tbuckley/cabot-search huggingface dataset:
Therapeutic relevance of eosinophilic inflammation and airway viral interactions in severe asthma
Authors: Hitasha Rupani, William W. Busse, Peter H. Howarth, Philip G. Bardin, Ian M. Adcock, Satoshi Konno, David J. Jackson
Journal: Allergy (2024)

The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. Biologic therapies targeting key molecules implicated in eosinophil-associated pathologies have been approved in patients with severe asthma and, therefore, the effects of depleting eosinophils in a clinical setting are of considerable interest. This review discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. We also highlight the significant reduction in asthma exacerbations seen with biologic therapies, even at the height of the respiratory virus season. Furthermore, we discuss the implications of these findings in relation to the role of eosinophils in inflammation and antiviral responses to respiratory virus infection in asthma.
Macrophage plasticity: signaling pathways, tissue repair, and regeneration
Authors: Lingfeng Yan, Jue Wang, Xin Cai, Yih‐Cherng Liou, Han‐Ming Shen, Jianlei Hao, Canhua Huang, Gaoxing Luo, Weifeng He
Journal: MedComm (2024)

Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt to diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) and alternatively activated (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay of signaling pathways, transcriptional regulators, and epigenetic modifications orchestrates macrophage polarization, allowing them to respond to various stimuli dynamically. Here, we provide a comprehensive overview of the signaling cascades governing macrophage plasticity, focusing on the roles of Toll‐like receptors, signal transducer and activator of transcription proteins, nuclear receptors, and microRNAs. We also discuss the emerging concepts of macrophage metabolic reprogramming and trained immunity, contributing to their functional adaptability. Macrophage plasticity plays a pivotal role in tissue repair and regeneration, with macrophages coordinating inflammation, angiogenesis, and matrix remodeling to restore tissue homeostasis. By harnessing the potential of macrophage plasticity, novel therapeutic strategies targeting macrophage polarization could be developed for various diseases, including chronic wounds, fibrotic disorders, and inflammatory conditions. Ultimately, a deeper understanding of the molecular mechanisms underpinning macrophage plasticity will pave the way for innovative regenerative medicine and tissue engineering approaches.
Epithelial–mesenchymal plasticity in cancer: signaling pathways and therapeutic targets
Authors: Xiangpeng Wang, Xiaoxia Xue, Mingshi Pang, Liuchunyang Yu, Jinxiu Qian, Xiaoyu Li, Meng Tian, Aiping Lyu, Cheng Lu, Yuanyan Liu
Journal: MedComm (2024)

Abstract Currently, cancer is still a leading cause of human death globally. Tumor deterioration comprises multiple events including metastasis, therapeutic resistance and immune evasion, all of which are tightly related to the phenotypic plasticity especially epithelial–mesenchymal plasticity (EMP). Tumor cells with EMP are manifest in three states as epithelial–mesenchymal transition (EMT), partial EMT, and mesenchymal–epithelial transition, which orchestrate the phenotypic switch and heterogeneity of tumor cells via transcriptional regulation and a series of signaling pathways, including transforming growth factor‐β, Wnt/β‐catenin, and Notch. However, due to the complicated nature of EMP, the diverse process of EMP is still not fully understood. In this review, we systematically conclude the biological background, regulating mechanisms of EMP as well as the role of EMP in therapy response. We also summarize a range of small molecule inhibitors, immune‐related therapeutic approaches, and combination therapies that have been developed to target EMP for the outstanding role of EMP‐driven tumor deterioration. Additionally, we explore the potential technique for EMP‐based tumor mechanistic investigation and therapeutic research, which may burst vigorous prospects. Overall, we elucidate the multifaceted aspects of EMP in tumor progression and suggest a promising direction of cancer treatment based on targeting EMP.
Renal cancer: signaling pathways and advances in targeted therapies
Authors: Aimin Jiang, Jinxin Li, Ziwei He, Ying Liu, Kun Qiao, Yu Fang, Le Qu, Peng Luo, Anqi Lin, Linhui Wang
Journal: MedComm (2024)

