bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 764: Automated walk away NGS sample preparation for constructing in-line molecular barcoded RNA libraries from Fresh Frozen and FFPE samples
Authors: Bigdeli Saharnaz , Arezi Bahram , Godoski Jan , Rhodes Denise , Aguilar Ryan , William Karen , Buehler Bernd , Zhu Ji , Allen Ronda 
Published: April 2023

Abstract
RNA-Seq is a revolutionary technology for transcriptome analysis, which has been used to quantify transcript levels, confirm gene annotation, identify novel transcripts, splice variants, and fusion detection. Traditionally, the usefulness of RNA-Seq has been limited by pre-analytical (sample availability, low integrity, tumor heterogeneity, complex protocols) and analytical factors (small mRNA fraction, high read duplicate rate), which can lead to higher costs, longer turnaround times, and false negative results. We have developed and automated a streamlined workflow for construction of highly complex RNA Libraries from fresh frozen and FFPE samples that addresses these concerns. We use target enrichment by bait selection with FFPE-derived samples, where rRNA depletion is found to be inconsistent and poly(A) enrichment cannot be used due to degradation of the source material. A fully automated protocol using pre-aliquoted reagents, has been optimized on the Magnis NGS Prep System for a wide range of RNA inputs (10-200 ng), various sample types (Intact and FFPE total RNA) and equipped with 192 Unique Dual sample Indices (UDI) to minimize the effects of possible index hopping and contamination. Addition of in-line molecular barcodes incorporated at the ligation step helps differentiate fragmentation from PCR duplicates, which increases the total number of reads available for further analysis (gene expression and fusion detection). With minimal risk of contamination, this automated protocol delivers up to eight target-enriched NGS Illumina sequencing-ready cDNA libraries from total RNA input per run in about 12 hours without the need of any user intervention. Both catalog and custom probes can be utilized, and PCR cycles can easily be adjusted from the touchscreen to optimize the library yields. For Research Use Only. Not for use in Diagnostic procedures.
Citation Format: Saharnaz Bigdeli, Bahram Arezi, Jan Godoski, Denise Rhodes, Ryan Aguilar, Karen William, Bernd Buehler, Ji Zhu, Ronda Allen. Automated walk away NGS sample preparation for constructing in-line molecular barcoded RNA libraries from Fresh Frozen and FFPE samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 764.
Abstract 766: A genome-wide association study identifies the association of common variants in the major histocompatibility complex with cervical cancer in black South African women
Authors: Kamiza Abram Bunya , Chen Wenlong Carl , Brandenberg Jean-Tristan , Ramsay Michele , Mathew Christopher G. 
Published: April 2023

Abstract
Cervical cancer is the second most common female gynaecological malignancy in sub-Saharan Africa (SSA). Previous genome-wide association studies (GWASs) identified genetic variants associated with cervical cancer in women of European and Asian ancestry, particularly within the major histocompatibility complex (MHC). However, owing to the complexity of linkage disequilibrium and varied environmental exposures in different ancestral populations, regional GWASs are needed to investigate the genetic contribution to the pathogenesis of cervical cancer in continental African populations. A total of 1,637 cervical cancer patients and 761 controls in women of African ancestry were identified from the Johannesburg Cancer Study and the AWI-Gen study, respectively. DNA samples were genotyped on the 2.3 million H3Africa GWAS SNP array and genotyped SNPs imputed to a total of 13,937,308 SNPs. The association between genetic variants and cervical cancer was tested using linear mixed models, adjusting for five principal components and cryptic relatedness. We identified one locus within the MHC region associated with cervical cancer at genome-wide significance, led by rs3129965 (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.87-0.92, P = 2.292 x 10-11) near HLA-DRA. Four other loci were strongly associated with cervical cancer (P&lt;5x10-7), including rs575105445 (OR=0.77, 95%CI=0.70-0.85, P = 2.188 x 10-07) near HLA-C,rs184053148 (OR =0.79, 95% CI = 0.72-0.86, P = 4.19 x 10-07) in TRIM31,rs12496921 (OR=0.88, 95%CI = 0.84-0.92, P = 1.32 x 10-07) in ROPN1B and rs114031308 (OR= 1.27, 95% CI =1.16-1.39, P =3.06 x 10-07) near TTC26. The genes in these loci are implicated in numerous pathways including antiviral immunity, DNA repair, the regulation of p53, apoptosis, cell growth and differentiation. These discoveries demonstrate the important contribution of common genetic variants to cervical cancer susceptibility and provide insights into its pathogenesis in women of African ancestry.
Citation Format: Abram Bunya Kamiza, Wenlong Carl Chen, Jean-Tristan Brandenberg, Michele Ramsay, Christopher G. Mathew. A genome-wide association study identifies the association of common variants in the major histocompatibility complex with cervical cancer in black South African women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 766.
Abstract 781: Clinical implications for returning polygenic risk information for skin cancer to ultra-high risk organ transplant recipients
Authors: Seviiri Mathias , Law Matthew H. , Hopkins Peter , Olsen Catherine M. , Whiteman David C. , MacGregor Stuart 
Published: April 2023

