bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO5-04-10: Clinical and prognostic value of MLN51 (Metastatic lymph node gene 51)/CASC3 (Cancer susceptibility candidate gene 3) in clinical breast cancer, connection with nodal and hormonal receptor status
Authors: Cong Binbin , Martin Tracey , Cao Xiaoshan , Mansel Robert E , Davies Eleri , Jiang Wen 
Published: May 2024

Abstract
Introduction: Metastatic Lymph Node Gene 51 Protein (MLN51) also known as Cancer Susceptibility Candidate Gene 3 Protein (CASC3) or Barentsz (BTZ) is a molecule that was first identified in malignant breast tumours. The CASC3 gene encodes the protein that binds to mRNA and is a key component of the exon junction complex (EJC), playing an important role in the metabolism of mRNA and in cellular recovery after stress responses. It is not clear, however, if MLN51 has a clinical value in assessing the disease progression of breast cancer.
Methods: We analysed the transcription expression levels of MLN51 in a cohort of human breast cancer tissues and correlated the expression pattern with clinical outcome, pathological type and hormonal receptor status.
Results: High levels of MLN51 was found to be a favourable prognostic indicator for overall survival (p=0.008, Hazard Ratio [HR=0.262]), the prognostic value being independent of other clinical and pathological factors. Likewise, high levels of MLN51 were also a significant and independent predictive factor for disease free survival (DFS) (p=0.003, HR=0.262). It was found that the favourable prediction in both OS and DFS was associated with node positive tumours, with significance with OS (p=0.004), compared in node negative tumours (p=0.143) and to DFS (p=0.001 in node positive compared with p=0.079 in node negative tumours). Levels of MLN51 had a significant correlation with EGFR in both normal and tumour mammary tissues but correlated with Her-2 and Her-3 in tumour tissues only. The prognostic power of MLN51 for DFS was significant in both Her-2 positive and Her-2 negative (p=0.003 and p=0.012) tumours and in ER negative tumours (p=0.003). The prediction for OS by MLN51 was particularly strong for Her-2 positive and ER positive (p=0.007 for both) tumours.
Conclusions: MLN51 (CASC3) is a favourable prognostic factor in patients with breast cancer. This is clearly linked to the nodal status and hormone receptor status, particularly ER and HER-2.
Citation Format: Binbin Cong, Tracey Martin, Xiaoshan Cao, Robert E Mansel, Eleri Davies, Wen Jiang. Clinical and prognostic value of MLN51 (Metastatic lymph node gene 51)/CASC3 (Cancer susceptibility candidate gene 3) in clinical breast cancer, connection with nodal and hormonal receptor status [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-10.
Abstract PO5-08-04: Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center
Authors: Karki Ujjwal , Rangarajan Tara , Zakalik Dana 
Published: May 2024

