tbuckley/cabot-search huggingface dataset:
Methylphenidate and Short-Term Cardiovascular Risk
Authors: Miguel Garcia-Argibay, Paul-Christian Bürkner, Paul Lichtenstein, Le Zhang, Brian M. D’Onofrio, Pontus Andell, Zheng Chang, Samuele Cortese, Henrik Larsson
Journal: JAMA Network Open (2024)

Importance There are concerns about the safety of medications for treatment of attention-deficit/hyperactivity disorder (ADHD), with mixed evidence on possible cardiovascular risk. Objective To assess whether short-term methylphenidate use is associated with risk of cardiovascular events. Design, Setting, and Participants This retrospective, population-based cohort study was based on national Swedish registry data. Participants were individuals with ADHD aged 12 to 60 years with dispensed prescriptions of methylphenidate between January 1, 2007, and June 30, 2012. Each person receiving methylphenidate (n = 26 710) was matched on birth date, sex, and county to up to 10 nonusers without ADHD (n = 225 672). Statistical analyses were performed from September 13, 2022, to May 16, 2023. Main Outcomes and Measures Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias, 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a bayesian within-individual design. Analyses were stratified by history of cardiovascular events. Results The cohort included 252 382 individuals (15 442 [57.8% men]; median age, 20 (IQR, 15-31) years). The overall incidence of cardiovascular events was 1.51 per 10 000 person-weeks (95% highest density interval [HDI], 1.35-1.69) for individuals receiving methylphenidate and 0.77 (95% HDI, 0.73-0.82) for the matched controls. Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41; 95% HDI, 1.09-1.88) compared with matched controls (IRR, 1.18; 95% HDI, 1.02-1.37). The posterior probabilities were 70% for at least a 10% increased risk of cardiovascular events in individuals receiving methylphenidate vs 49% in matched controls. No difference was found in this risk between individuals with and without a history of cardiovascular disease (IRR, 1.11; 95% HDI, 0.58-2.13). Conclusions and Relevance In this cohort study, individuals receiving methylphenidate had a small increased cardiovascular risk vs matched controls in the 6 months after treatment initiation. However, there was little evidence for an increased risk of 20% or higher and for differences in risk increase between people with and without a history of cardiovascular disease. Therefore, before treatment initiation, careful consideration of the risk-benefit trade-off of methylphenidate would be useful, regardless of cardiovascular history.
Determining individual glomerular proteinuria and periglomerular infiltration in a cleared murine kidney by a 3-dimensional fast marching algorithm
Authors: Alexander M.C. Böhner, Alexander Effland, Alice M. Jacob, Karin A.M. Böhner, Zeinab Abdullah, Sebastian Brähler, Ulrike I. Attenberger, Martin Rumpf, Christian Kurts
Journal: Kidney International (2024)

Three-dimensional imaging has advanced basic research and clinical medicine. However, limited resolution and imperfections of real-world 3D image material often preclude algorithmic image analysis. Here, we present a methodological framework for such imaging and analysis for functional and spatial relations in experimental nephritis. First, optical tissue clearing protocols were optimized to preserve fluorescence signals for light-sheet-fluorescence-microscopy and compensated attenuation effects using adjustable 3D correction fields. Next, we adapted the Fast — Marching — Algorithm to conduct backtracking in 3D environments and developed a tool to determine local concentrations of extractable objects. As a proof-of-concept application, we used this framework to determine in a glomerulonephritis model the individual proteinuria and periglomerular immune cell infiltration for all glomeruli of half a mouse kidney. A correlation between these parameters surprisingly did not support the intuitional assumption that the most inflamed glomeruli are the most proteinuric. Instead, the spatial density of adjacent glomeruli positively correlated with the proteinuria of a given glomerulus. Since proteinuric glomeruli appear clustered, this suggests that the exact location of a kidney biopsy may affect the observed severity of glomerular damage. Thus, our algorithmic pipeline described here allows analysis of various parameters of various organs composed of functional subunits, such as the kidney, and can theoretically be adapted to processing other image modalities.
In silico off-target profiling for enhanced drug safety assessment
Authors: Jin Liu, Yike Gui, Jingxin Rao, Jingjing Sun, Gang Wang, Qun Ren, Ning Qu, Buying Niu, Zhiyi Chen, Xia Sheng, Yitian Wang, Mingyue Zheng, Xutong Li
Journal: Acta Pharmaceutica Sinica B (2024)

Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through
Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases
Authors: Leticia Kawano-Dourado, Tejaswini Kulkarni, Christopher J Ryerson, Pilar Rivera-Ortega, Bruno Guedes Baldi, Nazia Chaudhuri, Manuela Funke-Chambour, Anna-Maria Hoffmann-Vold, Kerri A Johannson, Yet Hong Khor, Sydney B Montesi, Lucilla Piccari, Helmut Prosch, María Molina-Molina, Jacobo Sellares Torres, Iazsmin Bauer-Ventura, Sujeet Rajan, Joseph Jacob, Duncan Richards, Lisa G Spencer, Barbara Wendelberger, Tom Jensen, Melanie Quintana, Michael Kreuter, Anthony C Gordon, Fernando J Martinez, Naftali Kaminski, Victoria Cornelius, Roger Lewis, Wendy Adams, Gisli Jenkins
Journal: Thorax (2024)

Background Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD). Methods Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure. Results The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results. Conclusion By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.
Microplastics and Nanoplastics in Atheromas and Cardiovascular Events
Authors: Raffaele Marfella, Francesco Prattichizzo, Celestino Sardu, Gianluca Fulgenzi, Laura Graciotti, Tatiana Spadoni, Nunzia D'Onofrio, Lucia Scisciola, Rosalba La Grotta, Chiara Frigé, Valeria Pellegrini, Maurizio Municinò, Mario Siniscalchi, Fabio Spinetti, Gennaro Vigliotti, Carmine Vecchione, Albino Carrizzo, Giulio Accarino, Antonio Squillante, Giuseppe Spaziano, Davida Mirra, Renata Esposito, Simona Altieri, Giovanni Falco, Angelo Fenti, Simona Galoppo, Silvana Canzano, Ferdinando C Sasso, Giulia Matacchione, Fabiola Olivieri, Franca Ferraraccio, Iacopo Panarese, Pasquale Paolisso, Emanuele Barbato, Carmine Lubritto, Maria L Balestrieri, Ciro Mauro, Augusto E Caballero, Sanjay Rajagopalan, Antonio Ceriello, Bruno D'Agostino, Pasquale Iovino, Giuseppe Paolisso
Journal: New England Journal of Medicine (2024)

Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking.
Metabolic dysfunction–associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice guidance on nonalcoholic fatty liver disease
Authors: Fasiha Kanwal, Brent A. Neuschwander-Tetri, Rohit Loomba, Mary E. Rinella
Journal: Hepatology (2023)

This commentary discusses how clinicians and various stakeholders can utilize the recently published American Association for the Study of Liver Diseases nonalcoholic fatty liver disease (AASLD NAFLD) Practice Guidance in light of the change in the nomenclature to steatotic liver disease and its subcategories. The new terminologies explained in this commentary make it easier for the readers to interchangeably use metabolic dysfunction-associated steatotic liver disease (MASLD) in place of NAFLD and metabolic-dysfunction associated steatohepatitis (MASH) instead of nonalcoholic steatohepatitis (NASH), respectively, as they read the NAFLD Practice Guidance. The guidance document is relevant and can be utilized for the diagnosis, risk stratification, and management of patients with MASLD. This commentary serves as an accompanying article to the NAFLD Practice Guidance and helps it clinical application in the light of the new nomenclature.
Tumor-derived apoptotic extracellular vesicle-mediated intercellular communication promotes metastasis and stemness of lung adenocarcinoma
Authors: Xiaotian He, Yiyang Ma, Yingsheng Wen, Rusi Zhang, Dechang Zhao, Gongming Wang, Weidong Wang, Zirui Huang, Guangran Guo, Xuewen Zhang, Huayue Lin, Lanjun Zhang
Journal: Bioactive Materials (2024)

