bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastable Fe-based Prussian Blue Analogs Cathode for Sodium-Ion Battery
Authors: Liu Yuqing , Chu Wencheng , Xu Yaozu , Yuan Zijian , Zhao Haitao , Zhang Wu
Published: November 2024

Low-cost Iron-based Prussian blue analogs (PBAs) with ultra-high cycling performance is a promising cathode material for sodium-ion batteries. However, the presence of vacancies occupied by crystal water in the structure of PBA prepared by the traditional co-precipitation method leads to rapid capacity decay of the battery, which significantly limits its practical application. In the present work, we use a modified co-precipitation method to synthesize Fe-based PBAs, which has a cubic structure and offers a large Na+ insertion/extraction channel. The results show that 99.9% of the capacity (108.9 mAh g−1) retained after 100 cycles of tests for the sample with the most outstanding cycling stability (PB-15). In addition, the samples are heat-treated to remove the crystal water from the acquired PBAs. The freshly prepared PB-15 sample is further treated at 180 °C. Phase transformation from the cubic structure to the monoclinic phase of the samples is probed after heat treatment. The initial specific capacity of HT-PB-15 is higher than that of PB-15 by 10.2 mAh g−1 and the capacity remained at 117.6 mAh g−1 after 100 cycles, which is the most outstanding cycling performance in the reported results.
A Lifetime Evaluation Method for Lithium-Sulfur Batteries
Authors: Okanishi Kento , Hiraoka Koji , Watanabe Masayoshi , Seki Shiro
Published: November 2024

Lithium-sulfur (Li-S) batteries are attracting significant attention because of their high capacity and high energy density. For Li-S batteries using highly concentrated sulfolane-based electrolytes (i.e., sparingly solvating electrolytes for Li2S
x
) and S8 active materials, we developed a method of lifetime testing to evaluate the dynamic and static degradation behavior. Short- to medium-term discharge/charge tests and long-term storage tests were conducted. The capacity degradation after cycling in the medium term was attributed to changes in the utilization of long- and short-chain Li2S
x
due to the incomplete recovery to S8. Storage tests were conducted under different temperature and state-of-charge (SOC) conditions. The discharge capacity at SOC70% decreased significantly more than that at SOC100%, demonstrating the difference in degradation behavior compared to that of typical lithium-ion batteries. The capacity retention rate decreased linearly with storage time up to approximately 9 months, revealing that degradation was accelerated by 2 times at SOC100% compared with that at SOC0%, from a simple liner analysis. The capacity also decreased with increasing storage temperature, exhibiting ∼2.4 times more degradation at 333.1 K than at 303.2 K. This may be due to the enhanced dissolution of the Li2S
x
reaction intermediates in the electrolyte and the redox-shuttle effect.
Quantifying protein kinetics in vivo: influence of precursor dynamics on product labeling
Authors: Yao Huifang , Kelley Seamus , Zhou Dan , VanSickle Sophie , Wang Sheng-Ping , Piesvaux Jennifer , Zhou Haihong , Chen Hao , McKenney David , McLaren David G. , Ballard Jeanine E. , Previs Stephen F.
Published: November 2024

We demonstrate a simple and robust protocol for measuring protein synthesis, the work considers problems encountered in experimental design. The logic can enable biologists with limited resources and/or can facilitate scenarios where higher throughput experiments are needed.
Key Proteins for Regeneration in A. mexicanum
Authors: Del Moral-Morales Aylin , Sámano Cynthia , Ocampo-Cervantes José Antonio , Topf Maya , Baumbach Jan , Hernández Jossephlyn , Torres-Arciga Karla , González-Barrios Rodrigo , Soto-Reyes Ernesto
Published: November 2024

The axolotl, known for its remarkable regenerative abilities, is an excellent model for studying regenerative therapies. Nevertheless, the precise molecular mechanisms governing its regenerative potential remain uncertain. In this study, we collected samples from axolotls of different ages, including 8‐year‐old individuals and 8‐month‐old juveniles, obtaining their blastemas 10 days after amputation. Subsequently, we conducted a transcriptomic analysis comparing our samples to a set of previously published experiments. Our analysis unveiled a distinctive transcriptional response in the blastema, characterized by differential gene expression associated with processes such as bone and tissue remodeling, transcriptional regulation, angiogenesis, and intercellular communication. To gain deeper insights, we compared these findings with those from aged axolotls that showed no signs of regeneration 10 days after amputation. We identified four genes—FSTL1, ADAMTS17, GPX7, and CTHRC1—that showed higher expression in regenerating tissue compared to aged axolotls. Further scrutiny, including structural and homology analysis, revealed that these genes are conserved across vertebrate species. Our discoveries point to a group of proteins relevant to tissue regeneration, with their conservation in vertebrates suggesting critical roles in development. These findings also propose a novel gene set involved in axolotl regeneration, laying a promising foundation for future investigations across vertebrates.
Socioeconomic and Demographic Risk Factors Affecting Adult Participants With Hypertension in Bangladesh: A Cross‐Sectional Study
Authors: Afroja Sohani , Islam Rashedul , Majumder Uttam Kumar
Published: November 2024

Background: Globally, hypertension poses a serious threat to public health since it is a key contributor to atherosclerosis, a condition in which plaque accumulation in the arteries thickens and restricts blood flow. Cardiovascular diseases (CVDs) are mostly caused by atherosclerosis. Considering this, the main objective of our study was to determine the prevalence of hypertension and related risk factors in adult Bangladeshis. In addition, we want to determine significant factors for predicting hypertension.

