tbuckley/cabot-search huggingface dataset:
Photo‐Clickable Triazine‐Trione Thermosets as Promising 3D Scaffolds for Tissue Engineering Applications
Authors: Åshild Johansen, Jinjian Lin, Shuntaro Yamada, Samih Mohamed‐Ahmed, Mohammed A. Yassin, Cecilie Gjerde, Daniel J. Hutchinson, Kamal Mustafa, Michael Malkoch
Journal: Advanced Healthcare Materials (2024)

Abstract There is an overwhelming demand for new scaffolding materials for tissue engineering (TE) purposes. Polymeric scaffolds have been explored as TE materials; however, their high glass transition state (T g ) limits their applicability. In this study, a novel materials platform for fabricating TE scaffolds is proposed based on solvent‐free two‐component heterocyclic triazine‐trione (TATO) formulations, which cure at room temperature via thiol‐ene/yne photochemistry. Three ester‐containing thermosets, TATO‐1, TATO‐2, and TATO‐3, are used for the fabrication of TE scaffolds including rigid discs, elastic films, microporous sponges, and 3D printed objects. After 14 days’ incubation the materials covered a wide range of properties, from the soft TATO‐2 having a compression modulus of 19.3 MPa and a T g of 30.4 °C to the hard TATO‐3 having a compression modulus of 411 MPa and a T g of 62.5 °C. All materials exhibit micro‐ and nano‐surface morphologies suited for bone tissue engineering, and in vitro studies found them all to be cytocompatible, supporting fast cell proliferation while minimizing cell apoptosis and necrosis. Moreover, bone marrow‐derived mesenchymal stem cells on the surface of the materials are successfully differentiated into osteoblasts, adipocytes, and neuronal cells, underlining the broad potential for the biofabrication of TATO materials for TE clinical applications.
A High‐Throughput Screening Strategy for Synthesizing Molecularly Imprinted Polymer Nanoparticles Selectively Targeting Tumors
Authors: Qingmei Song, Yan Li, Liang Ma, Yuan Li, Yongqin Lv
Journal: Advanced Healthcare Materials (2024)

Abstract Molecularly imprinted polymers (MIPs) show significant promise as effective alternatives to antibodies in disease diagnosis and therapy. However, the challenging process of screening extensive libraries of monomer combinations and synthesis conditions to identify formulations with enhanced selectivity and affinity presents a notable time constraint. The need for expedient methods becomes clear in accelerating the strategic development of MIPs tailored for precise molecular recognition purposes. In this study, an innovative high‐throughput screening methodology designed to identify the optimal MIP formulation for targeting tumors is presented. Employing a microtiter plate format, over 100 polymer syntheses are conducted, incorporating diverse combinations of functional monomers. Evaluation of binding performance utilizes fluorescence‐based assays, focusing on an epitope of the epidermal growth factor receptor (EGFR). Through this meticulously structured screening process, synthesis conditions that produced MIP nanoparticles exhibiting substantial specificity for EGFR targeting ( K D = 10 −12 m ) are identified. These “bionic antibodies” demonstrate selective recognition of cancer cells in whole blood samples, even at concentrations as low as 5 cells mL −1 . Further validation through fluorescent imaging confirms the tumor‐specific localization of the MIPs in vivo. This highly efficient screening approach facilitates the strategic synthesis of imprinted polymers functioning as precision bioprobes.
Metal‐Coordinated Polydopamine Structures for Tumor Imaging and Therapy
Authors: Lihua Wang, Kaiyue Song, Cong Jiang, Shanping Liu, Shaorong Huang, Huang Yang, Xianglong Li, Feng Zhao
Journal: Advanced Healthcare Materials (2024)

Meticulously engineered nanomaterials achieve significant advances in the diagnosis and therapy of solid tumors by improving tumor delivery efficiency; and thereby, enhancing imaging and therapeutic efficacy. Currently, polydopamine (PDA) attracts widespread attention because of its biocompatibility, simplicity of preparation, abundant surface groups, and high photothermal conversion efficiency, which can be applied in drug delivery, photothermal therapy, theranostics, and other nanomedicine fields. Inspired by PDA structures that are rich in catechol and amino functional groups that can coordinate with various metal ions, which have charming qualities and characteristics, metal-coordinated PDA structures are exploited for tumor theranostics, but are not thoroughly summarized. Herein, this review summarizes the recent progress in the fabrication of metal-coordinated PDA structures and their availabilities in tumor imaging and therapy, with further in-depth discussion of the challenges and future perspectives of metal-coordinated PDA structures, with the aim that this systematic review can promote interdisciplinary intersections and provide inspiration for the further growth and clinical translation of PDA materials.
Innovative Substrate Design with Basement Membrane Components for Enhanced Endothelial Cell Function and Endothelization
Authors: Yuriy Snyder, Soumen Jana
Journal: Advanced Healthcare Materials (2024)