Abstract
Introduction: Organ transplant recipients (OTRs) have an elevated risk of developing keratinocyte cancer (KC). We have previously shown that a KC polygenic risk score (PRS) effectively triages OTRs for KC risk, with 50% of transplantees with high genetic risk developing KC within 3 years of follow up. However, readiness for clinical application of the KC PRS, its application to triage OTRs in the clinic and the return of the genetic risk information have not yet been assessed.
Objectives: 1) To evaluate patients’ readiness to receive genetic risk information for KC risk stratification in a lung transplant clinic. 2) To assess whether returning the PRS results to patients influences skin cancer screening, incidence, and sun protection behavior.
Methods: We recruited 100 lung transplantees from the Prince Charles Hospital in Queensland into the ASCOT prospective study. We assessed their attitude, knowledge, and perceptions of genetic testing for KC risk stratification. We also collected genetic data. We developed a KC risk stratification pipeline, and triaged the transplantees. PRS results and KC prevention advice were returned to the high risk group. All transplantees are being followed-up for sun protection and screening behaviors, and skin cancer outcomes.
Results: 50% of OTRs were highly likely to accept genetic testing for KC risk stratification. Following transplantation, there was a drastic change in the perception of KC risk and severity, and the majority of transplantees considered it a major health concern. Using the PRS pipeline, 40 patients were triaged into the high risk category for KC, and received their PRS results and health advice, and we are prospectively assessing whether this will influence skin cancer screening rates, skin cancer incidence, and sun protection behavior in this group. Findings will be shared.
Conclusion: There is positive patient-readiness to receive genetic risk information for KC risk stratification among transplantees. High-risk patients are currently being followed-up for KC outcomes and prevention service uptake including screening, and sun protection behaviors.
Citation Format: Mathias Seviiri, Matthew H. Law, Peter Hopkins, Catherine M. Olsen, David C. Whiteman, Stuart MacGregor. Clinical implications for returning polygenic risk information for skin cancer to ultra-high risk organ transplant recipients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 781.
Abstract 786: Single molecule methylation sequencing of circulating DNA identifies individuals with breast cancer
Authors: Lau Billy T. , Bai Xiangqi , Notestine Alison , Parkinson Brett , Ji Hanlee P. , Nadauld Lincoln 
Published: April 2023

Abstract
Liquid biopsies are being investigated for the detection of cancer from blood. Epigenetic characterization of cell free DNA (cfDNA), specifically DNA methylation, is an emerging approach for sensitive detection and quantification of tumor burden. For breast cancer detection from blood, existing approaches for testing cfDNA have demonstrated a low performance in identifying affected patients. For this study, we developed a new approach that overcame this issue. Addressing the challenge of detecting breast cancer from cfDNA, this new approach relied on single-molecule methylation profiling of cfDNA. We used nanopore single molecule sequencing to provide quantitative characterization of cfDNA methylomes. This study determined if this approach provided the methylation features required for detecting the presence of breast cancer. The study population consisted of an extended cohort (~200 with untreated breast cancer and ~400 healthy controls). We identified 5mC-specific profiles from the nanopore sequencing signals of cfDNA. Importantly, this approach did not require any biosulfite or biochemical processing steps for determining methylation. Thus, we determined methylation profiles that were directly extrapolated from native cfDNA at single molecule resolution. Our results from this study demonstrated higher sensitivity of detecting breast cancer compared to other cfDNA methylation tests. We developed a new analytical framework for characterizing the methylation profiles of individuals with breast cancer compared to healthy individuals. Using a supervised bootstrapped algorithm, we identified CpG sites that were differentially methylated between the case and control groups. Afterwards, we calculated the similarity of any sample’s methylation profile to a training data. Our method also accommodates sparse and missing data. Based on separate validation datasets, we accurately identified those individuals with breast cancer. We validated our study with a different, independent cohort of healthy controls and individuals with breast cancer. Overall, this study demonstrates that a nanopore-based cfDNA sequencing and methylation profiling detects breast cancer from blood with higher performance then has been previously reported.
Citation Format: Billy T. Lau, Xiangqi Bai, Alison Notestine, Brett Parkinson, Hanlee P. Ji, Lincoln Nadauld. Single molecule methylation sequencing of circulating DNA identifies individuals with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 786.
Abstract 793: Mechanism of interferon induction by cannabidiol (CBD) and analogues in lung cancer cells
Authors: Stock Leticia , Robinson-Mailman Lydia , Nguyen Long C. , Chen Shao-Nong , Pauli Guido F. , Rosner Marsha R. 
Published: April 2023

