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Establishment and characterization of 24 breast cancer cell lines and 3 breast cancer organoids reveals molecular heterogeneity and drug response variability in malignant pleural effusion-derived models
No full textIntratumoral heterogeneity of breast cancer cells causes undesired drug resistance and predispose to disease recurrence. We investigate the molecular heterogeneity of breast cancer cells derived from malignant pleural effusions (MPE) to understand variations in drug resistance and cellular evolution. MPE provides a unique environment, with cells experiencing significant microenvironmental changes that promote intratumoral heterogeneity and therapeutic resistance. By establishing 24 cell lines and 3 organoids from MPE samples of breast cancer patients, we performed extensive genomic, transcriptomic, and drug sensitivity analyses. Our findings reveal substantial genetic and transcriptomic diversity among MPE-derived cell lines, highlighting dynamic alterations in driver mutations and signaling pathways that correlate with variable drug responses. Notably, temporal and spatial heterogeneity within patient-derived samples emphasized the adaptability of breast cancer cells in MPE, as different subclones displayed distinct drug sensitivities. This work underscores the critical role of molecular profiling in understanding treatment resistance in breast cancer, presenting MPE-derived cell lines as valuable preclinical models for exploring personalized therapies in aggressive cancer phenotypes.Y
Meter-scale heterostructure printing for high-toughness fiber electrodes in intelligent digital apparel
No full textIntelligent digital apparel, which integrates electronic functionalities into clothing, represents the future of healthcare and ubiquitous control in wearable devices. Realizing such apparel necessitates developing meter-scale conductive fibers with high toughness, conductivity, stable conductance under deformation, and mechanical durability. In this study, we present a heterostructure printing method capable of producing meter-scale (similar to 50 m) biphasic conductive fibers that meet these criteria. Our approach involves encapsulating deformable liquid metal particles (LMPs) within a functionalized thermoplastic polyurethane matrix. This encapsulation induces in situ assembly of LMPs during fiber formation, creating a heterostructure that seamlessly integrates the matrix's durability with the LMPs' superior electrical performance. Unlike rigid conductive materials, deformable LMPs offer stretchability and toughness with a low gauge factor. Through precise twisting using an engineered annealing machine, multiple fiber strands are transformed into robust, electrically stable meter-scale electrodes. This advancement enhances their practicality in various intelligent digital apparel applications, such as stretchable displays, wearable healthcare systems, and digital controls.Y
A Case Report of Successful Vaginal Delivery for Cauda Equina Syndrome Combined with Complex Regional Pain Syndrome
No full textBackground: Cauda equina syndrome (CES) is defined as a complex clinical entity associated with simultaneous compression of several or all lumbosacral spine nerve roots. Complex regional pain syndrome (CRPS) is a chronic and non-treatable pain condition resulting in lifetime disability due to a tendency to relapse. Both diseases present with chronic pain and neuropathy. We aimed to report a unique patient with successful pregnancy and delivery although she had both CES and CRPS. Case Presentation: Here we present a female who was diagnosed as CES with CRPS after fall from a high building about 10 years previously. She became pregnant after two miscarriages, maintained her pregnancy with numerous pain killers and finally delivered a healthy baby vaginally. Interestingly, during her parturition, she was tolerable with labor pain unlike her chronic pain that came from CES and CRPS. Conclusion: She is a unique and significant case because of the rare condition that has two pain-associated diseased and success of vaginal delivery without any complication during pregnancy. This case may be helpful in counselling attending physicians and may inspire other pre-existing CES or CRPS patients who are afraid to decide on pregnancy.Y
Evaluating migration and cytotoxicity of tissue-resident and conventional NK cells in a 3D microphysiological system using live-cell imaging
No full textNatural killer (NK) cells are critical components of the immune response against cancer, recognized for their ability to target and eliminate malignant cells. Among NK cell subsets, intraepithelial ILC1 (ieILC1)-like tissue resident NK (trNK) cells exhibit distinct functional properties and enhanced cytotoxicity compared to conventional NK (cNK) cells, positioning them as promising candidates for cancer immunotherapy. However, the specific roles and mechanisms of these cytotoxic trNK cells within the tumor microenvironment (TME) remain to be further explored. In this study, we utilized a three-dimensional (3D) microphysiological system (MPS) to model the tumor-vascular interface and investigate the distinct capabilities of cytotoxic ieILC1-like trNK and cNK cells within the TME. Through the integration of live-cell imaging and cell-tracking analysis, we quantitatively assessed NK cell migration, tumor infiltration, and cytotoxic activity in real time. Our findings revealed that trNK cells demonstrate enhanced motility, sustained tumor interactions, and superior tumor-killing efficiency compared to cNK cells. This study highlights the unique properties of trNK cells, providing a robust foundation for developing next-generation cancer therapies that harness their potent cytotoxic capabilities.N
