bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-03-04: PIK3CA mutation prevalence in hormone receptor positive breast cancer patients in United Arab Emirates
Authors: Azribi Fathi , Hourani Mohammad , Magdub Sulaman , Alawadhi Aydah , Yousif Ali , Dawoud Emad , Qawasmeh Khaled Al , Ameri Mouza Al , Trad Diaeddine , Bennini Nouri , Ahmed Mohamed , Ansari Jawaher 
Published: March 2023

Abstract
Background: The Phosphatidylinositol-4,5-bisphosphonate 3-kinase catalytic subunit alpha (PIK3CA) gene is mutated in about 30-40% of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) breast cancer (BC) patients. For HR+/HER2- advanced breast cancer patients with disease progression following endocrine-based therapy, the NCCN guideline recommends testing for PIK3CA mutations with tumour or liquid biopsy to identify suitable patients for targeted therapy with alpelisib, an oral α-specific PI3K inhibitor in combination with fulvestrant. The primary objective of this study was to evaluate the proportion and distribution of PIK3CA mutational landscape of HR+ve BC patients at the largest cancer centre in the United Arab Emirates (UAE). Material and methods: Retrospective review of consecutive HR+ve BC patients at Tawam Hospital for whom PIK3CA testing was requested. DNA was extracted from the samples and a targeted resequencing assay was used for mutation detection in exons 7, 9 and 20 of the PIK3CA gene. Sequencing was carried out using the Next Generation Sequencing platform Ion GeneStudio S5 Prime System with a detection limit of 2-5% of the mutant allelic content. Results: 124 patients with HR+ve BC were enrolled in the present study. The pathology samples were considered unsuitable/unsatisfactory in 18 cases. The median age was 51.5 years (range 31-90). All patients were female, 54% were post-menopausal and 49% presented with de-novo metastatic disease. Of the 106 eligible patients, PIK3CA mutations were detected in 33 (31%) patients, the most common being H1047R (45%) and E545K (30%) mutations in exons 20 and 9, respectively. Other less common mutations included C420R mutations (6%) in exon 7, E542 (6%) in exon 9 and H1047Y (3%) in exon 20. 9% of patients had more than one hotspot mutations, primarily in exons 9 and 20. Of the 12 HER2 +ve patients tested, 3 had PIK3CA mutations, most commonly the H1047R mutation in exon 20. Conclusion: The prevalence of PIK3CA mutations and the presence of most common hotspot mutations in exons 20 and 9 was consistent with prior published studies. The clinical relevance of PIK3CA mutations in HER2 +ve BC patients needs further assessment.
Citation Format: Fathi Azribi, Mohammad Hourani, Sulaman Magdub, Aydah Alawadhi, Ali Yousif, Emad Dawoud, Khaled Al Qawasmeh, Mouza Al Ameri, Diaeddine Trad, Nouri Bennini, Mohamed Ahmed, Jawaher Ansari. PIK3CA mutation prevalence in hormone receptor positive breast cancer patients in United Arab Emirates [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 P5-03-04.
Abstract P6-05-18: Reasons for Delay in Indian Women Presenting with Primary Stage III or IV Breast Cancer: An Observational Study
Authors: KHARE SIDDHANT , Doda Vidushi , IRRINKI R N NAGA SANTOSH 
Published: March 2023

