There is currently a clear benefit for many countries to utilize wastewater-based epidemiology (WBE) as part of ongoing measures to manage the coronavirus disease 2019 (COVID-19) global pandemic. ...Since most wastewater virus concentration methods were developed and validated for nonenveloped viruses, it is imperative to determine the efficiency of the most commonly used methods for the enveloped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Municipal wastewater seeded with a human coronavirus (CoV) surrogate, murine hepatitis virus (MHV), was used to test the efficiency of seven wastewater virus concentration methods: (A–C) adsorption-extraction with three different pre-treatment options, (D–E) centrifugal filter device methods with two different devices, (F) polyethylene glycol (PEG 8000) precipitation, and (G) ultracentrifugation. MHV was quantified by reverse-transcription quantitative polymerase chain reaction and the recovery efficiency was calculated for each method. The mean MHV recoveries ranged from 26.7 to 65.7%. The most efficient methods were adsorption-extraction methods with MgCl2 pre-treatment (Method C), and without pre-treatment (Method B). The third most efficient method used the Amicon® Ultra-15 centrifugal filter device (Method D) and its recovery efficiency was not statistically different from the most efficient methods. The methods with the worst recovery efficiency included the adsorption-extraction method with acidification (A), followed by PEG precipitation (F). Our results suggest that absorption-extraction methods with minimal or without pre-treatment can provide suitably rapid, cost-effective and relatively straightforward recovery of enveloped viruses in wastewater. The MHV is a promising process control for SARS-CoV-2 surveillance and can be used as a quality control measure to support community-level epidemic mitigation and risk assessment.
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•Seven virus concentration methods were evaluated to recover CoV from wastewater.•The mean MHV recoveries ranged from 26.7 to 65.7%.•Adsorption-extraction with MgCl2 pre-treatment most efficiently concentrated MHV.•MHV seems to be an appropriate process control.
Highlights•The international multi-centre REQUITE study. •4438 breast, prostate or lung cancer patients undergoing radiotherapy. •Prospective standardised data and sample collection. •Validating ...predictive models and biomarkers for radiotherapy toxicity. •An accessible real-world resource for the radiotherapy community.
Abstract Many genes have been associated with radiotherapy toxicity, but most have only been found in a single study. Using our cohort of 480 breast cancer patients, we provide replicated evidence ...that a polymorphism near the LIG3 gene is associated with acute skin toxicity following radiotherapy.
An earlier study in the west of Scotland found no association between the duration of symptoms and the stage at presentation of 146 patients with cervical cancer. 2 Tumour proliferation rates were ...evaluated after in vivo labelling with the DNA precursor BrdUrd.
•Epistasis aware polygenic risk scores (PRSs) can predict late radiotherapy toxicity.•SNP-SNP interactions can be summarized to foster interpretability.•Allele combinations may be more informative ...with respect to single genetic variants.•Our interaction-aware score outperforms classical PRSs.
To identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi).
Analysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria, nocturia, decreased urinary stream. Among 43 literature-identified SNPs, the 30% most strongly associated with each toxicity were tested. SNP-SNP combinations (named SNP-allele sets) seen in ≥10% of the cohort were condensed into risk (RS) and protection (PS) scores, respectively indicating increased or decreased toxicity risk. Performance of RS and PS was evaluated by logistic regression. RS and PS were then combined into a single PRSi evaluated by area under the receiver operating characteristic curve (AUC).
Among 1,387 analysed patients, toxicity rates were 11.7% (rectal bleeding), 4.0% (urinary frequency), 5.5% (haematuria), 7.8% (nocturia) and 17.1% (decreased urinary stream). RS and PS combined 8 to 15 different SNP-allele sets, depending on the toxicity endpoint. Distributions of PRSi differed significantly in patients with/without toxicity with AUCs ranging from 0.61 to 0.78. PRSi was better than the classical summed PRS, particularly for the urinary frequency, haematuria and decreased urinary stream endpoints.
Our method incorporates SNP-SNP interactions when calculating PRS for radiotherapy toxicity. Our approach is better than classical summation in discriminating patients with toxicity and should enable incorporating genetic information to improve normal tissue complication probability models.
REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The ...purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors.
The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up. We used five separate late toxicity endpoints: ≥grade 1 late rectal bleeding, ≥grade 2 urinary frequency, ≥grade 1 haematuria, ≥ grade 2 nocturia, ≥ grade 1 decreased urinary stream. Forty-three single nucleotide polymorphisms (SNPs) already reported in the literature to be associated with the toxicity endpoints were included in the analysis. No SNP had been studied before in the REQUITE cohort. Deep Sparse AutoEncoders (DSAE) were trained to recognize features (SNPs) identifying patients with no toxicity and tested on a different independent mixed population including patients without and with toxicity.
One thousand, four hundred and one patients were included, and toxicity rates were: rectal bleeding 11.7%, urinary frequency 4%, haematuria 5.5%, nocturia 7.8%, decreased urinary stream 17.1%. Twenty-four of the 43 SNPs that were associated with the toxicity endpoints were validated as identifying patients with toxicity. Twenty of the 24 SNPs were associated with the same toxicity endpoint as reported in the literature: 9 SNPs for urinary symptoms and 11 SNPs for overall toxicity. The other 4 SNPs were associated with a different endpoint.
Deep learning algorithms can validate SNPs associated with toxicity after radiotherapy for prostate cancer. The method should be studied further to identify polygenic SNP risk signatures for radiotherapy toxicity. The signatures could then be included in integrated normal tissue complication probability models and tested for their ability to personalize radiotherapy treatment planning.
Principles of chemotherapy and radiotherapy Brown, Victoria; Sridhar, T; Symonds, R Paul
Obstetrics, gynaecology and reproductive medicine,
12/2011, Letnik:
21, Številka:
12
Journal Article
Recenzirano
Abstract The management of most malignancies is multidisciplinary with chemotherapy and radiotherapy widely employed. The reasons why tumours are destroyed and normal tissues recover after ...radiotherapy are complex and thought to be due to differences in intrinsic radiosensitivity and the ability to repair and repopulate between normal and malignant tissue. Some tumours are hypoxic which makes them radioresistant. Most radiotherapy treatments are carried out using a linear accelerator, which produces photons or high energy X-rays which are “skin-sparing” and can treat deep-seated tumours. Brachytherapy (short distance treatment) with implanted or internal radiation sources can also be used, and indeed is an essential part of the radical radiotherapy for cervical carcinoma. Chemotherapy consists of drugs of different classes and modes of actions. Chemotherapeutic agents currently in use are cytotoxic and affect both normal and malignant cells. Side effects include bone marrow suppression, nausea and vomiting, epilation, renal, cardiac and neurotoxicity. Combination chemotherapy using agents with different mechanisms of action is used to prevent potential drug resistance. Chemotherapy can also be given concurrently with radiotherapy to enhance the therapeutic effect. With advances in the understanding of the molecular biology of cancer, novel targeted therapies will likely play a major role in the future. Chemotherapy is generally employed in the palliative setting and therefore the risk/benefit ratio should be assessed for each patient.
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