bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB_A19: Genome-wide CRISPR/Cas9 screens for the identification of targeted vulnerabilties in PARP inhibitor-resistant PARG;BRCA2-deficient tumor cells: A focus on EXO1/FEN1-mediated DNA repair
Authors: Andronikou Christina , Burdova Kamila , Dibitetto Diego , Lieftink Cor , Beijersbergen Roderick L. , Hanzlikova Hana , Jonkers Jos , Rottenberg Sven 
Published: December 2023

Abstract
Targeting poly(ADP-ribose) glycohydrolase (PARG) is currently explored as a therapeutic approach to treat various cancer types, but we have a poor understanding of the specific genetic vulnerabilities that would make cancer cells susceptible to such a tailored therapy. Moreover, the identification of such vulnerabilities is of interest to target BRCA2;p53-deficient tumors that have acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi), through loss of PARG expression. Here, by performing whole genome CRISPR/Cas9 drop-out screens we identify various genes involved in DNA repair to be essential for the survival of PARG;BRCA2;p53-deficient cells. In particular, our findings reveal EXO1 and FEN1 as major synthetic lethal interactors to PARG loss. We provide evidence that PARG;BRCA2;p53-deficient cells exhibit compromised replication fork progression, DNA single-strand break repair and Okazaki fragment processing, alterations that exacerbate and become lethal upon EXO1/FEN1 inhibition. Since this sensitivity is dependent on BRCA2 defects, we propose EXO1/FEN1 targeting in PARPi-resistant tumors that have lost PARG activity. Moreover, EXO1/FEN1 targeting may be a useful strategy to enhance the effect of PARG inhibitors in HR-deficient tumors.
Citation Format: Christina Andronikou, Kamila Burdova, Diego Dibitetto, Cor Lieftink, Roderick L. Beijersbergen, Hana Hanzlikova, Jos Jonkers, Sven Rottenberg. Genome-wide CRISPR/Cas9 screens for the identification of targeted vulnerabilties in PARP inhibitor-resistant PARG;BRCA2-deficient tumor cells: A focus on EXO1/FEN1-mediated DNA repair [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A19.
Abstract LB_B18: Rapid and reproducible scaffold free organoid formation for personalized medicine: Multiomic analysis of in-vitro cancer patient model
Authors: Chang Ying-Chih 
Published: December 2023

Abstract
We have established a single cell derived 3D organoid culture platform, Rapid, Reproducible, Rare Cell 3D Expansion (R3CE), and demonstrated its ability to generate 3D organoids of solid tumors, normal tissues from surgical tissues and needle biopsies in one week. The successful banking of at least two passages with over 10^6 cells is over 90% (breast cancer ( n=7, stages I to IV), colorectal cancer (n = 9 stages I to III), hepatoma cancer (n = 2, stage IV), and ovarian cancer (n =2, stage IV)). The quick formation of patient derived organoids have been consistently passed over 20 passages, and their H&E staining, WES, and protein markers have shown their high fidelity from the original tissues and passages over 11th generation. The normal and tumor organoid pairs were recently tested for direct cytotoxic events by co-culturing with various immunotherapy, including CAR-T and autologous NK testing. This is the first 3D organoid system that does not require aggregation, or 3D scaffold such as matrigel system. Hence, it opens up the possibility for drug assays, from small molecules, large molecules to cell regiments.
Citation Format: Ying-Chih Chang. Rapid and reproducible scaffold free organoid formation for personalized medicine: Multiomic analysis of in-vitro cancer patient model [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B18.
Abstract A067: Perceptions and experiences of Black women on hereditary breast and ovarian cancer genetic testing
Authors: Riggan Kirsten A. , Halyard Michele , James Sarah E. , Kelly Marion , Phillips Daphne , Allyse Megan A. 
Published: December 2023