Abstract
CBD, an FDA approved drug for epilepsy, may have therapeutic potential for other diseases and is currently being tested for efficacy in cancer-related clinical trials. As the literature about CBD, especially in vitro reports, is often contradictory, increasing our understanding of its specific action on a molecular level will allow to determine whether CBD can become a useful therapy or exacerbates specific cancers in a context-dependent manner. Due to its relative lipophilicity, CBD is challenging to dispense at therapeutic concentrations; therefore, one goal is to identify cannabinoid congeners with greater efficacy and reduced drug delivery challenges. We recently showed that CBD activates interferons as a mechanism of inhibiting SARS-CoV-2 replication in lung carcinoma cells. As factors produced by the innate immune system, interferons have been implicated in both pro-survival and growth arrest and apoptosis signaling in cancer. Here we show that CBD induces interferon production and interferon stimulated genes (ISGs) through a mechanism involving NRF2 and MAVS in lung carcinoma cells. We also show that CBDV, which differs from CBD by 2 fewer aliphatic tail carbons, has limited potency, suggesting that CBD specifically interacts with one or more cellular proteins rather than having a non-specific effect. We also identified other CBD-related cannabinoids that are more effective at inducing ISGs. Taken together, these results characterize a novel mechanism by which CBD activates the innate immune system in lung cancer cells and identify related cannabinoids that have possible therapeutic potential in cancer treatment.
Citation Format: Leticia Stock, Lydia Robinson-Mailman, Long C. Nguyen, Shao-Nong Chen, Guido F. Pauli, Marsha R. Rosner. Mechanism of interferon induction by cannabidiol (CBD) and analogues in lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 793.
Abstract 799: Measuring the impact of the COVID-19 pandemic on breast cancer screening in Puerto Rico
Authors: Colón-López Vivian , Ortiz Hermilis Berrios , Contreras-Mora Hector , Disdier Orville M. , Pérez Cynthia M. , Ríos Nilda , Díaz Olga L. , Mejías Juan , Suárez-Pérez Erick L. 
Published: April 2023

Abstract
Introduction: The COVID-19 pandemic has caused major changes to healthcare services, especially those related to early detection and screening practices like breast cancer. In Puerto Rico, breast cancer is the main cause of death, representing 18.9% of cancer deaths in women, making early detection even more important to prevent morbidity and mortality. This study aims to describe the impact of COVID-19 on breast cancer screening and assess differences in health utilization by age group and health regions in Puerto Rico.
Methods: This study used data on breast cancer screening medical claims from Puerto Rico Track, a project in collaboration with the Puerto Rico Public Health System and the Puerto Rico Institute of Statistics that aims to assess health access and utilization patterns in Puerto Rico. Claims including unilateral and bilateral mammography, sonommamography, and MRI were analyzed. Descriptive statistics and percentual changes between the COVID-19 baseline year (2016) compared with 2020 and 2021 were performed (overall, by age-group and health region).
Results: A total of 193,793 screening tests were performed in 2016, compared to 66,463 in 2020, and 89,322 in 2021. Overall, a third of the medical claims for breast cancer screening (33.2%) were in the age group of 51-60 years. An overall decreasing percentual change was observed comparing 2016 vs. 2020 (65.7%), where the age group with the broadest gap reduction were among women 41-50 years old (68.2%). When comparing medical claims of 2016 (193,750) versus 2021 (89,320) (pre and post pandemic), an important decreasing change (53.9%) was observed. The age group with the highest decrease comparing 2016 to 2021 was the 41-50 years one (68.2%). The Western region of Mayagüez/Aguadilla had the highest decreasing percentual change, with a reduction of 73.6% in 2020 compared to 2016, and 62.6% when compared 2021 with 2016.
Conclusion: Breast cancer screening was notably affected by the COVID-19 pandemic in Puerto Rico. A pattern of decreasing breast cancer screening was observed by health regions and by age. These efforts provide evidence of the need of tailored evidence-based interventions to increase breast cancer screening in the island.
Citation Format: Vivian Colón-López, Hermilis Berrios Ortiz, Hector Contreras-Mora, Orville M. Disdier, Cynthia M. Pérez, Nilda Ríos, Olga L. Díaz, Juan Mejías, Erick L. Suárez-Pérez. Measuring the impact of the COVID-19 pandemic on breast cancer screening in Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 799.
Abstract 832: Exosome-based hybrid nanosystem for targeted TNBC therapy
Authors: Joshi Rohan , Lampe Jana , Vishwanatha Jamboor K. , Ranjan Amalendu P. 
Published: April 2023

