tbuckley/cabot-search huggingface dataset:
Elucidating allergic reaction mechanisms in response to <scp>SARS</scp>‐<scp>CoV</scp>‐2 <scp>mRNA</scp> vaccination in adults
Authors: Mihir M. Shah, Janice A. Layhadi, Dennis E. Hourcade, William T. Fulton, Tiak Ju Tan, Diane Dunham, Iris Chang, Monica S. Vel, Andrea Fernandes, Alexandra S. Lee, James Liu, Prabhu S. Arunachalam, Stephen J. Galli, Scott D. Boyd, Bali Pulendran, Mark M. Davis, Ruth O'Hara, Helen Park, Lynne M. Mitchell, Antonina Akk, Alexander Patterson, Maya R. Jerath, Jennifer M. Monroy, Zhen Ren, Peggy L. Kendall, Stephen R. Durham, Aleksandra Fedina, Bernhard F. Gibbs, Ioana Agache, Sharon Chinthrajah, Sayantani B. Sindher, Anja Heider, Cezmi A. Akdis, Mohamed H. Shamji, Christine T. N. Pham, Kari C. Nadeau
Journal: Allergy (2024)

Abstract Background During the COVID‐19 pandemic, novel nanoparticle‐based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. Methods To understand COVID‐19 vaccine‐mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. Results Vaccine‐mediated complement activation correlated with anti‐polyethelyne glycol (PEG) IgG (but not IgM) levels while anti‐PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine‐mediated basophil activation. Single‐cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll‐like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL‐13 and IL‐1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. Conclusion These findings provide insights into the mechanisms underlying allergic reactions to COVID‐19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.
CircARCN1 aggravates atherosclerosis by regulating HuR-mediated USP31 mRNA in macrophages
Authors: Zhicheng Pan, Jialan Lv, Liding Zhao, Kaidi Xing, Runze Ye, Yuesheng Zhang, Siyuan Chen, Peng Yang, Hailong Yu, Yangkai Lin, Ruobing Li, Dongfei Wang, Juan Fang, Yang Dong, Jianpeng Sheng, Xiaolin Wang, Ge Shan, Shan Zhang, Hongqiang Cheng, Qingbo Xu, Xiaogang Guo
Journal: Cardiovascular Research (2024)

Abstract Aims Circular RNAs (circRNAs) are considered important regulators of biological processes, but their impact on atherosclerosis development, a key factor in coronary artery disease (CAD), has not been fully elucidated. We aimed to investigate their potential use in patients with CAD and the pathogenesis of atherosclerosis. Methods and results Patients with stable angina (SA) or acute coronary syndrome (ACS) and controls were selected for transcriptomic screening and quantification of circRNAs in blood cells. We stained carotid plaque samples for circRNAs and performed gain- and loss-of-function studies in vitro. Western blots, protein interaction analysis, and molecular approaches were used to perform the mechanistic study. ApoE−/− mouse models were employed in functional studies with adeno-associated virus-mediated genetic intervention. We demonstrated elevated circARCN1 expression in peripheral blood mononuclear cells from patients with SA or ACS, especially in those with ACS. Furthermore, higher circARCN1 levels were associated with a higher risk of developing SA and ACS. We also observed elevated expression of circARCN1 in carotid artery plaques. Further analysis indicated that circARCN1 was mainly expressed in monocytes and macrophages, which was also confirmed in atherosclerotic plaques. Our in vitro studies provided evidence that circARCN1 affected the interaction between HuR and ubiquitin-specific peptidase 31 (USP31) mRNA, resulting in attenuated USP31-mediated NF-κB activation. Interestingly, macrophage accumulation and inflammation in atherosclerotic plaques were markedly decreased when circARCN1 was knocked down with adeno-associated virus in macrophages of ApoE−/− mice, while circARCN1 overexpression in the model exacerbated atherosclerotic lesions. Conclusions Our findings provide solid evidence macrophagic-expressed circARCN1 plays a role in atherosclerosis development by regulating HuR-mediated USP31 mRNA stability and NF-κB activation, suggesting that circARCN1 may serve as a factor for atherosclerotic lesion formation.
Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells
Authors: Feng Tian, Yuyan Cheng, Songlin Zhou, Qianbin Wang, Aboozar Monavarfeshani, Kun Gao, Weiqian Jiang, Riki Kawaguchi, Qing Wang, Mingjun Tang, Ryan Donahue, Huyan Meng, Yu Zhang, Anne Jacobi, Wenjun Yan, Jiani Yin, Xinyi Cai, Zhiyun Yang, Shane Hegarty, Joanna Stanicka, Phillip Dmitriev, Daniel Taub, Junjie Zhu, Clifford J. Woolf, Joshua R. Sanes, Daniel H. Geschwind, Zhigang He
Journal: Neuron (2024)
Application of 3D printing on the design and development of pharmaceutical oral dosage forms
Authors: Nicola Paccione, Víctor Guarnizo-Herrero, Murugan Ramalingam, Eider Larrarte, José Luis Pedraz
Journal: Journal of Controlled Release (2024)