Abstract Renal cancer is a highlyheterogeneous malignancy characterized by rising global incidence and mortalityrates. The complex interplay and dysregulation of multiple signaling pathways,including von Hippel–Lindau ( VHL )/hypoxia‐inducible factor ( HIF ), phosphoinositide 3‐kinase ( PI3K )/protein kinase B ( AKT )/mammalian target of rapamycin ( mTOR ), Hippo–yes‐associated protein ( YAP ), Wnt/ß‐catenin, cyclic adenosine monophosphate ( cAMP ), and hepatocyte growth factor ( HGF )/ c‐Met , contribute to theinitiation and progression of renal cancer. Although surgical resection is thestandard treatment for localized renal cancer, recurrence and metastasiscontinue to pose significant challenges. Advanced renal cancer is associatedwith a poor prognosis, and current therapies, such as targeted agents andimmunotherapies, have limitations. This review presents a comprehensiveoverview of the molecular mechanisms underlying aberrant signaling pathways inrenal cancer, emphasizing their intricate crosstalk and synergisticinteractions. We discuss recent advancements in targeted therapies, includingtyrosine kinase inhibitors, and immunotherapies, such as checkpoint inhibitors.Moreover, we underscore the importance of multiomics approaches and networkanalysis in elucidating the complex regulatory networks governing renal cancerpathogenesis. By integrating cutting‐edge research and clinical insights, this review contributesto the development of innovative diagnostic and therapeutic strategies, whichhave the potential to improve risk stratification, precision medicine, andultimately, patient outcomes in renal cancer.
Super-enhancer omics in stem cell
Authors: Hongying Ma, Jian Qu, Zicheng Pang, Jian Luo, Min Yan, Weixin Xu, Haihui Zhuang, Linxin Liu, Qiang Qu
Journal: Molecular Cancer (2024)

Abstract The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of “super-enhancer omics”, inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.
Characterizing atrial fibrillation in patients with and without heart failure across the ejection fraction spectrum: Incidence, prevalence, and treatment strategies
Authors: Valeria Valente, Giulia Ferrannini, Lina Benson, Paolo Gatti, Federica Guidetti, Michael Melin, Frieder Braunschweig, Cecilia Linde, Ulf Dahlström, Lars H. Lund, Marat Fudim, Gianluigi Savarese
Journal: European Journal of Heart Failure (2024)

Abstract Aims Heart failure (HF) and atrial fibrillation (AF) often coexist. We explored AF incidence, prevalence, and treatment strategies in patients with versus without HF across the ejection fraction (EF) spectrum. Methods and results We analysed patients with HF from the Swedish HF Registry (1 December 2005–31 December 2021), matched 1:1 by sex, age, and county of residence to patients without HF from Statistics Sweden. Two study cohorts were derived (i) to assess AF prevalence and treatments, and (ii) to evaluate AF incidence and related predictors. Overall, 195 106 patients were considered, 50% of them with HF (of whom 54% with HF with reduced [HFrEF], 23% mildly reduced [HFmrEF], and 23% with preserved EF [HFpEF]). From 2006 to 2021, AF prevalence increased in both patients with (57% to 58%) and without HF (8% to 11%). HF patients, particularly if with HFrEF, were more likely receiving AF treatments than those without HF. Over time, antiarrhythmic use decreased, while rate control drugs and oral anticoagulant use, and AF‐related procedures increased, regardless of HF and EF. During a median follow‐up of 3.7 years, in 86 210 patients without AF, incident AF risk was two‐fold higher in HF versus non‐HF (hazard ratio [HR] 2.76, 95% confidence interval [CI] 2.45–3.12), highest in HFpEF (HR 3.12, 95% CI 2.65–3.67) versus HFrEF (HR 2.68, 95% CI 2.34–3.06) and HFmrEF (HR 2.53, 95% CI 2.17–2.94). Conclusions Atrial fibrillation prevalence, anticoagulant use, and AF‐related procedures increased over time regardless of HF, with HF patients more likely receiving AF treatments. In HF, despite higher AF prevalence and incidence in HFpEF, AF treatment use remained modest, calling for further implementation.
Synergistic Strategies of Biomolecular Transport Technologies in Transdermal Healthcare Systems
Authors: Jieun Han, Yi‐Jeong Choi, Seung‐Kyun Kang
Journal: Advanced Healthcare Materials (2024)

Abstract Transdermal healthcare systems have gained significant attention for their painless and convenient drug administration, as well as their ability to detect biomarkers promptly. However, the skin barrier limits the candidates of biomolecules that can be transported, and reliance on simple diffusion poses a bottleneck for personalized diagnosis and treatment. Consequently, recent advancements in transdermal transport technologies have evolved toward active methods based on external energy sources. Multiple combinations of these technologies have also shown promise for increasing therapeutic effectiveness and diagnostic accuracy as delivery efficiency is maximized. Furthermore, wearable healthcare platforms are being developed in diverse aspects for patient convenience, safety, and on‐demand treatment. Herein, a comprehensive overview of active transdermal delivery technologies is provided, highlighting the combination‐based diagnostics, therapeutics, and theragnostics, along with the latest trends in platform advancements. This offers insights into the potential applications of next‐generation wearable transdermal medical devices for personalized autonomous healthcare.
Oral Piwi‐Interacting RNA Delivery Mediated by Green Tea‐Derived Exosome‐Like Nanovesicles for the Treatment of Aortic Dissection
Authors: Yan Liu, Hongzhao Qi, Jinbao Zong, Min Li, Yanyan Yang, Xiaolu Li, Tianxiang Li, Jae Youl Cho, Tao Yu
Journal: Advanced Healthcare Materials (2024)