Abstract Enhancing endothelial cell growth on small‐diameter vascular grafts produced from decellularized tissues or synthetic substrates is pivotal for preventing thrombosis. While optimized decellularization protocols can preserve the structure and many components of the extracellular matrix (ECM), the process can still lead to the loss of crucial basement membrane proteins, such as laminin, collagen IV, and perlecan, which are pivotal for endothelial cell adherence and functional growth. This loss can result in poor endothelialization and endothelial cell activation causing thrombosis and intimal hyperplasia. To address this, the basement membrane's ECM is emulated on fiber substrates, providing a more physiological environment for endothelial cells. Thus, fibroblasts are cultured on fiber substrates to produce an ECM membrane substrate (EMMS) with basement membrane proteins. The EMMS then underwent antigen removal (AR) treatment to eliminate antigens from the membrane while preserving essential proteins and producing an AR‐treated membrane substrate (AMS). Subsequently, human endothelial cells cultured on the AMS exhibited superior proliferation, nitric oxide production, and increased expression of endothelial markers of quiescence/homeostasis, along with autophagy and antithrombotic factors, compared to those on the decellularized aortic tissue. This strategy showed the potential of pre‐endowing fiber substrates with a basement membrane to enable better endothelization.
Cellular immunotherapies and immune cell depleting therapies in inflammatory bowel diseases: the next magic bullet?
Authors: Markus Friedrich Neurath, Bruce Eric Sands, Florian Rieder
Journal: Gut (2024)

Despite significant advances in biologic and small molecule treatments and the emergence of combination therapies to treat inflammatory bowel diseases (IBD) a large unmet need remains to control intestinal inflammation. New approaches targeting several pathways simultaneously with a favorable safety profile and agents that trigger anti-inflammatory pathways to drive durable resolution of inflammation are needed. This article discusses novel cellular immunotherapies and immune cell depleting therapies in IBD, including CAR-T cell approaches, Tr1 and T regulatory (Treg) cells and cell depleting antibodies such as rosnilimab. These novel approaches have the potential to overcome current therapeutic limitations in the treatment of IBD.
Covid-19 infection and vaccination during first trimester and risk of congenital anomalies: Nordic registry based study
Authors: Maria C Magnus, Jonas Söderling, Anne K Örtqvist, Anne-Marie Nybo Andersen, Olof Stephansson, Siri E Håberg, Stine Kjaer Urhoj
Journal: BMJ (2024)

To evaluate the risk of major congenital anomalies according to infection with or vaccination against covid-19 during the first trimester of pregnancy. Prospective Nordic registry based study. Sweden, Denmark, and Norway. 343 066 liveborn singleton infants in Sweden, Denmark, and Norway, with an estimated start of pregnancy between 1 March 2020 and 14 February 2022, identified using national health registries. Major congenital anomalies were categorised using EUROCAT (European Surveillance of Congenital Anomalies) definitions. The risk after covid-19 infection or vaccination during the first trimester was assessed by logistic regression, adjusting for maternal age, parity, education, income, country of origin, smoking, body mass index, chronic conditions, and estimated date of start of pregnancy. 17 704 (5.2%) infants had a major congenital anomaly. When evaluating risk associated with covid-19 infection during the first trimester, the adjusted odds ratio ranged from 0.84 (95% confidence interval 0.51 to 1.40) for eye anomalies to 1.12 (0.68 to 1.84) for oro-facial clefts. Similarly, the risk associated with covid-19 vaccination during the first trimester ranged from 0.84 (0.31 to 2.31) for nervous system anomalies to 1.69 (0.76 to 3.78) for abdominal wall defects. Estimates for 10 of 11 subgroups of anomalies were less than 1.04, indicating no notable increased risk. Covid-19 infection and vaccination during the first trimester of pregnancy were not associated with risk of congenital anomalies.
Clinical and molecular characteristics of extramedullary acute myeloid leukemias
Authors: Tariq Kewan, Waled S. Bahaj, Carmelo Gurnari, Olisaemeka D. Ogbue, Sudipto Mukherjee, Anjali Advani, James R. Cook, Heesun J. Rogers, Hetty E. Carraway, Suresh K. Balasubramanian, Valeria Visconte, Jaroslaw P. Maciejewski
Journal: Leukemia (2024)
Modeling on in vivo disposition and cellular transportation of RNA lipid nanoparticles via quantum mechanics/physiologically-based pharmacokinetic approaches
Authors: Wei Wang, Shiwei Deng, Jinzhong Lin, Defang Ouyang
Journal: Acta Pharmaceutica Sinica B (2024)

