bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Practice and Safety of Endoscopic Balloon Dilation for Crohn’s Disease–Related Strictures: A Nationwide Claim Database Analysis in Japan
Authors: Moroi Rintaro , Tarasawa Kunio , Nagai Hiroshi , Shimoyama Yusuke , Naito Takeo , Shiga Hisashi , Hamada Shin , Kakuta Yoichi , Fushimi Kiyohide , Fujimori Kenji , Kinouchi Yoshitaka , Masamune Atsushi
Published: November 2024

Introduction: Although endoscopic balloon dilation (EBD) is a common therapeutic approach for managing strictures associated with Crohn’s disease (CD), the clinical application and complication rates of EBD remain unclear.

Methods: We collected admission data for patients who underwent EBD using a nationwide database. We compared EBD outcomes between ileal and colonic strictures, CD and ulcerative colitis, and CD and anastomotic strictures arising from cancer‐related surgery. Subsequently, propensity score matching was employed to facilitate comparisons between each group.

Results: The median duration of hospital stay was 4 days. Endoscopic hemostasis and urgent surgery rates after EBD for CD‐related strictures were considerably low (0.035% and 0.11%, respectively). Most patients with CD underwent only one EBD procedure during a single admission. Although no significant differences in patient backgrounds and severe complications were observed between ileal and colonic stricture in CD, multiple EBD procedures were more commonly performed for ileal strictures than for colonic stricture. Moreover, EBD for ileal stricture was more frequently conducted in high‐volume centers than in low‐volume centers. Regarding severe complications after EBD, no significant differences were observed between CD‐related strictures and ulcerative colitis or anastomotic strictures related to cancer surgery.

Conclusion: Our findings support the safe and effective use of EBD for both ileal and colonic strictures associated with CD. The clinical practice and safety outcomes of EBD for CD‐related strictures were comparable to those for strictures stemming from other etiologies.
Effect of Inlet Flow Rate on the Electrolytic Performance of a Water Electrolytic Cell Under Microgravity Conditions
Authors: Zhang Hongzhe , Wu Yuanhang , Huang Tiankun , Wang Ningfei , Wu Zhiwen
Published: November 2024

The study developed a two‐dimensional nonisothermal two‐phase flow model and investigated the gas–liquid phase distribution and temperature variations in a proton exchange membrane (PEM) electrolytic cell under microgravity conditions at different inlet flow rates. The impact of microgravity and terrestrial conditions on water electrolytic cells was directly compared. The results indicate that the water electrolytic cell demonstrates effective operation only when the voltage exceeds 1.7 V in a microgravity environment. Furthermore, an increase in inlet flow rate is conducive to electrochemical reactions, resulting in higher average hydrogen concentration, average hydrogen flow rate, and average current density. Under microgravity conditions, the absence of gravity results in lower average hydrogen concentration, flow rate, and current density compared to terrestrial conditions. Furthermore, an increase in inlet flow rate leads to a greater disparity in the performance of the electrolytic cell between microgravity and terrestrial conditions.
Weight and Lipid Levels in People Living With HIV and Initiating a Dolutegravir‐Based Regimen in a Resource Limited Setting
Authors: Chakanetsa Rudo , Chikwati Raylton P. , Chitungo Itai , Musarurwa Cuthbert , Tanyanyiwa Donald M. , Manasa Justen , Kouamou Vinie
Published: November 2024

Background: Following the 2018 World Health Organization’s (WHO) guidelines on HIV treatment and management, the Zimbabwean government has embraced dolutegravir (DTG)‐based regimens as the preferred first‐line treatment for people living with HIV (PLWH). Despite this implementation, there remains a paucity of knowledge on the potential associations between DTG‐based regimens, body weight and blood lipid levels among PLWH in Zimbabwe. Thus, the aim of this study was to investigate variances in body weight and blood lipid levels at two distinct timepoints—baseline and 6‐month post‐DTG initiation.

Methods: We conducted this study between November 2021 and April 2023 among ART‐naïve individuals initiating a DTG‐based regimen. Participants were recruited from a tertiary clinic in Zimbabwe. Body weight, standing height and blood lipid levels were measured at baseline and 6‐month post‐DTG. Changes in weight, body mass index (BMI) and lipids levels were assessed using the paired Student’s t‐test and Wilcoxon signed rank test. Multivariable logistic and linear regression analysis was used to assess risk factors associated with changes in weight, BMI and lipid levels.

Results: A cohort comprising 130 study participants, characterised by a mean (±SD) age of 40.0 (±11.0) years at baseline, was subjected to a 6‐month regimen of DTG‐based therapy. The outcomes revealed statistically significant alterations in various physiological parameters. Specifically, post the DTG‐based intervention, there were substantial increases observed in body weight (p < 0.001), BMI (p = 0.003), total cholesterol (TC) levels (p = 0.002) and high‐density lipoprotein cholesterol (HDL‐C) levels (p < 0.001) in comparison to their baseline values. Intriguingly, the corresponding triglyceride (TG) levels exhibited a noteworthy decrease (p < 0.001). Notably, individuals aged 40 years or older exhibited a positive association (p = 0.022) with increased TC levels and concurrent weight gain. Furthermore, current employment emerged as another factor positively linked to increased TC levels and weight gain.

