scholarly journals Blood-Based Biomarkers for Glioma in the Context of Gliomagenesis: A Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Hamza Ali ◽  
Romée Harting ◽  
Ralph de Vries ◽  
Meedie Ali ◽  
Thomas Wurdinger ◽  
...  
Keyword(s):  
Systematic Review ◽  
Large Scale ◽  
Scale Validation ◽  
Statistical Significance ◽  
Area Under The Curve ◽  
Clinical Implementation ◽  
Glial Tumor ◽  
Multiple Biomarkers ◽  
Degree Of Malignancy ◽  
New Research

BackgroundGliomas are the most common and aggressive tumors of the central nervous system. A robust and widely used blood-based biomarker for glioma has not yet been identified. In recent years, a plethora of new research on blood-based biomarkers for glial tumors has been published. In this review, we question which molecules, including proteins, nucleic acids, circulating cells, and metabolomics, are most promising blood-based biomarkers for glioma diagnosis, prognosis, monitoring and other purposes, and align them to the seminal processes of cancer.MethodsThe Pubmed and Embase databases were systematically searched. Biomarkers were categorized in the identified biomolecules and biosources. Biomarker characteristics were assessed using the area under the curve (AUC), accuracy, sensitivity and/or specificity values and the degree of statistical significance among the assessed clinical groups was reported.Results7,919 references were identified: 3,596 in PubMed and 4,323 in Embase. Following screening of titles, abstracts and availability of full-text, 262 articles were included in the final systematic review. Panels of multiple biomarkers together consistently reached AUCs >0.8 and accuracies >80% for various purposes but especially for diagnostics. The accuracy of single biomarkers, consisting of only one measurement, was far more variable, but single microRNAs and proteins are generally more promising as compared to other biomarker types.ConclusionPanels of microRNAs and proteins are most promising biomarkers, while single biomarkers such as GFAP, IL-10 and individual miRNAs also hold promise. It is possible that panels are more accurate once these are involved in different, complementary cancer-related molecular pathways, because not all pathways may be dysregulated in cancer patients. As biomarkers seem to be increasingly dysregulated in patients with short survival, higher tumor grades and more pathological tumor types, it can be hypothesized that more pathways are dysregulated as the degree of malignancy of the glial tumor increases. Despite, none of the biomarkers found in the literature search seem to be currently ready for clinical implementation, and most of the studies report only preliminary application of the identified biomarkers. Hence, large-scale validation of currently identified and potential novel biomarkers to show clinical utility is warranted.

scholarly journals Immunotherapy Monitoring with Immune Checkpoint Inhibitors Based on [18F]FDG PET/CT in Metastatic Melanomas and Lung Cancer

2021 ◽  
Vol 10 (21) ◽  
pp. 5160
Author(s):  
Egesta Lopci
Keyword(s):  
Large Scale ◽  
Clinical Laboratory ◽  
Scale Validation ◽  
Checkpoint Inhibitors ◽  
Laboratory Data ◽  
Major Change ◽  
New Drugs ◽  
Response Criteria ◽  
Clinical Implementation ◽  
Pet Ct

Immunotherapy with checkpoint inhibitors has prompted a major change not only in cancer treatment but also in medical imaging. In parallel with the implementation of new drugs modulating the immune system, new response criteria have been developed, aiming to overcome clinical drawbacks related to the new, unusual, patterns of response characterizing both solid tumors and lymphoma during the course of immunotherapy. The acknowledgement of pseudo-progression, hyper-progression, immune-dissociated response and so forth, has become mandatory for all imagers dealing with this clinical scenario. A long list of acronyms, i.e., irRC, iRECIST, irRECIST, imRECIST, PECRIT, PERCIMT, imPERCIST, iPERCIST, depicts the enormous effort made by radiology and nuclear medicine physicians in the last decade to optimize imaging parameters for better prediction of clinical benefit in immunotherapy regimens. Quite frequently, a combination of clinical-laboratory data with imaging findings has been tested, proving the ability to stratify patients into various risk groups. The next steps necessarily require a large scale validation of the most robust criteria, as well as the clinical implementation of immune-targeting tracers for immuno-PET or the exploitation of radiomics and artificial intelligence as complementary tools during the course of immunotherapy administration. For the present review article, a summary of PET/CT role for immunotherapy monitoring will be provided. By scrolling into various cancer types and applied response criteria, the reader will obtain necessary information for better understanding the potentials and limitations of the modality in the clinical setting.

scholarly journals Predicting mortality in patients with sepsis in the emergency department by using combinations of biomarkers and clinical scoring systems: a systematic review.