Abstract
Black women experience significant disparities in morbidity and mortality related to hereditary breast and ovarian cancer (HBOC). Early identification of women with HBOC is essential for proactive screening and timely diagnosis but evidence suggests that Black women receive genetic testing for HBOC at lower rates than their White counterparts. To understand Black women’s perspectives on HBOC genetic testing and potential factors influencing this decision, we conducted in-depth qualitative interviews with 107 Black women with a personal or family history of breast or ovarian cancer. Participants were recruited via the networks of patient support organizations and sororities as well as at a family medicine safety net clinic in Jacksonville, FL. Participants frequently expressed a lack of awareness about their family cancer history; many cancer patients stated that they only became aware of extensive family history upon their own diagnosis. Lack of family history sharing was attributed to a culture of silence around medical issues and a desire to protect family members from difficult information. However, most participants indicated a strong desire to understand their own risk of HBOC and were interested in genetic testing. Participants with a personal diagnosis were motivated to undergo HBOC genetic testing to reduce the risk for future generations. Clinical experiences with the offer of HBOC genetic testing were variable, with a few expressing that they had to make repeated inquiries from a provider to understand the relevance of the test to their own health. These findings suggest that investigation into alternative clinical modalities to collect family health history may be beneficial to identify Black women who meet NCCN Guidelines for HBOC testing. In contrast to the literature suggesting hesitancy for HBOC genetic testing, many participants perceived genetic results as having a positive impact for their medical decision-making and family's health. The development of patient materials and provider education on cultural and social factors that influence the uptake of HBOC genetic testing is also needed.
Citation Format: Kirsten A. Riggan, Michele Halyard, Sarah E. James, Marion Kelly, Daphne Phillips, Megan A. Allyse. Perceptions and experiences of Black women on hereditary breast and ovarian cancer genetic testing [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A067.
Abstract B113: A multi-ethnic population-based study of multiple myeloma disparities: Results from a recruitment pilot
Authors: Vang April P. , Perez Angelica , Quino Juanita Elizabeth , Estrada Ana , Stewart Eric , Cress Rosemary , Carvajal-Carmona Luis 
Published: December 2023

Abstract
To understand multiple myeloma (MM) incidence and survivorship disparities, we established the Precision MEDicine, EqUity and Disparities Research in MultipLe MyeLomA (MEDULLA) study. Our study contacted 400 MM patients reported to the Cancer Registry of Greater California (CRGC) between 2013-2018. We contacted 100 adult individuals from four racial/ethnic groups: Blacks, Whites, Latinos, and Asians with MM diagnosis. Data collection included variables reported to the CRGC, a self-administered survey, and biospecimen saliva collection. The survey focused on demographics, risk factors, cancer treatment, family history, quality of life, and social determinants of health. We also used census tract level features obtained by the American Community Survey 2007-2011. A total of 95 patients participated in the survey (overall response rate = 24%). We performed chi-square test, fisher’s exact test, or Wilcoxon test to obtain two-sided p-values for univariate testing for associations with responding to the survey. We further perform multivariable logistic regression using a stepwise approach under the Akaike information criterion with age and sex kept as covariates. These methods were stratified by Whites and Non-Whites separately which we were able to find important trends. The highest response received was from Whites at 44.2%, with significantly lower rates in all minority groups (&lt;20% for all groups). Response rates were higher for patients living in areas with higher median annual incomes and education. For every 1% increase in poverty rates, Whites living in such neighborhoods were 3% less likely to respond to the survey (p=0.04). For every 10% increase in the proportion of individuals having a college degree, responding to the survey increased by 1.17 units for minorities in that neighborhood (p=0.07). Minorities living in neighborhoods with high proportions of adults without a high school diploma and high unemployment rates are less likely to respond (p=0.02 and p=0.047, respectively). In conclusion, we found significantly lower participation rates among minority groups, with socio-economic factors affecting response rates. We suggest that future studies develop community-focused and culturally tailored strategies to understand MM etiology and survivorship in such populations.
Citation Format: April P. Vang, Angelica Perez, Juanita Elizabeth Quino, Ana Estrada, Eric Stewart, Rosemary Cress, Luis Carvajal-Carmona. A multi-ethnic population-based study of multiple myeloma disparities: Results from a recruitment pilot [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B113.
Abstract IA035: Narrowing disparities in breast cancer: A multi-level perspective
Authors: McCullough Lauren E. 
Published: December 2023