Conclusions: Upon the initiation of DTG, discernible elevations were observed in body weight, BMI and lipid levels. This study represents the first comprehensive assessment of lipid profiles and weight gain among this population in Zimbabwe, filling a critical gap in the existing literature. These findings, while indicative of short‐term effects, underscore the imperative for further investigative efforts aimed at elucidating the prolonged consequences associated with DTG‐induced weight gain and increased lipid levels and its underlying mechanisms.
The Cancer Incidence Pattern in Isfahan Province: An Industrial Region in the Central Part of Iran
Authors: Lotfi Fereshte , Ravankhah Zahra , Rashidian Hamideh , Teimouri Fotooheh , Maracy Mohammad Reza , Javanmard Shaghyegh Haghjooy , Nahvijou Azin , Motlagh Ali Ghanbari , Roshandel Gholamreza , Zendehdel Kazem
Published: November 2024

Background: We aimed to study age‐standardized incidence rates (ASRs) of different cancer sites in Isfahan province, an industrialized city in the central part of Iran.

Method: We obtained cancer incidence data from 2014 to 2018 in the Isfahan population‐based cancer registry (PBCR). We studied quality indicators of PBCR and the validity of residential places for cancer patients. ASRs per 100,000 of common cancers were reported overall and at subprovincial levels.

Results: Overall, 42,994 new cancer cases were registered in Isfahan PBCR in 2014–2018, and 51.4% were male. A high percentage of microscopic verification (MV%) (78.1%) and a low percentage of death certificate‐only (DCO%) cases (7%) indicate the acceptable validity and completeness of this registry. The ASRs per 100,000 for all cancers combined were 173.7 in men and 171.1 in women. The most common cancers were prostate (ASR = 26.1), bladder (ASR = 19.9), and colorectum (ASR = 19.6) cancers in men and breast (ASR = 49.9), thyroid (ASR = 11.5), and colorectal (ASR = 15.6) cancers in women. Compared to the national reports in Iran, Isfahan province had a higher ASR of leukemia (13.6 in men and 8.9 in women), non‐Hodgkin lymphoma (14 in men and 9 in women), and bladder (19.9 in men and 3.4 in women) cancer. The ASR of childhood cancers was 182.7. Notably, the most frequent cancer was leukemia (ASR = 73.4). We observed a wide geographic heterogeneity of cancer incidence in different counties for some cancers like breast, prostate, leukemia, and colorectal cancers.

Conclusion: High incidence rates of hematological malignancies and bladder cancers in Isfahan province suggest further research to study the association between occupational and environmental exposures due to industrial pollution.
Switched Observer‐Based Event‐Triggered Safety Control for Delayed Networked Control Systems Under Aperiodic Cyber attacks
Authors: Li Shuqi , Chen Yiren , Shang Wenli , Deng Feiqi , Gao Xiaobin
Published: November 2024

The networked control systems (NCSs) under cyberattacks have received much attention in both industrial and academic fields, with rare attention on the delayed networked control systems (DNCSs). In order to well address the control problem of DNCSs, in this study, we consider the resilient event‐triggered safety control problem of the NCSs with time‐varying delays based on the switched observer subject to aperiodic denial‐of‐service (DoS) attacks. The observer‐based switched event‐triggered control (ETC) strategy is devised to cope with the DNCSs under aperiodic cyberattacks for the first time so as to decrease the transmission of control input under limited network channel resources. A new piecewise Lyapunov functional is proposed to analyze and synthesize the DNCSs with exponential stability. The quantitative relationship among the attack activated/sleeping period, exponential decay rate, event‐triggered parameters, sampling period, and maximum time‐delay are explored. Finally, we use both a numerical example and a practical example of offshore platform to show the effectiveness of our results.
CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis
Authors: MacLehose Richard F. , Ahern Thomas P. , Collin Lindsay J. , Li Aixin , Lash Timothy L.
Published: November 2024

Background:

We evaluated the impact of systematic bias due to loss of heterozygosity (LOH) and incomplete phenotyping in studies examining the relationship between CYP2D6 variants and breast cancer recurrence among women treated with tamoxifen.

Methods:

We performed a systematic review of the literature on tamoxifen, CYP2D6 variants, and breast cancer recurrence. A quantitative bias analysis was performed to adjust for LOH and incomplete phenotyping. Bias-adjusted results were then combined in a meta-analysis.

Results:

Thirty-three studies informed the bias analysis and meta-analysis on CYP2D6 variants and breast cancer recurrence and/or mortality. An unadjusted meta-analysis suggested increased risk of recurrence and/or mortality for poor relative to normal metabolizers [RR = 1.28; 95% simulation interval (SI), 1.04–1.58] with substantial heterogeneity (I2 = 27%; P for heterogeneity = 0.07). Adjusting for LOH and incomplete genotyping resulted in a slight change in the effect estimate and a decrease in heterogeneity (RR = 1.34; 95% SI, 1.10–1.63; I2 = 0%; P for heterogeneity = 0.17). Intermediate metabolizers had a slightly increased risk of recurrence and/or mortality relative to normal metabolizers (RR = 1.15; 95% SI, 1.00–1.34; I2 = 0%; P for heterogeneity = 0.89).

Conclusions:

Adjusting for biases such as LOH and incomplete genotyping reduced observed heterogeneity between studies. Individuals with poor CYP2D6 phenotypes were at increased risk for breast cancer outcomes compared with those with normal phenotypes.

Impact:

Reduction in CYP2D6 activity was associated with an increased risk of breast cancer recurrence and/or mortality, and results underscore the importance of quantitatively adjusting for biases when aggregating study results.