The lipid nanoparticle (LNP) has been so far proven as a strongly effective delivery system for mRNA and siRNA. However, the mechanisms of LNP's distribution, metabolism, and elimination are complicated, while the transportation and pharmacokinetics (PK) of LNP are just sparsely investigated and simply described. This study aimed to build a model for the transportation of RNA-LNP in Hela cells, rats, mice, and humans by physiologically based pharmacokinetic (PBPK) and quantum mechanics (QM) models with integrated multi-source data. LNPs with different ionizable lipids, particle sizes, and doses were modeled and compared by recognizing their critical parameters dominating PK. Some interesting results were found by the models. For example, the metabolism of ionizable lipids was first limited by the LNP disassembly rate instead of the hydrolyzation of ionizable lipids; the ability of RNA release from endosomes for three ionizable lipids was quantitively derived and can predict the probability of RNA release. Moreover, the biodegradability of three ionizable lipids was estimated by the QM method and the is generally consistent with the result of PBPK result. In summary, the transportation model of RNA LNP among various species for the first time was successfully constructed. Various
Strategic reuse of rapid antigen tests for coagulation status assessment: an integrated machine learning approach
Authors: Allan Sun, Arian Nasser, Chaohao Chen, Yunduo Charles Zhao, Haimei Zhao, Zihao Wang, Wenlong Cheng, Pierre Qian, Lining Arnold Ju
Journal: Med-X (2024)

Abstract Addressing the pressing demand for rapid and inexpensive coagulation testing in cardiovascular care, this study introduces a novel application of repurposed COVID-19 rapid antigen tests (RATs) as paper-based lateral flow assays (LFAs) combined with machine learning for coagulation status evaluation. By further developing a mobile app prototype, we present a platform that enables clinicians to perform immediate and accurate anticoagulant dosing adjustments using existing post-pandemic resources. Our proof-of-concept employs a random forest machine learning classifier to interpret image feature variations on RAT NC membrane, correlating red blood cell (RBC) wicked diffusion distance in recalcified citrated whole blood with changes in coagulative viscosity, easily interpreted. Enhanced by confocal imaging studies of paper microfluidics, our approach provides insights into the mechanisms dissecting coagulation components, achieving high classification precision, recall, and F1-scores. The inverse relationship between RBC wicked diffusion distance and enoxaparin concentration paves the way for machine learning to inform real-time dose prescription adjustments, aligning with individual patient profiles to optimize therapeutic outcomes. This study not only demonstrates the potential of leveraging surplus RATs for coagulation management but also exemplifies a cost-effective, rapid, and smart strategy to enhance clinical decision-making in the post-pandemic era. Graphical Abstract
Menin inhibitors for acute myeloid leukemia: latest updates from the 2023 ASH Annual Meeting
Authors: Zhuo-Yu An, Xiao-Hui Zhang
Journal: Journal of Hematology & Oncology (2024)

