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Marine Drugs Jul 2020Natural phenolic compounds are important classes of plant, microorganism, and algal secondary metabolites. They have well-documented beneficial biological activities.... (Review)
Review
Natural phenolic compounds are important classes of plant, microorganism, and algal secondary metabolites. They have well-documented beneficial biological activities. The marine environment is less explored than other environments but have huge potential for the discovery of new unique compounds with potential applications in, e.g., food, cosmetics, and pharmaceutical industries. To survive in a very harsh and challenging environment, marine organisms like several seaweed (macroalgae) species produce and accumulate several secondary metabolites, including marine phenolics in the cells. Traditionally, these compounds were extracted from their sample matrix using organic solvents. This conventional extraction method had several drawbacks such as a long extraction time, low extraction yield, co-extraction of other compounds, and usage of a huge volume of one or more organic solvents, which consequently results in environmental pollution. To mitigate these drawbacks, newly emerging technologies, such as enzyme-assisted extraction (EAE), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), pressurized liquid extraction (PLE), and supercritical fluid extraction (SFE) have received huge interest from researchers around the world. Therefore, in this review, the most recent and emerging technologies are discussed for the extraction of marine phenolic compounds of interest for their antioxidant and other bioactivity in, e.g., cosmetic and food industry. Moreover, the opportunities and the bottleneck for upscaling of these technologies are also presented.
Topics: Aquatic Organisms; Chemical Fractionation; Chromatography, Supercritical Fluid; Diffusion of Innovation; Enzymes; Microwaves; Phenols; Secondary Metabolism; Solvents; Ultrasonic Waves
PubMed: 32726930
DOI: 10.3390/md18080389 -
Asian Pacific Journal of Cancer... Feb 2024We aim to compare TRAK & TPS based isodose volumes in cervical cancer brachytherapy and assess the feasibility, accuracy and potential future implications of TRAK in...
OBJECTIVE
We aim to compare TRAK & TPS based isodose volumes in cervical cancer brachytherapy and assess the feasibility, accuracy and potential future implications of TRAK in this regard and as a newer emerging tool to assess treatment intensity in cervical cancer brachytherapy.
METHODS
one hundred patients with histologically proven squamous cell carcinoma of cervix uteri were assessed for brachytherapy (after completion of external radiation) and prospectively enrolled for the study. 60 Gy, 75 Gy, and 85 Gy isodose volumes were obtained from the TPS (VTPS) for 50, 25 & 25 patients with Manchester, Fletcher & interstitial implant respectively, receiving various fractionation schedules by Ir192 HDR remote after-loading system. Using the formula Vpred=4965(TRAK/dref)3/2+170(TRAK/dref)-1.5 the TRAK based isodose surface volumes (Vpred) were derived. Reference doses (dref) were calculated based on accumulated EBRT and brachytherapy doses. The two sets of volume were compared with respect to applicator type, standard, and optimised plan. Surrogate point A dose was also correlated.
RESULT
VTPS - Vpred were 5.24 ± 2.7%, all volumes being predicted within 10%. Correlation of TRAK vs VTPS60/ VTPS75/ VTPS85 showed R2 of 0.994, 0.987 and 0.971 respectively. There was no significant difference in predicted volumes with respect to applicator type. The surrogate point A showed mean volume and standard deviation of 7.44 ± 13.4%, 17.63 ± 16.38 and 3.5 ± 0.95 for Manchester optimised, Fletcher optimised and standard plans respectively. TRAK with point A (R2=0.5632), bladder (R2=0.2015) and rectal doses (R2=0.121) yielded no correlation.
CONCLUSION
Volumes calculated by TRAK correlate with TPS obtained volumes significantly and the formula predicting isodose surface volumes within 10% accuracy for ICBT applications and not for pure interstitial implants. However, TRAK fails to correlate with surrogate point A, bladder and rectal doses hence has questionable utility as a marker for biological response & treatment intensity.
Topics: Female; Humans; Radiotherapy Dosage; Brachytherapy; Uterine Cervical Neoplasms; Radiotherapy Planning, Computer-Assisted; Dose Fractionation, Radiation
PubMed: 38415545
DOI: 10.31557/APJCP.2024.25.2.587 -
Radiosurgery and fractionated stereotactic body radiotherapy for patients with lung oligometastases.BMC Cancer May 2020Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a...
BACKGROUND
Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimens. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT (fSBRT) in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes.
METHODS
Fifty-two patients with 94 LM treated with SFRS or fSBRT between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS) and progression-free survival.