See related In the Spotlight, p. 221
Abstract A012: g3bp1-mediated stress granule formation drives melanoma initiation in zebrafish
Authors: Drake Kyle D , Formato Emily , Zon Leonard
Published: November 2024

Stress granules confer cancer cells the ability to withstand harsh biological conditions and impart tumorigenic translational states through mRNA sequestration. Despite advances in in vitro knowledge, mechanistic understanding of the endogenous influence of stress granules during tumorigenesis in vivo remains understudied. To address this, we use a zebrafish melanoma model where oncogenic human BRAF V600E is driven by the melanocyte master regulator mitfa in a p53 -/- background. Through vector-based genetic engineering, endogenous melanoma induction in these zebrafish can be developmentally staged from single cell to tumor. BRAF V600E ::p53 -/- melanocytes form a cancerized field (CF), from which a subset upregulate the melanocyte master regulator mitfa, creating a cancer precursor zone (CPZ). Transformation of CPZ cells to an embryonic, neural crest-like state facilitates their formation of an early tumor patch that inevitable develops into an overt tumor. Single cell RNAseq analysis of cells representing each melanoma stage showed that CPZ cells upregulate core stress granule markers, including g3bp1, tia1, tia1l, and nufip2. Immunostaining of g3bp1 in CF, CPZ, patch, and tumor cells revealed a significant induction of stress granules from the CF to CPZ transition (2 vs 10 stress granules/cell; N=3; p=0.034) that persists during the patch and tumor stage, indicating cell stress accompanies melanoma initiation and progression. Genetic disruption of g3bp1 through cell autonomous, melanocyte-specific CRISPR editing in zebrafish (N=10-13) causes delayed CPZ onset (P=0.012) and fewer CPZs to form (P=0.021). In turn, g3bp1-edited zebrafish have delayed tumor formation (P=0.026) and develop fewer tumors (P=0.006). To decipher the RNAs sequestered by stress granules during melanomagenesis, we performed RIPseq for G3BP1 in human A375 melanoma cells stressed with sodium arsenite. RNAs significantly bound to G3BP1 upon stress induction include major tumor suppressors, such as CDKN2A, RBM5, BIK, and RHOB. Together, these results suggest that endogenous g3bp1-mediated stress granule formation in melanoma initiating cells is tumorigenic in vivo and operates through the sequestration of tumor suppressive RNAs.

Citation Format: Kyle D Drake, Emily Formato, Leonard Zon. g3bp1-mediated stress granule formation drives melanoma initiation in zebrafish [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 A012.
Abstract A016: YBX1 is a negative regulator of post-transcriptional program associated with invasion and metastasis in cSCC
Authors: Sol Stefano , Mandinova Anna , Boncimino Fabiana , Todorova Kristina , Di Cicco Emery , Tebaldi Toma , Bucciarelli Giorgia
Published: November 2024

Y-box binding protein 1 (YB-1), which is encoded by YBX1 gene, is a multifunctional cold-shock protein that binds both DNA and RNA to orchestrate transcription as well as RNA processing and translation. Recently, we demonstrated that YBX1 is a post-transcriptional effector required for the maintenance of epidermal homeostasis. Although it was well known that YBX1 plays prominent pro-oncogenic roles in malignant transformation and cell invasion in a wide variety of cancers, the role of YBX1 in cutaneous squamous cell carcinoma (SCC) is poorly understood. Here, we report that YBX1 protein level is higher in SCC tumor compared with non-neoplastic skin, but it goes down during tumor progression, in invasive and metastatic states. Indeed, both in vitro and in vivo experiments show that YBX1 acts as an antagonist of SCC progression, inhibiting its migration, invasiveness and metastasis. YBX1 is predominantly found in the cytoplasm of SCC cells. Therefore, we focused on the role of YBX1 as a posttranscriptional regulator and performed an eCLIP-seq (crosslinking immunoprecipitation sequencing) to identify its direct RNA targets. We found that YBX1 binds pro-invasive RNA associated with cell-cell and cell-matrix adhesions. From the integration of eCLIP-seq data with RNA-Bisulfite Seq data, an increased number of m5C modifications was observed to be located within the 3'UTR and CDS of tumor-enriched YBX1 target regions. Upon silencing of YBX1, polysome fractionation analysis revealed that YBX1 KD regulates targets involved in cancer motility, revealing that the loss of function of YBX1 promotes migration and invasion at the post-transcriptional

Citation Format: Stefano Sol, Anna Mandinova, Fabiana Boncimino, Kristina Todorova, Emery Di Cicco, Toma Tebaldi, Giorgia Bucciarelli. YBX1 is a negative regulator of post-transcriptional program associated with invasion and metastasis in cSCC [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 A016.
Abstract A019: Identification and Genomic Analysis of miRNA-mRNA Binding Site SNPs in Hepatitis C Virus-Associated Hepatocellular Carcinoma
Authors: Butt Azeem M , Qamar Anum , Siddique Shafiqa
Published: November 2024

Hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths globally. MicroRNAs (miRNAs) play critical roles in gene regulation, and single nucleotide polymorphisms (SNPs) within miRNA binding sites can disrupt this regulation, potentially influencing HCC pathogenesis. The present study aims to identify and characterize SNPs within miRNA binding sites of genes associated with HCV- induced HCC (HCV-HCC). A comprehensive bioinformatics analysis workflow was devised. HCV-specific differentially expressed (DE) miRNAs and mRNAs were extracted from literature and databases. SNPs in the 3' UTRs of HCV-HCC genes were identified, and their impact on miRNA binding was predicted using PoymiRTS and TargetScan. RNAhybrid was used to estimate minimum folding energy (MFE) differences (ΔMFE) between mutant and wild types. Functional enrichment analysis was conducted to elucidate the biological processes affected by these SNPs. Our analysis revealed several significant alterations in miRNA-mRNA binding pairs due to SNPs within genes associated with HCV-HCC. For instance, among the downregulated genes in HCV-HCC, the SNP in CTSB (rs3088245; 193T>C) predicted to increase the stability of the miR-27b - CTSB duplex (ΔMFE: 1.4), suggesting enhanced binding and potentially improved repression of CTSB. Conversely, the SNP in EGR2 (rs61865883; 287 T>A) decreased the stability of the miR-140-5p - EGR2 mRNA interaction (ΔMFE: -1.9), suggesting a weaker binding affinity and potentially reduced repression of EGR2 expression. Considering the tumor suppressor role of EGR2, presence of this SNP is likely to reflect good prognosis. For the upregulated gene oncogene, XIAP, the SNP (rs6648556; 5892 T>C) is predicted to enhance the binding of miR- 200c (ΔMFE: 1.5), likely resulting in increased suppression of XIAP expression in patients carrying this SNP and improved prognosis. Our study emphasizes the importance of considering genetic variations in miRNA binding sites in the context of HCV-HCC. These SNPs may serve as genetic modifiers influencing disease susceptibility and progression. Further experimental studies are warranted to explore their potential as therapeutic agents and predictors of prognosis in HCV-HCC patients.

