bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Water–Soluble Flavonoids From Lithocarpus litseifolius (Hance) Chun (Sweet Tea) Improve Glucose Homeostasis Through Multitarget Signalling in GDM Mice
Authors: Xu Junfei , Zhang Fenfang , Li Huanhuan , Li Pan , Zeng Junying , Wu Xianjin , Zhou Rong , Yang Chunyan , Zhang Juzuo
Published: November 2024

Background: The oral safety of Lithocarpus litseifolius (Hance) Chun (sweet tea) that has antihyperglycemic potential has been verified. However, its specific application and action mechanism in the treatment of gestational diabetes mellitus (GDM) are still unclear.

Methods: Total water–soluble flavonoids extracted from L. litseifolius (Hance) Chun (sweet tea) were applied to GDM mice. The glucose tolerance, insulin sensitivity, and histopathology of the GDM mice were evaluated through an intraperitoneal glucose tolerance test (IPGTT), an intraperitoneal insulin tolerance test (IPITT), and histochemistry. The possible mechanism was analysed through network pharmacology.

Results: Compared with those in GDM model mice (MD group), blood glucose levels indicating both glucose tolerance and insulin sensitivity were improved in GDM mice treated with total water–soluble flavonoids (LLHC group) but were greater than those in normal control mice (NC group). The number of apoptotic liver cells was significantly lower in the LLHC group than in the MD group, but greater than that in the NC group. Multiple targets and signalling pathways that were acted by eight main active ingredients were involved in the process by which total water–soluble flavonoids protect against GDM. The main mechanism involved quercetin (10 targets) and luteolin (8 targets), which acted on the effector target of GAA through six main signalling pathways around the AKT1 core axis.

Conclusion: Oral administration of total water–soluble flavonoids can alleviate glucose intolerance and insulin resistance via the inhibition of liver cell apoptosis. The main active ingredients act on GAA through the signalling pathways of the AKT1 core axis.
Effectiveness of Resistance Exercise for Depression, Fatigue, and Sleep Quality in Women With Fibromyalgia
Authors: Rodríguez-Domínguez Álvaro-José , Rebollo-Salas Manuel , Chillón-Martínez Raquel , Rosales-Tristancho Abel , Arana-Rodríguez Andrés , Jiménez-Rejano José-Jesús
Published: November 2024

Purpose: Fibromyalgia is a chronic disease that mainly affects women, deteriorating the quality of life of these patients. Resistance exercise (RE) has been shown to be beneficial in this disease. The objective of this study is to evaluate the effectiveness of RE for depression, fatigue, and sleep quality in women with fibromyalgia.

Design and Methods: A systematic review with meta‐analysis was conducted until September 1, 2024. Seven databases were searched as follows: PubMed, Cochrane Library, Web of Science, Scopus, Physiotherapy Evidence Database, Dialnet, and Cumulative Index to Nursing and Allied Health Literature. Randomized clinical trials were conducted in women with a diagnosis of fibromyalgia, including RE as the only intervention in any of the groups and to assess depression, fatigue, and sleep quality. For meta‐analyses, we calculated the standardized difference of means and its standard error. A random‐effects model was used. The risk of bias was assessed using the Cochrane risk‐of‐bias tool for randomized trials (RoB 2). PROSPERO Registration: CRD42021256162.

Findings: Eleven trials were included in the systematic review and eight in the meta‐analysis (n = 664). RE showed statistically significant improvements in depression (SMD = −0.54; 95% CI [−0.92, −0.16], p = 0.005) and fatigue (SMD = −0.83; 95% CI [−1.41–0.25], p = 0.005). No significant differences were found in sleep quality (SMD = −0.99; 95% CI [−2.40, 0.43], p = 0.17). In general, the methodological quality of the included trials was good.

Practice Implication: RE is an effective tool to improve depression and fatigue in women with fibromyalgia, achieving clinically relevant improvements of more than 50% in symptoms related to depression. RE did not show benefits for sleep quality, although this finding may be due to a lack of studies. More studies are needed to determine the effectiveness of RE on sleep quality.
Comparative Analysis of Cognitive and Psychiatric Functioning in People With Cushing’s Disease in Biochemical Remission and People With Nonfunctioning Adenomas
Authors: Fernandes Mary A. , Hickle Sabrina D. , Penna Suzanne , Ioachimescu Adriana G. , Tone Erin B.
Published: November 2024

