3714 research outputs found
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Considerations before the application of 5-hydroxymethylation levels of long non-coding RNAs for non-invasive cancer diagnosis
No full textPrevious studies have suggested that aberrant 5-hydroxymethylcytosines (5hmC) modifications are related to cancer pathobiology. Genome-wide profiling 5hmC in circulating cell-free DNA (cfDNA) using the highly sensitive chemical labeling-based 5hmC-Seal technique has been demonstrated to have the potential to be a robust epigenomic tool for cancer biomarker discovery. Prior studies have mostly focused on cfDNA-derived 5hmC-Seal data summarized in well-annotated genic features (e.g., gene bodies) or unbiased bins. Zhou et al. recently proposed long non-coding RNAs (lncRNAs) as an alternative molecular target for biomarker discovery using publicly available 5hmC-Seal data. Considering its potential clinical impact, we would like to comment on Zhou et al. and advocate more serious consideration of critical issues such as the availability of clinical information and technical variables, especially when performing secondary analysis using publicly available data, with the aim of improving data transparency and translatability
Engineered induced-pluripotent stem cell derived monocyte extracellular vesicles alter inflammation in HIV humanized mice
No full textAim: A peripheral inflammatory response can drive neuroinflammation in a number of infections including human immunodeficiency virus (HIV). Monocyte/macrophage (M/Mφ) activation is a hallmark of acute HIV infection and a source of chronic inflammation in a subset of HIV-infected individuals. We sought to decrease peripheral inflammation and M/Mφ transmigration after HIV infection by engineering extracellular vesicles (EV) to antagonize a microRNA (miR) associated with inflammation. We hypothesized that induced pluripotent stem cell (iPSC)-derived monocyte EVs (mEVs), engineered to contain an antagomir to miR-155 (αmiR mEV) would target monocyte inflammation and influence neuroinflammation in an HIV-infected humanized mice. Methods: mEVs were characterized by tetraspanins, nanoparticle tracking analysis, electron microscopy, and their preferential entry into circulating monocytes as well as testing for endogenous selected miRNAs. HIV-infected humanized mice were treated with control or antagomir155 mEVs. Plasma viral load was measured plus activation markers on lymphocytes and monocytes and the number of macrophages in the brain was quantified. Results: mEVs preferentially entered peripheral monocytes. HIV infection increased C-C chemokine receptor type 5 (CCR5) and major histocompatibility complex, class II, DR (HLA-DR) expression on T cells and monocytes. Treatments with mEVs did not decrease plasma HIV viral load; however, mEVs alone resulted in a decrease in %CCR5+ and %HLA-DR+ on T cells and an increase in %CCR5+ monocytes. αmiR mEVs decreased %CCR5 on M/Mφ. The mEV-treated HIV-infected mice did not show an increase in macrophage transmigration to the brain.Conclusion: mEVs alone caused an unexpected decrease in lymphocyte activation and increase in monocyte %CCR5; however, this did not translate to an increase in macrophage transmigration to the brain
Strategies to functionalize extracellular vesicles against HER2 for anticancer activity
No full textCell-secreted extracellular vesicles (EVs) are membranous particles highly heterogeneous in size and molecular cargo. Comprehensively, released EV sub-populations can show a wide range and selection of different protein, RNA, and lipid species, complementing cell communication signals. Recently, EVs represent a new source for developing targeted delivery systems. EVs are stable in biofluids, intrinsically biocompatible with low immunogenicity, and capable of transferring cargo molecules into “recipient” cells. The immune-mediated recognition represents a popular approach to functionalize and direct EVs towards receptor-positive cell populations. The human epidermal growth factor receptor 2 (HER2, also known as neu or ERBB2) is a tyrosine kinase of clinical relevance, targeted by several available antibodies, and a model receptor used to test the biodistribution and anticancer activity of bioformulations, including EVs. Here, we focus on recent strategies adopted for EV functionalization with fusion ligands able to recognize HER2, covering the enhanced expression of membrane-fusion proteins in “EV-donor” cells as well as post-isolation EV-surface modifications
Operative difficulty in laparoscopic cholecystectomy: considering the role of machine learning platforms in clinical practice
No full textAim: Computer vision is a subset of machine learning (ML) technology that allows automated analysis of large operative video datasets. The aim of this study was to use a commercially available ML-driven platform to evaluate a subjective grading of operative difficulty in laparoscopic cholecystectomy (LC). Methods: Patients undergoing LC prospectively consented, and their operations were recorded. The intra-operative findings were prospectively graded (1-4) based on intraoperative gallbladder appearance assessments. Deidentified videos were uploaded to Touch SurgeryTMand run through the platform’s algorithm, providing automated analytics including the total operative length and operative phase length. The rate of critical view of safety (CVS) achievement was also included in the analysis. Results: 206 LC were included. 