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Drugs Sep 2021Clinical metagenomics (CMg) is the process of sequencing nucleic acid of clinical samples to obtain clinically relevant information such as the identification of...
Clinical metagenomics (CMg) is the process of sequencing nucleic acid of clinical samples to obtain clinically relevant information such as the identification of microorganisms and their susceptibility to antimicrobials. Over the last decades, sequencing and bioinformatic solutions supporting CMg have much evolved and an increasing number of case reports and series covering various infectious diseases have been published. Metagenomics is a new approach to infectious disease diagnosis that is currently being developed and is certainly one of the most promising for the coming years. However, most CMg studies are retrospective, and few address the potential impact CMg could have on patient management, including initiation, adaptation, or cessation of antimicrobials. In this narrative review, we have discussed the potential role of CMg in bacteriology, virology, mycology, and parasitology. Several reports and case-series confirm that CMg is an innovative tool with which one can (i) identify more microorganisms than with conventional methods in a single test, (ii) obtain results within hours, and (iii) tailor the antimicrobial regimen of patients. However, the cost-efficiency of CMg and its real impact on patient management are still to be determined.
Topics: Anti-Infective Agents; Communicable Diseases; Computational Biology; Humans; Metagenomics; Nucleic Acid Amplification Techniques
PubMed: 34328626
DOI: 10.1007/s40265-021-01572-4 -
Neuroscience and Biobehavioral Reviews Sep 2021Brain development is a dynamic and lengthy process that includes cell proliferation, migration, neurogenesis, gliogenesis, synaptogenesis, and pruning. Disruption of any... (Review)
Review
The importance of non-coding RNAs in environmental stress-related developmental brain disorders: A systematic review of evidence associated with exposure to alcohol, anesthetic drugs, nicotine, and viral infections.
Brain development is a dynamic and lengthy process that includes cell proliferation, migration, neurogenesis, gliogenesis, synaptogenesis, and pruning. Disruption of any of these developmental events can result in long-term outcomes ranging from brain structural changes, to cognitive and behavioral abnormality, with the mechanisms largely unknown. Emerging evidence suggests non-coding RNAs (ncRNAs) as pivotal molecules that participate in normal brain development and neurodevelopmental disorders. NcRNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are transcribed from the genome but not translated into proteins. Many ncRNAs have been implicated as tuners of cell fate. In this review, we started with an introduction of the current knowledge of lncRNAs and miRNAs, and their potential roles in brain development in health and disorders. We then reviewed and discussed the evidence of ncRNA involvement in abnormal brain development resulted from alcohol, anesthetic drugs, nicotine, and viral infections. The complex connections among these ncRNAs were also discussed, along with potential overlapping ncRNA mechanisms, possible pharmacological targets for therapeutic/neuroprotective interventions, and potential biomarkers for brain developmental disorders.
Topics: Anesthetics; Brain Diseases; Humans; MicroRNAs; Nicotine; RNA, Untranslated; Virus Diseases
PubMed: 34186153
DOI: 10.1016/j.neubiorev.2021.06.033 -
The British Journal of Radiology Sep 2021Blood flow is the rate of blood movement and relevant to numerous processes, though understudied in gliomas. The aim of this review was to pool blood flow metrics...
OBJECTIVE
Blood flow is the rate of blood movement and relevant to numerous processes, though understudied in gliomas. The aim of this review was to pool blood flow metrics obtained from MRI modalities in adult supratentorial gliomas.
METHODS
MEDLINE, EMBASE and the Cochrane database were queried 01/01/2000-31/12/2019. Studies measuring blood flow in adult Grade II-IV supratentorial gliomas using dynamic susceptibility contrast (DSC) MRI, dynamic contrast enhanced MRI (DCE-MRI) or arterial spin labelling (ASL) were included. Absolute and relative cerebral blood flow (CBF), peritumoral blood flow and tumoral blood flow (TBF) were reported.
RESULTS
34 studies were included with 1415 patients and 1460 scans. The mean age was 52.4 ± 7.3 years. Most patients had glioblastoma ( = 880, 64.6%). The most common imaging modality was ASL ( = 765, 52.4%) followed by DSC ( = 538, 36.8%). Most studies were performed pre-operatively ( = 1268, 86.8%). With increasing glioma grade (II IV), TBF increased (70.8 145.5 ml/100 g/min, < 0.001) and CBF decreased (85.3 49.6 ml/100 g/min, < 0.001). In Grade IV gliomas, following treatment, CBF increased in ipsilateral (24.9 ± 1.2 26.1 ± 0.0 ml/100 g/min, < 0.001) and contralateral white matter (25.6 ± 0.2 26.0± 0.0 ml/100 g/min, < 0.001).