Abstract
Background:
Pathogenic variants (PVs) in ATM are associated with an increased risk of breast, pancreas, and other cancers. The clinical and pathological characteristics of ATM-associated breast cancers have not been well defined.
Methods:
Patients who underwent multigene panel testing between December 2012 and May 2023 and were identified to harbor ATM PVs were included in the study. We analyzed demographics, germline findings, histopathology, genomic recurrence score, and management of ATM PV carriers with breast cancer.
Results:
A total of 222 individuals were identified to have PVs in ATM, of whom 184 (83%) were female. The majority were Caucasian (n = 179, 81%) and of those, 22 (12%) had Ashkenazi Jewish ancestry. The median age at genetic testing was 52y, with a range of 20-90y. A total of 111 patients (50%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 70; 63%). The median age at breast cancer diagnosis was 53y, with a range of 25-84y. The most common histopathology was invasive ductal carcinoma (74%), followed by DCIS (21%), and invasive lobular carcinoma (5%). The majority of patients had breast tumors with stage 2 or 3 (78%), grade 2 or 3 (92%), ER and/or PR positive (92%) and HER2 negative (70%). One patient had triple-negative breast cancer. Forty-four percent of breast cancers were less than two centimeters, 23% were lymph node-positive, and 29% had lymphovascular invasion. Thirty-eight percent of patients underwent bilateral mastectomy, 54% received radiation therapy, 40% received adjuvant chemotherapy, 24% received neoadjuvant chemotherapy, and 70% received hormonal therapy. Of the 15 breast cancers with known 21-gene recurrence scores, 47% were intermediate (11-26), 33% were high (&gt;=26) and 20% were low (&lt; =10). Other notable cancers observed were pancreas (n = 9), colorectal (n = 6), prostate (n = 5), uterine (n = 4), melanoma (n = 4), and thyroid (n = 4).
Conclusion:
Our study outlines the clinical and pathological characteristics of ATM-associated breast cancer in a large academic center. The majority of breast cancers were invasive ductal type, early stage, intermediate or high grade, and hormone receptor-positive with an intermediate or high recurrence score. Despite the early stage, a significant proportion of patients underwent bilateral mastectomy. Further studies are needed to better elucidate the unique characteristics of breast cancer in ATM PV carriers in order to provide tailored management guidelines for this population.
Citation Format: Ujjwal Karki, Tara Rangarajan, Dana Zakalik. Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-04.
Abstract PO5-27-10: Next generation antibody drug conjugates: Multi-payload conjugates targeting multiple mechanisms of cell killing
Authors: Lobba Marco , Trinter Devin , Nguyen Maxwell , Gutierrez Daniel , Brady Samantha , Symister Chanez , Lau Andrew , Kendall Richard , Johri Saurabh , Francis Matthew 
Published: May 2024

Abstract
Background: ADCs have had tremendous impact on patient outcomes in breast cancer and are rapidly moving towards second line use. However, many patients fail to respond or relapse after treatment with ADC therapies due to tumor heterogeneity and resistance to ADC payloads. Method: CatenaBio has developed a novel Multi-Payload-Conjugate (MPC) system capable of attaching distinct payloads at different sites to the same antibody, enabling the production of single-molecule targeted combination therapies with defined DAR. Results: We screened combinations of different payloads targeting several different mechanisms attached to trastuzumab at different drug-antibody ratios to optimize tumor cell killing. These targeted combination ADCs demonstrated robust killing in both HER2 high and low tumor cell lines. Conclusion: Antibody Drug Conjugates have revolutionized the treatment of high HER2 positive breast cancer. More recently advances have been made in the design of ADCs to expand indications to include HER2 low as well as HER2 negative patients. These constructs offer the next step in ADC design and allow for the combination of multiple mechanisms of action in a single MPC that are highly effective across multiple breast cancer cell lines. These molecules offer the potential to circumvent tumor resistance pathways and deliver deeper and more durable responses. Disclosures: Marco Lobba, Devin Trinter, Maxwell Nguyen, Daniel Gutierrez, Samantha Brady, Chanez Symister, Andrew Lau, Richard Kendall, and Saurabh Johri are employed by Catena Biosciences. Matthew Francis is a co-founder and advisor to Catena Biosciences.
Citation Format: Marco Lobba, Devin Trinter, Maxwell Nguyen, Daniel Gutierrez, Samantha Brady, Chanez Symister, Andrew Lau, Richard Kendall, Saurabh Johri, Matthew Francis. Next generation antibody drug conjugates: Multi-payload conjugates targeting multiple mechanisms of cell killing [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-10.
Abstract PO5-27-11: A COMPARATIVE STUDY OF DIAGNOSTICS MADE BY FINE NEEDLE ASPIRATION (FNA) BIOPSY VERSUS TRU-CUT FOR BREAST PATHOLOGY IN A ONE STOP CLINIC PROGRAM IN MEDELLIN, COLOMBIA
Authors: Gil Sara , Agudelo Carlos , Castaño Jorge , Naranjo Melissa , Piedrahita Clara , Wilches Daniel , Corredor Kelly 
Published: May 2024

