bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 790: Sex and race-dependent variations in the mutational landscape of clonal hematopoiesis
Authors: Dhuri Kanaka , Alachkar Houda
Published: March 2024

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a significant precursor to hematological malignancies and is associated with several age-related diseases. Recent studies in relatively small disease specific cohorts have suggested that CHIP may exhibit variations among different races and between males and females raising intriguing questions about potential genetic and environmental influences. Understanding the differences in CHIP across races and between males and females may have implications for personalized cancer risk assessment and targeted therapeutic strategies.

Methods: Patient’s data were obtained from the Cancer Therapy and Clonal hematopoiesis via cBioportal. The original study was designed to examine clonal hematopoiesis mutations that were found in blood samples obtained from 24,146 patients with non-hematological cancers and their tumor-blood pairs were analyzed using targeting sequencing data MSK-IMPACT (Memorial Sloan Kettering-IMPACT). The cohort consisted of 45.7% males and 54.3% females; including 6.8% Asians, 6.2% Blacks, and 76.3% Whites. We examined mutation frequencies among these racial groups and between genders, employing the two-sided Fisher's exact test and adjusting p-values for multiple comparisons. Differences were considered significant when both P value and Q values are less than 0.05.

Results: DNMT3A mutations were substantially more prevalent in females than in males (38.94% vs 31.37%, p-value: <10−10, q-value: 6.19e−09), While ASXL1 mutations were more frequent in males than females (5.82% vs 2.69%, p-value: <10−10, q-value: 6.19e−09). In the racial cohorts with sufficient sample sizes, STAT5B and CSF1R mutations were most frequent in Asian (1.40% and 0.84%), followed by Black (0.98% and 0.24%) and White populations (0.29% and 0.09%), (p-value: 8.099e−04 and 7.490e−04, q-value: 0.0234 and 0.0232). Several other CHIP mutations were enriched in Black: RARA, SMAD2, CDKN1B, CENPA, CTLA4, EIF1AX, ELF3, MSI1, MYC, SOX17, AURKA. On the other hand, H3C1, H3C4, MYCL were enriched in the Asian cohort.

Conclusion: Our analysis provides insights into the complex interplay of sex and racial factors in shaping CHIP mutation frequencies. As CHIP continues to gain recognition as a critical precursor to malignancies, understanding these variations contributes to refining our understanding of its underlying mechanisms and clinical implications.

Citation Format: Kanaka Dhuri, Houda Alachkar. Sex and race-dependent variations in the mutational landscape of clonal hematopoiesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 790.
Abstract 791: Evaluation of BCR spike-in controls using DriverMap adaptive immune receptor (AIR) profiling technology
Authors: Chenchik Alex , Liu Tianbing , Makhanov Mikhail , Hu Dongfang , Ghias Khadija , Diehl Paul
Published: March 2024

The DriverMap™ Adaptive Immune Receptor (AIR) repertoire profiling assay employs multiplex RT-PCR for comprehensive profiling of CDR3 or full-length receptor profiling of all variable heavy and light chains of T-cell receptors (TCR) and B-cell receptors (BCR) from either RNA or DNA. In this study, initiated by a U.S. Food and Drug Administration (FDA) consortium to compare performance of different BCR repertoire profiling technologies, we tested spike-ins in peripheral blood mononuclear cell (PBMC) RNA and DNA control mixtures prepared from nine different B-cell lines. We measured the sensitivity, linearity and accuracy of AIR RNA and DNA BCR profiling for the IGH, IGK and IGL chains of the spike-in controls. Our comprehensive analysis, encompassing CDR3 profiling and full-length receptor profiling (CDR1, CDR2, and CDR3) sequencing, revealed a 100X increase in sensitivity of detection of spike-in controls in RNA compared to the DNA assay. The high sensitivity of the full-length DriverMap AIR RNA assay allowed the detection of controls from all nine cell lines, with 8 out of 9 cell lines detected in the DNA assay, which demonstrates the robustness of the DriverMap AIR profiling technology.

This study highlights the remarkable sensitivity of the AIR RNA assay in quantifying transcripts. This approach enables the detection of low-frequency BCR clonotypes, which is particularly advantageous when working with samples containing low numbers of B cells. Furthermore, our AIR DNA assay in combination with spike-in controls offers a quantitative tool for minimal residual disease (MRD) applications, providing accurate insight into cell numbers, which then facilitates tracking clonal expansion of immune cells.