Abstract
Treatment of metastatic Triple-Negative Breast Cancer (TNBC) remains a challenge despite an increasing number of newer drugs being approved in recent years. The major challenge for improved treatment outcomes for metastatic cancer originates from the fact that the drugs are unable to reach the targeted site and hence are not able to elicit the desired response. Recently, natural mesenchymal stem cells (MSC) cells and their exosomes have been shown to have tumor-homing properties. By exploiting these homing properties, we propose the development of an exosome-polymeric hybrid nanosystem (EPHN) by using exosomes for their targeting ability to enhance the targetability and thus the therapeutic efficacy of the drug against TNBC. In this study, we bioengineered MSC exosome-coated drug-loaded polymeric nanoparticles to deliver our chemotherapeutic drug in a targeted fashion. To isolate the MSC exosomes, we grew the cells in exosome-free media and used the ultracentrifugation standard method. The MSC exosomes had a size of approximately 70 ± 5 nm and a PDI of 0.3. Our exosome sample was positive for exosomal proteins and negative for all other extracellular vesicles. The optimal doxorubicin-loaded PLGA nanoparticles were prepared using a microfluidics method resulting in a higher entrapment efficiency of 42 ± 3% and a smaller size of 70 ± 3 nm and a PDI of 0.2. To make the exosome-coated NPs, we used the extrusion method. After extrusion, the zeta potential of our EPHN was closer to -11mV compared to PLGA NPs (-50mV), which demonstrates that our NPs were coated with an exosomal membrane. We were able to make MSC exosome-coated drug-loaded polymeric nanoparticles and show that they were stable and uniform in size. Microfluidics-assisted doxorubicin-loaded PLGA nanoparticles show uniform size and higher entrapment efficiency. Release kinetics showed a strong burst phase release over the first 8 hours and subsequent sustained release up to 72 hours. In vivo biodistribution of EPHN shows better tumor accumulation compared to PLGA NP. The next stage in this project is in vivo tumor efficacy testing in breast cancer tumor models. This targeted NP system can serve as a novel therapeutic platform for developing improved treatments for metastatic TNBC.
Citation Format: Rohan Joshi, Jana Lampe, Jamboor K. Vishwanatha, Amalendu P. Ranjan. Exosome-based hybrid nanosystem for targeted TNBC therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 832.
Abstract 834: Synergistic effect of bacterial ghosts loaded with belinostat and betaine nano-emulsion: A potential treatment strategy for breast cancer
Authors: Deghedy Sara H. , Mahmoud Hoda E. , Hussein Ahmed A. , El-Kholy Mohammed A. , Gaafar Passent M. , Ali Mai M. , Sultan Ahmed S. 
Published: April 2023

Abstract
Breast cancer resembles the second-highest incidence rate of cancers worldwide with highly remarkable incidence and mortality rates. Recently, the main target behind the current study is to reduce the toxicity along with targeted delivery of different drugs separately and simultaneously to enhance the treatment options for breast cancer. A promising strategy for overcoming poor drug delivery is to recruit the evacuated bacterial cells which are known as Bacterial Ghosts (BGs) for drug delivery. The present study focused on formulating a new complex delivery system using a highly purified and safety-confirmed BGs of Salmonella Typhimurium ATCC 1403 strain loaded with class II HDACI (Belinostat) associated with nano-emulsion droplets of constant and non-toxic natural compound (Betaine), a glycine with three additional methyl groups. The formulated new complex delivery system of BGs was tested on two breast cancer cell lines, ER-positive ZR-75-1 and TNBC, MDA-MB-231 respectively. Using WST-1 proliferation assay, our data reports a combination index (CI) &lt;1 indicating synergistic effect between Betaine nano-emulsion at low concentrations with Poly dispersity index less than 0.5 and BGs loaded with Belinostat per constant count of BGs CFU/ml. In comparison with treatment of either Betaine or Belinostat alone, the viability inhibition and apoptosis induction of both tested MDA-MB-231 and ZR-75-1 cells were amplified in the combined treatment of 72 hours. Furthermore, the achieved delivery showed a significant downregulated expression of angiogenesis-related markers such as VEGF and TSP-1 at concentrations of 1-mM Betaine nano-emulsion and 0.2-µM Belinostat after 24 hours of treatment. In conclusion, the proposed study introduced a new formulated delivery system of BGs with synergistic mechanistic effect of two different anti-cancer compounds as a promising strategy to inhibit breast cancer cell lines proliferation and angiogenesis.
Citation Format: Sara H. Deghedy, Hoda E. Mahmoud, Ahmed A. Hussein, Mohammed A. El-Kholy, Passent M. Gaafar, Mai M. Ali, Ahmed S. Sultan. Synergistic effect of bacterial ghosts loaded with belinostat and betaine nano-emulsion: A potential treatment strategy for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 834.