Abstract Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule‐targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi‐interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart‐apoptosis‐associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea‐derived plant exosome‐like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir‐HAAPIR‐nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir‐HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi‐interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle‐encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.
Progress Toward the Elimination of Hepatitis B and Hepatitis C in the Country of Georgia, April 2015–April 2024
Authors: Rania A. Tohme, Shaun Shadaker, Ekaterine Adamia, Irma Khonelidze, Ketevan Stvilia, Vladimer Getia, Maia Tsereteli, Maia Alkhazashvili, Akaki Abutidze, Maia Butsashvili, Maka Gogia, Nancy Glass, Sophia Surguladze, Irina Tskhomelidze Schumacher, Tamar Gabunia
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Hepatitis B and hepatitis C are leading causes of cirrhosis and liver cancer and caused 1.3 million deaths worldwide in 2022.Hepatitis B is preventable with vaccination, and hepatitis C is curable with direct-acting antivirals.In 2015, in collaboration with CDC and other partners, Georgia, a country at the intersection of Europe and Asia, launched a hepatitis C elimination program to reduce the prevalence of chronic hepatitis C; at that time, the prevalence was 5.4%, more than five times the global average of 1.0%.In 2016, the World Health Assembly endorsed a goal for the elimination of viral hepatitis as a public health problem by 2030.In 2024, 89% of the Georgian adult population have received screening for hepatitis C, 83% of persons with current chronic HCV infection have received a diagnosis, and 86% of those with diagnosed hepatitis C have started treatment.During 2015-2023, vaccination coverage with the hepatitis B birth dose and with 3 doses of hepatitis B vaccine among infants exceeded 90% for most years.In 2021, the prevalence of hepatitis B surface antigen was 0.03% among children and adolescents aged 5-17 years and 2.7% among adults.Georgia has demonstrated substantial progress toward hepatitis B and hepatitis C elimination.Using lessons from the hepatitis C elimination program, scale-up of screening and treatment for hepatitis B among adults would prevent further viral hepatitis-associated morbidity and mortality in Georgia and would accelerate progress toward hepatitis B and hepatitis C elimination by 2030.
<i>Notes from the Field:</i> Detection of Medetomidine Among Patients Evaluated in Emergency Departments for Suspected Opioid Overdoses — Missouri, Colorado, and Pennsylvania, September 2020–December 2023
Authors: Evan S. Schwarz, Jennie Buchanan, Kim Aldy, Joshua Shulman, Alex Krotulski, Sara Walton, Barry Logan, Paul Wax, Sharan Campleman, Jeffrey Brent, Rachel Culbreth, Alex F. Manini
Journal: MMWR Morbidity and Mortality Weekly Report (2024)
Lead Poisoning in a Mother and Her Four Children Using a Traditional Eye Cosmetic — New York City, 2012–2023
Authors: Paromita Hore, Slavenka Sedlar, Jacqueline Ehrlich
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Even low levels of lead in children's blood are associated with developmental delays, difficulty learning, and behavioral issues.Adults are also vulnerable to the detrimental health effects of lead exposure.The New York City (NYC) Department of Health and Mental Hygiene receives blood lead test results for NYC residents and conducts investigations of lead poisoning cases.Blood lead testing of a child aged 4 years in 2012 led to the discovery of blood lead levels above the CDC blood lead reference value of 3.5 μg/dL in the child as well as four other family members over a period of 11 years, including the child's mother and three younger siblings born during 2012-2016.The only potential source of lead exposure identified for all cases was the use of surma, a traditional eye cosmetic, which was found to contain 390,000 ppm lead.The cases in this report highlight the challenges of risk communication when deeply ingrained cultural practices, such as the use of surma, persist despite health warnings.Moreover, they highlight the intergenerational nature of such practices and the need for comprehensive family follow-up once a member is identified as being at risk.These products continue to be available globally, even in places such as the United States where sales are prohibited.Multistakeholder efforts involving local and global engagement could promote reformulation of these products at the countries of origin to eliminate lead as an ingredient.
<i>QuickStats:</i> Percentage* of Adult Day Services Centers† That Use Any Telehealth,§ by U.S. Census Bureau Region — United States, 2022¶
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

