bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 954: An evaluation of the combination of metformin and Y15 for the treatment of platinum-resistant ovarian cancer
Authors: Duarte Manuel A. , Garcia Kristal , Arriaga Marco A. , Chew Sue Anne , Levy Arkene S. , Mendez Isabela 
Published: March 2024

Abstract
Ovarian cancer is the fifth leading cause of cancer mortality among women. This high mortality rate is linked to the development of resistance to first-line chemotherapy with platinum compounds which has been attributed in part to increased activity of focal adhesion kinase (FAK). The anti-diabetic drug Metformin was previously shown to inhibit the proliferation and migration of ovarian cancer cells and thus, the combination of a FAK inhibitor, Y15, and Metformin may be a promising treatment for platinum-resistant ovarian cancer (PROC). The objective of this study was to evaluate the combination of Y15 and Metformin on PROC cell viability and the mechanism of cell death. An MTT assay was used to analyze cell viability in PROC OVCAR3 cells after 48 h of treatment by measuring the absorbance at 570 nm with a microplate reader. Western blot was used to determine the protein levels of the apoptosis marker cleaved PARP and the autophagy marker LC3B-II. The exposure of OVCAR3 platinum-resistant ovarian cancer cells to Metformin (4.5 mM) + Y15 (5.5 µM) resulted in a significantly enhanced cytotoxicity (32.6 ± 1.8%) compared to single drug treatment with either Metformin (4.5 mM) (65.0 ± 4.2%) or Y15 (5.5 µM) (66.0 ± 4.8%). A combination of Metformin (7.8 mM) + Y15 (5.5 µM) also resulted in a significantly enhanced cytotoxicity (22.8 ± 1.5%) compared to single drug treatment with either Metformin (7.8 mM) (50.7 ± 3.7%) or Y15 (5.5 µM) (66.0 ± 4.8%). Cells treated with the combination of Metformin and Y15 for 24, 48, and 72-hours showed an increase in cleaved PARP compared to the control, Metformin alone and Y15 alone. For Metformin alone, there was an increase in cleaved PARP compared to the control at all timepoints and increased from 24 hours to 72 hours. For Y15 alone, the amount of cleaved PARP was also higher compared to the control at all time points, however, decreased over time from 24 hours to 72 hours. Cells treated with Metformin, Y15, and a combination of Metformin and Y15 showed no conversion of LC3B-I to LC3B-II, which occurs during autophagy. Thus, it is concluded that the mechanism of cell death for both Metformin and Y15 is through apoptosis and not autophagy and apoptosis is enhanced with the combination of the drugs. The delivery of Metformin and Y15 can result in an additive effect on cell viability through apoptosis and can be further explored as a promising approach for the treatment of PROC.
Citation Format: Manuel A. Duarte, Kristal Garcia, Marco A. Arriaga, Sue Anne Chew, Arkene S. Levy, Isabela Mendez. An evaluation of the combination of metformin and Y15 for the treatment of platinum-resistant ovarian 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 954.
Abstract 97: A E2F6 ceRNA network suppresses dendritic cell function, via PBX1/IL-10 signaling, in ovarian cancer
Authors: Chan Michael W.Y. , Chen Yin-Chen , Lin Ching-Wen , Cheng Frank , Yan Ching-Cher Sanders , Hsu Chao-Ping , Chuang Yu-Min , Low Jie-Ting , Ma Xiaojing , Huang Yao-Ting , Chang Chia-Bin , Li Chin , Lai Hung-Cheng , Wu Shu-Fen , Hung Shih-Hsun , Tsai Je-Chiang 
Published: March 2024

