bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Hypertension and Its Clinical and Psychological Factors in Type 2 Diabetes Patients in Ghana: A Secondary Analysis of a Cross‐Sectional Study
Authors: Boima V. , Yorke E. , Ganu V. , Twumasi L. , Ekem-Ferguson G. , Dey D. , Kretchy I. A. , Agyabeng K. , Mate-Kole C. C.
Published: November 2024

Background: Hypertension (HTN) is common in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and HTN have a higher risk of heart disease, kidney disorders, and mortality than those with either HTN or T2DM alone. Patients’ psychological well‐being plays a significant role in the optimum management of these chronic conditions. This study is aimed at determining the current prevalence of HTN and its related clinical and psychological factors in patients with T2DM.

Methods: This cross‐sectional study was conducted at the Korle‐Bu Teaching Hospital with 156 patients diagnosed with T2DM. A structured questionnaire was used to obtain information on sociodemographic and clinical characteristics. In addition, the following information was obtained from the patients’ clinical files: blood pressure, height, weight, waist circumference, serum creatinine, and urine protein. Depression, resilience, and coping skills of the participants were measured using the Brief Symptom Inventory‐18, Resilience Scale for Adults, and Brief COPE Inventory, respectively. Data were analyzed using STATA version 18, with a significance level of p < 0.05.

Results: The median age of respondents was 62.0 (IQR: 51.50, 67.00) years. The majority was female (76.3%). The prevalence of HTN among the patients with T2DM was 79.9% (95% CI: 72.7–85.9). The average body mass index (BMI) of the patients was 28871kg/m2 with 34.8% and 36.2% being overweight and obese, respectively. The average HBA1C level was 8.6 ± 2.1 with 71.8% of the patients having poor glycemic control. Increasing age, caregiver, and personal resilience were factors significantly associated with HTN (p value of <0.05) among patients with T2DM.

Conclusion: The prevalence of HTN among T2DM patients was high; age, caregiver, and personal resilience significantly predicted HTN among T2DM patients. These findings have implications for healthcare providers in implementing strategies to reduce central obesity and incorporating resilience as an important factor in improving treatment outcomes in patients with T2DM.
Effects of a Tailored Mobile Messaging Intervention for Indoor Tanning Cessation in Young Females: A Randomized Clinical Trial
Authors: Mays Darren , Alalwan Mahmood A. , Long Lauren , Atkins Michael B. , Tercyak Kenneth P.
Published: November 2024

Background:

Indoor tanning increases the risk of skin cancer and can become addictive. There is little research on indoor tanning cessation interventions.

Methods:

From 2019 to 2022, we conducted a clinical trial (n = 265) testing a tailored mobile messaging cessation intervention in 18- to 30-year-old females screened for indoor tanning addiction. Participants were randomized to a control arm receiving standard risk education or a cessation intervention arm receiving tailored mobile messaging for 4 weeks. The main outcomes were indoor tanning cessation, motivation to quit, quit attempts, and indoor tanning cognitions assessed at the end of treatment and 3 months later.

Results:

At the end of treatment, intervention participants were more likely to report quitting indoor tanning [OR = 2.10, 95% confidence interval (CI) = 0.99–4.44; P < 0.05], but there were no significant differences by 3 months (OR = 1.54, 95% CI = 0.82–2.87; P = 0.17). Intervention participants who did not quit reported higher motivation to quit than control participants at the end of treatment (M = 3.40, SD = 1.72, M = 2.54, SD = 1.63; P < 0.01) and 3 months (M = 3.75, SD = 1.93, M = 2.85, SD = 1.85; P < 0.01).

Conclusions:

Tailored mobile messaging successfully affects indoor tanning cessation behaviors and cognitions in young adult females who meet the screening criteria for tanning addiction.

Impact:

This trial provides preliminary support for the efficacy of a mobile messaging cessation intervention for young adult females who meet the screening criteria for tanning addiction. Results indicate that additional intervention features should be tested to increase the durability of effects.
Abstract A005: Microbind affinity blood filter platform technology with affinity for heparan sulfate rapidly removes circulating epithelial tumor and cancer stem cells while downregulating VEGF A in patients with advanced and refractory solid tumors
Authors: ILIC Sanja , Premuzic Vedran , Ward Robert
Published: November 2024

Background: Vascular endothelial-derived growth factor A(VEGFA) has been proven to be integral in the molecular pathogenesis of metastasis and tumor growth. It is known that VEGF is responsible for encoding a heparin-binding protein, which exists as a disulfide-linked homodimer which serves to promote the propagation and movement of vascular endothelial cells. This is essential for both pathological and physiological angiogenesis. CETC and cancer stem cells are potent secretors of VEGFA which is an essential cytokine that facilitates new vascular vessel formation, thus further enabling metastatic tumor growth. Methods: We developed a new extracorporeal microbind affinity blood filter platform technology with active heparane sulfate receptors (onco seraph). Heparin is cleaved into short chains which are permanently covalently bound to ultrahigh molecular weight polyethylene (UHMWPE) surfaces to create a new composition of matter. Liquid biopsy established high capacity for the rapid removal of CETC and PDAC cancer stem cells. Onco seraph was investigated in a dose escalation phase I/II clinical trial in adult patients with advanced and relapsed/refractory solid (what) and/or PDAC after standard of care and other lines of therapy failed in preventing disease progression. Results: To date 12 patients have been treated with onco seraph. No patient experienced treatment related adverse effects. Best responses include complete responses and stable disease at a low oncoseraph dose. Greatest efficacy was observed for patients whose liquid biopsy revealed significant and rapid reduction of CETC and cancer stem cells, followed by greater than 50% reduction in circulating VEGFA. Conclusions: This data supports the conclusion that the onco seraph platform technology is safe and has a high therapeutic value as an extracorporeal treatment for metastatic solid tumors refractory to standard of care.

