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Journal of Clinical Lipidology 2023Intraplaque neovascularization (IPN), a key feature of vulnerable carotid plaque, is associated with adverse cardiovascular (CV) events. Statin therapy has been shown to... (Review)
Review
Intraplaque neovascularization (IPN), a key feature of vulnerable carotid plaque, is associated with adverse cardiovascular (CV) events. Statin therapy has been shown to diminish and stabilize atherosclerotic plaque, but its effect on IPN is uncertain. This review investigated the effects of common pharmacologic anti-atherosclerotic therapies on carotid IPN. Electronic databases (MEDLINE, EMBASE and Cochrane Library) were searched from inception until July 13, 2022. Studies evaluating the effect of anti-atherosclerotic therapy on carotid IPN among adults with carotid atherosclerosis were included. Sixteen studies were eligible for inclusion. Contrast-enhanced ultrasound (CEUS) was the most common IPN assessment modality (n=8), followed by dynamic contrast-enhanced MRI (DCE-MRI) (n=4), excised plaque histology (n=3) and superb microvascular imaging (n=2). In fifteen studies, statins were the therapy of interest and one study assessed PCSK9 inhibitors. Among CEUS studies, baseline statin use was associated with a lower frequency of carotid IPN (median OR = 0.45). Prospective studies showed regression of IPN after 6-12 months of lipid-lowering therapy, with more regression observed in treated participants compared to untreated controls. Our findings suggest that lipid-lowering therapy with statins or PCSK9 inhibitors is associated with IPN regression. However, there was no correlation between change in IPN parameters and change in serum lipids and inflammatory markers in statin-treated participants, so it is unclear whether these factors are mediators in the observed IPN changes. Lastly, this review was limited by study heterogeneity and small sample sizes, so larger trials are needed to validate findings.
Topics: Adult; Humans; Proprotein Convertase 9; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Prospective Studies; PCSK9 Inhibitors; Contrast Media; Carotid Arteries; Carotid Artery Diseases; Plaque, Atherosclerotic; Ultrasonography; Lipids; Carotid Stenosis
PubMed: 37173161
DOI: 10.1016/j.jacl.2023.04.009 -
Antibiotics (Basel, Switzerland) Mar 2023The dissemination of -harboring (KPC-) is considered a serious public health problem. This study provides an overview of the epidemiology of these isolates to try to... (Review)
Review
The dissemination of -harboring (KPC-) is considered a serious public health problem. This study provides an overview of the epidemiology of these isolates to try to elucidate novel mobilization platforms that could contribute to their worldwide spread. A systematic review in PubMed and EMBASE was performed to find articles published up to June 2022. In addition, a search algorithm using NCBI databases was developed to identify sequences that contain possible mobilization platforms. After that, the sequences were filtered and pair-aligned to describe the genetic environment. We found 691 KPC- isolates belonging to 41 different sequence types and recovered from 14 countries. Although the gene is still mobilized by the transposon Tn, the non-Tn elements (NTE) were the most frequent. Our analysis allowed us to identify 25 different NTE, mainly belonging to the NTE-I, and a new type (proposed as IVa) was also observed. This is the first systematic review that consolidates information about the behavior of the acquisition in and the genetic platforms implied in its successful worldwide spread. Our results show high NTE prevalence in and an accelerated dynamic of unrelated clones. All information collected in this review was used to build an interactive online map.
PubMed: 37107020
DOI: 10.3390/antibiotics12040658 -
International Journal of Molecular... Mar 2023Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor...
Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment.
Topics: Humans; Ecosystem; Neuroma, Acoustic; Treatment Outcome; Tumor Burden; Tumor Microenvironment
PubMed: 37047498
DOI: 10.3390/ijms24076522 -
Frontiers in Plant Science 2023Drought stress is one of the most limiting factors for agriculture and ecosystem productivity. Climate change exacerbates this threat by inducing increasingly intense...
AIMS
Drought stress is one of the most limiting factors for agriculture and ecosystem productivity. Climate change exacerbates this threat by inducing increasingly intense and frequent drought events. Root plasticity during both drought and post-drought recovery is regarded as fundamental to understanding plant climate resilience and maximizing production. We mapped the different research areas and trends that focus on the role of roots in plant response to drought and rewatering and asked if important topics were overlooked.
METHODS
We performed a comprehensive bibliometric analysis based on journal articles indexed in the Web of Science platform from 1900-2022. We evaluated a) research areas and temporal evolution of keyword frequencies, b) temporal evolution and scientific mapping of the outputs over time, c) trends in the research topics analysis, d) marked journals and citation analysis, and e) competitive countries and dominant institutions to understand the temporal trends of root plasticity during both drought and recovery in the past 120 years.
