Subsequent Fractions Research Articles

Incorporating patient-specific information for the development of rectal tumor auto-segmentation models for online adaptive magnetic resonance Image-guided radiotherapy

Background and purposeIn online adaptive magnetic resonance image (MRI)-guided radiotherapy (MRIgRT), manual contouring of rectal tumors on daily images is labor-intensive and time-consuming. Automation of this task is complex due to substantial variation in tumor shape and location between patients. The aim of this work was to investigate different approaches of propagating patient-specific prior information to the online adaptive treatment fractions to improve deep-learning based auto-segmentation of rectal tumors. Materials and methods243 T2-weighted MRI scans of 49 rectal cancer patients treated on the 1.5T MR-Linear accelerator (MR-Linac) were utilized to train models to segment rectal tumors. As benchmark, an MRI_only auto-segmentation model was trained. Three approaches of including a patient-specific prior were studied: 1. include the segmentations of fraction 1 as extra input channel for the auto-segmentation of subsequent fractions, 2. fine-tuning of the MRI_only model to fraction 1 (PSF_1) and 3. fine-tuning of the MRI_only model on all earlier fractions (PSF_cumulative). Auto-segmentations were compared to the manual segmentation using geometric similarity metrics. Clinical impact was assessed by evaluating post-treatment target coverage. ResultsAll patient-specific methods outperformed the MRI_only segmentation approach. Median 95th percentile Hausdorff (95HD) were 22.0 (range: 6.1–76.6) mm for MRI_only segmentation, 9.9 (range: 2.5–38.2) mm for MRI+prior segmentation, 6.4 (range: 2.4–17.8) mm for PSF_1 and 4.8 (range: 1.7–26.9) mm for PSF_cumulative. PSF_cumulative was found to be superior to PSF_1 from fraction 4 onward (p = 0.014). ConclusionPatient-specific fine-tuning of automatically segmented rectal tumors, using images and segmentations from all previous fractions, yields superior quality compared to other auto-segmentation approaches.

In vitro Cytotoxic and Anti-ROS Potentials of the Aerial Part of Pyrrosia lanceolata on A549 Cells and Cell Free Condition

Antioxidants and cancer are somewhat related to each other. The study was designated to evaluate the antioxidant activities of the aerial parts of Pyrosia lanceolata (P. lanceilata, Fam. Polypodiaceae) and their cytotoxic potential in a lung cancer cell line (A549). The extraction of plant material was performed by using methanol (CME), followed by solvent-solvent partitioning with different solvents. The methanol (CME) and its subsequent fractions (pet-ether PEF, chloroform CHF, ethyl acetate EAF and aqueous AQF fractions) confirmed the presence of alkaloids, flavonoids, phenols, tannins and terpenoids at different degrees. The phenolic and flavonoid content were found to be 69.46, 37.93, 64.61, 126.74 and 60.64 mg of GAE/gm and 33.93, 4.11, 45.68, 146.95, and 44.36 mg of CAE/gm of dried CME, PEF, CHF, EAF and AQF, respectively. The overall antioxidant and iron reduction capacities of CME and all the fractions were in the following order: EAF > CHF > CME > AQF > PEF and EAF > CHF > CME > AQF > PEF, respectively. Among the fractions, EAF significantly scavenged DPPH (IC50 of 1.34 μg/ml) and OH radicals (IC50 of 4.38 μg/ml), which closely resembled those of standard BHT (IC50 of 0.9 μg/ml) and CA (IC50 of 2.73 μg/ml), respectively. Moreover, EAF (IC50 of 14.06 μg/ml) demonstrated a similar effect on inhibiting lipid peroxidation when compared to standard CA (IC50 of 13.86 μg/ml). In addition, CHF (24.25%) and EAF (14.9%) showed a potent cytotoxic effect in A549 cells. Our results suggest that P. lanceolata might be a good source of anticancer potential having antioxidant activity. Bangladesh Pharmaceutical Journal 27(2): 137-148, 2024 (July)

Applying UPLC-QTOF-MS/MS to profile the phytochemical constituents associated with docking studies of major components of Ziziphora capitata L as well as antimicrobial and antioxidant activity assessments of its subsequent fractions