Citation Format: Azeem M Butt, Anum Qamar, Shafiqa Siddique. Identification and Genomic Analysis of miRNA-mRNA Binding Site SNPs in Hepatitis C Virus-Associated Hepatocellular Carcinoma [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 A019.
Abstract I004: Systematic Discovery and Annotation of Cancer Emergent Orphan non-coding RNAs in human Cancers
Authors: Goodarzi Hani
Published: November 2024

We recently described orphan non-coding RNAs (oncRNAs) as a class of cancer-specific small RNAs with the potential to play functional roles in breast cancer progression1. Here, we report a systematic search to annotate and characterize cancer-emergent oncRNAs across 32 tumor types. We also leverage large-scale in vivo genetic screens in xenografted mice to functionally identify driver oncRNAs in multiple tumor types. We have not only discovered a large repertoire of oncRNAs, but also found that their presence and absence represent a digital molecular barcode that faithfully captures the types and subtypes of cancer. Importantly, we discovered that this molecular barcode is partially accessible from the cell-free space as some oncRNAs are secreted by cancer cells. In a large retrospective study across 192 breast cancer patients, we showed that oncRNAs can be reliably detected in the blood and that changes in the cell-free oncRNA burden captures both short-term and long-term clinical outcomes upon completion of a neoadjuvant chemotherapy regimen.

Citation Format: Hani Goodarzi. Systematic Discovery and Annotation of Cancer Emergent Orphan non-coding RNAs in human Cancers [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 I004.
Abstract PR001: Targeting mRNA methyltransferase in RNA-dependent DNA repair in cancer therapy
Authors: Lan Li
Published: November 2024

The treatment of many solid tumors presents significant challenges with chemotherapy, radiation therapy, and the limited effectiveness of immunotherapy. Targeted therapy offers a promising approach, yet the lack of validated targets limits its applicability across the spectrum of solid tumors. Our past studies have revealed that an R-loop and mRNA-dependent DNA repair (RDDR) pathway, induced by damage at the transcribed regions of the genome, contributes to cell survival and drug resistance in cancer cells. This is particularly due to the high levels of transcription and DNA damage in these cells. We identified the RNA methyltransferase TRDMT1 as the primary modifier of mRNA methyl-5-cytosine in the RDDR pathway. Overcoming technical difficulties in monitoring RNA modifications, we developed the first TRDMT1 inhibitor (TRDMT1i) using in-house built cell-based and in vitro assays. We have identified highly potent and specific lead compounds that significantly reduce TRDMT1 activity at nanomolar concentrations. Our current lead TRDMT1 inhibitors meets most of the criteria that are required for optimal lead. Initial assessments involving the screening of normal and cancer cell lines, xenograft models, and patient specimens indicate that TRDMT1i sensitizes tumors with genomic instability when used as monotherapy. We aim to develop TRDMT1i as an investigational new drug (IND) for future clinical trials, initially targeting ovarian cancer as a monotherapy or in combination therapy for first-line maintenance and systematic therapy. Our goal is to pioneer the discovery of the RDDR pathway, leading to the development of innovative platforms and next-generation medications to revolutionize the targeting of mRNA modifications in cancer treatment.

Citation Format: Li Lan. Targeting mRNA methyltransferase in RNA-dependent DNA repair in cancer therapy [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 PR001.
Abstract PR003: Preventing and treating HPV-related Cancer with mRNA Therapy Expressing A DC-targeting Antigen
Authors: Jia William
Published: November 2024

Persistent human papillomavirus (HPV) infection is linked to several malignancies, highlighting the need for effective therapeutic vaccines. In this study, we tested a lipid nanoparticle-encapsulated mRNA vaccine expressing tHA-mE7-mE6. By mutating the E6 and E7 proteins to reduce their tumorigenicity and fusing them with a truncated influenza hemagglutinin protein (tHA) for better antigen uptake, we improved the vaccine’s efficacy. The tHA-mE7-mE6 mRNA vaccine showed superior results compared to mE7-mE6 mRNA, achieving complete tumor regression and preventing new tumors in an E6 and E7 positive model. It elicited a strong CD8+ T-cell response, with antigen-specific CD8+ T-cells found in the spleen, blood, and tumors. Additionally, the therapy increased DC and NK cell infiltration into tumors. Overall, this study demonstrates that the tHA-mE7-mE6 mRNA vaccine induces a potent anti-tumor immune response, showing promise for treating HPV-induced cancers and preventing recurrence.