CONCLUSION
Our findings demonstrate that increased mass effect from high-grade gliomas impairs blood flow within the surrounding brain that can improve with surgery.
ADVANCES IN KNOWLEDGE
This systematic review demonstrates how mass effect from brain tumours impairs blood flow in the surrounding brain parenchyma that can improve with treatment.
Topics: Adult; Brain; Brain Neoplasms; Cerebrovascular Circulation; Glioma; Humans; Magnetic Resonance Imaging; Neoplasm Grading
PubMed: 34106749
DOI: 10.1259/bjr.20201450 -
Frontiers in Immunology 2021Dynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists.
METHODS
We performed meta-analysis and meta regression to analyze the associations of plasma D-dimer with 106 clinical variables to identify a panoramic view of the derangements of fibrinolysis in 14,862 patients of 42 studies. There were no limitations of age, gender, race, and country. Raw data of each group were extracted separately by two investigators. Individual data of case series, median and interquartile range, and ranges of median or mean were converted to SDM (standard deviation of mean).
FINDINGS
The weighted mean difference of D-dimer was 0.97 µg/mL (95% CI 0.65, 1.29) between mild and severe groups, as shown by meta-analysis. Publication bias was significant. Meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels. Of these, 11 readouts were negatively related to the level of plasma D-dimer. Further, age and gender were confounding factors. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K, glucose, SpO2, BUN (blood urea nitrogen), bilirubin, ALT (alanine aminotransferase), AST (aspartate aminotransferase), systolic blood pressure, and CK (creatine kinase).
INTERPRETATION
These findings support elevated D-dimer as an independent predictor for both mortality and complications. The identified D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and pulmonary hyperactive derangements of fibrinolysis, and the D-dimer-associated clinical biomarkers, and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.
Topics: Biomarkers; COVID-19; Diagnostic Tests, Routine; Disease Progression; Fibrin Fibrinogen Degradation Products; Humans; Patient Admission; SARS-CoV-2; Severity of Illness Index
PubMed: 34025688
DOI: 10.3389/fimmu.2021.691249 -
Virology Journal May 2021In recent years, oncolytic viruses (OVs) have drawn attention as a novel therapy to various types of cancers, both in clinical and preclinical cancer studies all around... (Review)
Review
BACKGROUND
In recent years, oncolytic viruses (OVs) have drawn attention as a novel therapy to various types of cancers, both in clinical and preclinical cancer studies all around the world. Consequently, researchers have been actively working on enhancing cancer therapy since the early twentieth century. This study presents a systematic review of the literature on OVs, discusses underlying research clusters and, presents future directions of OVs research.
METHODS
A total of 1626 published articles related to OVs as cancer therapy were obtained from the Web of Science (WoS) database published between January 2000 and March 2020. Various aspects of OVs research, including the countries/territories, institutions, journals, authors, citations, research areas, and content analysis to find trending and emerging topics, were analysed using the bibliometrix package in the R-software.
RESULTS
In terms of the number of publications, the USA based researchers were the most productive (n = 611) followed by Chinese (n = 197), and Canadian (n = 153) researchers. The Molecular Therapy journal ranked first both in terms of the number of publications (n = 133) and local citations (n = 1384). The most prominent institution was Mayo Clinic from the USA (n = 117) followed by the University of Ottawa from Canada (n = 72), and the University of Helsinki from Finland (n = 63). The most impactful author was Bell J.C with the highest number of articles (n = 67) and total local citations (n = 885). The most impactful article was published in the Cell journal. In addition, the latest OVs research mainly builds on four research clusters.
CONCLUSION
The domain of OVs research has increased at a rapid rate from 2000 to 2020. Based on the synthesis of reviewed studies, adenovirus, herpes simplex virus, reovirus, and Newcastle disease virus have shown potent anti-cancer activity. Developed countries such as the USA, Canada, the UK, and Finland were the most productive, hence, contributed most to this field. Further collaboration will help improve the clinical research translation of this therapy and bring benefits to cancer patients worldwide.