Citation Format: Alex Chenchik, Tianbing Liu, Mikhail Makhanov, Dongfang Hu, Khadija Ghias, Paul Diehl. Evaluation of BCR spike-in controls using DriverMap adaptive immune receptor (AIR) profiling technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 791.
Abstract 838: Population attributable fraction of occupational carcinogens for cancer incidence among Korean adults in 2020
Authors: Kim Eun Mi , Koh Dong-Hee , Park Sue K , Choi Yoon-Jung , Seo Hong Gwan , Kim Inah , Im Jeong-Soo
Published: March 2024

Assessing the level and scope of exposure to occupational carcinogens on a country-specific basis presents challenges, and as a result, it has been appraised as uncertain when compared with other factors in the estimation of the burden of cancer. The Korean CARcinogen Exposure (K-CAREX) developed in 2021 is utilized to estimate the population at risk in industrial work environments in Korea (Koh et al., 2021). Our goal is to estimate preventable cancer incidence attributable to occupational carcinogens in Korea, utilizing the K-CAREX program and employing appropriate methodology. Among the exposures classified as Group 1 factors by IARC, considering the possibility of occupational exposure. Population attributable fractions (PAFs) were computed using Levin's Formula (1953), considering a latency period of 15 years between exposure and cancer in our assessment. The prevalence of exposure was calculated using K-CAREX program and census data. The relative risk (RR) for incidence was derived from a meta-analysis of literature. It was possible to calculate PAFs for 11 occupational factors linked with 8 cancer types. This estimation was chosen based on a combination of exposure and sufficient evidence of human carcinogenicity. As a result, Population attributable fractions (PAFs) for cancer incidence associated with occupational carcinogens was estimated at 1% in 2020. Lung cancer (approximately 90%) was found to be the most prevalent type of cancer attributable to occupational factors, as widely acknowledged. The prevalence of exposure to occupational carcinogens was 22%, with Diesel engine exhaust being the most significant source for both genders. Since the early 2000s, the exposure levels of asbestos, subject to usage prohibition and restriction measures, were estimated to be at a lower level compared to other countries. It is evident that these estimates reflect the characteristics of the Korean industry. This is anticipated to provide a foundation for the development of methodologies and indicators essential for measuring the burden of occupational cancer in the country.

Citation Format: Eun Mi Kim, Dong-Hee Koh, Sue K Park, Yoon-Jung Choi, Hong Gwan Seo, Inah Kim, Jeong-Soo Im. Population attributable fraction of occupational carcinogens for cancer incidence among Korean adults in 2020 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 838.
Abstract 839: Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer
Authors: Tadesse Deborah , Rothman Nathaniel , Xie Shuai , Hurwitz Lauren , Friesen Melissa C. , Baris Dalsu , Schwenn Molly , Johnson Alison , Karagas Margaret , Silverman Debra T. , Koutros Stella
Published: March 2024

Introduction: Recent studies have reported an increased bladder cancer risk with occupational exposure to organic solvents, including exposure to benzene, toluene, and xylene (BTX). The metabolism of solvents is known to be influenced by genetic susceptibility. Here, we evaluated the association between BTX and bladder cancer, stratified by genotype in known bladder cancer susceptibility loci and in variants shown to impact the metabolism of solvents.

Methods: We evaluated if single-nucleotide polymorphisms (SNPs) modified the association between BTX exposure and bladder cancer risk in 1182 cases and 1408 controls from a population-based case-control study in New England. Ever and cumulative lifetime exposure to BTX was assessed using occupational histories obtained by personal interviews and exposure-oriented modules in conjunction with a job-exposure matrix. Genotyping was conducted using Illumina arrays and GSTM1 and GSTT1 deletion were determined using melt curve/copy number assays. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between BTX exposure and bladder cancer, stratified by genotype and to calculate p-values for multiplicative interaction.

Results: Ever exposure to BTX was more strongly associated with bladder cancer risk among individuals with the GSTT1 null (deletion) genotype (OR 3.53, 95% CI 1.26-9.89), while exposed individuals with the GSTT1 active genotype had a diminished risk (OR 1.40, 95% CI 0.93-2.10, P-interaction = 0.06). The association between benzene exposure and bladder cancer was similarly modified by GSTT1 genotype (carriers of the deletion: OR 5.19, 95% CI 1.91, 14.13; carriers of one or two copies: OR 1.22, 95% CI 0.79, 1.89, p-interaction=0.008).

Conclusion: GSTT1 genotype has been shown to impair the metabolism of solvents, particularly for benzene. Here we show that bladder cancer risk is higher among those exposed to solvents who also harbor a common deletion in GSTT1, adding to the evidence of a plausible link between BTX exposures and bladder cancer risk.

