tbuckley/cabot-search huggingface dataset:
Fibrosis‐Encapsulated Tumoroid, A Solid Cancer Assembloid Model for Cancer Research and Drug Screening
Authors: Yeonsue Jang, Suki Kang, Hyunho Han, Chang Moo Kang, Nam Hoon Cho, Baek Gil Kim
Journal: Advanced Healthcare Materials (2024)

Abstract Peritumoral fibrosis is known to promote cancer progression and confer treatment resistance in various solid tumors. Consequently, developing accurate cancer research and drug screening models that replicate the structure and function of a fibrosis‐surrounded tumor mass is imperative. Previous studies have shown that self‐assembly three‐dimensional (3D) co‐cultures primarily produce cancer‐encapsulated fibrosis or maintain a fibrosis‐encapsulated tumor mass for a short period, which is inadequate to replicate the function of fibrosis, particularly as a physical barrier. To address this limitation, a multi‐layer spheroid formation method is developed to create a fibrosis‐encapsulated tumoroid (FET) structure that maintains structural stability for up to 14 days. FETs exhibited faster tumor growth, higher expression of immunosuppressive cytokines, and equal or greater resistance to anticancer drugs compared to their parental tumoroids. Additionally, FETs serve as a versatile model for traditional cancer research, enabling the study of exosomal miRNA and gene functions, as well as for mechanobiology research when combined with alginate hydrogel. Our findings suggest that the FET represents an advanced model that more accurately mimics solid cancer tissue with peritumoral fibrosis. It may show potential superiority over self‐assembly‐based 3D co‐cultures for cancer research and drug screening, and holds promise for personalized drug selection in cancer treatment.
A novel plasma p-tau181 assay as a specific biomarker of tau pathology in Alzheimer's disease
Authors: Kenji Tagai, Harutsugu Tatebe, Sayo Matsuura, Zhang Hong, Naomi Kokubo, Kiwamu Matsuoka, Hironobu Endo, Asaka Oyama, Kosei Hirata, Hitoshi Shinotoh, Yuko Kataoka, Hideki Matsumoto, Masaki Oya, Shin Kurose, Keisuke Takahata, Masanori Ichihashi, Manabu Kubota, Chie Seki, Hitoshi Shimada, Yuhei Takado, Kazunori Kawamura, Ming-Rong Zhang, Yoshiyuki Soeda, Akihiko Takashima, Makoto Higuchi, Takahiko Tokuda
Journal: Translational Neurodegeneration (2024)
Derivation, external and clinical validation of a deep learning approach for detecting intracranial hypertension
Authors: Faris Gulamali, Pushkala Jayaraman, Ashwin S Sawant, Jacob Desman, Benjamin Fox, Annette Chang, Brian Y Soong, Naveen Arivazagan, Alexandra S Reynolds, Son Q Duong, Akhil Vaid, Patricia Kovatch, Robert Freeman, Ira S Hofer, Ankit Sakhuja, Neha S Dangayach, David S Reich, Alexander W Charney, Girish N Nadkarni
Journal: npj Digital Medicine (2024)
Loss of Annexin A1 in macrophages restrains efferocytosis and remodels immune microenvironment in pancreatic cancer by activating the cGAS/STING pathway
Authors: Zelin Hou, Fengchun Lu, Jiajing Lin, Yuwei Wu, Linjin Chen, Haizong Fang, Linlin Chen, Shihan Zhang, Heguang Huang, Yu Pan
Journal: Journal for ImmunoTherapy of Cancer (2024)

Pancreatic cancer is an incurable malignant disease with extremely poor prognosis and a complex tumor microenvironment. We sought to characterize the role of Annexin A1 (ANXA1) in pancreatic cancer, including its ability to promote efferocytosis and antitumor immune responses.
Predicting rapid progression in knee osteoarthritis: a novel and interpretable automated machine learning approach, with specific focus on young patients and early disease
Authors: Simone Castagno, Mark Birch, Mihaela van der Schaar, Andrew McCaskie
Journal: Annals of the Rheumatic Diseases (2024)

