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Cancers May 2024Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on... (Review)
Review
Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on individual anatomy. Adaptation for individual tumour biology remains elusive. There is an unmet need for biomarkers of intrinsic radiosensitivity that can predict tumour response to radiation to facilitate individualised decision-making, dosing and treatment planning. Over the last few decades, the use of high throughput molecular biology technologies has led to an explosion of newly discovered cancer biomarkers. Gene expression signatures are now used routinely in clinic to aid decision-making regarding adjuvant systemic therapy. They have great potential as radiotherapy biomarkers. A previous systematic review published in 2015 reported only five studies of signatures evaluated for their ability to predict radiotherapy benefits in clinical cohorts. This updated systematic review encompasses the expanded number of studies reported in the last decade. An additional 27 studies were identified. In total, 22 distinct signatures were recognised (5 pre-2015, 17 post-2015). Seventeen signatures were 'radiosensitivity' signatures and five were breast cancer prognostic signatures aiming to identify patients at an increased risk of local recurrence and therefore were more likely to benefit from adjuvant radiation. Most signatures (15/22) had not progressed beyond the discovery phase of development, with no suitable validated clinical-grade assay for application. Very few signatures (4/17 'radiosensitivity' signatures) had undergone any laboratory-based biological validation of their ability to predict tumour radiosensitivity. No signatures have been assessed prospectively in a phase III biomarker-led trial to date and none are recommended for routine use in clinical guidelines. A phase III prospective evaluation is ongoing for two breast cancer prognostic signatures. The most promising radiosensitivity signature remains the radiosensitivity index (RSI), which is used to calculate a genomic adjusted radiation dose (GARD). There is an ongoing phase II prospective biomarker-led study of RSI/GARD in triple negative breast cancer. The results of these trials are eagerly anticipated over the coming years. Future work in this area should focus on (1) robust biological validation; (2) building biobanks alongside large radiotherapy randomised controlled trials with dose variance (to demonstrate an interaction between radiosensitivity signature and dose); (3) a validation of clinical-grade cost-effective assays that are deliverable within current healthcare infrastructure; and (4) an integration with biomarkers of other determinants of radiation response.
PubMed: 38792019
DOI: 10.3390/cancers16101942 -
BioRxiv : the Preprint Server For... May 2024High-content image-based assays have fueled significant discoveries in the life sciences in the past decade (2013-2023), including novel insights into disease etiology,...
High-content image-based assays have fueled significant discoveries in the life sciences in the past decade (2013-2023), including novel insights into disease etiology, mechanism of action, new therapeutics, and toxicology predictions. Here, we systematically review the substantial methodological advancements and applications of Cell Painting. Advancements include improvements in the Cell Painting protocol, assay adaptations for different types of perturbations and applications, and improved methodologies for feature extraction, quality control, and batch effect correction. Moreover, machine learning methods recently surpassed classical approaches in their ability to extract biologically useful information from Cell Painting images. Cell Painting data have been used alone or in combination with other - omics data to decipher the mechanism of action of a compound, its toxicity profile, and many other biological effects. Overall, key methodological advances have expanded Cell Painting's ability to capture cellular responses to various perturbations. Future advances will likely lie in advancing computational and experimental techniques, developing new publicly available datasets, and integrating them with other high-content data types.
PubMed: 38766203
DOI: 10.1101/2024.05.04.592531 -
ArXiv May 2024High-content image-based assays have fueled significant discoveries in the life sciences in the past decade (2013-2023), including novel insights into disease etiology,...
High-content image-based assays have fueled significant discoveries in the life sciences in the past decade (2013-2023), including novel insights into disease etiology, mechanism of action, new therapeutics, and toxicology predictions. Here, we systematically review the substantial methodological advancements and applications of Cell Painting. Advancements include improvements in the Cell Painting protocol, assay adaptations for different types of perturbations and applications, and improved methodologies for feature extraction, quality control, and batch effect correction. Moreover, machine learning methods recently surpassed classical approaches in their ability to extract biologically useful information from Cell Painting images. Cell Painting data have been used alone or in combination with other -omics data to decipher the mechanism of action of a compound, its toxicity profile, and many other biological effects. Overall, key methodological advances have expanded Cell Painting's ability to capture cellular responses to various perturbations. Future advances will likely lie in advancing computational and experimental techniques, developing new publicly available datasets, and integrating them with other high-content data types.
