bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P6-04-04: Clinical Relevance of PD-L1 and CD8 Expression in Triple Negative Breast Cancer
Authors: Bago-Horvath Zsuzsanna , Marhold Maximilian , Heber Ulrike , Bartsch Rupert , Fitzal Florian , Singer Christian F. , Filipits Martin
Published: March 2023

Background: Immune checkpoint inhibitors such as PD-L1 are promising therapy targets in triple negative breast cancer (TNBC). In the present study, we examined the clinical relevance of PD-L1 and CD8 expression in TNBC patients treated with adjuvant chemotherapy. Methods: FFPE tumor material from 118 patients with early TNBC treated between 1999 and 2012 was included in our analysis. Immunohistochemical (IHC) expression of PD-L1 was determined by immune score using the diagnostic antibody SP142 (Ventana). CD8 IHC was performed using the SP57 antibody (Ventana). Follow-up data were available for all 118 patients with a median follow up time of 19.4 years. Biomarkers were examined as continuous or categorical variable (predefined cutoffs). Invasive disease-free survival (IDFS) and overall survival (OS) were analyzed using Cox regression models. Results: The median PD-L1 immune score was 1% and PD-L1 expression was classified as positive in 79/116 (68.1%, cutoff ≥1%) cases. Median CD8 expression was 10% and was scored as positive in 51/115 (44.3%, cutoff >10%) samples. Significant associations were observed between PD-L1 expression and tumor grade, Ki67, and CD8 expression. PD-L1-positive tumors were more frequently in the G3 group (p=0.006) and had higher Ki67 (p< 0.001) and higher CD8 expression (p< 0.001). PD-L1 but not CD8 expression was associated with IDFS or OS. Univariate Cox regression analyses showed that PD-L1-negative patients had a shorter IDFS (HR 0.52, 95%CI 0.30-0.89, p=0.02) and showed a trend towards shorter OS (HR 0.56, 95%CI 0.30-1.03, p=0.06). CD8 expression was neither associated with IDFS (HR 0.74, 95%CI 0.43-1.27, p=0.27) nor with OS (HR 0.87, 95%CI 0.48-1.60, p=0.66). In multivariate analyses, PD-L1 expression was an independent prognostic factor for IDFS (HR 0.51, 95%CI 0.29-0.88, p=0.016) but not for OS (HR 0.53, 95%CI 0.28-1.01, p=0.052). Conclusions: Our results suggest that PD-L1 but not CD8 expression assessed by IHC predicted outcome in TNBC. Further analysis of larger, suitable patient cohorts is warranted to further assess the prognostic and predictive value of PD-L1 expression.

Citation Format: Zsuzsanna Bago-Horvath, Maximilian Marhold, Ulrike Heber, Rupert Bartsch, Florian Fitzal, Christian F. Singer, Martin Filipits. Clinical Relevance of PD-L1 and CD8 Expression in Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-04.
Abstract P6-09-05: Using Mixed Methods to Examine Clinician and Patient Use of Terminology to Describe Trastuzumab Biosimilars
Authors: Papautsky Elizabeth , Salunke Devika , Montague Hannah , Carlson Martha , Johnson Sheila , Attai Deanna , Lustberg Maryam
Published: March 2023

Although the uptake of trastuzumab biosimilars to treat HER2-positive breast cancer is growing, knowledge gaps remain for both, patients and clinicians. In a mixed-methods study, inconsistencies in terminology used to describe trastuzumab biosimilars. We analyzed open-ended questions from surveys (n = 143 breast cancer patients, n = 33 medical oncologists) and interviews (n = 8 patients, n = 4 oncologist, nurse, pharmacists) indentifying terminology as an a priori (top-down) category for qualitative thematic analysis. We specifically looked for examples of inconsistent or incorrect use of terminology in the interviews. Findings suggest that 1) terminology used to refer to trastuzumab biosimilars is variable across patients and some is not representative of the formal definition (e.g. generic, generic-like, interchangeable, Herceptin, generic Herceptin (as per how their oncologist refers to biosimilars) and 2) clinicians discussed the challenges of talking about biosimilars in a manner that is both understandable to patients and accurate. Specifically, one pharmacist highlighted concerns around this complexity and suggested that it should be part of clinician education to use the correct terminology, rather than using the term generic. A medical oncologist said that “Explaining biosimilars to a patient can be challenging” as part of their survey response. Lack of consistent terminology for trastuzumab biosimilars is a potential barrier to effective patient-clinician communication on this topic and may perpetuate lack of comprehension on the part of patients. Further, the intentional use (to make information more digestible to patients) of incorrect terminology by clinicians has the potential to negatively impact the patient-clinician relationship in cases where patients identify conflicting information on their own. The adoption of terminology that is consistent across clinicians and patient-facing resources on the introduction and description of trastuzumab biosimilars, may serve to facilitate common grounding among all roles.