Abstract
It is reported that long-term use of estrogen could increase the risk of ovarian cancer. However, the role of estrogen in immunoevasion is not fully explored. We have previously demonstrated that estrogen-mediated upregulation of E2F6, and, c-Kit, by epigenetic silencing of miR-193a, and a competing endogenous (ceRNA) mechanism. In this study, we found that PBX1, a transcriptional activator of the immunosuppressive cytokine, IL-10, is also a target of miR-193a. Importantly, overexpression of the E2F6 3’UTR upregulates both E2F6 and, PBX1, as well as IL10 in ovarian cancer cell lines, suggesting that ceRNA mechanism exists between E2F6 and PBX1. These phenomena are further supported by our stochastic simulation of the estrogen-mediated E2F6 ceRNA network on the distribution of E2F6 and PBX1 mRNA in cancer cells, which is consistent with the TCGA ovarian cancer RNA-Seq dataset. Importantly, monocyte-derived dendritic cell activation of T-cell function was inhibited by pretreatment of conditioned media derived from ovarian cancer cells overexpressing E2F6 3’UTR; such inhibition was rescueable by an anti-IL-10 antibody. Clinically, IL10 level was higher in ovarian cancer patients with higher E2F6 and PBX1, and in ovarian cancer cell lines overexpressed with E2F6 3’UTR. Taken together, these results showed that E2F6 could suppress anti-tumor immune response of dendritic cell, E2F6 ceRNA network. Epigenetic intervention in restoring the expression of miR-193a may be able to enhance anti-tumor immune response against ovarian cancer.
Citation Format: Michael W.Y. Chan, Yin-Chen Chen, Ching-Wen Lin, Frank Cheng, Ching-Cher Sanders Yan, Chao-Ping Hsu, Yu-Min Chuang, Jie-Ting Low, Xiaojing Ma, Yao-Ting Huang, Chia-Bin Chang, Chin Li, Hung-Cheng Lai, Shu-Fen Wu, Shih-Hsun Hung, Je-Chiang Tsai. A E2F6 ceRNA network suppresses dendritic cell function, via PBX1/IL-10 signaling, in ovarian 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 97.
Abstract 992: The impact of tamoxifen on autophagic and epigenetic regulation in endometrial cancer
Authors: Thota Shilpa , Begum Rizwana , Chintala Naveen , Pandit Abhishek , Sapkota Biplov , Francis Joseph 
Published: March 2024

Abstract
Background: Endometrial cancer, predominantly endometrioid adenocarcinoma, ranks as the fourth most common cancer in women globally, with an increasing incidence over the last two decades. Tamoxifen, well-known for its antiestrogenic characteristics in the treatment of breast cancer, paradoxically increases the risk of endometrial cancer. Understanding this dual role of tamoxifen is crucial for optimizing breast cancer therapy while mitigating endometrial cancer risk. This study aims to elucidate the molecular alterations induced by tamoxifen in endometrial thickening and its potential to induce cancer, particularly focusing on autophagy, epithelial-mesenchymal transition (EMT), and cancer stem-like cells (CSCs).
Methods: In this study, female BALB/c mice were administered tamoxifen (20 mg/ml) orally for five consecutive days. We monitored changes in EMT markers, autophagy-related genes, and stem cell markers over 1 to 5 months. Furthermore, we investigated the epigenetic modulation of key genes involved in these processes.
Results: Tamoxifen treatment led to altered expression of both epithelial and mesenchymal EMT markers, autophagy-related genes (p62, LC3B, Beclin-1, mTOR, ATG12, ATG16), and stem cell markers (Nanog, SOX2, ALDH1). Notably, we observed significant epigenetic changes, including increased methylation of E-cadherin and decreased methylation of Twist. Furthermore, we observed hypermethylation (a process often linked to the silencing of tumor-suppressing genes) in MGMT (Methylguanine methyltransferase), a DNA repair enzyme involved in chemoresistance, and DAPK (Death-associated protein kinase), a kinase associated with apoptosis, autophagy, and inflammation. We also observed hypermethylation in the CpG promoter regions of autophagy-related genes (Beclin-1 and LC3B) highlighting a potential mechanism for tamoxifen-induced tumorigenic changes.
Conclusion: Our findings demonstrate tamoxifen's influence on cellular and molecular pathways, highlighting the complex interplay between drug treatment and cancer progression. The observed epigenetic changes provide insight into the mechanisms by which tamoxifen may contribute to endometrial cancer risk, suggesting potential targets for therapeutic intervention.
Citation Format: Shilpa Thota, Rizwana Begum, Naveen Chintala, Abhishek Pandit, Biplov Sapkota, Joseph Francis. The impact of tamoxifen on autophagic and epigenetic regulation in endometrial 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 992.
Examination of the Effect of the Real-Life Meaning of the Stimulus on the Self-Motion Illusion
Authors: Jiang Moyou , Guo Xuanru , Seno Takeharu , Remijn Gerard B. , Nakamura Shinji 
Published: March 2024