RESULTS
Plant physiological factors, especially in the aboveground part (such as "photosynthesis", "gas-exchange", "abscisic-acid") in model plants Arabidopsis, crops such as wheat and maize, and trees were found to be the most popular study areas; they were also combined with other abiotic factors such as salinity, nitrogen, and climate change, while dynamic root growth and root system architecture responses received less attention. Co-occurrence network analysis showed that three clusters were classified for the keywords including 1) photosynthesis response; 2) physiological traits tolerance (e.g. abscisic acid); 3) root hydraulic transport. Thematically, themes evolved from classical agricultural and ecological research molecular physiology to root plasticity during drought and recovery. The most productive (number of publications) and cited countries and institutions were situated on drylands in the USA, China, and Australia. In the past decades, scientists approached the topic mostly from a soil-plant hydraulic perspective and strongly focused on aboveground physiological regulation, whereas the actual belowground processes seemed to have been the elephant in the room. There is a strong need for better investigation into root and rhizosphere traits during drought and recovery using novel root phenotyping methods and mathematical modeling.
PubMed: 37008469
DOI: 10.3389/fpls.2023.1084355 -
Anaesthesia, Critical Care & Pain... Jun 2023The efficacy of the short-axis out-of-plane (SA-OOP) approach with and without dynamic needle tip positioning (DNTP) remains unclear. This systematic review with network... (Meta-Analysis)
Meta-Analysis Review
Ultrasound-guided short-axis out-of-plane approach with or without dynamic needle tip positioning for arterial line insertion in children: A systematic review with network meta-analysis.
The efficacy of the short-axis out-of-plane (SA-OOP) approach with and without dynamic needle tip positioning (DNTP) remains unclear. This systematic review with network meta-analysis aimed to compare the success rate of arterial line insertion in children using the SA-OOP approach with and without DNTP and the palpation technique. We searched MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials. We included randomized controlled trials that compared two of the following techniques for arterial line insertion in children: (1) the ultrasound-guided SA-OOP approach with DNTP; (2) the ultrasound-guided SA-OOP approach without DNTP; and (3) the palpation technique. A network meta-analysis was performed. The outcomes were first-attempt and overall success rates. Eight studies were finally included in this network meta-analysis. The ultrasound-guided SA-OOP approach with DNTP was associated with increased first-attempt (relative risk RR = 3.45 [95% confidence interval (CI) 2.51-4.74]) and overall success rates (RR = 1.81 [1.41-2.32]) when compared with palpation. The same approach performed without DNTP was also associated with increased first-attempt (RR = 1.96 [1.59-2.42]) and overall success rates (RR = 1.25 [1.05-1.49]) when compared with palpation. The ultrasound-guided SA-OOP approach with DNTP was associated with increased first-attempt (RR = 1.76 [1.26-2.44]) and overall success rates (RR = 1.45 [1.10-1.91]) when compared with the same approach performed without DNTP. DNTP should be performed during the ultrasound-guided SA-OOP approach for arterial line insertion in children, as this can help increase first attempt and overall success rates.
Topics: Humans; Child; Ultrasonography, Interventional; Catheterization, Peripheral; Network Meta-Analysis; Radial Artery; Vascular Access Devices
PubMed: 36858256
DOI: 10.1016/j.accpm.2023.101206 -
PloS One 2023Sepsis-associated encephalopathy (SAE) is characterized by a diffuse cerebral dysfunction that accompanies sepsis in the absence of direct central nervous system... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis-associated encephalopathy (SAE) is characterized by a diffuse cerebral dysfunction that accompanies sepsis in the absence of direct central nervous system infection. The endothelial glycocalyx is a dynamic mesh containing heparan sulfate linked to proteoglycans and glycoproteins, including selectins and vascular/intercellular adhesion molecules (V/I-CAMs), which protects the endothelium while mediating mechano-signal transduction between the blood and vascular wall. During severe inflammatory states, components of the glycocalyx are shed into the circulation and can be detected in soluble forms. Currently, SAE remains a diagnosis of exclusion and limited information is available on the utility of glycocalyx-associated molecules as biomarkers for SAE. We set out to synthesize all available evidence on the association between circulating molecules released from the endothelial glycocalyx surface during sepsis and sepsis-associated encephalopathy.
METHODS
MEDLINE (PubMed) and EMBASE were searched since inception until May 2, 2022 to identify eligible studies. Any comparative observational study: i) evaluating the association between sepsis and cognitive decline and ii) providing information on level of circulating glycocalyx-associated molecules was eligible for inclusion.