Citation Format: Elizabeth Papautsky, Devika Salunke, Hannah Montague, Martha Carlson, Sheila Johnson, Deanna Attai, Maryam Lustberg. Using Mixed Methods to Examine Clinician and Patient Use of Terminology to Describe Trastuzumab Biosimilars [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-09-05.
Abstract P6-11-13: Ferroptosis Heterogeneity in Triple-Negative Breast Cancer Reveals an Innovative Immunotherapy Combination Strategy
Authors: Yang Fan , Xiao Yi , Ding Jia-Han , Jiang Yi-Zhou , Shao Zhi-Ming
Published: March 2023

Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration of metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic strategies. Here, we integrated the multiomics data of our large TNBC cohort (n=465) to develop the ferroptosis atlas. We discovered that TNBCs had heterogeneous phenotypes in ferroptosis-related metabolites and metabolic pathways. The luminal androgen receptor (LAR) subtype of TNBC was characterized by the upregulation of oxidized phosphatidylethanolamines and glutathione metabolism (especially GPX4), which allowed the utilization of GPX4 inhibitors to induce ferroptosis. Furthermore, we verified that GPX4 inhibition not only induced tumor ferroptosis but also enhanced antitumor immunity. The combination of GPX4 inhibitors and anti-PD1 possessed greater therapeutic efficacy than monotherapy. Clinically, higher GPX4 expression correlated with lower cytolytic scores and worse prognosis in immunotherapy cohorts. Collectively, this study demonstrated the ferroptosis landscape of TNBC and revealed an innovative immunotherapy combination strategy for refractory LAR tumors.

Citation Format: Fan Yang, Yi Xiao, Jia-Han Ding, Yi-Zhou Jiang, Zhi-Ming Shao. Ferroptosis Heterogeneity in Triple-Negative Breast Cancer Reveals an Innovative Immunotherapy Combination Strategy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-11-13.
Abstract P6-12-02: Connecting Fluctuations in Estrogen Production, Release, and Action with Hormone-Dependent Gene Expression in Breast Cancers
Authors: Kim Hyung Bum , Kraus William L.
Published: March 2023

Estrogens are steroid hormones that play a key role in a wide range of physiological and pathological processes. Estrogen receptor-alpha, ERɑ, functions primarily as a nuclear transcription factor (TF) through ligand-dependent activation by 17β-estradiol (E2), the predominant naturally-occurring estrogen. This results in dimerization, DNA binding to cis-regulatory elements called enhancers, and gene regulatory function of ERɑ. In vivo, E2 production and action fluctuates during reproductive cycles and possibly even in a circadian manner. In tissues and cells, E2-regulated gene expression is dynamic, with rapid induction of enhancer formation and target gene expression (or repression), followed by enhancer “decommissioning” and cessation of the gene regulatory effects. The effects of sustained E2 production and signaling, fluctuations in E2 levels, and removal of E2 on estrogen-regulated gene expression are unknown. Classical experiments exploring the gene regulatory effects of E2 involve stimulation of cultured cells throughout the duration of the experiment with a continuous and typically high dose of hormone, with the cells harvested at the end of the stimulation period. While this has allowed us to understand the molecular underpinnings of signal-dependent transcription, it has not allowed analysis of physiological fluctuations in estrogen signaling involving periods of stimulation (i.e., the presence of hormone) and non-stimulation (i.e., the absence of hormone). In our studies, we are applying a combination of next generation sequencing techniques and fluorescence microscopy to investigate signal-dependent responses to fluctuating and short duration E2 exposures using ERɑ-positive MCF-7 human breast cancer cells after E2 treatment and removal. Our initial results suggest that different E2 target genes respond differently to low dose E2 treatment and E2 withdrawal. Moreover, for some E2 target genes, sustained E2 treatment may not be required for a complete E2 transcriptional response. With these studies, we hope to connect physiological aspects of E2 production, release, and action with the molecular mechanisms of E2-dependent gene expression - an aspect of our understanding of estrogen signaling that has been lacking.

Citation Format: Hyung Bum Kim, William L. Kraus. Connecting Fluctuations in Estrogen Production, Release, and Action with Hormone-Dependent Gene Expression in Breast Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-12-02.
Abstract P6-13-01: EPITHELIAL-MESENCHYMAL TRANSITION AND TUMOR STEM CELLS NETWORK IDENTIFICATION IN BREAST CARCINOMAS: IN SILICO STUDY
Authors: Dybal Vanessa , Cavalcante Bruno R. , Rocha Gisele V. , Gurgel Clarissa
Published: March 2023

INTRODUCTION: Breast cancer (BC) is the most prevalent malignant tumor in the female population, except for skin tumors. Despite therapeutic advances, over 20% of patients with localized disease will relapse. The research of epithelial-mesenchymal transition (EMT), tumor stem cells (TSC), and the biological mechanisms related to refractoriness and metastasis development is, therefore, an opportunity for new therapeutic strategies and better results. OBJECTIVES: To identify breast cancer cellular markers related to EMT and TSC according to their histological subtypes, stage and to analyze their relationship with clinical outcomes. METHODS: After selecting a public breast cancer patients database with interactome, we identified differentially expressed genes, their associated processes, coexpression networks and interactions with pathways related to the stem phenotype and epithelial-mesenchymal transition. The characterization of key genes and the correlation with histological subtypes and clinical outcome allowed us to determine a group of genes as potential breast cancer EMT/TSC prognostic markers. RESULTS: In the 989 patients studied, 1033 differentially expressed genes (DEGs) were found, categorized according to histological subtype (hormone receptor positive, HER2 positive, triple negative) and stage IV. Seven communities of gene coexpression were found, with the gray community showing greater interaction with hormone positive tumors, the green community with HER2 positive, and the turquoise community with the triple negative one. The hormone positive disease was related to extracellular matrix processes and neuronal communication, the HER2 positive to the extracellular matrix interaction and the triple negative tumors to mitotic processes. Investigation networks with EMT and TSC related genes demonstrated a strong correlation with HER2-positive and triple-negative tumors; being eight genes in HER2 positive subtypes correlated with survival (SYNDIG1, ​​COL10A1, SLC24A2, LINC00922, KLKP1, MMP11 and ECM2); and one of the hormone positive subtype (ITIH5). ECM2 was highlighted in terms of EMT/TSC connectivity and survival. CONCLUSION:The EMT/TSC processes are significant in the various subtypes of breast cancer and impact on survival, especially in the HER2 positive subtype.

