tbuckley/cabot-search huggingface dataset:
Hydrogel Activation of Mincle Receptors for Tumor Cell Processing: A Novel Approach in Cancer Immunotherapy
Authors: Jiake Lin, Yuemin Zhou, Chen Li, Benke Li, Haibin Hao, Fengchao Tian, Huixin Li, Zhenyu Liu, Guangchuan Wang, Xing-Can Shen, Ruikang Tang, Xiaoyu Wang
Journal: Biomaterials (2024)
Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization
Authors: Yongguo Xiang, Zhu Qiu, Yuanfu Ding, Miaomiao Du, Ning Gao, Huijie Cao, Hangjia Zuo, Hong Cheng, Xiang Gao, Shijie Zheng, Wenjuan Wan, Xiaobei Huang, Ke Hu
Journal: Journal of Controlled Release (2024)

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin β1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.
Chemotherapy-Induced Peripheral Neuropathy in Patients With Gastroesophageal Cancer
Authors: Merel J.M. van Velzen, Marieke Pape, Mirjam A.G. Sprangers, Jessy Joy van Kleef, Bianca Mostert, Laurens V. Beerepoot, Marije Slingerland, Elske C. Gootjes, Ronald Hoekstra, Lonneke V. van de Poll-Franse, Nadia Haj Mohammad, Hanneke W.M. van Laarhoven
Journal: Journal of the National Comprehensive Cancer Network (2024)

Chemotherapy for various stages of gastroesophageal cancer (GEC) is often neurotoxic. Chemotherapy-induced peripheral neuropathy (CIPN) impairs health-related quality of life (HRQoL). This study investigates the incidence and severity of CIPN and its association with HRQoL in patients with GEC.
Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccines
Authors: Jeffrey Schlom, Renee N Donahue, Claudia Palena, Sofia R Gameiro, James W Hodge, Duane H Hamilton, James L Gulley
Journal: Journal for ImmunoTherapy of Cancer (2024)

The development of vaccines, especially RNA-based, directed against patient-specific tumor neoepitopes is an active and productive area of cancer immunotherapy. Promising clinical results in melanoma and other solid tumor types are emerging. As with all cancer therapy modalities, neoepitope vaccine development and delivery also has some drawbacks, including the level of effort to develop a patient-specific product, accuracy of algorithms to predict neoepitopes, and with the exception of melanoma and some other tumor types, biopsies of metastatic lesions of solid tumors are often not available. We hypothesize that in some circumstances the use of rationally designed combinations of “off-the-shelf” agents may prove an additional path to enable the patient to produce his/her own “neoepitope vaccine” in situ. These combination therapies may consist of agents to activate a tumor-associated T-cell response, potentiate that response, reduce or eliminate immunosuppressive entities in the tumor microenvironment, and/or alter the phenotype of tumor cells to render them more susceptible to immune-mediated lysis. Examples are provided in both preclinical and clinical studies in which combinations of “off-the-shelf” agents lead to the generation of T cells directed against tumor-derived neoepitopes with consequent antitumor activity.
IL-4 acts on skin-derived dendritic cells to promote the TH2 response to cutaneous sensitization and the development of allergic skin inflammation
Authors: Juan Manuel Leyva-Castillo, Mrinmoy Das, Maria Strakosha, Alex McGurk, Emilie Artru, Christy Kam, Mohammed Alasharee, Duane R Wesemann, Michio Tomura, Hajime Karasuyama, Frank Brombacher, Raif S Geha
Journal: Journal of Allergy and Clinical Immunology (2024)
ENVIRONMENTAL FOOTPRINT AND MATERIAL COMPOSITION COMPARISON OF SINGLE-USE AND REUSABLE DUODENOSCOPES
Authors: Pedro López-Muñoz, Rubén Martín-Cabezuelo, Vicente Lorenzo-Zúñiga, Marina García-Castellanos, Guillermo Vilariño-Feltrer, Isabel Tort-Ausina, Alberto Campillo-Fernández, Vicente Pons Beltrán
Journal: Endoscopy (2024)