Abstract
Background: Developing countries like India share higher burden of deaths due to breast cancer, despite having lower incidence than the west. Greater proportion of patients presenting with advanced stages of cancer is one of the reasons for this disparity. Since the factors leading to such delay have not been well studied in Indian patients, we decided to perform this study. Methodology: This was an observational study conducted from Jan 2021 to July 2022. Purposive Non-Random sampling was used and patients who had stage 3 or 4 breast cancer and were between 18-80 years of age were recruited. Interview was done on a one-to-one basis in a secluded area. Descriptive statistics were used, and chi-square was used to study the association of socio-demographic and clinical variables with the delay status of the breast cancer. Results: A total of 75 participants were enrolled in the study with mean age of 52.5 years and SD of 12.5 years. Out of these, 74 had lump as their first symptom. Only 14 of these 74 presented early i.e., within 3 months of onset of symptoms. Rest 60 participants presented late (more than 3 months after onset of symptoms). Between these two groups, difference in incidences of pregnancy associated lumps (0% in &lt; 3 months vs 13.1% in ≥ 3 months, p=0.002), patients being afraid of treatment related complications (0% in &lt; 3months vs 6.6% in ≥ 3 months, p=0.039) and their inability to decide because of lack of knowledge (0% in &lt; 3months vs 6.6% in ≥ 3 months, p=0.039) were statistically significant. To our surprise, the thought that the lump was harmless and painless, embarrassment, limited access to healthcare and distance from the nearest healthcare facility, financial limitations, educational status, socio-economic status, family history of breast cancer, fear of mutilating surgeries and use of traditional medicine or spiritual care didn’t have significant effect on whether the patients presented within or after 3 months of onset of symptoms. On the question of COVID pandemic related delay, only 16% of all patients cited this as an additional reason for delay and this was again, not different between the patients who presented within or after 3 months of onset of symptoms. Conclusions: Health promotion in terms of proper evaluation of pregnancy related lumps and awareness about the management options of breast cancer may help patients to present earlier to healthcare facilities and may help in improving breast cancer related outcomes in developing countries like India.
Citation Format: SIDDHANT KHARE, Vidushi Doda, R N NAGA SANTOSH IRRINKI. Reasons for Delay in Indian Women Presenting with Primary Stage III or IV Breast Cancer: An Observational 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 P6-05-18.
Abstract P6-05-60: People with metastatic breast cancer face barriers to finding information and support
Authors: Pugh-Yi Robin H. , Welcsh Piri , Owens Kelly , Rose Diane , Kuhn Erica , Dearfield Craig T. , Friedman Susan 
Published: March 2023

Abstract
People with metastatic breast cancer face barriers to finding information and support Background FORCE, a national nonprofit organization developed a health communication tool to help patients assess research relevance, key findings, and the quality of media reporting on cancer to support informed and shared health decision-making. People with metastatic breast cancer (mBC) are a priority population. Methods The organization conducted a survey about awareness of and access to breast cancer information and supportive services for people living with metastatic breast cancer. The organization promoted the survey through e-mail and social media, and a network of partner organizations that serve the metastatic breast cancer community. The survey invited respondents to volunteer to participate in focus groups and a follow-up survey in order to support efforts to serve this priority population. Results and Conclusions While interest in clinical trials was high, many users reported that thy do not know how to find an appropriate clinical trial. A majority of the 335 respondents were interested in information about clinical trials, treatment side effects, research findings, long-term health issues, diet/exercise, fatigue, and emotional health. Three quarters of the respondents indicated that they had never participated in a clinical trial, 67% indicated they would be interested in participating in the future, and about 40% indicated they did not know how to find a clinical trial recruiting people with metastatic breast cancer. Approximately one-third of participants were unable to obtain referrals to services they sought. Other barriers to services included lack of insurance coverage, lack of availability, and the COVID-19 public health emergency. Focus group responses indicate that women with mBC find the health communication tool to be useful, and appropriate in language, images, and tone. Results indicate that women with mBC are interested in finding information about clinical trials and other topics related to treatment side effects and quality of life. FORCE and partners are incorporating these results into tailored online resources to meet the needs of the mBC community.
Citation Format: Robin H. Pugh-Yi, Piri Welcsh, Kelly Owens, Diane Rose, Erica Kuhn, Craig T. Dearfield, Susan Friedman. People with metastatic breast cancer face barriers to finding information and support [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 P6-05-60.
Abstract P6-14-01: Invasively distinct subpopulations cooperate via a laminin-332/Rac1 axis in triple-negative breast cancer
Authors: Yoon Sung Bo (Joseph) , Mouw Janna , Chen Luxiao , Wu Hao , Marcus Adam 
Published: March 2023