Pathology-Independent Expansion of Indications for Rapid-Deployment Aortic Valve Replacement: Midterm Outcomes
No full textBackground This study evaluated the midterm outcomes of rapid deployment aortic valve replacement (RDAVR) performed regardless of pathology for various aortic valve diseases at a single center. Methods Of the 344 patients who underwent RDAVR using Edwards INTUITY during the study period at our institution, 176 had bicuspid valve diseases (51.2%), 20 had pure aortic regurgitation (5.8%), and 4 had infective endocarditis (1.2%). Median follow-up duration was 28.6 months (maximum: 86.4 months). Midterm clinical outcomes were evaluated, and the changes of valve hemodynamics from early postoperative period to 5 years after surgery were also investigated. Results Mean age was 68.9 +/- 9.8 years, and 46.2% of the patients were female. Isolated RDAVR was performed in 90 patients (26.2%), and concomitant procedures, including aortic surgery (48.8%), mitral valve surgery (20.3%), arrhythmia surgery (9.0%), tricuspid valve surgery (7.0%), and coronary artery bypass grafting (5.5%), were performed in 254 patients (73.8%). Operative mortality occurred in 11 patients (3.2%), and permanent pacemaker implantation was required in 5 patients (1.5%) in early postoperative period. Overall survival rate was 86.9% at 5 years, and cumulative incidence of cardiac death was 6.3% at 5 years. No deterioration of valve hemodynamics was observed at midterm echocardiographic evaluation in either the overall population or for each size of valve. Conclusion Isolated or concomitant aortic valve replacement using rapid-deployment valves was performed for various aortic valve diseases regardless of the underlying pathology at our institution, and the clinical and hemodynamic outcomes were excellent for up to 5 years.N
Efficacy, safety, and patient-reported outcomes across young to older age groups of patients with HR+/HER2-advanced breast cancer treated with ribociclib plus endocrine therapy in the randomized MONALEESA-2,-3, and-7 trials
No full textBackground: Ribociclib + endocrine therapy (ET) showed significant progression-free survival (PFS) and overall survival (OS) benefits in the MONALEESA trials in patients with HR+ /HER2 - advanced breast cancer (ABC). We report efficacy, safety, and patient-reported outcomes (PROs) across age groups, including older patients, in these trials. Methods: Data from the MONALEESA-2, -3, and -7 trials for pre- and postmenopausal patients receiving first-line treatment for ABC were pooled and analyzed by age (<65y, 65-74y, and >= 75y). PFS, OS, time to first chemotherapy (TTC), and time to definitive deterioration (TTD) in PROs were evaluated using Kaplan-Meier methods; a Cox regression model stratified by study and liver/lung metastasis was used for hazard ratios. Results: Among 1229 patients included, 63 % were < 65y, 27 % were 65-74y, and 10 % were >= 75y. Baseline characteristics were generally well balanced. Regardless of patient age, ribociclib+ET showed a consistent PFS and OS benefit and delayed TTC. With ribociclib+ET, the most common first subsequent treatment was ET. Safety results were consistent with those in the overall trial population; no new signals were identified. Rates of discontinuation due to AEs with ribociclib+ET were numerically higher in patients >= 75y. Among patients who discontinued treatment due to AEs, the percentage without prior dose reduction was higher in those >= 75y. A PRO benefit with ribociclib+ET was observed across all age groups for pain and fatigue scores. Conclusions: This analysis demonstrated that ribociclib+ET is an effective and well-tolerated treatment for patients of all age groups with HR+ /HER2 - ABC, including older patients. (MONALEESA-2, NCT01958021; MONALEESA-3, NCT02422615; MONALEESA-7, NCT02278120)N
Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience
No full textPurpose Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.N
Uniform growth of perovskite nanocrystals
No full textMonodisperse perovskite nanocrystals are formed by using a diffusion-mediated growth mechanism that controls converted monomer concentration such that premature termination or secondary growth processes are prevented.N
DHR: Dual Features-Driven Hierarchical Rebalancing in Inter- and Intra-Class Regions for Weakly-Supervised Semantic Segmentation
No full textWeakly-supervised semantic segmentation (WSS) ensures high-quality segmentation with limited data and excels when employed as input seed masks for large-scale vision models such as Segment Anything. However, WSS faces challenges related to minor classes since those are overlooked in images with adjacent multiple classes, a limitation originating from the overfitting of traditional expansion methods like Random Walk. We first address this by employing unsupervised and weakly-supervised feature maps instead of conventional methodologies, allowing for hierarchical mask enhancement. This method distinctly categorizes higher-level classes and subsequently separates their associated lower-level classes, ensuring all classes are correctly restored in the mask without losing minor ones. Our approach, validated through extensive experimentation, significantly improves WSS across five benchmarks (VOC: 79.8%, COCO: 53.9%, Context: 49.0%, ADE: 32.9%, Stuff: 37.4%), reducing the gap with fully supervised methods by over 84% on the VOC validation set. Code is available at https://github.com/shjoapril/DHR.N