had no significant main effects on outcomes. Marketing theme × nicotine formulation interactions were significant; candy-themed (vs standard) packaging elevated composite appeal (Bdifference [estimated mean difference between marketing themes]=7.7), liking (Bdifference=8.4), and sweetness (Bdifference=5.7) ratings in free-base but not salt nicotine formulations. Marketing theme did not affect smoothness, harshness and bitterness ratings regardless of nicotine formulation.

Conclusion

Candy-themed marketing may heighten the appeal and sweet sensory experience of vaping flavoured free-base nicotine e-cigarettes. While marketing restrictions are predominantly intended to prevent e-cigarette initiation, candy-themed marketing restrictions could also prevent persistent use by lowering the appeal of flavoured free-base nicotine e-cigarettes.
Biophysical risk in 189 Italian prisons: an inference analysis from the second to the fourth wave of the COVID-19 pandemic
Authors: Franchi Cristiano , Gaudio Pasqualino , Malizia Andrea , Albano Alessandro , Suriano Giovanni , Palma Mauro , D’Ettore Felice Maurizio , Di Giovanni Daniele
Published: October 2024

Previous studies have highlighted how SARS-CoV-2 has entered Italian prisons, causing a slightly higher number of infections compared to the Italian population. This result has not been confirmed, on the contrary, with regard to the values of "Reproductive number over time" (R(t)) and "Prevalence of hospitalisation" (H). In particular, R(t), i.e. the average number of secondary transmissions caused by an infected person, is a useful parameter for measuring the infectivity of bioagents and the effectiveness of public health measures to control the spread of the infectious disease. Previous results have been obtained from data collected from all Italian prisons and therefore represent averages of many and varied realities. On the contrary, the aim of this study is to analyse and compare the Infected (I) and the R(t), in each prison, and to search for the side variables that may favour the spread of the virus in these places. The R(t) evaluation is obtained using a differential equation based on the SIR model, but unlike its usual application, no simplification has been made (i.e. population (N) ≠ susceptible (S)). Preliminary results focus on the period between September 2020 and March 2022. They show that during the second and third waves, the infection rate followed a gradient from north to south and to the islands, while the maximum R(t) values were randomly distributed across the peninsula. Moreover, we describe as the maximum R(t) values are poorly correlated with the crowding rate of each prison and the same was obtained when examining other variables such as the type of prison and the presence/absence of health isolation sections. On the contrary, there is a significant correlation when the independent variable is the presence of staff. This analysis will provide the basis for the development of other linear and nonlinear physical models that could be helpful in predicting the spread of infectious diseases in closed and controlled places.
Prompt-gamma imaging in particle therapy
Authors: Pinto Marco
Published: October 2024

Prompt-gamma imaging has been a source of intensive research over the years since its first proposal in 2003. Several detection approaches have been researched and developed, and many studies on prompt-gamma imaging have been conducted on its feasibility, detection systems optimisation, and possible workflows. Now, this form of particle therapy monitoring is finally arriving in clinical settings and showing impressive results. Prompt-gamma imaging may be the key to enabling crucial improvements in particle therapy, namely when considering more complex workflow scenarios, like adaptive radiotherapy using ion beams. Herein, several aspects related to prompt-gamma imaging are introduced, covering both its advantages and limitations. The need for particle therapy monitoring, the different prompt-gamma radiation detection systems, the difficulties with dealing with low emission yields and with the tools used to simulate it, the prediction tools for prompt-gamma radiation, and the translation into clinical applications are presented and discussed. Finally, some considerations are also made on the future of prompt-gamma imaging and what it may bring into particle therapy, ultimately benefiting patients worldwide.
A Synergistic Multi-Attribute Decision-Making Strategy for Selecting Sustainable Educational Institution Site Using Parameterized Single-Valued Neutrosophic Soft Sets
Authors: Rahman Atiqe Ur , El-Morsy Salwa , Rahman Haseeb Ur , Malik Muhammad Yasir Hayat
Published: October 2024

Selecting the ideal site for an educational institution is a challenging task that calls for a deep understanding of the available resources, the educational needs of society, and projected development patterns. To cope with such intricacies, this study proposes a novel mathematical context: A single-valued neutrosophic parameterized single-valued neutrosophic soft set ([Formula: see text]-set) that merges the versatility and adaptability of single-valued neutrosophic sets with parameterized single-valued neutrosophic soft settings. Using [Formula: see text]-set-based information, the study emphasizes the intrinsic uncertainty and inaccuracies in the decision-making process and enables a more thorough portrayal of the many criteria involved in site selection. In the first stage, the elementary notions of [Formula: see text]-set are explored with the description of understandable examples. In the second stage of the study, a decision-assistance mechanism is presented, and a strong algorithm is developed and evaluated using a case study prototype that focuses on choosing an appropriate location for an educational institution to be established. By guaranteeing that the chosen site satisfies the essential requirements for ideal placement, the algorithm proves its efficacy and improves the decision-making process.
Non-Conservative Maximum Flow by Centiles-Method in Uncertain Network
Authors: Pangeni Badri Prasad , Dhamala Tanka Nath
Published: October 2024