Citation Format: Sanja ILIC, Vedran Premuzic, Robert Ward. Microbind affinity blood filter platform technology with affinity for heparan sulfate rapidly removes circulating epithelial tumor and cancer stem cells while downregulating VEGF A in patients with advanced and refractory solid tumors [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 A005.
Abstract A023: Advancing RNA liquid biopsy technology via long-read sequencing
Authors: Kim Daniel H.
Published: November 2024

Recent studies have begun to highlight the advantages of RNA-based liquid biopsy technology for cancer early detection, and we sought to further advance the development of RNA liquid biopsies by incorporating single-molecule, long-read sequencing technology. Cell-free RNAs are dynamically secreted by the cells that comprise our tissues and organs but are thought to be largely degraded in the blood. To determine the true length of cell-free RNAs, we performed long-read nanopore sequencing on cell-free RNAs isolated from pancreatic and esophageal cancer patient plasma and found that thousands of genes are detectable as full-length cell-free RNAs in vivo. By creating a custom annotation of the transcriptome for cell-free RNA quantification, we found that cancer patients exhibit high levels of repetitive cell-free RNAs in plasma, with full-length, SINE-derived cell-free RNAs being among the most abundant repetitive RNAs. Moreover, we found that utilizing repetitive cell-free RNA features substantially improved the performance of our machine learning models for cancer classification. Notably, nanopore sequencing enabled us to discover over 250,000 novel cell-free RNAs that have not been previously annotated in the human genome. Our findings highlight the value and utility of long-read nanopore sequencing of cell-free RNAs for discovering and leveraging novel RNA biomarkers for cancer early detection via RNA liquid biopsy technology.

Citation Format: Daniel H. Kim. Advancing RNA liquid biopsy technology via long-read sequencing [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 A023.
Abstract A028: Precise monitoring of osteosarcoma patients by noninvasive assessment of matrix metalloproteinases activities in plasma extracellular vesicles
Authors: Lee Junseok , Ji You-Ren , Kim Hyoyong , Chen Zhao , Zhang Ryan , Banuet Diego , Mathkour Yusef , Vo Kenny , Jonas Steven , Zhu Yazhen , Tseng Hsian-Rong
Published: November 2024

Osteosarcoma (OS) is the most prevalent bone cancer in children, characterized by aggressive primary tumors and high metastatic potential. Current treatment protocols involve a combination of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy, tailored based on histological grade and metastatic risk. Identifying metastatic lesions through routine imaging significantly impacts treatment outcomes, highlighting the need for innovative diagnostic tools for timely monitoring. Noninvasive in vitro diagnostics, analyzing circulating tumor components like tumor-derived extracellular vesicles (EVs), would offer promise for monitoring treatment responses in pediatric sarcomas. Matrix metalloproteinases (MMPs) play a crucial role in tumor progression by degradation of the extracellular matrix; thus, recent research has focused on understanding their functional roles by profiling their proteolytic activities. Tumor EVs are crucial in transporting MMPs to facilitate invasion and metastasis, making them suitable surrogate for noninvasive profiling of MMP activities. Herein, we introduce an innovative OS EV MMP Activity Assay to assess MMP activities in OS patients noninvasively. This assay evaluates six different combinations of surface markers on OS EVs and OS-associated MMPs, generating a unique profile for each patient. Using a logistic regression model, an OS EV MMP Activity Score is generated from the most effective combinations. This Score has shown excellent performance in distinguishing between metastatic and localized OS. In a longitudinal study of six OS patients undergoing treatment, the Score strongly correlated with treatment response as measured by routine imaging. The assay represents a significant advancement in harnessing tumor EVs for diagnostics, providing a noninvasive, quantitative, and reliable approach to assess MMP activities in solid tumors.

Citation Format: Junseok Lee, You-Ren Ji, Hyoyong Kim, Zhao Chen, Ryan Zhang, Diego Banuet, Yusef Mathkour, Kenny Vo, Steven Jonas, Yazhen Zhu, Hsian-Rong Tseng. Precise monitoring of osteosarcoma patients by noninvasive assessment of matrix metalloproteinases activities in plasma extracellular vesicles [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 A028.
Abstract A054: Oncogenic functions of alternatively spliced MDM2-ALT2 isoform in retroperitoneal liposarcoma
Authors: de Faria Fernanda Costas C. , Khurshid Safiya , Sarchet Patricia , Tahara Sayumi , Casadei Lucia , Grignol Valerie , Karna Roma , Rentsch Sydney , Sp Nippin , Beane Joal D , Mazzoccoli Luciano , Montes Matias , Nigita Giovanni , Sharick Joe T , Leigth Jennifer L , Calore Federica , Chandler Dawn , Pollock Raphael E
Published: November 2024