2020 ◽  
Author(s):  
Kirby Tong-Minh ◽  
Iris Welten ◽  
Henrik Endeman ◽  
Tjebbe Hagenaars ◽  
Christian Ramakers ◽  
...  
Keyword(s):  
Systematic Review ◽  
Emergency Department ◽  
Diagnostic Accuracy ◽  
Scoring System ◽  
Early Stage ◽  
Area Under The Curve ◽  
Scoring Systems ◽  
Simplified Acute Physiology Score ◽  
Multiple Biomarkers ◽  
Clinical Scoring

Abstract Introduction Sepsis can be detected in an early stage in the emergency department (ED) by biomarkers and clinical scoring systems. A combination of multiple biomarkers or biomarker with clinical scoring system might result in a higher predictive value on mortality. The goal of this systematic review is to evaluate the available literature on combinations of biomarkers and clinical scoring systems on 1-month mortality in patients with sepsis in the ED.Methods We performed a systematic search using MEDLINE, PubMed, EMBASE and Google Scholar. Articles were included if they evaluated at least one biomarker combined with another biomarker or clinical scoring system and reported the diagnostic accuracy on 28 or 30 day mortality by area under the curve (AUC) in patients with sepsis. Results We found 18 articles in this systematic review. In these 18 articles, a total of 35 combinations of biomarkers and clinical scoring systems were studied of which 33 unique combinations. In total, seven different clinical scoring systems and 21 different biomarkers were investigated. The combination of procalcitonin (PCT), lactate, interleukin-6 (IL-6) and Simplified Acute Physiology Score-2 (SAPS-2) resulted in the highest AUC on 1-month mortality. Conclusion In this systematic review, the combination of PCT, IL-6, lactate and the SAPS-2 score had the highest AUC on 1-month mortality in patients with sepsis in the ED. The studies we found in this review were too heterogeneous to conclude that a certain combination it should be used in the ED to predict 1-month mortality in patients with sepsis.

scholarly journals PRM-MS Quantitative Analysis of Isomeric N-Glycopeptides Derived From Human Serum Haptoglobin of Patients With Cirrhosis and Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Cristian D. Gutierrez Reyes ◽  
Yifan Huang ◽  
Mojgan Atashi ◽  
Jie Zhang ◽  
Jianhui Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Detection ◽  
Large Scale ◽  
Scale Validation ◽  
Area Under The Curve ◽  
Glycosylation Site ◽  
Protein Glycosylation ◽  
Serum Haptoglobin ◽  
Parallel Reaction Monitoring ◽  
Early Hcc

Abstract Currently surveillance strategies have inadequate performance for the early detection of hepatocellular carcinoma (HCC). Protein glycosylation is a potential source of biomarkers to differentiate between cirrhosis and HCC. We performed a comprehensive LC-PRM-MS approach where a targeted parallel reaction monitoring (PRM) strategy was coupled to a powerful LC system to study the microheterogeneity of haptoglobin (Hp) extracted from 15 patients with cirrhosis and 15 with HCC. We found that our strategy was able to identify a large number of isomeric N-glycopeptides mainly located in the glycosylation site Asn207. Nine out of twelve N-glycopeptides, located in the Asn207 site, had significant differences in abundance between patients with cirrhosis and HCC (p < 0.05). The area under the curve (AUC) of alpha-fetoprotein (AFP) was alone 0.85, which improved to 0.95 (95% CI: 0.88, 1) when NLF_5613 Isomer 1 was combined with AFP. When comparing the early HCC vs. cirrhosis, four sialylated-fucosylated glycopeptides better estimated AUCs with respect to AFP (AUCAFP = 0.66, and AUCN−glycopeptides = 0.86, 0.84, 0.88, and 0.80, respectively). Further large scale validation of glycopeptides for the early detection of HCC is warranted.

scholarly journals ASSA: Fast identification of statistically significant interactions between long RNAs

2018 ◽  
Vol 16 (01) ◽  
pp. 1840001 ◽  
Author(s):  
Ivan Antonov ◽  
Andrey Marakhonov ◽  
Maria Zamkova ◽  
Yulia Medvedeva
Keyword(s):  
Sequence Alignment ◽  
Large Scale ◽  
Statistical Significance ◽  
Noncoding Rnas ◽  
Area Under The Curve ◽  
Interaction Energies ◽  
Computational Pipeline ◽  
Efficient Prediction ◽  
Test Sets ◽  
Post Transcriptional Regulation