Topics: Bibliometrics; Databases, Factual; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 33980264
DOI: 10.1186/s12985-021-01571-7 -
Cancer Epidemiology, Biomarkers &... Jun 2021Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy balance through exercise and/or caloric restriction, decreases risk of breast cancer recurrence.
METHODS
We investigated the effects of lifestyle modifications (exercise only, or combined caloric restriction and exercise) on adipokines, IL2, IL6, IL8, IL10, C-reactive protein (CRP), and TNFα biomarkers in breast cancer survivors. Searches were completed in June and July of 2019 to identify randomized controlled trials that met inclusion criteria. Weighted mean difference was calculated using random- or fixed-effects models based on the heterogeneity of the studies.
RESULTS
2501 records were identified, with 30 ultimately meeting inclusion criteria of the systematic review; 21 studies provided data suitable for meta-analysis. We observed leptin levels were significantly reduced in the exercise-only group compared with sedentary control [WMD -5.66; 95% confidence interval (CI), -11.0 to -0.33; = 0.04].
CONCLUSIONS
Leptin may be a primary mediator of exercise-induced improvements in breast cancer recurrence.
IMPACT
This is the first review and meta-analysis to examine combined exercise and caloric restriction programs in breast cancer survivors. Future studies should further examine combined programs and their efficacy for altering leptin.
Topics: Biomarkers; Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; Cancer Survivors; Diet, Healthy; Exercise; Female; Humans; Inflammation; Leptin; Neoplasm Recurrence, Local; Weight Loss
PubMed: 33737299
DOI: 10.1158/1055-9965.EPI-20-1029 -
Frontiers in Oncology 2020Studies on the prognostic value of the soluble programmed death ligand 1 (sPD-L1) in cancer patients have not yielded consistent results.
BACKGROUND
Studies on the prognostic value of the soluble programmed death ligand 1 (sPD-L1) in cancer patients have not yielded consistent results.
OBJECTIVE
This meta-analysis was performed to assess the association between sPD-L1 and the prognosis of cancer patients.
METHODS
Published articles in Pubmed, EMBASE, and Cochrane clinical trial databases were searched from the inception to September 2020. Overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) data were evaluated using a hazard ratio (HR) at 95% confidence interval (95% CI).
RESULTS
A total 31 studies involving 17 tumors and 3,780 patients were included. The overexpression of sPD-L1 was associated with shorter OS (HR 1.85, 95% CI 1.59-2.15, I = 33%). High sPD-L1 had worse PFS (HR 2.40, 95% CI 1.55-3.72, I = 83%), and worse DFS (HR 2.92, 95% CI 2.02-4.29, I = 40%), without significant statistical difference in RFS (HR 2.08, 95% CI 0.99-4.40, I = 0%).
CONCLUSIONS
High sPD-L1 levels were associated with worse survival prognosis in cancer patients. The sPD-L1 may be a potential prognostic, non-invasive, and dynamic monitoring biomarker for cancers in the future.
PubMed: 33718120
DOI: 10.3389/fonc.2020.626932 -
Biomedicine & Pharmacotherapy =... May 2021All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected... (Meta-Analysis)
Meta-Analysis
Repurposing potential of Ayurvedic medicinal plants derived active principles against SARS-CoV-2 associated target proteins revealed by molecular docking, molecular dynamics and MM-PBSA studies.
All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected secondary metabolites have been experimentally validated and reported as potent antiviral agents against genetically-close human viruses. The plants have also been used as a folk medicine to treat cold, cough, asthma, bronchitis, and severe acute respiratory syndrome in India and across the globe since time immemorial. The present study aimed to assess the repurposing possibility of potent antiviral compounds with SARS-CoV-2 target proteins and also with host-specific receptor and activator protease that facilitates the viral entry into the host body. Molecular docking (MDc) was performed to study molecular affinities of antiviral compounds with aforesaid target proteins. The top-scoring conformations identified through docking analysis were further validated by 100 ns molecular dynamic (MD) simulation run. The stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method. Finally, the binding affinities of all the compounds were also compared with a reference ligand, remdesivir, against the target protein RdRp. Additionally, pharmacophore features, 3D structure alignment of potent compounds and Bayesian machine learning model were also used to support the MDc and MD simulation. Overall, the study emphasized that curcumin possesses a strong binding ability with host-specific receptors, furin and ACE2. In contrast, gingerol has shown strong interactions with spike protein, and RdRp and quercetin with main protease (M) of SARS-CoV-2. In fact, all these target proteins play an essential role in mediating viral replication, and therefore, compounds targeting aforesaid target proteins are expected to block the viral replication and transcription. Overall, gingerol, curcumin and quercetin own multitarget binding ability that can be used alone or in combination to enhance therapeutic efficacy against COVID-19. The obtained results encourage further in vitro and in vivo investigations and also support the traditional use of antiviral plants preventively.