Citation Format: Deborah Tadesse, Nathaniel Rothman, Shuai Xie, Lauren Hurwitz, Melissa C. Friesen, Dalsu Baris, Molly Schwenn, Alison Johnson, Margaret Karagas, Debra T. Silverman, Stella Koutros. Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 839.
Abstract 840: Serum concentrations of per- and polyfluorinated substances and risk of non-Hodgkin lymphoma
Authors: Rhee Jongeun , Koponen Jani , Sampson Joshua N. , Keil Alexander P. , Ward Mary H. , Hofmann Jonathan N. , Huang Wen-Yi , Silverman Debra T. , Rantakokko Panu , Purdue Mark P.
Published: March 2024

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants, some immunotoxic, that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and non-Hodgkin lymphoma (NHL); however, it is unknown whether associations exist at lower exposure levels that are more common in the general population. To address this knowledge gap, we conducted a nested case-control study investigating serum PFAS concentrations and NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations (collected between 1993-2001) of five PFAS among 706 cases and 706 controls individually matched on the basis of age at baseline, sex, self-reported race and ethnicity, study center, calendar year of blood collection, and number of prior serum thaws. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for PFAS concentrations in relation to NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with NHL for any of the five PFAS in analyses adjusting for all measured PFAS. In analyses of histologic subtypes, we observed a positive association between perfluorohexane sulfonate (PFHxS) and DLBCL (OR per doubling in concentration=1.27, 95% CI=1.07, 1.50) which remained for cases diagnosed ≥10 years after blood collection (OR=1.34, 95% CI=1.09, 1.64). We also observed inverse associations with PFNA for all subtypes (DLBCL, OR=0.84, 95% CI=0.72, 0.98; FL, OR=0.86, 95% CI=0.69, 1.08; LPL/MZL, OR=0.86, 95% CI=0.66, 1.12), although these associations were null among participants with blood drawn prior to 1997 (DLBCL: OR<1997=0.95, OR≥1997=0.67, Pinteraction=0.001; FL: OR<1997=1.01, OR≥1997=0.77, Pinteraction =0.08; LPL/MZL: OR<1997=1.26, OR≥1997=0.88, Pinteraction =0.03). In conclusion, our findings from a cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation.

Citation Format: Jongeun Rhee, Jani Koponen, Joshua N. Sampson, Alexander P. Keil, Mary H. Ward, Jonathan N. Hofmann, Wen-Yi Huang, Debra T. Silverman, Panu Rantakokko, Mark P. Purdue. Serum concentrations of per- and polyfluorinated substances and risk of non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 840.
Abstract 853: Assessment of racial and ethnic disparities in environmental exposure-related cancer burden
Authors: Bobbitt Jessica R. , Liu Fangzhou , Cullen Jennifer , Keri Ruth A.
Published: March 2024

The United States Environmental Protection Agency designates superfund sites as regions contaminated with hazardous waste. These sites have previously been associated with adverse health outcomes, including an increased incidence of cancer. Historically, communities with racial and ethnic minorities and people of low socioeconomic status have served as prime locations for these sites, as these communities have lacked the ability to advocate against this land use. Here, we ask whether racial and ethnic minorities are disproportionately exposed to these sites or other regions of hazardous waste in our catchment area at the Case Comprehensive Cancer Center, and in the state of Ohio. Further, we are examining whether areas of high exposure are associated with adverse health outcomes including higher cancer incidence and mortality. We utilized the Environmental Justice Index (EJI) database from the Centers for Disease Control and Prevention to assess, on a census tract level, the percent of racial and ethnic minorities in a region, defined as all persons except white, non-Hispanic individuals. We also queried hazardous and toxic waste sites including regions with a national priority list site, a toxic release inventory site, treatment, storage, and disposal sites, risk management plan sites, coal mines, and lead mines. We intersected these data and found that census tracts with a higher percentage of minority persons were more likely to be exposed to hazardous and toxic sites. Our current studies are assessing whether this high environmental burden is contributing to disproportionately worse cancer burden for these individuals. We will test this by comparing EJI data with data from the Ohio Cancer Incidence Surveillance System database to assess cancer incidence and mortality in Ohio. This will also provide an avenue for identifying specific exposures that may contribute to different cancer types. Further, we plan to assess if persons with low socioeconomic status or those living with disabilities are disproportionately affected by environmental burden. Overall, understanding environmental burden and health outcomes will facilitate the prioritization of communities at greatest need, contributing to greater health equity.

Citation Format: Jessica R. Bobbitt, Fangzhou Liu, Jennifer Cullen, Ruth A. Keri. Assessment of racial and ethnic disparities in environmental exposure-related cancer burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 853.
Abstract 888: Uncovering clinically relevant omics signatures from pan-cancer imaging and multi-omics data integration
Authors: Wang Joshua , Hong Runyu , Tan Jimin , Liu Wenke , Fenyȯ David
Published: March 2024

Despite advancements in deep learning for histopathology, integrating these insights with multi-omics data to uncover clinically relevant omics pathway-level signatures remains a challenge. Our study addresses this gap by applying unsupervised learning techniques on pan-cancer multi-omics data, leveraging 3,080 Hematoxylin and Eosin (H&E) images from 1,010 patients in Clinical Proteomic Tumor Analysis Consortium (CPTAC) to uncover omics pathway-level signatures that drive discernable morphology phenotypes at the tissue level. First, imaging models were trained to predict clinical and mutation outcomes, and thereafter, integrated with transcriptomic and proteomic expression data using sparse canonical correlation analysis. Our findings reveal that images of TP53 mutated samples exhibited increased nuclear size and dense lymphoplasmacytic infiltration. These morphological changes correlated with neutrophil and macrophage signaling at the proteomic level, and IL-1 mediated signaling at the transcriptomic level, highlighting the complementary perspectives different omics can provide.