Retroperitoneal liposarcoma (RPLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS). Complete surgical resection remains the mainstay treatment while the high rate of locoregional recurrence constitutes the predominant cause of mortality. Well- differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are the most frequent subtypes of RPLPS and present amplified MDM2 gene as a hallmark. However, there are few reports evaluating the role of alternatively spliced MDM2 transcripts in RPLPS. In this study, we assessed MDM2-ALT2 expression levels in a cohort of RPLPS patients and evaluated biological functions of MDM2-ALT2 isoform in vitro in DDLPS cell lines. Using BaseScope™ and qPCR, we demonstrated that MDM2-Full Length (MDM2-FL) and MDM2-ALT2 expression levels were upregulated in RPLPS patient-derived tissue samples compared to normal adjacent to tumor tissue (NAT). DDLPS cells overexpressing MDM2-FL or MDM2-ALT2 had higher proliferation rates and increased migration and invasion capacities, as well as increased protein levels of p- AKT, mTOR, p70S6K, MMP2 and cJun. Simultaneous overexpression of MDM2-ALT2 and AKT silencing showed that AKT inhibition impaired p-p70S6K and MMP2 protein increased levels and led to significantly decreased proliferation and migration rates compared to cells overexpressing MDM2-ALT2 only. Taken together, our data suggest that MDM2-ALT2 may promote RPLPS progression.

Citation Format: Fernanda Costas C. de Faria, Safiya Khurshid, Patricia Sarchet, Sayumi Tahara, Lucia Casadei, Valerie Grignol, Roma Karna, Sydney Rentsch, Nippin Sp, Joal D Beane, Luciano Mazzoccoli, Matias Montes, Giovanni Nigita, Joe T Sharick, Jennifer L Leigth, Federica Calore, Dawn Chandler, Raphael E Pollock. Oncogenic functions of alternatively spliced MDM2-ALT2 isoform in retroperitoneal liposarcoma [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 A054.
Abstract A057: Cancer-induced epigenomic changes in circulating immune cells enable breast, colorectal and lung cancer detection
Authors: Guler Gulfem D , Mognol Giuliana P , Ning Yuhong , Fraire Carolina , Haan David , Kesling Michael , Malta Roger , Peters Melissa , Bergamaschi Anna , Phillips Tierney , Chowdhury Shimul , Volkmuth Wayne , Levy Samuel
Published: November 2024

Background: Epigenomic changes via the measurement of 5-hydroxymethylation cytosine (5hmC) in DNA have been shown to enable detection in a variety of cancers including pancreatic and ovarian cancer in plasma-derived cell-free DNA (cfDNA). Here, we investigated whether blood-based 5hmC profiling of genomic DNA (gDNA) derived from cells of the buffy coat (BC) possess signals that enable the detection of breast, colorectal and lung cancers. Method: Blood samples collected in Streck tubes from cancer patients or non-cancer controls were processed to obtain buffy coat and plasma samples. gDNA and cfDNA was isolated from buffy coat and plasma, respectively. gDNA or cfDNA was then subjected to 5hmC enrichment by click chemistry followed by preparation of sequencing libraries. Sequencing was performed to obtain genome-wide 5hmC profiles of buffy coat gDNA and cfDNA samples. Results: Differential hydroxymethylation analysis of BC gDNA revealed increased 5hmC over genes associated with myeloid lineage in breast, colorectal and lung cancers relative to non-cancer controls. Flow cytometry analysis confirmed increases in myeloid cells in cancer samples relative to non-cancer controls. 5hmC patterns in BC gDNA showed a larger number of cancer-associated changes compared to cfDNA, in particular this was found in early-stage disease. 5hmC features from BC gDNA or plasma-derived cfDNA were used to build prediction models that yielded cancer classification with overall sensitivity of 51.3% and 52.6% at 98% specificity, for BC or cfDNA, respectively. For early-stage cancer, the sensitivity at 98% specificity was 46.5% for the BC and 28.2% for cfDNA model. A final prediction model incorporating features from both tissue sources achieved superior classification (65.8% sensitivity) at 98% specificity, compared with using features from either tissue source alone, particularly for early-stage cancer which achieved 53.5% sensitivity of cancer detection. Conclusion: Our results demonstrate that cancer impacts the 5hmC profiles of buffy coat cells which can be leveraged for cancer detection using blood.

Citation Format: Gulfem D Guler, Giuliana P Mognol, Yuhong Ning, Carolina Fraire, David Haan, Michael Kesling, Roger Malta, Melissa Peters, Anna Bergamaschi, Tierney Phillips, Shimul Chowdhury, Wayne Volkmuth, Samuel Levy. Cancer-induced epigenomic changes in circulating immune cells enable breast, colorectal and lung cancer detection [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 A057.
Abstract A067: lncTransformer: Identifying novel prognostic biomarkers for pancreatic cancer using deep learning models
Authors: Singh Shivali
Published: November 2024