The flow maximization problem being a leading problem in network optimization is widely studied with many applications. In this work, we find the maximum flow pulled out from the source and sent to the sink using the uncertainty theory. We develop a flow function to get maximum flow for the network having uncertain arc capacities and sufficient storage capacities at the intermediate vertices. The centiles-method is used to find the maximum flow value and an algorithm is proposed to get non-conservative maximum flow. The result is also illustrated by an example. The flow values are compared graphically to see the dominance of the non-conservative maximum flow over the conservative maximum flow.
Secure Blockchain Assisted Attribute-Based Keyword Search for Collaborative E-Healthcare
Authors: Routray Kasturi , Manikonda Abhiram , Bera Padmalochan
Published: October 2024

In the age of technological advancement, collaborative E-healthcare emerges as a transformative system eliminating traditional location and accessibility barriers in healthcare services. Here, Searchable Encryption (SE) plays a key role in enabling healthcare providers to outsource encrypted medical data and search services to third parties like cloud servers, thereby reducing storage and management expenses. This intermediary approach poses challenges of single-point failure, privacy breaches, and potentially untrustworthy results. State-of-the-art public key-based SE methods use a cloud-assisted architecture that doesn’t support reliable and practical searches with fine-grained permissions. Also, such systems require additional support to address potential privacy leakages and ensure data availability at the storage server. To address these concerns, we propose a
B
lockchain-assisted
E
fficient and
S
ecure
K
eyword
S
earch (BESKS) scheme to enforce fine-grained keyword search privilege control while achieving practical search complexity. Our scheme employs a ciphertext policy attribute-based keyword search mechanism where keywords are encrypted using expressive access policies to build an inverted index structure. The encrypted indexes are stored on the blockchain while encrypted medical documents are stored on InterPlanetary File System (IPFS) nodes to enhance availability and ensure the reliability and scalability of our approach. Our scheme utilizes blockchain-based smart contract for efficient, secure search operations and ensures financial fairness in fine-grained searches. Search tokens are generated based on user attributes and query keywords to facilitate private searches on-chain. To enhance the search process, our secure index enables exact match for a query keyword in constant time to ensure expensive authorization operations are performed only once. Theoretical analysis suggests that our BESKS is more efficient and secure than state-of-the-art schemes. Prototype implementation results on the Ethereum blockchain network further validate its feasibility for real-world applications, demonstrating the scheme's practical applicability in collaborative E-Healthcare systems.
Criminology and Corporate Crime: The Art of Scientific Cross-Pollination
Authors: Simpson Sally S.
Published: October 2024

Born of sociology while absorbing ideas and scholarship from other specialties, criminology can legitimately tout its interdisciplinary bona fides. Yet within the field, integration and cross-pollination across subject areas is, far too often, absent. Concentrating on corporate crime and summarizing the literature across a variety of different domains, I demonstrate that criminology, as a discipline, benefits from knowledge generated by corporate crime scholarship and vice versa. I discuss why it is essential to build a multidisciplinary knowledge base that informs and draws from corporate crime scholarship while also addressing critical epistemological challenges and knowledge gaps that confound integrative efforts. I conclude with potential areas of synergy ranging from the theoretical (organizational life cycle/life course and decision-making in different contexts) to new/old forms of crime and crime control associated with the emergence of artificial intelligence and machine learning.
Short-Term Mindsets and Crime
Authors: van Gelder Jean-Louis , Frankenhuis Willem E.
Published: October 2024

We propose the concept of short-term mindsets as an alternative to self-control as envisioned in Gottfredson & Hirschi's self-control theory (SCT). We lay out a competing perspective, short-term mindsets theory (STMT), based on this novel concept. STMT assumes that short-term mindsets are partly rooted in enduring individual differences and in part develop in response to criminogenic environments, events, and experiences. STMT connects individual-level perspectives to sociogenic views by explaining how several risk factors of crime (e.g., negative parenting, delinquent peers, substance use) all impact on short-term mindsets. Exposure to one risk factor encourages short-term mindsets that, in turn, make exposure to other risk factors more likely, thereby increasing the likelihood of crime. We show that STMT enjoys stronger empirical support than SCT, better aligns with other theory, and can account for phenomena typically considered at odds with, or outside the purview of, SCT.
Beyond the Seductions of the State: Toward Freeing Criminology from Governments’ Blinders
Authors: Katz Jack , Roldán Nahuel
Published: October 2024

Criminology is haunted by state-structured biases. We discuss five. (a) With the spatial boundaries and the binary deontology they use to count crime, governments draw researchers into ecological fog and sometimes fallacy. (b) All legal systems encourage criminologists to promote untenable implications of socially stratified criminality. (c) To degrees that vary by time and place, the scope of criminological research is compromised by methodological nationalism. (d) State agencies use chronologies that repeatedly draw researchers away from examining the nonlinear temporalities that shape variations in criminal behavior. (e) State agencies produce data that facilitate explaining the why of crime, but scientific naturalism would first work out what is to be explained. We recommend a criminology that begins by describing causal contingencies in social life independent of governments’ labeling of crime.
Local Government Spending: Policing Versus Social Services
Authors: Beck Brenden
Published: October 2024