Abstract
Seminar Abstract: Despite improvements in breast cancer detection and treatment, racial disparities in breast cancer outcomes persist. In the United States, particularly the southeastern region, Black women are more likely to experience breast cancer-related mortality than any other race or ethnic group—regardless of subtype, age, or socioeconomic status. The drivers of disparities are likely multifactoral and include interacting factors (e.g., tumor, treatment, patient, and neighborhood characteristics) that contribute to race differences in breast cancer-specific mortality. Emerging data suggest that the excess breast cancer mortality experienced by Black women is linked to broader systems of oppression that impact everything from access and quality of care to tumor aggressiveness and treatment response—the imprints of which may be detectable in tumor biology. Comprehensive, multi-level approaches to addressing disparities will aid the identification of causal and contributing factors, moving us beyond merely documenting differences to creating action-oriented models aimed at achieving equitable cancer care within the social contexts of the communities affected.
Citation Format: Lauren E. McCullough. Narrowing disparities in breast cancer: A multi-level perspective [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA035.
Cancer Prevention Perspective: The University of Kansas Cancer Center
Authors: Jensen Roy A. , Befort Christie A. 
Published: December 2023

Abstract
Despite the incredible progress that has been made against cancer over the last few decades, the demographic trends in the United States predict that we will see significant increases in cancer incidence and mortality by the year 2030. This, coupled with an aging cancer workforce, would suggest that we will have major challenges ahead in dealing with the increasing burden from cancer. Clearly a critical part of our strategy must be to focus on cancer prevention and control (CPC) efforts and not solely rely on treatment to mitigate this concerning trend. This review discusses how the University of Kansas Cancer Center has had a longstanding emphasis on CPC and has leveraged this expertise to enhance the effectiveness and impact of our community outreach and engagement efforts.
Abstract A036: Development of a stirred-tank bioreactor scale-up approach to allogeneic natural killer cell culture
Authors: Yogalingam Mathura , Jagroop Rebecca , Khalajzadeh Alireza , Irrazabal Thergiory , Perea Melissa , Pushparaj Pooja , Roshankhah Roxana , Bowles Paul , Le Michael 
Published: December 2023

Abstract
Natural killer (NK) cells are innate lymphocytes that play a critical role in the immune response, as they recognize and eliminate virus-infected, cancerous, and other abnormal cells in an antigen-independent manner. This unique method of recognition makes NK cells an attractive target for utilization as an immunotherapy, as studies have demonstrated they reduce both the induction of graft-versus-host disease and the risk of cytokine release syndrome compared to T-cell based therapies. Additionally, these advantages over canonical T-cell therapies make NK therapies attractive candidates for allogeneic, as opposed to autologous, products. Given their cost-effective scale-up potential, developing a stirred-tank bioreactor (STR)-based NK cell expansion platform to achieve clinical-level expansion is of significant interest, as it would reduce the cost of producing such therapies and improve patient accessibility. To test ideal culture conditions for STR expansion, NK cells were first isolated from healthy donor Leukopaks prior to cryopreservation. Frozen, isolated NK cells were then thawed, co-cultured with varying ratios of irradiated K562 cells and supplemental cytokines from Cytiva in a 6-well G-Rex or DASbox® STR. Finally, cells were harvested for downstream analytics, including identity and functional characterization by flow cytometry and potency assays. A fold expansion of greater than 100 was achieved once the ratio of irradiated K562 to NK cells was optimized. One of the primary challenges encountered was donor-to-donor variation, not only with respect to proliferative capacity, but NK functional phenotype and activity as well. Therefore, a small-scale donor screen was conducted and donors with similar proliferative and functional capabilities were selected for large-scale expansion. Future work will focus on optimizing NK cell transduction to enable genetic customization and scaling-up to a clinically-relevant STR. The successful small-scale NK expansion in an STR demonstrated here lays the groundwork for an expansion platform that enables the manufacturing of various NK-based therapeutics at clinical scale.
Citation Format: Mathura Yogalingam, Rebecca Jagroop, Alireza Khalajzadeh, Thergiory Irrazabal, Melissa Perea, Pooja Pushparaj, Roxana Roshankhah, Paul Bowles, Michael Le. Development of a stirred-tank bioreactor scale-up approach to allogeneic natural killer cell culture [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A036.
Drying kinetics of modification cassava-seaweed noodles using an oven
Authors: Budiarti Gita Indah , Sulistiawati Endah , Juwitaningtyas Titisari , Shitophyta Lukhi Mulia , Purba Irene Enjeli , Setiyani Seila 
Published: December 2023