This study aimed to investigate the phytochemical constituents, antimicrobial activity, and antioxidant effects of successive extracts of Ziziphora capitata L. aerial parts. UPLC-QTOF-MS/MS identified 79 phytoconstituents, including phenolic acids, alkaloids, flavonoids, and anthocyanins, as major phytoconstituents. Additionally, primary phytochemical investigations revealed the presence of terpenoids, steroids, flavonoids, alkaloids, tannins, and saponins in various plant fractions. The MICs of successive extracts were tested against a range of microorganisms, including gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Streptococcus mutants, Enterococcus faecalis, Methicillin-Resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis), gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhimurium, and Enterobacter cloacae), fungi (Aspergillus niger and Penicillium aurantiogriseum), and yeast (Candida albicans and Candida tropicalis), using the disk diffusion technique. The ethyl acetate and 95% ethanol extracts exhibited significant antibacterial activity against the tested microorganisms; however, the hexane fraction affected only P. aeruginosa. The effects of the CHCl3 and H2O fractions varied in their activities against most of the bacteria examined. Additionally, the AcOEt and 95% EtOH extracts exhibited significant antioxidant activity with IC50 = 18.6 ± 0.97 and 30.4 ± 1.86 µg/mL, respectively, compared to that of ascorbic acid (IC50 = 10.6 ± 0.8 µg/mL, reference drug). Antibacterial and antioxidant activities can be attributed to phytoconstituents, which were identified using UPLC-QTOF-MS/MS. Furthermore, docking simulations of the top ten phytochemicals of the 70% methanolic extract were carried out inside the active site of S. aureus DNA gyrase (PDB: 2XCT) and dihydropteroate synthase (DHPS) from S. pneumoniae (PDB: 2VEG) as bacterial targets and these compounds exhibited good binding modes with different types of interactions.Graphical

Bio-chelate assisted leaching for enhanced heavy metal remediation in municipal solid waste compost

Municipal solid waste compost, the circular economy's closed-loop product often contains excessive amounts of toxic heavy metals, leading to market rejection and disposal as waste material. To address this issue, the study develops a novel approach based on: (i) utilizing plant-based biodegradable chelating agent, l-glutamic acid, N,N-diacetic acid (GLDA) to remediate heavy metals from contaminated MSW compost, (ii) comparative assessment of GLDA removal efficiency at optimal conditions with conventional nonbiodegradable chelator EDTA, and (iii) enhanced pre- and post-leaching to evaluate the mobility, toxicity, and bioavailability of heavy metals. The impact of treatment variables, such as GLDA concentration, pH, and retention time, on the removal of heavy metals was investigated. The process was optimized using response surface methodology to achieve the highest removal effectiveness. The findings indicated that under optimal conditions (GLDA concentration of 150 mM, pH of 2.9, retention time for 120 min), the maximum removal efficiencies were as follows: Cd-90.32%, Cu-81.96%, Pb-91.62%, and Zn-80.34%. This process followed a pseudo-second-order kinetic equation. Following GLDA-assisted leaching, the geochemical fractions were studied and the distribution highlighted Cd, Cu, and Pb's potential remobilization in exchangeable fractions, while Zn displayed integration with the compost matrix. GLDA-assisted leaching and subsequent fractions illustrated transformation and stability. Therefore, this process could be a sustainable alternative for industrial applications (agricultural fertilizers and bioenergy) and social benefits (waste reduction, urban landscaping, and carbon sequestration) as it has controlled environmental footprints. Hence, the proposed remediation strategy, chemically assisted leaching, could be a practical option for extracting heavy metals from MSW compost, thereby boosting circular economy.

The high-throughput solid-phase extraction of cis-cyclo(L-Leu-L-Pro) and cis-cyclo(L-Phe-L-Pro) from Lactobacillus plantarum demonstrates efficacy against multidrug-resistant bacteria and influenza A (H3N2) virus.

Introduction: 2,5-diketopiperazines are the simplest forms of cyclic dipeptides (CDPs) and have diverse frameworks with chiral side chains that are useful for drug development. Previous research has investigated the antimicrobial properties of proline-linked CDPs and their combinations in the culture filtrate (CF) of Lactobacillus plantarum LBP-K10 using anion exchange chromatography (AEC). However, the quantity of CDPs showcasing notable anti-influenza virus activity derived from AECs was generally lower than those originating from Lactobacillus CF. Methods: To address this issue, the study aims to propose a more efficient method for isolating CDPs and to introduce the antiviral combinations of CDPs obtained using a new method. The study employed a novel technique entailing high-throughput C18-based solid-phase extraction with a methanol gradient (MeSPE). The MeSPE method involved increasing the methanol concentration from 5% to 50% in 5% increments. Results: The methanol SPE fractions (MeSPEfs) eluted with methanol concentrations between 35% and 45% evinced substantial efficacy in inhibiting the influenza A/H3N2 virus via plaque-forming assay. MeSPEf-45, the 45% MeSPEf, exhibited exceptional efficacy in preventing viral infections in Madin-Darby kidney cells, surpassing both individual CDPs and the entire set of MeSPEfs. To identify the specific antiviral components of MeSPEf-45, all MeSPEfs were further fractionated through preparative high-performance liquid chromatography (prep-HPLC). MeSPEf-45 fractions S8 and S11 presented the highest activity against multidrug-resistant bacteria and influenza A/H3N2 virus among all MeSPEfs, with 11 common fractions. Antiviral fractions S8 and S11 were identified as proline-based CDPs, specifically cis-cyclo(L-Leu-L-Pro) and cis-cyclo(L-Phe-L-Pro), using gas chromatography-mass spectrometry. The combination of MeSPEf-45 fractions S8 and S11 displayed superior antibacterial and anti-influenza virus effects compared to the individual fractions S8 and S11. Discussion: High-throughput MeSPE-derived MeSPEfs and subsequent HPLC-fractionated fractions presents an innovative approach to selectively purify large amounts of potent antimicrobial CDPs from bacterial CF. The findings also show the effectiveness of physiologically bioactive combinations that utilize fractions not containing CDP. This study provides the initial evidence demonstrating the antimicrobial properties of CDPs acquired through high-throughput SPE techniques.