Infection outbreaks associated with contaminated reusable duodenoscopes (RUDs) have induced the development of novel single-use duodenoscopes (SUDs). This study aimed to analyze the material composition and life cycle assessment (LCA) of RUDs and SUDs to assess the sustainability of global and partial SUD implementation.
Ruxolitinib in treatment-naive or corticosteroid-refractory paediatric patients with chronic graft-versus-host disease (REACH5): interim analysis of a single-arm, multicentre, phase 2 study
Authors: Franco Locatelli, Bulent Antmen, Hyoung Jin Kang, Katsuyoshi Koh, Yoshiyuki Takahashi, Alphan Kupesiz, Maria Gabriela A Dias Matos, Yogi Chopra, Sunil Bhat, Ho Joon Im, Tayfun Güngör, Meng-Yao Lu, Tommaso Stefanelli, Christine Rosko, Annie St Pierre, Karin Burock, Yvonne Smith, Karen Sinclair, Cristina Diaz-de-Heredia
Journal: The Lancet Haematology (2024)
Rare Autosomal Trisomies and Adverse Perinatal Outcomes
Authors: Lore Lannoo, Kris Van Den Bogaert, Nathalie Brison, Luc Dehaspe, Eftychia Dimitriadou, Steffen Fieuws, Cindy Melotte, Armelle Duquenne, Ilse Parijs, Yves Sznajer, Leen Vancoillie, Hilde Vandecruys, Joris R. Vermeesch, Koen Devriendt, Kristel Van Calsteren
Journal: New England Journal of Medicine (2024)
Nirsevimab and Hospitalization for RSV Bronchiolitis
Authors: Zein Assad, Anne-Sophie Romain, Camille Aupiais, Mickaël Shum, Cécile Schrimpf, Mathie Lorrot, Harriet Corvol, Blandine Prevost, Charlène Ferrandiz, Anna Giolito, Zaba Valtuille, Matthieu Bendavid, Jérémie F. Cohen, Julie Toubiana, Loïc de Pontual, Camille F. Delande, Michael Levy, Perrine See, Robert Cohen, Corinne Levy, François Angoulvant, Léa Lenglart, Maud Gits-Muselli, Valérie Biran, Kadiatou Diallo, Oluwafunmilola Alemede, Mohamed M. El Hebil, Xavier Durrmeyer, Géraldine Labouret, Natacha Casanovas, Benjamin Hallak, Olympe Maréchal, Camille Jung, Camille Bréhin, Naïm Ouldali
Journal: New England Journal of Medicine (2024)

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear.
Oral Hedgehog Inhibitor, Vismodegib, for Locally Advanced Periorbital and Orbital Basal Cell Carcinoma
Authors: Edward J Wladis, Vinay K Aakalu, M Reza Vagefi, Jeremiah P Tao, Timothy J McCulley, Suzanne K Freitag, Jill A Foster, Stephen J Kim
Journal: Ophthalmology (2024)
Hepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation
Authors: Liangjun Zhang, Pingfan Xie, Mingqiao Li, Xiaoxun Zhang, Shuke Fei, Nan Zhao, Ling Li, Qiaoling Xie, Ziqian Xu, Wan Tang, Guanyu Zhu, Zhixian Zhu, Zuzhi Xu, Jianwei Li, Chengcheng Zhang, James L. Boyer, Wensheng Chen, Shi-Ying Cai, Qiong Pan, Jin Chai
Journal: Hepatology (2024)

Background and Aims: Inflammatory response is crucial for bile acid (BA)-induced cholestatic liver injury, but molecular mechanisms remain to be elucidated. Solute Carrier Family 35 Member C1 (SLC35C1) can transport Guanosine diphosphate-fucose into the Golgi to facilitate protein glycosylation. Its mutation leads to the deficiency of leukocyte adhesion and enhances inflammation in humans. However, little is known about its role in liver diseases. Approach and Results: Hepatic SLC35C1 mRNA transcripts and protein expression were significantly increased in patients with obstructive cholestasis and mouse models of cholestasis. Immunofluorescence revealed that the upregulated SLC35C1 expression mainly occurred in hepatocytes. Liver-specific ablation of Slc35c1 ( Slc35c1 cKO ) significantly aggravated liver injury in mouse models of cholestasis induced by bile duct ligation and 1% cholic acid–feeding, evidenced by increased liver necrosis, inflammation, fibrosis, and bile ductular proliferation. The Slc35c1 cKO increased hepatic chemokine Ccl2 and Cxcl2 expression and T cell, neutrophil, and F4/80 macrophage infiltration but did not affect the levels of serum and liver BA in mouse models of cholestasis. Liquid chromatography with tandem mass spectrometry analysis revealed that hepatic Slc35c1 deficiency substantially reduced the fucosylation of cell-cell adhesion protein CEACAM1 at N153. Mechanistically, cholestatic levels of conjugated BAs stimulated SLC35C1 expression by activating the STAT3 signaling to facilitate CEACAM1 fucosylation at N153, and deficiency in the fucosylation of CEACAM1 at N135 enhanced the BA-stimulated CCL2 and CXCL2 mRNA expression in primary mouse hepatocytes and Primary Liver Carcinoma/Poliomyelitis Research Foundation/5- ASBT cells. Conclusions: Elevated hepatic SLC35C1 expression attenuates cholestatic liver injury by enhancing CEACAM1 fucosylation to suppress CCL2 and CXCL2 expression and liver inflammation.
SLC10A5 deficiency causes hypercholanemia
Authors: Yuqing Xu, Yeqing Qian, Ying Yu, Xin Zhan, Pengzhen Jin, Jiawei Hong, Minyue Dong
Journal: Hepatology (2024)