Citation Format: Vanessa Dybal, Bruno R. Cavalcante, Gisele V. Rocha, Clarissa Gurgel. EPITHELIAL-MESENCHYMAL TRANSITION AND TUMOR STEM CELLS NETWORK IDENTIFICATION IN BREAST CARCINOMAS: IN SILICO STUDY. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-13-01.
Abstract PD15-08: PD15-08 Brazilian Randomized Study - BREAST-MRI Trial - Impact of Preoperative Magnetic Resonance in the Evaluation for Breast Cancer Conservative Surgery: Local recurrence and surgical outcomes
Authors: Mota Bruna S. , Reis Yedda N. , Barros Nestor , Cardoso Natalia , Mota Rosa s. , Shimizu Carlos , Tucunduva Tatiana , Gonçalves Rodrigo , Doria Maira T. , Ferreira Vera , Ricci Marcos , Trinconi Angela , Riera Rachel , Baracat Edmund C. , Soares José Maria , Filassi Jose Roberto
Published: March 2023

Introduction: Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. However, controversy remains as to whether preoperative staging with breast MRI impacts surgical outcomes and local recurrence. Materials and Methods: BREAST-MRI is a randomized, open-label trial including female breast cancer patients older than 18 years old, with stage 0-III disease, eligible for BCS. We performed a 1:1 stratified randomization by breast density according to ACR-BIRADS to divide patients into two groups; one in which preoperative MRI was used and the control group where the MRI was not used. The primary outcome was local relapse-free survival (LR). Secondary outcomes were overall survival (OS), repeat operation, and the proportion of patients whose surgical management was modified to mastectomy. Results: 524 were randomized, 257 included in the MRI group, and 267 in the control group. The baseline characteristics were similar between groups, except for chemotherapy use (table 1). The survival analysis showed a 6-year local recurrence-free survival was 99.2% in MRI group versus 98.9% in the control group, p=0.702, overall survival of 95.3% in the MRI group versus 96.3% in the control group, p=0.481. No difference was found in reoperation rates, 22 (8.7%) in the MRI group versus 23 (8.7%) in the control group (p= 0.85)(table2). Surgical management changed in 21 ipsilateral breasts in the MRI group; 21 (8.3%) had mastectomies versus 1 in the control group (p< 0.01). Conclusion: Preoperative MRI evaluation increased the mastectomy rates by 8%. The use of preoperative MRI did not influence local relapse-free survival, overall survival, or reoperation rates Keywords: breast magnetic resonance imaging; breast cancer; conservative surgery; MRI accuracy, surgical outcomes, randomized clinical trial

Citation Format: Bruna S. Mota, Yedda N. Reis, Nestor Barros, Natalia Cardoso, Rosa s. Mota, Carlos Shimizu, Tatiana Tucunduva, Rodrigo Gonçalves, Maira T. Doria, Vera Ferreira, Marcos Ricci, Angela Trinconi, Rachel Riera, Edmund C. Baracat, José Maria Soares Jr, Jose Roberto Filassi. PD15-08 Brazilian Randomized Study - BREAST-MRI Trial - Impact of Preoperative Magnetic Resonance in the Evaluation for Breast Cancer Conservative Surgery: Local recurrence and surgical outcomes [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-08.
Abstract PD3-06: Robotic Stereotactic APBI for Early-Stage Breast Cancer: 2-year Outcomes of a Prospective Multi-Institutional Trial
Authors: Cantalino Jonathan M. , D’Ambrosio David , Hirsch Arica , Collins Brian , Danner Malika , Matsanka Dawn , Rudra Sonali , Suy Simeng , Collins Sean , Marin Monica Pernia , Good Michael , Feng Jing , Lamond John , Markiewicz Deborah , Lanciano Rachelle , Obayomi-Davies Olusola
Published: March 2023