RESULTS
Four case-control studies with 160 patients met the inclusion criteria. Meta-analysis of biomarkers ICAM-1 (SMD 0.41; 95% CI 0.05-0.76; p = 0.03; I2 = 50%) and VCAM-1 (SMD 0.55; 95% CI 0.12-0.98; p = 0.01; I2 = 82%) revealed higher pooled mean concentration in patients with SAE compared to the patients with sepsis alone. Single studies reported elevated levels of P-selectin (MD 0.80; 95% CI -17.77-19.37), E-selectin (MD 96.40; 95% Cl 37.90-154.90), heparan sulfate NS2S (MD 19.41; 95% CI 13.37-25.46), and heparan sulfate NS+NS2S+NS6S (MD 67.00; 95% CI 31.00-103.00) in patients with SAE compared to the patients with sepsis alone.
CONCLUSION
Plasma glycocalyx-associated molecules are elevated in SAE and may be useful for early identification of cognitive decline in sepsis patients.
Topics: Humans; Glycocalyx; Sepsis-Associated Encephalopathy; Sepsis; Cell Adhesion Molecules; Heparitin Sulfate; Biomarkers; Observational Studies as Topic
PubMed: 36802387
DOI: 10.1371/journal.pone.0281941 -
European Journal of Nuclear Medicine... May 2023Pharmacokinetic modelling with arterial sampling is the gold standard for analysing dynamic PET data of the brain. However, the invasive character of arterial sampling...
Pharmacokinetic modelling with arterial sampling is the gold standard for analysing dynamic PET data of the brain. However, the invasive character of arterial sampling prevents its widespread clinical application. Several methods have been developed to avoid arterial sampling, in particular reference region methods. Unfortunately, for some tracers or diseases, no suitable reference region can be defined. For these cases, other potentially non-invasive approaches have been proposed: (1) a population based input function (PBIF), (2) an image derived input function (IDIF), or (3) simultaneous estimation of the input function (SIME). This systematic review aims to assess the correspondence of these non-invasive methods with the gold standard. Studies comparing non-invasive pharmacokinetic modelling methods with the current gold standard methods using an input function derived from arterial blood samples were retrieved from PubMed/MEDLINE (until December 2021). Correlation measurements were extracted from the studies. The search yielded 30 studies that correlated outcome parameters (V, DVR, or BP for reversible tracers; K or CMR for irreversible tracers) from a potentially non-invasive method with those obtained from modelling using an arterial input function. Some studies provided similar results for PBIF, IDIF, and SIME-based methods as for modelling with an arterial input function (R = 0.59-1.00, R = 0.71-1.00, R = 0.56-0.96, respectively), if the non-invasive input curve was calibrated with arterial blood samples. Even when the non-invasive input curve was calibrated with venous blood samples or when no calibration was applied, moderate to good correlations were reported, especially for the IDIF and SIME (R = 0.71-1.00 and R = 0.36-0.96, respectively). Overall, this systematic review illustrates that non-invasive methods to generate an input function are still in their infancy. Yet, IDIF and SIME performed well, not only with arterial blood calibration, but also with venous or no blood calibration, especially for some tracers without plasma metabolites, which would potentially make these methods better suited for clinical application. However, these methods should still be properly validated for each individual tracer and application before implementation.
Topics: Humans; Arteries; Brain; Kinetics; Positron-Emission Tomography; Veins
PubMed: 36651951
DOI: 10.1007/s00259-022-06057-4 -
Current Computer-aided Drug Design 2023Indian traditional medicinal plants are known for their great potential in combating viral diseases. Previously, we reported a systematic review approach of seven...
Identification of Kaempferol as Viral Entry Inhibitor and DL-Arginine as Viral Replication Inhibitor from Selected Plants of Indian Traditional Medicine against COVID-19: An Guided in vitro Approach.
BACKGROUND
Indian traditional medicinal plants are known for their great potential in combating viral diseases. Previously, we reported a systematic review approach of seven plausible traditional Indian medicinal plants against SARS-CoV-2.
METHODS
Molecular docking was conducted with Biovia Discovery Studio. Three binding domains for spike glycoprotein (PDB IDs: 6LZG, 6M17, 6M0J) and one binding domain of RdRp (PDB ID: 7BTF) were used. Among 100 phytoconstituents listed from seven plants by the IMPPAT database used for virtual screening, the best six compounds were again filtered using Swiss ADME prediction and Lipinski's rule. Additionally, a pseudovirion assay was performed to study the interaction of SARS-CoV-2 S1-protein with the ACE 2 receptor to further confirm the effect.