Abstract
Intratumoral heterogeneity poses a significant hurdle for cancer treatment, yet is under-characterized in the context of tumor invasion. Cancer cells from solid tumors can invade through two predominant modes: collective invasion, whereby cancer cells invade in multi-cellular packs or streams marked by intact cell-cell junctions; and single-cell invasion, whereby cells invade independently without intercellular adhesion. We have observed that collective and single-cell invasion co-occur within the same tumor microenvironment in triple-negative breast cancer, suggesting that invasive heterogeneity supports cooperative behavior between tumor subpopulations. To test this, we used a novel, published technique developed by the lab (SaGA) to isolate pure subpopulations of 4T1 cells that collectively invade (collectives) or single cells that invade alone (singles). 3-D spheroids of SaGA-purified collectives and singles exhibited almost exclusively collective and single-cell invasion, respectively, and these invasive phenotypes were retained over multiple passages. Integration of RNA sequencing and methylation array data obtained from RNA and DNA isolates, respectively, of collectives and singles revealed that collectives exhibit drastic overexpression and promoter hypomethylation of two laminin genes that form the laminin-332 complex, Lama3 and Lamc2. Additionally, an unbiased proteomic analysis of secreted proteins also revealed an overabundance of these laminins in collectives media. We found that singles have increased expression of integrin α6 and β4, which together have been found to specifically bind to laminin-332 to activate the Rac1 GTPase. Interestingly, our RNA sequencing data revealed a binary overexpression of a Rac1 GTPase, Prex1 in singles, suggesting that singles have enhanced Rac1 activation when compared to collectives with the potential for hyperactivation upon laminin-332 binding. Indeed, laminin-332 resulted in higher GTP-bound Rac1 in singles and subsequently increased invasion of singles in 3-D models. Additionally, laminin-332 induced cell elongation at the leading edge of singles spheroids, which was reversable by treatment with a Rac1 inhibitor. Together, our data suggests that distinct subpopulations amidst a heterogeneous tumor cooperate via laminin-332 and Rac1 to facilitate tumor invasion in metastatic triple-negative breast cancer.
Citation Format: Sung Bo (Joseph) Yoon, Janna Mouw, Luxiao Chen, Hao Wu, Adam Marcus. Invasively distinct subpopulations cooperate via a laminin-332/Rac1 axis 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 P6-14-01.
JMJD6 Shapes a Pro-tumor Microenvironment via ANXA1-Dependent Macrophage Polarization in Breast Cancer
Authors: Cioni Bianca , Ratti Silvia , Piva Annamaria , Tripodi Irene , Milani Matteo , Menichetti Francesca , Langella Tiziana , Botti Laura , De Cecco Loris , Chiodoni Claudia , Lecis Daniele , Colombo Mario P. 
Published: March 2023

Abstract

Breast cancer is the most common type of cancer in women worldwide, with the luminal subtype being the most widespread. Although characterized by better prognosis compared with other subtypes, luminal breast cancer is still considered a threatening disease due to therapy resistance, which occurs via both cell- and non–cell-autonomous mechanisms. Jumonji domain-containing 6, arginine demethylase and lysine hydroxylase (JMJD6) is endowed with a negative prognostic value in luminal breast cancer and, via its epigenetic activity, it is known to regulate many intrinsic cancer cell pathways. So far, the effect of JMJD6 in molding the surrounding microenvironment has not been explored.
Here, we describe a novel function of JMJD6 showing that its genetic inhibition in breast cancer cells suppresses lipid droplet formation and ANXA1 expression, via estrogen receptor alpha and PPARα modulation. Reduction of intracellular ANXA1 results in decreased release in the tumor microenvironment (TME), ultimately preventing M2-type macrophage polarization and tumor aggressiveness.