People with Cushing’s disease (CD) often experience both mood/anxiety disorders and cognitive impairments that persist during long‐term biochemical remission. The relationship between persistent neurocognitive and psychiatric problems in patients with CD is not well understood. Also, mechanisms other than hypercortisolism are poorly understood, and studies comparing CD with nonfunctioning adenomas (NFA) patients postoperatively are scarce. We compared neuropsychological functioning in two groups: individuals with CD in remission (n = 20; 80% female; 61.6 [44.13] months since remission) and individuals with NFAs (n = 20). Evaluation was performed, on average, 4.9 years following pituitary surgery. We used mediation models to evaluate psychiatric dysfunction as a possible mediator of cognitive outcomes and assessed the influence of demographic and medical factors (age at diagnosis, remission duration, and radiation therapy) on neuropsychological outcomes. Neuropsychological outcomes did not differ significantly between groups; however, up to 30% of patients demonstrated mild impairments in attention, processing speed, executive functioning, and visual memory. Time since remission in the CD group was inversely correlated with processing speed; however, this relationship was no longer significant after controlling for the presence of hypertension and diabetes mellitus. Levels of anxiety, depression, or somatization were reported in up to 40% of people with CD. Further, 70% of people with CD and 35% of people with NFA reported continuous depressive symptoms lasting at least 2 years. In conclusion, neuropsychological screening in clinical practice and longitudinal studies in individuals with NFA and CD are needed to identify patients at risk for long‐term neuropsychological dysfunction. Appropriate support and treatment are recommended for persistent cognitive and/or psychiatric dysfunction for both patient groups.
Early Impacts of COVID‐19 Pandemic on the Crude Oil Prices and Demand in Sub‐Saharan Africa: A Review
Authors: Mwape Mwewa Chikonkolo , Mpofu Nonsikelelo Sheron , Malanda Clement Hastings , Kimutai Isaiah K.
Published: November 2024

In March 2020, the World Health Organization (WHO) proclaimed the novel coronavirus 2019 (COVID‐19) a global pandemic with no therapy/vaccination or universally accepted therapeutic modalities. This resulted in the implementation of containment measures such as lockdowns, which hindered economic activities and, as a result, hampered global demand, consumption, and product transportation. The global crude oil supply chain was one of the most affected. As a result, this study was done to examine the effects of COVID‐19 on global crude oil markets and its consequences in sub‐Saharan Africa (SSA), using Kenya and Tanzania as case studies. Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA)‐based content analysis approaches were utilized to analyze data from multiple sources, and the COVID‐19‐induced oil price crisis was compared to previous global crude oil gluts from 1970 to 2020. It has been determined that global crude oil prices dropped by 65.96% from around $69.25/barrel in January 2020 to $23.57/barrel in June 2020, with West Texas Intermediate (WTI) reaching −$36.98/barrel in March 2020 (one of the highest in recent times). As a result, petroleum prices in Kenya and Tanzania fell by 30%. This, however, did not result in long‐term energy price stability in the SSA due to a lack of logistical and storage capabilities. More research on energy storage, consumption, analysis, modeling, and preparedness for COVID‐19‐like disasters are suggested.
Water Extracts of Moringa oleifera Leaves Alter Oxidative Stress–Induced Neurotoxicity in Human Neuroblastoma SH‐SY5Y Cells
Authors: Barinda Agian Jeffilano , Arozal Wawaimuli , Hardi Harri , Dewi Yulia Ratna , Safutra Muhamad Sadam , Lee Hee Jae
Published: November 2024

Moringa oleifera (MO) has been an important plant for food and traditional medicine in Asian countries, including Indonesia. The leaves of these plants are reported to be rich in antioxidants, vitamins, and micronutrients and have been proven to have nootropic properties. Therefore, we investigated whether MO could provide protective effects on SH‐SY5Y neuroblastoma cells exposed to H2O2. In this study, we observed cotreating water‐extracted MO leaves on the inhibition of reactive oxygen species (ROS). We found that this treatment enhanced the activities of glutathione peroxidase, catalase, and superoxide dismutase. In addition, it suppressed the mRNA expression levels of apoptotic gene‐related genes, specifically Bcl‐2 associated protein X (BAX) and caspase 3. Furthermore, it promoted neuroplasticity by increasing the brain‐derived neurotropic factor (BDNF) mRNA expression in SH‐SY5Y cells. The protein expression of phosphorylated‐Akt and phosphorylated‐CREB, essential genes in neuroplasticity, was also increased in cells treated with H2O2 and MO. Therefore, the neuroprotective effects of MO against oxidative stress are attributed to its antioxidant and antiapoptotic properties, as well as its ability to modify the neuronal signaling pathway.
Determination of Minimum Miscible Pressure and Phase Behavior of CO2–Shale Oil in Nanopores
Authors: Wang Yuhan , Lei Zhengdong , Liu Yishan , Xu Zhenhua , Chen Zhewei , Pan Xiuxiu , Liu Pengcheng
Published: November 2024

CO2 injection into shale oil reservoirs has gained widespread attention as it not only enhances oil recovery but also facilitates the geological storage of CO2. Shale oil reservoirs are characterized by numerous nanopores, and the resident fluid exhibits unique phase behavior due to nanoconfinement effects, resulting in the failure of the traditional theoretical model and microfluidic experiment in depicting the minimum miscible pressure (MMP) of CO2–shale oil in nanopores. This study proposes a method for calculating the MMP of CO2–shale oil in nanopores. It combines the three‐phase equilibrium calculation method of gas phase–liquid phase–adsorbed phase with the multiple mixing cell (MMC) method. The method considers capillary pressure and corrects the critical properties influenced by the nano‐limited domain effect. Using this approach, the phase behavior of CO2–shale oil in nanopores and the MMP are investigated. It is found that as the pore radius decreases, the area of the two‐phase region surrounded by the phase envelope of multicomponent fluids gradually shrinks. The smaller the pore radius, the more significant the shrinkage of the two‐phase region. The entire phase envelope and the critical point shift to the left and down on the coordinates, and this phenomenon is more pronounced for pore radii less than 20 nm. The presence of CO2 increases the system’s critical condensation pressure and decreases the critical condensation temperature. The MMP of the 6‐component system of CO2–shale oil for a pore radius of 5 nm in this paper is 63.7 bar at 101°C.
Ensemble Feature Selection Using Neighbourhood Rough Set–Based Multicriterion Fusion
Authors: Ma Zhen
Published: November 2024