Topics: Antiviral Agents; Catechols; Curcumin; Drug Repositioning; Fatty Alcohols; Humans; Medicine, Ayurvedic; Molecular Docking Simulation; Quercetin; SARS-CoV-2; Viral Proteins; COVID-19 Drug Treatment
PubMed: 33561649
DOI: 10.1016/j.biopha.2021.111356 -
Expert Review of Molecular Diagnostics May 2021The COVID-19 pandemic is still escalating and has shaped an extraordinary and pressing need for rapid diagnostics with high sensitivity and specificity. Prompt diagnosis...
INTRODUCTION
The COVID-19 pandemic is still escalating and has shaped an extraordinary and pressing need for rapid diagnostics with high sensitivity and specificity. Prompt diagnosis is the key to mitigate this situation. As several diagnostic tools for COVID-19 are already available and others are still under development, mandating a comprehensive review of the efficacy of existing tools and evaluate the potential of others.
AREAS COVERED
Currently explored platforms for SARS-CoV-2 diagnostics and surveillance centered on qRT-PCR, RT-PCR, CRISPR, microarray, LAMP, lateral flow immunoassays, proteomics-based approaches, and radiological scans are overviewed and summarized in this review along with their advantages and downsides. A narrative literature review was carried out by accessing the freely available online databases to encapsulate the developments in medical diagnostics.
EXPERT OPINION
An ideal detection method should be sensitive, specific, rapid, cost-effective, and should allow early diagnosis of the infection as near as possible to the point of care that could alter the current situation for the better. Medical diagnostics is a highly dynamic field as no diagnostic method available for SARS-CoV-2 detection offers a perfect solution and requires more attention and continuous R&D to challenge the present-day pandemic situation.
Topics: COVID-19; COVID-19 Nucleic Acid Testing; COVID-19 Testing; Clustered Regularly Interspaced Short Palindromic Repeats; Humans; Immunoassay; Molecular Diagnostic Techniques; Neutralization Tests; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction; Proteomics; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 33423567
DOI: 10.1080/14737159.2021.1874354 -
American Journal of Physiology. Heart... Apr 2021Atherosclerosis is a dynamic process starting with endothelial dysfunction and inflammation and eventually leading to life-threatening arterial plaques. Exercise...
Atherosclerosis is a dynamic process starting with endothelial dysfunction and inflammation and eventually leading to life-threatening arterial plaques. Exercise generally improves endothelial function in a dose-dependent manner by altering hemodynamics, specifically by increased arterial pressure, pulsatility, and shear stress. However, athletes who regularly participate in high-intensity training can develop arterial plaques, suggesting alternative mechanisms through which excessive exercise promotes vascular disease. Understanding the mechanisms that drive atherosclerosis in sedentary versus exercise states may lead to novel rehabilitative methods aimed at improving exercise compliance and physical activity. Preclinical tools, including in vitro cell assays, in vivo animal models, and in silico computational methods, broaden our capabilities to study the mechanisms through which exercise impacts atherogenesis, from molecular maladaptation to vascular remodeling. Here, we describe how preclinical research tools have and can be used to study exercise effects on atherosclerosis. We then propose how advanced bioengineering techniques can be used to address gaps in our current understanding of vascular pathophysiology, including integrating in vitro, in vivo, and in silico studies across multiple tissue systems and size scales. Improving our understanding of the antiatherogenic exercise effects will enable engaging, targeted, and individualized exercise recommendations to promote cardiovascular health rather than treating cardiovascular disease that results from a sedentary lifestyle.
Topics: Animals; Arteries; Atherosclerosis; Bioengineering; Cells, Cultured; Computer Simulation; Disease Models, Animal; Endothelium, Vascular; Exercise Therapy; Hemodynamics; Humans; Microfluidic Analytical Techniques; Models, Cardiovascular; Plaque, Atherosclerotic; Sedentary Behavior
PubMed: 33385323
DOI: 10.1152/ajpheart.00719.2020