Background and Aims: Solute Carrier Family 10 Member 5 (SLC10A5) is a member of SLC10, comprising transporters of bile acids, steroidal hormones, and other substrates, but its function remains unclear. The aim of the current investigation was to clarify its function in the metabolism of bile acid and hypercholanemia. Approach and Results: Whole-exome sequencing and Sanger sequencing were used to identify and confirm the variant in the subjects of hypercholanemia. CRISPR/Cas9-mediated genome engineering was used to establish the knockout and point mutation mice. Primary mouse hepatocytes were isolated, and cell lines were cultured. SLC10A5 was silenced by siRNA and overexpressed by wild-type and mutant plasmids. The fluorescent bile acid derivative was used for the bile acid uptake assay. Bile acids were assessed with ultra-performance liquid chromatography tandem mass spectrometry. A heterozygous variant SLC10A5 : c.994_995del (p.D332X) was identified in subjects with elevated total bile acid or altered bile acid profiles. Bile acids were increased in the serum and liver of knockout and point mutation mice. The expressions of FXR and SHP, regulators involved in the negative feedback of bile acid synthesis, were downregulated, while the bile acid synthesis genes CYP7A1 and CYP8B1 were upregulated in both gene-edited mice. Both the wild and mutant SLC10A5 proteins were localized on the plasma membrane. Knockdown, knockout, or targeted mutation of SLC10A5 led to the inhibition of bile acid uptake by cell lines and primary mouse hepatocytes. Conclusion: SLC10A5 is involved in the uptake of bile acid, and its deficiency causes hypercholanemia.
Endometriosis: recent advances that could accelerate diagnosis and improve care
Authors: Meaghan J. Griffiths, Andrew W. Horne, Douglas A. Gibson, Neil Roberts, Philippa T.K. Saunders
Journal: Trends in Molecular Medicine (2024)

Endometriosis is a common disorder associated with pain, gastrointestinal and urinary symptoms, infertility, and fatigue. It is defined by the presence of endometrial-like lesions found predominantly in the pelvis. Mechanisms that contribute to disease aetiology include changes in hormonal, inflammatory, and pain pathways. In this article, we focus on recent developments in imaging technologies, on our improved understanding of mechanisms contributing to infertility, on drug therapies that are in clinical trials, and on insights from studies on the gut that offer potential to support self-management strategies. We postulate that improvements in the quality of life of patients will be accelerated by reframing endometriosis as a multi-system disorder and learning from treatments targeting symptoms shared between endometriosis, neuroinflammatory, and gastrointestinal disorders.
Vascular restoration through local delivery of angiogenic factors stimulates bone regeneration in critical size defects
Authors: Liang Fang, Zhongting Liu, Cuicui Wang, Meng Shi, Yonghua He, Aiwu Lu, Xiaofei Li, Tiandao Li, Donghui Zhu, Bo Zhang, Jianjun Guan, Jie Shen
Journal: Bioactive Materials (2024)