Feature selection refers to finding a compact feature subset in which redundant and irrelevant information is reduced. It is generally aimed at simplifying the learning model and improving the learning performance simultaneously. To further enhance the traditional feature selection, ensemble feature selection has been developed vigorously in recent years. In this study, a novel ensemble feature selection algorithm that fuses multiple scores induced by multiple neighbourhood rough set–based feature evaluation criteria is presented. In detail, three different neighbourhood rough set–based feature evaluation criteria are applied, including neighbourhood approximation quality, neighbourhood recognition rate, and neighbourhood discrimination index. These representative measures serve as ensemble bases to induce multiple feature scores. Then, an aggregation method is proposed to fuse these scores for quantifying the feature importance quality. Finally, a searching algorithm based on this neighbourhood score by multicriterion fusion is devised. Experimental results on 16 UCI data sets prove that the proposed method outperforms other feature selection algorithms in classification task.
El Caso Audios bajo la lupa de la Gestión Documental
Authors: Mercado Beatriz
Published: November 2024

El artículo analiza el caso "Audios" o caso Hermosilla desde la perspectiva de la gestión documental y las tecnologías de información. Este caso, considerado uno de los mayores escándalos de corrupción en Chile, se inició con la filtración de un audio de 105 minutos en noviembre de 2023, revelando presuntos sobornos a funcionarios públicos. El análisis se centra en tres aspectos principales: 1) El valor del documento digital como evidencia, incluyendo grabaciones de audio; 2) El papel de la inteligencia artificial en la investigación, específicamente el uso del software forense Cellebrite para analizar más de 770 mil páginas de información del teléfono de Hermosilla; y 3) Las implicaciones de las nuevas tecnologías de comunicación, particularmente WhatsApp, en relación con la trazabilidad documental y la preservación digital. El artículo también aborda la tensión entre privacidad y transparencia en la era digital, así como los desafíos que presentan las nuevas tecnologías para los sistemas judiciales y la gestión documental.
Inclusión Financiera y brecha de género, ¿hemos avanzado?
Authors: Ortiz Rodrigo , Vallejos Benjamín , Salinas Julio
Published: November 2024

El artículo analiza el grado de inclusión financiera en Chile y su evolución entre 2011 y 2024, enfocándose en el acceso de las personas a servicios financieros. Utilizando datos del Global Findex del Banco Mundial, se evidencia un avance sostenido en la inclusión financiera chilena, particularmente en acceso al crédito y tenencia de tarjetas. El estudio destaca la reducción de la brecha de género en servicios financieros, posicionando a Chile favorablemente en comparación con otros países de América Latina. Se analiza el rol fundamental del BancoEstado como banca de desarrollo y la implementación del Sistema de Finanzas Abiertas (SFA) para mejorar la transparencia y competitividad del mercado financiero. El artículo concluye destacando los avances significativos en inclusión financiera y propone recomendaciones para fortalecer la alfabetización financiera y la resiliencia de sectores vulnerables.
Abstract A002: The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients
Authors: Woo Hyeongjung , Shin Hyun Young , Oh So Yeon , Lee Sun Min , Kim Minseok S.
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR002) of the Conference Program/Proceedings.

Citation Format: Hyeongjung Woo, Hyun Young Shin, So Yeon Oh, Sun Min Lee, Minseok S. Kim. The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A002.
Abstract A013: Quality control of the biobanked matched tissue: Blood samples for the development of diverse liquid based molecular assays
Authors: Gatalica Zoran , Stafford Phillip , Diehnelt Chris , Rose Inga
Published: November 2024

The availability of high-quality matched biological samples (tumor-blood) is the major limiting factor for research and development of novel, liquid biopsy-based assays in oncology. Frequently, ongoing specifically timed collections of blood samples are required. De-identified tissue blocks (formalin-fixed, paraffin embedded (FFPE) or flash frozen) matched with patient's blood samples collected in fixative-containing (Streck) of EDTA containing tubes, were collected at worldwide geographic locations and transferred to biobanking facility (Reference Medicine, Phoenix, AZ). Additional blood samples were collected at various times regarding the cancer surgery. Plasma and buffy coat samples were locally prepared and shipped to the biobank. A subset of blood samples without matched tissues from healthy donors were also collected. All samples were shipped under strict transport conditions. Quality control performed at the biobanking facility included pathology review and nucleic acids quality assessment. A total of over 3,000 cases were collected and provided to end-users working on various assays based on cfDNA (e.g. monitoring for minimal residual disease or multi-cancer early detection). Immuno-reactivity to various antigens in samples collected in Streck and EDTA tubes (from 50 patients) was assessed by peptide microarray binding assay. Feedback information on the quality of samples was shared in 900 cases. Approximately 4% of cases had failed internal pathology review, due to poor preservation, lack of adequate tissue composition, or low tumor volume and 11% failed internal nucleic acid quality assessment (DNA concetration and integrity). The blood collection tubes had no significant impact on serologic testing using peptide microarary assay. Customer feedback data showed that overall success rate exceeded 85%. Type of blood collection tubes (Streck vs EDTA) had no impact on serologic testing and studies looking at predicted neoantigens based on NGS data can be confirmed using peptide epitope arrays. Blood collected for NGS works without compromise on peptide arrays. Future validation of other collection tubes for blood or other types of fluids is needed to confirm their adequacy for specific assays.

