tbuckley/cabot-search huggingface dataset:
Automated decision making in Barrett’s oesophagus: development and deployment of a natural language processing tool
Authors: Agathe Zecevic, Laurence Jackson, Xinyue Zhang, Polychronis Pavlidis, Jason Dunn, Nigel Trudgill, Shahd Ahmed, Pierfrancesco Visaggi, Zanil YoonusNizar, Angus Roberts, Sebastian S. Zeki
Journal: npj Digital Medicine (2024)

Manual decisions regarding the timing of surveillance endoscopy for premalignant Barrett's oesophagus (BO) is error-prone. This leads to inefficient resource usage and safety risks. To automate decision-making, we fine-tuned Bidirectional Encoder Representations from Transformers (BERT) models to categorize BO length (EndoBERT) and worst histopathological grade (PathBERT) on 4,831 endoscopy and 4,581 pathology reports from Guy's and St Thomas' Hospital (GSTT). The accuracies for EndoBERT test sets from GSTT, King's College Hospital (KCH), and Sandwell and West Birmingham Hospitals (SWB) were 0.95, 0.86, and 0.99, respectively. Average accuracies for PathBERT were 0.93, 0.91, and 0.92, respectively. A retrospective analysis of 1640 GSTT reports revealed a 27% discrepancy between endoscopists' decisions and model recommendations. This study underscores the development and deployment of NLP-based software in BO surveillance, demonstrating high performance at multiple sites. The analysis emphasizes the potential efficiency of automation in enhancing precision and guideline adherence in clinical decision-making.
COVID-19 infection is associated with an elevated risk for autoimmune blistering diseases while COVID-19 vaccination decreases the risk: A large-scale population-based cohort study of 112 million individuals
Authors: Philip Curman, Khalaf Kridin, Henner Zirpel, Gema Hernandez, Mehmet Akyuz, Diamant Thaci, Enno Schmidt, Ralf J Ludwig
Journal: Journal of the American Academy of Dermatology (2024)

Numerous diseases associated with COVID-19 infection and vaccination have been reported, including conditions such as the autoimmune blistering diseases (AIBD) pemphigus and pemphigoid. However, robust evidence supporting these associations is lacking. To investigate the risk of developing AIBD following COVID-19 infection and vaccination. Population-based retrospective cohort study utilizing data from over 112 million patients. The risk of AIBD within three months was compared among three cohorts: COVID-19 infection, COVID-19 vaccination, and controls, along with seven sensitivity analyses. COVID-19 infection was associated with an increased risk of AIBD (HR 1.508, 95% CI 1.260-1.805), with the risk being more pronounced for pemphigus (HR 2.432, 1.618-3.657) compared to bullous pemphigoid (HR 1.376, 1.019-1.857). Conversely, COVID-19 vaccination was associated with an almost halved risk of AIBD (HR 0.514, 0.394-0.672), with the risk reduction most significant for pemphigus (HR 0.477, 0.241-0.946). Comparisons between COVID-19 infection and vaccination revealed a more than threefold increased risk of AIBD in the infection cohort (HR 3.130, 2.411-4.063), particularly for pemphigus (HR 5.508, 2.973-10.205). Retrospective design and potential underreporting of COVID-19 cases and vaccinations. COVID-19 infection significantly increases the risk of AIBD while vaccination appears to reduce this risk.
Exploration of the mutational landscape of cutaneous leiomyoma confirms <i>FH</i> as a driver gene and identifies targeting purine metabolism as a potential therapeutic strategy
Authors: Louise van der Weyden, Martin Del Castillo Velasco-Herrera, Saamin Cheema, Kim Wong, Jacqueline M Boccacino, Ian Vermes, Victoria Offord, Alastair Droop, David R A Jones, Elizabeth Anderson, Claire Hardy, Nicolas de Saint Aubain, Peter M Ferguson, Carolin Mogler, Neil Rajan, Derek Frew, Paul W Harms, Steven D Billings, Désirée Schatton, Marc Segarra-Mondejar, Mark J Arends, Ingrid Ferreira, Thomas Brenn, Christian Frezza, David J Adams
Journal: British Journal of Dermatology (2024)