Purpose: Outcomes following adjuvant accelerated partial breast irradiation (APBI) in select women with early-stage breast cancer are comparable to whole breast irradiation. Robotic stereotactic accelerated partial breast irradiation (RSAPBI) with fiducial tracking is an attractive treatment option, but limited outcomes data are available for this approach. We report 2-year outcomes for a prospective multi-institutional trial treating select women with RSAPBI. Materials and Methods: Post-menopausal women with DCIS and Stage IA breast cancer were treated over a five-year period extending from November 2015 to November 2020 and were followed for a minimum of 18 months. Treatments were delivered with a robotic radiosurgery system. Four gold fiducials were implanted around the lumpectomy cavity prior to the start of treatment for tumor bed delineation and target tracking. The CTV was defined as the lumpectomy cavity with a uniform 5-15 mm expansion confined to the breast tissue and the PTV was defined as the CTV with a 0-5 mm uniform expansion. The PTV was prescribed 30 Gy in 5 fractions. Disease status assessments were completed at 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months and yearly intervals thereafter for five years. Results: Eighty-one patients (median age 68 years) with hormone receptor-positive tumors were treated over a median 9 days (range, 5-15). Sixty-eight women had invasive ductal carcinoma (84%) and thirteen had DCIS (16%). The median treated PTV was 108 cm3 (IQR 66-156) and the median prescription isodose line was 81% (IQR 79-83). The median CTV expansion was 10 mm (range 5-10) and the median PTV expansion was 3 mm (range 0-5). At a median follow up of 2 years there was one new ipsilateral breast tumor diagnosed. There were no local, regional, or distant treatment failures. Conclusions: Two-year results suggest that RSAPBI with fiducial tracking is an effective technique for the adjuvant treatment of post-menopausal women with hormone receptor-positive early-stage breast cancer. Additional follow-up is planned to confirm this preliminary finding.

Citation Format: Jonathan M. Cantalino, David D’Ambrosio, Arica Hirsch, Brian Collins, Malika Danner, Dawn Matsanka, Sonali Rudra, Simeng Suy, Sean Collins, Monica Pernia Marin, Michael Good, Jing Feng, John Lamond, Deborah Markiewicz, Rachelle Lanciano, Olusola Obayomi-Davies. Robotic Stereotactic APBI for Early-Stage Breast Cancer: 2-year Outcomes of a Prospective Multi-Institutional Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-06.
Abstract PD6-02: PD6-02 Health-Related Quality of Life Trajectories and Predictors among Older Breast Cancer Survivors: A SEER-MHOS analysis
Authors: Lee Eunkyung , Rupesh Sushantti , Ferdowsi Katia , Hines Robert , Loerzel Victoria
Published: March 2023

Health-related quality of life (HRQOL) is an important issue for breast cancer patients and clinicians in the treatment decision process. In addition, older women are more vulnerable due to pre-existing comorbidities and socioeconomic status. This study explored 10-year trajectories of HRQoL in older breast cancer survivors and their predictors using patient-reported outcomes data queried from the Surveillance, Epidemiology and End Results - Medicare Health Outcomes Survey (SEER-MHOS) data resources among Medicare beneficiaries. Older women diagnosed with breast cancer in 1998-2012 and who participated in the surveys before and at least once after diagnosis were included in the analysis. HRQOL was measured using SF-36/VR-12 questionnaire and summarized as Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score. Latent Class Growth Mixture Modeling was conducted to identify distinct groups of women with a similar trajectory of HRQOL. A total of 1089 women with breast cancer completed surveys an average of 2.6 times (range 2 - 19). The results showed that there were three latent classes of PCS trajectory: high-declining (46% of the sample), mid-declining (37%), and low-improving (17%). Two latent classes of MCS trajectory were identified: high-stable (76%) and low-declining (24%). The univariate analysis showed that age at diagnosis, body mass index, level of education, geographic region, tumor grade, tumor size, and the number of comorbidities were related to PCS and MCS scores. Multivariable multinomial logistic regression analysis identified the number of comorbidities as the most significant predictor for PCS score and level of education as the most significant predictor for MCS score. Future research needs to identify the most common comorbidities that influence HRQOL deterioration in older breast cancer survivors to develop interventions that better the physical HRQOL in patients. Also, interventions that target less educated, underserved patients to improve mental HRQOL.

Citation Format: Eunkyung Lee, Sushantti Rupesh, Katia Ferdowsi, Robert Hines, Victoria Loerzel. PD6-02 Health-Related Quality of Life Trajectories and Predictors among Older Breast Cancer Survivors: A SEER-MHOS analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-02.
Abstract PD9-01: Stromal mediators of lymphocyte exclusion and dysfunction in triple negative breast cancer
Authors: Chen Julia , Wu Sunny , Ruan Travis , Slapetova Iveta , Millar Ewan , Lim Elgene , Swarbrick Alex
Published: March 2023