To further elucidate immune interactions, we applied multi-omics deconvolution to identify 7 immune subtypes, characterizing each with gene set enrichment, germline DNA variations, and kinase activations. We show that imaging models trained to predict these subtypes differentiate tissue morphologies corresponding to immune enrichment (AUROC: 0.84). To further confirm the robustness of our approach, we trained models to predict co-regulated proteomic modules clustered by independent component analysis. We demonstrate a signature in pan-squamous tumors, consisting of T cell markers and interferon-gamma response proteins like CD4, CD48, and GBP5, which imaging models can successfully predict from histopathology. Manual review from pathologists confirmed lymphocytic T-cell density as a differentiator in samples with the highest and lowest T-cell signaling.

Together, these approaches demonstrate that genomic characteristics discovered via unbiased mining of pan-cancer multi-omics data manifest as quantitative imaging phenotypes. These results underscore the potential of multi-omics and digital pathology to integratively uncover and confirm new cancer biology. Our ongoing work will explore predicting drug response and survival from morphology patterns related to multi-omics signatures.

Citation Format: Joshua Wang, Runyu Hong, Jimin Tan, Wenke Liu, David Fenyȯ. Uncovering clinically relevant omics signatures from pan-cancer imaging and multi-omics data integration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 888.
Abstract 946: Landscape of HRD aberration in EGFR mutated lung cancer and the role of PARP-inhibitor in EGFR mutated lung cancer with HRD aberration
Authors: Kim Jinah , Choi Horyun , Chung Liam Il-Young , Chae Young Kwang
Published: March 2024

Introduction: Olaparib, an oral poly polymerase (PARP) inhibitor has received approval for treating malignancies displaying homologous recombination deficiency (HRD). Current data is insufficient in establishing the role of PARP inhibitors in non-small cell lung cancer (NSCLC) in the setting of third generation EGFR tyrosine kinase inhibitor (TKI) use. Preclinical investigation suggests heightened PARP inhibitor sensitivity of TKI-resistant EGFR mutant NSCLC cells compared to TKI-sensitive cells.

Methods: We utilized The Cancer Genome Atlas (TCGA) to investigate the prevalence of HRD gene mutations in patients with NSCLC harboring EGFR mutations. We also present a case demonstrating a favorable response to the dual therapy of olaparib and osimertinib in NSCLC harboring EGFR, RAD50, and ARID1A mutations that progressed on osimertinib.

Results: There were 2298 patients in the NSCLC cohort (MSKCC database). Among 687 patients with EGFR mutations, 24 patients (3.5%) exhibited ARID1A mutations, 8 patients (1.2%) had BRCA1 mutations, 11 patients (1.6%) had BRCA2 mutations, and 5 (0.7%) had RAD50 mutations. A 71-year-old female presented with stage IV adenocarcinoma of the lung. She had recurrent malignant pericardial effusion requiring pericardiocentesis for previous cardiac tamponade. Computed tomography (CT) of the chest revealed a 3cm irregular left hilar mass with bilateral mediastinal and hilar lymph nodes. Tissue next generation sequencing (NGS) at baseline identified EGFR exon19 deletion along with RAD50 R726H which is a HRD pathway gene. Circulating tumor DNA (ct-DNA) NGS (Guardant360) showed EGFR E746_A750del 4.8%. The patient achieved partial response to osimertinib for 28 months. Follow-up CT showed disease progression. Olaparib 200mg twice daily was added to osimertinib based on repeat ct-DNA NGS indicating a new ARID1A alteration (splice site SNV) along with the known BRCA1 mutation. Follow up scans currently have consistently demonstrated ongoing partial response for 19 months. Combining olaparib with osimertinib can be effective in an osimertinib-resistant NSCLC patient with EGFR mutation and HRD aberration. The favorable response could be attributed not only to pre-existing RAD50 mutation but also to acquired mutations in ARID1A HRD genes.

Conclusion: HRD aberrations are uncommon in EGFR mutated lung cancer patients. Further investigation on the role of PARP inhibitor in EGFR mutated lung cancer is warranted.

Citation Format: Jinah Kim, Horyun Choi, Liam Il-Young Chung, Young Kwang Chae. Landscape of HRD aberration in EGFR mutated lung cancer and the role of PARP-inhibitor in EGFR mutated lung cancer with HRD aberration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 946.
Abstract 997: Bringing the first prehabilitation program to American Indian cancer patients
Authors: Erdrich Jennifer , Hernandez Adriena , Bea Jennifer W. , Thomson Cynthia A.
Published: March 2024

Purpose. American Indian/Alaska Native (AI/AN) people have the worst cancer survival rates of any US racial group, are underrepresented in clinical trials and research, and have never been recruited for participation in any published prehabilitation (prehab) intervention conducted prior to cancer surgery.