Pancreatic cancer remains a formidable challenge due to high mortality rates and limited therapeutic options due to late detection of the cancer. Recent literature has focused on investigating the potential of long noncoding RNAs (lncRNAs) as biomarkers in several cancers. To identify significantly altered expression of lncRNA in pancreatic cancer, I collected information from the Cancer Genome Atlas (TCGA) and extracted RNA-sequencing (RNA-seq) transcriptomic profiles of pancreatic carcinomas. Out of 60,660 gene transcripts shared between 151 pancreatic cancer patients, 38 lncRNAs were identified to be significantly differentially expressed. To find the lncRNAs related to metastatic progression of pancreatic cancer, different machine learning algorithms, including logistic regression (LR), support vector machine (SVM), random forest classifier (RFC), and a custom autoencoder model were trained to identify potential prognostic biomarkers. The custom deep learning model predicted metastatic prognostic biomarkers with a 92% accuracy, with the second-best accuracies coming from the SVM and RFC models, having an accuracy of 76%. Using the deep learning model, the following novel lncRNA and gene biomarkers were identified: LINC01300, SERPINB13, AC010789.1, TMPRSS15, DUSP5-DT, AL513128.3, MIR205HG, LINC00486, RF00019, LINC01115, and AC133530.1. Further investigating these results, specifically the identified lncRNA, the LINC01300 was identified to be potentially circulating in the blood. If further analysis proves this hypothesis correct then LINC01300 along with other identified genes could serve as a biomarker panel for a liquid biopsy. The identified biomarkers would be especially helpful in rural areas with lower accessibility to healthcare as it would allow for an easier, more efficient, and cost-effective method of pancreatic cancer detection. Based on these findings, further investigations of this gene panel are being conducted, in vitro and in vivo, to create a novel liquid biopsy to assist in the prognostic diagnosis of metastatic progression of pancreatic cancer.

Citation Format: Shivali Singh. lncTransformer: Identifying novel prognostic biomarkers for pancreatic cancer using deep learning models [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 A067.
Abstract B041: High purity CTC RNA sequencing identifies poor prognosis lineage states in castrate resistant prostate cancer
Authors: Sharifi Marina N , Sperger Jamie M , Taylor Amy K , Tippins Katharine E , Reese Shannon R , Carreno Viridiana , Kaufmann Katherine R , Chang Alex H , Nunamaker Luke A , Linebarger Charlotte , Helzer Kyle T , Bootsma Matthew , Blitzer Grace C , Floberg John , Kosoff David , McKay Rana R , Wei Xiao X , Zhao Shuang G , Lang Joshua M
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 (PR010) of the Conference Program/Proceedings.

Citation Format: Marina N Sharifi, Jamie M Sperger, Amy K Taylor, Katharine E Tippins, Shannon R Reese, Viridiana Carreno, Katherine R Kaufmann, Alex H Chang, Luke A Nunamaker, Charlotte Linebarger, Kyle T Helzer, Matthew Bootsma, Grace C Blitzer, John Floberg, David Kosoff, Rana R McKay, Xiao X Wei, Shuang G Zhao, Joshua M Lang. High purity CTC RNA sequencing identifies poor prognosis lineage states in castrate resistant prostate cancer [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 B041.
Abstract B070: Dissecting EV dynamics in the sequestration of doxorubicin from breast cancer cells
Authors: Halvaei Sina , Xu Jing , Chittaranjan Suganthi , Gorski Sharon , Williams Karla
Published: November 2024

Background: Extracellular vesicles (EVs) are one of the three main analytes sought for in liquid biopsy development. EVs are released by all cell types including cancer cells and play a crucial role in cell-cell communication. Breast cancer cells have been shown to utilize EVs as a mechanism to sequester chemotherapeutic agents, thereby conferring resistance to treatment. This study investigates the role of EVs in doxorubicin (DOX) resistance in MDA-MB-231 breast cancer cells. Method: MDA-MB-231 cells were exposed to increasing dose of anthracycline for 6 and 12 months. Resistance was confirmed by cytotoxicity assay and western blot. Resistant and parent cells were labeled for immunohistochemistry and their EVs were isolated via ultracentrifugation. EVs were analysed using nanoscale flow cytometry and sent for mass spectrophotometry. Result: Using nanoscale flow cytometry, we optimized a method to detect DOX-carrying EVs based on the intrinsic fluorescence of the drug. We found that DOX-resistant cells exhibited lower intracellular DOX accumulation and higher expression of the EV marker CD63 compared to their parental counterparts. Conclusion: These results suggest that chemoresistant breast cancer cells may alter their EV production machinery to evade the lethal effects of DOX. Understanding this mechanism could lead to novel strategies to overcome chemoresistance in breast cancer.

Citation Format: Sina Halvaei, Jing Xu, Suganthi Chittaranjan, Sharon Gorski, Karla Williams. Dissecting EV dynamics in the sequestration of doxorubicin from breast cancer cells [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 B070.
Abstract IA004: Early cancer dissemination: Circulating tumor cells in ductal carcinoma in situ patients
Authors: Nagrath Sunitha , Nagpal Neha , Rupp Brittany , Hong Yan , Behbod Fariba , Wicha Max
Published: November 2024