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with poor prognosis and limited treatment options. One of the mechanisms contributing to this is the ability of TNBC tumors to evade anti-tumour response, limiting the success of immune-checkpoint therapy. In recent studies of the tumor microenvironment, stromal cells have emerged as potential important mediators of lymphocyte function in TNBC. Multi-omics studies from our group and others have elucidated the heterogeneity of stromal cells and their interactions with immune cells in TNBC. However, the clinical relevance and functional characteristics of these relationships remain poorly explored. Our previous work revealed functionally distinct subpopulations of stromal cells in breast cancer: endothelial cells, myofibroblast-like cancer-associated fibroblasts (myCAFs), inflammatory-CAFs (iCAFs), and perivascular-like cells which resemble pericyte and smooth muscle cells in immature and differentiated states (imPVLs; dPVLs), respectively. Here we directly explored the clinical relevance of these stromal subpopulations and their association with immune evasion in a large independent TNBC cohort with long-term survival data. Using markers derived from our single-cell multi-omics studies, we performed multiplex immunofluorescence using the OPAL9 platform on tumor microarrays from 222 TNBC patients to mark myCAFs, iCAFs, dPVLs, endothelial cells, CD8 and/or PD1 positive T-cells. Digital imaging analysis (QuPath) revealed a significant negative correlation between the abundance of stromal cells and CD8 T cells. This cytotoxic T-cell exclusion is primarily driven by smooth muscle dPVLs. Parallel to this T-cell exclusion, our functional studies demonstrate that stromal cells suppress T-cell proliferation. Using multiple ex vivo co-culture models of primary TNBC CAFs and peripheral blood mononuclear cells (PBMCs) from healthy and matched donors, we show that CAFs suppress the proliferative capability of CD4 and CD8 T-cells. ScRNA-seq of these co-culture models demonstrate that CAF educated T cells are driven into a LAG3+ exhausted state enriched for canonical pathways of immunosuppressive cytokine signaling. Our findings suggest that manipulation of these stromal subpopulations could elicit a more effective immune response in a subset of patients through inhibiting T-cell dysfunction and exclusion.

Citation Format: Julia Chen, Sunny Wu, Travis Ruan, Iveta Slapetova, Ewan Millar, Elgene Lim, Alex Swarbrick. Stromal mediators of lymphocyte exclusion and dysfunction in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD9-01.
Abstract WS1-2: How to measure and improve drug adherence in clinical trials
Authors: Hershman Dawn
Published: March 2023

The past decade has seen a dramatic increase in the number of Food and Drug Administration approval of oral anti-cancer drugs (OACDs). In 2018 alone, OACDs comprised ten of the sixteen newly approved oncology therapeutics in the United States. Despite the clinical benefits and convenience of OACDs, these new oral options present potential challenges, including polypharmacy, and can result in increased toxicities, drug–drug interactions (DDIs), inappropriate consumption of medications, and medication non-adherence. Adverse drug events have the potential to affect quality of life, healthcare utilization, treatment response, and survival.

For the treatment of breast cancer, Endocrine therapies have remained a critical component of care for early stage and advance disease. Despite the proven efficacy adherence to therapy is suboptimal. Issues related to non-adherence are increasingly important, as analyses from prospective randomized trials show compliance to endocrine therapy is associated with improved disease-free survival. The reasons for non-adherence to hormonal therapy are multifactorial. Barriers to compliance include patient, physician, medication and system related variables and poor compliance is usually associated with a combination of these factors. Characteristics associated with non-adherence include very high and low age, minority race, being single, increased number of comorbidities, lack of knowledge about efficacy of AI therapy, history of non-adherence to other chronic medications, limited insurance status, and higher out of pocket costs. Side effects from hormonal therapy is the most common reason for early discontinuation. An understanding of factors that contribute to non-adherence and interventions that have been tested to improve adherence will be discussed.

Medication compliance has become a more salient issue in cancer care with the increased availability of oral antineoplastic therapies for breast cancer. The treatment of BC now routinely encompasses targeted therapies such as oral poly(ADP-ribose) polymerase (PARP) inhibitors and cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors, PI3 Kinase(Pi3K) Inhibitors, in addition to traditional ET. Furthermore, as advances in BC treatment have improved long-term prognosis, the management of other chronic conditions has become an essential component of BC survivorship care. It remains unclear how this increased oral medication burden on BC survivors affects compliance with both ET and other chronic medications. Issues related to adherence measurement will be discussed.

Citation Format: Dawn Hershman. How to measure and improve drug adherence in clinical trials [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr WS1-2.
The Effectiveness of Various Types of Local Hydromacrophytes on The Phytoremediation Process of Catfish Pond Wastewater using a Batch Culture System
Authors:   Biology Department, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Sa'adah Umi , Siswanto Dian ,   Biology Department, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Retnaningdyah Catur ,   Biology Department, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya
Published: March 2023

This study aimed to determine the effectivity of various types of local hydromacrophytes on the remediation of wastewater from catfish culture ponds in Gondosuli village, Gondang, Tulungagung, East Java, Indonesia, using a batch culture system. This experiment used a completely random design and was conducted in the glasshouse. The batch culture system was conducted in a 30 L tank containing sand and gravel as the medium for hydromacrophytes. This research consisted of five treatments (emer-gent, submerged, floating leaf, polyculture of 3 types of hydromacrophytes, and control without hydro macrophytes). This study was repeated three times at the same time. The effectiveness of the phytoremediation model was monitored using indicators of water physicochemical parameters and the biotic index of phytoplankton.The biotic indices were used the Shannon-Wiener diversity index (H') of phytoplankton and the diatom biotic index (Trophic Diatom Index (TDI) and Percentage of Pollution Toler-ant Value (%PTV)). After giving the treatment, monitoring was carried out on days 0, 10, 20, 30, and 40. The results showed that the batch culture system for phytoremedi-ation post-harvest catfish pond wastewater with local hydromacrophytes improved the water quality. However, not all water physicochemical parameters after treatments meet Indonesian water quality standards. Abundance showed water quality fluctua-tions over time, while Shannon Wiener's diversity index (H' value) decreased as water quality decreased. This study's PTV value demonstrated that pollutant levels vary by treatment. Only the control and submerged hydromacrophytes improved their TDI status; another treatment remained moderate. The best treatment was 40 days after acclimatization with polyculture treatment of three types of local hydromacrophytes. Research and othersystems like continuous culture are needed for optimal results to improve water quality. Keywords:Batch culture, Catfish pond, Hydromacrophyte, Remediation, Wastewater, Water qualit
Antioxidant Activity of Unripe Sapodilla Fruit Extract (Manilkara zapota L.) through Nrf2 and SOD Expression in Type 1 Diabetic Mice
Authors:   Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, 65145, Indonesia, Sari Fikriya , Samoedra Rizky ,   Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, 65145, Indonesia, Pratama Setyaki ,   Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, 65145, Indonesia, Rahayu Sri ,   Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, 65145, Indonesia, Soewondo Aris ,   Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, 65145, Indonesia, Natsir Muhammad ,   Faculty of Animal Science, Brawijaya University, Malang, 65145, Indonesia, Rifa'i Muhaimin ,   Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, 65145, Indonesia
Published: March 2023