27 LC were excluded due to incomplete video recording and were therefore not amenable to the final data analysis. Grade 1 and 2 patients had significantly shorter operative time than grade 3 and 4 patients [17min and 53s (IQR 15min and 24s- 21min and 38s) vs. 25 min and 49s (IQR 20min and 12s-38min and 38s) (P < 0.010)]. The operative phases for each step were significantly longer in patients with gallbladders graded 3 or 4 compared to those patients graded 1 or 2 (P < 0.043). The CVS was achieved in 94% of grade 1 patients, 88% of grade 2 patients, 85% of grade 3 patients and 73% of grade 4 patients (P = 0.177).Conclusion: Increased operative time and decreased ability to achieve the CVS with more difficult intraoperative findings supports the utility of the proposed grading system. ML in surgery is a nascent field, but this study demonstrates the potential of commercially available platforms for use in operative analytics, documentation, audit and training of future surgeons
Recent developments in understanding brain aging: sex differences, mechanisms, and implications in diseases
No full textExemplified by the disproportionate cases of Alzheimer’s disease among women, many diseases show considerable sexual disparity in the aging process. Given that such a sex bias varies significantly in different neurological conditions, considering sex differences is necessary for the diagnosis as well as the treatment of neurological disorders. However, currently, relatively few studies have specifically focused on sex differences in brain aging or the general aging process, which has prevented the development of precision medicine for these sex-different diseases. Here, we summarize age-related disparities relating to cognitive function and dysfunction for males and females from human cross-sectional and longitudinal studies. By discussing potential anatomical and physiological bases underlying such differences, we highlight the importance of sex for aging studies in this review, which may hopefully shed light on understanding the precise causes of different brain diseases
Chronic obstructive pulmonary disease (COPD) and metabolic fatty liver syndromes: a dangerous but neglected liaison
No full textThis perspective article aims at addressing the potential commonalities associated with chronic obstructive pulmonary disease (COPD) and the two metabolic fatty liver syndromes: nonalcoholic fatty liver disease (NAFLD) and metabolic (associated) fatty liver disease (MAFLD). To this end, we briefly review the definitions and burdens of COPD and NAFLD and highlight the differences in the diagnostic criteria of NAFLD and MAFLD. We also critically discuss the recent line of research trying to identify an association between COPD and NAFLD. Moreover, among the chief co-morbidities of COPD patients, we identify significant six that exert a major impact on the natural course of COPD: major cardiovascular events, cardiac arrhythmias, metabolic syndrome, obstructive sleep apnea, osteoporosis, and psychodepression. The potential role of NAFLD in each of these COPD co-morbidities is accurately examined based on published studies. We conclude that both COPD and NAFLD/MAFLD are heterogeneous systemic syndromes. While the complex mechanistic links underlying the association of NAFLD/MAFLD with COPD and its co-morbidities remain to be fully elucidated, we highlight that the diagnosis of metabolic fatty liver syndromes in patients with COPD might be clinically relevant, as it might allow identifying a subset of COPD individuals who, being at risk of severe clinical outcomes, would need more comprehensive treatment approaches
Solidification for solid-state lithium batteries with high energy density and long cycle life
No full textConventional lithium-ion batteries with inflammable organic liquid electrolytes are required to make a breakthrough regarding their bottlenecks of energy density and safety, as demanded by the ever-increasing development of electric vehicles and grids. In this context, solid-state lithium batteries (SSLBs), which replace liquid electrolytes with solid counterparts, have become a popular research topic due to their excellent potential in the realization of improved energy density and safety. However, in practice, the energy density of SSLBs is limited by the cathode mass loading, electrolyte thickness and anode stability. Moreover, the crucial interfacial issues related to the rigid and heterogeneous solid-solid contacts between the electrolytes and electrodes, including inhomogeneous local potential distributions, sluggish ion transport, side reactions, space charge barriers and stability degradation, severely deteriorate the cycle life of SSLBs. Solidification, which converts a liquid into a solid inside a solid battery, represents a powerful tool to overcome the aforementioned obstacles. The liquid precursors fully wet the interfaces and infiltrate the electrodes, followed by in-situ conformal solidification under certain conditions for the all-in-one construction of cells with highly conducting, closely contacted and sustainable electrode/electrolyte interfaces, thereby enabling high energy density and long cycle life. Therefore, in this review, we address the research progress regarding the latest strategies toward the solidification of the electrolyte layers and the interfaces between the electrodes and electrolytes. The critical challenges and future research directions are proposed for the solidification strategies in SSLBs from both science and engineering perspectives
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