US cities have recently increased the share of their budgets devoted to policing and decreased the share devoted to social services. However, a growing body of research demonstrates that social services can durably reduce crime, raising the question of whether spending more on police and less on social services reduces crime in the short term only to increase it in the long term. This review addresses this question by first recounting recent trends in municipal budgeting. Then, it summarizes the causal evidence for which local government functions best reduce crime, focusing on policing, education, employment, and housing. Research suggests that education spending efficiently and durably reduces crime with fewer negative externalities than policing but with longer delays. Evidence that housing and employment spending suppresses crime is promising but nascent. Finally, the review recommends turning renewed scholarly attention to government budgets and the root causes of crime trends.
Formulation Development of Directly Compressible Tablets Incorporating Trisamo Extract With Synergistic Antioxidant Activity
Authors: Suksaeree Jirapornchai , Wunnakup Thaniya , Chankana Natawat , Charoenchai Laksana , Monton Chaowalit
Published: October 2024

This work investigates the synergistic antioxidant activity of the compositions of Trisamo (TSM) herbal formula containing the dried fruits of Terminalia chebula, Terminalia arjuna, and Terminalia bellirica. An augmented simplex lattice design was utilized to investigate the synergistic antioxidant activity, finding an equal mass ratio among the three herbal drugs to exhibit optimal synergistic antioxidant activity, with a combination index of less than 0.8. The optimal TSM extract was used to prepare directly compressible tablets employing a Box–Behnken design response surface methodology, optimizing compressional force (500, 1000, and 1500 psi), sodium starch glycolate (0%, 2%, and 4%), and magnesium stearate (0.5%, 1.0%, and 1.5%). Optimal parameters were a compressional force of 1000 psi, 2% sodium starch glycolate, and 0.5% magnesium stearate. The TSM extract tablet had a weight of 600.06 mg, a diameter of 12.78 mm, a thickness of 4.12 mm, a hardness of 6.85 kP, a friability of 0.30%, and a disintegration time of 1.81 min. Computer model predictions were verified with a low percentage error (≤ 10.00%). After 6 h, phenolic compounds were dissolved to an extent of approximately 40%–80%, including gallic acid (57.11%), corilagin (38.64%), chebulagic acid (58.49%), and chebulinic acid (81.44%). Stability data revealed that the phenolic compounds were retained for 3 months compared to the initial time point, with gallic acid at 81.43% and 100.27%, corilagin at 94.81% and 87.85%, chebulagic acid at 92.22% and 69.83%, and chebulinic acid at 107.00% and 85.54% at 30°C/75% RH and 45°C/75% RH, respectively. The summation of these four compounds did not change significantly when stored under either set of conditions. In summary, mixture design and response surface design were successfully utilized in the optimization of TSM extract tablets with synergistic antioxidant activity.
Supplemental Figure 3 from Chemotherapy Enriches for Proinflammatory Macrophage Phenotypes that Support Cancer Stem-Like Cells and Disease Progression in Ovarian Cancer
Authors: Cruz Luisjesus S. , Robinson Mikella , Stevenson Denay , Amador Isabella C. , Jordan Gregory J. , Valencia Sofia , Navarrete Carolina , House Carrie D.
Published: October 2024

Baseline secretory profile
The Development of an Intradisciplinary Staff Training Intervention on the Optimal Management of Behavioural and Psychological Symptoms of Dementia: A Qualitative Study
Authors: Carrier Daphnée , Toulouse Élodie , Rochefort Christian M.
Published: October 2024

Introduction: Behavioural and psychological symptoms of dementia (BPSDs) are a group of highly prevalent symptoms in residents with a neurocognitive disorder, including agitation and depressive symptoms. Caregiving staff often mention knowledge and skills deficits regarding optimal BPSD management. While several staff training on BPSDs management exist internationally, their transferability to other clinical contexts is limited, owing to methodological challenges. Therefore, to address this implementation gap, there is a strong need for training based on high-quality research to strengthen existing evidence, and ensure feasibility and reproducibility. Methods: This qualitative study, part of a larger research project, occurred in 2022 on long-term care (LTC) centre unit and an alternate level of care (ALC) hospital unit located in the Province of Quebec, Canada. This study aimed to (1) evaluate the needs and perceptions of staff caregivers regarding BPSD management, (2) identify the training content and modalities to prioritize according to experts, (3) develop intradisciplinary training on BPSD management, and (4) pretest the preliminary version of the training. Objectives one and two were evaluated using focus groups and objective four using individual cognitive interviews. Qualitative interview data was audio-recorded with participants’ consent, transcribed verbatim, and thematically content analysed using an established method. Results: Overall, thirteen caregivers participated in objective one (8 from the LTC unit, and 6 from the ALC unit). The main staff training need identified on each site was the management of resident’s aggressive behaviours. Staff verbalized a preference for virtual training. Objective 2 involved a panel of eight experts. Experts recommended the use of an online training platform, and certain training models and indicators. Based on caregivers’ and experts’ input, five interactive online staff training capsules lasting from 20 to 25 min each and an algorithm guiding the evaluation and management of BPSDs were created. The training capsules and the algorithm were iteratively improved following cognitive interviews with 4 caregivers from the participating sites. Conclusion: An interactive virtual staff training on BPSD management was created based on staff and expert consultation. The next step in the investigation will be to evaluate the feasibility and acceptability of the training.
The Challenges of Diagnosing Gestational Diabetes after Bariatric Surgery: Where Do We Stand?
Authors: Rodrigues-Martins Diana , Nunes Inês , Monteiro Mariana P.
Published: October 2024