This research aims to analyze the effect of unripe sapodilla fruit extract on endogenous antioxidant expression in T1DM BALB/c mice and its free radical scavenging activity. Manilkara zapota extract (MzE) is an aqueous extract of unripe sapodilla fruit and was obtained by maceration and freeze-drying process. This study used 25 male BALB/c mice with 7-weeks-old of age. They were divided randomly into five groups (n=5) before treatment. A single high dose (145 mg/kg BW) of streptozotocin (STZ) was intraperitoneally injected to induce type 1 diabetes mellitus (T1DM). MzE was given orally once each day for 14 days. Liver cells were isolated and immunoassay with anti-superoxide dismutase (SOD) and anti-nuclear factor erythroid 2-related Factor 2 (Nrf2), and then the results were analyzed by flow cytometry. Diphenylpicrylhydrazyl (DPPH) assay was performed to analyze free radical scavenging. Data were analyzed statistically with one-way ANOVA (p<0.05). The result showed that the glucose levels in diabetic mice after MzE administration were significantly lower than in the DM group. MzE treatment increased the expression of Nrf2 and SOD in diabetic mice. MzE could scavenge DPPH with the IC50 value obtained at 48.35 μg/mL, while ascorbic acid as a control could scavenge DPPH with the IC50 value at 22.24 μg/mL. The increase in the scavenging activity is in line with the increase in extract concentration. In conclusion, this study revealed that MzE can be an endogenous antioxidant enhancer by improving the expression of Nrf-2, SOD and can inhibit free radicals as an exogenous antioxidant in T1DM
An Overview of Stress-Tolerant Promoting Endophytic Fungal Isolates from Hiyung Chilli Grown in South Kalimantan
Authors:   Universitas Lambung Mangkurat, Imaningsih witiyasti , Ekowati Nuraeni ,   Biology Faculty, Universitas Jenderal Soedirman, 53122, ,Purwokerto-Central Java, Indonesia, Salamiah Salamiah ,   Plant Protection Study Program, Faculty of Agriculture, Universitas Lambung Mangkurat, 70714, Banjabaru-South Kalimantan, Indonesia, Ratnaningtyas Nuniek ,   Biology Faculty, Universitas Jenderal Soedirman, 53122, ,Purwokerto-Central Java, Indonesia, Soesanto Loekas ,   Faculty of Agriculture, Universitas Jenderal Soedirman, 53122, Purwokerto-Central Java, Indonesia
Published: March 2023

Endophytic fungi are a unique class of microorganisms that lives in plant tissues. These fungi could spread from roots to shoots and interact with nearly all plants in a symbiotic, mutualistic, or commensal manner. Endophytic fungi are believed to exert several roles related to plant growth, including the ability to tolerate stress, especially in Hiyung chilli plants. This plant is widely cultivated in Indonesia and is a well-known host for endophytic fungi. The Hiyung chilli is a popular variety grown in the South Kalimantan Province, which receives national recognition and is geographically certified by the Indonesian government. This wetland-cultivated chilli plant has a uniquely high capsaicin content and long fruit shelf life compared to other varieties. Although endophytic fungal isolates are prevalently found on chilli plants, their potential to influence the growth of their host remains to be proven beyond a doubt. This review emphasizes the sparse reports on the potential of these antagonistic fungi in protecting chilli plants against other pathogens by producing auxin/Indole-3-Acetic Acid (IAA) and capsaicin. The study hypothesised that the antagonistic abilities of these endophytic fungi against other fungal pathogens are related to their IAA- and capsaicin production that synergistically increase the chili plants' threshold against biotic and abiotic stress.
Intraarterial Transplantation of Mitochondria After Ischemic Stroke Reduces Cerebral Infarction
Authors: Norat Pedro , Sokolowski Jennifer D. , Gorick Catherine M. , Soldozy Sauson , Kumar Jeyan S. , Chae Youngrok , Yagmurlu Kaan , Nilak Joelle , Sharifi Khadijeh A. , Walker Melanie , Levitt Michael R. , Klibanov Alexander L. , Yan Zhen , Price Richard J. , Tvrdik Petr , Kalani Mohammad Yashar S.
Published: March 2023

Background

Transplantation of autologous mitochondria into ischemic tissue may mitigate injury caused by ischemia and reperfusion.