RESULTS
Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1-5). The median planning target volume (PTV)-encompassing dose for SFRS was 24 Gy (range: 17-26) compared to 45 Gy (range: 20-60) in 2-12 fractions with fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89 and 83% vs. 75 and 59%, respectively (p = 0.026). LM treated with SFSR were significantly smaller (p = 0.001). The 1 and 2-year OS rates for all patients were 84 and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED < 100 Gy were significantly associated with better LC. However, none of these parameters remained significant in the multivariate Cox regression model. OS was significantly better in patients with negative lymph nodes (N0), Karnofsky performance status (KPS) > 70% and time to first metastasis ≥12 months. There was no grade 3 acute or late toxicity.
CONCLUSIONS
Longer time to first metastasis, good KPS and N0 predicted better OS. Good LC and low toxicity rates were achieved after short SBRT schedules.
Topics: Adult; Aged; Aged, 80 and over; Dose Fractionation, Radiation; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prognosis; Radiosurgery; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Retrospective Studies; Survival Rate
PubMed: 32393261
DOI: 10.1186/s12885-020-06892-4 -
International Journal of Radiation... Jan 2020To develop and validate combined ion-beam with constant relative biological effectiveness (RBE) (CICR) particle therapy in single field arrangements for improved...
PURPOSE
To develop and validate combined ion-beam with constant relative biological effectiveness (RBE) (CICR) particle therapy in single field arrangements for improved treatment efficacy, robustness, and normal tissue sparing.
METHODS AND MATERIALS
The PRECISE (PaRticle thErapy using single and Combined Ion optimization StratEgies) treatment planning system was developed to investigate clinical viability of CICR treatments. Single-field uniform dose (SFUD) with a single ion (proton [p], helium [He], or carbon [C]) and CICR (C-p and C-He) treatments were generated for 3 patient cases with a clinically prescribed dose of 3 Gy (RBE) per fraction. Spread-out Bragg peak plans were irradiated in homogenous and clinical-like settings using an anthropomorphic head phantom. A dosimetric and biological verification of CICR treatments using a murine glioma cell line (GL261) was performed.
RESULTS
CICR treatment plans for the 3 patients presented highly uniform physical dose while reducing high dose-averaged linear energy transfer gradients compared with carbon ions alone. When considering uncertainty in tissue parameter (α/β) assignment and RBE modeling, the CICR treatment exhibited enhanced biophysical stability within the target volume, similar to protons alone. CICR treatments reduced dose to normal tissue surrounding the target, exhibiting similar or improved dosimetric features compared with SFUD. For both CICR and SFUD treatments, measurements verified the planned dose in the target within ∼3%. Planned versus measured target RBE values were 1.38 ± 0.02 and 1.39 ± 0.07 (<1% deviation), respectively, for the CICR treatment in heterogenous settings.
CONCLUSIONS
Here, we demonstrate that by combining 2 (or more) ions in a single field arrangement, more robust biological and more conformal dose distributions can be delivered compared with conventional particle therapy treatment planning. This work constitutes the first dosimetric and biological verification of multi-ion particle therapy in homogeneous as well as heterogenous settings.
Topics: Animals; Brain Neoplasms; Carbon; Carcinoma, Adenoid Cystic; Cell Line, Tumor; Chordoma; Combined Modality Therapy; Dose Fractionation, Radiation; Glioma; Heavy Ion Radiotherapy; Helium; Humans; Linear Energy Transfer; Mice; Organ Sparing Treatments; Organs at Risk; Phantoms, Imaging; Proton Therapy; Radiation Injuries; Radiotherapy Planning, Computer-Assisted; Relative Biological Effectiveness; Sacrum; Spinal Neoplasms
PubMed: 31610250
DOI: 10.1016/j.ijrobp.2019.10.008 -
Strahlentherapie Und Onkologie : Organ... Jul 2020To investigate the dosimetric influence of daily interfractional (inter) setup errors and intrafractional (intra) target motion on the planning target volume (PTV) and...
PURPOSE
To investigate the dosimetric influence of daily interfractional (inter) setup errors and intrafractional (intra) target motion on the planning target volume (PTV) and the possibility of an offline adaptive radiotherapy (ART) method to correct larger patient positioning uncertainties in image-guided radiotherapy for prostate cancer (PCa).
MATERIALS AND METHODS
A CTV (clinical target volume)-to-PTV margin ranging from 15 mm in LR (left-right) and SI (superior-inferior) and 5-10 mm in AP (anterior-posterior) direction was applied to all patients. The dosimetric influence of this margin was retrospectively calculated by analysing systematic and random components of inter and intra errors of 31 consecutive intermediate- and high-risk localized PCa patients using daily cone beam computed tomography and kV/kV (kilo-Voltage) imaging. For each patient inter variation was assessed by observing the first 4 treatment days, which led to an offline ART-based treatment plan in case of larger variations.