Background: Obesity, gestational diabetes mellitus (GDM), and bariatric metabolic surgery (BMS) are increasingly common conditions during pregnancy. Summary: However, clinical knowledge regarding GDM that occurs after BMS remains full of uncertainties. Given its prevalence and potential consequences for the dyad pregnant and offspring, it is imperative to increase knowledge about GDM after BMS, define diagnostic criteria and consequently strategies capable of improving pregnancy outcomes. Key Messages: This paper aimed to review GDM screening methods after BMS and gives insights regarding new paths of research on this paramount obstetric condition.
Abstract Mo003: Concomitant administration of dantrolene is sufficient to protect against doxorubicin-induced cardiomyopathy
Authors: Nakamura Yoshihide , Yamamoto Takeshi , Kobayashi Shigeki , Suetomi Takeshi , Uchinoumi Hitoshi , Yano Masafumi
Published: October 2024

Background:
Doxorubicin (DOX), a commonly used anticancer agent, causes irreversible cardiac dysfunction, which remains a clinical challenge. It has been reported that DOX induces the release of Ca
2+
through ryanodine receptor 2 (RYR2) of the sarcoplasmic reticulum (SR) and increases the Ca
2+
level in the cytoplasm.

Objectives:
we aimed to investigate whether RYR2 stabilization could suppress DOX-induced cardiomyopathy (DIC) and, if so, the optimal duration of dantrolene treatment (a pharmacological method).

Methods:
We investigated the relationship between DOX cardiotoxicity and RYR2 stabilization
in vivo
and
in vitro
experiments.

Results:
DOX caused calmodulin dissociation, marked Ca
2+
leakage from RYR2, and increased oxidative stress in isolated cardiomyocytes, which were suppressed by enhancing calmodulin binding affinity of RYR2 and stabilizing its tetramer structure pharmacologically (by dantrolene) or genetically (by RYR2 V3599K mutation). In DIC model mice, cardiac function was impaired, fibrosis and TUNEL-positive cells increased, accompanied by a decrease in GRP78 and increased lipid peroxide levels, which led to endoplasmic reticulum stress and ferroptosis respectively. These cardiac dysfunctions were ameliorated by continuous dantrolene administration or RYR2 V3599K mutation. Interestingly, dantrolene was sufficiently effective for myocardial protection even when terminated 7 days after DOX administration.

Conclusions:
The short-term concomitant use of dantrolene may be an innovative and clinically feasible DIC preventive strategy. Furthermore, because dantrolene is already safely used clinically as a specific drug for malignant hyperthermia, the results of this study are expected to lead to drug repositioning in the near future.
Abstract Mo015: Myeloid Specific PD-L1 Deletion Promotes Cardiac Dysfunction And Myocardial Inflammation
Authors: Toro Cora Angelica , Sethi Rohan , zhang qinkun , Lal Hind , Sultan Tousif
Published: October 2024

Background:
Immunotherapy, particularly PD-1/PD-L1 blockers, is effective in cancer treatment but can cause rare, but potentially fatal heart issues. Despite the significant impact of these adverse events, there is limited research into the underlying mechanisms of immune checkpoint inhibitor (ICI)-mediated cardiotoxicity. PD-L1, which is abundantly expressed in cardiac tissue, particularly exhibits high expression levels over myeloid cells. However, the precise role of myeloid-specific PD-L1 signaling in mediating autoimmune cardiac disease pathology remains unclear.

Methods and Results:
To study the role of myeloid cell-specific PD-L1 (myeloid-PD-L1) in cardiac pathophysiology, we generated myeloid-specific PD-L1 KO mice, using Lyz2tm1(Cre) Ifo systems. As expected, PD-L1 expression was significantly down-regulated in Mφs from myeloid-PD-L1 KOs. The cardiac function was followed by echocardiography. Controls and myeloid-PD-L1-KO hearts had comparable ventricular function at 1 month of age. Interestingly, as early as 2 months of age, myeloid-PD-L1-KOs displayed marked cardiac dysfunction as reflected by reduced LVEF, LVFS, and HF markers. Immune profiling was conducted whether chronic inflammation contributes to cardiac dysfunction and remodeling at a later age as observed at 2 and 3 months of age. Interestingly, excessive systemic inflammation and substantial immune infiltration (innate and adoptive), activation, and a pro-inflammatory cytokine storm were detected in the KO hearts. Furthermore, myeloid-PD-L1 KO hearts showed increased recruitment of pro-inflammatory CCR2+ monocytes and macrophages.