To comprehensively explore the mutational landscape of cutaneous leiomyoma (cLM) and identify candidate driver events, we performed a retrospective, multi-institutional, whole-exome sequencing and RNA sequencing study. We confirmed that a large proportion of patients with cLM have germline FH variants and additionally showed that somatic alteration of FH also drives cLM, with biallelic inactivation of FH being a frequent event. Treatment of Fh1-proficient and -deficient cell lines with the purine antagonist and chemotherapeutic agent, mercaptopurine, significantly decreased growth/colony formation, however, the addition of nucleosides was only able to rescue the Fh1-proficient cells, suggesting that purine metabolism is a targetable vulnerability for FH deficient cLMs.
Conjugation mediates large-scale chromosomal transfer in <i>Streptomyces</i> driving diversification of antibiotic biosynthetic gene clusters
Authors: Caroline Choufa, Pauline Gascht, Hugo Leblond, Anthony Gauthier, Michiel Vos, Cyril Bontemps, Pierre Leblond
Journal: Molecular Biology and Evolution (2024)

Abstract Streptomyces are ubiquitous soil-dwelling bacteria with large, linear genomes that are of special importance as a source of metabolites used in human and veterinary medicine, agronomy, and industry. Conjugative elements (actinomycetes integrative and conjugative elements, AICEs) are the main drivers of Streptomyces Horizontal Gene Transfer. AICE transfer has long been known to be accompanied by mobilization of chromosomal DNA. However, the magnitude of DNA transfer, or the localization of acquired DNA across their linear chromosome, has remained undetermined. We here show that conjugative crossings in sympatric strains of Streptomyces result in the large-scale, genome-wide distributed replacement of up to one-third of the recipient chromosome, a phenomenon for which we propose the name “Streptomyces Chromosomal Transfer” (SCT). Such chromosome blending results in the acquisition, loss, and hybridization of Specialized Metabolite Biosynthetic Gene Clusters, leading to a novel metabolic arsenal in exconjugant offspring. Harnessing conjugation-mediated specialized metabolite biosynthesis gene cluster diversification holds great promise in the discovery of new bioactive compounds including antibiotics.
Near‐Infrared Light‐Responsive Cu<sub>2</sub>MoS<sub>4</sub>@GelMA Hydrogel with Photothermal Therapy, Antibacterial Effect and Bone Immunomodulation for Accelerating Infection Elimination and Fracture Healing
Authors: Haonan Xiu, Kaili Yang, Li Dong, Haohua Lai, Zhangyu Zhu, Dongdong Jiang, Junwei Yan, Chen Shi, Shaowei Pan, Zhaowei Yin, Lihui Yuwen, Bin Liang
Journal: Advanced Healthcare Materials (2024)

Abstract Managing fracture infections is a significant challenge in trauma orthopedics, given the limited self‐healing capacity of fractures and the difficulty in eradicating infections. In this study, Cu 2 MoS 4 nanoparticles (CMSs) with are prepared enzyme‐like activity and both pH and near‐infrared (NIR) light responsiveness. These CMSs are combined with methacrylated gelatin (GelMA) to synthesize CMSs hydrogels (CMSs@Gel) with antimicrobial and bone tissue repair‐promoting capabilities. In vitro and in vivo experiments, the CMSs@Gel demonstrated good biocompatibility; peroxidase‐like (POD), oxidase‐like (OXD), and catalase‐like (CAT) activities; excellent photothermal conversion efficiency; and immunomodulatory capacity. Furthermore, the CMSs@Gel exhibited slow degradation, enabling it to exert different pH‐responsive enzyme activities and modulate the production of reactive oxygen species (ROS) and the polarization of macrophages throughout the treatment process. Notably, these effects are significantly enhanced under near‐infrared (NIR) light. Additionally, under NIR irradiation, the CMSs@Gel maintained the fracture environment at a mild temperature (40–42 °C), promoting osteogenesis and angiogenesis. In summary, the CMSs@Gel enhances bactericidal activity during fracture infection and effectively promotes fracture healing after infection control, providing long‐term therapeutic effects. This study offers a robust theoretical basis for the staged and long‐term treatment of fracture infections in the future.
Anthracene‐Based Endoperoxides as Self‐Sensitized Singlet Oxygen Carriers for Hypoxic‐Tumor Photodynamic Therapy
Authors: Yan‐Qin He, Jian‐Hong Tang
Journal: Advanced Healthcare Materials (2024)

