tbuckley/cabot-search huggingface dataset:
Engineering Microgel Packing to Tailor the Physical and Biological Properties of Gelatin Methacryloyl Granular Hydrogel Scaffolds
Authors: Arian Jaberi, Alexander Kedzierski, Sina Kheirabadi, Yerbol Tagay, Zaman Ataie, Saman Zavari, Mohammad Naghashnejad, Olivia Waldron, Daksh Adhikari, Gerald Lester, Colin Gallagher, Ali Borhan, Dino Ravnic, Erdem Tabdanov, Amir Sheikhi
Journal: Advanced Healthcare Materials (2024)

Abstract Granular hydrogel scaffolds (GHS) are fabricated via placing hydrogel microparticles (HMP) in close contact (packing), followed by physical and/or chemical interparticle bond formation. Gelatin methacryloyl (GelMA) GHS have recently emerged as a promising platform for biomedical applications; however, little is known about how the packing of building blocks, physically crosslinked soft GelMA HMP, affects the physical (pore microarchitecture and mechanical/rheological properties) and biological (in vitro and in vivo) attributes of GHS. Here, the GHS pore microarchitecture is engineered via the external (centrifugal) force‐induced packing and deformation of GelMA HMP to regulate GHS mechanical and rheological properties, as well as biological responses in vitro and in vivo. Increasing the magnitude and duration of centrifugal force increases the HMP deformation/packing, decreases GHS void fraction and median pore diameter, and increases GHS compressive and storage moduli. MDA‐MB‐231 human triple negative breast adenocarcinoma cells spread and flatten on the GelMA HMP surface in loosely packed GHS, whereas they adopt an elongated morphology in highly packed GHS as a result of spatial confinement. Via culturing untreated or blebbistatin‐treated cells in GHS, the effect of non‐muscle myosin II‐driven contractility on cell morphology is shown. In vivo subcutaneous implantation in mice confirms a significantly higher endothelial, fibroblast, and macrophage cell infiltration within the GHS with a lower packing density, which is in accordance with the in vitro cell migration outcome. These results indicate that the packing state of GelMA GHS may enable the engineering of cell response in vitro and tissue response in vivo. This research is a fundamental step forward in standardizing and engineering GelMA GHS microarchitecture for tissue engineering and regeneration.
3D Humanized Bioprinted Tubulointerstitium Model to Emulate Renal Fibrosis In Vitro
Authors: Gabriele Addario, Julia Fernández‐Pérez, Chiara Formica, Konstantinos Karyniotakis, Lea Herkens, Sonja Djudjaj, Peter Boor, Lorenzo Moroni, Carlos Mota
Journal: Advanced Healthcare Materials (2024)

Abstract Chronic kidney disease (CKD) leads to a gradual loss of kidney function, with fibrosis as pathological endpoint, which is characterized by extracellular matrix (ECM) deposition and remodeling. Traditionally, in vivo models are used to study interstitial fibrosis, through histological characterization of biopsy tissue. However, ethical considerations and the 3Rs (replacement, reduction, and refinement) regulations emphasizes the need for humanized 3D in vitro models. This study introduces a bioprinted in vitro model which combines primary human cells and decellularized and partially digested extracellular matrix (ddECM). A protocol was established to decellularize kidney pig tissue and the ddECM was used to encapsulate human renal cells. To investigate fibrosis progression, cells were treated with transforming growth factor beta 1 (TGF‐β1), and the mechanical properties of the ddECM hydrogel were modulated using vitamin B2 crosslinking. The bioprinting perfusable model replicates the renal tubulointerstitium. Results show an increased Young's modulus over time, together with the increase of ECM components and cell dedifferentiation toward myofibroblasts. Multiple fibrotic genes resulted upregulated, and the model closely resembled fibrotic human tissue in terms of collagen deposition. This 3D bioprinted model offers a more physiologically relevant platform for studying kidney fibrosis, potentially improving disease progression research and high‐throughput drug screening.
Engineering a Microfluidic Platform to Cryopreserve Stem Cells: A DMSO‐Free Sustainable Approach
Authors: Saman Modaresi, Settimio Pacelli, Aishik Chakraborty, Ali Coyle, Wei Luo, Irtisha Singh, Arghya Paul
Journal: Advanced Healthcare Materials (2024)