RESULTS
Systematic inter uncertainties were larger (1.12 in LR, 2.28 in SI and 1.48 mm in AP) than intra systematic errors (0.44 in LR, 0.69 in SI and 0.80 mm in AP). Same findings for the random error in SI direction with 3.19 (inter) and 2.30 mm (intra), whereas in LR and AP results were alike with 1.89 (inter) and 1.91 mm (intra) and 2.10 (inter) and 2.27 mm (intra), respectively. The calculated margin revealed dimensions of 4-5 mm in LR, 8-9 mm in SI and 6-7 mm in AP direction. Treatment plans which had to be adapted showed smaller variations with 1.12 (LR) and 1.72 mm (SI) for Σ and 4.17 (LR) and 3.75 mm (SI) for σ compared to initial plans with 1.77 and 2.62 mm for Σ and 4.46 and 5.39 mm for σ in LR and SI, respectively.
CONCLUSION
The currently clinically used margin of 15 mm in LR and SI and 5-10 mm in AP direction includes inter and intra uncertainties. The results show that offline ART is feasible which becomes a necessity with further reductions in PTV margins.
Topics: Adenocarcinoma; Aged; Aged, 80 and over; Artifacts; Combined Modality Therapy; Cone-Beam Computed Tomography; Dose Fractionation, Radiation; Fiducial Markers; Humans; Male; Motion; Organs at Risk; Patient Positioning; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy Setup Errors; Radiotherapy, Image-Guided; Radiotherapy, Intensity-Modulated; Rectum; Retrospective Studies; Uncertainty
PubMed: 32157345
DOI: 10.1007/s00066-020-01596-x -
The Science of the Total Environment Aug 2022A sensitive analytical method has been developed and validated for the determination of 16 polyfluorinated alkyl substances (PFAS) in fine airborne particulate matter...
A new on-line SPE LC-HRMS method for the analysis of Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) in PM and its application for screening atmospheric particulates from Dublin and Enniscorthy, Ireland.
A sensitive analytical method has been developed and validated for the determination of 16 polyfluorinated alkyl substances (PFAS) in fine airborne particulate matter (PM) using on-line solid phase extraction (SPE) coupled with liquid chromatography (LC) - negative electrospray ionisation high resolution mass spectrometry (-) ESI-HRMS. On-line SPE allows simultaneous sample clean-up from interfering matrices and lower limits of detection (LODs) by injecting a large volume of sample into the LC system without compromising chromatographic efficiency and resolution. The method provides LODs in the range 0.08-0.5 pg/mL of sample extract allowing detection of selected PFAS in aerosol particles at low fg/m level and showed good tolerance to the considered PM matrix. The validated method was applied for analysis of PFAS in ambient PM samples collected at two urban locations in Ireland, i.e., Enniscorthy and Dublin. Several PFAS were observed above the detection limit, including perfluorobutyrate (PFBA), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorobutanesulfonic acid (L-PFBS) and perfluorononanoic acid (PFNA), as well as fluorotelomer sulfonates: 4:2 FTS, 6:2 FTS and 8:2 FTS. The results indicate that some toxic PFAS, such as PFOS and PFOA, are still detected in the environment despite being phased out from production and subject to restricted use in the EU and USA for more than two decades. Observation of fluorotelomer sulfonates (4:2 FTS, 6:2 FTS and 8:2 FTS, which are used as alternatives for legacy PFOA and PFOS) in ambient PM samples raises a concern about their persistence in the atmosphere and impact on human health considering emerging evidence that they could have similar health endpoints as PFOA and PFOS. To our knowledge, this is the first study to identify PFAS in ambient PM at urban locations in Ireland and also the first study to detect 4:2 and 8:2 fluorotelomer sulfonates in atmospheric aerosol particles.
Topics: Alkanesulfonic Acids; Chromatography, Liquid; Dust; Fluorocarbons; Humans; Ireland; Particulate Matter; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization
PubMed: 35483471
DOI: 10.1016/j.scitotenv.2022.155496 -
Lung Cancer (Amsterdam, Netherlands) Mar 2024Post-therapy pneumonitis (PTP) is a relevant side effect of thoracic radiotherapy and immunotherapy with checkpoint inhibitors (ICI). The influence of the combination of...