Critical size bone defects represent a significant challenge worldwide, often leading to persistent pain and physical disability that profoundly impact patients' quality of life and mental well-being. To address the intricate and complex repair processes involved in these defects, we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue. Specifically, we observed a decrease in progenitor lineage cells and endothelial cells, coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue. Furthermore, our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects, notably influenced by reduction of Spp1 and Cxcl12 expression. This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells, underscoring its significance in the regeneration process. In response to these findings, we developed an innovative approach to enhance bone regeneration in critical size bone defects. Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12. This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo. To evaluate the efficacy of our approach, we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects. Our results demonstrated restored angiogenesis, accelerated bone regeneration, alleviated pain responses and improved mobility in treated mice.
Intestinal IL-33 promotes microbiota-derived trimethylamine N-oxide synthesis and drives metabolic dysfunction-associated steatotic liver disease progression by exerting dual regulation on HIF-1α
Authors: Suping Hai, Xitang Li, Erliang Xie, Wenhui Wu, Qiang Gao, Binghui Yu, Junjian Hu, Feiyang Xu, Xizhe Zheng, Bin-hao Zhang, Di Wu, Weiming Yan, Qin Ning, Xiaojing Wang
Journal: Hepatology (2024)

Background and Aims: Gut microbiota plays a prominent role in the pathogenesis of metabolic dysfunction–associated steatotic liver disease (MASLD). IL-33 is highly expressed at mucosal barrier sites and regulates intestinal homeostasis. Herein, we aimed to investigate the role and mechanism of intestinal IL-33 in MASLD. Approach and Results: In both humans and mice with MASLD, hepatic expression of IL-33 and its receptor suppression of tumorigenicity 2 (ST2) showed no significant change compared to controls, while serum soluble ST2 levels in humans, as well as intestinal IL-33 and ST2 expression in mice were significantly increased in MASLD. Deletion of global or intestinal IL-33 in mice alleviated metabolic disorders, inflammation, and fibrosis associated with MASLD by reducing intestinal barrier permeability and rectifying gut microbiota dysbiosis. Transplantation of gut microbiota from IL-33 deficiency mice prevented MASLD progression in wild-type mice. Moreover, IL-33 deficiency resulted in a decrease in the abundance of trimethylamine N -oxide–producing bacteria. Inhibition of trimethylamine N -oxide synthesis by 3,3-dimethyl-1-butanol mitigated hepatic oxidative stress in mice with MASLD. Nuclear IL-33 bound to hypoxia-inducible factor-1α and suppressed its activation, directly damaging the integrity of the intestinal barrier. Extracellular IL-33 destroyed the balance of intestinal Th1/Th17 and facilitated Th1 differentiation through the ST2- Hif1a - Tbx21 axis. Knockout of ST2 resulted in a diminished MASLD phenotype resembling that observed in IL-33 deficiency mice. Conclusions: Intestinal IL-33 enhanced gut microbiota–derived trimethylamine N -oxide synthesis and aggravated MASLD progression through dual regulation on hypoxia-inducible factor-1α. Targeting IL-33 and its associated microbiota may provide a potential therapeutic strategy for managing MASLD.
Management of Iron Deficiency in Heart Failure
Authors: Kazuhiko Kido, Craig J Beavers, Kenneth Dulnuan, Nadia Fida, Maya Guglin, Onyedika J Ilonze, Robert J Mentz, Nikhil Narang, Navin Rajagopalan, Bhavadharini Ramu, Yasar Sattar, George Sokos, Ewa A Jankowska
Journal: JACC Heart Failure (2024)
Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver
Authors: Yeping Huang, Fan Yu, Yue Ding, Hong Zhang, Xinyue Li, Xiao Wang, Xiaoshan Wu, Jie Xu, Liang Wang, Chenxu Tian, Min Jiang, Rong Zhang, Chenyan Yan, Yingxiang Song, Haijun Huang, Guangzhong Xu, Qiurong Ding, Xiao Ye, Yan Lu, Cheng Hu
Journal: Hepatology (2024)