Citation Format: Zoran Gatalica, Phillip Stafford, Chris Diehnelt, Inga Rose. Quality control of the biobanked matched tissue: Blood samples for the development of diverse liquid based molecular assays [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A013.
Abstract A044: Utilizing breast cancer-specific micronuclei DNA features from erythrocytes for early detection of breast carcinoma
Authors: Mo Wenjv , Yao Xingyun , Sun Haobo , Liang Honghao , Jin Jie , Ding Xiaowen , Gao Xiaofei
Published: November 2024

Background: Alongside traditional imaging, current development in non-invasive breast carcinoma (BC) diagnosis, such as cell-free DNA-based technologies, have demonstrated promising potential in BC diagnosis. However, achieving early detection remains a challenge. Micronuclei (MN) are extranuclear bodies containing damaged chromosome segments indicative of genomic instability. Elevated levels of MN-containing erythrocytes have been studied in genotoxicity testing and cancer diagnosis. Here, we sequenced the isolated and purified micronuclei DNA (MN-DNA) from erythrocytes in 2ml peripheral blood using a method we previously developed (WO2021/228246 A1) and identified a series of distinct features in read counts that enabled to detect early-stage BC patients. Methods: We collected a clinical study cohort of 172 BC patients and 216 non-BC controls from 1-2ml peripheral blood. MN-DNA was isolated from erythrocytes and performed whole-genome sequencing. We selected distinctive tumor-associated MN-DNA features identified by genome-wide analysis to differentiate between controls and BC for KEGG pathway enrichment and constructed a classification model based on these features. Results: Genome-wide analysis of MN-DNA revealed significant regions between controls and BC patients. Based on covered genes, we observed significant enrichment in the estrogen signaling pathway. Utilizing these distinct MN- DNA features, we constructed a classification model that achieved an AUC of 96%, with a 95% specificity and 88% sensitivity in the test cohort. The model identified early BC (stage 0-I) and advanced BC (stage II-IV) with sensitivities of 100% or 84%, respectively. Conclusions: Our findings highlight that MN-DNA, a form of cytoplasmic DNA, provides a valuable tool for the accurate detection of BC, particularly in its early stages. The MN-DNA pattern is linked to the estrogen signaling pathway, offering novel insights and mechanisms that differ from current diagnostic approaches. Research sponsor: Timing Biotech. Early Detection of Primary Cancer and Relapse

Citation Format: Wenjv Mo, Xingyun Yao, Haobo Sun, Honghao Liang, Jie Jin, Xiaowen Ding, Xiaofei Gao. Utilizing breast cancer-specific micronuclei DNA features from erythrocytes for early detection of breast carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A044.
Abstract A061: A cost-effective two-step approach for multi-cancer early detection in general population
Authors: Mao Mao , Geng shuai peng  , Li shi yong  , Wei Wu , Yin Chang Yin
Published: November 2024

In population-wide cancer screening, three key issues need to be focused on: number of cancer cases identified, the issue of false positives, and cost. A high false positive rate can result in a significant waste of healthcare resources. Large-scale screening inevitably leads to significant financial burdens on the healthcare system which is a key factor constraining nationwide screening. OncoSeek is a multi-cancer early detection (MCED) test using a panel of seven plasma protein tumor markers (PTMs) and artificial intelligence (AI). SeekInCare is a MCED test that integrates the seven PTMs and four cancer genomic features (aneuploidy, fragment size, end motifs, and oncogenic viruses) from cell-free DNA (cfDNA) by shallow whole-genome sequencing (sWGS). In a two-step approach, the initial screening is conducted using OncoSeek and SeekInCare is then used as the secondary test for those individuals who tested positive by OncoSeek. In a case-control study (n = 1197) including both OncoSeek and SeekInCare testing results, OncoSeek showed 49.9% sensitivity at 91.0% specificity, while SeekInCare demonstrated 60.0% sensitivity at 98.3% specificity. In the two-step process, specificity significantly increased from 91.0% to 99.3%, while sensitivity decreased from 49.9% to 39.9%. We modeled a screening in five million adults aged ≥ 50 years with a cancer incidence rate of 1.9%. The simulated real-world sensitivities of OncoSeek and two-step were adjusted downward proportionally to 28.0% and 22.4% based on the sensitivity differences observed between GRAIL’s CCGA study (case-control, 51.5%) and PATHFINDER study (prospective, 28.9%). While at 91.0% specificity OncoSeek had 441,450 cases of false positives, using the two-step approach significantly reduced false positives to 34,335 (0.7%). Although Galleri ($949 per test) identified more cancer cases than the two-step MCED, with 27,455 and 21,280 cases respectively, its total cost for the former reached $4,745 million. As the positive predictive value (PPV) of two-step (38.3%) was the same as Galleri (38.3%), it reduced cost 6.6-fold, amounting to a total cost of $713.6 million and a cost of $143 per individual screened. The cost of per cancer case detected using Galleri is $172,828 compared to $33,534 using the two-step MCED, which represents a 5.2-fold difference. In conclusion, the two-step approach not only significantly reduces false positives, but also cuts the screening cost down substantially, making it a cost-effective strategy for population-wide cancer screening.