To facilitate the stratification of patients with osteoarthritis (OA) for new treatment development and clinical trial recruitment, we created an automated machine learning (autoML) tool predicting the rapid progression of knee OA over a 2-year period. We developed autoML models integrating clinical, biochemical, X-ray and MRI data. Using two data sets within the OA Initiative-the Foundation for the National Institutes of Health OA Biomarker Consortium for training and hold-out validation, and the Pivotal Osteoarthritis Initiative MRI Analyses study for external validation-we employed two distinct definitions of clinical outcomes: Multiclass (categorising OA progression into pain and/or radiographic) and binary. Key predictors of progression were identified through advanced interpretability techniques, and subgroup analyses were conducted by age, sex and ethnicity with a focus on early-stage disease. Although the most reliable models incorporated all available features, simpler models including only clinical variables achieved robust external validation performance, with area under the precision-recall curve (AUC-PRC) 0.727 (95% CI: 0.726 to 0.728) for multiclass predictions; and AUC-PRC 0.764 (95% CI: 0.762 to 0.766) for binary predictions. Multiclass models performed best in patients with early-stage OA (AUC-PRC 0.724-0.806) whereas binary models were more reliable in patients younger than 60 (AUC-PRC 0.617-0.693). Patient-reported outcomes and MRI features emerged as key predictors of progression, though subgroup differences were noted. Finally, we developed web-based applications to visualise our personalised predictions. Our novel tool's transparency and reliability in predicting rapid knee OA progression distinguish it from conventional 'black-box' methods and are more likely to facilitate its acceptance by clinicians and patients, enabling effective implementation in clinical practice.
A Pooled Analysis of Trastuzumab Deruxtecan in Patients With HER2-Positive Metastatic Breast Cancer With Brain Metastases
Authors: F André, J Cortés, G Curigliano, S Modi, W Li, Y H Park, W-P Chung, S-B Kim, T Yamashita, J L Pedrini, S-A Im, L-M Tseng, N Harbeck, I Krop, S Nakatani, K Tecson, S Ashfaque, A Egorov, S A Hurvitz
Journal: Annals of Oncology (2024)
Generation of cytotoxic aptamers specifically targeting fibroblast-like synoviocytes by CSCT-SELEX for treatment of rheumatoid arthritis
Authors: Fang Qiu, Duoli Xie, Hongzhen Chen, Zhuqian Wang, Jie Huang, Chunhao Cao, Yiying Liang, Xu Yang, Dong-Yi He, Xuekun Fu, Aiping Lu, Chao Liang
Journal: Annals of the Rheumatic Diseases (2024)

Objectives Rheumatoid arthritis (RA) is an autoimmune disease characterised by aggressive fibroblast-like synoviocytes (FLSs). Very few RA patients-derived FLSs (RA-FLSs)-specific surface signatures have been identified, and there is currently no approved targeted therapy for RA-FLSs. This study aimed to screen therapeutic aptamers with cell-targeting and cytotoxic properties against RA-FLSs and to uncover the molecular targets and mechanism of action of the screened aptamers. Methods We developed a cell-specific and cytotoxic systematic evolution of ligands by exponential enrichment (CSCT-SELEX) method to screen the therapeutic aptamers without prior knowledge of the surface signatures of RA-FLSs. The molecular targets and mechanisms of action of the screened aptamers were determined by pull-down assays and RNA sequencing. The therapeutic efficacy of the screened aptamers was examined in arthritic mouse models. Results We obtained an aptamer SAPT8 that selectively recognised and killed RA-FLSs. The molecular target of SAPT8 was nucleolin (NCL), a shuttling protein overexpressed on the surface and involved in the tumor-like transformation of RA-FLSs. Mechanistically, SAPT8 interacted with the surface NCL and was internalised to achieve lysosomal degradation of NCL, leading to the upregulation of proapoptotic p53 and downregulation of antiapoptotic B-cell lymphoma 2 (Bcl-2) in RA-FLSs. When administrated systemically to arthritic mice, SAPT8 accumulated in the inflamed FLSs of joints. SAPT8 monotherapy or its combination with tumour necrosis factor (TNF)-targeted biologics was shown to relieve arthritis in mouse models. Conclusions CSCT-SELEX could be a promising strategy for developing cell-targeting and cytotoxic aptamers. SAPT8 aptamer selectively ablates RA-FLSs via modulating NCL-p53/Bcl-2 signalling, representing a potential alternative or complementary therapy for RA.
ATEC23 Challenge: Automated prediction of treatment effectiveness in ovarian cancer using histopathological images
Authors: Ching-Wei Wang, Nabila Puspita Firdi, Tzu-Chiao Chu, Mohammad Faiz Iqbal Faiz, Mohammad Zafar Iqbal, Yifan Li, Bo Yang, Mayur Mallya, Ali Bashashati, Fei Li, Haipeng Wang, Mengkang Lu, Yong Xia, Tai-Kuang Chao
Journal: Medical Image Analysis (2024)
Multiple‐Effect Combined Hydrogels: “Temporal Regulation” Treatment of Osteosarcoma‐Associated Bone Defects with Switchable Hyperthermia and Bioactive Agents
Authors: Lin Li, Yating Lin, Kun Liu, Runshan Huang, Wei Wen, Yadong Huang, Mingxian Liu, Changren Zhou, Shan Ding, Binghong Luo
Journal: Advanced Healthcare Materials (2024)