NationalNortheast Midwest South West PercentageRegion * With 95% CIs indicated by error bars.† Adult day services centers are state-regulated and further defined at https://www.cdc.gov/nchs/data/npals/NPALS-2022-survey-method-doc.pdf.§ Based on a "yes" response by adult day services center directors to the following question: "In the last 12 months, did this center use any of the following types of telehealth tools to assess, diagnose, monitor, or treat participants?a. Telephone audio; b.Videoconference software with audio (e.g.Zoom, Webex, FaceTime)." ¶ Adult day services centers with missing data or with directors who responded "don't know" were excluded.In 2022, 46% of U.S. adult day services centers used any telehealth tools.Approximately one half of centers in the Northeast and West used any telehealth, compared with approximately one third of centers in the Midwest and South.
Hybrid hair follicle stem cell extracellular vesicles co-delivering finasteride and gold nanoparticles for androgenetic alopecia treatment
Authors: Xiaochuan Wu, Xiajie Huang, Qi Zhu, Jucong Zhang, Jiahao Hu, Yanling Song, Yuchan You, Luwen Zhu, Jingyi Lu, Xinyi Xu, Minjiang Chen, Wei Wang, Xiuzu Song, Jiansong Ji, Yongzhong Du
Journal: Journal of Controlled Release (2024)
AI-enhanced reconstruction of the 12-lead electrocardiogram via 3-leads with accurate clinical assessment
Authors: Federico Mason, Amitabh C. Pandey, Matteo Gadaleta, Eric J. Topol, Evan D. Muse, Giorgio Quer
Journal: npj Digital Medicine (2024)

Abstract The 12-lead electrocardiogram (ECG) is an integral component to the diagnosis of a multitude of cardiovascular conditions. It is performed using a complex set of skin surface electrodes, limiting its use outside traditional clinical settings. We developed an artificial intelligence algorithm, trained over 600,000 clinically acquired ECGs, to explore whether fewer leads as input are sufficient to reconstruct a 12-lead ECG. Two limb leads (I and II) and one precordial lead (V3) were required to generate a reconstructed 12-lead ECG highly correlated with the original ECG. An automatic algorithm for detection of ECG features consistent with acute myocardial infarction (MI) performed similarly for original and reconstructed ECGs (AUC = 0.95). When interpreted by cardiologists, reconstructed ECGs achieved an accuracy of 81.4 ± 5.0% in identifying ECG features of ST-segment elevation MI, comparable with the original 12-lead ECGs (accuracy 84.6 ± 4.6%). These results will impact development efforts to innovate ECG acquisition methods with simplified tools in non-specialized settings.
The burden of diabetes-associated multiple long-term conditions on years of life spent and lost
Authors: Edward W. Gregg, Adrian Pratt, Alex Owens, Emma Barron, Rupert Dunbar-Rees, Eirion T. Slade, Nasrin Hafezparast, Chirag Bakhai, Paul Chappell, Victoria Cornelius, Desmond G. Johnston, Jacqueline Mathews, Jason Pickles, Ellie Bragan Turner, Gary Wainman, Kate Roberts, Kamlesh Khunti, Jonathan Valabhji
Journal: Nature Medicine (2024)

Abstract Diabetes mellitus is a central driver of multiple long-term conditions (MLTCs), but population-based studies have not clearly characterized the burden across the life course. We estimated the age of onset, years of life spent and loss associated with diabetes-related MLTCs among 46 million English adults. We found that morbidity patterns extend beyond classic diabetes complications and accelerate the onset of severe MLTCs by 20 years earlier in life in women and 15 years earlier in men. By the age of 50 years, one-third of those with diabetes have at least three conditions, spend &gt;20 years with them and die 11 years earlier than the general population. Each additional condition at the age of 50 years is associated with four fewer years of life. Hypertension, depression, cancer and coronary heart disease contribute heavily to MLTCs in older age and create the greatest community-level burden on years spent (813 to 3,908 years per 1,000 individuals) and lost (900 to 1,417 years per 1,000 individuals). However, in younger adulthood, depression, severe mental illness, learning disabilities, alcohol dependence and asthma have larger roles, and when they occur, all except alcohol dependence were associated with long periods of life spent (11–14 years) and all except asthma associated with many years of life lost (11–15 years). These findings provide a baseline for population monitoring and underscore the need to prioritize effective prevention and management approaches.
Retraction Note: AMLnet, A deep-learning pipeline for the differential diagnosis of acute myeloid leukemia from bone marrow smears
Authors: Zebin Yu, Jianhu Li, Xiang Wen, Yingli Han, Penglei Jiang, Meng Zhu, Minmin Wang, Xiangli Gao, Dan Shen, Ting Zhang, Shuqi Zhao, Yijing Zhu, Jixiang Tong, Shuchong Yuan, HongHu Zhu, He Huang, Pengxu Qian
Journal: Journal of Hematology & Oncology (2024)