Abstract
Breast cancer is the leading cause of morbidity and mortality among women in Colombia due to non-communicable chronic diseases. This has prompted health insurance companies to develop innovative initiatives to mitigate these negative outcomes. Since September 2018, Ayudas Diagnósticas SURA, in alliance with the Gustave Roussy Hospital and General Electric Healthcare has promoted a “One-stop clinic” program called: “TIEMPO PARA TI”. One of the primary challenges was to demonstrate that breast cytology, based on the Yokohama guidelines approved by The International Academy of Cytology has a high sensitivity, specificity, and diagnostic accuracy. The Yokohama system for classifying breast cytology is comprised of five categories: C1 not satisfactory, C2 benign, C3 atypical, C4 malignancy suspected, and C5 malignant. From September 2018 to December 2022, consecutive patients referred for breast biopsy and suspected of having breast cancer underwent triple assessment of breast tumor and were included in this retrospective study. Descriptive analysis was made using STATA v17 software to compare fine needle aspiration (FNA) biopsy versus Tru-cut. A total of 14,501 patients were included, 14.398 FNA and 14.401 trucut biopsies were performed. The comparative analysis showed a 99% concordance between categories 2, which correspond to benign lesions and 96.7% between categories 5, which correspond to malignant lesions. Our findings demonstrate that a well-executed FNA biopsy is not inferior to a trucut biopsy, as revealed by the Yokohama system, and offers significant advantages, such as cost-effectiveness and prompt diagnosis. Both techniques should be used with caution, considering their advantages and disadvantages.
Citation Format: Sara Gil, Carlos Agudelo, Jorge Castaño, Melissa Naranjo, Clara Piedrahita, Daniel Wilches, Kelly Corredor. A COMPARATIVE STUDY OF DIAGNOSTICS MADE BY FINE NEEDLE ASPIRATION (FNA) BIOPSY VERSUS TRU-CUT FOR BREAST PATHOLOGY IN A ONE STOP CLINIC PROGRAM IN MEDELLIN, COLOMBIA [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-11.
Economic Considerations for Implementing Tobacco Cessation Programs in Cancer Care Settings
Authors: Salloum Ramzi G. , Shoenbill Kimberly A. , Goldstein Adam O. 
Published: May 2024

AbstractIncreasingly, research demonstrates economic benefits of tobacco cessation in cancer care, as seen in a new study by Kypriotakis and colleagues of the MD Anderson cessation program, demonstrating median health care cost savings of $1,095 per patient over 3 months. While the cost-effectiveness of tobacco cessation programs from a hospital perspective is important, implementation decisions in a predominantly fee-for-service system, such as in the United States, too often insufficiently value this outcome. Economic barriers, stakeholder disincentives, and payment models all impact program implementation. Combining economic evaluation with implementation research, including assessment of return-on-investment, may enhance sustainability and inform decision-making in cancer care settings.See related article by Kypriotakis et al., p. 217
Trem2 Agonist Reprograms Foamy Macrophages to Promote Atherosclerotic Plaque Stability—Brief Report
Authors: Patterson Michael T. , Xu Yingzheng , Hillman Hannah , Osinski Victoria , Schrank Patricia R. , Kennedy Ainsley E. , Barrow Fanta , Zhu Alisha , Tollison Samuel , Shekhar Sia , Stromnes Ingunn M. , Tassi Ilaria , Wu Dick , Revelo Xavier S. , Binstadt Bryce A. , Williams Jesse W. 
Published: May 2024

BACKGROUND:
Trem2 (triggering receptor on myeloid cells 2), a surface lipid receptor, is expressed on foamy macrophages within atherosclerotic lesions and regulates cell survival, proliferation, and anti-inflammatory responses. Studies examining the role of Trem2 in atherosclerosis have shown that deletion of Trem2 leads to impaired foamy macrophage lipid uptake, proliferation, survival, and cholesterol efflux. Thus, we tested the hypothesis that administration of a Trem2 agonist antibody (AL002a) to atherogenic mice would enhance macrophage survival and decrease necrotic core formation to improve plaque stability.

METHODS:

To model a therapeutic intervention approach, atherosclerosis-prone mice (Ldlr [low-density lipoprotein receptor]
−/−
) were fed a high-fat diet for 8 weeks, then transitioned to treatment with AL002a or isotype control for an additional 8 weeks while continuing on a high-fat diet.