PubMed: 38745696
DOI: No ID Found -
Talanta Aug 2024Neonicotinoids, sometimes abbreviated as neonics, represent a class of neuro-active insecticides with chemical similarities to nicotine. Neonicotinoids are the most... (Review)
Review
Neonicotinoids, sometimes abbreviated as neonics, represent a class of neuro-active insecticides with chemical similarities to nicotine. Neonicotinoids are the most widely adopted group of insecticides globally since their discovery in the late 1980s. Their physiochemical properties surpass those of previously established insecticides, contributing to their popularity in various sectors such as agriculture and wood treatment. The environmental impact of neonicotinoids, often overlooked, underscores the urgency to develop tools for their detection and understanding of their behavior. Conventional methods for pesticide detection have limitations. Chromatographic techniques are sensitive but expensive, generate waste, and require complex sample preparation. Bioassays lack specificity and accuracy, making them suitable as preliminary tests in conjunction with instrumental methods. Aptamer-based biosensor is recognized as an advantageous tool for neonicotinoids detection due to its rapid response, user-friendly nature, cost-effectiveness, and suitability for on-site detection. This comprehensive review represents the inaugural in-depth analysis of advancements in aptamer-based biosensors targeting neonicotinoids such as imidacloprid, thiamethoxam, clothianidin, acetamiprid, thiacloprid, nitenpyram, and dinotefuran. Additionally, the review offers valuable insights into the critical challenges requiring prompt attention for the successful transition from research to practical field applications.
Topics: Insecticides; Aptamers, Nucleotide; Biosensing Techniques; Neonicotinoids; Guanidines; Thiamethoxam; Thiazoles; Nitro Compounds; Environmental Monitoring; Environmental Pollutants; Thiazines
PubMed: 38703483
DOI: 10.1016/j.talanta.2024.126190 -
Autoimmunity Reviews May 2024Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a... (Meta-Analysis)
Meta-Analysis Review
Prevalence of anti-Ro52-kDa/SSA (TRIM21) antibodies and associated clinical phenotype in systemic sclerosis: Data from a French cohort, a systematic review and meta-analysis.
OBJECTIVES
Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort.
METHODS
Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719).
FINDINGS
In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]).
INTERPRETATION
Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.
Topics: Humans; Scleroderma, Systemic; Autoantibodies; Ribonucleoproteins; France; Phenotype; Antibodies, Antinuclear; Prevalence; Female; Cross-Sectional Studies; Male
PubMed: 38555075
DOI: 10.1016/j.autrev.2024.103536 -
Toxicological Sciences : An Official... May 2024Formaldehyde is recognized as carcinogenic for the portal of entry sites, though conclusions are mixed regarding lymphohematopoietic (LHP) cancers. This systematic... (Meta-Analysis)
Meta-Analysis
Assessment of associations between inhaled formaldehyde and lymphohematopoietic cancer through the integration of epidemiological and toxicological evidence with biological plausibility.
Formaldehyde is recognized as carcinogenic for the portal of entry sites, though conclusions are mixed regarding lymphohematopoietic (LHP) cancers. This systematic review assesses the likelihood of a causal relationship between formaldehyde and LHP cancers by integrating components recommended by NASEM. Four experimental rodent bioassays and 16 observational studies in humans were included following the implementation of the a priori protocol. All studies were assessed for risk of bias (RoB), and meta-analyses were conducted on epidemiological studies, followed by a structured assessment of causation based on GRADE and Bradford Hill. RoB analysis identified systemic limitations precluding confidence in the epidemiological evidence due to inadequate characterization of formaldehyde exposure and a failure to adequately adjust for confounders or effect modifiers, thus suggesting that effect estimates are likely to be impacted by systemic bias. Mixed findings were reported in individual studies; meta-analyses did not identify significant associations between formaldehyde inhalation (when measured as ever/never exposure) and LHP outcomes, with meta-SMRs ranging from 0.50 to 1.51, depending on LHP subtype. No associations with LHP-related lesions were reported in reliable animal bioassays. No biologically plausible explanation linking the inhalation of FA and LHP was identified, supported primarily by the lack of systemic distribution and in vivo genotoxicity. In conclusion, the inconsistent associations reported in a subset of the evidence were not considered causal when integrated with the totality of the epidemiological evidence, toxicological data, and considerations of biological plausibility. The impact of systemic biases identified herein could be quantitatively assessed to better inform causality and use in risk assessment.