Raised awareness about the importance of early breast cancer diagnostics has led to an increased detection rate of ductal carcinoma in situ (DCIS) through mammographic screening. DCIS, often termed as 'Stage 0' carcinoma, is characterized by neoplastic cells confined within the basement membrane. Despite the significant treatment efforts for most DCIS patients, the 20-year breast cancer mortality rate post-diagnosis, with or without treatment, remains at 3.3%. To deepen the understanding of breast cancer oncogenesis, recent studies have highlighted the clonal diversity within the DCIS tumor microenvironment and the presence of disseminated tumor cells in DCIS patients. Nonetheless, significant gaps persist in identifying diagnostic characteristics that predict which DCIS patients are more likely to experience progression or recurrence. Ultimately, this project aims to enhance DCIS patient stratification through the high-throughput isolation and analysis of circulating biomarkers. In this study, we establish a novel workflow that addresses the limitations of traditional tissue-based diagnostics by transitioning to liquid biopsies. This research not only builds upon emerging evidence of early breast cancer cell dissemination during carcinogenesis but also explores the utility of circulating tumor cells (CTCs) as biomarkers in DCIS. The use of the labyrinth, a high-throughput inertial microfluidic device, has shown success in isolating CTCs based on their larger size relative to white blood cells. Unlike antigen- based isolation methods, inertial microfluidic devices can capture heterogeneous CTCs with varying surface proteins. Leveraging this technology, we successfully isolated and identified CTCs in DCIS patients. Furthermore, single-cell RNA sequencing of the isolated DCIS CTCs allowed us to identify prognostically significant signatures. Overall, our study presents a workflow capable of identifying characteristics associated with a greater risk of progression, thus contributing valuable insights into the stratification and management of DCIS patients.

Citation Format: Sunitha Nagrath, Neha Nagpal, Brittany Rupp, Yan Hong, Fariba Behbod, Max Wicha. Early cancer dissemination: Circulating tumor cells in ductal carcinoma in situ 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 IA004.
Abstract IA021: Plasma-only ultrasensitive liquid biopsy to monitor tumor burden and clonal evolution
Authors: Widman Adam , Cheng Alexandre P. , Zinno John , Rajagopalan Srinivas , Saxena Ashish , Altorki Nasser , Landau Dan A.
Published: November 2024

Individual bulk tumor biopsies are invasive and may fail to capture clonal heterogeneity within primary tumors and metastatic sites of disease. Further, analyses of subclonal variants are often hindered by background error rates related to tissue preservation methods (e.g. FFPE) and sequencing artifact. Use of plasma-only ultrasensitive liquid biopsy approaches may allow for noninvasive inference of clonality and dynamically track changes in tumor burden. We previously developed MRD-EDGE, a tumor-informed machine learning classifier for ultrasensitive liquid biopsy monitoring of single nucleotide variants (SNVs) and copy number variants (CNVs) using standard plasma whole genome sequencing. For SNVs, MRD- EDGE uses a novel machine learning framework to classify individual cell free DNA (cfDNA) fragments as circulating tumor DNA or cfDNA sequencing artifact. We demonstrated the potential of plasma-only MRD-EDGE to identify SNVs in advanced melanoma and monitor tumor burden throughout treatment with immune checkpoint inhibiton. In tumor-informed settings, MRD-EDGE was used to identify minimal residual disease at tumor fractions (TFs) of 1:100,000 and below. Accurate SNV classification is a function of classifier performance and background error rate. To reduce error rates, we combined MRD-EDGE SNV with paired plus- minus sequencing (ppmSeq) from Ultima Genomics. ppmSeq is a PCR-free approach that leverages the hydrogen bonds of complementary DNA to carry matched native strands directly into sequencing, enabling scalable duplex sequencing. Use of MRD-EDGE SNV together with ppmSeq enables ultrasensitive tracking of early-stage non-small cell lung cancer throughout neoadjuvant immunotherapy. Plasma-only MRD-EDGE is therefore poised to enable dynamic monitoring of tumor burden and clonal composition outside the scope of tumor-informed approaches, including the comparison of SNV composition in cancer recurrence with preoperative disease.

Citation Format: Adam Widman, Alexandre P. Cheng, John Zinno, Srinivas Rajagopalan, Ashish Saxena, Nasser Altorki, Dan A. Landau. Plasma-only ultrasensitive liquid biopsy to monitor tumor burden and clonal evolution [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 IA021.
Abstract IA024: Validation of liquid biopsy approaches for the care of children with cancer
Authors: Crompton Brian
Published: November 2024

Pediatric cancers are driven by a unique set of mutations, destinct from the variants that typically drive adult cancers. Therefore, widely available liquid biopsy assays are often not relevant for detection, quantificaiton, or profiling of circulating tumor DNA in childhood cancer. Custom liquid biopsy approaches have been developed by the Crompton lab and others and these assays demonstrate that ctDNA levels provide valuable prognostic information and can guide some therapeutic choices in pediatrics. Implementation of liquid biopsies into national phase 3 trials for children with cancer will require translation of these approaches into a clinical molecular laboratory environment.

Citation Format: Brian Crompton. Validation of liquid biopsy approaches for the care of children with cancer [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 IA024.
Abstract IA026: Methods for tumor subtype classification using cell-free DNA
Authors: Ha Gavin
Published: November 2024

Accurately diagnosing the tumor histological subtype is crucial for clinical care. Changes in subtype can emerge during treatment resistance. However, obtaining a biopsy to determine the tumor histology presents challenges for patients with advanced cancers. Circulating tumor DNA (ctDNA) is a non-invasive 'liquid biopsy' solution that overcomes this limitation of tissue accessibility. Current ctDNA approaches primarily focuses on detecting genetic mutations, but these alterations alone may not fully delineate tumor histological subtypes or explain treatment resistance. Recent advancements highlight the value of epigenetic information obtained from profiling nucleosome positioning and accessibility in ctDNA. I will discuss how we applied these concepts to develop computational methods for predicting transcriptional activity and classifying tumor subtypes and phenotypes in breast, prostate, and lung cancers. These tools have applications in monitoring treatment-induced phenotype changes and expand on the utility of ctDNA for precision oncology.