Apoptosis has long been recognized as a significant mechanism for inhibiting tumor formation, and a plethora of stimuli can induce apoptosis during the progression and treatment of tumors. Moreover, tumor-derived apoptotic extracellular vesicles (apoEVs) are inevitably phagocytosed by live tumor cells, promoting tumor heterogeneity. Understanding the mechanism by which apoEVs regulate tumor cells is imperative for enhancing our knowledge of tumor metastasis and recurrence. Herein, we conducted a series of in vivo and in vitro experiments, and we report that tumor-derived apoEVs promoted lung adenocarcinoma (LUAD) metastasis, self-renewal and chemoresistance. Mechanistically, we demonstrated that apoEVs facilitated tumor metastasis and stemness by initiating the epithelial-mesenchymal transition program and upregulating the transcription of the stem cell factor SOX2. In addition, we found that ALDH1A1, which was transported by apoEVs, activated the NF-κB signaling pathway by increasing aldehyde dehydrogenase enzyme activity in recipient tumor cells. Furthermore, targeting apoEVs-ALDH1A1 significantly abrogated these effects. Collectively, our findings elucidate a novel mechanism of apoEV-dependent intercellular communication between apoptotic tumor cells and live tumor cells that promotes the formation of cancer stem cell-like populations, and these findings reveal that apoEVs-ALDH1A1 may be a potential therapeutic target and biomarker for LUAD metastasis and recurrence.
Evolution of a restriction factor by domestication of a yeast retrotransposon
Authors: J Adam Hannon-Hatfield, Jingxuan Chen, Casey M Bergman, David J Garfinkel
Journal: Molecular Biology and Evolution (2024)

Abstract Transposable elements drive genome evolution in all branches of life. Transposable element insertions are often deleterious to their hosts and necessitate evolution of control mechanisms to limit their spread. The long terminal repeat retrotransposon Ty1 prime (Ty1′), a subfamily of the Ty1 family, is present in many Saccharomyces cerevisiae strains, but little is known about what controls its copy number. Here, we provide evidence that a novel gene from an exapted Ty1′ sequence, domesticated restriction of Ty1′ relic 2 (DRT2), encodes a restriction factor that inhibits Ty1′ movement. DRT2 arose through domestication of a Ty1′ GAG gene and contains the C-terminal domain of capsid, which in the related Ty1 canonical subfamily functions as a self-encoded restriction factor. Bioinformatic analysis reveals the widespread nature of DRT2, its evolutionary history, and pronounced structural variation at the Ty1′ relic 2 locus. Ty1′ retromobility analyses demonstrate DRT2 restriction factor functionality, and northern blot and RNA-seq analysis indicate that DRT2 is transcribed in multiple strains. Velocity cosedimentation profiles indicate an association between Drt2 and Ty1′ virus-like particles or assembly complexes. Chimeric Ty1′ elements containing DRT2 retain retromobility, suggesting an ancestral role of productive Gag C-terminal domain of capsid functionality is present in the sequence. Unlike Ty1 canonical, Ty1′ retromobility increases with copy number, suggesting that C-terminal domain of capsid–based restriction is not limited to the Ty1 canonical subfamily self-encoded restriction factor and drove the endogenization of DRT2. The discovery of an exapted Ty1′ restriction factor provides insight into the evolution of the Ty1 family, evolutionary hot-spots, and host–transposable element interactions.
Cellulase-assisted platelet-rich plasma release from nanofibrillated cellulose hydrogel enhances wound healing
Authors: Elle Koivunotko, Raili Koivuniemi, Julia Monola, Riina Harjumäki, Chris S. Pridgeon, Mari Madetoja, Jere Linden, Lauri Paasonen, Saara Laitinen, Marjo Yliperttula
Journal: Journal of Controlled Release (2024)