Abstract Singlet oxygen is a crucial reactive oxygen species (ROS) in photodynamic therapy (PDT). However, the hypoxic tumor microenvironment limits the production of cytotoxic singlet oxygen through the light irradiation of PDT photosensitizers (PSs). This restriction poses a major challenge in improving the effectiveness of PDT. To overcome this challenge, researchers have explored the development of singlet oxygen carriers that can capture and release singlet oxygen in physiological conditions. Among these developments, anthracene‐based endoperoxides, initially discovered almost 100 years ago, have shown the ability to generate singlet oxygen controllably under thermal or photo stimuli. Recent advancements have led to the development of a new class of self‐sensitized anthracene‐endoperoxides, with potential applications in enhancing PDT effects for hypoxic tumors. This review discusses the current research progress in utilizing self‐sensitized anthracene‐endoperoxides as singlet oxygen carriers for improved PDT. It covers anthracene‐conjugated small organic molecules, metal–organic complexes, polymeric structures, and other self‐sensitized nano‐structures. The molecular structural designs, mechanisms, and characteristics of these systems will be discussed. This review aims to provide valuable insights for developing high‐performance singlet oxygen carriers for hypoxic‐tumor PDT.
Host–Guest Adduct as a Stimuli‐Responsive Prodrug: Enzyme‐Triggered Self‐Assembly Process of a Short Peptide Within Mitochondria to Induce Cell Apoptosis
Authors: Sandip Sarkar, Atin Chatterjee, Dohyun Kim, Cevella Saritha, Surajit Barman, Batakrishna Jana, Ja‐Hyoung Ryu, Amitava Das
Journal: Advanced Healthcare Materials (2024)

To address the issue of nonspecific biodistribution of a chemotherapeutic drug, stable [2]pseudorotaxane complexes (PK@CAOPP and PR@CAOPP) are used to demonstrate a proof of concept. Cationic -PPh3 + moiety in CAOPP allows specific localization of the PK@CAOPP/ PR@CAOPP in the mitochondrial membrane (MM). Electrostatic interaction between the cationic LysinePK or ArgininePR moiety and the negatively charged phosphoesterCAOPP functionality in CAOPP favours strong adduct formation. The ALP-induced hydrolytic cleavage of the phosphoester moiety in cancer cells triggers dephosphorylation and releases PK/ PR moiety from PK@CAOPP/PR@CAOPP. PK or PR, derived from the Phe-Phe dipeptide, formed fibril-like molecular aggregates in the MM to induce dysfunction, depolarization, ROS generation and apoptotic MCF7 cell death. Such phenomena were not observed in ALP-negative HEK293 normal cells. These propositions were confirmed through control studies using NBDK and PE, other guest molecules. Smaller size and inclusion of the short peptides (PK or PR) within the hydrophobic interior of CAOPP, were attributed to their stability in blood serum. Thus, we have demonstrated the use of supramolecular adducts as a potential therapeutic option for treating cancer cells without affecting healthy cells. The efficacy was also established with an in-vivo MCF7 tumour xenograft model using Balb/c nude mice.
Interpenetrating Polymer Network Hydrogels with Tunable Viscoelasticity and Proteolytic Cleavability to Direct Stem Cells In Vitro
Authors: Prannoy Seth, Jens Friedrichs, Yanuar Dwi Putra Limasale, Nicole Fertala, Uwe Freudenberg, Yixin Zhang, Ayala Lampel, Carsten Werner
Journal: Advanced Healthcare Materials (2024)

The dynamic nature of cellular microenvironments, regulated by the viscoelasticity and enzymatic cleavage of the extracellular matrix, remains challenging to emulate in engineered synthetic biomaterials. To address this, a novel platform of cell-instructive hydrogels is introduced, composed of two concurrently forming interpenetrating polymer networks (IPNs). These IPNs consist of the same basic building blocks - four-armed poly(ethylene glycol) and the sulfated glycosaminoglycan (sGAG) heparin - are cross-linked through either chemical or physical interactions, allowing for precise and selective tuning of the hydrogel's stiffness, viscoelasticity, and proteolytic cleavability. The studies of the individual and combined effects of these parameters on stem cell behavior revealed that human mesenchymal stem cells exhibited increased spreading and Yes-associated protein transcriptional activity in more viscoelastic and cleavable sGAG-IPN hydrogels. Furthermore, human induced pluripotent stem cell (iPSC) cysts displayed enhanced lumen formation, growth, and pluripotency maintenance when cultured in sGAG-IPN hydrogels with higher viscoelasticity. Inhibition studies emphasized the pivotal roles of actin dynamics and matrix metalloproteinase activity in iPSC cyst morphology, which varied with the viscoelastic properties of the hydrogels. Thus, the introduced sGAG-IPN hydrogel platform offers a powerful methodology for exogenous stem cell fate control.
A Pro‐Angiogenic Immunoprotective Membrane for Cell Therapies
Authors: Huifeng Wang, Chongwen Duan, Ruyue Luo, Yugang Liu, Ophelia Tong, Julia Demski, Jonathan Rivnay, Guillermo A. Ameer
Journal: Advanced Healthcare Materials (2024)