Citation Format: Gavin Ha. Methods for tumor subtype classification using cell-free DNA [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 IA026.
Supplementary Data from Genomic Features of Newly Diagnosed Large B-cell Lymphoma with or without Subsequent Disease Progression
Authors: Landsburg Daniel J. , Morrissette Jennifer J.D. , Nasta Sunita D. , Barta Stefan K. , Schuster Stephen J. , Chong Elise A. , Svoboda Jakub , Barlev Ashley , Bagg Adam , Priore Salvatore F.
Published: November 2024

All Supplementary Data
Safety of Oral Food Challenges for Individuals with Low Levels of Cow’s Milk-Specific Immunoglobulin E Antibodies
Authors: Yoshida Takanobu , Kido Jun , Ogata Mika , Watanabe Suguru , Nishi Natsuko , Shimomura Sachiko , Hirai Nami , Tanaka Kenichi , Yanai Masaaki , Mizukami Tomoyuki , Nakamura Kimitoshi
Published: November 2024

Introduction: Cow’s milk (CM) is one of the most common food allergens in Japan. The oral food challenge (OFC) of CM is important for the definite diagnosis of children with CM allergy, and it is recommended to be actively and safely performed in individuals with low CM-sIgE levels. This study aimed to investigate the safety of low-dose CM-OFC in individuals with low CM-sIgE levels and discuss the prognostic factors and appropriate approaches for assessing the starting doses of CM-OFC in these individuals. Methods: We retrospectively analyzed 6,929 OFC tests conducted between January 1, 2017, and December 31, 2021; of which, 1,390 were CM-OFC tests. The characteristics, OFC-positive rates, CM loading, and related factors were analyzed in 138 cases involving low CM-sIgE levels. Stepwise OFC tests were conducted according to the food allergies guidelines in Japan using an open and unblinded method. Results: Among 138 individuals with low CM-sIgE levels, 110 (79.7%) passed the OFC test without any symptoms. Among the cases with OFC-positive status, 50.0% (14/28) cases showed symptoms with low-dose OFC (30–105 mg CM protein). Moreover, complete CM elimination was associated with a significantly high OFC-positive rate, and 60.0% (12/20) of the cases involving complete CM elimination showed symptoms with low-dose OFC. Conclusion: Eighty percent of the patients with low CM-sIgE levels safely completed the OFC test. Nevertheless, careful observation is essential during low-dose OFC test in cases with low CM-sIgE levels, especially in the cases with complete elimination. The starting dose of the OFC test should be reevaluated, and modified using baked milk or a lower dose of CM to ensure safety and early outgrowth of CM allergy.
Prevalence of Undernutrition and Its Contributing Factors Among Cancer Patients in Africa – A Systematic Review and Meta-Analysis of Observational Studies
Authors: Najah Qasi , Selim Rasha , Almosilhy Nereen A. , Asar Ahmed , Ibrahim Moustafa , Sabe Alerab Ameerh Dana , Aldieb Ebtesam
Published: November 2024

Introduction: Cancer poses a significant burden in Africa, where limited resources and infrastructure compound the challenges of managing the disease. Undernutrition, a critical concern among cancer patients, can profoundly affect treatment outcomes and overall prognosis. Despite its importance, the prevalence of undernutrition among African cancer patients remains poorly understood.
Methods: Five major databases were searched for observational studies that reported the prevalence of undernutrition, from inception till February 2024. Study selection, data extraction, and quality assessment were conducted by at least two independent reviewers. The NIH criteria for observational studies were used for quality assessment. A random-effects meta-analysis model was used to estimate the overall undernutrition prevalence, with subgroup analyses conducted based on country and population characteristics.
Results: Twenty-four studies involving 4,283 participants met the inclusion criteria, most studies included children (41%), followed by adults (37%), and women (19%). The overall undernutrition prevalence among African cancer patients was estimated at 32.8% (95% CI, 25.1%, 41.67%) with substantial heterogeneity observed (I² = 95.4%, P < 0.0001). Subgroup analyses revealed significant variations in prevalence across countries and population groups.
Conclusion: Undernutrition is a serious issue among African cancer patients and requires an urgent response with targeted interventions. Tailored nutritional support strategies, considering demographic and regional contexts, are essential for improving patient outcomes.
Clinical Profile of Stroke Chameleons Receiving Intravenous Thrombolysis: Insights from a Single-Center Experience
Authors: Brunser Alejandro M. , Lavados Pablo M. , Muñoz-Venturelli Paula , Olavarría Verónica V. , Mansilla Eloy , Cavada Gabriel , Trejo Maria Elena , González Pablo E.
Published: November 2024