Citation Format: Mao Mao, Geng shuai peng, Li shi yong, Wu Wei, Chang Yin Yin. A cost-effective two-step approach for multi-cancer early detection in general population [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A061.
Abstract A062: Insightful analysis: Harnessing aqueous humor ctDNA for retinoblastoma stratification
Authors: Montigel Sophia H , Ryl Tatsiana , Volz Stefanie , Afanasyeva Elena , Wedig Tatjana , Schwarz Nathalie , Pfister Stefan M , Pajtler Kristian W , Ketteler Petra , Maaß Kendra K
Published: November 2024

Retinoblastoma (RB) the most common intraocular malignancy in children poses a significant challenge as traditional tissue biopsies are not feasible. Due to its critical location within the eye and the high risk of tumor seeding, clinicians are limited in performing molecular analysis-based risk stratification prior to enucleation. In this study, we explored the potential of aqueous humor (AH) as a source for minimally invasive liquid biopsies, aiming to establish a molecular profiling methodology for circulating tumor DNA (ctDNA) for risk stratification. We analyzed AH samples and corresponding tumor tissues from 19 enucleated eyes of patients diagnosed with RB. The extracted ctDNA from AH underwent low-coverage whole-genome sequencing (lcWGS) and methylation profiling. These data were then compared with the genomic and methylation landscapes of the matched tumor DNA. Additionally, we assessed the ability of AH- derived ctDNA to predict retinoblastoma methylation cluster. Our findings demonstrate a high concordance between ctDNA from AH and the primary tumor DNA in both methylation patterns and genomic alterations detected by lcWGS allowing the correct prediction of the retinoblastoma molecular group. The shared aberrations underscore the potential of AH as a reliable surrogate for tumor tissue in retinoblastoma. Additionally, the methylation profiles revealed consistent epigenetic modifications, further supporting the accuracy of AH-derived ctDNA in reflecting the tumor’s molecular characteristics. This study highlights the feasibility and effectiveness of using AH for molecular ctDNA genetic analysis in retinoblastoma. The overall high concordance between ctDNA profiles with primary tumor DNA and the ability to accurately predict RB methylation classes, highlights the superiority of the liquid biopsy approach overcoming the limitations of traditional biopsies and transforming the potential for early molecular analysis and risk stratification. This revolutionary technique could redefine pre-enucleation diagnostics, offering unprecedented insights and paving the way for tailored, precision medicine in retinoblastoma care.

Citation Format: Sophia H Montigel, Tatsiana Ryl, Stefanie Volz, Elena Afanasyeva, Tatjana Wedig, Nathalie Schwarz, Stefan M Pfister, Kristian W Pajtler, Petra Ketteler, Kendra K Maaß. Insightful analysis: Harnessing aqueous humor ctDNA for retinoblastoma stratification [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A062.
Abstract A063: Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers
Authors: Mudgal Poorva , Bandoski Cheryl , Opheim Zachary , Mehnert Martin , Anschau Valesca , Isaac Issa , Ezrin Alan , Hembrough Todd
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR013) of the Conference Program/Proceedings.

Citation Format: Poorva Mudgal, Cheryl Bandoski, Zachary Opheim, Martin Mehnert, Valesca Anschau, Issa Isaac, Alan Ezrin, Todd Hembrough. Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A063.
Abstract A069: Effect of different voided urine sample storage time and temperature, and preservatives, on analysis with the multiplex bead-based Oncuria® bladder cancer immunoassay
Authors: Tanaka Sunao , Murakami Kaoru , Sakatani Toru , Lee Riko , Hogrefe Wayne , Siguencia Fernando , Smith Steven M , Rosser Charles J , Furuya Hideki
Published: November 2024

Urinalysis accuracy requires reliable sample stability that is dependent on the chosen collection and storage conditions. If urine sample storage at room temperature (20°C) does not affect sample quality, this may reduce laboratory handling time and expense. This study evaluated whether different voided urine sample collection and storage parameters affected subsequent biomarker analysis by the multiplex Oncuria® bladder cancer immunoassay. The Oncuria® immunoassay simultaneously quantifies 10 protein analytes in urine to generate a bladder cancer diagnostic signature. Samples were stored at varied temperatures (20°C, 4°C, -80°C) for up to 1 month. The effects of adding two commercial urine sample stabilizers and antibiotics (trimethoprim) were also assessed. Subsequently, multiple potential biospecimen stabilizers were added to urine samples and evaluated with Oncuria® in hopes of allowing the urine sample to remain at room temperature for extended periods of time. First, it was demonstrated that voided urine samples stored at room temperate without such stabilizers had different levels of the 10 analytes associated with the Oncuria® test compared to voided urine samples stored at 4°C. Next, we evaluated the effects of commercially available biospecimen stabilizers. Despite the addition of these stabilizers, the levels of the 10 analytes were altered when the samples were stored at room temperature for prolonged periods of time. Therefore, we could not identify a suitable biospecimen stabilizer that would not require sample refrigeration. In conclusion, to minimize sample degradation/alteration after collection, voided urine samples should be refrigerated until analyzed with Oncuria® as the refrigeration is advantageous for the storage and the transport of these urine samples.