The discovery of thousands of long noncoding RNAs (lncRNAs) in mammals raises a question about their functionality. It has been shown that some of them are involved in post-transcriptional regulation of other RNAs and form inter-molecular duplexes with their targets. Sequence alignment tools have been used for transcriptome-wide prediction of RNA–RNA interactions. However, such approaches have poor prediction accuracy since they ignore RNA’s secondary structure. Application of the thermodynamics-based algorithms to long transcripts is not computationally feasible on a large scale. Here, we describe a new computational pipeline ASSA that combines sequence alignment and thermodynamics-based tools for efficient prediction of RNA–RNA interactions between long transcripts. To measure the hybridization strength, the sum energy of all the putative duplexes is computed. The main novelty implemented in ASSA is the ability to quickly estimate the statistical significance of the observed interaction energies. Most of the functional hybridizations between long RNAs were classified as statistically significant. ASSA outperformed 11 other tools in terms of the Area Under the Curve on two out of four test sets. Additionally, our results emphasized a unique property of the [Formula: see text] repeats with respect to the RNA–RNA interactions in the human transcriptome. ASSA is available at https://sourceforge.net/projects/assa/

scholarly journals Non-Invasive Tool to Distinguish Between Acute Rejection and Stable Graft Function Using Urinary mRNA Signature Reflecting Allograft Status in Kidney Transplantation

2020 ◽  
Author(s):  
Jung-Woo Seo ◽  
Yu-Ho Lee ◽  
Dong Hyun Tae ◽  
Seon Hwa Park ◽  
Ju-Young Moon ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Candidate Genes ◽  
Large Scale ◽  
Scale Validation ◽  
Graft Function ◽  
Area Under The Curve ◽  
Binary Logistic Regression ◽  
Cross Sectional ◽  
Non Invasive

Abstract Background: Urine has been regarded as the best resource based on the assumption that urine can directly reflect the state of the allograft or ongoing injury in kidney transplantation. Previous studies, suggesting the usefulness of urinary mRNA as a biomarker of acute rejection, imply that urinary mRNA mirrors the transcriptional activity of the kidneys. Methods: We absolutely measured 14 data-driven candidate genes using quantitative PCR without pre-amplification in the cross-sectional specimens collected from Korean kidney transplant patients. We developed a clinical application model adopting urinary mRNAs for allograft rejection using a binary logistic regression and finally verified its usefulness in a large-scale validation group.Results: We measured the candidate genes in 103 training samples. Expression of 8/14 genes were significantly different between acute rejection and stable graft function with normal pathology and long-term graft survival. Also, CXCL9 was distinctly expressed in allografts with acute rejection in in situ hybridization analysis. This result, consistent with the qPCR result, implies that urinary mRNA could reflect the magnitude of allograft injury. We developed AR prediction model by differently combined mRNAs and the area under the curve (AUC) of the model was 0.89 in training set. The model was validated in 391 independent samples, and the AUC of the model was 0.84 with a fixed manner. In addition, the decision curve analysis indicated a range of reasonable threshold probabilities for biopsy. Conclusions. Therefore, we suggest urinary mRNA signature may serve as a non-invasive monitoring tool of acute rejection and intragraft immune injury.

scholarly journals Renal Cell Tumors: Uncovering the Biomarker Potential of ncRNAs

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2214
Author(s):  
Gonçalo Outeiro-Pinho ◽  
Daniela Barros-Silva ◽  
Margareta P. Correia ◽  
Rui Henrique ◽  
Carmen Jerónimo
Keyword(s):  
Renal Cell ◽  
Large Scale ◽  
Patient Management ◽  
Scale Validation ◽  
Clinical Importance ◽  
Limited Information ◽  
Clinical Implementation ◽  
Renal Cell Tumors ◽  
Patient Responsiveness ◽  
Improve Patient Management

Renal cell tumors (RCT) remain as one of the most common and lethal urological tumors worldwide. Discrimination between (1) benign and malignant disease, (2) indolent and aggressive tumors, and (3) patient responsiveness to a specific therapy is of major clinical importance, allowing for a more efficient patient management. Nonetheless, currently available tools provide limited information and novel strategies are needed. Over the years, a putative role of non-coding RNAs (ncRNAs) as disease biomarkers has gained relevance and is now one of the most prolific fields in biological sciences. Herein, we extensively sought the most significant reports on ncRNAs as potential RCTs’ diagnostic, prognostic, predictive, and monitoring biomarkers. We could conclude that ncRNAs, either alone or in combination with currently used clinical and pathological parameters, might represent key elements to improve patient management, potentiating the implementation of precision medicine. Nevertheless, most ncRNA biomarkers require large-scale validation studies, prior to clinical implementation.

scholarly journals Predicting Mortality in Adult Patients With Sepsis in the Emergency Department by Using Combinations of Biomarkers and Clinical Scoring Systems: A Systematic Review.