Implications:
Our findings identify JMJD6 as a determinant of breast cancer aggressiveness and provide the rationale for the development of inhibitory molecules to reduce disease progression also through the remodeling of TME composition.
Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng 
Published: March 2023

Abstract

Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase (HDAC) inhibitor with anticancer effects via epigenetic and non-epigenetic mechanisms. The role of SAHA in metabolic rewiring and epigenomic reprogramming to inhibit pro-tumorigenic cascades in lung cancer remains unknown. In this study, we aimed to investigate the regulation of mitochondrial metabolism, DNA methylome reprogramming, and transcriptomic gene expression by SAHA in lipopolysaccharide (LPS)-induced inflammatory model of lung epithelial BEAS-2B cells. LC/MS was used for metabolomic analysis, while next-generation sequencing was done to study epigenetic changes. The metabolomic study reveals that SAHA treatment significantly regulated methionine, glutathione, and nicotinamide metabolism with alteration of the metabolite levels of methionine, S-adenosylmethionine, S-adenosylhomocysteine, glutathione, nicotinamide, 1-methylnicotinamide, and nicotinamide adenine dinucleotide in BEAS-2B cells. Epigenomic CpG methyl-seq shows SAHA revoked a list of differentially methylated regions in the promoter region of the genes, such as HDAC11, miR4509–1, and miR3191. Transcriptomic RNA sequencing (RNA-seq) reveals SAHA abrogated LPS-induced differentially expressed genes encoding proinflammatory cytokines, including interleukin 1α (IL1α), IL1β, IL2, IL6, IL24, and IL32. Integrative analysis of DNA methylome-RNA transcriptome displays a list of genes, of which CpG methylation correlated with changes in gene expression. qPCR validation of transcriptomic RNA-seq data shows that SAHA treatment significantly reduced the LPS-induced mRNA levels of IL1β, IL6, DNA methyltransferase 1 (DNMT1), and DNMT3A in BEAS-2B cells. Altogether, SAHA treatment alters the mitochondrial metabolism, epigenetic CpG methylation, and transcriptomic gene expression to inhibit LPS-induced inflammatory responses in lung epithelial cells, which may provide novel molecular targets to inhibit the inflammation component of lung carcinogenesis.

Prevention Relevance:
Inflammation increases the risk of lung cancer and blocking inflammation could reduce the incidence of lung cancer. Herein, we demonstrate that histone deacetylase inhibitor suberoylanilide hydroxamic acid regulates metabolic rewiring and epigenetic reprogramming to attenuate lipopolysaccharide-driven inflammation in lung epithelial cells.
How Well Must Surface Vorticity Be Organized for Tornadogenesis?
Authors: Parker Matthew D. 
Published: March 2023

Abstract
This study investigates whether quasi-random surface vertical vorticity is sufficient for tornadogenesis when combined with an updraft typical of tornadic supercells. The viability of this pathway could mean that a coherent process to produce well-organized surface vertical vorticity is rather unimportant. Highly idealized simulations are used to establish random noise as a possible seed for the production of tornado-like vortices (TLVs). A number of sensitivities are then examined across the simulations. The most explanatory predictor of whether a TLV will form (and how strong it will become) is the maximal value of initial surface circulation found near the updraft. Perhaps surprisingly, sufficient circulation for tornadogenesis is often present even when the surface vertical vorticity field lacks any obvious organized structure. The other key ingredient for TLV formation is confirmed to be a large vertical gradient in vertical velocity close to the ground (to promote stretching). Overall, it appears that random surface vertical vorticity is indeed sufficient for TLV formation given adequate stretching. However, it is shown that longer-wavelength noise is more likely to be associated with substantial surface circulation (because it is the areal integral of vertical vorticity). Thus, coherent vorticity sources that produce longer-wavelength structures are likely to be the most supportive of tornadogenesis.
Neighbourhood characteristics and the treated incidence rate of borderline personality pathology among young people
Authors: O’Donoghue Brian , Michel Chantal , Thompson Katherine N , Cavelti Marialuisa , Eaton Scott , Betts Jennifer K , Fowler Claire , Luebbers Stefan , Kaess Michael , Chanen Andrew M 
Published: March 2023