Citation Format: William Jia. Preventing and treating HPV-related Cancer with mRNA Therapy Expressing A DC-targeting Antigen [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 PR003.
Abstract PR014: PVT1 fusion on extrachromosomal DNA (ecDNA) increases oncogene RNA stability and cancer cell growth
Authors: Yi Hyerim , Zhang Shu , Jones Matthew G , Belk Julia A , Swinderman Jason , Shi Quanming , Curtis Ellis J , Kanakaveti Vishnu P , Mischel Paul S , Chang Howard Y
Published: November 2024

Extrachromosomal DNA (ecDNA), highly amplified circular DNA, is widespread in human cancers and serves as a primary location for oncogene amplification. Due to its dynamic structural rearrangement and asymmetric inheritance during cell division, ecDNA increases tumor genome complexity, contributing to drug resistance and shortened patient survival. Here, we show that ecDNA-mediated genomic amplification is highly associated with transcript fusion events, which are prevalent in cancer and often lead to tumor development. We discovered that transcripts with the highest fusion events originate from genes amplified on ecDNA across ecDNA(+) cell lines. Notably, PVT1 (Plasmacytoma Variant Translocation 1) long noncoding RNA, which is known to be a hotspot for chromosomal translocation, is the most frequently fused RNA species in MYC/PVT1-amplified ecDNA(+) cancer cells. Exon 1 of PVT1 is the predominant fusion partner and confers RNA stability, increasing the RNA abundance of the partner oncogene. Using a model cell line with PVT1-MYC fusion on ecDNA, we found that RNA expression of PVT1-MYC increases in vivo in an ecDNA-dependent manner, while canonical MYC does not show a prominent increase. Additionally, ectopic expression of PVT1- MYC in MYC-depleted cancer cells provides higher rescue efficiency than canonical MYC. In contrast, a PVT1-MYC mutant that is unable to enhance RNA stability fails to rescue, highlighting the functional significance of PVT1-mediated RNA stabilization in cancer. This study unveils the link between PVT1 fusion and ecDNA in cancer, providing insights for developing diagnostic and therapeutic approaches tailored to target ecDNA.

Citation Format: Hyerim Yi, Shu Zhang, Matthew G Jones, Julia A Belk, Jason Swinderman, Quanming Shi, Ellis J Curtis, Vishnu P Kanakaveti, Paul S Mischel, Howard Y Chang. PVT1 fusion on extrachromosomal DNA (ecDNA) increases oncogene RNA stability and cancer cell growth [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 PR014.
Supplementary Figure S.15 from Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers
Authors: Kuznetsov Maxim , Adhikarla Vikram , Caserta Enrico , Wang Xiuli , Shively John E. , Pichiorri Flavia , Rockne Russell C.
Published: November 2024

Supplementary Figure S.15
O Bibliófilo Aprendiz
Authors: Moraes Rubens Borba de
Published: November 2024

“Colecionismo é atividade que demanda engenho e arte. No caso dos livros, exige-se tanto conhecimento quanto sensibilidade, isso porque, como nos ensina Rubens Borba de Moraes neste precioso O Bibliófilo Aprendiz, uma boa biblioteca é fruto de estudo, análise e reflexão, mas também da busca paciente e hodierna pelo objeto desejado. Porém, de nada adiantaria tanto esforço e investimento material, não fosse o colecionador dotado de espírito para reconhecer, nos pequenos detalhes, o caráter original e raro de um livro. A reedição cuidadosa e refinada desse clássico da bibliofilia constitui uma homenagem justa ao colecionador que não apenas amou e logrou constituir uma importante biblioteca, mas refletiu e deixou um legado fundamental para a bibliografia e a história dos livros”.
Espaço Profano e Espaço Sagrado na Música Luso-Brasileira do Século XVIII
Authors: Nery Ruy Vieira
Published: November 2024

O presente artigo pretende propor como linhas gerais de reflexão histórica para a abordagem da realidade musical luso-brasileira do Antigo Regime que, dadas as limitações do processo de laicização e de emergência da sociedade civil no Portugal e no Brasil setecentistas: 1. Na vida musical em todo o espaço lusófono o espaço profano tem menos peso do que nos outros países, e dentro dele o espaço privado sobrepõe-se de longe ao espaço público; 2. O espaço religioso continua a assegurar uma acumulação de práticas e funções sociais e artísticas muito mais amplo do que sucederia em outros países europeus e nas respectivas colónias; 3. Esta acumulação tem antecedentes históricos profundos que remontam já à prática do vilancico religioso dos séculos XVI e XVII;4. Como conseqüência destes factores, a própria natureza estética, estilística e técnico-musical da música sacra luso-brasileira do século XVIII acumula características "sacras" e "profanas"; 5. Nenhuma destas características pode ou deve ser lida como indicador de um factor de "atraso" em função de uma suposta bitola única da evolução musical européia; 6. A partilha de tendências estéticas à escala européia por parte da Música luso-brasileira do Antigo Regime deve procurar-se na análise da própria música e não no carácter profano ou religioso dos seus contextos de execução.
A Relação de Meio Século com a Música e Músicos de Portugal
Authors: Martins José Eduardo
Published: November 2024

O relacionamento de um músico com a panorâmica musical de uma nação pode ser estabelecido através das mais diversas vertentes: a admiração pelas Culturas de um povo, motivada por estágio curto ou prolongado, mas impregnante pela intensidade; laços a ratificarem o genético e o atávico; apreensão espontânea, esta, muitas vezes, independendo da presença física do estudioso; idealização de um modelo cultural, a emergir em determinado momento, movido pelas mais variadas causas. Seriam estas, basicamente as amarras necessárias para que haja a relação.
Abstract 4138427: Frailty Measured by The Risk Analysis Index as a Predictor of In-hospital Outcomes After PCI: A Retrospective Nationwide Analysis of 449,857 Patients
Authors: Fouad Michele , Nawlo Ahmad , Abdelsayed Kerollos , Alshaker Hassan , Abbas Kirellos Said , Akkawi Abdul Rahman , Almohtasib Yazan , Abdelazeem Basel , Kawsara Mohammad
Published: November 2024

Background:
Frailty emerges as an independent predictor of adverse outcomes post-cardiac procedures including percutaneous coronary intervention (PCI). Various indices have been developed to assess frailty, but no gold standard exists. The Risk Analysis Index (RAI) is a promising frailty index that enables better preoperative evaluation for personalized care.