Platelet-rich plasma (PRP) is a source of growth factors, which are implicated in active tissue regeneration. However, after transplantation the efficacy of these bioactive compounds is often diminished due to rapid degradation and untargeted localization. For this reason, we evaluated the potential of nanofibrillated cellulose (NFC) hydrogel as a PRP carrier. NFC hydrogel is an animal-free biomaterial that, when doped with cellulase, can assist the release of PRP in a wound site. In this study, we examined the effects of 0.5% (m/v) NFC hydrogel formulations, including PRP and cellulase, on the migration and proliferation of skin cells via an in vitro scratch wound model. The suitability of the 0.8% NFC hydrogel formulations for accelerated wound healing and PRP carrying was studied in vitro in diffusion studies and in vivo in a full-thickness excisional wound model in SKH1 mice. None of the NFC hydrogel formulations with or without PRP and cellulase disturbed the normal cell behavior in vitro, and cellulase was successfully used to degrade NFC. NFC hydrogel slowed fibroblast migration rate in vitro. In vivo, NFC hydrogel treatment showed significantly enhanced re-epithelialization compared to control and supported collagen deposition. In addition, angiogenesis was significantly induced via PRP release after degrading NFC hydrogel with cellulase without abnormal host reaction. This study demonstrates the potential of NFC hydrogel with cellulase as a carrier for PRP with controlled release in future skin tissue engineering applications.
Dandelion-derived vesicles-laden hydrogel dressings capable of neutralizing Staphylococcus aureus exotoxins for the care of invasive wounds
Authors: Shenyu Tan, Zhuoya Liu, Minghui Cong, Xiaoqing Zhong, Yinping Mao, Mingjie Fan, Fangwen Jiao, Hongzhi Qiao
Journal: Journal of Controlled Release (2024)
Harnessing generative AI for glioma diagnosis: A step forward in neuro-oncologic imaging
Authors: Matthew D Lee, Rajan Jain
Journal: Neuro-Oncology (2024)

Journal Article Corrected proof Harnessing generative AI for glioma diagnosis: A step forward in neuro-oncologic imaging Get access Matthew D Lee, Matthew D Lee Department of Radiology, NYU Grossman School of Medicine, New York, New York, USA Corresponding Author: Matthew D. Lee, MD, Department of Radiology, NYU Grossman School of Medicine, 660 First Avenue, New York, NY 10016, USA (matthew.lee4@nyulangone.org). https://orcid.org/0000-0001-8816-1076 Search for other works by this author on: Oxford Academic PubMed Google Scholar Rajan Jain Rajan Jain Department of Radiology, NYU Grossman School of Medicine, New York, New York, USADepartment of Neurosurgery, NYU Grossman School of Medicine, New York, New York, USA https://orcid.org/0000-0002-4879-0457 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae043, https://doi.org/10.1093/neuonc/noae043 Published: 05 March 2024 Article history Published: 05 March 2024 Corrected and typeset: 28 March 2024
HIF1α/ATF3 partake in PGK1 K191/K192 succinylation by modulating P4HA1/succinate signaling in glioblastoma
Authors: Shixue Yang, Qi Zhan, Dongyuan Su, Xiaoteng Cui, Jixing Zhao, Qixue Wang, Biao Hong, Jiasheng Ju, Chunchao Cheng, Eryan Yang, Chunsheng Kang
Journal: Neuro-Oncology (2024)