Citation Format: Sunao Tanaka, Kaoru Murakami, Toru Sakatani, Riko Lee, Wayne Hogrefe, Fernando Siguencia, Steven M Smith, Charles J Rosser, Hideki Furuya. Effect of different voided urine sample storage time and temperature, and preservatives, on analysis with the multiplex bead-based Oncuria® bladder cancer immunoassay [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A069.
Abstract A073: The potential of multi-cancer early detection screening for reducing cancer mortality
Authors: Chhatwal Jagpreet , Xiao Jade , ElHabr Andrew , Tyson Christopher , Cao Xiting , Raoof Sana , Fendrick A. Mark , Ozbay A. Burak , Limburg Paul , Beer Tomasz M. , Deshmukh Ashish , Briggs Andrew
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR006) of the Conference Program/Proceedings.

Citation Format: Jagpreet Chhatwal, Jade Xiao, Andrew ElHabr, Christopher Tyson, Xiting Cao, Sana Raoof, A. Mark Fendrick, A. Burak Ozbay, Paul Limburg, Tomasz M. Beer, Ashish Deshmukh, Andrew Briggs. The potential of multi-cancer early detection screening for reducing cancer mortality [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A073.
Abstract B001: ctDNA release kinetics and fragmentation to monitor treatment response and resistance in esophageal adenocarcinoma
Authors: Bartolomucci Alexandra , Kienzle Laura , Ferrier Sarah Tadhg , Edward Lisa-Monique , Bruce Jeffrey , Joung Kwang-Bo , Prokopec Stephenie , Zeng Wotan , Sharma Abirami , Dickinson Kyle , Bertos Nicholas , Cools-Lartigue Jonathan , Ferri Lorenzo , Pugh Trevor J. , Burnier Julia V.
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR003) of the Conference Program/Proceedings.

Citation Format: Alexandra Bartolomucci, Laura Kienzle, Sarah Tadhg Ferrier, Lisa-Monique Edward, Jeffrey Bruce, Kwang-Bo Joung, Stephenie Prokopec, Wotan Zeng, Abirami Sharma, Kyle Dickinson, Nicholas Bertos, Jonathan Cools-Lartigue, Lorenzo Ferri, Trevor J. Pugh, Julia V. Burnier. ctDNA release kinetics and fragmentation to monitor treatment response and resistance in esophageal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B001.
Abstract B004: Biological insights into tissue-agnostic plasma cfDNA methylation signature for surveillance of head and neck tumor recurrence
Authors: Newton Yulia , Burgener Justin , Gruca Margaret , Melton Collin , Min Jun , Licon Abel , Bratman Scott , Williams Alan , De Carvalho Daniel D
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR004) of the Conference Program/Proceedings.

Citation Format: Yulia Newton, Justin Burgener, Margaret Gruca, Collin Melton, Jun Min, Abel Licon, Scott Bratman, Alan Williams, Daniel D De Carvalho. Biological insights into tissue-agnostic plasma cfDNA methylation signature for surveillance of head and neck tumor recurrence [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B004.
Abstract B006: Qualitative research study on the use of minimal residual disease as an intermediate endpoint in multiple myeloma clinical trials in Saudi Arabia
Authors: Alnasser Albandari A , Alqurayshah Tariq H
Published: November 2024

Introduction: The U.S. Food and Drug Administration has recently considered minimal residual disease (MRD) as an acceptable accelerated approval endpoint in multiple myeloma (MM). Meta-analysis studies have shown the clinical benefit of MRD negativity in certain hematological cancers such as MM. Objectives: This qualitative research study, with a unique focus on the Saudi context, aims to assess the opinions and experiences of hematology and oncology specialists and consultants in Saudi Arabia. The study is particularly interested in their views on the use of MRD as an intermediate endpoint in early-phase clinical trials for fast-track drug approval by the Saudi Food and Drug Authority in the context of multiple myeloma. This includes assessing the use of MRD in both newly diagnosed and relapsed/refractory MM. The secondary objective is to gather information about the feasibility and availability of sensitive MRD detection methods in real-world medical practice and clinical trials in Saudi Arabia. Study Design: The study will involve interviewing 30 registered male or female physicians specialized in hematology and oncology in Saudi Arabia. The physicians will be included in the study using purposive sampling methods. The study will collect the physicians’ opinions and experiences about MRD. The interviews will be conducted through a single focus group and several face-to- face interviews or performed online, using ZOOM. Participants should have more than one year of experience post-residency or post-fellowship training. The predetermined set of semi- structured questions will cover topics such as the definition of MRD, its clinical and research significance, MRD detection thresholds, duration of MRD negativity, and its correlation with other clinical endpoints, such as progression-free survival and overall survival. The interviews will be conducted by scientific oncology and hematology evaluation experts at the Saudi Food and Drug Authority, who play a crucial role in this study. The study will consist of 5–10 semi- structured one-to-one interviews and focused group discussions of as few as four participants. Before starting any interview, participants will complete consent forms, including the study’s goals and who will conduct the study. Qualitative data will be prepared and analyzed by an expert in data analysis, ensuring the highest research standards. The results will be presented using descriptive and interpretive methods.