Methods: The dataset used in this study was derived from the Bangladesh Demographic and Health Survey (BDHS) 2017–18 in Bangladesh, with a total of 11,961 adult respondents over the age of 18. To identify the association, we performed chi‐squared tests. The multinomial logistic regression model was used to determine the most significant variables to the development of hypertension and prehypertension in Bangladesh.

Results: Individuals over the age of 65 (adjusted odds ratio [AOR] = 9.423, confidence interval [CI]: 7.806–11.378) were almost 10 times more likely to develop hypertension in Bangladesh. In Bangladesh, those who are obese had a 4.36 times higher risk of hypertension and a 2.56 times higher risk of developing prehypertension. Therefore, we can conclude that the development of prehypertension and hypertension was significantly influenced by age, obesity, and diabetes.

Conclusion: These findings suggested that age, overweight, marital status, wealth index, education, and diabetes were significant risk factors for hypertension and prehypertension. The study’s findings will help Bangladesh’s government and policymakers develop effective policies and initiatives to prevent hypertension in adults.
User Preferences for Medical Digital Transformation: A Case Study of Orthodontic Services
Authors: Tsai I-Ching , Wei Hui-Chi , Chen Peng-Ting
Published: November 2024

Medical service digitalization not only simplifies the work of professionals but also facilitates communication with patients. However, how medical providers can implement digital transformation with limited resources and invest in digital technologies to achieve the best benefits is yet unknown. In this study, a review of the literature related to the orthodontic process and interviews with relevant orthodontics digital transformation stakeholders were conducted. Content analysis was subsequently performed to construct an evaluation framework for the digital transformation of the orthodontic service. Next, this study conducted questionnaire design, DRA model construction, and DEMATEL analysis. This research constructed an evaluation framework of the digital transformation of four procedures, namely, clinical evaluation (CE), therapeutic communication (TC), treatment procedures (TPs), and patient tracking (PT). Taking Taiwan as a case, a total of 88 valid questionnaires were obtained from orthodontic digital transformation stakeholders. The results of the DRA‐NRM show that the healthcare digital transformation process in Taiwan starts at CE and that the project needs policy support or business transformation. Next, the TC project is considered to be the most important stage of the medical digitalization transformation and requires a full investment of resources. In the subsequent TP phase, marketing efforts need to be stepped up to convince stakeholders of the benefits of medical digitization. Finally, PT can be postponed during digitalization until sufficient support and resource inputs are available. This study makes strategic recommendations for orthodontic digital conversion and establishes a plan and future direction for the digital transformation of healthcare services.
Aberrant Activation of Wound-Healing Programs within the Metastatic Niche Facilitates Lung Colonization by Osteosarcoma Cells
Authors: Reinecke James B. , Jimenez Garcia Leyre , Gross Amy C. , Cam Maren , Cannon Matthew V. , Gust Matthew J. , Sheridan Jeffrey P. , Gryder Berkley E. , Dries Ruben , Roberts Ryan D.
Published: November 2024

Purpose:

Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant bone cells coerce the lung microenvironment to support metastatic growth is unclear. The purpose of this study is to identify metastasis-specific therapeutic vulnerabilities by delineating the cellular and molecular mechanisms underlying osteosarcoma lung metastatic niche formation.

Experimental Design:

Using single-cell RNA sequencing, we characterized genome- and tissue-wide molecular changes induced within lung tissues by disseminated osteosarcoma cells in both immunocompetent murine models of metastasis and patient samples. We confirmed transcriptomic findings at the protein level and determined spatial relationships with multiparameter immunofluorescence and spatial transcriptomics. Based on these findings, we evaluated the ability of nintedanib, a kinase inhibitor used to treat patients with pulmonary fibrosis, to impair metastasis progression in both immunocompetent murine osteosarcoma and immunodeficient human xenograft models. Single-nucleus and spatial transcriptomics were used to perform molecular pharmacodynamic studies that define the effects of nintedanib on tumor and nontumor cells within the metastatic microenvironment.

Results:

Osteosarcoma cells induced acute alveolar epithelial injury upon lung dissemination. Single-cell RNA sequencing demonstrated that the surrounding lung stroma adopts a chronic, nonresolving wound-healing phenotype similar to that seen in other models of lung injury. Accordingly, the metastasis-associated lung demonstrated marked fibrosis, likely because of the accumulation of pathogenic, profibrotic, partially differentiated epithelial intermediates and macrophages. Our data demonstrated that nintedanib prevented metastatic progression in multiple murine and human xenograft models by inhibiting osteosarcoma-induced fibrosis.

Conclusions:

Fibrosis represents a targetable vulnerability to block the progression of osteosarcoma lung metastasis. Our data support a model wherein interactions between osteosarcoma cells and epithelial cells create a prometastatic niche by inducing tumor deposition of extracellular matrix proteins such as fibronectin that is disrupted by the antifibrotic tyrosine kinase inhibitor (TKI) nintedanib. Our data shed light on the non–cell-autonomous effects of TKIs on metastasis and provide a roadmap for using single-cell and spatial transcriptomics to define the mechanism of action of TKI on metastases in animal models.
Abstract A018: Alternative Polyadenylation Regulates Pancreatic Cancer Fibroblast Metabolism
Authors: Chaubey Aditi H , Feigin Michael E , Wagner Eric J
Published: November 2024