Conclusion:
Our data with myeloid-PD-L1 KOs suggest that deleting PD-L1 in myeloid lineage promotes myocardial and systemic inflammation through innate and adaptive immune cell activation and recruitment of CCR2+ MΦs. Subsequently, this leads to impaired cardiac pathophysiology. Thus, these translational studies will directly evaluate the potential of targeting myeloid-PD-L1 signaling to alleviate cardiac damage.
Abstract Mo032: Biofabrication of Small Vascular Graft using Human Amniotic Membrane
Authors: Wang Bo
Published: October 2024

Vascular diseases encompass a spectrum of pathological conditions affecting blood vessels, including cerebrovascular disease, coronary heart disease, aneurysms, deep vein thrombosis, and peripheral arterial disease. In severe cases, surgical interventions such as bypass grafting or vascular replacement surgeries are necessary to restore blood flow by bypassing obstructed vessels with functional vascular substitutes.

Autologous blood vessels harvested from patients are considered the gold standard for vascular surgeries. However, their availability is limited in patients with pre-existing chronic diseases or previous vessel harvest, and the associated morbidities of vessel harvesting and subsequent surgeries further restrict their therapeutic applicability.

Synthetic grafts, including polytetrafluoroethylene (e-PTFE), polyethylene terephthalate (PET), and polyurethane (PU), have obtained FDA approval for clinical application and have shown satisfactory outcomes in large vessel surgeries (internal diameter > 6mm). However, clinical trials targeting medium (6-10 mm) to small (< 6mm) vessels often yield unsatisfactory results.

This study aims to develop a small vascular graft using human amniotic membrane (HAM) that meets the structural, mechanical, and biological requirements for human vascular reconstructive surgeries.

Fresh HAMs were decellularized with 1% Triton X-100 and 0.1% sodium dodecyl sulfate to prepare decellularized HAM (DAM). The DAM was trimmed into a rectangular shape and rolled around a catheter to prepare a tubular-shaped DAM vascular graft. After rolling, the DAM grafts were crosslinked with 1% genipin for 24 hours followed by thorough water washing. The final DAM vascular graft exhibited a multi-layered wall structure and comparable dimensions and mechanical properties to native arteries.

The DAM vascular graft was further evaluated in vivo by replacing part of the rat abdominal aorta and part of the carotid artery in pigs. Both small and large animal studies demonstrated vascular patency with no neointimal hyperplasia (NIH), suggesting that the DAM graft holds significant promise as a small tissue-engineered vascular graft for future vascular reconstruction surgeries.
Abstract Mo033: Circulating Long Noncoding RNA Expression Signature Predicts Adverse Cardiovascular Outcomes in Patients with Coronary Artery Disease
Authors: Song Wei Lun , Yeh Chih-Fan , YANG Kai-Chien
Published: October 2024

Background:
Patients with coronary artery disease (CAD) have increased risks of subsequent major adverse cardiovascular events (MACE). Currently, there are no reliable tools to predict recurrent MACE in CAD patients.

Objective:
To determine if circulating long noncoding RNA (lncRNA) expression signature predicts recurrent MACE in CAD patients.

Methods:
As part of the Taiwan Biosignature Study, this prospective nested case-control study included 168 CAD patients who experienced MACE during the follow-up and another 108 CAD patients who remained free of MACE after a≥24-month follow-up. Plasma lncRNAs were profiled to determine their prognostic values for MACE in CAD patients.

Results:
Initially, RNA sequencing in 59 CAD patients (41 with recurrent MACE) revealed that a total of 124 plasma lncRNAs were dysregulated in CAD patients with recurrent MACE. Subsequent analyses showed that the expression signature of these lncRNAs classified CAD patients with vs. without recurrent MACE with an accuracy of 93%. Elevated levels of plasma
lnc-NCF1-1, BRE-AS1, lnc-ZFAT-6, lnc-SLC46A3-5, lnc-CXCL3-2
and
lnc-EBF3-4
were associated with increased risks of recurrent MACE. Additional studies in the remaining 217 CAD patients (127 with recurrent MACE) validated that increased plasma levels of
lnc- NCF1-1, BRE-AS1, lnc-ZFAT-6,
and
lnc-EBF3-4
were significant predictors of recurrent MACE. In addition, lnc-SCORE, an index calculated from MACE-associated plasma lncRNA levels, was shown to be a strong independent predictor (adjusted HR, 2.70 [95% CI 1.78-4.09]) of recurrent MACE in CAD patients.
BRE-AS1
and
lnc-ZFAT-6
, two endothelium-enriched MACE-associated lncRNAs, were specifically dysregulated in cardiomyopathy of ischemic, but not of non-ischemic, origin, suggesting their potential contribution to the development of myocardial ischemia. Moreover, knocking
BRE-AS1
reversed hypoxia-induced upregulation of VCAM-1 in human aortic endothelial cells, suggesting its functional contribution to vascular inflammation upon ischemia.