Citation Format: Albandari A Alnasser, Tariq H Alqurayshah. Qualitative research study on the use of minimal residual disease as an intermediate endpoint in multiple myeloma clinical trials in Saudi Arabia [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B006.
Abstract B009: Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers
Authors: Salomon Rob , Chen Wenhan , Shale Charles , Toumari Mojgan , Lowe Aileen , Li Wenyan , Chen Jingwei , Razavi-Bazaz Sajad , Barahona Paulette , Cui Louise , Mayoh Chelsea , El-Kamand Sam , Tyrrell Vanessa , Wong-Erasmus Marie , Lau Loretta , Fuentes-Bolanos Noemi , Cuppen Edwin , Khoung-Quang Dong-Anh , Staunton Jordan , Mateos Marion K , Trahair Toby , Haber Michelle , Ziegler David S , Ekert Paul , Priestley Peter , Cowley Mark
Published: November 2024

While the use of ctDNA-based minimal residual disease (MRD) monitoring is gaining popularity in adult cancers, this approach is not yet widely adopted in pediatric cancers (PCs). We developed a robust and sensitive assay to monitor ctDNA in PCs, which overcomes PC-specific challenges including low tumor mutational burden, paucity of hotspot mutations and low blood volume. To address these challenges, our innovations include personalized panel design that targets primary tumor mutations from each patient, a fixed panel targeting hotspot mutations, error suppression from duplex deep sequencing and customized pipeline for tumor burden estimation. We retrospectively analyzed 661 blood or cerebrospinal fluid (CSF) samples from 168 patients. We achieved an average detection limit of 0.005% ctDNA purity leading to MRD detected ranging from 0.001% to 100% with brain tumor consistently showing a low MRD. At disease diagnosis, progression and relapse, our assay identified ctDNA in over 93% of extra- cranial solid tumors, 90% of leukemia, 89% of sarcoma, and 90% of neuroblastoma. For brain tumors, we detected MRD in ∼90% of CSF samples, and in ∼60% of blood samples, a major advance over previous approaches. Importantly, we detected MRD in ∼ 20% of cases with a clinically complete response, predicting relapse up to 6 months before clinical confirmation. Overall, these results demonstrate that our monitoring assay for PCs is an important addition to standard of care for precision-guided treatment.

Citation Format: Rob Salomon, Wenhan Chen, Charles Shale, Mojgan Toumari, Aileen Lowe, Wenyan Li, Jingwei Chen, Sajad Razavi-Bazaz, Paulette Barahona, Louise Cui, Chelsea Mayoh, Sam El-Kamand, Vanessa Tyrrell, Marie Wong-Erasmus, Loretta MS Lau, Noemi Fuentes-Bolanos, Edwin Cuppen, Dong-Anh Khoung-Quang, Jordan Staunton, Marion K Mateos, Toby Trahair, Michelle Haber, David S Ziegler, Paul Ekert, Peter Priestley, Mark Cowley. Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B009.
Abstract B010: Prognostic value of circulating tumor cells in stage III and IV melanoma: A systematic review and meta-analysis
Authors: Chen Jennifer H. , Hwang Hyunsoo , Dong Bamboo , Sarli Vanessa N. , Upshaw Joshua R. , Meas Salyna , Lucci Anthony
Published: November 2024

Introduction: Previous studies have demonstrated a role for assessing circulating tumor cells (CTC) in melanoma, but significant heterogeneity among studies has limited application in the clinical setting. We sought to evaluate the prognostic value of CTCs in advanced stage melanoma using a standardized CTC enumeration platform. Methods: A PubMed literature search was conducted up to March 2024. All studies evaluating CTC enumeration using CellSearchTM with outcomes data were included. Student's t-test was used to compare differences between groups. Hazard ratios (HR) were pooled using random effects model to assess the association of CTCs with overall survival (OS). I 2 statistic and Cochran’s Q test, sensitivity analyses, and Egger’s test of asymmetry were used to assess study heterogeneity, differential impact of individual studies, and publication bias, respectively. Results: Of the 12 studies identified, nine met inclusion criteria. A total of 678 patients were included, of which 337 (49.6%) were stage III and 342 (50.4%) were stage IV. The majority of studies reported CTC rates using a cut-off of ≥ 1 (6 studies, 66.7%), while three studies used ≥ 2 and five studies used both. Median follow-up time was available for six studies and ranged from 5.9-48 months (median 13.4). Average CTC detection rate (≥ 1 or 2) was 41% (SD 14.0) and was significantly higher using a cut-off of ≥ 1 (45.4%, SD 12.6) compared to ≥ 2 (26.1%, SD 2.7, p = 0.02). Pooled analysis of two studies demonstrated significantly worse OS with CTC ≥ 1 (HR 1.6, 95% CI: 1.0-2.6, p = 0.04). Similarly, pooled analysis of five studies with available HRs demonstrated significantly worse OS with CTC ≥ 2 (HR 2.1, 95% CI: 1.4-3.1, p = 0.0003). Among these five studies, moderate heterogeneity was observed (I2 = 43.4%), although this was not statistically significant (Q statistic p = 0.13). Sensitivity analyses confirmed the prognostic value of CTC ≥ 2, with pooled HRs ranging from 1.9-2.4 after consecutive omission of each study from the overall analysis. Conclusion: Regardless of the CTC cutoff used (≥ 1 or 2), presence of any CTCs was a strong prognostic marker in patients with advanced stage melanoma. Incorporation of CTC assessments in clinical practice may help risk stratify patients and guide treatment decisions. Further studies are needed to determine the optimal cut-off point for CTC status in assessing prognosis.