Introduction: In emergency rooms (ERs), 5% of patients experiencing an acute ischemic stroke (AIS) receive an alternative diagnosis; these cases are known as stroke chameleons (SC). The percentage of SC treated with intravenous thrombolysis (IVT) and the characteristics have not been well described. We aimed at investigating the variables associated with the probability receiving IVT. Methods: In this prospective study, we included consecutive patients with SC admitted at the ER of Clínica Alemana between September 2014 and October 2023. Results: Among 1,193 stroke patients; sixty-three (5.2%) corresponded to SC. Ten of these cases (15.8%, 95% CI: 8.8–26.8) were treated with IVT, mean door-to-needle (DTN) time of 85.7 (SD 35) min, median of 73.5 (IQR 62–113) min. SCs who underwent IVT were younger (p = 0.01), with higher NIHSS (p = 0.05). They presented more frequently with altered level of consciousness in the NIHSS (p = 0.01), language abnormities (p = 0.001), and dysarthria (p = 0.01). In multivariate analysis, none of the variables were significantly associated with IVT. A secondary analysis showed that only time to brain imaging was significantly associated with IVT (OR: 0.99; 95% CI: 0.98–0.99; p = 0.01). Conclusions: Almost 1 out of every 7 SC could be treated with IVT but with a prolonged DTN time; the chance of being treated is associated with time to brain imaging.
Introduction: In emergency rooms (ERs), 5% of patients experiencing an acute ischemic stroke (AIS) receive an alternative diagnosis; these cases are known as stroke chameleons (SC). The percentage of SC treated with intravenous thrombolysis (IVT) and the characteristics have not been well described. We aimed at investigating the variables associated with the probability receiving IVT. Methods: In this prospective study, we included consecutive patients with SC admitted at the ER of Clínica Alemana between September 2014 and October 2023. Results: Among 1,193 stroke patients; sixty-three (5.2%) corresponded to SC. Ten of these cases (15.8%, 95% CI: 8.8–26.8) were treated with IVT, mean door-to-needle (DTN) time of 85.7 (SD 35) min, median of 73.5 (IQR 62–113) min. SCs who underwent IVT were younger (p = 0.01), with higher NIHSS (p = 0.05). They presented more frequently with altered level of consciousness in the NIHSS (p = 0.01), language abnormities (p = 0.001), and dysarthria (p = 0.01). In multivariate analysis, none of the variables were significantly associated with IVT. A secondary analysis showed that only time to brain imaging was significantly associated with IVT (OR: 0.99; 95% CI: 0.98–0.99; p = 0.01). Conclusions: Almost 1 out of every 7 SC could be treated with IVT but with a prolonged DTN time; the chance of being treated is associated with time to brain imaging.
Evaluating the Causal Association between Circulating Plasma Proteins, 731 Immune Cell Phenotypes, and Atopic Dermatitis: A Mediation Mendelian Randomization Study
Authors: Zhang Wenjing , Wei Shanshan , Li Qian , Yin Li , Zhu Junhao , Yang Shan , Zhu Silang , Lai Kuan
Published: November 2024

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions and severe itching. However, its pathogenesis has not yet been fully elucidated. The aim of this study was to investigate the causal relationship between plasma proteins and AD, as well as to identify and quantify the potential roles of immune cell phenotypes as mediators. Methods: We utilized summary-level data from genome-wide association studies and conducted a two-sample Mendelian randomization (MR) analysis involving 4,907 circulating plasma proteins, 731 immune cell phenotypes, and AD. Initially, we conducted bidirectional univariate MR analyses to forecast causal effects linking circulating plasma proteins and AD. Subsequently, we employed a two-step MR analysis to scrutinize the immune cell phenotypes that could mediate these effects. The inverse variance weighted was the main method employed for MR analysis, while the Cochran’s Q test and MR-Egger intercept test were used to assess the presence of heterogeneity and pleiotropy, respectively. We then determined whether our results could be influenced by individual single-nucleotide polymorphisms using the “leave-one-out” test. Results: Positive correlations were observed between KRT1, IL18R1, and SEMA6A and the risk of AD, whereas BDH2, ADAMTS3, ANKRD1, TIAM1, MID2, and IFNA16 all showed negative correlations with the risk of AD. Mediation analysis indicated that CD8 on CM CD8br cells acted as a mediator between IFNA16 and AD, with a mediation effect proportion of 11.2%. In addition, sensitivity analyses did not reveal significant heterogeneity or level pleiotropy. Conclusion: Our findings indicated the presence of a one-way causal relationship between the circulating plasma protein IFNA16 and AD. This study also explored immune cell phenotypes that may serve as mediators, offering novel insights into the etiology, pathogenesis, and potential clinical interventions in AD. Nevertheless, these findings need to be validated by clinical and laboratory studies.
The Anti-Elixir Triad: Non-Synced Circadian Rhythm, Gut Dysbiosis, and Telomeric Damage
Authors: Mani Anup Kumar , Parvathi Venkatachalam Deepa , Ravindran Sumitha
Published: November 2024