Conclusions:
This study shows the prognostic roles of circulating lncRNAs in predicting recurrent MACE in CAD patients. Endothelium-enriched lncRNA
BRE-AS1
is involved in ischemia-induced vascular inflammation.
Abstract Mo037: Cardiac-Selective TRPV1 Afferent Ablation in Subacute Myocardial Infarction Ameliorates Adverse Remodeling and Ventricular Arrhythmogenesis
Authors: Masuyama Kiyoshi , Chung Wei-Hsin , Cha Steven , Patel Janaki , Haridas Sahil , Doan Nhi , Abhyankar Devaki , Challita Ronald , Su Maureen , Ajijola Olujimi
Published: October 2024

Background:
Ventricular arrhythmias (VT/VF), the most common cause of sudden death after myocardial infarction (MI), can be ameliorated by cardiac-selective transient receptor potential cation channel subfamily V member 1 (TRPV1) afferent ablation at the time of infarction in animal models. To enable translation to human, it remains unknown whether afferent depletion in the subacute phase of MI will reduce arrhythmias and mitigate long-term structural remodeling.

Objectives:
To assess the role of cardiac-selective TRPV1 afferent ablation two weeks after MI on the long-term ventricular arrhythmogenesis and adverse structural remodeling.

Methods:
Yorkshire pigs were randomized to resiniferatoxin (RTX 5.0µg/ml: n=10) or vehicle(n=6) 14days after the left anterior descending artery infarct. Four weeks later, terminal experiments were conducted to evaluate the effect of RTX on cardiac structural and functional remodeling, ventricular arrhythmogenesis, and autonomic reflex function.

Results:
Cardiac afferent depletion via RTX administration was confirmed by diminished sympathetic response to TRPV1 agonists (bradykinin and capsaicin) and by immunohistochemical analysis of ventricular innervation.

Compared to the vehicle treated group, the RTX administration reduced LV dimension (p<0.01), repolarization heterogeneity (p<0.01) and ventricular arrhythmogenesis (program stimulation; p=0.01 and CsCl induced PVCs;p<0.01).

In the scar-border zone, myocytolysis and nerve sprouting, which are associated with VT/VF, were attenuated in the RTX group (abnormality score; p=0.01 and nerve sprouting index; p < 0.01). T cell infiltration in dorsal root ganglia was suppressed in the RTX group (p = 0.02). RNA-sequencing of stellate ganglia revealed downregulation of adrenergic genes tyrosine hydroxylase and neuropeptide-Y in the RTX group.

Taken together, these results suggest that cardiac afferent ablation in subacute MI alleviates adverse structural remodeling and ventricular arrhythmogenesis by targeting neuroinflammation and reducing stellate ganglion sympathetic overexcitation.

Conclusion:
Cardiac TRPV1 afferent depletion in subacute MI is a promising disease altering treatment for patients suffering from MI.
Abstract Mo050: Fluoroquinolones and the Risk of Aortic Aneurysm or Aortic Dissection: Evidence From a Nationwide Nested Case-Control Study Paralleled With Matched Experimental Models
Authors: Wesley Callan , Strange Jarl , Holt Anders , Gislason Gunnar , Neutel Cedric , Krüger Dustin , Civati Celine , Theunis Mart , Naessen Tania , Roth Lynn , De Meyer Guido , Martinet Wim , Rasmussen Peter Vibe , Guns Pieter-Jan
Published: October 2024

Background and Aims:
Fluoroquinolones (FQ) have been linked to aortic aneurysms and dissections (AA/AD), resulting in an official warning. However, recent large-scale epidemiological studies have reported lack of FQ-AA/AD association. This study aimed to scrutinize FQ-AA/AD risk by implementing a combined epidemiological and experimental approach.

Methods:
Danish nationwide registers (2003-2021) were used for a nested case-control analysis. FQ-AA/AD risk was evaluated in a main and high-risk FDA cohort. Further, mortality and aortic interventions linked to FQ were investigated in patients with aortic disease. Additionally, ciprofloxacin (100 mg/kg/day, 2x2 weeks) was administered to wild-type, hypertensive or Marfan mice. Aortic diameters and pulse wave velocity (PWV) were measured longitudinally to investigate aortic remodelling.

Results:
The main cohort comprised 5.10 million individuals with 58,919 cases and 1,767,510 sampled controls. Compared with amoxicillin exposure. FQ exposure was not associated with increased AA/AD risk (30-day hazard ratios (HR) 1.00 [95% confidence intervals (CI): 0.74-1.34]; 90-day HR 1.07 [CI 0.94-1.22]; 1-year HR 0.95 [0.90-1.01]). In a high-risk cohort, there was no FQ-AA/AD association (30-day HR 0.83 [0.61-1.12]; 90-day HR 0.99 [0.86-1.15]; 1-year HR 0.97 [0.90-1.05]). In patients with aortic disease, FQ were not associated with increased aortic interventions or mortality (30-day HR 0.98 [0.79-1.22]; 90-day HR 1.06 [0.95-1.19]). Additionally, ciprofloxacin did not affect aortic diameters or PWV in wild type, hypertensive, and Marfan mice, while differences between models proved the sensitivity of the methodology.