Citation Format: Jennifer H. Chen, Hyunsoo Hwang, Bamboo Dong, Vanessa N. Sarli, Joshua R. Upshaw, Salyna Meas, Anthony Lucci. Prognostic value of circulating tumor cells in stage III and IV melanoma: A systematic review and meta-analysis [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B010.
Abstract B029: Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction
Authors: Li Xinxing , Liu Tao , Bacchiocchi Antonella , Li Mengxing , Cheng Wen , Wittkop Tobias , Mendez Fernando , Wang Yingyu , Tang Paul , Yeung George , Yao Qianqian , Bosenberg Marcus , Sznol Mario , Yan Qin , Faham Malek , Weng Li , Halaban Ruth , Jin Hai , Hu Zhiqian
Published: November 2024

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for detection of molecularresidual disease (MRD), its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read level, achieving an error rate of 4.2 × 10-7, which is about two orders of magnitude lower than a read-centric de-noising method. Application of AccuScan to MRD demonstrated analytical sensitivity down to 10-6 circulating tumor allele fraction at 99% sample level specificity. AccuScan showed 90% landmark sensitivity (within 6 weeks after surgery) and 100% specificity for predicting relapse in colorectal cancer. It also showed 67% sensitivity and 100% specificity with esophageal cancer using samples collected within one week after surgery. When AccuScan was applied to monitor immunotherapy in melanoma patients, the circulating tumor DNA (ctDNA) levels and dynamic profiles were consistent with clinical outcomes. Overall, AccuScan provides a highly accurate WGS solution for MRD detection, empowering ctDNA detection at parts per million rangewithout requiring high sample input or personalized reagents.

Citation Format: Xinxing Li, Tao Liu, Antonella Bacchiocchi, Mengxing Li, Wen Cheng, Tobias Wittkop, Fernando Mendez, Yingyu Wang, Paul Tang, George Yeung, Qianqian Yao, Marcus Bosenberg, Mario Sznol, Qin Yan, Malek Faham, Li Weng, Ruth Halaban, Hai Jin, Zhiqian Hu. Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B029.
Abstract B033: Towards magnetic resonance microscopy for liquid biopsy in cancer therapy monitoring
Authors: Briegel Karl D. , Allert Robin D. , Bucher Dominik B. , Draeger Julia D. , Grafenstein Nick R v. , Nie Linyan
Published: November 2024

The advancement of liquid biopsy techniques promises to revolutionize cancer diagnostics and therapy monitoring, by offering a minimally invasive approach to track tumor progression and treatment efficacy. One central issue preventing advancements are innovations in sensor technology, necessary to enable the detection of molecular and cellular biomarkers with sufficient precision. Over the past decade, atomic-scale quantum sensors have emerged as powerful detectors, offering the ability to perform precise measurements of temperature, pressure, and magnetic fields on the single cell scale. These sensors, based on the interaction of spin qubits with their environment, have the unique capability to amplify and exploit environmental interactions for highly accurate detection, making them ideal for complex biological applications. In this context, we present an advanced quantum sensing platform specifically tailored for liquid biopsy applications in cancer therapy monitoring. This platform integrates the capabilities of optical microscopy with magnetic resonance imaging (MRI) techniques, utilizing nitrogen-vacancy (NV) centers in diamond as quantum sensors by converting magnetic resonance signals into optical signals, which are subsequently captured by a high-speed camera. Our platform offers a novel approach, promising quantitative analysis of single cancer cells from liquid samples with unprecedented accuracy. Unlike traditional MRI, our method captures signals over a wide field of view directly in real space. Each camera pixel records a magnetic resonance spectrum, providing detailed multicomponent information about the sample, such as molecular concentration, diffusion, and relaxation behavior, which are critical for understanding the tumor’s microenvironment. Our quantum sensing technology holds significant potential for enhancing the sensitivity of liquid biopsies. By capturing detailed molecular information from blood or other body fluids, it will enable in-depth analysis of Circulating Tumor Cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and other biomarkers.

Citation Format: Karl D. Briegel, Robin D. Allert, Dominik B. Bucher, Julia D. Draeger, Nick R v. Grafenstein, Linyan Nie. Towards magnetic resonance microscopy for liquid biopsy in cancer therapy monitoring [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B033.