Abstract Human adipose‐derived stem cells (hASCs) are cryopreserved traditionally using dimethyl sulfoxide (DMSO) as the cryoprotectant agent. DMSO penetrates cell membranes and prevents cellular damage during cryopreservation. However, DMSO is not inert to cells, inducing cytotoxic effects by causing mitochondrial dysfunction, reduced cell proliferation, and impaired hASCs transplantation. Additionally, large‐scale production of DMSO and contamination can adversely impact the environment. A sustainable, green alternative to DMSO is trehalose, a natural disaccharide cryoprotectant agent that does not pose any risk of cytotoxicity. However, the cellular permeability of trehalose is less compared to DMSO. Here, a microfluidic chip is developed for the intracellular delivery of trehalose in hASCs. The chip is designed for mechanoporation, which creates transient pores in cell membranes by mechanical deformation. Mechanoporation allows the sparingly permeable trehalose to be internalized within the cell cytosol. The amount of trehalose delivered intracellularly is quantified and optimized based on cellular compatibility and functionality. Furthermore, whole‐transcriptome sequencing confirms that less than 1% of all target genes display at least a twofold change in expression when cells are passed through the chip compared to untreated cells. Overall, the results confirm the feasibility and effectiveness of using this microfluidic chip for DMSO‐free cryopreservation of hASCs.
Hydrogels for Nucleic Acid Drugs Delivery
Authors: Jiaping Liu, Ziyue Xi, Chuanyong Fan, Yihua Mei, Jiale Zhao, Yingying Jiang, Ming Zhao, Lu Xu
Journal: Advanced Healthcare Materials (2024)

Abstract Nucleic acid drugs are one of the hot spots in the field of biomedicine in recent years, and play a crucial role in the treatment of many diseases. However, its low stability and difficulty in target drug delivery are the bottlenecks restricting its application. Hydrogels are proven to be promising for improving the stability of nucleic acid drugs, reducing the adverse effects of rapid degradation, sudden release, and unnecessary diffusion of nucleic acid drugs. In this review, the strategies of loading nucleic acid drugs in hydrogels are summarized for various biomedical research, and classify the mechanism principles of these strategies, including electrostatic binding, hydrogen bond based binding, hydrophobic binding, covalent bond based binding and indirect binding using various carriers. In addition, this review also describes the release strategies of nucleic acid drugs, including photostimulation‐based release, enzyme‐responsive release, pH‐responsive release, and temperature‐responsive release. Finally, the applications and future research directions of hydrogels for delivering nucleic acid drugs in the field of medicine are discussed.
Model-informed precision dosing: State of the art and future perspectives
Authors: I K Minichmayr, E Dreesen, M Centanni, Z Wang, Y Hoffert, L E Friberg, S G Wicha
Journal: Advanced Drug Delivery Reviews (2024)