3D printing technologies confer an unparalleled degree of control over the material distribution on the structures they produce, which has led them to become an extremely attractive research topic in pharmaceutical dosage form development, especially for the design of personalized treatments. With fine tuning in material selection and careful design, these technologies allow to tailor not only the amount of drug administered but the biopharmaceutical behaviour of the dosage forms as well. While fused deposition modelling (FDM) is still the most studied 3D printing technology in this area, others are gaining more relevance, which has led to many new and exciting dosage forms developed during 2022 and 2023. Considering that these technologies, in time, will join the current manufacturing methods and with the ever-increasing knowledge on this topic, our review aims to explore the advantages and limitations of 3D printing technologies employed in the design and development of pharmaceutical oral dosage forms, giving special focus to the most important aspects governing the resulting drug release profiles.
PARP4 interacts with hnRNPM to regulate splicing during lung cancer progression
Authors: Yi Fei Lee, Cheryl Zi Jin Phua, Ju Yuan, Bin Zhang, May Yin Lee, Srinivasaraghavan Kannan, Yui Hei Jasper Chiu, Casslynn Wei Qian Koh, Choon Kong Yap, Edwin Kok Hao Lim, Jianbin Chen, Yuhua Lim, Jane Jia Hui Lee, Anders Jacobsen Skanderup, Zhenxun Wang, Weiwei Zhai, Nguan Soon Tan, Chandra S. Verma, Yvonne Tay, Daniel Shao Weng Tan, Wai Leong Tam
Journal: Genome Medicine (2024)

The identification of cancer driver genes from sequencing data has been crucial in deepening our understanding of tumor biology and expanding targeted therapy options. However, apart from the most commonly altered genes, the mechanisms underlying the contribution of other mutations to cancer acquisition remain understudied. Leveraging on our whole-exome sequencing of the largest Asian lung adenocarcinoma (LUAD) cohort (n = 302), we now functionally assess the mechanistic role of a novel driver, PARP4.
Nano-enabled regulation of DNA damage in tumor cells to enhance neoantigen-based pancreatic cancer immunotherapy
Authors: Jilong Wang, Chenghu Wu, Yiran Wang, Yecheng Shen, Kerui Wu, Yikai Shi, Tianshou Cao, Shanshan Yuan, Yuting Zhu, Yongheng Bai, Jinhai Huang, Yan Zhang, Junjie Deng
Journal: Biomaterials (2024)
Realizing precision medicine in chronic lymphocytic leukemia: Remaining challenges and potential opportunities
Authors: Kostas Stamatopoulos, Sarka Pavlova, Othman Al‐Sawaf, Thomas Chatzikonstantinou, Christina Karamanidou, Gianluca Gaidano, Florence Cymbalista, Arnon P. Kater, Andy Rawstron, Lydia Scarfò, Paolo Ghia, Richard Rosenquist
Journal: HemaSphere (2024)

Abstract Patients with chronic lymphocytic leukemia (CLL) exhibit diverse clinical outcomes. An expanding array of genetic tests is now employed to facilitate the identification of patients with high‐risk disease and inform treatment decisions. These tests encompass molecular cytogenetic analysis, focusing on recurrent chromosomal alterations, particularly del(17p). Additionally, sequencing is utilized to identify TP53 mutations and to determine the somatic hypermutation status of the immunoglobulin heavy variable gene. Concurrently, a swift advancement of targeted treatment has led to the implementation of novel strategies for patients with CLL, including kinase and BCL2 inhibitors. This review explores both current and emerging diagnostic tests aimed at identifying high‐risk patients who should benefit from targeted therapies. We outline existing treatment paradigms, emphasizing the importance of matching the right treatment to the right patient beyond genetic stratification, considering the crucial balance between safety and efficacy. We also take into consideration the practical and logistical issues when choosing a management strategy for each individual patient. Furthermore, we delve into the mechanisms underlying therapy resistance and stress the relevance of monitoring measurable residual disease to guide treatment decisions. Finally, we underscore the necessity of aggregating real‐world data, adopting a global perspective, and ensuring patient engagement. Taken together, we argue that precision medicine is not the mere application of precision diagnostics and accessibility of precision therapies in CLL but encompasses various aspects of the patient journey (e.g., lifestyle exposures and comorbidities) and their preferences toward achieving true personalized medicine for patients with CLL.
Extracellular Matrix‐Surrogate Advanced Functional Composite Biomaterials for Tissue Repair and Regeneration
Authors: Milad Vahidi, Amin S. Rizkalla, Kibret Mequanint
Journal: Advanced Healthcare Materials (2024)