Consumption of noodles in the world is always increasing. Noodles made from wheat flour are unhealthy because they cause diabetes, so alternative noodles are needed, such as modified cassava flour and seaweed. Modification cassava is used because it does not contain gluten and seaweed has nutritional value to make healthy, low-calorie noodles. The purpose of this study was to determine the temperature and time of the drying parameters of seaweed noodles. The drying method uses an oven with variable temperature (60, 70, 80, and 90 ) and drying time (2, 4, 6, 8, and 10 hours). The results of the study obtained optimal water content at 60 with 6 hours of 11.75%. The drying kinetics evaluated by logarithmic equation, optimal drying constant value at 80 of 0.67 h<sup>-1</sup> with R2 0.9391. Effective moisture diffusivity (D<sub>eff</sub>) maximum evaluated by second Fick law obtained 9.35×10<sup>7</sup> m<sup>2</sup>/sec at temperature 90 with R2=0.9227. The proximate value of ash content is 12.11%, protein is 9.46%, lipid is 0.10%, and carbohydrates is 65.08%.
Safe Deferral of Coronary Computed Tomography Angiography for Patients With a Low Pretest Probability of Coronary Artery Disease in 2019 European Society of Cardiology Guidelines
Authors: Varho Ville , Uusitalo Valtteri , Vaara Satu M. , Syväranta Suvi , Rajala Helena , Sinisalo Juha 
Published: December 2023

Background
Coronary computed tomography angiography is increasingly used as the first‐line test for suspected coronary artery disease. Its overuse in a low pretest probability (PTP) population may lead to low diagnostic yield without change in patient management. We evaluated the clinical consequences of the updated 2019 European Society of Cardiology (ESC) chronic coronary syndromes guidelines’ PTP estimation and whether imaging could be safely deferred in patients with a low PTP.

Methods and Results
This retrospective cohort included all 1753 consecutive patients who underwent coronary computed tomography angiography for suspected coronary artery disease at Helsinki University Hospital between 2009 and 2017. PTP was calculated according to the 2013 and 2019 ESC guidelines. The overall mortality, cardiac deaths, myocardial infarctions, and hospitalizations for unstable angina were acquired from national registry data for 1 to 10 years of follow‐up (median, 4 years). Updated 2019 ESC guidelines classified 72% of the patients as having low PTP, whose imaging could have been deferred. The revascularization rate (4.7%) and annual cardiac mortality (0.4%) were low in the 857 patients reclassified from the recommendation to test, according to the 2013 ESC guideline, to deferral of coronary computed tomography angiography, according to the new 2019 guideline.