Description of Procedure. We are collaborating with tribal partners to design the first prehab translational clinical trial for AI patients diagnosed with obesity-related cancer, to be implemented prior to surgical resection of the tumor. Program components have been developed with community input through semi-structured interviews and guidance from the sponsoring tribal health facility, the San Carlos Apache Healthcare Corporation. Patients preparing for cancer surgery will engage in a 3-week multimodal intervention that entails home-based exercise, supervised fitness sessions, promotion of anti-inflammatory foods, and health education materials adapted for and by community members. Serum and tissue biomarkers, as well as lifestyle behavioral measures, will be compared pre and post intervention to assess responsiveness. In respect of tribal sovereignty, the experimental procedure includes protocol refinement and approval by the tribal health facility’s IRB and tribal council.

Summary of Data. Our qualitative data reveal AI cancer survivors from the partnering tribal community have high interest in prehab and attest they would have participated if offered (100%). Their consensus feedback fashioned the specifics of the prehab translational clinical trial: 30 minutes daily walking, 60 minutes supervised resistance training twice weekly, 2 ounces walnut consumption daily, nutrition counseling, transportation assistance, and education/encouragement from staff and peers. Biospecimen sampling can be a sensitive topic for AI audiences, which we addressed early and found 75% of the interviewed survivors agreed to biospecimen collection without stipulation; this increased to 100% support once the rationale for biospecimens was explained.

Conclusions: Published prehab studies in other populations administered for 3-5 weeks between diagnosis and surgery have shown improvements in functional capacity, attenuation of surgery-induced losses, alterations of inflammatory biomarkers, and patient safety. Our community-informed prehab translational clinical trial for AI patients is the first of its kind, and anticipated to demonstrate feasibility, patient acceptability, behavioral changes in lifestyle, and the potential to modulate inflammatory biomarkers.

Citation Format: Jennifer Erdrich, Adriena Hernandez, Jennifer W. Bea, Cynthia A. Thomson. Bringing the first prehabilitation program to American Indian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 997.
Disparities in Access to Liver Transplant Referral and Evaluation among Patients with Hepatocellular Carcinoma in Georgia
Authors: Ross-Driscoll Katherine , Ayuk-Arrey Arrey-Takor , Lynch Raymond , McCullough Lauren E. , Roccaro Giorgio , Nephew Lauren , Hundley Jonathan , Rubin Raymond A. , Patzer Rachel
Published: March 2024

Liver transplantation offers the best survival for patients with early-stage hepatocellular carcinoma (HCC). Prior studies have demonstrated disparities in transplant access; none have examined the early steps of the transplant process. We identified determinants of access to transplant referral and evaluation among patients with HCC with a single tumor either within Milan or meeting downstaging criteria in Georgia.

Population-based cancer registry data from 2010 to 2019 were linked to liver transplant centers in Georgia. Primary cohort: adult patients with HCC with a single tumor ≤8 cm in diameter, no extrahepatic involvement, and no vascular involvement. Secondary cohort: primary cohort plus patients with multiple tumors confined to one lobe. We estimated time to transplant referral, evaluation initiation, and evaluation completion, accounting for the competing risk of death. In sensitivity analyses, we also accounted for non-transplant cancer treatment.

Among 1,379 patients with early-stage HCC in Georgia, 26% were referred to liver transplant. Private insurance and younger age were associated with increased likelihood of referral, while requiring downstaging was associated with lower likelihood of referral. Patients living in census tracts with ≥20% of residents in poverty were less likely to initiate evaluation among those referred [cause-specific hazard ratio (csHR): 0.62, 95% confidence interval (CI): 0.42–0.94]. Medicaid patients were less likely to complete the evaluation once initiated (csHR: 0.53, 95% CI: 0.32–0.89).

Different sociodemographic factors were associated with each stage of the transplant process among patients with early-stage HCC in Georgia, emphasizing unique barriers to access and the need for targeted interventions at each step.

Significance:

Among patients with early-stage HCC in Georgia, age and insurance type were associated with referral to liver transplant, race, and poverty with evaluation initiation, and insurance type with evaluation completion. Opportunities to improve transplant access include informing referring providers about insurance requirements, addressing barriers to evaluation initiation, and streamlining the evaluation process.
Versican Associates with Tumor Immune Phenotype and Limits T-cell Trafficking via Chondroitin Sulfate
Authors: Hirani Priyanka , McDermott Jacqueline , Rajeeve Vinothini , Cutillas Pedro R. , Jones J. Louise , Pennington Daniel J. , Wight Thomas N. , Santamaria Salvatore , Alonge Kimberly M. , Pearce Oliver M.T.
Published: March 2024