Aging is an inevitable life process which is accelerated by lifestyle and environmental factors. It is an irreversible accretion of molecular and cellular damage associated with changes in the body composition and deterioration in physiological functions. Each cell (other than stem cells) reaches the limit of its ability to replicate, known as cellular or replicative senescence, and consequently, the organs lose their physiological functions, resulting in overall impairment. Other factors that promote aging include smoking, alcohol, UV rays, sleep habits, food, stress, sedentary lifestyle, and genetic abnormalities. These stress factors can alter our endogenous clock (the circadian rhythm) and the microbial commensals. As a result of the effect of these stressors, the microorganisms that generally support human physiological processes become baleful. The disturbance of natural physiology instigates many age-related pathologies, such as cardiovascular diseases, chronic obstructive pulmonary disorder, cerebrovascular diseases, opportunistic infections, high blood pressure, cancer, diabetes, kidney diseases, dementia, and Alzheimer’s disease. The present review covers the three most essential processes of the circadian clock; the circadian gene mechanism and regulation, the mitotic clock (which plays a vital role in the telomere’s attrition) and the gut microbiota and their metabolome that drive aging and lead to age-related pathologies. In conclusion, maintaining a synchronized circadian rhythm, a healthy gut microbiome, and telomere integrity is essential for mitigating the effects of aging and promoting longevity. The interplay among these factors underscores the importance of lifestyle choices in enhancing overall health and lifespan.
Best Approach for Incomplete Colonoscopy: Colon Capsule Endoscopy or Repeat Conventional Colonoscopy?
Authors: Lima Capela Tiago , Cúrdia Gonçalves Tiago , Rosa Bruno , Cotter José
Published: November 2024

Background: The most appropriate strategy for completing a previous incomplete colonoscopy (IC) is not standardized. We aimed to compare the efficacy and safety of two strategies for completing a previous IC: colon capsule endoscopy (CCE) versus repeat conventional colonoscopy. Methods: A retrospective cohort study that included consecutive adult patients referred to our center after IC under sedation due to irreducible loop formation or colonic fixed angulation was performed. Patients underwent CCE (PillCam COLON2 Medtronic®) or repetition of conventional colonoscopy under sedation. In this setting, an appropriate CCE progression was defined as the capsule reaching the segment achieved during the previous IC. Repeated conventional colonoscopy was considered complete when cecal intubation was accomplished. We compared the rate of appropriate CCE colon progression with the cecal intubation rate from repeated conventional colonoscopy. Quality of colon preparation, diagnostic yield, and rate of adverse events for CCE and colonoscopy was also analyzed. Results: A total of 192 CCE and 181 colonoscopies were performed for IC, primarily due to fixed angulation of the left colon (69.2%, n = 258). There were no significant differences between the two groups (CCE vs. colonoscopy) concerning age, sex, overweight/obesity status, previous abdominal surgery, and reasons for IC. The rate of appropriate colon progression with CCE was not significantly different from the cecal intubation rate of repeated colonoscopy (95.3% vs. 90.1%, p = 0.073, respectively), even after adjusting for the quality of colon preparation (p = 0.122), which differed significantly between the groups (76.0% vs. 92.8%, p < 0.001, respectively). There were no significant differences in overall colorectal findings identified between the CCE and colonoscopy groups (55.2% vs. 62.4%, p = 0.172, respectively), and no adverse events were reported in either group. Conclusions: Our findings suggest that both CCE and repeat conventional colonoscopy are effective and safe options for completing a previous IC.
Excesso e dispêndio: ressoâncias nietzschianas na noção de economia geral, em Georges Bataille
Authors: Lima João Pedro Azevedo
Published: November 2024

Georges Bataille (1897-1962) fue, por segundo momento de la recepción francesa de la filosofía de Friedrich Nietzsche (1844-1900), a partir de la década de 1930, una figura central. Puede decirse que en su filosofía del exceso y la transgresión, Bataille fue el principal precursor del “Nietzsche francés”: el filósofo encuentra en él una defensa de lo que tradicionalmente se consideraba, desde la filosofía socrático-platónica, como irracional: el cuerpo, el inconsciente, el instinto, los impulsos, nociones que reflejan la idea de gasto de Bataille, concepto que busca discutir, con cierta sistematicidad, en textos como “La noción de gasto” y en “La parte maldita”. Dicho esto, el presente trabajo pretende presentar el “Nietzsche de Bataille”, y, específicamente, dilucidar las resonancias del pensamiento nietzscheano en los conceptos de economía general y restringida, tal como los elabora el filósofo francés.
A máscara de couro: o ápice da desfiguração humana
Authors: Pereira Gabriela de Melo
Published: November 2024

La clásica máscara de cuero utilizada en los rituales masoquistas, a pesar de ocultarse, nos revela, según Georges Bataille, “la encarnación misma del caos”: un cubrimiento adherente/artificial sobre los rostros, que trae consigo algo imaginario y profundo. La familiaridad se desvanece y solo queda la certeza de lo impredecible.Como nos describe Eliane Robert Moraes (2017), el rostro es la última etapa del largo proceso de desfiguración humana, que se inicia a mediados del siglo XIX, en la figura de Lautréamont, y finaliza en Bataille, con su mitológico acéfalo. Dado que esta descomposición de lo humano sigue a la descomposición de la figura divina, la mujer enmascarada, para Michel Leiris, se convierte en una nueva divinidad: el horror de esta figura sin rostro es sagrado, ya que es precisamente la experiencia del no ser.El primer collage, realizado de forma analógica, a partir de recortes, composiciones, superposiciones y descomposiciones de imágenes, estaba compuesto por periódicos, papel origami y otros recortes, en papel especial negro de 120g, en formato A4.El segundo collage, a diferencia del primero, se hizo digitalmente en una aplicación de teléfono inteligente y con imágenes cuidadosamente seleccionadas de Internet, en un formato de 1080x1350 píxeles. Ambos tienen composiciones y encuadres que buscan una estética urbana, gótica y sensorial, además de traer fuertes elementos de la cultura bondage japonesa.