Abstract Immunoisolation strategies that rely on porous membranes play an important role in cell transplantation therapies to protect cells from the host's immune system. These membranes must possess immunoprotective properties while facilitating the transport of nutrients and cell products to maintain the functional integrity of encapsulated cells. An easy and scalable process is described to fabricate a dual function porous polymeric membrane that shields cells against immune cell attack and promotes vascularization to address the nutritional and oxygen requirements of transplanted cells. The fabrication process results in a membrane cross‐section with a gradient of nanopores to micropores that support cell immunoisolation and interfacial vascularization requirements, respectively. The membranes demonstrate excellent cell compatibility and effectively prevent T cell transmigration without compromising glucose diffusion and oxygen permeability. In a murine subcutaneous implantation model, membranes are stable for 60 days and exhibit significantly reduced fibrous capsules, with enhanced vascularization near the membrane. These porous polymeric membranes can potentially be used as pro‐angiogenic immunoprotective membranes for cell transplantation applications where maximizing cell viability and function is of critical importance.
Therapeutic Controlled Release Strategies for Human Osteoarthritis
Authors: Dan Wang, Wei Liu, Jagadeesh K. Venkatesan, Henning Madry, Magali Cucchiarini
Journal: Advanced Healthcare Materials (2024)

Abstract Osteoarthritis is a progressive, irreversible debilitating whole joint disease that affects millions of people worldwide. Despite the availability of various options (non‐pharmacological and pharmacological treatments and therapy, orthobiologics, and surgical interventions), none of them can definitively cure osteoarthritis in patients. Strategies based on the controlled release of therapeutic compounds via biocompatible materials may provide powerful tools to enhance the spatiotemporal delivery, expression, and activities of the candidate agents as a means to durably manage the pathological progression of osteoarthritis in the affected joints upon convenient intra‐articular (injectable) delivery while reducing their clearance, dissemination, or side effects. The goal of this review is to describe the current knowledge and advancements of controlled release to treat osteoarthritis, from basic principles to applications in vivo using therapeutic recombinant molecules and drugs and more innovatively gene sequences, providing a degree of confidence to manage the disease in patients in a close future.
The perceived quality of life in adult patients with inherited ichthyosis: a qualitative interview study
Authors: Fauve C A P van Veen, S Vanya J Rossel, Peter M Steijlen, Albine Moser, Karin Veldman, Michel van Geel, Julia M K Clabbers, Jolien van der Geugten, Antoni H Gostyński
Journal: British Journal of Dermatology (2024)

This qualitative interview study aimed to gain insight into the perceived impact of ichthyosis on the biopsychosocial QoL of adult and elderly patients. Fifteen patients (with a diagnosis of autosomal recessive congenital ichthyosis (n=10), X-linked ichthyosis (n=3), and epidermolytic hyperkeratosis (n=2)) highlighted the multifaceted impact of growing older with ichthyosis within the biological (e.g., excessive scaling and overheating), psychological (e.g., low self-esteem and complex reproductive decision making), and social domain (e.g., limited career options and being bullied). Suggestions for healthcare improvements include long-term management of ichthyosis, psychological support, societal awareness, medication reimbursement, and research into reproductive and age-related issues.
Response to Valerio Nardone et al.’s “Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: A retrospective analysis.”
Authors: Syeda Laiba Sajid, Muhammad Aizaz Ur Rehman, Syeda Akifa Sajid, Nayab Shahid
Journal: Journal of the American Academy of Dermatology (2024)
ECM Proteins Nidogen‐1 and Decorin Restore Functionality of Human Islets of Langerhans upon Hypoxic Conditions
Authors: Abiramy Jeyagaran, Max Urbanczyk, Daniel Carvajal‐Berrio, Teresa Baldissera, Philipp D. Kaiser, Laurence Kuhlburger, Stefan Czemmel, Sven Nahnsen, Garry P. Duffy, Sara Y. Brucker, Shannon L. Layland, Katja Schenke‐Layland
Journal: Advanced Healthcare Materials (2024)