RESULTS:
AL002a-treated mice had increased lesion size in both the aortic root and whole mount aorta, which correlated with an expansion of plaque macrophage area. This expansion was due to increased macrophage survival and proliferation in plaques. Importantly, plaques from AL002a-treated mice showed improved features of plaque stability, including smaller necrotic cores, increased fibrous caps, and greater collagen deposition. Single-cell RNA sequencing of whole aorta suspensions from isotype- and AL002a-treated atherosclerotic mice revealed that Trem2 agonism dramatically altered foamy macrophage transcriptome. This included upregulation of oxidative phosphorylation and increased expression of collagen genes. In vitro studies validated that Trem2 agonism with AL002a promoted foamy macrophage oxidized low-density lipoprotein uptake, survival, and cholesterol efflux.

CONCLUSIONS:
Trem2 agonism expands atherosclerotic plaque macrophages by promoting cell survival and proliferation but improves features of plaque stability by rewiring foamy macrophage function to enhance cholesterol efflux and collagen deposition.
Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial
Authors: Nakamura Kenta , Henry Timothy D. , Traverse Jay H. , Latter David A. , Mokadam Nahush A. , Answini Geoffrey A. , Williams Adam R. , Sun Benjamin C. , Burke Christopher R. , Bakaeen Faisal G. , DiCarli Marcelo F. , Chaitman Bernard R. , Peterson Mark W. , Byrnes Dawn G. , Ohman E. Magnus , Pepine Carl J. , Crystal Ronald G. , Rosengart Todd K. , Kowalewski Elaine , Koch Gary G. , Dittrich Howard C. , Povsic Thomas J. ,   on behalf of the EXACT Trial Investigators
Published: May 2024

BACKGROUND:
XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina.

METHODS:

In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×10
11
viral particles) via transepicardial delivery.

RESULTS:
There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients were related to the surgical procedure. Total exercise duration increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months; +88.3 [95% CI, 37.1–139.5], +84.5 [95% CI, 34.1–134.9], and +115.5 [95% CI, 59.1–171.9]). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI, −3.1% to 23.5%), 14.3% (95% CI, 2.8%–25.7%), and 10.2% (95% CI, −0.8% to −21.2%). Angina frequency decreased from a mean±SD 12.2±12.5 episodes to 5.2±7.2 (3 months), 5.1±7.8 (6 months), and 2.7±4.8 (12 months), with an average decrease of 7.7 (95% CI, 4.1–11.3), 6.6 (95% CI, 3.5–9.7), and 8.8 (4.6–13.0) episodes at 3, 6, and 12 months. Angina class improved in 81% of participants at 6 months.

CONCLUSIONS:
XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04125732.
Contributions of Basal Ganglia Circuits to Perception, Attention, and Consciousness
Authors: Redinbaugh Michelle J. , Saalmann Yuri B. 
Published: May 2024

Abstract
Research into ascending sensory pathways and cortical networks has generated detailed models of perception. These same cortical regions are strongly connected to subcortical structures, such as the basal ganglia (BG), which have been conceptualized as playing key roles in reinforcement learning and action selection. However, because the BG amasses experiential evidence from higher and lower levels of cortical hierarchies, as well as higher-order thalamus, it is well positioned to dynamically influence perception. Here, we review anatomical, functional, and clinical evidence to demonstrate how the BG can influence perceptual processing and conscious states. This depends on the integrative relationship between cortex, BG, and thalamus, which allows contributions to sensory gating, predictive processing, selective attention, and representation of the temporal structure of events.
The Battle at Lake Changjin: The Influence of Korean War Memory on Contemporary Chinese War Films
Authors: Kotowski Matthew 
Published: May 2024