Abstract Native tissues, comprising multiple cell types and extracellular matrix components, are inherently composites. Mimicking the intricate structure, functionality, and dynamic properties of native composite tissues represents a significant frontier in biomaterials science and tissue engineering research. Biomimetic composite biomaterials combine the benefits of different components, such as polymers, ceramics, metals, and biomolecules, to create tissue‐template materials that closely simulate the structure and functionality of native tissues. While the design of composite biomaterials and their in vitro testing are frequently reviewed, there is a considerable gap in whole animal studies that provides insight into the progress toward clinical translation. Herein, we provide an insightful critical review of advanced composite biomaterials applicable in several tissues. The incorporation of bioactive cues and signaling molecules into composite biomaterials to mimic the native microenvironment is discussed. Strategies for the spatiotemporal release of growth factors, cytokines, and extracellular matrix proteins are elucidated, highlighting their role in guiding cellular behavior, promoting tissue regeneration, and modulating immune responses. Advanced composite biomaterials design challenges, such as achieving optimal mechanical properties, improving long‐term stability, and integrating multifunctionality into composite biomaterials and future directions, are discussed. We believe that this manuscript provides the reader with a timely perspective on composite biomaterials.
Genome-wide association meta-analysis identifies five loci associated with postpartum hemorrhage
Authors: David Westergaard, Valgerdur Steinthorsdottir, Lilja Stefansdottir, Palle Duun Rohde, Xiaoping Wu, Frank Geller, Jaakko Tyrmi, Aki S Havulinna, Pol Solé-Navais, Christopher Flatley, Sisse Rye Ostrowski, Ole Birger Pedersen, Christian Erikstrup, Erik Sørensen, Christina Mikkelsen, Mie Topholm Bruun, Bitten Aagaard Jensen, Thorsten Brodersen, Henrik Ullum, Per Magnus, Ole A Andreassen, Pål R Njolstad, Astrid Marie Kolte, Lone Krebs, Mette Nyegaard, Thomas Folkmann Hansen, Bjarke Feenstra, Mark Daly, Cecilia M Lindgren, Gudmar Thorleifsson, Olafur A Stefansson, Gardar Sveinbjornsson, Daniel F Gudbjartsson, Unnur Thorsteinsdottir, Karina Banasik, Bo Jacobsson, Triin Laisk, Hannele Laivuori, Kari Stefansson, Søren Brunak, Henriette Svarre Nielsen
Journal: Nature Genetics (2024)

Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severe impact on maternal-fetal health. We identified five genetic loci linked to PPH in a meta-analysis. Functional annotation analysis indicated candidate genes HAND2, TBX3 and RAP2C/FRMD7 at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors. There were strong genetic correlations with birth weight, gestational duration and uterine fibroids. Bleeding in early pregnancy yielded no genome-wide association signals but showed strong genetic correlation with various human traits, suggesting a potentially complex, polygenic etiology. Our results suggest that PPH is related to progesterone signaling dysregulation, whereas early bleeding is a complex trait associated with underlying health and possibly socioeconomic status and may include genetic factors that have not yet been identified.
Mitochondrial DNA mosaicism in normal human somatic cells
Authors: Jisong An, Chang Hyun Nam, Ryul Kim, Yunah Lee, Hyein Won, Seongyeol Park, Won Hee Lee, Hansol Park, Christopher J. Yoon, Yohan An, Jie-Hyun Kim, Jong Kwan Jun, Jeong Mo Bae, Eui-Cheol Shin, Bun Kim, Yong Jun Cha, Hyun Woo Kwon, Ji Won Oh, Jee Yoon Park, Min Jung Kim, Young Seok Ju
Journal: Nature Genetics (2024)