Dense, fibrotic stroma is a defining feature of pancreatic ductal adenocarcinoma (PDAC), comprising up to 90% of tumor volume. Multiple studies have shown that this stroma strongly influences cancer progression and response to treatment. Cancer Associated Fibroblasts (CAFs) make up the majority of the Tumor Microenvironment (TME) and directly alter the tumor landscape and response to therapeutics. CAFs are a heterogenous population comprising of a mixture of inflammatory, myofibroblastic, and antigen-presenting CAFs, with both pro- and anti- tumorigenic functions. While we have been able to define CAFs phenotypically, we lack a deeper understanding of the mechanisms underlying their transcriptional heterogeneity and ultimately their contribution to driving PDAC progression. Our lab has previously shown 3’UTR-Alternative Polyadenylation (APA) to be an important driver of genetic dysregulation in PDAC. APA is an important process regulating mRNA stability, protein localization, and expression, ultimately determining cellular processes such as proliferation, metastasis, and migration. We have also shown that increased 3’ UTR shortening is associated with the pro- tumorigenic inflammatory CAF subtype. However, how APA regulates CAF function is unknown. We are now trying to understand the possible mechanisms of these changes in vitro using human-derived CAF cell lines and treating them with a known pharmacological modulator of APA. We performed PAC-Seq analyses on these samples and show that important drivers of CAF metabolism are hindered by APA, ultimately affecting the ability of CAFs to support cancer cell growth. We find that inhibition of APA drives CAF migration and senescence phenotype and alters gene expression of critical genes required for CAF function, and metabolism. We identified a novel mechanism by which a key metabolic gene SLC7A11 is regulated by APA. To our knowledge, our work is one of the first studies to study how APA is an important regulator of CAF function.

Citation Format: Aditi H Chaubey, Michael E Feigin, Eric J Wagner. Alternative Polyadenylation Regulates Pancreatic Cancer Fibroblast Metabolism [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 A018.
Abstract B008: Exploring the Dual Roles of RNAs as Oncogenic Drivers and Therapeutic Targets in Cancer: A Cross-Sectional Study
Authors: Gameel Fathelrahman M
Published: November 2024

RNAs have emerged as pivotal molecules in the complex landscape of cancer biology, acting as both drivers of oncogenesis and therapeutic targets. This cross-sectional experimental design research explores the dual roles of RNAs, particularly focusing on the interplay between non-coding RNAs (ncRNAs), messenger RNAs (mRNAs), and their regulatory networks in various cancer types. The study systematically analyzes RNA expression profiles across a broad spectrum of cancer samples, employing high-throughput sequencing technologies combined with bioinformatics tools to identify key RNA species that contribute to tumorigenesis. The experimental design includes the collection of tumor and adjacent normal tissues from patients diagnosed with breast, lung, and colorectal cancers. RNA extraction and sequencing are performed to generate comprehensive expression profiles. Differential expression analysis is conducted to pinpoint RNAs that are significantly dysregulated in cancerous tissues compared to their normal counterparts. Subsequently, functional assays, including RNA interference (RNAi) and CRISPR/Cas9-mediated gene editing, are utilized to validate the oncogenic or tumor-suppressive roles of these RNAs in cancer cell lines. To further elucidate the mechanistic pathways, the study integrates data from RNA-binding protein immunoprecipitation (RIP) and crosslinking immunoprecipitation (CLIP) assays, providing insights into the RNA-protein interactions that influence cancer progression. Additionally, the research evaluates the therapeutic potential of targeting these RNAs, using small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) in preclinical cancer models. Preliminary findings highlight the significance of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) in modulating key signaling pathways involved in cell proliferation, apoptosis, and metastasis. This study underscores the importance of RNA-based diagnostics and therapeutics, paving the way for innovative treatment strategies in cancer management.

Citation Format: Fathelrahman M Gameel. Exploring the Dual Roles of RNAs as Oncogenic Drivers and Therapeutic Targets in Cancer: A Cross-Sectional Study [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 B008.
Abstract I007: Cellular response to dsRNA and PACT-mediated regulation
Authors: Ahmad Sadeem , Hur Sun
Published: November 2024

The innate immune sensor PKR for double-stranded RNA (dsRNA) is critical for antiviral defense, but its aberrant activation by cellular dsRNA is linked to various diseases. The dsRNA-binding protein PACT plays a critical yet controversial role in the PKR pathway. We demonstrate that PACT is a direct and specific suppressor of PKR against endogenous dsRNA ligands like inverted-repeat Alu RNAs, which robustly activate PKR in the absence of PACT. PACT-mediated inhibition does not require dsRNA sequestration; instead, a substoichiometric amount of PACT is sufficient. PACT inhibits PKR through low-affinity interactions that are most effective when both are bound to the same dsRNA molecule. Consequently, PACT’s inhibition of PKR is more robust with longer and less abundant dsRNA, and minimal with abundant or short dsRNA. Thus, PACT functions as a rheostat, setting the PKR activation threshold for long endogenous dsRNA without altering its inherent activity, revealing new mechanisms for establishing self-tolerance.