Abstract Recent developments in menin inhibitors for relapsed or refractory acute myeloid leukemia (AML) were highlighted at the 2023 ASH Annual Meeting. Notably, revumenib showed promising efficacy, achieving a 100% ORR when combined with decitabine/cedazuridine and venetoclax. These findings underscore the potential of menin inhibitors in transforming AML treatment, particularly in genetically defined subgroups, offering hope for improved patient outcomes. Ongoing studies, like KOMET-008, further explore the synergistic potential of menin inhibitors in combination regimens, shaping future AML management strategies.
Tau protein profiling in tauopathies: a human brain study
Authors: Juan Lantero-Rodriguez, Elena Camporesi, Laia Montoliu-Gaya, Johan Gobom, Diana Piotrowska, Maria Olsson, Irena Matečko Burmann, Bruno Becker, Ann Brinkmalm, Björn M. Burmann, Michael Perkinton, Nicholas J. Ashton, Nick C. Fox, Tammaryn Lashley, Henrik Zetterberg, Kaj Blennow, Gunnar Brinkmalm
Journal: Molecular Neurodegeneration (2024)

Abstract Abnormal accumulation of misfolded and hyperphosphorylated tau protein in brain is the defining feature of several neurodegenerative diseases called tauopathies, including Alzheimer’s disease (AD). In AD, this pathological change is reflected by highly specific cerebrospinal fluid (CSF) tau biomarkers, including both phosphorylated and non-phosphorylated variants. Interestingly, despite tau pathology being at the core of all tauopathies, CSF tau biomarkers remain unchanged in certain tauopathies, e.g., progressive supranuclear palsy (PSP), Pick’s disease (PiD), and corticobasal neurodegeneration (CBD). To better understand commonalities and differences between tauopathies, we report a multiplex assay combining immunoprecipitation and high-resolution mass spectrometry capable of detecting and quantifying peptides from different tau protein isoforms as well as non-phosphorylated and phosphorylated peptides, including those carrying multiple phosphorylations. We investigated the tau proteoforms in soluble and insoluble fractions of brain tissue from subjects with autopsy-confirmed tauopathies, including sporadic AD ( n = 10), PSP ( n = 11), PiD ( n = 10), and CBD ( n = 10), and controls ( n = 10). Our results demonstrate that non-phosphorylated tau profiles differ across tauopathies, generally showing high abundance of microtubule-binding region (MTBR)-containing peptides in insoluble protein fractions compared with controls; the AD group showed 12–72 times higher levels of MTBR-containing aggregates. Quantification of tau isoforms showed the 3R being more abundant in PiD and the 4R isoform being more abundant in CBD and PSP in the insoluble fraction. Twenty-three different phosphorylated peptides were quantified. Most phosphorylated peptides were measurable in all investigated tauopathies. All phosphorylated peptides were significantly increased in AD insoluble fraction. However, doubly and triply phosphorylated peptides were significantly increased in AD even in the soluble fraction. Results were replicated using a validation cohort comprising AD ( n = 10), CBD ( n = 10), and controls ( n = 10). Our study demonstrates that abnormal levels of phosphorylation and aggregation do indeed occur in non-AD tauopathies, however, both appear pronouncedly increased in AD, becoming a distinctive characteristic of AD pathology.
Recent Clinical Implications of FAPI
Authors: Mahshid Kiani, Safura Jokar, Leila Hassanzadeh, Hossein Behnammanesh, Omid Bavi, Davood Beiki, Majid Assadi
Journal: Clinical Nuclear Medicine (2024)

The fibroblast activation protein (FAP) is a biomarker that is selectively overexpressed on cancer-associated fibroblasts (CAFs) in various types of tumoral tissues and some nonmalignant diseases, including fibrosis, arthritis, cardiovascular, and metabolic diseases. FAP plays a critical role in tumor microenvironment through facilitating proliferation, invasion, angiogenesis, immunosuppression, and drug resistance. Recent studies reveal that FAP might be regarded as a promising target for cancer diagnosis and treatment. FAP-targeted imaging modalities, especially PET, have shown high sensitivity and specificity in detecting FAP-expressing tumors. FAP-targeted imaging can potentially enhance tumor detection, staging, and monitoring of treatment response, and facilitate the development of personalized treatment strategies. This study provides a comprehensive view of FAP and its function in the pathophysiology of cancer and nonmalignant diseases. It also will discuss the characteristics of radiolabeled FAP inhibitors, particularly those based on small molecules, their recent clinical implications in imaging and therapy, and the associated clinical challenges with them. In addition, we present the results of imaging and biodistribution radiotracer 68 Ga-FAPI-46 in patients with nonmalignant diseases, including interstitial lung disease, primary biliary cirrhosis, and myocardial infarction, who were referred to our department. Our results show that cardiac FAP-targeted imaging can provide a novel potential biomarker for managing left ventricle remodeling. Moreover, this study has been organized and presented in a manner that offers a comprehensive overview of the current status and prospects of FAPI inhibitors in the diagnosis and treatment of diseases.
A Rare Atypical Intrapericardial Prostate Adenocarcinoma Metastasis With 68Ga-PSMA-11 PET/CT
Authors: Aurélie Moreau, Mayeul Tabutin, Amine Bouhamama, David Kryza
Journal: Clinical Nuclear Medicine (2024)