Anti-Diabetic, Anti-Cholinesterase, and Anti-Inflammatory Potential of Plant Derived Extracts and Column Semi-Purified Fractions of Ficus benghalensis.

The present study aimed to investigate the in-vitro anti-diabetic, anti-cholinesterase, and anti-inflammatory potential of extracts from different parts of Ficus benghalensis, including leaves, stem, and roots, as well as isolated column fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C). The extracts and subsequent fractions were evaluated for their inhibitory activity against key enzymes involved in diabetes [α-glucosidase and α-amylase], neurodegenerative diseases [acetylcholinesterase and butyrylcholinesterase], and inflammation (cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX)). The results showed that F. benghalensis leaf extract exhibited the highest α-glucosidase inhibitory activity (73.84%) and α-amylase inhibitory activity (76.29%) at 1000 µg/mL. The stem extract (65.50%) and F-B-2 C fraction (69.67%) also demonstrated significant α-glucosidase inhibitory activity. In terms of anti-cholinesterase activity, the extracts of roots, leaves, and stem showed promising inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with half maximal inhibitory concentration (IC50) values ranging from 50.50 to 474.83 µg/mL. The derived fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C) also exhibited notable inhibition of AChE and BChE, with IC50 values from 91.85 to 337.94 µg/mL. Moreover, the F-B-3 C fraction demonstrated the highest COX-2 inhibitory potential (85.72%), followed by F-B-1 C (83.13%), the stem extract (80.85%), and the leaves extract (79.00%). The F-B-1 C fraction showed the highest 5-LOX inhibitory activity (87.63%), while the root extract exhibited the lowest inhibition (73.39%). The results demonstrated promising bioactivity, suggesting the potential of F. benghalensis as a source of natural compounds with therapeutic applications. Further studies are required to identify and isolate the active components responsible for these effects and to evaluate their in-vivo efficacy and safety.

A Pilot Study of Simulation-Free Hippocampal-Avoidance Whole Brain Radiation Therapy Using Diagnostic MRI-Based and Online Adaptive Planning

We aimed to demonstrate the clinical feasibility and safety of simulation-free hippocampal avoidance whole brain radiation therapy (HA-WBRT) in a pilot study (National Clinical Trial 05096286). Ten HA-WBRT candidates were enrolled for treatment on a commercially available computed tomography (CT)-guided linear accelerator with online adaptive capabilities. Planning structures were contoured on patient-specific diagnostic magnetic resonance imaging (MRI), which were registered to a CT of similar head shape, obtained from an atlas-based database (AB-CT). These patient-specific diagnostic MRI and AB-CT data sets were used for preplan calculation, using NRG-CC001 constraints. At first fraction, AB-CTs were used as primary data sets and deformed to patient-specific cone beam CTs (CBCT) to give patient-matched density information. Brain, ventricle, and brain stem contours were matched through rigid translation and rotation to the corresponding anatomy on CBCT. Lens, optic nerve, and brain contours were manually edited based on CBCT visualization. Preplans were then reoptimized through online adaptation to create final, simulation-free plans, which were used if they met all objectives. Workflow tasks were timed. In addition, patients underwent CT-simulation to create immobilization devices and for prospective dosimetric comparison of simulation-free and simulation-based plans. Median time from MRI importation to completion of "preplan" was 1 weekday (range, 1-4). Median on-table workflow duration was 41 minutes (range, 34-70). NRG-CC001 constraints were achieved by 90% of the simulation-free plans. One patient's simulation-free plan failed a planning target volume coverage objective (89% instead of 90% coverage); this was deemed acceptable for first-fraction delivery, with an offline replan used for subsequent fractions. Both simulation-free and simulation CT-based plans otherwise met constraints, without clinically meaningful differences. Simulation-free HA-WBRT using online adaptive radiation therapy is feasible, safe, and results in dosimetrically comparable treatment plans to simulation CT-based workflows while providing convenience and time savings for patients.