Conclusion:
The data clearly do not support the current precautions and warnings pertaining to risks of aortopathies and FQ should not be discouraged when clinically indicated.
Abstract Mo054: Long Noncoding RNA LINC00667 Downregulation Leads to SCN5A Alternative Splicing and Arrhythmogenesis
Authors: Kang Gyeoung-Jin , Kim Eun Ji , Xie An , Dudley Samuel
Published: October 2024

Background:
The voltage-gated sodium channel SCN5A, which encodes the Nav1.5 protein, is integral to the propagation of electrical signals in cardiac tissue. SCN5A expression is diminished in cardiomyopathy, significantly increasing the susceptibility to arrhythmias. This reduction in channel activity can be attributed to decreased mRNA stability coupled with aberrant mRNA splicing. The underlying mechanisms driving the dysregulation of mRNA splicing under pathophysiological conditions remain poorly understood.

Objective:
This study explores the role of long noncoding RNA LINC00667 in the abnormal alternative splicing of SCN5A mRNA.

Methods:
LINC00667 expression was analyzed using public databases, human heart tissue, iPSC-derived cardiomyocytes (iPSCMs), and cell lines. The impact of SCN5A on action potentials and sodium currents was studied in iPSCMs. LINC00667 and SCN5A expressions were measured using qRT-PCR, while Nav1.5 protein levels were assessed through Western blot. Alternative splicing of SCN5A mRNA was examined using PCR with exon-specific primers. Gene ontology and in silico analysis identified RNA binding proteins (RBPs) potentially interacting with LINC00667. RNA immunoprecipitation (RIP) assays confirmed direct binding with key splice factors. Group differences were assessed using 2-tailed Student’s t-tests, with P < 0.05 indicating significance.

Results:
LINC00667, found at chromosome 18p11.31, is expressed in the human heart and associated cells, including cardiomyocytes. Its levels are inversely related to arrhythmic risk, decreasing in heart failure and ischemic cardiomyopathy as well as under hypoxic conditions. Gene ontology linked RBPs to SCN5A mRNA splicing, with RBM25, RBM5, and TIA1 identified as LINC00667 interactors. LINC00667 reduction affected regions of SCN5A mRNA encompassing Exons 6, 24, and 28, which could potentially be linked to decreased function/expression or increased unfolded protein response (UPR). Abnormal RNA splicing decreased SCN5A-encoded sodium current, reduced action potential upstroke velocity, and shortened AP duration without altering resting membrane potential.

Conclusion:
Decreased LINC00667 releases splicing factors that result in abnormal SCN5A mRNA splicing and reduced sodium current. Since LINC00667 is reduced in cardiomyopathy, overexpression may be antiarrhythmic by preventing sodium channel downregulation.
Abstract Mo070: Metabolic Syndrome Alters cAMP Homeostasis and Contractile Function of Cardiomyocytes
Authors: Pizzo Emanuele , Cervantes Daniel , Ripa Valentina , Jagana Vineeta , Ketkar harshada , Singh Kanwardeep , Jacobson Jason , Jain Sudhir , Bisserier Malik , Rota Marcello
Published: October 2024

Approximately one third of the population in the US has metabolic syndrome (MetS), a condition associated with increased risk for coronary artery disease and myocardial infarction. But whether MetS alters properties of the myocardium before the occurrence of ischemic insults remains to be fully elucidated. For this purpose, MetS was induced in C57Bl/6 female mice with a dietary paradigm recapitulating Western-style alimentary habits in humans. Animals on regular chow were used as control (Ctrl). Cardiac function was assessed by echocardiography and myocytes were studied under field stimulation, following enzymatic dissociation. From 3-12 months on the diet, MetS mice had increased body weight, impaired glucose metabolism, augmented left ventricular (LV) mass, but preserved cardiac function, with respect to Ctrl mice. Using ECGs, heart rate variability was attenuated in MetS mice, suggesting that metabolic disorders alter cardiac sympathovagal balance. At the cellular level, LV myocytes from MetS mice had increased volume (+24%), enhanced fractional cell shortening (+42%), and faster kinetics of relaxation (-27%), with respect to Ctrl myocytes. Because cAMP and protein Kinase A (PKA) modulates myocardial contractility upon activation of G-protein coupled receptors, including beta-adrenergic receptors (B-AR), levels of these molecules were assessed by ELISA assay. Consistent with enhanced cell shortening and faster relaxation, levels of cAMP and PKA activity were, respectively, 1.8-fold and 1.9-fold larger in MetS myocytes, in comparison to Ctrl cells. Interestingly, inhibition of PKA with H-89 reduced cell shortening (-30%) and delayed kinetics of relaxation (+50%) in MetS myocytes but had no major effects on Ctrl cells. To establish the contribution of the cAMP/PKA signaling in the functional behavior of the heart with MetS, mice were treated with the B-AR blocker propranolol. Under this condition, MetS mice had reduced ejection fraction and impaired indices of diastolic function, with respect to Ctrl animals. Interestingly, myocytes obtained from Ctrl and MetS mice treated with the B-AR blocker had comparable cell shortening and kinetics of relaxation. Collectively, these results indicate that metabolic syndrome alters the functional properties of the myocytes and heart by affecting cAMP homeostasis. These properties may increase myocardial oxygen demand predisposing the heart to ischemic insults.
Abstract Mo109: Importance of Myocyte Serine De Novo Biosynthesis and its Downregulation in Heart Failure
Authors: Keykhaei Mohammad , Koleini Navid , Meddeb Mariam , Tajdini Masih , Farshidfar Farnaz , Liu Kejun , Kass David
Published: October 2024