Background and Aims: An imbalance in lipid metabolism is the main cause of NAFLD. While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of IL-22 protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain. Approach and Results: This study shows that hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly 3 beta-hydroxy-5-cholestenoic acid (3β HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3β HCA deposition through the activating transcription factor 3/oxysterol 7 alpha-hydroxylase axis. Notably, 3β HCA facilitates lipogenesis in mouse primary hepatocytes and human liver organoids by activating liver X receptor-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring oxysterol 7 alpha-hydroxylase or silencing hepatic activating transcription factor 3 reduces both hepatic 3β HCA and lipid contents in hepatocyte-specific Il22ra1 knockout mice. Conclusions: These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an activating transcription factor 3/oxysterol 7 alpha-hydroxylase-dependent manner and establish a link between 3β HCA and hepatic lipid homeostasis.
2-Dimensional Echocardiographic Global Longitudinal Strain With Artificial Intelligence Using Open Data From a UK-Wide Collaborative
Authors: Catherine C. Stowell, James P. Howard, Tiffany Ng, Graham D. Cole, Sanjeev Bhattacharyya, Jobanpreet Sehmi, Maysaa Alzetani, Camelia D. Demetrescu, Adam Hartley, Amar Singh, Arjun Ghosh, Kavitha Vimalesvaran, Kenneth Mangion, Ronak Rajani, Bushra S. Rana, Massoud Zolgharni, Darrel P. Francis, Matthew J. Shun-Shin
Journal: JACC. Cardiovascular imaging (2024)

Global longitudinal strain (GLS) is reported to be more reproducible and prognostic than ejection fraction. Automated, transparent methods may increase trust and uptake. The authors developed open machine-learning–based GLS methodology and validate it using multiexpert consensus from the Unity UK Echocardiography AI Collaborative. We trained a multi-image neural network (Unity-GLS) to identify annulus, apex, and endocardial curve on 6,819 apical 4-, 2-, and 3-chamber images. The external validation dataset comprised those 3 views from 100 echocardiograms. End-systolic and -diastolic frames were each labelled by 11 experts to form consensus tracings and points. They also ordered the echocardiograms by visual grading of longitudinal function. One expert calculated global strain using 2 proprietary packages. The median GLS, averaged across the 11 individual experts, was −16.1 (IQR: −19.3 to −12.5). Using each case's expert consensus measurement as the reference standard, individual expert measurements had a median absolute error of 2.00 GLS units. In comparison, the errors of the machine methods were: Unity-GLS 1.3, proprietary A 2.5, proprietary B 2.2. The correlations with the expert consensus values were for individual experts 0.85, Unity-GLS 0.91, proprietary A 0.73, proprietary B 0.79. Using the multiexpert visual ranking as the reference, individual expert strain measurements found a median rank correlation of 0.72, Unity-GLS 0.77, proprietary A 0.70, and proprietary B 0.74. Our open-source approach to calculating GLS agrees with experts' consensus as strongly as the individual expert measurements and proprietary machine solutions. The training data, code, and trained networks are freely available online.
Myocardial Characteristics, Cardiac Structure, and Cardiac Function in Systemic Light-Chain Amyloidosis
Authors: Olivier F Clerc, Sarah A M Cuddy, Michael Jerosch-Herold, Dominik C Benz, Ethan Katznelson, Jocelyn Canseco Neri, Alexandra Taylor, Marie Foley Kijewski, Giada Bianchi, Frederick L Ruberg, Marcelo F Di Carli, Ronglih Liao, Raymond Y Kwong, Rodney H Falk, Sharmila Dorbala
Journal: JACC. Cardiovascular imaging (2024)
Quantification and Timing of Epicardial Vasodilation by Sublingual Nitrates
Authors: Konstantinos Bermpeis, Fabian A. Pauwels, Michele Mattia Viscusi, Thabo Mahendiran, Dario T. Bertolone, Giulia Botti, Sofie Brouwers, Carlos Collet, Bernard de Bruyne, Takuya Mizukami
Journal: JACC. Cardiovascular imaging (2024)
Longitudinal Evaluation of Coronary Arteries and Myocardium in Breast Cancer Using Coronary Computed Tomographic Angiography
Authors: Chunrong Tu, Hesong Shen, Xiaoqin Li, Xing Wang, Zhiming Miao, Wei Deng, Renwei Liu, Xiaosong Lan, Huifang Chen, Jiuquan Zhang
Journal: JACC. Cardiovascular imaging (2024)
Detection of Cardiac Involvement in Eosinophilic Granulomatosis With Polyangiitis (EGPA) With Multiparametric Cardiovascular Magnetic Resonance (CMR)
Authors: Alina Hua, Agata Sularz, Peter Wheen, Vardah Alam, Ronak Rajani, Amedeo Chiribiri, David D'Cruz, Michelle Fernando, Jaideep Dhariwal, Alexandra M Nanzer, David J Jackson, Tevfik F Ismail
Journal: JACC. Cardiovascular imaging (2024)