Abstract
Vection refers to the illusory self-motion perception mainly induced by the motion of a visual stimulus. This phenomenon concerns presence and immersion in the illusion of self-motion, especially in virtual reality. In the present study, we investigated how the real-life meaning of stimuli contributes to vection by using animations of objects that can move by themselves. In two psychophysical experiments, we first employed animated cars presented with or without wheel rotation as the visual inducer, using various motion directions and postures; then we added the road scenery, which was either moving (in the same or opposite direction to the cars) or still, as a contextual background in the visual stimulus. The results of Experiment 1 showed that in conditions with forward- and backward-moving cars, vection was stronger than in conditions with upward-moving and inverted cars. The results of Experiment 2 showed that vection was weakest in the still road scenery condition and that the cars’ wheel rotation could facilitate vection. This suggests that the more natural the stimulus meanings, the stronger the vection. It is a feasible and effective application prospect to enhance the vection experience by changing the naturalness of the stimulus to further increase the sense of presence and immersion. Therefore, the perceived naturalness and the assumed immobility of the visual inducer are two important cognitive factors in visual self-motion perception and presence in the virtual world.
‘De voix femmenine’: Self, Voice and Emotive Display in Jean d’Arras’s Mélusine
Authors: R. de la Torre Meritxell 
Published: March 2024

Abstract
The 14th century French romance Mélusine ou la Noble Histoire de Lusignan focuses on the peculiar founding mother of the house of Lusignan, who, due to a curse imposed by her fairy mother, is forced to transform in secrecy into a half-serpent, half-human figure every Saturday. The romance depicts her life after the curse and her ultimate exile after her husband discovers her in her hybrid form. As the lady flies away fully transformed into a giant serpent, however, marks of her enduring selfhood prevail: first, in a mark embedded in a windowsill in the shape of a foot and later, as a voiced emotional complaint, described as the voice of a woman. The serpent’s emotive display confirms the existence of a stable, yet malleable core selfhood in the character that prevails through her embodied changes. The goal is to establish emotive display as an effective tool to access narrated selfhood in the romance.
Long-term Outcomes of Primary Hip Arthroscopy: Multicenter Analysis at Minimum 10-Year Follow-up With Attention to Labral and Capsular Management
Authors: Boos Alexander M. , Wang Allen S. , Lamba Abhinav , Okoroha Kelechi R. , Ortiguera Cedric J. , Levy Bruce A. , Krych Aaron J. , Hevesi Mario 
Published: March 2024