Citation Format: Sadeem Ahmad, Sun Hur. Cellular response to dsRNA and PACT-mediated regulation [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 I007.
Abstract I009: Leveraging engineered virus-like particles for protein and RNA delivery
Authors: Raguram Aditya
Published: November 2024

Precision gene editing agents enable the manipulation of genomic DNA in living organisms and raise the possibility of treating the root cause of many genetic diseases. However, realizing the full promise of therapeutic gene editing requires the ability to safely and efficiently deliver gene editing agents into relevant tissues and cell types. We developed engineered virus-like particles (eVLPs) that efficiently package and deliver gene editing proteins or RNAs into cells in culture and in mice1. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient gene editing in several primary mouse and human cell types. Single injections of eVLPs into mice supported therapeutic levels of gene editing in multiple tissues, including liver and retina. Off-target gene editing from eVLPs was virtually undetected, an improvement over canonical viral delivery methods. Recently, we further improved the delivery potency of eVLPs by applying a novel directed evolution platform to identify eVLP capsid mutants that exhibit improved properties. Collectively, these results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and non-viral delivery. 1. S. Banskota*; A. Raguram*; S. Suh; S. W. Du; J. R. Davis; E. H. Choi; X. Wang; S. C. Nielsen; G. A. Newby; P. B. Randolph; M. J. Osborn; K. Musunuru; K. Palczewski; D. R. Liu. Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins. Cell 185, 250–265 (2022).

Citation Format: Aditya Raguram. Leveraging engineered virus-like particles for protein and RNA delivery [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 I009.
Abstract PR007: To the tumor and beyond: Tales of a holistic miRNA delivery vehicle
Authors: Kasinski Andrea L
Published: November 2024

Like the challenges and skepticism that faced the antibody therapeutics field over a decade ago, RNA therapeutics is facing the same. And, like the antibody therapeutics field, we are beginning to realize the clinical impact of RNA therapeutics amiss these challenges. This is most clearly highlighted with the recent approval of mRNA vaccines and RNAi drugs targeted to the liver. Unfortunately, RNA-based drugs targeted to tumors is lagging behind, even with countless years of work that has revealed the power of using RNAi for treating oncological diseases. Lack of success is attributed to inability to deliver RNAi safely and effectively. A successful delivery agent requires multiple features. First, the agent must deliver the RNA specifically to the intended cells. Second, the agent must have a large therapeutic window, meaning that toxicity, if observed, should occur at doses that are orders of magnitude higher than the therapeutic dose. Third, if delivery of the RNA is by way of a specific ligand and receptor pair, as is the case herein, the RNA must successfully escape the endosome. Simply swelling the endosome is not enough if noncovalent interactions between the ligand and the receptor cannot be disrupted. Fourth, the RNA should include appropriate stabilizing modifications to increase intracellular half-life that will reduce dosing and cost. Through hard work and dedication, we have come up with an inclusive, easily synthesized, intramolecular molecule that achieves all of these essential features. Here, the challenges we face, the hurdles we have overcome, and the barriers that still remain with achieving success in reveling the clinical potential of miRNAs as anti-cancer therapeutics will be presented.

Citation Format: Andrea L Kasinski. To the tumor and beyond: Tales of a holistic miRNA delivery vehicle [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 PR007.
Asymptomatic parasitic worm thelazia callipaeda infection found during phacoemulsification: A case report
Authors: Chen Xinzhu , Guo Hanmu , Li Yanting , Lu Peirong
Published: November 2024

Introduction:We report a case of asymptomatic thelazia callipaeda infection discovered incidentally during phacoemulsification cataract surgery in March 2024. Case presentation: A 77-year-old male patient presented with complaints of blurred vision. During a slit-lamp examination, trichiasis was observed, but the patient had no foreign body sensation or itching. He was diagnosed with cataract and underwent phacoemulsification cataract surgery. During the surgery, a white, wriggling worm was discovered in the conjunctival sac and removed. It was later identified as thelazia callipaeda. The surgical eye was thoroughly washed and received anti-inflammatory medication postoperatively. No recurrence or new symptoms were reported during the 3-month follow-up period. Conclusions: Thelazia callipaeda infection can be asymptomatic and incidentally discovered. A detailed preoperative examination, such as turning over the upper and lower eyelids to check the conjunctival sac, is necessary before the surgery. When a worm is discovered during surgery, it is crucial to remove it completely and thoroughly clean and disinfect the conjunctival sac.
Combined [18F]-FDG PET-MR Imaging: A promising tool for diagnostics of small bowel Crohn’s disease
Authors: Mattila Juho , Kallio Johanna , Löyttyniemi Eliisa , Nuutila Pirjo , Koffert Jukka
Published: November 2024

Introduction

Diagnostics of small bowel Crohn’s disease (CD) can be difficult. Combined positron emission tomography-magnetic resonance enterography (PET-MRE) can be used to evaluate intestinal metabolism, but clinical use has been limited due to accessibility, costs, absence of standardized methods and diagnostic thresholds. Our aim was to show that combined PET-MRE can be used to diagnose active small bowel CD.

Methods

We performed a fusion PET-MRE-scan with [18F]-FDG-tracer to 30 patients with suspected small bowel CD in colonoscopy. Standardized uptake values (SUV) were measured from small bowel. The diagnosis was confirmed with small bowel capsule endoscopy. Clinicians chose appropriate medication to each patient blinded from SUV-results. Endoscopic, laboratory and MRE-findings were investigated in relation to SUV.

Results

Fusion PET-MRE outperformed MRE in diagnostic accuracy. Patients diagnosed with CD (N=24) had higher SUV than patients not diagnosed with CD (N=6) (3.34 vs. 1.84, p=0.022). A diagnostic cut-off at SUV at 2.5. could be used (AUROC=0.81). A higher SUV predicts need for immunosuppressive medication (p=0.0026) and biologics (p=0.0005). SUV correlates positively with SES-CD-score (Simple Endoscopic Score for Crohn’s Disease), fecal calprotectin and CRP and negatively with Hb and serum albumin.