Small-Scale Serial Size Exclusion Chromatography (s3SEC) for High Sensitivity Top-Down Proteomics of Large Proteoforms.

Top-down-mass spectrometry (MS)-based proteomics has emerged as a premier technology to examine proteins at the proteoform level, enabling characterization of genetic mutations, alternative splicing, and post-translational modifications. However, significant challenges that remain in top-down proteomics include the analysis of large proteoforms and the sensitivity required to examine proteoforms from minimal amounts of sample. To address these challenges, we have developed a new method termed "small-scale serial Size Exclusion Chromatography" (s3SEC), which incorporates a small-scale protein extraction (1 mg of tissue) and serial SEC without postfractionation sample handling, coupled with online high sensitivity capillary reversed-phase liquid chromatography tandem MS (RPLC-MS/MS) for analysis of large proteoforms. The s3SEC-RPLC-MS/MS method significantly enhanced the sensitivity and reduced the proteome complexity across the fractions, enabling the detection of high MW proteoforms previously undetected in one-dimensional (1D)-RPLC analysis. Importantly, we observed a drastic improvement in the signal intensity of high MW proteoforms in early fractions when using the s3SEC-RPLC method. Moreover, we demonstrate that this s3SEC-RPLC-MS/MS method also allows the analysis of lower MW proteoforms in subsequent fractions without significant alteration in proteoform abundance and equivalent or improved fragmentation efficiency to that of the 1D-RPLC approach. Although this study focuses on the use of cardiac tissue, the s3SEC-RPLC-MS/MS method could be broadly applicable to other systems with limited sample inputs.

A new clustering model based on the seminal plasma/serum ratios of multiple trace element concentrations in male patients with subfertility.

To investigate whether seminal plasma (SP)/serum ratios of multiple trace elements (TEs) can classify patients with male subfertility. SP/serum ratios of 20 TEs (lithium, sodium, magnesium, phosphorus, sulfur, potassium, calcium, manganese, iron, cobalt, copper, zinc, arsenic, selenium, rubidium, strontium, molybdenum, cesium, barium, and thallium) were calculated for healthy volunteers (n = 4) and those consulting for male subfertility (n = 245). Volunteer semen samples were collected by split ejaculation into early and subsequent fractions, and SP/serum ratio data were compared between fractions. The patients' SP/serum ratio data were used in an unsupervised clustering analysis and qualitatively compared with the data from the fractions of ejaculation from the volunteers. Semen quality parameters and pregnancy outcomes were compared between patient clusters. The early fraction of volunteers was characterized by lower phosphorus and arsenic and 18 other higher TEs than the subsequent fraction. Cluster analysis classified patients into four distinct clusters, one sharing characteristics with the early fraction and another with the subsequent fraction. One cluster with the early fraction characteristics had significantly lower semen volume and higher pregnancy rates from spontaneous pregnancies or intrauterine insemination. Classification of patients based on SP/serum ratios of multiple TEs represents the dominance of fractions of ejaculation samples.

Factors affecting the dosimetry of high-dose rate intracavitary brachytherapy in cervical cancer

Abstract Background: Intracavitary brachytherapy (ICBT) is essential in managing locally advanced cervical cancer. Brachytherapy as a modality has the advantage of a higher dose to the tumour with a dose fall off at the periphery as per the inverse square law. The dose per fraction is much higher than external beam radiotherapy. So proper application and dosimetry are of paramount importance to reduce late toxicity. Methods: A retrospective analysis of 69 patients who underwent three ICBT applications of 7 Gray in each fraction was done. The factors under consideration were the type of pain management (spinal anaesthesia (SA) versus conscious sedation (CS)), the initial size of the disease (bulky and non-bulky) and subsequent fractions (first fraction versus third fraction). The dosimetric parameters analysed were the doses received by points A, B and P and that of the critical organs (bladder, rectum and sigmoid colon). Results: The dose received by critical organs was comparable concerning all the factors under consideration. The dose to point P on the left side was significantly lower in the CS group than in the SA group (p-value = 0·031). Also, the dose to point P on the right side was significantly lower in the third fraction compared with the first fraction (p-value = 0·016). Conclusions: ICBT under spinal anaesthesia resulted in a higher dose to the pelvic wall. The initial size of the tumour or the subsequent fractions does not significantly affect the dose received by critical organs.

Anesthetic Challenges during Endobronchial Brachytherapy: A Case Report.

Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy (EBBT) has been shown to provide palliative therapy. It is the insertion of a radioactive material near the mass to reduce tumor size, thereby improving airway obstruction. This is the first case of EBBT done in our institution during the COVID-19 pandemic. A 53-year-old male, 60 kg, ASA Physical Status 2 for hypertension, smoker, malignancy, and previous pulmonary tuberculosis patient, presented with a cough and dyspnea. An endobronchial mass almost obstructing the right mainstem bronchus was seen on a computed tomography (CT) scan. He was diagnosed with squamous cell carcinoma of the lung and underwent radiotherapy and erlotinib chemotherapy. On repeat CT scan, there was no noted decrease in the size of the mass. EBBT was suggested, and a multi-disciplinary team was formed for the planned procedure. Pulmonology, radiation oncology, and anesthesiology teams were identified, and thorough planning was done prior to the actual procedure. Three fractions of EBBT were done under sedation using midazolam, fentanyl, and dexmedetomidine infusion. Lidocaine spray and transtracheal block were also performed as adjuncts prior to sedation. The procedure went as planned, and points for improvement were discussed for subsequent fractions. Due to persistent cough and discomfort from the catheter, additional ipratropium nebulization for minimization of secretions, and oral dextromethorphan for cough suppression were incorporated. After each fraction, the patient was monitored post-procedure for any side effects both from the radiotherapy and anesthetic technique. Qualitative reduction in mass size was noted in subsequent fractions. The patient was able to complete 3 fractions and was advised to follow-up after a month. EBBT is an emerging palliative and treatment modality for lung cancer, especially for intraluminal masses. Anesthetic considerations will depend on each case's characteristics such as airway anatomy, patient comfort and capacity, and procedural requirements. Conscious sedation with topical anesthesia is an adequate and appropriate anesthetic option, especially in cases where severe airway obstruction may compromise ventilation if airway reflexes are blunted. A multidisciplinary approach with different services and stakeholders is important for the proper planning, execution, and management of such patients.

In Vivo Verification of Electron Paramagnetic Resonance Biodosimetry Using Patients Undergoing Radiation Therapy Treatment

PurposeElectron paramagnetic resonance (EPR) biodosimetry, used to triage large numbers of individuals incidentally exposed to unknown doses of ionizing radiation, is based on detecting a stable physical response in the body that is subject to quantifiable variation following exposure. In vivo measurement is essential to fully characterize the radiation response relevant to a living tooth measured in situ. The purpose of this study was to verify EPR spectroscopy in vivo by estimating the radiation dose received in participants’ teeth. MethodsA continuous wave L-band spectrometer was used for EPR measurements. Participants included healthy volunteers and patients undergoing head and neck (H&N) and total body irradiation (TBI) treatments. Healthy volunteers completed one measurement each, while patients underwent measurement prior to starting treatment and between subsequent fractions. Optically stimulated luminescent dosimeters and diodes were used to determine the dose delivered to the teeth to validate EPR measurements. ResultsSeventy measurements were acquired from 4 TBI and 6 H&N patients over 15 months. Patient data showed a linear increase of EPR signal with delivered dose across the dose range tested. A linear least-squares weighted fit of the data gave a statistically significant correlation between EPR signal and absorbed dose (p-value <0.0001). The standard error of inverse prediction (SEIP), used to assess the usefulness of fits, was 1.92 Gy for the dose range most relevant for immediate triage (≤ 7 Gy). Correcting for natural background radiation based on patient age reduced the SEIP to 1.51 Gy. ConclusionThis study demonstrated the feasibility of using spectroscopic measurements from radiotherapy patients to validate in vivo EPR biodosimetry. The data illustrated a statistically significant correlation between the magnitude of EPR signals and absorbed dose. The SEIP of 1.51 Gy, obtained under clinical conditions, indicates the potential value of this technique in response to large radiation events.

Volumes Changes in Adrenal Metastases during Delivery of 5-Fraction Stereotactic Magnetic Resonance-Guided Adaptive Radiotherapy