Model-informed precision dosing (MIPD) stands as a significant development in personalized medicine to tailor drug dosing to individual patient characteristics. MIPD moves beyond traditional therapeutic drug monitoring (TDM) by integrating mathematical predictions of dosing, and considering patient-specific factors (patient characteristics, drug measurements) as well as different sources of variability. For this purpose, rigorous model qualification is required for the application of MIPD in patients. This review delves into new methods in model selection and validation, also highlighting the role of machine learning in improving MIPD, the utilization of biosensors for real-time monitoring, as well as the potential of models integrating biomarkers for efficacy or toxicity for precision dosing. The clinical evidence of TDM and MIPD is discussed for various medical fields including infection medicine, oncology, transplant medicine, and inflammatory bowel diseases, thereby underscoring the role of pharmacokinetics/pharmacodynamics and specific biomarkers. Further research, particularly randomized clinical trials, is warranted to corroborate the value of MIPD in enhancing patient outcomes and advancing personalized medicine.
pH-Responsive and Nanoenzyme-Loaded Artificial Nanocells Relieved Osteomyelitis Efficiently by Synergistic Chemodynamic and Cuproptosis Therapy
Authors: Yuanhui Li, Jian Li, Yuxuan Zhong, Qingshun Zhang, Yuchun Wu, Jinpeng Huang, Kaicheng Pang, Yuanyue Zhou, Tong Xiao, Zenghui Wu, Wei Sun, Chao He
Journal: Biomaterials (2024)
Rethinking masked image modeling for medical image representation
Authors: Yutong Xie, Lin Gu, Tatsuya Harada, Jianpeng Zhang, Yong Xia, Qi Wu
Journal: Medical Image Analysis (2024)

Masked Image Modelling (MIM), a form of self-supervised learning, has garnered significant success in computer vision by improving image representations using unannotated data. Traditional MIMs typically employ a strategy of random sampling across the image. However, this random masking technique may not be ideally suited for medical imaging, which possesses distinct characteristics divergent from natural images. In medical imaging, particularly in pathology, disease-related features are often exceedingly sparse and localized, while the remaining regions appear normal and undifferentiated. Additionally, medical images frequently accompany reports, directly pinpointing pathological changes' location. Inspired by this, we propose Masked medical Image Modelling (MedIM), a novel approach, to our knowledge, the first research that employs radiological reports to guide the masking and restore the informative areas of images, encouraging the network to explore the stronger semantic representations from medical images. We introduce two mutual comprehensive masking strategies, knowledge-driven masking (KDM), and sentence-driven masking (SDM). KDM uses Medical Subject Headings (MeSH) words unique to radiology reports to identify symptom clues mapped to MeSH words (e.g., cardiac, edema, vascular, pulmonary) and guide the mask generation. Recognizing that radiological reports often comprise several sentences detailing varied findings, SDM integrates sentence-level information to identify key regions for masking. MedIM reconstructs images informed by this masking from the KDM and SDM modules, promoting a comprehensive and enriched medical image representation. Our extensive experiments on seven downstream tasks covering multi-label/class image classification, pneumothorax segmentation, and medical image-report analysis, demonstrate that MedIM with report-guided masking achieves competitive performance. Our method substantially outperforms ImageNet pre-training, MIM-based pre-training, and medical image-report pre-training counterparts. Codes are available at https://github.com/YtongXie/MedIM.
Cocrystal@protein-anchoring nanococktail for combinatorially treating multidrug-resistant cancer
Authors: Jiahui Zou, Xuyang Xing, Chao Teng, Qingling Zhao, Wei He, Xuri Wu, Yuanzheng Xia
Journal: Acta Pharmaceutica Sinica B (2024)