Conclusion

In future, [18F]-FDG PET-MRE can be used in diagnostics of small bowel CD as a safe alternative for capsule endoscopy. High SUV can predict a more progressive disease course and need for more advanced therapies.
Domenico Scarlatti em Portugal: o som Italiano no MM 58 da Universidade de Coimbra
Authors: Cardoso José Maria Pedrosa
Published: November 2024

Para conhecer Domenico Scarlatti (1685-1757), a sua vida e a sua obra, é obrigatório segui-lo em Portugal. Todavia, para além de estudos pontuais, não existe uma avaliação rigorosa e completa do rasto português de Scarlatti. Do mesmo modo, falta a correcta avaliação e justificação da sua obra portuguesa: a que foi intencional e a que produziu e deixou ao cuidado e interesse dos seus amigos. Sem pretender eliminar a lacuna do conhecimento, este trabalho responde simplesmente a um desafio feito à sombra da celebração do tricentenário do nascimento de Carlos Seixas (1704-1742) e à luz dos manuscritos da Universidade de Coimbra: explicar a presença de uma sonata de Domenico Scarlatti, como nº 10 do índice de um volume com 30 Tocatas de Carlos Seixas.
A Interpretação Pianística da Fantasía Bætica (1919) de Manuel de Falla
Authors: Harper Nancy Lee
Published: November 2024

Manuel de Falla é conhecido como compositor de obras de carácter espanhol. No entanto, apesar de possuir características bem andalusas, a sua última obra de virtuosidade pianística - a Fantasía Bætica (1919) - é considerada como a obra mais abstracta que alguma vez ele compusera para piano a solo. A obra revela toda a sua polémica nas várias gravações disponíveis, tanto históricas, como actuais. Cheia de figuras guitarrísticas - pouco pianísticas - o desafio técnico é grande. É, de facto, uma obra simplesmente incómoda de tocar. No entanto, o maior problema situa-se a nível da interpretação. Poucos pianistas conseguem entender a sonoridade e expressão necessárias para ultrapassar os problemas técnicos. Na opinião da autora, a obra reúne características francesas revestidas numa postura espanhola. Serão aqui oferecidas algumas considerações históricas e analíticas, para melhor poder decifrar o problema da interpretação desta peça.
Abstract 4119908: Outcomes for heart failure patients with reduced ejection fraction attending emergency department and discharged within 24 hours versus those admitted patients in heart failure unit.
Authors: Alalawi Mohamed , Begum Taheba , Eltahir Aya , Peterzan Mark , Knott Kristopher , Ray Robin , Shanmugam Nesan , Anderson Lisa , Ghazal Heba , Jouhra Fadi , Macken Elizabeth Lilly
Published: November 2024

Introduction:
Heart failure (HF) is a clinical syndrome with increasing prevalence. Currently, there are extensive evidence-based therapies targeted at managing patients with heart failure and reduced ejection fraction (HFrEF) to improve outcomes. The National Heart Failure Audit shows the quality of inpatient care (specialist review, discharge medication etc) is related to outcome. This study aimed to evaluate the current practice at a London tertiary centre hospital in managing patients with heart failure and compared outcomes in patients who had a short course of admission (less than 1 day) with those who had a more prolonged course of admission.

Method:
Retrospective data was collected from a London tertiary centre hospital database for consecutive patients from Sep/2022 till Sep/2023. Statistical analysis was performed using Chi-Square test. The eligibility criteria included a new or previous diagnosis of HF with left ventricular ejection fraction (LVEF) < 40%. Patients were divided into two groups: Group A included 40 eligible patients who were admitted and discharged from the emergency department (ED) within 24 hours. Group B included 37 eligible patients who were admitted and discharged from the dedicated heart failure unit after 10-15 days of hospital admission.

Results:
In Group A, prescribing guideline-directed medical therapy (GDMT) was lower compared to Group B; Renin-Angiotensin-Aldosterone Inhibitors (47.50% vs. 94.59%), beta blockers (55% vs. 91.89%), mineralocorticoid receptor antagonists (12.50 %vs. 94.59%), and sodium-glucose co-transporter 2 inhibitors (15% vs. 89.19%). More patients in Group B received all four pillars of GDMT (86.49%) compared to Group A (5%). At 6-month follow-up,18.75% were on 4 GDMT in Group A versus 92% in group Group B. Re-admission within 6 months was higher in Group A (30%) compared to Group B (16.22%); however, the difference was not statistically significant (P value: 0.153). Higher mortality rates were observed in Group A (mortality rate: 20%) compared to Group B (mortality rate: 2.70%), with statistical significance (P value: 0.018).

Conclusion:
This study showed that HFrEF patients admitted to a specialist heart failure unit achieve higher rates of GDMT and have significantly improved outcomes compared to those who had a shorter inpatient stay and discharged from the emergency department. These findings underscore the high risks associated with rapid discharge from hospital on incomplete medical therapy.
Abstract 4138242: Association of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with procedural complications and in-hospital outcomes from left atrial appendage occlusion (LAAO) device implantation in elderly (>80 yrs) patients with atrial fibrillation (AF)
Authors: Ahmed asmaa , Osama Muhammad , Naeem Nauman , CHUPRUN DMITRY , Rao Mohan
Published: November 2024

Background:
LAAO has been used as an alternative strategy for stroke prevention in selected patients with AF, however there is very limited data about the outcomes in elderly patients with kidney disease.