2021 ◽  
Author(s):  
Kirby Tong-Minh ◽  
Iris Welten ◽  
Henrik Endeman ◽  
Tjebbe Hagenaars ◽  
Christian Ramakers ◽  
...  
Keyword(s):  
Systematic Review ◽  
Emergency Department ◽  
Scoring System ◽  
Early Stage ◽  
Area Under The Curve ◽  
Scoring Systems ◽  
Simplified Acute Physiology Score ◽  
Prognostic Accuracy ◽  
Multiple Biomarkers ◽  
Clinical Scoring

Abstract IntroductionSepsis can be detected in an early stage in the emergency department (ED) by biomarkers and clinical scoring systems. A combination of multiple biomarkers or biomarker with clinical scoring system might result in a higher predictive value on mortality. The goal of this systematic review is to evaluate the available literature on combinations of biomarkers and clinical scoring systems on 1-month mortality in patients with sepsis in the ED.MethodsWe performed a systematic search using MEDLINE, EMBASE and Google Scholar. Articles were included if they evaluated at least one biomarker combined with another biomarker or clinical scoring system and reported the prognostic accuracy on 28 or 30 day mortality by area under the curve (AUC) in patients with sepsis. ResultsWe included 18 articles in which a total of 35 combinations of biomarkers and clinical scoring systems were studied, of which 33 unique combinations. In total, seven different clinical scoring systems and 21 different biomarkers were investigated. The combination of procalcitonin (PCT), lactate, interleukin-6 (IL-6) and Simplified Acute Physiology Score-2 (SAPS-2) resulted in the highest AUC on 1-month mortality. ConclusionThe combination of PCT, IL-6, lactate and the SAPS-2 score had the highest AUC on 1-month mortality in patients with sepsis in the ED. The studies we found in this review were too heterogeneous to conclude that a certain combination it should be used in the ED to predict 1-month mortality in patients with sepsis.

Therapy of post-stroke depression – a systematic review

2013 ◽  
Vol 10 (02) ◽  
pp. 108-129 ◽  
Author(s):  
W. Gaebel ◽  
W. Wannagat ◽  
J. Zielasek
Keyword(s):  
Systematic Review ◽  
Large Scale ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Placebo Control ◽  
Post Stroke ◽  
Pharmacological Studies ◽  
Post Stroke Depression ◽  
Control Procedures ◽  
Antidepressant Pharmacotherapy

SummaryWe performed a systematic review of randomized placebo-controlled pharmacological and non-pharmacological trials for the therapy and prevention of post-stroke depression that have been published between 1980 and 2011. We initially identified 2 260 records of which 28 studies were finally included into this review. A meta-analytic approach was hampered by considerable differences regarding the kinds of therapeutic regimens and the study durations. Modest effects favoring treatment of post-stroke depression could be found for pharmacological treatment as well as repetitive transcranial magnetic stimulation. For the prevention of post-stroke depression, antidepressant pharmacotherapy showed promising results. However, large-scale studies with better standardized study populations, optimized placebo control procedures in non-pharmacological studies, and replication in larger follow-up studies are still necessary to find the optimal therapeutic regimens to prevent and treat post-stroke depression.

Dietary Patterns: A New Therapeutic Approach for Depression?

2019 ◽  
Vol 20 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Mariana Jesus ◽  
Tânia Silva ◽  
César Cagigal ◽  
Vera Martins ◽  
Carla Silva
Keyword(s):  
Depressive Symptoms ◽  
Dietary Patterns ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Dietary Intervention ◽  
Common Mental Disorder ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Inverse Association ◽  
The Impact

Introduction: The field of nutritional psychiatry is a fast-growing one. Although initially, it focused on the effects of vitamins and micronutrients in mental health, in the last decade, its focus also extended to the dietary patterns. The possibility of a dietary cost-effective intervention in the most common mental disorder, depression, cannot be overlooked due to its potential large-scale impact. Method: A classic review of the literature was conducted, and studies published between 2010 and 2018 focusing on the impact of dietary patterns in depression and depressive symptoms were included. Results: We found 10 studies that matched our criteria. Most studies showed an inverse association between healthy dietary patterns, rich in fruits, vegetables, lean meats, nuts and whole grains, and with low intake of processed and sugary foods, and depression and depressive symptoms throughout an array of age groups, although some authors reported statistical significance only in women. While most studies were of cross-sectional design, making it difficult to infer causality, a randomized controlled trial presented similar results. Discussion: he association between dietary patterns and depression is now well-established, although the exact etiological pathways are still unknown. Dietary intervention, with the implementation of healthier dietary patterns, closer to the traditional ones, can play an important role in the prevention and adjunctive therapy of depression and depressive symptoms. Conclusion: More large-scale randomized clinical trials need to be conducted, in order to confirm the association between high-quality dietary patterns and lower risk of depression and depressive symptoms.

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