Objective: The impact of the wider social environment, such as neighbourhood characteristics, has not been examined in the development of borderline personality disorder. This study aimed to determine whether the treated incidence rate of full-threshold borderline personality disorder and sub-threshold borderline personality disorder, collectively termed borderline personality pathology, was associated with the specific neighbourhood characteristics of social deprivation and social fragmentation. Method: This study included young people, aged 15–24 years, who attended Orygen’s Helping Young People Early programme, a specialist early intervention service for young people with borderline personality pathology, from 1 August 2000–1 February 2008. Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Personality Disorders, and census data from 2006 were used to determine the at-risk population and to obtain measures of social deprivation and fragmentation. Results: The study included 282 young people, of these 78.0% ( n = 220) were female and the mean age was 18.3 years (SD = ±2.7). A total of 42.9% ( n = 121) met criteria for full-threshold borderline personality disorder, and 57.1% ( n = 161) had sub-threshold borderline personality disorder, defined as having three or four of the nine Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) borderline personality disorder criteria. There was more than a sixfold increase in the treated incidence rate of borderline personality pathology in the neighbourhoods of above average deprivation (Quartile 3) (incidence rate ratio = 6.45, 95% confidence interval: [4.62, 8.98], p < 0.001), and this was consistent in the borderline personality disorder sub-groups. This association was also present in the most socially deprived neighbourhood (Quartile 4) (incidence rate ratio = 1.63, 95% confidence interval: [1.10, 2.44]), however, only for those with sub-threshold borderline personality disorder. The treated incidence of borderline personality pathology increased incrementally with the level of social fragmentation (Quartile 3: incidence rate ratio = 1.93, 95% confidence interval: [1.37, 2.72], Quartile 4: incidence rate ratio = 2.38, 95% confidence interval: [1.77, 3.21]). Conclusion: Borderline personality pathology has a higher treated incidence in the more socially deprived and fragmented neighbourhoods. These findings have implications for funding and location of clinical services for young people with borderline personality pathology. Prospective, longitudinal studies should examine neighbourhood characteristics as potential aetiological factors for borderline personality pathology.
What is in a Mandate? Introducing the UN Peace Mission Mandates Dataset
Authors: Hellmüller Sara , Tan Xiang-Yun Rosalind , Bara Corinne 
Published: March 2023

UN peace missions are constantly evolving. Yet, we lack a detailed understanding of the shifting types and objectives of peace missions beyond broad categorizations that distinguish for instance between observer, traditional, multidimensional, and peace enforcement missions. To address this gap, we present the UN Peace Mission Mandates (UNPMM) dataset. With global coverage, 30 years of data between 1991 and 2020, a broad scope that includes peacekeeping and political missions, and information on 41 mandate tasks, the UNPMM represents one of the most detailed and up-to-date datasets on UN peace mission mandates. We use it to highlight how mission types, objectives, and specific tasks have changed since the end of the Cold War, and to analyze what factors influence the kind of missions the UN is willing to authorize. The descriptive statistics and empirical analysis reaffirm the need for a greater disaggregation of data on UN peace missions and their mandates.
Loneliness as a Potential Mechanism of the Association Between Ageism and Mental Health Outcomes in the Chilean Context
Authors: Rosell Javiera , Vergés Alvaro 
Published: March 2023

The negative impact of ageism on the mental health of older persons has been well studied, but the mechanisms underlying this relationship have not been explored in detail. The present study examines the relationship of ageism with depressive and anxious symptoms in older people, evaluating the indirect effect via loneliness. The analysis was carried out with a sample of 577 older adults living in Chile, using structural equation modeling to assess the direct and indirect effects of the proposed model. The results showed the direct and indirect association of ageism with mental health outcomes. Ageism is positively related to loneliness and, in turn, to increased depressive and anxious symptoms. We discuss how loneliness linked with an ageist context contributes to anxiety and depressive symptomatology in the older population and the need to reduce ageism to favor the mental health of this age group.