Stereotactic MR-guided adaptive radiotherapy (SMART) improves adrenal target coverage and reduces organ at risk doses. Changes in adrenal tumor volumes were observed during contouring for daily-adaptive planning. We hypothesized that such changes in GTV may correlate with long-term outcomes. An Ethics approved institutional database was accessed for details of 5-fraction adrenal SABR treatments on a 0.35T MR-Linac between 2016-2023. Volumetric MR-scans were acquired at baseline, and prior to each of 5 fractions. Manually contoured GTVs were accessed. Volume changes between simulation and first fraction (ΔPF1), as well as between first and subsequent fractions (ΔF1F2 to ΔF1F5) were computed. Daily relative adrenal volume change (DRVC) and the absolute volume change (DAVC) before treatment, were calculated by dividing ΔPF1 by the number of days between simulation and F1. Paired Wilcoxon tests were used to compare volumes at different timepoints. Univariate linear regression (LinR) models were created to study per-treatment volume changes. A logistic regression (LogR) analysis explored associations between baseline characteristics and volumetric changes with radiological complete response (CR) at the date of last news. Adrenal SMART in 5 fractions of either 8 or 10Gy was delivered to 70 patients. The median interval between simulation and F1 was 13 days (range, 2-35), and 13 days between F1-F5 (range, 9-31). Solitary metastasis comprised 44%; metastases were mainly from non-small cell lung (64%) or renal (9%) primaries. Concurrent systemic therapy (± 3 months) was delivered in 41% of patients. Mean baseline GTV at simulation and F1 were respectively 38.5 and 41.4cc (p<0.001). Mean ΔPF1 was +9.1% (-10.2% to +50.1%) or +2.9cc (-4.4 to +27.4cc). Mean DRVC was +0.8% per day (-1.0% to +8.4%), and did not correlate with histology, GTV or concurrent systemic treatment. Mean DAVC was +0.26cc per day (-0.31 to +2.4cc), and was associated with GTV size (p = 0.04). In total, 47% of adrenal GTVs decreased in volume at F5 compared to F1. A ≥10% increase in GTV was observed in 39% of patients during SMART. GTV variations of ≥20% occurred in 36% patients at some point during SMART. At a median follow-up of 20.3 months, radiological CR was seen in 23% of 64 evaluable patients. Radiological CR was significantly associated with baseline GTV (p = 0.03) and ΔF1F5 (p = 0.03), but not DRVC (p = 0.6) or ΔF1F3 (p = 0.3). Local relapses were seen in 6% of patients. Changes in adrenal volumes during SMART were common, with variations ≥20% occurring in 36% patients. The probability of a radiological CR correlated with both baseline GTV size and median relative volume decline between fractions 1 and 5. These changes support use of daily SABR plan adaptation.

Comparison of three analgesic regimens in women undergoing cervical brachytherapy

PURPOSEEffective periprocedural analgesia is an important aspect of cervical brachytherapy delivery, with implications for patient comfort and attendance for subsequent fractions. We compared the efficacy and safety of three analgesic modalities: intravenous patient-controlled analgesia (IV-PCA), continuous epidural infusion (CEI) and programmed-intermittent epidural bolus with patient-controlled epidural analgesia (PIEB-PCEA). METHODS AND MATERIALSNinety-seven brachytherapy episodes involving 36 patients between July 2016 and June 2019 in a single tertiary center were retrospectively reviewed. Episodes were divided into two key phases: Phase 1 (while applicator remained in situ) and Phase 2 (following applicator removal until discharge or 4 h). For the primary endpoint, pain scores were retrieved and analyzed by analgesic modality with respect to median score and an internally defined “unacceptable” pain experience (>20% of scores being ≥4/10; i.e., moderate or greater). Total nonepidural oral morphine equivalent dose (OMED) and toxicity/complication events were reported as secondary endpoints. RESULTSIn Phase 1, there was a significantly higher median pain score (p < 0.001) and more episodes with unacceptable pain scores (46%) in the IV-PCA group compared with either epidural modality (6–14%; p < 0.001).In Phase 2, we observed a greater median pain score (p = 0.007) and higher proportion of patient episodes with unacceptable pain scores (38%) in the CEI group compared with both the IV-PCA (13%) and PIEB-PCEA (14%) groups (p = 0.001).There was a significant difference in median OMED used throughout all phases across the PIEB-PCEA (0 mg), IV-PCA (70 mg), and CEI (15 mg) groups (p < 0.001). CONCLUSIONSPIEB-PCEA is safe and offers superior analgesia compared to IV-PCA or CEI for pain control after applicator placement in cervical brachytherapy.

Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin-induced allergic-asthma model in guinea-pigs: Evidences from ex vivo, in silico and in vivo studies.