Topics: Formaldehyde; Humans; Animals; Inhalation Exposure; Hematologic Neoplasms; Risk Assessment; Carcinogens
PubMed: 38547404
DOI: 10.1093/toxsci/kfae039 -
The Science of the Total Environment Jun 2024Waste disposal in landfills remains a global concern. Despite technological developments, landfill leachate poses a hazard to ecosystems and human health since it acts... (Review)
Review
Waste disposal in landfills remains a global concern. Despite technological developments, landfill leachate poses a hazard to ecosystems and human health since it acts as a secondary reservoir for legacy and emerging pollutants. This study provides a systematic and scientometric review of the nature and toxicity of pollutants generated by landfills and means of assessing their potential risks. Regarding human health, unregulated waste disposal and pathogens in leachate are the leading causes of diseases reported in local populations. Both in vitro and in vivo approaches have been employed in the ecotoxicological risk assessment of landfill leachate, with model organisms ranging from bacteria to birds. These studies demonstrate a wide range of toxic effects that reflect the complex composition of leachate and geographical variations in climate, resource availability and management practices. Based on bioassay (and other) evidence, categories of persistent chemicals of most concern include brominated flame retardants, per- and polyfluorinated chemicals, pharmaceuticals and alkyl phenol ethoxylates. However, the emerging and more general literature on microplastic toxicity suggests that these particles might also be problematic in leachate. Various mitigation strategies have been identified, with most focussing on improving landfill design or leachate treatment, developing alternative disposal methods and reducing waste volume through recycling or using more sustainable materials. The success of these efforts will rely on policies and practices and their enforcement, which is seen as a particular challenge in developing nations and at the international (and transboundary) level. Artificial intelligence and machine learning afford a wide range of options for evaluating and reducing the risks associated with leachates and gaseous emissions from landfills, and various approaches tested or having potential are discussed. However, addressing the limitations in data collection, model accuracy, real-time monitoring and our understanding of environmental impacts will be critical for realising this potential.
Topics: Humans; Artificial Intelligence; Ecotoxicology; Environmental Monitoring; Environmental Policy; Refuse Disposal; Risk Assessment; Waste Disposal Facilities; Water Pollutants, Chemical
PubMed: 38513865
DOI: 10.1016/j.scitotenv.2024.171804 -
Prevalence of latent tuberculosis infection in Asian nations: A systematic review and meta-analysis.Immunity, Inflammation and Disease Feb 2024Tuberculosis (TB) is a serious public health concern around the world including Asia. TB burden is high in Asian countries and significant population harbor latent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis (TB) is a serious public health concern around the world including Asia. TB burden is high in Asian countries and significant population harbor latent tuberculosis infection(LTBI).
AIM
This systematic review and meta-analysis aims to evaluate the prevalence of LTBI in Asian countries.
METHOD
We performed a systematic literature search on PubMed, Embase, and ScienceDirect to identify relevant articles published between January 1, 2005, and January 1, 2023 investigating the overall prevalence of latent TB among people of Asia. Subgroup analysis was done for Asian subregions during the study period of 2011 to 2016 and 2017 to 2023, for tuberculin skin test (TST) and interferon gamma release assay (IGRA), respectively, as well as for QuantiFERON-TB (QFT) and TSPOT TB tests. Der Simonian and Laird's random-effects model was used to pool the prevalence of LTBI found using TST and IGRA.