Methods:
The National Inpatient Sample was queried for LAAO in the US between 2015–2020. Hospital outcomes were assessed for elderly patients undergoing LAAO in three cohorts; no CKD, CKD and ESRD.

Results:
A total of 31,360 elderly patients undergoing LAAO were identified in the study period; 23,250 (74.1%) had no CKD, 7,610 (24.2%) had CKD, and 500 (1.5%) had ESRD. CKD and ESRD were independently associated with higher odds of in-hospital mortality [aOR 3.06, 95 % CI (1.805-5.207), p <0.001)] & [ aOR 9.69 ,95% CI (3.52-26.64), p <0.001], cardiovascular complications [ aOR 1.43 ,95% CI (1.208-1.696), p <0.001] &[ aOR 3.41 ,95% CI (2.12-5.48), p <0.001], p <0.001], neurological complications [aOR 1.2 ,95% CI (1.05-1.36), p=0.006] &[aOR 1.58 ,95% CI (1.07-2.33), p=0.019], gastrointestinal and hematological complications [aOR 1.22 ,95% CI (1.06-1.39), p=0.003] &[ aOR 1.71 ,95% CI (1.16-2.52), p <0.001] respectively when compared to patients with no CKD. CKD was independently associated with higher odds of renal complications compared to patients with no CKD [aOR 5.34 ,95% CI (4.532-6.303), p <0.001]. In comparison to patients with ESRD, patients with CKD had significantly higher odds of renal complications [aOR 8.01 ,95% CI (3.28-19.57), p <0.001] with no significant difference in the odds of in-hospital mortality [aOR 0.4 ,95% CI (0.14-1.12), p=0.08]. In terms of resource utilization, length of stay didn’t differ with different kidney functions (1(1-1) for the three cohorts). However the ESRD cohort had the highest hospitalization costs compared to the CKD and no CKD cohorts ($26.113 ($19.728 -$34.362) vs. $25.799 ($20.231-$32.943) vs. $24.894 ($19.641-$31.373), p <0.001).

Conclusion:
The prevalence of CKD and ESRD was around 25.7% in elderly patients with AF undergoing LAOO. CKD and ESRD were independently associated with higher odds of in-hospital mortality compared to patients with no CKD while CKD was independently associated with higher odds of renal complications after LAAO.
Abstract 4138273: Acceptability and Gain of Knowledge of Community Educational Tools About Rheumatic Heart Disease Integrated With Screening In Low-Income Settings
Authors: Abrams Jessica , Sable Craig , Spaziani Alison , Zuhlke Liesl , Cardoso Clareci , Vinhal Wanessa , Ribeiro Isabely , Oliveira Kaciane , Amaral Ingred Beatriz , Nunes Maria , Diniz Marina , Fraga Lucas , Paula Luiza , Coelho Cecilia , TACURI CHAVEZ LUZ MARINA , Lemos Larissa , Correia Julliane , Ribeiro Antonio , Nascimento Bruno
Published: November 2024

Background:
Rheumatic heart disease (RHD) causes 305,000 premature annual deaths, and education is one of the strategies to diminish disease burden. International RHD foundations aim do provide preventive and control efforts for RHD. We aimed to assess the acceptability and gain of knowledge of a series of education flipcharts presented during screening programs in high-burden areas of Brazil.

Methods:
Four flipcharts (“Introduction to rheumatic fever (RF) and RHD”, “RHD and pregnancy”, “RHD and surgery” and “RHD community awareness”) were developed over 3 years and taught during 36 months to patients, community, health and education professionals in Minas Gerais state. Training included in-person interactions and virtual workshops. Pre and post-training questionnaires were applied through an online and printed surveys in 2021 and 2022, and post-education evaluations were conducted from January 2023 to April, 2024.

Results:
Flipchart training was successfully delivered to 112 education professionals, 574 health providers and 598 community members (N=1284): 899 (70%) were enrolled in primary care, and 1109 (86%) responded the surveys. Among respondents of the survey for health and education professionals (N=589), 240 (41%) had been educated about RHD in the previous year. 569 (96%) learned any new information; the content was all new for 21 (4%). Nearly all professionals reported that flipcharts could improve patients’ lives (571, 97%) and felt confident to use the tool with someone with no knowledge about RHD (533, 91%); 86% of the teachers said they would use flipcharts as educational tools. In the survey for community / schoolchildren (N=520) only 128 (25%) respondents had previous education on RHD, 510 (98%) reported that learned new information, and content was completely new for 242 (47%). A total of 430 (83%) individuals reported that they will discuss RHD with families and community. All qualitative written reports were positive. In 2021/2022, 218/485 (45%) health and education professionals responded the pre/post questionnaire. Knowledge about RHD increased after training: RF as the cause of RHD (56% vs 86%), use of Benzathine Penicillin G (50% vs 97%), frequency of antibiotic prophylaxis (32% vs 90%) and overall moderate or expert understanding of RF or RHD (30% vs 82%).

Conclusion:
Flipchart educational sessions about RHD had a very positive acceptability in high-risk Brazilian populations, with remarkable gain of knowledge for health professionals.
Abstract 4138281: Relationship of Collagen Metabolism Biomarkers, Left Atrial Fibrosis and Ablation Outcome in Atrial Fibrillation
Authors: Malas Waddah , Poellinger Nicholas , Diaz Gabriel , Ikram Mashaal , Joyce Cara , Hoppensteadt Debra , Fareed Jawed , Vasaiwala Smit , Wilber David , Syed Mushabbar
Published: November 2024

Introduction:
Inflammation and fibrinogenesis in the left atrium are hypothesized to play a major role in the development of atrial fibrillation (AF). We previously showed that collagen metabolism biomarkers (CMB) are significantly elevated in patients with AF compared to healthy controls.