Transplantation of donor islets of Langerhans is a potential therapeutic approach for patients with diabetes mellitus; however, its success is limited by islet death and dysfunction during the initial hypoxic conditions at the transplantation site. This highlights the need to support the donor islets in the days post-transplantation until the site is vascularized. It was previously demonstrated that the extracellular matrix (ECM) proteins nidogen-1 (NID1) and decorin (DCN) improve the functionality and survival of the β-cell line, EndoC-βH3, and the viability of human islets post-isolation. To advance the use of these ECM proteins toward a clinical application and elucidate the mechanisms of action in primary islets, the study assesses the effects of ECM proteins NID1 and DCN on isolated human donor islets cultured in normoxic and hypoxic conditions. NID1- and DCN-treatment restore β-cell functionality of human donor islets in a hypoxic environment through upregulation of genes involved in glycolytic pathways and reducing DNA fragmentation in hypoxic conditions comparable to normoxic control islets. The results demonstrate that the utilization of NID1 or DCN with islets of Langerhans may have the potential to overcome the hypoxia-induced cell death observed post-transplantation and improve transplant outcomes.
Thermoforming for Small Feature Replication in Melt Electrowritten Membranes to Model Kidney Proximal Tubule
Authors: Marta G Valverde, Claudia Stampa Zamorano, Dora Kožinec, Laura Benito Zarza, Anne Metje van Genderen, Robine Janssen, Miguel Castilho, Andrei Hrynevich, Tina Vermonden, Jos Malda, Mylene de Ruijter, Rosalinde Masereeuw, Silvia M Mihăilă
Journal: Advanced Healthcare Materials (2024)

Abstract A novel approach merging melt electrowriting (MEW) with matched die thermoforming to achieve scaffolds with micron‐sized curvatures (200 – 800 µm versus 1000 µm of mandrel printing) for in vitro modeling of the kidney proximal tubule (PT) is proposed. Recent advances in this field emphasize the relevance of accurately replicating the intricate tissue microenvironment, particularly the curvature of the nephrons’ tubular segments. While MEW offers promising capabilities for fabricating highly and porous precise 3D structures mimicking the PT, challenges persist in approximating the diameter of tubular scaffolds to match the actual PT. The thermoformed MEW membranes retain the initial MEW printing design parameters (rhombus geometry, porosity &gt; 45%) while accurately following the imprinted curvature (ratios between 0.67‐0.95). PT epithelial cells cultured on these membranes demonstrate the ability to fill in the large pores of the membrane by secreting their own collagen IV‐rich extracellular matrix and form an organized, functional, and tight monolayer expressing characteristic PT markers. Besides approximating PT architecture, this setup maximizes the usable surface area for cell culture and molecular readouts. By closely mimicking the structural intricacies of native tissue architecture, this approach enhances the biomimetic fidelity of engineered scaffolds, offering potential applications beyond kidney tissue engineering.
In Situ Forming Supramolecular Nanofiber Hydrogel as a Biodegradable Liquid Embolic Agent for Postembolization Tissue Remodeling
Authors: Akihiro Nishiguchi, Miho Ohta, Debabrata Palai, Shima Ito, Kensaku Mori, Ryotaro Akagi, Christophe Bajan, Guillaume Lambard, Keitaro Sodeyama, Tetsushi Taguchi
Journal: Advanced Healthcare Materials (2024)

Embolic agents have been widely used to treat blood vessel abnormalities in interventional radiology as a minimally invasive procedure. However, only a few biodegradable liquid embolic agents exhibit high embolization performance, biodegradability, and operability. Herein, the design of in situ-forming supramolecular nanofiber (SNF) hydrogels is reported as biodegradable liquid embolic agents with the assistance of Bayesian optimization through an active learning pipeline. Chemically modified gelatin with hydrogen-bonding moieties produces fibrin-inspired nanofiber-based hydrogels with a high blood coagulation capacity. The low viscosity of the SNF hydrogels makes them injectable using a microcatheter, and the hydrogel shows sufficient tissue adhesion to the blood vessel walls and very weak adhesion to the catheter tubes. Moreover, the SNF hydrogels exhibit high blood compatibility, cytocompatibility, cell-adhesive properties, and biodegradability (in vitro and in vivo). Intravascularly delivered SNF hydrogels induce embolization of rat femoral arteries. This biodegradable liquid embolic agent could be a powerful tool for interventional radiology in the treatment of various diseases, including aortic aneurysm stent grafting, gynecological diseases, and liver cancer.