Abstract Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of ≳0.3%. While the majority of these variants were unique to individual clones, suggesting stochastic acquisition with age, 409 variants (6%) were shared across multiple embryonic lineages, indicating their origin from heteroplasmy in fertilized eggs. The mutational spectrum exhibited replication-strand bias, implicating mtDNA replication as a major mutational process. We evaluated the mtDNA mutation rate (5.0 × 10 −8 per base pair) and a turnover frequency of 10–20 per year, which are fundamental components shaping the landscape of mtDNA mosaicism over a lifetime. The expansion of mtDNA-truncating mutations toward homoplasmy was substantially suppressed. Our findings provide comprehensive insights into the origins, dynamics and functional consequences of mtDNA mosaicism in human somatic cells.
Mitochondrial Control of Proteasomal Psmb5 Drives the Differentiation of Tissue‐Resident Memory T Cells in Patients with Rheumatoid Arthritis
Authors: Tong Wu, Danhua Su, Lei Zhang, Ting Liu, Qianliang Wang, Chenchu Yan, Mengdi Liu, Huiyan Ji, Jiaxin Lei, Ming Zheng, Zhenke Wen
Journal: Arthritis & Rheumatology (2024)

To explore T cell-intrinsic mechanisms underpinning the mal-differentiation of tissue-resident memory T (Trm) cells in patients with rheumatoid arthritis (RA).
Radiation therapy for locally advanced pancreatic adenocarcinoma: a therapeutic option which should not be forgotten. Letter to the Editor regarding: “Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up” by Huguet et al.
Authors: F. Huguet, C. Bouchart, A.M.E. Bruynzeel, M.A. Hawkins, S. Mukherjee, J.J. Nuyttens, O. Riou, M. Scorsetti, E. Versteijne, M. Loi, V. Vendrely
Journal: Annals of Oncology (2024)
Reply to the Letter to the Editor ‘Radiation therapy for locally advanced pancreatic adenocarcinoma: a therapeutic option which should not be forgotten’ (in regard to “Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up”) by Huguet et al.
Authors: T. Conroy, K. Haustermans, M. Ducreux
Journal: Annals of Oncology (2024)
Efficacy of botulinum toxin in male androgenetic alopecia: A triple-blind, randomized clinical trial
Authors: Daniel Fernandes Melo, Paulo Müller-Ramos, Rita Fernanda Cortez de Almeida, Carla Jorge Machado, Sidney Frattini, André Luiz Vairo Donda, Daniela Alves Pereira Antelo, Carlos Baptista Barcaui
Journal: Journal of the American Academy of Dermatology (2024)
Association of fatty liver index with sudden cardiac arrest in young adults
Authors: Joo Hee Jeong, Yun Gi Kim, Kyung-Do Han, Seung-Young Roh, Hyoung Seok Lee, Yun Young Choi, Sun Young Yim, Jaemin Shim, Young-Hoon Kim, Jong-Il Choi
Journal: Metabolism (2024)
Analysis of dermatology away rotations available on the Visiting Student Learning Opportunities database and implications for diversity in dermatology: A national cross-sectional study
Authors: Zahna Bigham, Ruhi Kanwar, Sofia Milosavljevic, Nana Ama Adjei-Frimpong, Carlos Salazar, Vinod E. Nambudiri
Journal: Journal of the American Academy of Dermatology (2024)
Lipidomic Risk Score to Enhance Cardiovascular Risk Stratification for Primary Prevention
Authors: Jingqin Wu, Corey Giles, Aleksandar Dakic, Habtamu B Beyene, Kevin Huynh, Tingting Wang, Thomas Meikle, Gavriel Olshansky, Agus Salim, Thy Duong, Gerald F Watts, Joseph Hung, Jennie Hui, Gemma Cadby, John Beilby, John Blangero, Eric K Moses, Jonathan E Shaw, Dianna J Magliano, Dantong Zhu, Jean Y Yang, Stuart M Grieve, Andrew Wilson, Clara K Chow, Stephen T Vernon, Michael P Gray, Gemma A Figtree, Melinda J Carrington, Mike Inouye, Thomas H Marwick, Peter J Meikle
Journal: Journal of the American College of Cardiology (2024)