Abstract Achieving the clinically staged treatment of osteosarcoma‐associated bone defects encounters the multiple challenges of promptly removing postoperative residual tumor cells and bacterial infection, followed by bone reconstruction. Herein, a core/shell hydrogel with multiple‐effect combination is designed to first exert antitumor and antibacterial activities and then promote osteogenesis. Specifically, doxorubicin (DOX) is loaded by magnesium‐iron‐based layered double hydroxide (LDH) to prepare LDOX, which is introduced into a thermo‐sensitive hydrogel to serve as an outer shell of the core/shell hydrogel, meanwhile, LDH‐contained liquid crystal hydrogel, abbreviated as LCgel‐L, is served as an inner core. At the early stage of treatment, the dissociation of the outer shell triggered by moderate hyperthermia led to the thermo‐sensitive release of LDOX, which can be targeted for the release of DOX within tumor cells, thereby promptly removing postoperative residual tumor cells based on the synergistic effect of photothermal therapy (PTT) and DOX, and postoperative bacterial infection can also be effectively prevented by PTT simultaneously. More importantly, the dissociation of the outer shell prompted the full exposure of the inner core, which will exert osteogenic activity based on the synergy of liquid crystal hydrogel as well as LDH‐induced mild hyperthermia and ion effects, thereby enabling “temporal regulation” treatment of osteosarcoma‐associated bone defects. This study provides a valuable insight for the development of osteosarcoma‐associated bone repair materials.
Tocilizumab provides dual benefits in treating immune checkpoint inhibitor-associated arthritis and preventing relapse during ICI rechallenge: the TAPIR study
Authors: P-F Petit, D Daoudlarian, S Latifyan, H Bouchaab, N Mederos, J Doms, K Abdelhamid, N Ferahta, L Mencarelli, V Joo, R Bartolini, A Stravodimou, K Shabafrouz, G Pantaleo, S Peters, M Obeid
Journal: Annals of Oncology (2024)
Phase II trial of elotuzumab with pomalidomide and dexamethasone for daratumumab-refractory multiple myeloma
Authors: Ricardo D Parrondo, Betsy R LaPlant, Jamie Elliott, Andre Fernandez, Caitlin J Flott, Diedre Arrington, Dustin Chapin, Jade Brown, Saurav Das, Vivek Roy, Asher A Chanan-Khan, Sikander Ailawadhi
Journal: Blood Cancer Journal (2024)
scRNA+ TCR-seq revealed dual TCR T cells antitumor response in the TME of NSCLC
Authors: Qi Peng, Yuanyuan Xu, Xinsheng Yao
Journal: Journal for ImmunoTherapy of Cancer (2024)

The intricate origins, subsets, and characteristics of TCR (T Cell Receptor) s, along with the mechanisms underpinning the antitumor response of tumor-infiltrating T lymphocytes within the tumor microenvironment (TME) remain enigmatic. Recently, the advent of single-cell RNA+TCR-sequencing (scRNA+TCR seq) has revolutionized TME analysis, providing unprecedented insight into the origins, cell subsets, TCR CDR3 compositions, and the expression patterns of response/depletion factors within individual tumor-infiltrating T lymphocytes. Our analysis of the shared scRNA+TCR seq dataset revealed a substantial presence of dual TCR T cells, characterized by clonal hyperplasia and remarkable migratory prowess across various tissues, including blood, normal, peritumoral, and tumor tissues in non-small cell lung cancer patients. Notably, dual TCR CD8+T cells predominantly fell within the CXCL13+subset, displaying potent antitumor activity and a strong preference for tumor tissue residency. Conversely, dual TCR CD4+T cells were predominantly classified as CD5+ or LMNA+subsets, exhibiting a more even distribution across diverse tissue types. By harnessing scRNA+TCR seq and other cutting-edge technologies, we can delve deeper into the effects and mechanisms that regulate the antitumor response or tolerance of dual TCR T cells. This innovative approach holds immense promise in offering fresh perspectives and avenues for advancing research on TIL (Tumor infiltrating lymphocyte)s within the TME.
State of the art and the future of microbiome-based biomarkers: a multidisciplinary Delphi consensus
Authors: Julie Rodriguez, Zahra Hassani, Carolina Alves Costa Silva, Fay Betsou, Federica Carraturo, Alessio Fasano, Mads Israelsen, Anandhi Iyappan, Aleksander Krag, Amira Metwaly, Robert Schierwagen, Jonel Trebicka, Hub Zwart, Joel Doré, Magali Cordaillat-Simmons, Celine Druart
Journal: The Lancet Microbe (2024)
3D bioprinted breast cancer model reveals stroma-mediated modulation of extracellular matrix and radiosensitivity
Authors: Theo Desigaux, Leo Comperat, Nathalie Dusserre, Marie-Laure Stachowicz, Malou Lea, Jean-William Dupuy, Anthony Vial, Michael Molinari, Jean-Christophe Fricain, François Paris, Hugo Oliveira
Journal: Bioactive Materials (2024)
Microbiota‐immune‐brain interactions: A new vision in the understanding of periodontal health and disease
Authors: Torbjørn Jarle Breivik, Per Gjermo, Yngvar Gundersen, Per Kristian Opstad, Robert Murison, Anders Hugoson, Stephan von Hörsten, Inge Fristad
Journal: Periodontology 2000 (2024)