Hypoxia is a pathological hallmark in most cancers, including glioblastoma (GBM). Hypoxic signaling activation and post-translational modification (PTM) of oncogenic proteins are well-studied in cancers. Accumulating studies indicate glycolytic enzyme PGK1 plays a crucial role in tumorigenesis, yet the underlying mechanisms remain unknown.
Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion
Authors: Xinggui Tian, Corina Vater, Deepak Bushan Raina, Lisa Findeisen, Lucas-Maximilian Matuszewski, Magnus Tägil, Lars Lidgren, Anja Winkler, Robert Gottwald, Niels Modler, Klaus-Dieter Schaser, Alexander C. Disch, Stefan Zwingenberger
Journal: Bioactive Materials (2024)

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this
Resmetirom for NASH: balancing promise and prudence
Authors: None The Lancet Gastroenterology & Hepatology
Journal: The Lancet. Gastroenterology & hepatology (2024)

Drug development for non-alcoholic steatohepatitis (NASH; also known as metabolic dysfunction-associated steatohepatitis, MASH) with fibrosis has been a far from straightforward endeavour. Obeticholic acid, an agonist of the farnesoid X receptor and the first drug to have supportive phase 3 histological data for fibrotic NASH, was refused FDA approval on the basis of modest treatment efficacy and safety issues, including drug-induced liver injury. Selonsertib (an inhibitor of apoptosis signal-regulating kinase 1), elafibranor (a PPAR α/δ agonist), and cenicriviroc (a chemokine receptor type 2 and 5 antagonist) all failed to show benefit in phase 3 trials.
Increasing Racial and Ethnic Disparities in Ambient Air Pollution-Attributable Morbidity and Mortality in the United States
Authors: Gaige Hunter Kerr, Aaron van Donkelaar, Randall V. Martin, Michael Brauer, Katrin Bukart, Sarah Wozniak, Daniel L. Goldberg, Susan C. Anenberg
Journal: Environmental Health Perspectives (2024)

Ambient nitrogen dioxide (NO2) and fine particulate matter with aerodynamic diameter ≤2.5μm (PM2.5) threaten public health in the US, and systemic racism has led to modern-day disparities in the distribution and associated health impacts of these pollutants.
Enhancing surgical outcomes in solid pseudopapillary neoplasm patients: unraveling the dynamics of gastrointestinal function and mental stress postoperatively
Authors: Guangwei Qing, Bo Wei, Yuanjian Yang
Journal: International Journal of Surgery (2024)

aDepartment of Psychiatry, Jiangxi Mental Hospital & Affiliated Mental Hospital of Nanchang University, Nanchang, Jiangxi 330029, China bThird Clinical Medical College, Nanchang University, Nanchang, Jiangxi 330006, China cNanchang City Key Laboratory of Biological Psychiatry, Jiangxi Provincial Clinical Research Center on Mental Disorders, Jiangxi Mental Hospital, Nanchang, Jiangxi 330029, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Department of Psychiatry, Jiangxi Mental Hospital & Affiliated Mental Hospital of Nanchang University, Nanchang 330029, Jiangxi, China. E-mail address: [email protected] (B. Wei). *Corresponding author. Address: Department of Psychiatry, Jiangxi Mental Hospital & Affiliated Mental Hospital of Nanchang University, Nanchang 330029, Jiangxi, China. E-mail address: [email protected] (Y. Yang). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
A commentary on ‘Organ preservation strategies after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer: a multicenter retrospective cohort study’
Authors: Yuanyuan Wang, Limei Zhan, Yongchao He, Xiaoyu Liu, Shasha Sun
Journal: International Journal of Surgery (2024)

aPulmonary and Critical Care Medicine, Yantai Yuhuangding Hospital,Yantai,Shandong, China bDisinfection Supply Center,Yantai Yuhuangding Hospital, Yantai, Shandong, China cOperating Room,Yantai Yuhuangding Hospital, Yantai, Shandong, China dDepartment of Emergency,Jinan Children's Hospital, Jinan, Shandong, China Co-authors: Yuanyuan Wang and Limei Zhan equally contributed to the article. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Pulmonary and Critical Care Medicine, Yantai Yuhuangding Hospital, Yantai, Shandong, China. E-mail address: [email protected] (S. Sun). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/