Accurate risk stratification is vital for primary prevention of cardiovascular disease (CVD). However, traditional tools such as the Framingham Risk Score (FRS) may underperform within the diverse intermediate-risk group, which includes individuals requiring distinct management strategies. This study aimed to develop a lipidomic-enhanced risk score (LRS), specifically targeting risk prediction and reclassification within the intermediate group, benchmarked against the FRS. The LRS was developed via a machine learning workflow using ridge regression on the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab; n = 10,339). It was externally validated with the Busselton Health Study (n = 4,492), and its predictive utility for coronary artery calcium scoring (CACS)–based outcomes was independently validated in the BioHEART cohort (n = 994). LRS significantly improved discrimination metrics for the intermediate-risk group in both AusDiab and Busselton Health Study cohorts (all P < 0.001), increasing the area under the curve for CVD events by 0.114 (95% CI: 0.1123-0.1157) and 0.077 (95% CI: 0.0755-0.0785), with a net reclassification improvement of 0.36 (95% CI: 0.21-0.51) and 0.33 (95% CI: 0.15-0.49), respectively. For CACS-based outcomes in BioHEART, LRS achieved a significant area under the curve improvement of 0.02 over the FRS (0.76 vs 0.74; P < 1.0 × 10-5). A simplified, clinically applicable version of LRS was also created that had comparable performance to the original LRS. LRS, augmenting the FRS, presents potential to improve intermediate-risk stratification and to predict atherosclerotic markers using a simple blood test, suitable for clinical application. This could facilitate the triage of individuals for noninvasive imaging such as CACS, fostering precision medicine in CVD prevention and management.
Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents
Authors: Yu-Jung Jenny Wei, Almut G. Winterstein, Siegfried Schmidt, Roger B. Fillingim, Michael J. Daniels, Steven T. DeKosky, Stephan Schmidt
Journal: Annals of Internal Medicine (2024)

Limited evidence exists on the safety of pharmacokinetic interactions of cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids with antidepressants among older nursing home (NH) residents.
Shifting Trends in the Indication of Glucagon-like Peptide-1 Receptor Agonist Prescriptions: A Nationwide Analysis
Authors: Yee Hui Yeo, Ali Rezaie, Tina Yi-Jin Hsieh, Xiaoqin Hu, Srinivas Gaddam, Kevin Sheng-Kai Ma, Ghada Mohamed, Gin Yi Lee, Pin-Chia Huang, Rabindra Watson, Ghada Mohamed, Gin Yi Lee, Pin-Chia Huang, Rabindra Watson
Journal: Annals of Internal Medicine (2024)
Association of Adverse Clinical Outcomes With Peri-Infarct Ischemia Detected by Stress Cardiac Magnetic Imaging
Authors: Benedikt Bernhard, Yin Ge, Panagiotis Antiochos, Bobak Heydari, Sabeeh Islam, Natalia Sanchez Santiuste, Kevin E Steel, Scott Bingham, J Ronald Mikolich, Andrew E Arai, W Patricia Bandettini, Amit R Patel, Sujata M Shanbhag, Afshin Farzaneh-Far, John F Heitner, Chetan Shenoy, Steve W Leung, Jorge A Gonzalez, Subha V Raman, Victor A Ferrari, Dipan J Shah, Jeanette Schulz-Menger, Matthias Stuber, Orlando P Simonetti, Raymond Y Kwong
Journal: Journal of the American College of Cardiology (2024)
Mortality After Procedural or Spontaneous Myocardial Infarction
Authors: Alessandro Spirito, Samantha Sartori, Anoop N Koshy, Yihan Feng, Birgit Vogel, Usman Baber, Joseph Sweeny, Sahil Khera, Annapoorna S Kini, Stephan Windecker, George Dangas, Samin K Sharma, Roxana Mehran
Journal: Journal of the American College of Cardiology (2024)
Regulatory Framework for Cannabis: A Position Paper From the American College of Physicians
Authors: Ryan Crowley, Katelan Cline, David Hilden, Micah Beachy, David Hilden, Micah Beachy, Jan K. Carney, Haidn Foster, Austin Hoeg, Matthew Hollon, Cynthia Jumper, Selvam Joseph Mascarenhas, Ankita Sagar, Jenny R. Silberger, Jamar Slocum, Michael Tan, Elham A. Yousef
Journal: Annals of Internal Medicine (2024)

Cannabis, also known as marijuana, is the dried flowers, stems, seeds, and leaves of the
Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance
Authors: María-Victoria Mateos, Joaquin Martínez-López, Paula Rodriguez Otero, Verónica González-Calle, Marta Sonia Gonzalez, Albert Oriol, Norma C. Gutiérrez, Rafael Ríos-Tamayo, Laura Rosiñol, Miguel Angel Alvarez Rivas, Joan Bargay, Ana Pilar Gonzalez-Rodriguez, Adrián Alegre, Fernando Escalante, María Belén Iñigo Rodríguez, Javier De La Rubia, Ana Isabel Teruel, Felipe de Arriba, Luis Palomera, Miguel T. Hernández, Javier Lopez Jiménez, Marta Reinoso-Segura, Aránzazu García Mateo, Enrique M. Ocio, Bruno Paiva, Noemi Puig, M. Teresa Cedena, Joan Bladé, Juan Jose Lahuerta, Jesus F. San-Miguel
Journal: Journal of Clinical Oncology (2024)

Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). We conducted this trial with curative intention using a treatment approach employed for newly diagnosed patients with MM.