Multidrug resistance (MDR), the major mechanism by which various cancers develop specific resistance to therapeutic agents, has set up enormous obstacles to many forms of tumor chemotherapy. Traditional cocktail therapy administration, based on the combination of multiple drugs for anti-MDR chemotherapy, often suffers from inconsistent
Integrative Drug Screening and Multiomic Characterization of Patient-derived Bladder Cancer Organoids Reveal Novel Molecular Correlates of Gemcitabine Response
Authors: Nathan M Merrill, Samuel D Kaffenberger, Liwei Bao, Nathalie Vandecan, Laura Goo, Athena Apfel, Xu Cheng, Zhaoping Qin, Chia-Jen Liu, Armand Bankhead, Yin Wang, Varun Kathawate, Lila Tudrick, Habib A Serhan, Zackariah Farah, Chad Ellimoottil, Khaled S Hafez, Lindsey A Herrel, Jeffrey S Montgomery, Todd M Morgan, Simpa S Salami, Alon Z Weizer, Peter J Ulintz, Mark L Day, Matthew B Soellner, Phillip L Palmbos, Sofia D Merajver, Aaron M Udager
Journal: European Urology (2024)
European Association of Urology Guidelines on Non–muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)—A Summary of the 2024 Guidelines Update
Authors: Paolo Gontero, Alison Birtle, Otakar Capoun, Eva Compérat, José L Dominguez-Escrig, Fredrik Liedberg, Paramananthan Mariappan, Alexandra Masson-Lecomte, Hugh A Mostafid, Benjamin Pradere, Bhavan P Rai, Bas W G van Rhijn, Thomas Seisen, Shahrokh F Shariat, Francesco Soria, Viktor Soukup, Robert Wood, Evanguelos N Xylinas
Journal: European Urology (2024)
Reply to Sandra P. García Nader, Cesar A. Díaz Ritter, and Valentina Garcia Perez’s Letter to the Editor re: Carlotta Nedbal, Patrick Juliebø-Jones, Eamonn Rogers, et al. Improving Patient Information and Enhanced Consent in Urology: The Impact of Simulation and Multimedia Tools. A Systematic Literature Review from the European Association of Urology Patient Office. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.04.009
Authors: Carlotta Nedbal, Bhaskar Kumar Somani
Journal: European Urology (2024)
CD19-CAR T-cell therapy induces deep tissue depletion of B cells
Authors: Carlo Tur, Markus Eckstein, Joachim Velden, Simon Rauber, Christina Bergmann, Janina Auth, Laura Bucci, Giulia Corte, Melanie Hagen, Andreas Wirsching, Ricardo Grieshaber-Bouyer, Petra Reis, Nicolai Kittan, Jochen Wacker, Aleix Rius Rigau, Andreas Ramming, Maria-Antonietta D'Agostino, Arndt Hartmann, Fabian Müller, Andreas Mackensen, Aline Bozec, Georg Schett, Maria Gabriella Raimondo
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Objectives</h3> CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo. <h3>Methods</h3> Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs. Results were compared with lymph node biopsies from rituximab (RTX)-treated AID patients with absence of peripheral B cells. Conventional and immunohistochemistry staining were performed on lymph node tissue to assess architecture as well the number of B cells, follicular dendritic cells (FDCs), plasma cells, T cells and macrophages. <h3>Results</h3> Sequential lymph node biopsies were analysed from five patients with AID before and after CD19-CAR T-cell therapy and from five patients with AID after RTX treatment. In addition, non-lymphoid organ biopsies (colon, kidney and gallbladder) from three additional patients with AID after CD19-CAR T-cell therapy were analysed. CD19<sup>+</sup> and CD20<sup>+</sup> B cells were completely depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX treatment. Plasma cells, T cells and macrophages in the lymph nodes remained unchanged. Follicular structures were disrupted and FDCs were depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX. Non-lymphoid organs were completely depleted of B cells. <h3>Discussion</h3> This study demonstrates complete B-cell depletion in secondary lymphoid tissues of patients with AIDs following CD19-CAR T-cell therapy combined with standard lymphodepleting therapy.
Pulmonary fibrosis may begin in infancy: from childhood to adult interstitial lung disease
Authors: Matthias Griese, Geoffrey Kurland, Michal Cidon, Robin R Deterding, Ralph Epaud, Nadia Nathan, Nicolaus Schwerk, David Warburton, Jason P Weinman, Lisa R Young, Gail H Deutsch
Journal: Thorax (2024)