Conclusions
The updated 2019 ESC guideline PTP score aids clinicians in safely preventing the overuse of cardiac imaging in patients deemed at low PTP of coronary artery disease. Diagnostic yield, revascularization rate, and cardiac mortality are low in patients with low pretest risk.
Excess Bed Days and Hospitalization Costs Associated With 30‐Day Complications Following Catheter Ablation of Atrial Fibrillation
Authors: Ngo Linh , Denman Russell , Hay Karen , Kaambwa Billingsley , Ganesan Anand , Ranasinghe Isuru 
Published: December 2023

Background
The incidence and type of complications following catheter ablation of atrial fibrillation have been extensively examined, but the impact associated with these complications on the length of stay and hospitalization costs is unknown.

Methods and Results
This cohort study included 20 117 adult patients (mean age 62.6±11.4 years, 30.3% women, median length of stay 1 day [interquartile range 1–2 days]) undergoing atrial fibrillation ablation in financial years 2011 to 2017 in Australia with available cost data from the National Hospital Cost Data Collection, which determines government reimbursement of health services provided. The primary outcome was the costs associated with complications occurring up to 30 days postdischarge adjusted for inflation to 2021 Australian dollars. We used generalized linear models to estimate the increase in length of stay and cost associated with complications, adjusting for patient characteristics. Within 30 days of hospital discharge, 1151 (5.72%) patients experienced a complication with bleeding (3.35%) and pericardial effusion (0.75%) being the most common. On average, the occurrence of a complication was associated with an adjusted 3.3 (95% CI, 3.1–3.6) excess bed days of hospital care (totaling 3851 days), and a $7812 (95% CI, $6754–$8870) increase in hospitalization cost (totaling $9.0 million). Most of the total excess cost was attributable to bleeding ($3.8 million, 41.9% of total excess cost) and pericardial effusion ($1.6 million, 18.2%).

Conclusions
Complications following atrial fibrillation ablation were associated with significant increase in length of stay and hospitalization costs, most of which were attributable to bleeding and pericardial effusion. Strategies to improve procedural safety and reduce health care costs should focus on these complications.
Resting Heart Rate Independent of Cardiovascular Disease Risk Factors Is Associated With End‐Stage Renal Disease: A Cohort Study Based on 476 347 Adults
Authors: Tsai Min‐Kuang , Gao Wayne , Chien Kuo‐Liong , Kyaw Thu Win , Baw Chin‐Kun , Hsu Chih‐Cheng , Wen Chi‐Pang 
Published: December 2023

Background
The relationship between resting heart rate (RHR) and the risk of end‐stage renal disease (ESRD) among those without cardiovascular disease remains unclear. We aim to establish temporal consistency and elucidate the independent relationship between RHR and the risk of ESRD.

Methods and Results
This cohort enrolled participants from 476 347 individuals who had taken part in a screening program from 1996 to 2017. We identified 2504 participants who had ESRD, and the median follow‐up was 13 years. RHR was extracted from electrocardiography results, and the study assessed the relationship between RHR and the risk of ESRD using the Cox proportional hazards model. Of the participants, 32.6% had an RHR of 60 to 69 beats per minute (bpm), and 22.2% had an RHR of ≥80 bpm. Participants with an RHR of ≥80 bpm had a higher stage of chronic kidney disease, lower estimated glomerular filtration rate, and more proteinuria than those with an RHR of 60 to 69 bpm. Participants with an RHR of 80 to 89 and ≥90 bpm had a 24% (hazard ratio [HR], 1.24 [95% CI, 1.09–1.42]) and 64% (HR, 1.64 [95% CI, 1.42–1.90]) higher risk of ESRD, respectively. The risk of ESRD remained significantly elevated (HR, 1.32 [95% CI, 1.10–1.58] per 10‐beat increase from 60 bpm) after excluding participants who smoked; had hypertension, diabetes, or hyperlipidemia; or were overweight.

Conclusions
An RHR of ≥80 bpm is significantly associated with an increased risk of ESRD. These results suggest that RHR may serve as a risk factor for kidney disease in individuals without established cardiovascular disease risk factors.