Introduction:
The failing heart exhibits metabolic inflexibility and dysregulated metabolism. Serine is a non-essential amino acid that contributes to purine synthesis, redox, and amino acid synthesis. It is transported into cells from the circulation or formed by de novo synthesis (SdS). We have found human failing myocardium has reduced serine (Circ 2023;147:1147) and lower expression of SdS genes (Circ 2021;143:120). Yet, little is known about the role of SdS or its depression in myocardium.

Hypothesis:
Reduced serine biosynthesis impairs myocyte energy and redox balance that could contribute to heart failure.

Methods/Results:
Immunoblots of human HF myocardium found phosphoglycerate dihydrogen-ase (PHGDH, rate limiting SdS enzyme) and other SdS enzymes were reduced in HF, and moreso in HF with preserved ejection fraction. Expression of plasmalemmal serine transporters SLC1A4, SLC1A5, SLC12A4 were consistently depressed in HFpEF. To assess the relative contribution of exogenous serine versus SdS, we inhibited PHGDH by siRNA or an inhibitor (NCT503). The former reduced serine by 71% despite exogenous sources, and both induced greater cytotoxicity than from solely depleting exogenous sources. Inhibiting PHGDH in serine/glycine-free media induced cytotoxicity after 1hr, whereas with exogenous serine, this occurred by 24 hours. 24 hr PHGDH knockdown reduced ATP and GTP levels, mitochondrial DNA. In response to endothelin-1 stimulation, basal and maximal mitochondrial O
2
consumption increased along with PHGDH gene expression. These changes in mitochondrial respiration were essentially prevented by gene silencing of PHDGH coupled to a decline in TCA metabolites. PHGDH inhibition also increased oxidative stress (increased GSSG/GSH) and reduced NAD levels. The cytotoxicity induced by 24 hr SdS inhibition by PHGDH knockdown could be offset by supplementing myocytes with ribose (purine precursor) and DTT (antioxidant).

Conclusion:
This study identifies SdS as a pivotal metabolic pathway in myocyte energy metabolism homeostasis, and its depression may play a role in HF, particularly HFpEF. These results support enhancing serine metabolic pathways as a therapeutic strategy for these diseases.
Abstract Mo126: A sex-specific CD4
+
T cell response limits Coxsackievirus B pathogenesis in mice.
Authors: Robinson Christopher , Pattnaik Aryamav , Dhalech Adeeba , Condotta Stephanie , Corn Caleb , Richer Martin , Snell Laura
Published: October 2024

Coxsackievirus B3 (CVB3) is an enteric virus that is a primary cause of inflammation of the heart muscle, known as viral myocarditis. Viral myocarditis is a significant cause of heart failure, and nearly 40,000 cases are reported each year. Unfortunately, approximately 5% of CVB3 infections are fatal. Unfortunately, no vaccines or drugs are available for this virus. Interestingly, there is a sex bias in viral myocarditis where men are more susceptible than women. Unfortunately, the underlying basis for the sex bias in infection is incompletely understood. We recently determined that T cells play an essential role in CVB3 clearance using a novel oral inoculation mouse model. Here, we show a sex difference in the CD4
+
T cell response to CVB3 that is important in limiting viral pathogenesis. We found that CVB3 induced CD4
+
cell expansion in female mice but not in male mice. CVB3 infection also led to the expansion of CD62L
lo
CD4
+
T cells in the mesenteric lymph node and spleen of female but not male mice as early as five days post-inoculation, indicative of activation. Using a recombinant CVB3 virus expressing a model CD4
+
T cell epitope, we found that the expansion of CD4
+
T cells in females is viral-specific and not due to bystander activation. Finally, the depletion of CD4
+
T cells before infection led to enhanced mortality, indicating that CD4
+
T cells protect against CVB3 in female mice. We are also currently investigating the impact of CD4
+
T cell subtypes, and the role of intestinal T cells play in limiting intestinal CVB3 replication and dissemination. These data demonstrate that CVB3 induces a CD4
+
T cell response in female mice and highlight the importance of sex-specific immune responses to viral pathogens.