Tylophora indica (Burm. f.) Merr is a climbing perennial plant reported in Indian traditional system of medicine for its use in allergy and asthma. However, only few scientific studies have been performed in the past to validate its antiasthmatic potential. The present study deals with investigation of airway smooth muscle relaxant and antiasthmatic potential of extract and subsequent fractions prepared from T.indica. The most active fraction of T.indica leaves selected through bio-guided activity was subjected to liquid chromatography-mass spectrometry (LC-MS) analysis for chemical profiling. The binding affinity of identified compounds in fraction towards M3 and H1 receptors was determined by molecular docking study. F-2 (chloroform fraction prepared from methanolic extract of T.indica leaves) was examined for its smooth muscle relaxant properties using isolated trachea of guinea-pig. Further, F-2 was evaluated through in vivo studies employing ovalbumin-induced asthma model in guinea-pigs. F-2 was found most effective in bioassay-guided fractionation. Characterization by LC-MS analysis revealed presence of five major bioactive compounds in F-2 that showed good docking interactions with M3 and H1 receptors. The ex vivo study demonstrated that F-2 could significantly relax tracheal rings via targeting multiple signalling pathways videlicet, namely, noncompetitive antagonism of the histamine and muscarinic receptors, β2-adrenergic stimulation and activation of soluble guanylyl cyclase. In in vivo studies, F-2 ameliorated airway hyperresponsiveness and decreased broncho alveolar lavage fluid (BALF) levels of inflammatory cytokines and immunoglobulin E (IgE). These results confirm the traditional use of T.indica as an antiasthmatic agent which are evidenced through ex vivo, in silico and in vivo studies.

The application of freezing technology for zinc removal from Faro pit mine-impacted water, Yukon, Canada

The application of freezing technology (cryopurification) could be a viable water treatment solution to the environmental industry, especially in northern climates as it holds several advantages, including high energy efficiency, the absence of chemical pre-treatment and cost-efficiency. The use of cryopurificiation in Northern Canada is of interest, considering three of the five largest federal contaminated mine sites where water treatment is typically required are located within Yukon and Northwest Territories. The current research aims to address the problem of elevated zinc concentrations in mine-impacted water (Faro Mine, Yukon, Canada) by applying cryopurification. The paper scope includes laboratory testing to quantitatively describe zinc removal from Faro Mine's water using cryopurification under various initial and boundary conditions. Based on laboratory testing results, zinc could be removed with an efficiency of above 75% and 95% using single-stage freezing under no mixing and constant mixing conditions, respectively and up to 97% in freezing-melting tests. The results reveal the purest ice production at freezing temperature range from −0.5 to −5 °C. Ice is purer with each subsequent melt fraction according to the results of freezing-melting laboratory tests. The addition of seed ice crystals enhances the purity of ice up to 10–14% and ice block shape has an effect on the purification process, as the results of laboratory testing show. The effect of mixing shows 23–72% improvement in overall removal efficiency depending on freezing temperature. The outcomes of current research form a foundation toward the development of an exceptional water treatment process utilizing northern climates' cold temperature conditions and having a potential to be scaled up.

Optimizing protein recovery from plant substrate using ultrafiltration: A case study on wheatgrass

Providing the world's population with valuable food and proteins is considered as one of the greatest challenges of the upcoming decade. In this study, a process to recover nitrogen/protein concentrates from wheatgrass using a cascaded ultrafiltration was investigated. First, washing of wheatgrass during a mechanical extraction was examined with a ratio up to 1:2 (press cake/washing fluid, w/w). This was followed by a statistical investigation (full factorial experimental design) on the influences of substrate storage conditions (SSC), pre-shredding (PS) and washing conditions (WC) on the protein content of the resulting fraction, expressed by a nitrogen recovery rate (NRR). Washing of wheatgrass during the mechanical extraction was found to increase NRR by up to 29%–67.8% at a 1:2 ratio (1:0–46.0%, 1:0.5–53.0%, 1:1–58.0%). Significant effects (p-value <0.05) were found in the resulting crude juice for the variation of SSC between fresh and frozen/thawed wheatgrass (NRR 80.5%/62.8%) and for washing/non-washing during the mechanical extraction (NRR 76.1%/67.2%). These significant influences were detected in almost all subsequent fractions, whereas no significant effect was found for the influence of pre-shredding (p-value >0.05). An optimal process consisting of processing freshly harvested wheatgrass and a washing ratio of 1:2 during mechanical extraction led to a protein-rich fraction by ultrafiltration with a NRR of 34.4%. This NRR is comparable to recovery rates achieved with established substrates and processes. The protein-rich fraction can meet the daily requirements of protein quantities and macro minerals such as potassium, magnesium and phosphorous, providing more than 100% of the recommended intake. It was noted that 41.6% of the nitrogen in wheatgrass fell to by-product streams that need to be utilized to increase economic potential (biorefinery).

Utility of an Artificial Intelligence Enabled Electrocardiogram for Risk Assessment in Liver Transplant Candidates.