Objective:
To assess RAI as a preoperative assessment tool for predicting post-PCI in-hospital outcomes.

Methods:
In this retrospective cohort analysis, The National Inpatient Sample was queried from 2016 to 2020 for patients who underwent PCI. Our cohort was stratified depending on RAI score into Robust, Prefrail, Frail, and Very Frail (
Figure 1.A
). Primary outcomes were non-home discharge (NHD), mortality, and extended length of stay (defined as length of stay exceeding 75% of the cohort) (eLOS). The statistical significance of difference in the primary outcomes was assessed amongst the four frailty groups using The Chi-square test (

x
2

). In addition, RAI was tested for its ability to predict the primary outcomes using the area under the curve (AUC).

Results:
The study sample included 449,857 unweighted admissions, of which 67.09% were males, the median age was 50 (IQR: 46-54), 22.6% were Robust, 54.9% were Prefrail, 19% were Frail, and 3.5% were Very Frail (
Figure 1.A
). Increasing RAI frailty scores (robust versus very frail) correlated with significantly higher NHD (7.64% vs. 61.54%;
p<0.0001
), eLOS (11.42% vs. 54.33%;
p<0.0001
), and mortality (1.25% vs. 7.06%;
p<0.0001
) (
Figure 1.B
). RAI effectively predicted NHD (C-statistic 0.73; 95% CI 0.72-0.73), eLOS (C-statistic 0.68; 95% CI 0.67-0.68), and mortality (C-statistic 0.66; 95% CI 0.65-0.66) (
Figure 1.C
).

Conclusion:
Frailty, measured by RAI, is a significant predictor of post-PCI in-hospital outcomes, including eLOS, NHD, and mortality. RAI facilitates better patient stratification and personalized care strategies in clinical practice.
Abstract 4138472: Bioactive Oxylipins Predict Coronary Artery Calcification Severity in Heart Failure with Preserved Ejection Fraction
Authors: Aradhyula Vaishnavi , Fares Anas , Vergis John , Dube Prabhatchandra , Sherafati Alborz , Kloster Alex , XKhatib-ShahidiX XBellaX , Elzanaty Ahmed , Sajdeya Omar , Manandhar Sareeta , Brewster Pamela , Maddipati Krishna Rao , Smith Robert , Haller Steven , Kennedy David , Khouri Samer , Gupta Rajesh
Published: November 2024

Background:
Inflammation is a common underlying cause in atherosclerosis and heart failure with preserved ejection fraction (HFpEF). Recent data have highlighted the critical role of circulating bioactive polyunsaturated fatty acid oxidized lipids, or oxylipins, in initiating and resolving inflammation. We sought to study the role of oxylipins in predicting coronary artery calcification (CAC) in HFpEF.

Hypothesis:
We hypothesize that oxylipins can predict and distinguish CAC severity in HFpEF patients.

Methods:
We collected venous blood samples during right heart catheterization from 71 HFpEF patients. We categorized patients by CT-based CAC severity: none (control; n=16), mild (<25% CAC, n=7), moderate (26-50% CAC, n=22), and severe (>50% CAC, n=26). We measured 143 oxylipins in all study participants using mass spectrometry. Along with unpaired T-tests, machine learning analysis was used to determine lipid permutation importance and evaluate predictive accuracy for CAC severity.

Results:
Demographic variables showed no significant differences between groups. Increased total cholesterol (p=0.031) and low HDL (p=0.011) were associated with CAC severity. Pro-inflammatory 12(S)-HHTrE (a degradation product of TxA2) levels were elevated in severe CAC vs control (p=0.031). The inactivated anti-inflammatory 5,6 DiHETrE levels were higher in moderate CAC vs control (p=0.032) and severe CAC vs control (p=0.021). Out of 143 oxylipins, the panel of LTB5, 11(R)-HEDE, 20-HETE, 5-HEPE, 11(12)-EpETrE, 14(15)-EpETE, 19,20-DiHDoPE, PD1, and 5-oxoETE were the most significant predictors of severe vs non-severe (none, mild, moderate) CAC, with 88.88% predictive accuracy.

Conclusion:
In HFpEF patients, CAC severity can be predicted by a novel panel of circulating, bioactive venous oxylipins.
Abstract 4138488: Association Between Guideline-directed Medical Therapy and Reintervention Risk at 2 Years Following Peripheral Vascular Interventions
Authors: Callegari Santiago , Cleman Jacob , Rahman Mufti , Capuano Isabella , Smolderen Kim , Mena-Hurtado Carlos , Romain Gaelle
Published: November 2024

Introduction:
Patients with peripheral artery disease (PAD) undergoing peripheral vascular interventions (PVI) face frequent reinterventions. The association between the use of guideline-directed medical therapy (GDMT) and reintervention risk is unclear, we therefore aimed to study the association between GDMT and 2-year reintervention risk using the largest national vascular registry.