Abstract This review highlights the significance of interactions between the microbiota, immune system, nervous and hormonal systems, and the brain on periodontal health and disease. Microorganisms in the microbiota, immune cells, and neurons communicate via homeostatic nervous and hormonal systems, regulating vital body functions. By modulating pro‐inflammatory and anti‐inflammatory adaptive immune responses, these systems control the composition and number of microorganisms in the microbiota. The strength of these brain‐controlled responses is genetically determined but is sensitive to early childhood stressors, which can permanently alter their responsiveness via epigenetic mechanisms, and to adult stressors, causing temporary changes. Clinical evidence and research with humans and animal models indicate that factors linked to severe periodontitis enhance the responsiveness of these homeostatic systems, leading to persistent hyperactivation. This weakens the immune defense against invasive symbiotic microorganisms (pathobionts) while strengthening the defense against non‐invasive symbionts at the gingival margin. The result is an increased gingival tissue load of pathobionts, including Gram‐negative bacteria, followed by an excessive innate immune response, which prevents infection but simultaneously destroys gingival and periodontal tissues. Thus, the balance between pro‐inflammatory and anti‐inflammatory adaptive immunity is crucial in controlling the microbiota, and the responsiveness of brain‐controlled homeostatic systems determines periodontal health.
Sleep and periodontal health
Authors: Maria Clotilde Carra, Pauline Balagny, Philippe Bouchard
Journal: Periodontology 2000 (2024)

Abstract Sleep is fundamental for health and well‐being. An adequate amount and quality of sleep is a cardinal component of a healthy lifestyle at the basis of the prevention of many non‐communicable chronic diseases. Recent evidence suggests that sleep disorders, particularly obstructive sleep apnea, represent an emerging risk factor for periodontal health. This review article provides a critical appraisal of the existing literature concerning the association between sleep duration, sleep quality, sleep disorders in general, and obstructive sleep apnea with periodontal diseases, including gingivitis and periodontitis. The putative mechanisms underlying these associations are described as well as the potential clinical implications for diagnosis and treatment.
Global prevalence and characteristics of infections and clinical outcomes in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium
Authors: Zhujun Cao, Florence Wong, Ashok K Choudhury, Patrick S Kamath, Mark Topazian, Aldo Torre, Peter C Hayes, Jacob George, Ramazan Idilman, Wai-Kay Seto, Hailemichael Desalegn, Mario Reis Alvares-da-Silva, Brian J Bush, Leroy R Thacker, Qing Xie, Jasmohan S Bajaj
Journal: The Lancet. Gastroenterology & hepatology (2024)
Prostate cancer incidence and mortality in Europe and implications for screening activities: population based study
Authors: Salvatore Vaccarella, Mengmeng Li, Freddie Bray, Rune Kvale, Diego Serraino, Valentina Lorenzoni, Anssi Auvinen, Luigino Dal Maso
Journal: BMJ (2024)