Background Childhood interstitial lung disease (chILD) encompasses a group of rare heterogeneous respiratory conditions associated with significant morbidity and mortality. Reports suggest that many patients diagnosed with chILD continue to have potentially progressive or fibrosing disease into adulthood. Over the last decade, the spectrum of conditions within chILD has widened substantially, with the discovery of novel entities through advanced genetic testing. However, most evidence is often limited to small case series, with reports disseminated across an array of subspecialty, clinical and molecular journals. In particular, the frequency, management and outcome of paediatric pulmonary fibrosis is not well characterised, unlike in adults, where clear diagnosis and treatment guidelines are available. Methods and results This review assesses the current understanding of pulmonary fibrosis in chILD. Based on registry data, we have provisionally estimated the occurrence of fibrosis in various manifestations of chILD, with 47 different potentially fibrotic chILD entities identified. Published evidence for fibrosis in the spectrum of chILD entities is assessed, and current and future issues in management of pulmonary fibrosis in childhood, continuing into adulthood, are considered. Conclusions There is a need for improved knowledge of chILD among pulmonologists to optimise the transition of care from paediatric to adult facilities. Updated evidence-based guidelines are needed that incorporate recommendations for the diagnosis and management of immune-mediated disorders, as well as chILD in older children approaching adulthood.
Reproductive tract complication risks following Chlamydia trachomatis infections: a long-term prospective cohort study from 2008 to 2022
Authors: Zoïe W Alexiou, Bernice M Hoenderboom, Christian J P A Hoebe, Nicole H T M Dukers-Muijrers, Hannelore M Götz, Marianne A B van der Sande, Henry J C de Vries, Janneke E den Hartog, Servaas A Morré, Birgit H B van Benthem
Journal: The Lancet Regional Health - Europe (2024)

The clinical and public health relevance of widespread testing for asymptomatic
Treatment with oncolytic vaccinia virus infects tumor-infiltrating regulatory and exhausted T cells
Authors: Kristin DePeaux, William G Gunn, Dayana B Rivadeneira, Greg M Delgoffe
Journal: Journal for ImmunoTherapy of Cancer (2024)

Oncolytic viruses (OVs) are an attractive way to increase immune infiltration into an otherwise cold tumor. While OVs are engineered to selectively infect tumor cells, there is evidence that they can infect other non-malignant cells in the tumor. We sought to determine if oncolytic vaccinia virus (VV) can infect lymphocytes in the tumor and, if so, how this was linked to therapeutic efficacy.
Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis
Authors: Mohamed G Shiha, Annalisa Schiepatti, Stiliano Maimaris, NIcoletta Nandi, Hugo A Penny, David S Sanders
Journal: Gut (2024)

Potential coeliac disease (PCD) is characterised by positive serological and genetic markers of coeliac disease with architecturally preserved duodenal mucosa. The clinical outcomes and rates of progression to overt coeliac disease in patients with PCD remain uncertain. In this systematic review and meta-analysis, we aimed to evaluate the clinical outcomes of patients with PCD.
Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation
Authors: John Alan Gambril, Sanam M. Ghazi, Stephen Sansoterra, Mussammat Ferdousi, Onaopepo Kola-Kehinde, Patrick Ruz, Adam S. Kittai, Kerry Rogers, Michael Grever, Seema Bhat, Tracy Wiczer, John C. Byrd, Jennifer Woyach, Daniel Addison
Journal: Leukemia (2024)