Objective:
We sought to investigate the relationship between CMB, Left Atrial Fibrosis (LAF) and AF recurrence after ablation.

Methods:
Patients with AF undergoing ablation evaluation (N= 96) were prospectively enrolled between 2015 – 2020. Plasma samples were collected prior to ablation and analyzed for CMB using commercially available ELISA kits. Sixty-four patients underwent AF ablation and were followed for 6 months for AF recurrence. CMR was performed in 48 patients using cine and 3D high resolution, late gadolinium enhancement imaging on 3T MRI to measure LAF. Patients were classified into 2 groups dichotomized by the median LAF value.

Results:
Mean age was 60.3 ± 10.3 years, mean BMI 29.7 ± 4.9 kg/m2, mean CHA2DS2-VASc score 1.9 ± 1.4 and 27% were women. Paroxysmal AF was present in 52.5%. The median LAF score was 13.6% (IQR 9.8 – 21.7). High PINP, high CITP and low TIMP-2 were associated with high LAF score (Table 1). High CITP was also associated with recurrence of AF after ablation {4.26 ng/ml (IQR 3.22 - 4.65) vs 3.26 ng/ml (IQR1.92 - 4.25), P = 0.02}.

Conclusion:
Higher levels of PINP and CITP were significantly associated with higher LAF score in AF patients. TIMP-2 was associated with low LAF. Higher CITP was also associated with AF recurrence after ablation. Further larger studies are needed to better understand the relationship between collagen biomarkers, LA fibrosis and their clinical impact on rhythm control in AF.
Abstract 4138292: Smoking cessation is linked to regression of electrocardiographic left ventricular hypertrophy
Authors: Ninomiya Yuichi , Kawasoe Shin , Kubozono Takuro , Sai Eiko , Nuruki Norihito , Enokizono Kei , Kamada Hiroyuki , Yoshimoto Issei , Iriki Yasuhisa , Miyahara Hironori , Tokushige Koichi , Ohishi Mitsuru
Published: November 2024

Introduction/Background:
Electrocardiographic left ventricular hypertrophy is a strong predictor of cardiovascular morbidity and mortality. Further, smoking cessation provides a range of health benefits; however, its association with left ventricular hypertrophy is unclear.

Research Questions/Hypothesis:
What impact does smoking cessation have on left ventricular hypertrophy regression?

Goals/Aims:
We investigated the association between smoking cessation and regression of left ventricular hypertrophy.

Methods/Approach:
We compared electrocardiographic left ventricular hypertrophy between baseline and 6 years after smoking cessation follow-up visits in 752 non-hypertensive subjects (695 males, 47.8±9.2 years), from available datasets of 234 596 health check-ups. Left ventricular hypertrophy on ECG was assessed using the Sokolow-Lyon voltage criteria: SV1+RV5 (mV), with left ventricular hypertrophy defined as >3.5 mV.

Results/Data:
After 6 years of smoking cessation, body weight was found to increase (from 65.7±10.5 to 68.1±10.8 kg,
p
<0.0001) and systolic blood pressure also increased (from 112.9±12.7 to 122.0±14.2 mmHg,
p
<0.0001). Nevertheless, left ventricular hypertrophy on ECG regressed significantly (from 2.47 to 2.41 mV,
p
<0.0001), and the proportion fulfilling the criteria for left ventricular hypertrophy also decreased from 8.4 to 6.5%. In addition, the antihypertensive drug prescription rate due to elevated blood pressure after 6 years was 13.7% (103/752). Therefore, the regression of left ventricular hypertrophy with or without antihypertensive drug use was assessed. The results showed that left ventricular hypertrophy regressed significantly both [2.68→2.45 mV (
p
<0.0001)] and [2.44→2.40 mV (
p
=0.01)] in the groups administered (n=103) and not administered (n=649) antihypertensive drugs, respectively.

Conclusions:
Smoking cessation was found to be associated with regression of electrocardiographic left ventricular hypertrophy, despite being potentially associated with future weight gain, increased blood pressure, and with or without antihypertensive drugs. The results indicated that the health benefits of left ventricular hypertrophy regression from smoking cessation may outweigh the negative effects of weight gain and increased blood pressure from smoking cessation.
Abstract 4138321: Marine Microplastic Levels and the Prevalence of Cardio-Metabolic Diseases in Coastline Counties: An Ecological Analysis
Authors: Makwana Bhargav , khadke sumanth , Kumar Ashish , Nasir Khurram , Sheth Sudip , Shah Rikin , Wadhera Rishi , Kong Yixin , Navas-Acien Ana , Adamkiewicz Gary , Rajagopalan Sanjay , Al-Kindi Sadeer , Dani Sourbha , Moffatt-Bruce Susan , Ganatra Sarju
Published: November 2024

Background:
Micro- and nanoplastics are an emerging risk factor for the development of cardiovascular diseases. The association of marine microplastic levels (MMLs) with the burden of cardiometabolic diseases at a population level remains unexplored.

Aim:
To investigate the association between the average microplastic concentration in the ocean water body within 200 nautical miles of US coastline surveyed between 2015 and 2020, assigned to its most adjacent coastline county, and the prevalence of type 2 diabetes (T2D), coronary artery disease (CAD), and stroke in those counties.

