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Cancers Apr 2023Liquid biopsy (LB) analysis using (ctDNA)/cell-free DNA (cfDNA) is an emerging alternative to tissue profiling in (NSCLC). LB is used to guide treatment decisions,... (Review)
Review
BACKGROUND
Liquid biopsy (LB) analysis using (ctDNA)/cell-free DNA (cfDNA) is an emerging alternative to tissue profiling in (NSCLC). LB is used to guide treatment decisions, detect resistance mechanisms, and predicts responses, and, therefore, outcomes. This systematic review and meta-analysis evaluated the impact of LB quantification on clinical outcomes in molecularly altered advanced NSCLC undergoing targeted therapies.
METHODS
We searched Embase, MEDLINE, PubMed, and Cochrane Database, between 1 January 2020 and 31 August 2022. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR), sensitivity, and specificity. Age stratification was performed based on the mean age of the individual study population. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS).
RESULTS
A total of 27 studies (3419 patients) were included in the analysis. Association of baseline ctDNA with PFS was reported in 11 studies (1359 patients), while that of dynamic changes with PFS was reported in 16 studies (1659 patients). Baseline ctDNA-negative patients had a trend towards improved PFS (pooled hazard ratio [pHR] = 1.35; 95%CI: 0.83-1.87; < 0.001; I = 96%) than ctDNA-positive patients. Early reduction/clearance of ctDNA levels after treatment was related to improved PFS (pHR = 2.71; 95%CI: 1.85-3.65; I = 89.4%) compared to those with no reduction/persistence in ctDNA levels. The sensitivity analysis based on study quality (NOS) demonstrated improved PFS only for good [pHR = 1.95; 95%CI: 1.52-2.38] and fair [pHR = 1.99; 95%CI: 1.09-2.89] quality studies, but not for poor quality studies. There was, however, a high level of heterogeneity (I = 89.4%) along with significant publication bias in our analysis.
CONCLUSIONS
This large systematic review, despite heterogeneity, found that baseline negative ctDNA levels and early reduction in ctDNA following treatment could be strong prognostic markers for PFS and OS in patients undergoing targeted therapies for advanced NSCLC. Future randomised clinical trials should incorporate serial ctDNA monitoring to further establish the clinical utility in advanced NSCLC management.
PubMed: 37173891
DOI: 10.3390/cancers15092425 -
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 -
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 -
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 -
Malaria Journal Nov 2022This review article aims to investigate the genotypic profiles of Plasmodium falciparum and Plasmodium vivax isolates collected across a wide geographic region and their... (Review)
Review
This review article aims to investigate the genotypic profiles of Plasmodium falciparum and Plasmodium vivax isolates collected across a wide geographic region and their association with resistance to anti-malarial drugs used in Indonesia. A systematic review was conducted between 1991 and date. Search engines, such as PubMed, Science Direct, and Google Scholar, were used for articles published in English and Indonesian to search the literature. Of the 471 initially identified studies, 61 were selected for 4316 P. falciparum and 1950 P. vivax individual infections. The studies included 23 molecular studies and 38 therapeutic efficacy studies. K76T was the most common pfcrt mutation. K76N (2.1%) was associated with the haplotype CVMNN. By following dihydroartemisinin-piperaquine (DHA-PPQ) therapy, the mutant pfmdr1 alleles 86Y and 1034C were selected. Low prevalence of haplotype N86Y/Y184/D1246Y pfmdr1 reduces susceptibility to AS-AQ. SNP mutation pvmdr1 Y976F reached 96.1% in Papua and East Nusa Tenggara. Polymorphism analysis in the pfdhfr gene revealed 94/111 (84.7%) double mutants S108N/C59R or S108T/A16V in Central Java. The predominant pfdhfr haplotypes (based on alleles 16, 51, 59,108, 164) found in Indonesia were ANCNI, ANCSI, ANRNI, and ANRNL. Some isolates carried A437G (35.3%) or A437G/K540E SNPs (26.5%) in pfdhps. Two novel pfdhps mutant alleles, I588F/G and K540T, were associated with six pfdhps haplotypes. The highest prevalence of pvdhfr quadruple mutation (F57L/S58R/T61M/S117T) (61.8%) was detected in Papua. In pvdhps, the only polymorphism before and after 2008 was 383G mutation with 19% prevalence. There were no mutations in the pfk13 gene reported with validated and candidate or associated k13 mutation. An increased copy number of pfpm2, associated with piperaquine resistance, was found only in cases of reinfection. Meanwhile, mutation of pvk12 and pvpm4 I165V is unlikely associated with ART and PPQ drug resistance. DHA-PPQ is still effective in treating uncomplicated falciparum and vivax malaria. Serious consideration should be given to interrupt local malaria transmission and dynamic patterns of resistance to anti-malarial drugs to modify chemotherapeutic policy treatment strategies. The presence of several changes in pfk13 in the parasite population is of concern and highlights the importance of further evaluation of parasitic ART susceptibility in Indonesia.
Topics: Plasmodium vivax; Plasmodium falciparum; Indonesia; Antimalarials; Artemisinins; Polymorphism, Single Nucleotide; Drug Resistance
PubMed: 36443817
DOI: 10.1186/s12936-022-04385-2 -
International Journal of Molecular... Nov 2022Aldehydes, particularly acetaldehyde, are carcinogenic molecules and their concentrations in foodstuffs should be controlled to avoid upper aerodigestive tract (UADT)... (Review)
Review
Aldehydes, particularly acetaldehyde, are carcinogenic molecules and their concentrations in foodstuffs should be controlled to avoid upper aerodigestive tract (UADT) and liver cancers. Highly reactive, acetaldehyde forms DNA and protein adducts, impairing physiological functions and leading to the development of pathological conditions. The consumption of aged beer, outside of the ethanol metabolism, exposes habitual drinkers to this carcinogen, whose concentrations can be over-increased due to post-brewing chemical and biochemical reactions. Storage-related changes are a challenge faced by the brewing industry, impacting volatile compound formation and triggering flavor instability. Aldehydes are among the volatile compounds formed during beer aging, recognized as off-flavor compounds. To track and understand aldehyde formation through multiple pathways during beer storage, consequent changes in flavor but particularly quality losses and harmful compound formation, this systematic review reunited data on volatile compound profiles through gas chromatography analyses from 2011 to 2021. Conditions to avoid flavor instability and successful methods for reducing beer staling, and consequent acetaldehyde accumulation, were raised by exploring the dynamic conversion between free and bound-state aldehydes. Future research should focus on implementing sensory analyses to investigate whether adding aldehyde-binding agents, e.g., cysteine and bisulfite, would contribute to consumer acceptance, restore beer flavor, and minimize acetaldehyde-related health damage.
Topics: Humans; Aged; Acetaldehyde; Aldehydes; Beer; Carcinogens; Carcinogenesis
PubMed: 36430619
DOI: 10.3390/ijms232214147