Background: Hip arthroscopy is rapidly advancing, with positive published outcomes at short- and midterm follow-up; however, available long-term data remain limited. Purpose: To evaluate outcomes of primary hip arthroscopy at a minimum 10-year follow-up at 2 academic centers by describing patient-reported outcomes and determining reoperation and total hip arthroplasty (THA) rates. Study Design: Case series; Level of evidence, 4. Methods: Patients with primary hip arthroscopy performed between January 1988 and April 2013 at 2 academic centers were evaluated for postoperative patient-reported outcomes—including the visual analog scale, Tegner Activity Scale score, Hip Outcome Score Activities of Daily Living and Sport Specific subscales, modified Harris Hip Score, Nonarthritic Hip Score, 12-item International Hip Outcome Tool, surgery satisfaction, and reoperations. Results: A total of 294 patients undergoing primary hip arthroscopy (age, 40 ± 14 years; 66% women; body mass index, 27 ± 6) were followed for 12 ± 3 years (range, 10-24 years) postoperatively. Labral debridement and repair were performed in 41% and 59% of patients, respectively. Of all patients who underwent interportal capsulotomy, 2% were extended to a T-capsulotomy, and 11% underwent capsular repair. At final follow-up, patients reported a mean visual analog scale at rest of 2 ± 2 and with use of 3 ± 3, a 12-item International Hip Outcome Tool of 68 ± 27, a Nonarthritic Hip Score of 81 ± 18, a modified Harris Hip Score of 79 ± 17, and a Hip Outcome Score Activities of Daily Living of 82 ± 19 and Sport Specific subscale of 74 ± 25. The mean surgical satisfaction was 8.4 ± 2.4 on a 10-point scale, with 10 representing the highest level of satisfaction. In total, 96 hips (33%) underwent reoperation—including 65 hips (22%) converting to THA. THA risk factors included older age, higher body mass index, lower lateral center-edge angle, larger alpha angle, higher preoperative Tönnis grade, as well as labral debridement and capsular nonrepair ( P≤ .039). Patients undergoing combined labral and capsular repair demonstrated a THA conversion rate of 3% compared with 31% for patients undergoing combined labral debridement and capsular nonrepair ( P = .006). Labral repair trended toward increased 10-year THA-free survival (84% vs 77%; P = .085), while capsular repair demonstrated significantly increased 10-year THA-free survival (97% vs 79%; P = .033). Conclusion: At a minimum 10-year follow-up, patients undergoing primary hip arthroscopy demonstrated high satisfaction and acceptable outcome scores. In total, 33% of patients underwent reoperation—including 22% who underwent THA. Conversion to THA was associated with patient factors including older age, higher Tönnis grade, and potentially modifiable surgical factors such as labral debridement and capsular nonrepair.
Tuberculosis preventive treatment uptake among adults living with human immunodeficiency virus: Analysis of Zimbabwe population-based human immunodeficiency virus impact assessment 2020
Authors: Maphosa Talent , Mirkovic Kelsey , Weber Rachel A. , Musuka Godfrey , Mapingure Munyaradzi P. , Ershova Julia , Laws Rebecca , Dobbs Trudy , Coggin William , Sandy Charles , Apollo Tsitsi , Mugurungi Owen , Melchior Michael , Farahani Mansoor S. 
Published: March 2024

Background Tuberculosis remains the leading cause of death by an infectious disease among people living with HIV (PLHIV). TB Preventive Treatment (TPT) is a cost-effective intervention known to reduce morbidity and mortality. We used data from ZIMPHIA 2020 to assess TPT uptake and factors associated with its use. Methodology ZIMPHIA a cross-sectional household survey, estimated HIV treatment outcomes among PLHIV aged ≥15 years. Randomly selected participants provided demographic and clinical information. We applied multivariable logistic regression models using survey weights. Variances were estimated via the Jackknife series to determine factors associated with TPT uptake. Results The sample of 2419 PLHIV ≥15 years had 65% females, 44% had no primary education, and 29% lived in urban centers. Overall, 38% had ever taken TPT, including 15% currently taking TPT. Controlling for other variables, those screened for TB at last HIV-related visit, those who visited a TB clinic in the previous 12 months, and those who had HIV viral load suppression were more likely to take TPT. Conclusion The findings show suboptimal TPT coverage among PLHIV. There is a need for targeted interventions and policies to address the barriers to TPT uptake, to reduce TB morbidity and mortality among PLHIV.
Bronchopulmonary Dysplasia in a Tertiary Level Neonatal Unit of North India: Risk Factors and Outcome: A Case-control Study
Authors: Mishra Pragya , Tripathi Shalini , Sharma Akhil , Sonkar Gyanendra Kumar , Kumar Mala , Singh SN 
Published: March 2024