Abstract
The 2021 film The Battle at Lake Changjin (长津湖) is China’s highest-grossing film. Together with its sequel, its success as a political tool rests on appealing to a broad audience while engaging with familiar themes embedded in collective memory. The Chinese Communist Party, which commissioned the films, leveraged preexisting tropes regarding the conflict and repackaged them for a modern audience. This paper will proceed in three parts. First, it will trace the deliberate development of collective memory of the conflict from its inception up to President Xi Jinping’s gaining power in 2012. Next, it will explore the new emphasis on the Korean War in the 2010s and 2020s, and the political objectives Xi seeks to achieve by propagandizing the Korean War. Finally, it will provide a thematic analysis of the films and how the intended political messaging interacted with the embedded collective memory.
Taxonomic revision of Mozambique dung beetle species in the genus Diastellopalpus van Lansberge, 1886 (Coleoptera: Scarabaeidae: Scarabaeinae)
Authors: DANIEL GIMO M. , STRÜMPHER WERNER P. , JOSSO JEAN-FRANÇOIS , DAVIS ADRIAN L.V. 
Published: May 2024

Recently, there has been growing attention paid to the Mozambican dung beetle fauna, including the description of several new species. In this paper, we revise the taxonomy of species recorded from Mozambique in the genus Diastellopalpus van Lansberge, 1886, including the description of Diastellopalpus scholtzi Daniel, Strümpher, Josso & Davis, new species. We also report a new country record for Diastellopalpus neavei (d’Orbigny, 1914). Moreover, Diastellopalpus orbignyi Péringuey, 1904 is removed from subjective synonymy with Diastellopalpus infernalis van Lansberge, 1887 and proposed as a valid species. Currently, Mozambique encompasses five valid species of the genus Diastellopalpus, namely: Diastellopalpus infernalis van Lansberge, 1887, D. quinquedens Bates, 1888, D. neavei, D. orbignyi and D. scholtzi, new species. We redescribe the former four species and include an examination of the types of their junior synonyms. Furthermore, we diagnose, illustrate, and provide a distribution map for all five species and compare them to the morphologically most similar species in the genus. We designate lectotypes for the following species-group taxa: Diastellopalpus nyassicus Kolbe, 1901, D. orbignyi, D. quinquedens Bates, 1888, Onthophagus ponderosus Péringuey, 1896, and O. tridepressus d’Orbigny, 1902. Finally, we provide an updated identification key for the species of Diastellopalpus recorded from Mozambique.
A Numerical Study of Smoke Concentration Distribution near Low-Intensity Fires: Sensitivity to Vertical Canopy Structure and Fire Heat Source Strength
Authors: Kiefer Michael T. , Zhong Shiyuan , Charney Joseph J. , Bian Xindi , Heilman Warren E. , Seitz Joseph 
Published: May 2024

Abstract
Broadly speaking, prediction of the negative impacts of prescribed fire on air quality is limited by gaps in our understanding of the underlying fire, fuels, and atmospheric processes. These knowledge gaps hinder our ability to accurately predict smoke concentration distributions, leading to unintended smoke intrusions into nearby communities and subsequent threats to public health and safety. In this study, numerical simulations are performed using the Flexible Particle Weather Research and Forecasting (FLEXPART-WRF) Model, a Lagrangian particle dispersion model, with particle motion driven by output from a full-physics atmospheric model with a forest canopy submodel and 10-m horizontal grid spacing [Advanced Regional Prediction System (ARPS)-CANOPY], to address two research questions. First, what is the relationship between near-fire (within ∼50–150 m of fire) smoke concentration distribution and (i) vertical canopy structure and (ii) fire heat source strength? Second, what roles do mean transport (i.e., transport by the mean wind) and turbulent diffusion play in shaping the near-fire smoke concentration distribution? To address these questions, simulations are run with 25 combinations of plant area density profile and fire sensible heat flux magnitude, and smoke is represented by particles with diameters ≤ 2.5 μm (PM2.5). Results show that near-fire PM2.5 concentration distribution is primarily controlled by vertical canopy structure, with fire heat source strength primarily controlling the PM2.5 concentration magnitude. Analysis of the underlying ARPS-CANOPY variables driving the FLEXPART-WRF particle dispersion helps elucidate the roles of mean transport and turbulent diffusion. In total, the study findings suggest that the vertical distribution of canopy vegetation and fire heat source strength are important factors influencing PM2.5 dispersion and concentration distribution near low-intensity fires.