Abstract Objective To provide a baseline comparative assessment of the main epidemiological features of prostate cancer in European populations as background for the proposed EU screening initiatives. Design Population based study. Setting 26 European countries, 19 in the EU, 1980-2017. National or subnational incidence data were extracted from population based cancer registries from the International Agency for Research on Cancer’s Global Cancer Observatory, and mortality data from the World Health Organization. Population Men aged 35-84 years from 26 eligible countries. Results Over the past decades, incidence rates for prostate cancer varied markedly in both magnitude and rate of change, in parallel with temporal variations in prostate specific antigen testing. The variation in incidence across countries was largest around the mid-2000s, with rates spanning from 46 (Ukraine) to 336 (France) per 100 000 men. Thereafter, incidence started to decline in several countries, but with the latest rates nevertheless remaining raised and increasing again in the most recent quinquennium in several countries. Mortality rates during 1980-2020 were much lower and less variable than incidence rates, with steady declines in most countries and lesser temporal differences between countries. Overall, the up to 20-fold variation in prostate cancer incidence contrasts with a corresponding fivefold variation in mortality. Also, the inverse U-shape of the age specific curves for incidence contrasted with the mortality pattern, which increased progressively with age. The difference between the highest and lowest incidence rates across countries ranged from 89.6 per 100 000 men in 1985 to 385.8 per 100 000 men in 2007, while mortality rates across countries ranged from 23.7 per 100 000 men in 1983 to 35.6 per 100 000 men in 2006. Conclusions The epidemiological features of prostate cancer presented here are indicative of overdiagnosis varying over time and across populations. Although the results are ecological in nature and must be interpreted with caution, they do support previous recommendations that any future implementation of prostate cancer screening must be carefully designed with an emphasis on minimising the harms of overdiagnosis.
Safety and immunogenicity of a live-attenuated chikungunya virus vaccine in endemic areas of Brazil: interim results of a double-blind, randomised, placebo-controlled phase 3 trial in adolescents
Authors: Vera Buerger, Sandra Hadl, Martina Schneider, Michaela Schaden, Romana Hochreiter, Annegret Bitzer, Karin Kosulin, Robert Mader, Oliver Zoihsl, Andrea Pfeiffer, Ana Paula Loch, Eolo Morandi, Mauricio Lacerda Nogueira, Carlos Alexandre Antunes de Brito, Julio Croda, Mauro Martins Teixeira, Ivo Castelo-Branco Coelho, Ricardo Gurgel, Allex Jardim da Fonseca, Marcus Vinícius Guimarães de Lacerda, Edson Duarte Moreira, Ana Paula Rocha Veiga, Katrin Dubischar, Nina Wressnigg, Susanne Eder-Lingelbach, Juan Carlos Jaramillo
Journal: The Lancet Infectious Diseases (2024)
Cell death pathways: molecular mechanisms and therapeutic targets for cancer
Authors: Shaohui Wang, Sa Guo, Jing Guo, Qinyun Du, Cen Wu, Yeke Wu, Yi Zhang
Journal: MedComm (2024)

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell death can provide novel therapeutic strategies for battling cancer. This review explores several key cell death mechanisms of apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis. The research gap addressed involves a thorough analysis of how these cell death pathways can be precisely targeted for cancer therapy, considering tumor heterogeneity and adaptation. It delves into genetic and epigenetic factors and signaling cascades like the phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MAPK/ERK) pathways, which are critical for the regulation of cell death. Additionally, the interaction of the microenvironment with tumor cells, and particularly the influence of hypoxia, nutrient deprivation, and immune cellular interactions, are explored. Emphasizing therapeutic strategies, this review highlights emerging modulators and inducers such as B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, and innovative approaches to induce ferroptosis and pyroptosis. This review provides insights into cancer therapy's future direction, focusing on multifaceted approaches to influence cell death pathways and circumvent drug resistance. This examination of evolving strategies underlines the considerable clinical potential and the continuous necessity for in‐depth exploration within this scientific domain.
Circular RNAs in human diseases
Authors: Yuanyong Wang, Jin Zhang, Yuchen Yang, Zhuofeng Liu, Sijia Sun, Rui Li, Hui Zhu, Tian Li, Jin Zheng, Jie Li, Litian Ma
Journal: MedComm (2024)

Abstract Circular RNAs (circRNAs) are a unique class of RNA molecules formed through back‐splicing rather than linear splicing. As an emerging field in molecular biology, circRNAs have garnered significant attention due to their distinct structure and potential functional implications. A comprehensive understanding of circRNAs’ functions and potential clinical applications remains elusive despite accumulating evidence of their involvement in disease pathogenesis. Recent research highlights their significant roles in various human diseases, but comprehensive reviews on their functions and applications remain scarce. This review provides an in‐depth examination of circRNAs, focusing first on their involvement in non‐neoplastic diseases such as respiratory, endocrine, metabolic, musculoskeletal, cardiovascular, and renal disorders. We then explore their roles in tumors, with particular emphasis on exosomal circular RNAs, which are crucial for cancer initiation, progression, and resistance to treatment. By detailing their biogenesis, functions, and impact on disease mechanisms, this review underscores the potential of circRNAs as diagnostic biomarkers and therapeutic targets. The review not only enhances our understanding of circRNAs’ roles in specific diseases and tumor types but also highlights their potential as novel diagnostic and therapeutic tools, thereby paving the way for future clinical investigations and potential therapeutic interventions.