Methods

Using murine stroke models of middle cerebral artery occlusion, we sought to evaluate feasibility of delivery of viable mitochondria to ischemic brain parenchyma. We evaluated the effects of concurrent focused ultrasound activation of microbubbles, which serves to open the blood–brain barrier, on efficacy of delivery of mitochondria.

Results

Following intraarterial delivery, mitochondria distribute through the stroked hemisphere and integrate into neural and glial cells in the brain parenchyma. Consistent with functional integration in the ischemic tissue, the transplanted mitochondria elevate concentration of adenosine triphosphate in the stroked hemisphere, reduce infarct volume and increase cell viability. The addition of focused ultrasound leads to improved blood–brain barrier opening without hemorrhagic complications.

Conclusion

Our results have implications for the development of interventional strategies after ischemic stroke and suggest a novel potential modality of therapy after mechanical thrombectomy.
Problematizing Realism: Confronting Colonial Perspectives and Engaging Complexities of Landscape Through “Ghost Textures”
Authors: Ackerman Aidan , Koudelka Christopher , Hirsch Paul , Zaengle Owen
Published: March 2023

Realistic virtual reality visualizations of a physical place, whether historic or contemporary, can exude a sense of certainty about their accuracy. They can also evade complexity by excluding underrepresented narratives about place such as those held by indigenous and other marginalized communities. Through engaging with a framework of complexity, ethics, and humility, we propose a technique of immersive virtual storytelling (IVS) that foregrounds uncertainty through a combination of realistic material treatments and translucent, ephemeral “ghost textures.” By applying these treatments to two virtual three-dimensional models telling a pre- and post-construction story of a World War II-era rifle range, we were able to test the use of these treatments in exposing gaps in archival data. This highlighted the predominance of a colonial lens in guiding historic site visualization, raising a question of how other narratives might be included without conforming to a colonial framework.
Removal of the Vertical Structure Ambiguity in the Thermodynamic Retrieval from Multiple-Doppler Radar Synthesized Wind Fields
Authors: Liou Yu-Chieng , Teng Yung-Lin
Published: March 2023

It has been long recognized that in the retrieved thermodynamic fields using multiple-Doppler radar synthesized winds, an unknown constant exists on each horizontal level, leading to an ambiguity in the retrieved vertical structure. In this study, the traditional thermodynamic retrieval scheme is significantly improved by the implementation of the Equation of State (EoS) as an additional constraint. With this new formulation, the ambiguity of the vertical structure can be explicitly identified and removed from the retrieved three-dimensional thermodynamic fields. The only in situ independent observations needed to perform the correction are the pressure and temperature measurements taken at a single surface station. If data from multiple surface stations are available, a strategy is proposed to obtain a better estimate of the unknown constant. Experiments in this research were conducted under the observation system simulation experiment (OSSE) framework to demonstrate the validity of the new approach. Problems and possible solutions associated with using real datasets and potential future extended applications of this new method are discussed.
Naples Prognostic Score and Prediction of Left Ventricular Ejection Fraction in STEMI Patients
Authors: Birdal Oğuzhan , Pay Levent , Aksakal Emrah , Yumurtaş Ahmet Çağdaş , Çinier Göksel , Yücel Enver , Tanboğa İbrahim Halil , Karagöz Ali , Oduncu Vecih
Published: March 2023

The Naples score is a new prognostic score developed according to inflammatory and nutritional status and frequently evaluated in cancer patients. The present study aimed to evaluate using the Naples prognostic score (NPS) to predict the development of decreased left ventricular ejection fraction (LVEF) after acute ST-segment elevation myocardial infarction (STEMI). The study has a multicenter and retrospective design and included 2280 patients with STEMI who underwent primary percutaneous coronary intervention (pPCI) between 2017 and 2022. All participants were divided into 2 groups according to their NPS. The relationship between these 2 groups and LVEF was evaluated. The low-Naples risk group (Group-1) included 799 patients, and the high-Naples risk group (Group-2) had 1481 patients. Hospital mortality, shock, and no-reflow rates were found to be higher in Group 2 compared with Group 1 ( P < .001, P = .032, P = .004). The NPS was significantly inversely associated with discharge LVEF (B coefficient: −1.51, 95% CI-2.26; −.76, P = .001). NPS, a simple and easily calculated risk score, may help identify high-risk STEMI patients. To the best of our knowledge, the present study is the first to demonstrate the relationship between low LVEF and NPS in patients with STEMI.
Analysis of the fracture characteristic volume (FCV) for laminated composite structures with stress concentrations in compression
Authors: Hochard Christian , Cocchi Aldo , Montagnier Olivier
Published: March 2023