Abstract Bruton’s tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B-cell malignancies, but link with cardiotoxicity, including atrial fibrillation (AF). Burden, severity, and implications of BTKi-related AF are unknown. Leveraging a large-cohort of consecutive B-cell malignancy patients initiated on BTKi from 2009–2020, we identified patients with extended ambulatory rhythm monitoring. The primary outcome was AF burden after BTKi-initiation. Secondary outcomes included ventricular arrhythmia burden and other arrhythmias. Observed incident-AF rates and burden with next-generation BTKi’s were compared to ibrutinib. Multivariable regression defined association between rhythm measures and major adverse cardiac events (MACE), and mortality. There were 98 BTKi-treated patients [38.8% next-generation BTKi’s, 14.3% prior-AF], with 28,224 h of monitoring. Median duration BTKi-use was 34 months. Over mean duration 12 days monitoring, 72.4% developed arrhythmias (16.3% incident-AF, 31.6% other SVTs, 14.3% ventricular tachycardia). 14.3% had high AF-burden. AF-burden was similar between ibrutinib and next-generation BTKi’s. No single antiarrhythmic-therapy prevented BTKi-related AF. However, antiarrhythmic initiation associated with reduction in arrhythmic burden ( P = 0.009). In a multivariable model accounting for traditional cardiovascular risk factors, prior-AF associated with increased post-BTKi AF-burden. In follow-up, high AF burden associated with MACE (HR 3.12, P = 0.005) and mortality (HR 2.97, P = 0.007). Among BTKi-treated patients, high AF burden prognosticates future MACE and mortality risk.
Plasma proteome profiling in giant cell arteritis
Authors: Kevin Y Cunningham, Benjamin Hur, Vinod K Gupta, Matthew J Koster, Cornelia M Weyand, David Cuthbertson, Nader A Khalidi, Curry L Koening, Carol A Langford, Carol A McAlear, Paul A Monach, Larry W Moreland, Christian Pagnoux, Rennie L Rhee, Philip Seo, Peter A Merkel, Kenneth J Warrington, Jaeyun Sung
Journal: Annals of the Rheumatic Diseases (2024)

This study aimed to identify plasma proteomic signatures that differentiate active and inactive giant cell arteritis (GCA) from non-disease controls. By comprehensively profiling the plasma proteome of both patients with GCA and controls, we aimed to identify plasma proteins that (1) distinguish patients from controls and (2) associate with disease activity in GCA.
Sport PRactice and its Effects on aortic size and valve function in bicuspid Aortic valve Disease: a cross-sectional report from the SPREAD study
Authors: Flavio D'Ascenzi, Luna Cavigli, Matteo Cameli, Guido Claessen, Emeline M van Craenenbroeck, Elena Cavarretta, Antonello D'Andrea, Maria Sanz De la Garza, Thijs M H Eijsvogels, Roland R J van Kimmenade, Laura Galian-Gay, Martin Halle, Giulia Elena Mandoli, Valentina Mantegazza, Antonella Moreo, Bibi Schreurs, Laura Stefani, Jose L Zamorano, Antonio Pelliccia, Michael Papadakis
Journal: British Journal of Sports Medicine (2024)

Concerns exist about the possible detrimental effects of exercise training on aortic size and valve function in individuals with bicuspid aortic valve (BAV). This multicentre international study aimed to determine the characteristics of aortic size and valve function in athletes versus non-athletes with BAV and athletes with tricuspid aortic valve (TAV).
XBB.1.16‐RBD‐based trimeric protein vaccine can effectively inhibit XBB.1.16‐included XBB subvariant infection
Authors: Dandan Peng, Cai He, Zimin Chen, Hong Lei, Xiya Huang, Chunjun Ye, Binhan Wang, Ying Hao, Xinyi Du, Shuaiyao Lu, Hongbo Hu, Wei Cheng, Haohao Dong, Jian Lei, Xikun Zhou, Xiangrong Song, Guangwen Lu, Xiawei Wei
Journal: MedComm (2024)

The newly identified XBB.1.16-containing sublineages, including XBB.1.5, have become the prevailing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant in circulation. Unlike previous Omicron XBB variants (e.g., XBB.1.5 and XBB.1.9) harboring the F486P substitution, XBB.1.16 also carries a T478R substitution in the receptor-binding domain (RBD). Numerous researchers have delved into the high transmissibility and immune evasion of XBB.1.16 subvariant. Therefore, developing a new vaccine targeting XBB.1.16, including variants of concern (VOCs), is paramount. In our study, we engineered a recombinant protein by directly linking the S-RBD sequence of the XBB.1.16 strain of SARS-CoV-2 to the sequences of two heptad repeat sequences (HR1 and HR2) from the SARS-CoV-2 S2 subunit. Named the recombinant RBD