RESULT
A total of 15 studies were included after a systematic search from standard electronic databases. The analysis showed that the prevalence of latent TB in Asia was 21% (95% confidence interval [CI]: 19%-23%) and 36% (95% CI: 12%-59%) according to IGRAs and TSTs (cut off 10 mm) results, respectively. Based on IGRA, the prevalence of latent TB was 20% (95% CI: 13%-25%) in 2011 to 2016 and 21% (95% CI: 18%-24%) in 2017 to 2023. Using QFT, the prevalence was 19% (95% CI: 17%-22%) and using TSPOT, the prevalence was 26% (95% CI: 21%-31%). According to the United Nations division of Asia, the prevalence was higher for the Southern region and least for the Western region using TST and higher in the South-Eastern region and least in the Western region using the IGRA test.
CONCLUSION
Almost a quarter of the Asian population has LTBI. Its diagnosis often poses a diagnostic challenge due to the unavailability of standard test in certain areas. Given this prevalence, a mass screening program is suggested with the available standard test and public awareness along with anti-TB regimen should be considered for individuals who test positive. However, for it to be implemented effectively, we need to take the affordability, availability, and cost-effectiveness of such interventions into account.
Topics: Humans; Latent Tuberculosis; Prevalence; Biological Assay; Databases, Factual
PubMed: 38411377
DOI: 10.1002/iid3.1200 -
International Journal of Molecular... Jan 2024The chorioallantoic membrane (CAM) model, generated during avian development, can be used in cancer research as an alternative in vivo model to perform tumorigenesis in... (Review)
Review
The chorioallantoic membrane (CAM) model, generated during avian development, can be used in cancer research as an alternative in vivo model to perform tumorigenesis in ovo due to advantages such as simplicity, low cost, rapid growth, and being naturally immunodeficient. The aim of this systematic review has been to compile and analyze all studies that use the CAM assay as a tumor induction model. For that, a systematic search was carried out in four different databases: PubMed, Scopus, Cochrane, and WOS. After eliminating duplicates and following the established inclusion and exclusion criteria, a total of 74 articles were included. Of these, 62% use the in ovo technique, 13% use the ex ovo technique, 9% study the formation of metastasis, and 16% induce tumors from patient biopsies. Regarding the methodology followed, the main species used is chicken (95%), although some studies use quail eggs (4%), and one article uses ostrich eggs. Therefore, the CAM assay is a revolutionary technique that allows a simple and effective way to induce tumors, test the effectiveness of treatments, carry out metastasis studies, perform biopsy grafts of patients, and carry out personalized medicine. However, unification of the methodology used is necessary.
Topics: Animals; Chick Embryo; Humans; Biological Assay; Chorioallantoic Membrane; Neoplasms, Experimental; Precision Medicine
PubMed: 38255911
DOI: 10.3390/ijms25020837 -
International Journal of Molecular... Dec 2023The dental material industry is rapidly developing resin-based composites (RBCs), which find widespread use in a variety of clinical settings. As such, their... (Review)
Review
The dental material industry is rapidly developing resin-based composites (RBCs), which find widespread use in a variety of clinical settings. As such, their biocompatibility has gained increasing interest. This literature review presents a summary of research into the cytotoxicity of methacrylate-based composites published from 2017 to 2023. Subject to analysis were 14 in vitro studies on human and murine cell lines. Cytotoxicity in the included studies was measured via MTT assay, LDH assay, and WST-1 assay. The QUIN Risk of Bias Tool was performed to validate the included studies. Included studies (based entirely on the results of in vitro studies) provide evidence of dose- and time-dependent cytotoxicity of dental resin-based composites. Oxidative stress and the depletion of cellular glutathione (GSH) were suggested as reasons for cytotoxicity. Induction of apoptosis by RBCs was indicated. While composites remain the golden standard of dental restorative materials, their potential cytotoxicity cannot be ignored due to direct long-term exposure. Further in vitro investigations and clinical trials are required to understand the molecular mechanism of cytotoxicity and produce novel materials with improved safety profiles.
Topics: Humans; Animals; Mice; Apoptosis; Biological Assay; Cell Line; Dental Materials; Glutathione
PubMed: 38203323
DOI: 10.3390/ijms25010152