The failure of laminated composite structures is linked to the numerous mechanisms that can appear during the material degradation phase under loading. The approach proposed here is to use Continuum Damage Mechanics to describe the matrix degradation at the ply scale and a non-local criterion, called Fracture Characteristic Volume (FCV), to predict the failure in the fiber direction. The FCV is a circular cylinder with a thickness equal to that of the ply where it is applied. The criterion is defined by comparing an average value inside the FCV, the stress in the fiber direction for example, to a maximum allowable value. This approach has been validated for the prediction of failure for complex geometries with stress concentrations in tension. The objective of this paper is to study the effectiveness of this criterion on different laminates and concentration types in the case of compression.
Improved performance of biopolymer composite electrolyte based cellulose acetate/Zinc Oxide filler for supercapacitors
Authors: Sadiq Mohd , Khan M. Ajmal , Raza Mohammad Moeen Hasan , Zulfequar Mohammad , Ali Javid
Published: March 2023

Biopolymer composite electrolytes consisting of cellulose acetate and magnesium perchlorate with different weight percent (wt.%) of Zinc Oxide fillers were prepared using the standard solution cast technique. The effect of incorporating various amounts of ZnO fillers in our composite electrolytes was investigated for their electrical and structural properties, and ion transference numbers. The ionic conductivity of 40 wt.% ZnO filler was found to be 8.75× 10−4 S/cm at 30 °C along with a 4.2 V electrochemical stability window. The ion transference number has been found to be 0.97 for CA + 40 wt.% of Mg(ClO4)2 + 40 wt.% with ZnO fillers. Furthermore, the electrochemical performances of the prepared electrolytes have also been investigated. The fabricated cell with this electrolyte shows an enhanced energy and high-power density of 2.78 Wh/Kg and 1000 W/Kg, respectively. An increase in the above-mentioned densities may be attributed to the high ionic conductivity ZnO fillers in the biopolymer matrix. Additionally, it shows 100% capacitance retention along with high coulombic efficiency after the 129th cycle.
What makes cities happy? Factors contributing to life satisfaction in European cities
Authors: Castelli Chiara , d’Hombres Beatrice , Dominicis Laura de , Dijkstra Lewis , Montalto Valentina , Pontarollo Nicola
Published: March 2023

The purpose of this study is to identify the main factors of city life satisfaction across Europe. Data come from the recent fifth survey on quality of life in European cities and cover 83 cities located in the European Union, the European Free Trade Association countries, the United Kingdom, the Western Balkan Region and Turkey. In addition to running classical econometric analysis, we quantify the relative importance of the various determinants of overall satisfaction with life in cities, thus offering novel insights to shape evidence-based urban policies. The results highlight that two main policy-relevant areas contribute to the satisfaction with city life: the presence of amenities, on the one hand, and the inclusiveness and safety feeling, on the other hand. Socio-economic characteristics are generally not relevant, with the exception of economic insecurity.

JEL Codes: R10, R58, I31
Safety Assessment of Cocos nucifera (Coconut)-Derived Ingredients as Used in Cosmetics
Authors: Akinsulie Alice , Burnett Christina , Bergfeld Wilma F. , Belsito Donald V. , Cohen David E. , Klaassen Curtis D. , Liebler Daniel C. , Marks James G. , Peterson Lisa A. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Heldreth Bart
Published: March 2023

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 11 Cocos nucifera (coconut)-derived ingredients, most of which are reported to function as skin-conditioning agents in cosmetic products. The Panel reviewed the available data to determine the safety of these ingredients. The Panel concluded that 10 ingredients, derived from coconut flower, fruit, and liquid endosperm, are safe in cosmetics in the present practices of use and concentration described in this safety assessment, and that the available data are insufficient to make a determination of safety for Cocos Nucifera (Coconut) Shell Powder under the intended conditions of use in cosmetic formulations.
Masculinity in crisis? Reticent / han-xu politics against danmei and male effeminacy
Authors: Hu Tingting , Ge Liang , Chen Ziyao , Xia Xu
Published: March 2023

This article examines the tension between public gender expressions and official regulations in mainland China. Utilizing a critical discourse analysis, we investigate a transition in state-initiated criticism and censorship against the danmei genre and male effeminacy. Focusing on the pandemic period, we use official regulations and state media feature articles as data, ‘reticent / han-xu’ politics as a grounding theoretical basis, and statements from mainstream media platforms as secondary resources. We argue that han-xu politics functions as the Chinese party-state's strategic response to a perceived ‘crisis of masculinity’. They first invisibilize and marginalize soft masculinities, and if this is not effective, then suppress and prohibit cultural forms that violate hegemonic masculinity, which works to perpetuate the hetero-patriarchal social-familial system.
Effect of travel speed on the microstructure and mechanical properties of laser beam welded nitronic-50 stainless steel joints
Authors: Palanisamy S. , Rajendran R. , Shashi Kumar S.
Published: March 2023

In this study, fiber laser beam welding was used to join 3 mm-thick nitronic-50 stainless steel. The effect of travel speed on the mechanical, microstructural, and corrosion properties of the weld joints was studied. The experimental findings reveal that travel speed significantly affected the size of bead geometry and the fusion boundary of the weld joints. The microstructure of columnar grains transformed into equiaxed dendritic grains at the center of the weld nugget due to fast cooling at higher travel speeds. The increase in ferrite content was due to the incomplete transformation of ferrite to austenite at higher travel speeds, which led to higher strength and microhardness in the weld joints. Similarly, the corrosion studies demonstrate that the weld joints made at higher travel speeds have superior corrosion resistance due to a higher fraction of equiaxed dendritic grains and smaller dendrites with less inter-dendritic arm spacing.