Background Bronchopulmonary dysplasia (BPD) in preterm neonates is a dreadful complication that increases the length of neonatal intensive care unit (NICU) stay, increases the cost of treatment, and poses long-term respiratory morbidity. Methods This was a case-control study to determine risk factors for BPD among preterm neonates (gestational age <32 weeks). Also, the proportion of BPD neonates developing secondary pulmonary arterial hypertension (PAH), vitamin D levels, and their outcomes were studied. Results Of 70 neonates with a mean birth weight of 1392 ± 544.28 grams and a mean gestational age of 30.14 ± 1.12 weeks, 35 cases of BPD (mild 42%, moderate 27%, severe 31%) and 35 controls were enrolled. After multivariate analysis, SGA (adjusted odds ratio [AOR] 12.6 with 95% CI 1.5-109.3; 0.022), lack of antenatal steroids (AOR 9.4 with 95% CI 1.8-50.7; 0.009), mechanical ventilation [MV] within the first 48 hours of life (AOR 8.7 with 95% CI 1.4-54.1; 0.021), and lack of surfactant administration (AOR 16.5% CI 3-89.1; 0.005) were independent risk factors. No significant difference was reported in vitamin D levels between BPD and non-BPD neonates (33.89 ± 22.50 ng/mL vs. 27.00 ± 8.17 ng/mL; 0.356). 14.3 % of BPD neonates expired, and 23% developed PAH. Neonates had a longer NICU stay than controls (46.66 ± 7.96 vs. 21 ± 8.82 days; <0.001) Conclusion We found SGA, lack of antenatal steroids, MV, and lack of surfactant administration to be independent risk factors for BPD. BPD neonates had dismal outcomes (one-fourth expired and left against medical advice), and one-fifth had PAH among survivors, increasing the length of their NICU stay.
Early Recognition and Institution of Treatment is Associated with a Good Prognosis in Peripheral Ischemic Lesions in Rheumatic Diseases
Authors: Dhakad Urmila , Mehta Pankti , Kishor Kriti 
Published: March 2024

Introduction: Peripheral ischemic lesions in rheumatic diseases have variable presentations, prognoses and outcomes that have not been well studied in published literature. The present study aimed to investigate the clinical presentation, aetiology, prognosis and outcomes of peripheral ischemic lesions in rheumatic diseases. Material and methods: A medical records review of all patients who presented with peripheral ischemic lesions was conducted in the Department of Clinical Immunology and Rheumatology of a tertiary care institution in Northern India. Data from March 2013 to December 2017 was collected in the form of demographic and clinical details, investigations, treatment and outcomes. Results: Of 103 patients that presented with peripheral ischemic lesions, 80 (77.6%) had an underlying rheumatic disease. In the group with rheumatic causes, the mean age was 29.31 years, and the majority (87%) presented in the winter season. The most common rheumatic cause was vasculitis (55%) followed by systemic sclerosis (17.5%), systemic lupus erythematosus (15%) and primary antiphospholipid antibody syndrome (6, 7.5%). Amputation (either surgical or auto-amputation) was observed in 55% of the cases, while the remaining recovered completely or near completely with medical treatment. Conclusions: Peripheral ischemic lesions may present as the initial or predominant manifestation of rheumatic disease with vasculitis being the most common cause. Late referral or presentation to the hospital, delayed specific management and presentation as gangrene resulted in poorer outcomes in these patients.
Novel pathogenic variants of SLC38A8 gene and literature review
Authors: Ren Xiaofang , Huang Lijuan , Cheng Shan , Wang Jing , Li Ningdong 
Published: March 2024

Purpose This study aimed to analyze the clinical and genetic characteristics of 6 Chinese patients with foveal hypoplasia (FH) caused by the variants of solute carrier family 38 member 8 ( SLC38A8), and to describe the genotype and phenotype of SLC38A8 variants from previous literature. Methods All subjects underwent comprehensive ophthalmic examinations. Optical coherence tomography (OCT) was performed to evaluate the structural grade of FH. Pathogenic variants of SLC38A8 gene were identified using panel-based next-generation sequencing and direct Sanger sequencing techniques. Further, all previously reported cases of SLC38A8 variants were re-analyzed together with the novel ones identified in this study. Results Nystagmus and FH were present in 6 patients with variants of SLC38A8 gene, accompanied by a normal anterior segment. Grade 4 FH was identified in 4 patients. A total of 12 variants of SLC38A8 gene were identified, including 9 novel variants. Systematical analysis revealed that half of the variants (30/60) were missense, the majority of which (23/30) were distributed in the transmembrane (TM) domains. Grade 4 FH was detected in the majority of patients (66%, 23/35). There was no statistical difference in the clinical features between the subgroups of patients with 0, 1 and 2 missense variants. Conclusion Severe arrest of foveal development was identified in patients with variants of SLC38A8. This study provides a brief summary of the clinical and genetic characteristics of the pathogenic SLC38A8 variants, which is helpful in the differentiation diagnosis of FH.