Immunotherapies for cancers of epithelial origin have limited efficacy, and a growing body of evidence links the composition of extracellular matrix (ECM) with the likelihood of a favorable response to treatment. The ECM may be considered an immunologic barrier, restricting the localization of cytotoxic immune cells to stromal areas and inhibiting their contact with tumor cells. Identifying ECM components of this immunologic barrier could provide targets that whether degraded in situ may support antitumor immunity and improve immunotherapy response. Using a library of primary triple-negative breast cancer tissues, we correlated CD8+ T-cell tumor contact with ECM composition and identified a proteoglycan, versican (VCAN), as a putative member of the immunologic barrier. Our analysis reveals that CD8+ T-cell contact with tumor associates with the location of VCAN expression, the specific glycovariant of VCAN [defined through the pattern of posttranslational attachments of glycosaminoglycans (GAG)], and the cell types that produce the variant. In functional studies, the isomers of chondroitin sulfate presented on VCAN have opposing roles being either supportive or inhibiting of T-cell trafficking, and removal of the GAGs ameliorates these effects on T-cell trafficking. Overall, we conclude that VCAN can either support or inhibit T-cell trafficking within the tumor microenvironment depending on the pattern of GAGs present, and that VCAN is a major component of the ECM immunologic barrier that defines the type of response to immunotherapy.

Significance:

The response to immunotherapy has been poor toward solid tumors despite immune cells infiltrating into the tumor. The ECM has been associated with impacting T-cell infiltration toward the tumor and in this article we have identified VCAN and its structural modification, chondroitin sulfate as having a key role in T-cell invasion.
Giant Conjunctival Cyst of the Orbit in a Patient with Previous Enucleation
Authors: Ponces Ramalhão João , Rodrigues Diogo , Vieira Beatriz , Gonçalves Afonso Miguel , Baptista Pedro Manuel , Lamas Nuno Jorge , Araújo Maria
Published: March 2024

Introduction: Conjunctival cysts of the orbit development are a rare complication in enucleated patients. They result from the entrapment of conjunctival epithelium within the orbit. Case Presentation: We report the case of a 25-year-old man with a history of enucleation for a retinoblastoma of the right eye who presented with difficulty in fitting his eye prothesis. On his past medical records, there was no reference to the placement of any orbital implant at the time of the surgery. Biomicroscopy of the right eye revealed a thickened bulbar conjunctiva, an inferior symblepharon, and a translucid central area with vascularization. Imaging was remarkable for a cystic cavity filling the whole right orbit. Biopsy revealed the diagnosis of a conjunctival cyst, and drainage was performed, alleviating the patient’s symptoms. Conclusion: Orbital conjunctival cysts may pose a clinical problem, and treatment modalities include surgical excision, absolute alcohol injection, and trichloroacetic acid injection.
Fundoplication: Old Concept for Novel Challenges?
Authors: Bonavina Luigi , Bona Davide , Aiolfi Alberto , Shabat Galyna , Annese Vito , Galassi Luca
Published: March 2024

Background: Gastroesophageal reflux disease (GERD), the most common esophageal disorder worldwide, is a progressive condition that may lead to Barrett’s esophagus and adenocarcinoma. Upfront therapy with proton pump inhibitors is ineffective in up to 40% of patients. The scope of surgical therapy is to reconstruct the natural antireflux barrier provided by the diaphragmatic crura, the lower esophageal sphincter, and the gastroesophageal flap valve. Summary: For 70 years, the 360° Nissen fundoplication has dominated the surgical scenario and is still considered the gold-standard treatment. However, over the past two decades, the Toupet and Dor partial fundoplications have emerged as alternative options to decrease the incidence of dysphagia and gas-bloat syndrome. Randomized and observational clinical studies have shown that the outcomes of partial fundoplication compare favorably with those of the Nissen and can provide satisfactory quality of life minimizing the risk of side effects. However, reflux control and anatomical integrity of partial fundoplications may fade away over time. Further research and close scrutiny of new surgical procedures and technologies is in progress to improve clinical outcomes and provide a more personalized and durable antireflux therapy. Key Messages: Laparoscopic antireflux surgery is a safe and effective therapy for GERD. It should be performed in centers offering a comprehensive diagnostic pathway and a spectrum of techniques tailored to the individual GERD phenotype.
Effect of Neonatal Unit Interventions Designed to Increase Breastfeeding in Preterm Infants: An Overview of Systematic Reviews
Authors: Hilditch Cathie , Rumbold Alice R. , Keir Amy , Middleton Philippa , Gomersall Judith
Published: March 2024