Post-operative cardiac complications occur infrequently but contribute to mortality after liver transplantation (LT). Artificial intelligence-based algorithms based on electrocardiogram (AI-ECG) are attractive for use during pre-operative evaluation to screen for risk of post-operative cardiac complications, but their use for this purpose is unknown. The aim of this study was to evaluate the performance of an AI-ECG algorithm in predicting cardiac factors such as asymptomatic left ventricular systolic dysfunction or potential for developing post-operative atrial fibrillation (AF) in cohorts of patients with end-stage liver disease either undergoing evaluation for transplant or receiving a liver transplant. A retrospective study was performed in two consecutive adult cohorts of patients who were either evaluated for LT or underwent LT at a single center between 2017 and 2019. ECG were analyzed using an AI-ECG trained to recognize patterns from a standard 12-lead ECG which could identify the presence of left ventricular systolic dysfunction (LVEF < 50%) or subsequent atrial fibrillation. The performance of AI-ECG in patients undergoing LT evaluation is similar to that in a general population but was lower in the presence of prolonged QTc. AI-ECG analysis on ECG in sinus rhythm had an AUROC of 0.69 for prediction of de novo post-transplant AF. Although post-transplant cardiac dysfunction occurred in only 2.3% of patients in the study cohorts, AI-ECG had an AUROC of 0.69 for prediction of subsequent low left ventricular ejection fraction. A positive screen for low EF or AF on AI-ECG can alert to risk of post-operative cardiac dysfunction or predict new onset atrial fibrillation after LT. The use of an AI-ECG can be a useful adjunct in persons undergoing transplant evaluation that can be readily implemented in clinical practice.

Sigmoid dose accumulation and reporting for multifractionated brachytherapy for cervical cancer: Methodological development of sigmoid points through virtual endoscopic method

PURPOSEThe sigmoid is an important organ at risk for gynecological brachytherapy (BT). However, the reliability of localization of high-dose regions during multi-fractionated treatment is limited. This work reports the methodological development of sigmoid points to summate multi-fractionated doses. METHODS AND MATERIALTen paired MRI data sets of ring-based intracavitary brachytherapy were obtained. Simulating a virtual endoscope, a reference line was created along the central axis of the anorectosigmoid for each implant. A trendline was generated, and linear dose was determined. Three-dimensional (3D) coordinates of high-dose regions were identified, and overlap was determined. In the next step, 3D coordinates of high-dose sigmoid points were localized in reference to cervical os and re-verified for location in reference to sigmoid lumen and corroboration with 2cc doses. With minor modifications, sigmoid points were proposed. RESULTSIn 6 of 10 patients, high-dose regions co-localized in subsequent fractions of BT. Three high-dose regions were identified along the sigmoid length and proposed as sigmoid points in reference to cervical os. (S1’= 0.5 cm right, 1.5 cm posterior, and 2.4 cm cranial; S2’ = 0.3 cm anterior and 4.5 cm cranial; S3’ = 2.7 cm left, 3 cm anterior, and 3.6 cm cranial to the cervical os). S1’ and S2’ were located in the sigmoid in 70% and 60% of data sets. The mean difference between D2cc and S1’/S2’ was 0.30 Gy and 1.06 Gy respectively. S3’ had limited corroboration to sigmoid lumen or 2 cc doses. The points S1’ and S2’ were further modified (minor) for applicability and proposed as sigmoid points 1 and 2 (SP1 0.5 right,1.5 posterior and 2.5 cm cranial to cervical os and SP2 (0.5 cm anterior and 4.5 cm cranial to cervical os)). CONCLUSIONSP1 and SP 2 are proposed as a surrogate for 2 cc sigmoid doses and may provide a method of reliable inter-fraction dose summation. This pilot work requires further validation.

Method of Dose Delivery in Brachytherapy for Cervical Cancer

A method is proposed for delivering an absorbed dose to a target during brachytherapy for cervical cancer by using a new applicator, which consists of an annular part and two uterine canals. The design of the applicator makes it possible to implement it to the required depth, taking into account the anatomical features, to widely cover the cervix and corporis of a womb with a 100 % isodose of irradiation, which makes it possible to deliver the planned dose. The patient admitted to the brachytherapy department received the first treatment fraction using the Interstitial Ring applicator, the second and subsequent fractions were performed using the proposed applicator (6 fractions in total). In comparison with the standard applicator Interstitial Ring, the use of the proposed applicator made it possible to increase the coverage of the target with the prescribed dose from 69.2 to 95.5 %. This led to an increase in the absorbed dose per target for a course of radiation therapy from the planned 70.4 to 85.4 Gy. Twelve treatment plans for 3 patients were analyzed using different dose fractionation schemes. In all three cases, it was possible to increase the coverage of the target with the prescribed dose, which led to an increase in the total absorbed dose per target, which was more than 85 Gy. The proposed method has been successfully applied in the N. N. Alexandrov National Cancer Centre during brachytherapy for cancer of the cervix and corporis of a womb.