Methods:
PVI procedures in patients with claudication or chronic limb-threatening ischemia between 2017-2018 were abstracted from the Vascular Quality Initiative (VQI) registry. GDMT was defined as statin, antiplatelet, and ACE/ARB if hypertensive prescribed at discharge. Reintervention was obtained from Medicare claims data. Propensity score of no GDMT vs. GDMT was calculated using 22 preprocedural variables followed by 1:1 matching of patients. The 2-year cumulative incidence of reintervention and subhazard ratios (sHR) for 2-year reintervention risk in no GDMT vs. GDMT were assessed using Aalen-Johansen method and Fine-Gray model, respectively, to account for the competing risk of death.

Results:
A total of 13,244 patients (6,622 by GDMT group) were included after 1:1 matching (mean age 72.0 ± 9.9, female 38.9%, white 79.4% Black or African American 15.3%) . At 2 years, the cumulative incidence of reintervention was 43.0% (95% CI 41.0%-44.9%) for patients with no GDMT vs. 41.2% (95%CI 39.4-43.0) for the GDMT group (P=0.293). Not receiving GDMT was not associated with 2-year risk of reintervention (sHR: 1.03 95%CI 0.97-1.10; P=0.293).

Conclusion:
Around 40% of patients undergoing a PVI will have a reintervention at 2 years. The receipt of GDMT at discharge was not associated with a lower reintervention risk at 2 years, as currently assessed. Further granular measures of GDMT should integrate adherence information, as well as information on other lifestyle and cardiovascular risk management to obtain a more complete assessment of a potential association with reintervention risk.
Abstract 4138494: Remote Blood Pressure Monitoring and Intervention as a better and cost-effective method of Hypertension control compared to Usual care: A Systematic Review
Authors: Meda Venkata Sai Abhilash , Adhikari Ashok , Tadigotla Chandana , Gaddam Ashwith Reddy , Vaghamashi Yogeshkumar , Gupta Umang , Panjiyar Binay
Published: November 2024

Introduction/Background:
Hypertension is a leading cause of morbidity and mortality. Despite treatment recommendations and encouragement of lifestyle changes, the actual rate of blood pressure control is still not at par. Remote intervention methods have been shown to achieve better rates of blood pressure control utilising lesser resources and lower healthcare costs. We conducted a systematic review by qualitatively evaluating the potential impact of remote monitoring and interventions compared to usual care in controlling Hypertension.

Research Question:
Are remote monitoring techniques and interventions better than usual in-person blood pressure checks for hypertension control?

Methods:
We did a comprehensive literature search of Pubmed/MEDLINE, Google scholar, Cochrane central Library, PLOS ONE, ScienceDirect and Clinicaltrials.gov to identify eligible randomised control trials and clinical trials published between July 2013 and May 2025. A Risk of Bias assessment was conducted using Cochrane Risk of Bias tools such as ROB-2 for randomised control trials and ROBINS-1 for cohort studies. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results:
Of the 5,185 records analysed, 10 randomised control trials, 1 cohort study and 1 implementation study satisfied our inclusion criteria. Compared to usual care, remote monitoring methods showed significant difference in systolic blood pressure control at 6-12 months in 9 out of 12 studies, while 3 studies did not show any significant difference. Quality of life, physical health, mental health and drug compliance have also shown a significant positive difference in patients. Remote self monitoring interventions were found to be more cost-effective than usual care. They also reduced the load of patients seeking appointments for hypertension control thereby improving the quality of patient care.

Conclusion:
The management of clinical hypertension is a challenging entity. Conventional methods of regular in-office blood pressure checks are both tedious and resource consuming. Using remote monitoring methods have shown to significantly improve blood pressure control compared to routine methods. It also eliminates white-coat hypertension during follow-up blood pressure checks which leads to more appropriate interventions. Remote monitoring and intervention for hypertension control is time-effective, cost-effective and improves quality of life.
Abstract 4138545: Mitral Valve Replacement is associated with favourable Functional and Clinical Outcome as compared with Restrictive Mitral Annuloplasty in Patients with Severe Ischemic Mitral Regurgitation. A prospective longitudinal analysis
Authors: Fino Carlo , D'Alonzo Michele , iacovoni attilio , Maccarana Agnese , Magne Julien , Pibarot Philippe , Merlo Maurizio , terzi amedeo , SENNI MICHELE , Bichi Samuele , Simon Caterina , BELLAVIA DIEGO
Published: November 2024

Background:
Restrictive mitral annuloplasty (RMA) and chordal-sparing mitral valve replacement (MVR) are common options for treatment of chronic severe ischemic mitral regurgitation.

Research question:
in patients with severe ischemic mitral regurgitation the most effective surgical approach remains controversial

Aim:
to test whether MVR provides superior clinical and functional outcomes compared with RMA.

Methods:
a prospective longitudinal analysis on 187 patients (age: 66 ± 9 year; EF:35 ± 8 %) undergoing MVR or RMA and CABG for severe ischemic mitral regurgitation. Six-minute walking test and echocardiography were performed at preoperative baseline, at 1 year and at a median FU of 5 year (interquartile range: 2.9). Brain natriuretic peptide levels were also obtained. Mitral regurgitation was defined through a comprehensive and integrative approach. Recurrent mitral regurgitation was defined as a vena contracta ≥ 3 mm at follow-up, in patients with no persistent regurgitation at discharge.

The primary outcome was a 5-year composite of all-cause mortality and rehospitalization for heart failure.

Survival analysis was performed with Kaplan-Meier method. Cox regression analysis was used to verify any independent predictor of composite end-point

Results:
Baseline preoperative data were similar between the two group. Mitral valve replacement was performed in 49% of patients (n=92) and RMA in 51 % (n=95).