Abstract We report the case of an 88-year-old man recently diagnosed with prostate cancer. The patient underwent a 68 Ga–prostate-specific membrane antigen–11 PET/CT for staging assessment. This examination revealed intense and expected uptake in the primary prostate cancer, widespread metastatic involvement including typical adenopathy and bone metastasis, and a less common pulmonary lymphangitic carcinomatosis. Most notably, we discovered a rare intrapericardial metastasis, which is an atypical site for metastasis in general and particularly for prostate adenocarcinoma.
An artificial intelligence-assisted system versus white light endoscopy alone for adenoma detection in individuals with Lynch syndrome (TIMELY): an international, multicentre, randomised controlled trial
Authors: Oswaldo Ortiz, Maria Daca-Alvarez, Liseth Rivero-Sanchez, Antonio Z Gimeno-Garcia, Marta Carrillo-Palau, Victoria Alvarez, Alejandro Ledo-Rodriguez, Luigi Ricciardiello, Chiera Pierantoni, Robert Hüneburg, Jacob Nattermann, Raf Bisschops, Sabine Tejpar, Alain Huerta, Faust Riu Pons, Cristina Alvarez-Urturi, Jorge López-Vicente, Alessandro Repici, Cessare Hassan, Lucia Cid, Giulia Martina Cavestro, Cristina Romero-Mascarell, Jordi Gordillo, Ignasi Puig, Maite Herraiz, Maite Betes, Jesús Herrero, Rodrigo Jover, Francesc Balaguer, Maria Pellisé
Journal: The Lancet. Gastroenterology & hepatology (2024)
Phenotypic and genotypic risk factors for invasive melanoma by sex and body site
Authors: Catherine M Olsen, Nirmala Pandeya, Rachel E Neale, Matthew H Law, David C Whiteman
Journal: British Journal of Dermatology (2024)

Abstract Background Cutaneous melanoma incidence varies consistently across body sites between men and women, but the underlying causes of these differences remain unclear. To date, no prospective studies have examined risk factors for melanoma separately for men and women according to body site. Objectives We aimed to examine the association between identified constitutional, genetic and environmental risk factors for invasive melanoma of different body sites among men and women. Methods We compared the association between constitutional, genetic and environmental risk factors for invasive melanoma on different body sites separately for men and women in a population-based prospective cohort study of 17 774 men and 21 070 women aged between 40 and 69 years who were residents of Queensland, Australia at baseline in 2011. Participants were followed until December 2021. We examined risk factors including hair colour, tanning ability, naevus density and proxies for high cumulative sun exposure, all self-reported at baseline. We also examined polygenic risk score (PRS) derived from summary statistics from a melanoma genome-wide association study meta-analysis. Results During a median 10.4 years of follow-up, 455 men and 331 women developed an incident invasive melanoma; the mean age at diagnosis was lower in women than in men (62.6 vs. 65.0 years). The most common body site was the trunk in men (45.1%), and the upper (36.8%) and lower limbs (27.4%) in women. High naevus density and proxy measures of high cumulative sun exposure were similarly associated with melanoma at all sites in men and women. In both sexes, high genetic risk was associated with melanoma on all body sites except the head and neck. We observed differences between men and women in the association between PRS and melanoma of the trunk [highest vs. lowest tertile of PRS: hazard ratio (HR) 2.78, 95% confidence interval (CI) 1.64–4.69 for men; HR 1.55, 95% CI 0.63–3.80 for women] and nonsignificant but large differences for the lower limbs (HR 5.25, 95% CI 1.80–15.27 for men; HR 1.75, 95% CI 0.88–3.47 for women). Conclusions While there are a number of potential explanations for these findings, this raises the possibility that genetic factors other than those related to pigmentation and naevus phenotypes may play a role in the predilection for melanoma to arise on different sites in men and women.