OBJECTIVES
Post-therapy pneumonitis (PTP) is a relevant side effect of thoracic radiotherapy and immunotherapy with checkpoint inhibitors (ICI). The influence of the combination of both, including dose fractionation schemes on PTP development is still unclear. This study aims to improve the PTP risk estimation after radio(chemo)therapy (R(C)T) for lung cancer with and without ICI by investigation of the impact of dose fractionation on machine learning (ML)-based prediction.
MATERIALS AND METHODS
Data from 100 patients who received fractionated R(C)T were collected. 39 patients received additional ICI therapy. Computed Tomography (CT), RT segmentation and dose data were extracted and physical doses were converted to 2-Gy equivalent doses (EQD2) to account for different fractionation schemes. Features were reduced using Pearson intercorrelation and the Boruta algorithm within 1000-fold bootstrapping. Six single (clinics, Dose Volume Histogram (DVH), ICI, chemotherapy, radiomics, dosiomics) and four combined models (radiomics + dosiomics, radiomics + DVH + Clinics, dosiomics + DVH + Clinics, radiomics + dosiomics + DVH + Clinics) were trained to predict PTP. Dose-based models were tested using physical dose and EQD2. Four ML-algorithms (random forest (rf), logistic elastic net regression, support vector machine, logitBoost) were trained and tested using 5-fold nested cross validation and Synthetic Minority Oversampling Technique (SMOTE) for resampling in R. Prediction was evaluated using the area under the receiver operating characteristic curve (AUC) on the test sets of the outer folds.
RESULTS
The combined model of all features using EQD2 surpassed all other models (AUC = 0.77, Confidence Interval CI 0.76-0.78). DVH, clinical data and ICI therapy had minor impact on PTP prediction with AUC values between 0.42 and 0.57. All EQD2-based models outperformed models based on physical dose.
CONCLUSIONS
Radiomics + dosiomics based ML models combined with clinical and dosimetric models were found to be suited best for PTP prediction after R(C)T and could improve pre-treatment decision making. Different RT dose fractionation schemes should be considered for dose-based ML approaches.
Topics: Humans; Immune Checkpoint Inhibitors; Radiomics; Lung Neoplasms; Radiation Oncology; Pneumonia
PubMed: 38394745
DOI: 10.1016/j.lungcan.2024.107507 -
Environmental Toxicology and Chemistry Nov 2020Effects-directed analysis (EDA) is used to identify the principal toxic components within a complex mixture using iterative steps of chemical fractionation guided by...
Effects-directed analysis (EDA) is used to identify the principal toxic components within a complex mixture using iterative steps of chemical fractionation guided by bioassay results. Bioassay selection can be limited in EDA because of the volume requirements for many standardized test methods, and therefore, a reduced-volume acute toxicity test that also provides whole-organism responses is beneficial. To address this need, a static, 7-d, water-only, reduced-volume method (50 mL, 10 organisms) was developed for Hyalella azteca that substantially decreases the volume requirements of standard-volume acute test exposures (200-500 mL of test solution, 15-20 organisms) while maintaining water quality and meeting control survival criteria. Standard- and reduced-volume methods were compared by conducting concurrent toxicity tests with 2 inorganic toxicants (KCl and CdCl ) and 2 organic mixtures of naphthenic acid fraction components (NAFCs) to evaluate test performance. There was no difference between methods when comparing the median lethal concentrations (LC50s) for KCl and both NAFC mixtures (p > 0.05). The LC50s for CdCl were statistically different (p = 0.0002); however, this was not considered biologically meaningful because the difference between LC50s was <2-fold. In conclusion, the reduced-volume H. azteca test method generated results comparable to standard-volume test methods and is suitable for use in situations where limited testing material is available, such as when conducting EDA. Environ Toxicol Chem 2020;39:2221-2227. © Her Majesty the Queen in Right of Canada 2020. Reproduced with the permission of the Minister of Environment and Climate Change Canada.
Topics: Amphipoda; Animals; Cadmium Chloride; Carboxylic Acids; Female; Fresh Water; Lethal Dose 50; Potassium Chloride; Toxicity Tests, Acute; Water Pollutants, Chemical; Water Quality
PubMed: 32761933
DOI: 10.1002/etc.4840 -
Radiation Oncology (London, England) Dec 2021To report prostate deformation during treatment, based on an analysis of fiducial marker positional differences in a large sample.
BACKGROUND
To report prostate deformation during treatment, based on an analysis of fiducial marker positional differences in a large sample.