At 5 year patients referred to prostheses showed significant improvement in six-minute walking test as compared to RMA (MVR: 290 ± 70 meters vs MRA: 165± 56 meters) (p > 0.01) (
Figure 1
). The brain natriuretic peptide values did not differ between the two group at 1 year whereas were significantly lower in the MVR group at 5 years (MVR: 135 pg/ml; interquartile range:100 vs RMA: 486 pg/ml; interquartile range: 68 (p<0.01) (
Figure 2
). At 5 years freedom from all-cause death and rehospitalization for heart failure was higher in the MVR group as compared to RMA (84 ±8.9% vs 61 ±12%, p<0.01) (
Figure 3
). According to the Cox analysis recurrent mitral regurgitation was found to be a predictor of clinical outcome (HR:5.4, 95% CI:1.3-23.2, p= 0.023).

Conclusions:
In patients with severe ischemic mitral regurgitation referred for surgery, chordal- sparing MVR and CABG may improve functional capacity, clinical outcome and brain natriuretic peptide levels, compared with RMA and CABG. The impact of these findings remains to be defined by larger studies on longer term
Abstract 4138701: Phenotypic clustering of HFpEF using cardiac magnetic resonance imaging
Authors: Garcia-Arango Mariana , Chen Yimin , Sahai Aditya , Tu Wanxin , El Shaer Ahmed , Kenarsary Aria , Gallegos Arthur , Jones Kathryn , Abed Anas , Arif Abdul Wahab , Park Yeonhee , Raza Farhan
Published: November 2024

Background:
Improved understanding of the high-risk features associated with HFpEF may facilitate risk stratification. Cardiac magnetic resonance (CMR)-based strain and structural data can define detailed myocardial structure, which can be leveraged to define heterogenous HFpEF phenotypes. This study used phenotypic clustering integrating CMR-based strain and structural data to identify a high-risk HFpEF phenotype.

Methods:
Retrospective analyses of 48 HFpEF participants, who underwent cardiac MRI and invasive cardiopulmonary exercise testing (median time between the two studies=40 days), was performed. We conducted unsupervised and unbiased K-means clustering analyses using CMR-based strain and myocardial structural variables. We associated two identified clusters with mortality using Cox proportional hazards modeling and constructed Kaplan-Meier survival curves. A p-value was considered significant if < 0.05.

Results:
We identified a low (n=32) and high-risk (n=16) cluster. Patients in the identified clusters had similar ages and comorbidities. The high-risk cluster had more male participants and hemodynamically had a higher exercise mPAP/CO and PAWP/CO slope, which are metrics of pulmonary vascular disease. The high-risk cluster displayed greater LV mass, worse biventricular longitudinal strain, decreased right ventricular ejection fraction, and greater interventricular septal angle (all P<0.05) as characterized by CMR as compared to the low-risk cluster (Table 1, Figure 1A). Mortality for the high-risk cluster was 5.43 times that for the low-risk cluster at 12 months (95% CI 1.69-17.42, Figure 1B).

Conclusions:
Using clustering analyses with CMR strain and structural variables, we identified a high-risk HFpEF phenotype with increased LV mass, reduced biventricular strain, and reduced RV ejection fraction.
Abstract 4138730: Analysis of Coronary Artery Disease and COPD Mortality in Older Adults in the United States, 1999-2020: CDC Data on Geographic, Gender, and Racial Trends in Mortality
Authors: Naveed Muhammad Abdullah , Alboushi Aldabagh Mohammad , Ali Ahila , Ahmed Faizan , Omer Rehan Muhammad , Azeem Bazil , Iqbal Rabia , Cheema Mustafa Sajjad , Daggubati Ramesh , sattar yasar
Published: November 2024

Background:
The coexistence of coronary artery disease (CAD) and Chronic Obstructive Pulmonary Disease (COPD) represents a major health challenge for older adults in the United States. This study designed to examine the variations in mortality rates associated with CAD and COPD among individuals aged 65 and above from 1999 to 2020.

Methods:
Using the CDC WONDER database, a retrospective analysis was conducted on death certificate data from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, and trends were evaluated using Average Annual Percentage Change (AAPC) and Annual Percentage Change (APC). The data were stratified by year, sex, race/ethnicity, and geographical region.

Results:
Between 1999 and 2020, coronary artery disease (CAD) and Chronic Obstructive Pulmonary Disease (COPD) were responsible for 881,875 deaths among adults aged 65 and older in the United States. The majority of these deaths occurred in medical facilities (40.3%) and in the decedents' homes (28.3%). The overall Age-Adjusted Mortality Rate (AAMR) decreased from 119.4 in 1999 to 86.9 in 2020, with an Annual Percent Change (APC) of -1.65 (p < 0.000001). Notably, AAMRs moderately decreased from 1999 to 2018 (APC: -2.13, p = 0.025195), followed by a significant increase from 2018 to 2020 (APC: 2.95, p = 0.296341). Men had notably higher AAMRs than women (men: 139.8; women: 67.4), with both sexes experiencing almost equal declines over the study period. In terms of race, Whites had the highest AAMRs (106.5), followed by Native Americans (87.3), Blacks (60.7), Hispanics (51.0), and Asians (30.4). While all racial groups experienced decrease in AAMR , the decline was more signficance in Asians [AAPC: -3.26, (CI: -4.30 to -2.27) (p-value < 0.000001)]. Geographically, AAMRs varied widely among states, with the highest mortality rates observed in the Midwestern region. Nonmetropolitan areas generally had higher AAMRs than metropolitan areas, and both showed decreases from 1999 to 2020, with greater declines in metropolitan areas. Figure 1

Conclusion:
This research emphasizes the temporal trends and demographic discrepancies in mortality rates linked to CAD and COPD among older adults aged 65 and above in the United States. Despite an overall decrease in mortality rates, the recent rise necessitates additional investigation and focused interventions to address inequalities and improve outcomes in affected demographic groups.