Methods:
Microplastic concentration data within 200 nautical miles of the US coastline was spatially analyzed in ArcGIS Online to calculate mean MMLs. The coastal counties were stratified into four categories based on MMLs in the adjacent ocean water body: low (0-0.005 pieces/m
3
), medium (0.005-1 pieces/m
3
), high (1-10 pieces/m
3
), or very high (≥10 pieces/m
3
). BRFSS 2019-2020 survey data was used to correlate with the prevalence of type 2 diabetes (T2D), coronary artery disease (CAD), and stroke in these counties. Univariate and population-weighted multivariate quasi-Poisson regression adjusted for median county age, sex, physician access, and baseline community vulnerability theme of the US climate vulnerability index (CVI) was used to evaluate unadjusted and adjusted associations between disease prevalence and MMLs.

Results:
The mean age of the population was 43 ± 6 years. The mean prevalence of T2D, CAD, and stroke was significantly higher in counties with very high MMLs (13.03%, 8.94%, and 4.17%, respectively) compared to low MMLs (11.23%, 7.43%, and 3.51%, respectively, p < 0.001). The counties with very high MMLs exhibited an 18% higher adjusted prevalence of T2D (PR: 1.18 [1.13 – 1.23], p < 0.001), 7% higher adjusted prevalence of CAD (PR: 1.07, [1.03 – 1.11], p < 0.001), and 9% higher adjusted prevalence of stroke (PR: 1.09, 95% CI: 1.05 – 1.13, p < 0.001) compared to those with low levels.

Conclusion:
Our study establishes a significant association between marine microplastic levels and cardiometabolic disease prevalence in coastal counties.
Abstract 4138334: Identification and Immunological Characterization of Arrhythmia-Related Molecular Clusters in Ischemic Cardiomyopathy
Authors: Yang Hui , Wu Chenlu , Zhou Shenghua
Published: November 2024

Ischemic cardiomyopathy, a severe cardiac condition resulting from prolonged myocardial ischemia, is characterized by ventricular dilation, dysfunction, and an increased risk of life-threatening arrhythmias. Arrhythmia, a common complication in ischemic cardiomyopathy, is associated with poor clinical outcomes. Recent studies have indicated that the molecular heterogeneity of ischemic cardiomyopathy may contribute to the development of arrhythmias. Therefore, our study aimed to explore arrhythmia-related molecular clusters in ischemic cardiomyopathy and establish a prediction model for risk stratification.

Based on gene expression profiles of ischemic cardiomyopathy patients, we analyzed the dysregulation of arrhythmia-associated genes and the associated immune characteristics (Figure 1A-C). Using unsupervised clustering analysis, we identified distinct arrhythmia-related molecular clusters in ischemic cardiomyopathy patients (Figure 1D-F). Cluster-specific differentially expressed genes were further identified using weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis revealed significant differences in biological processes and pathways between the clusters (Figure 1G-H). Subsequently, we developed a prediction model using a random forest algorithm, which showed superior performance in distinguishing patients with different arrhythmia risks (Figure 1I-J). This forest model demonstrated excellent performance in one external validation datasets with AUC values of 0.891.

In conclusion, our study provides novel insights into the molecular basis of arrhythmias in ischemic cardiomyopathy and establishes a prediction model with potential clinical utility for risk stratification and targeted therapies. Further investigation into the specific mechanisms underlying the identified molecular clusters may reveal new therapeutic targets for the management of arrhythmias in ischemic cardiomyopathy patients.
Abstract 4138344: High fat diet induced the premature senescence of white adipose tissue through downregulating SIRT1 expression and promoting its S-nitroslyation modification
Authors: Xiang Qunyan , Guo Liling , Xu Jin , Xie Yingying , Zhu Liyuan , Wen Tie , Liu Ling
Published: November 2024

Background and Objectives:
The dysfunction of subcutaneous white adipose tissue is one of the early manifestations of obesity, which was associated with accelerated cellular process in aging induced by high fat-diet. The premature senescence of adipose-derived mesenchymal stem cells (AMSCs) is the key factor contributing to the aging of subcutaneous white adipose tissue. However, the underlying mechanism was not clear. Here, we explored the role and mechanism of obesity on the aging of white adipose tissue and AMSCs, and evaluated the anti-aging effect of resveratrol on this process.

Methods:
Subcutaneous white adipose tissue in non-elderly obese individuals and mice fed with high fat-diet was obtained to detect the TG metabolism and premature senescence. Then the postprandial triglyceride-rich lipoproteins (TRL) after high-fat diet was extracted, and the role and mechanism of TRL on the senescence of AMSCs were explored. Finally, the anti-aging effect of resveratrol on the white adipose tissue and AMSCs was evaluated.

Results:
Postprandial TG metabolism was abnormal in non-elderly obese humans and mice, and high-fat diet remarkably aggravated white adipose tissue senescence in mice (Fig. 1). TRL induced the premature senescence of AMSCs, with the downregulation of of silent mating-type information regulation 2 homolog 1 (SIRT1) via protein kinase B/forkhead box protein O1 pathway. Besides, the S-nitrosylation of SIRT1 was increased which was regulated by ten-eleven translocation 1/S-nitrosoglutathione reductase pathway. Resveratrol, a SIRT1 agonist, inhibited the TRL-induced AMSCs senescence, resulting in the amelioration of white adipose tissue senescence in obese mice (Fig. 2).

Conclusions:
These findings established a new mechanism for high-fat diet-induced white adipose tissue senescence and provided a potential therapeutic strategy for high-fat diet induced white adipose tissue senescence and metabolic disorders.