RESULTS
Chebulagic acid (52.06 Kcal/mol) and kaempferol (48.84 Kcal/mol) showed increased interaction energy compared to umifenovir (33.68 Kcal/mol) for the 6LZG binding domain of spike glycoprotein. Epicatechin gallate (36.95 Kcal/mol) and arachidic acid (26.09 Kcal/mol) showed equally comparable interaction energy compared to umifenovir (38.20 Kcal/mol) for the 6M17 binding domain of spike glycoprotein. Trihydroxychalcone (35.23 Kcal/mol) and kaempferol (36.96 Kcal/mol) showed equally comparable interaction energy with umifenovir (36.60 Kcal/mol) for 6M0J binding domain of spike glycoprotein. Upon analyzing the phytoconstituents against RdRp binding domain, DL-arginine (41.78 Kcal/mol) showed comparable results with the positive control remdesivir (47.61 Kcal/mol). ADME analysis performed using Swiss ADME revealed that kaempferol and DL arginine showed drug-like properties with appropriate pharmacokinetic parameters. Further in vitro analysis of kaempferol by pseudovirion assay confirmed an acceptable decrease of the lentiviral particles in transfected HEK293T-hACE2 cells.
CONCLUSION
The study highlights that kaempferol and DL-arginine could be the significant molecules to exhibit potent action against SARS-CoV-2 and its variants.
Topics: Humans; COVID-19; Kaempferols; SARS-CoV-2; HEK293 Cells; Molecular Docking Simulation; Virus Internalization; Medicine, Traditional; Arginine; Glycoproteins; RNA-Dependent RNA Polymerase; Antiviral Agents; Molecular Dynamics Simulation
PubMed: 36635906
DOI: 10.2174/1573409919666230112123213 -
Computational and Structural... 2023Filamentous structures are ubiquitous in nature, are studied in diverse scientific fields, and span vastly different spatial scales. Filamentous structures in biological... (Review)
Review
Filamentous structures are ubiquitous in nature, are studied in diverse scientific fields, and span vastly different spatial scales. Filamentous structures in biological systems fulfill different functions and often form dynamic networks that respond to perturbations. Therefore, characterizing the properties of filamentous structures and the networks they form is important to gain better understanding of systems level functions and dynamics. Filamentous structures are captured by various imaging technologies, and analysis of the resulting imaging data addresses two problems: (i) identification (tracing) of filamentous structures in a single snapshot and (ii) characterizing the dynamics (., tracking) of filamentous structures over time. Therefore, considerable research efforts have been made in developing automated methods for tracing and tracking of filamentous structures. Here, we provide a systematic review in which we present, categorize, and discuss the state-of-the-art methods for tracing and tracking of filamentous structures in sparse and dense networks. We highlight the mathematical approaches, assumptions, and constraints particular for each method, allowing us to pinpoint outstanding challenges and offer perspectives for future research aimed at gaining better understanding of filamentous structures in biological systems.
PubMed: 36618983
DOI: 10.1016/j.csbj.2022.12.023 -
BMC Medical Research Methodology Dec 2022Clinical prediction models are often not evaluated properly in specific settings or updated, for instance, with information from new markers. These key steps are needed...
BACKGROUND
Clinical prediction models are often not evaluated properly in specific settings or updated, for instance, with information from new markers. These key steps are needed such that models are fit for purpose and remain relevant in the long-term. We aimed to present an overview of methodological guidance for the evaluation (i.e., validation and impact assessment) and updating of clinical prediction models.
METHODS
We systematically searched nine databases from January 2000 to January 2022 for articles in English with methodological recommendations for the post-derivation stages of interest. Qualitative analysis was used to summarize the 70 selected guidance papers.
RESULTS
Key aspects for validation are the assessment of statistical performance using measures for discrimination (e.g., C-statistic) and calibration (e.g., calibration-in-the-large and calibration slope). For assessing impact or usefulness in clinical decision-making, recent papers advise using decision-analytic measures (e.g., the Net Benefit) over simplistic classification measures that ignore clinical consequences (e.g., accuracy, overall Net Reclassification Index). Commonly recommended methods for model updating are recalibration (i.e., adjustment of intercept or baseline hazard and/or slope), revision (i.e., re-estimation of individual predictor effects), and extension (i.e., addition of new markers). Additional methodological guidance is needed for newer types of updating (e.g., meta-model and dynamic updating) and machine learning-based models.
CONCLUSION
Substantial guidance was found for model evaluation and more conventional updating of regression-based models. An important development in model evaluation is the introduction of a decision-analytic framework for assessing clinical usefulness. Consensus is emerging on methods for model updating.
Topics: Humans; Calibration; Prognosis; Models, Statistical
PubMed: 36510134
DOI: 10.1186/s12874-022-01801-8