Introduction: This overview aims to systematically review evidence regarding effects of interventions undertaken in neonatal units to increase breastfeeding in preterm infants. Methods: We followed Cochrane methodology. Systematic reviews published to October 31, 2022, reporting meta-analysis of effects from original studies on breastfeeding rates in preterm infants of neonatal unit interventions designed to increase breastfeeding were included. Results: Avoidance of bottles during breastfeed establishment (comparator breastfeeds with bottle-feeds) demonstrated clear evidence of benefit for any breastfeeding at discharge and exclusive breastfeeding 3 months post-discharge, and possible evidence of benefit for exclusive breastfeeding at discharge, and any breastfeeding post-discharge. Kangaroo mother care (KMC) (comparator usual care) demonstrated clear evidence of benefit for any and exclusive breastfeeding at discharge and possible benefit for any breastfeeding post-discharge. Quality improvement (QI) bundle(s) to enable breastfeeds (comparator conventional care) showed possible evidence of benefit for any breastfeeding at discharge. Cup feeding (comparator other supplemental enteral feeding forms) demonstrated possible evidence of benefit for exclusive breastfeeding at discharge and any breastfeeding 3 months after. Early onset KMC (commenced <24 h post-birth), oral stimulation, and oropharyngeal colostrum administration, showed no evidence of benefit. No meta-analyses reported pooled effects for gestational age or birthweight subgroups. Conclusion: There is ample evidence to support investment in KMC, avoidance of bottles during breastfeed establishment, cup feeding, and QI bundles targeted at better supporting breastfeeding in neonatal units to increase prevalence of breastfeeding in preterm infants and promote equal access to breastmilk. Stratifying effects by relevant subgroups is a research priority.
The effect of character-charged maritime textbooks on increasing students’ character values
Authors: Nuraeni Nuraeni , Sarilah Sarilah , Lestari Gunarti Dwi , Yulianingsih Wiwin , Tahir Muhammad
Published: March 2024

Teaching and learning activities for early childhood students currently do not support increasing the character values of graduates, and the emphasis is still on learning whose output leads to competency according to standards. Using character-charged maritime textbooks is a solution to assist teachers in facilitating the application of character values in marine learning. The purpose of this research is to evaluate the impact of character-focused marine textbooks on students’ moral development. The method of research is quasi-experimental, with a pretest-posttest design. The sampling technique is convenience sampling. Two classes use the method, B1 for experimental purposes (with 80 students) and B2 for comparison (with 80 students). Independent T-tests were used in data analysis to compare differences in students’ average scores in the experimental and control groups before the intervention. N-Gain was used to compare the character growth of control and intervention students. The study’s findings indicate that students’ character values significantly influence adoption of morally edifying maritime textbooks. This shows increased student character values, namely responsibility, honesty, discipline, love and affection, caring, courage, independence, and hard work, after being taught using character-charged maritime textbooks. Thus, it can be concluded that character-charged maritime textbooks can significantly increase students’ character values.
Enhancing decision-making skills through geoscience education for sustainable development
Authors: Hariyono Eko , Madlazim Madlazim , Hidaayatullaah Hasan Nuurul , Ichinose Tomonori
Published: March 2024

Sustainable development (SD) can be achieved through education. The goal of incorporating SD principles into education is to enhance both the present and future quality of human life. This study analyzes learning effectiveness by developing education for sustainable development (ESD) based inquiry to improve students’ decision-making skills. Specifically, this study aimed to explore ESD-based inquiry learning tools, analyze student decision-making skills, and analyze student responses to ESD-based inquiry learning tools. The development research used is a 4D model (define, design, develop, and disseminate) and a one-group pre-test-posttest design. Validation sheets, tests, and questionnaires are employed as data-gathering tools. Data analysis using percentage, mean, n-gain, and paired sample t-test techniques. The results showed the following: i) ESD-based inquiry learning tools developed according to the assessment of experts and practitioners are in the valid and reliable category in terms of both construction and substance; ii) the ESD-based inquiry learning is effective in improving students’ decision-making skills with an average gain (gain score) in the high category; and iii) the student's response to each learning process using ESD-based inquiry learning is very good and is considered more exciting and motivating. This finding contributes to educators developing various ESD-based learning materials, especially geoscience materials, to achieve quality learning.
Wayang Edu: digital application for Wayang Kulit Kelantan
Authors: Jufry Fara Dayana Mohd , Husain Nor Masharah , Ariffin Mohammad Naquiddin Tajul
Published: March 2024

Wayang Kulit Kelantan (WKK) is a traditional performance that has a long process in the learning session. This covers various aspects such as the background of the performance, repertoire, gambalan (puppets), as well as musical instruments and songs. This knowledge requires at least a year to understand the skills and techniques used. Therefore, Wayang Edu is a digital application built based on the analyze, design, development, implementation, evaluation (ADDIE) model to save learning time with traditional practitioners. The majority of users acknowledge that Wayang Edu offers a wealth of information and enables them to gain in-depth knowledge. Consequently, utilizing visual elements to convey messages is more impactful compared to traditional learning methods. Apart from that, Wayang Edu can be used anywhere at the user’s convenience. With the interaction found in the application, Wayang Edu has been used by students as a platform to get additional information about WKK.
Educational video games to improve the learning process
Authors: Cachay-Gutierrez Alejandro , Cabanillas-Carbonell Michael
Published: March 2024