MATERIAL AND METHODS
This study included 144 patients treated with prostate stereotactic body radiation therapy after implantation in each of 4 gold fiducial markers (FMs), which were located and numbered consistently. The center of mass of the FMs was recorded for every pair of X-ray images taken during treatment. The distance between each pair of fiducials in the live X-ray images is calculated and compared with the respective distances as determined in the CT volume. The RBE is the difference between these distances. Mean RBE and intrafraction and interfraction RBE were evaluated. The intrafraction and intefraction RBE variability were defined as the standard deviation, respectively, of all RBE during 1 treatment fraction and of the mean daily RBE over the whole treatment course.
RESULTS
We analyzed 720 treatment fractions comprising 24,453 orthogonal X-ray image acquisitions. We observed a trend to higher RBE related to FM4 (apex) during treatment. The fiducial marker in the prostate apex could not be used in 16% of observations, in which RBE was > 2.5 mm. The mean RBEavg was 0.93 ± 0.39 mm (range 0.32-1.79 mm) over the 5 fractions. The RBEavg was significantly lower for the first and second fraction compared with the others (P < .001). The interfraction variability of RBEavg was 0.26 ± 0.16 mm (range 0.04-0.74 mm). The mean intrafraction variability of all FMs was 0.45 ± 0.25 mm. The highest Pearson correlation coefficient was observed between FM2 and FM3 (middle left and right prostate) (R = 0.78; P < .001). Every combination with FM4 yielded lower coefficients (range 0.66-0.71; P < .001), indicating different deformation of the prostate apex.
CONCLUSIONS
Ideally, prostate deformation is generally small, but it is very sensitive to rectal and bladder filling. We observed RBE up to 11.3 mm. The overall correlation between FMs was affected by shifts of individual fiducials, indicating that the prostate is not a "rigid" organ. Systematic change of RBE average between subsequent fractions indicates a systematic change in prostate shape.
Topics: Fiducial Markers; Humans; Image Processing, Computer-Assisted; Male; Movement; Prostatic Neoplasms; Prostheses and Implants; Radiation Dose Hypofractionation; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided; Radiotherapy, Intensity-Modulated; Tomography, X-Ray Computed
PubMed: 34876173
DOI: 10.1186/s13014-021-01958-4 -
Journal of Advanced Veterinary and... Sep 2023This research aims to identify the effect of various organic solvents such as n-hexane, ethyl acetate (EtOAc), and methanol (MeOH) on the antioxidant and antibacterial...
OBJECTIVE
This research aims to identify the effect of various organic solvents such as n-hexane, ethyl acetate (EtOAc), and methanol (MeOH) on the antioxidant and antibacterial activities of extract, against three Gram-positive bacteria, namely and , and three Gram-negative bacteria, namely and .
MATERIALS AND METHODS
As much as 1 kg of white turmeric rhizome () was extracted two times for 24 h using 3 l of MeOH before evaporating. The extract was then fractionated using n-hexane six times per 2 h, with each volume of 500 ml, and continued with the EtOAc fractionation. The MeOH fraction was added to 300 ml of water before adding 400 ml of EtOAc. Once the fractionation process was complete, all fractions were concentrated using a rotary evaporator.
RESULTS
The extract fractioned using MeOH produces alkaloids, phenolics, flavonoids, saponins, and coumarin compounds. The fractionation with EtOAc also produces alkaloids, phenolics, flavonoids, saponins, coumarin compounds, and triterpenoids. Meanwhile, fractionation with n-hexane only produces alkaloids and triterpenoid compounds. EtOAc and MeOH fractions had good activity in reducing free radicals produced by 2,2-diphenyl-1-picrylhydrazyl (DPPH), with an average IC value of 153.49 ± 2.66 and 185.77 ± 3.91 ppm, respectively. In contrast, the n-hexane fraction has weak antioxidant activity with an IC value of 837.92 ± 5.32 ppm. The n-hexane fraction has better activity compared to MeOH and EtOAc. The lowest concentration required was 2,500 ppm for all types of bacteria.
CONCLUSION
extract produces alkaloids, phenolics, flavonoids, saponins, coumarins, and triterpenoids when fractionated with MeOH or EtOAc. Only alkaloids and triterpenoids are produced using n-hexane. EtOAc and MeOH fractions have good activity in reducing free radicals generated by DPPH, with an average IC value of 153.49 ± 2.66 and 185.77 ± 3.91 ppm, respectively. However, n-hexane has weak antioxidant activity, with an average IC value of 837.92 ± 5.32 ppm. All fractions have moderate antibacterial activity, but the extract of n-hexane from has better antibacterial activity compared to MeOH and EtOAc. The lowest concentration required is 2,500 ppm for all types of bacteria.
PubMed: 37969790
DOI: 10.5455/javar.2023.j687