The pandemic has made us quickly migrate to virtual environments, for this reason, we must look for quality education mechanisms, thus continuing with the same level of traditional teaching. This research aims to determine the influence of an educational video game in improving the learning process, for which a study was carried out on first-cycle university students. The level of the research is explanatory, of the applied type, with a quantitative approach and quasi-experimental design. We worked with two groups already formed in which 65 students participated. The following results were obtained: an increase in the grade of motivation of 12.9%, an improvement in the acquired knowledge indicator of 46.34%, and an improvement in the obtained qualification indicator of 12.77%. Therefore, it is concluded that an educational video game influences the motivation, acquisition, and application of learning.
Which one is more accurate, BILOG or R program? (a comparison for score test equating)
Authors: Purnama Dian Normalitasari , Hadi Samsul , Sukirno Sukirno , Retnawati Heri , Amelia Rizki Nor
Published: March 2024

Evaluation may be carried out using different tests that are not necessarily parallel. Students with lower abilities may get higher scores while those with higher abilities get lower scores. Measurement errors caused by this condition require test equating. Several computer programs, including Bilog and the R program, can be used for test equating. Each program has a different level of accuracy, and the accuracy of the equating results will affect the standard errors of equating. This study aimed to find out the most accurate equating test method and the accuracy of the estimated BILOG and R program. This research used two sets of tests with equivalent group designs. The determination of the most accurate equating method was based on the root mean square deviation (RMSD) value. Equating test packages, A to package B with BILOG program estimation on the mean and Sigma method resulted in RMSD value of 0.320. In the mean and mean method, RMSD value is 0.250. Meanwhile, equating package A to package B using R program on the mean and sigma resulted in RMSD value of 0.300, and the mean and mean method with the RMSD value is 0.272. The mean and mean yield RMSD values smaller than the mean and sigma methods. Therefore, the mean and mean method is more accurate and applicable. Moreover, the estimation results of the BILOG program are more accurate and can be used in test equating.
The construct validity of self-regulated learning questionnaire for senior high school students: a Rasch model analysis
Authors: Ramadhani Rahmi , Syahputra Edi , Simamora Elmanani
Published: March 2024

Self-regulated learning (SLR) is a condition in which students actively participate in the process of acquiring knowledge, and it closely relates to students’ metacognitive, motivational, and behavioral aspects. In order to measure this variable, an instrument was developed by referring to the Zimmerman cycle in the form of a questionnaire. Therefore, this study aims to analyze the construct validity of SLR questionnaires designed for high school students through Rasch model analysis. The method employed was descriptive quantitative research. The analyzed questionnaire consists of 50 positive statements, rated on 4-point Likert scale, and arranged of forethought, performance, and self-reflection phases. Furthermore, the construct validity was conducted on 235 third grade (XII) high school students in Gunungsitoli City (Indonesia), with a gender distribution of 58.29% female and 41.70% male. The results showed that the questionnaire with 4-rating scales satisfied the criteria for validity, gender inclusiveness, and unidimensionality based on Rasch model analysis for 25 statements. The implication of this research shows that the SLR questionnaire developed is valid and can be used in wider field research, especially in mathematics learning.
A systematic literature review: how do we support students to become numerate?
Authors: Adelia Viona , Putri Ratu Ilma Indra , Zulkardi Zulkardi
Published: March 2024

Numeracy is the essential skill for life situations that involve mathematical elements and developing students’ numeracy skills is considered a primary goal of mathematics education. Despite its importance, numeracy can be challenging to teach, and it is not a guaranteed result of classroom mathematics learning. Through a systematic literature review, 35 studies about supporting students in becoming numerate in classrooms or courses are explored, this literature review also explained abilities included as numeracy, recommendations for teachers are given as well as some examples was given, also opportunities and directions for further research are identified, including guidelines for enhancing students’ numeracy competence.
Course design aspects of blended learning in undergraduate education
Authors: Senanayake Sanjeewanie Hemamali Dias , Sandanayake Thanuja Chandani
Published: March 2024

Blended learning is a popular teaching mode in today’s higher education system. Course design for blended education presents a challenge for educational specialists. This research aims to identify the essential aspects of course design in undergraduate blended learning. Course content, course structure and delivery, collaborative engagement, learner facilitation, and assessment and evaluation were discovered as aspects of blended learning course design. Based on the identified aspects, a survey questionnaire was designed and pilot tested to check the reliability and validity of the measurement tool. The analysis revealed that the questionnaire was acceptable in terms of psychometric characteristics after removing four items. Therefore, 23 items remained in the final questionnaire, which was considered reliable and valid for the context. The information was gathered using an online questionnaire from academic staff at Sri Lankan state universities attached to the departments conducting degree programs in the computing discipline. There were 97 participants included in the final dataset. The results were analyzed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The results revealed that ‘assessment and evaluation’ was highly considered when designing undergraduate blended learning courses, while other aspects which are also imperative, have been paid less attention by the university academicians.