Multiple Fractions Research Articles

Advantages of single high-dose radiation therapy compared with conventional fractionated radiation therapy in overcoming radioresistance

Background Radioresistance is a major clinical challenge in cancer treatment, as it reduces the effectiveness of radiation therapy (RT). While advances in radiation delivery have enabled the clinical use of high-dose hypofractionated RT, its impact on radioresistant tumors remains unclear. This study aimed to compare the effects of single high-dose RT with conventional fractionated RT on radioresistant breast cancer cells and explore the underlying mechanisms. Methods Radioresistant cell lines were previously established by exposing SK-BR-3 and MCF-7 cells to 48 Gy and 70 Gy of radiation, respectively, in multiple fractions. We compared the effects of 2 Gy × 5 and 7 Gy × 1 fractions on these cells using clonogenic survival assays and western blot analysis. In vivo antitumor effects were assessed in SR tumor-bearing BALB/c mice irradiated with either 2 Gy × 5 or 7 Gy × 1 fractions. Results 7 Gy x1 was more efficient at killing radioresistant breast cancer cells than 2 Gy x5. Furthermore, the 7 Gy x1 fraction produced higher levels of reactive oxygen species (ROS) and decreased the expression of radioresistance factors such as p-STAT3, ACSL4, FOXM1, RAD51, Bcl-xL, and survivin. Consistent with the in vitro studies, the 7 Gy × 1 fraction also showed superior antitumor effects in SR tumor-bearing BALB/c mice. Conclusions Single high-dose RT offers superior advantages over conventional fractionated RT in regard to overcoming radioresistance, supporting its potential as a promising treatment for recurrent tumors.

ASW^2DF: Census of the obscured star formation in a galaxy cluster in formation at z=2.2

We report the results of the deep and wide Atacama Large Millimeter/submillimeter Array (ALMA) 1.2\,mm mapping of the Spiderweb protocluster at $z=2.16$. The observations were divided into six contiguous fields covering a survey area of 19.3\,arcmin$^2$. With sim 13h of on-source time, the final maps in the six fields reach the 1sigma rms noise in a range of $40.3-57.1\ at a spatial resolution of $0 By using different source extraction codes and careful visual inspection, we detected 47 ALMA sources at a significance higher than 4sigma . We constructed the differential and cumulative number counts down to $ after the correction for purity and completeness obtained from Monte Carlo simulations. The ALMA 1.2\,mm number counts of dusty star-forming galaxies (DSFGs) in the Spiderweb protocluster are overall two times that of general fields, with some regions showing even higher overdensities (more than a factor of three). This is consistent with the results from previous studies over a larger scale using single-dish instruments. Comparison of the spatial distributions between different populations indicates that our ALMA sources are likely drawn from the same distribution as CO(1-0) emitters from the COALAS large program but are distinct from that of Halpha emitters. The cosmic star formation rate density of the ALMA sources is consistent with previous results (e.g., LABOCA 870\,mu m observations) after accounting for the difference in volume. We show that molecular gas masses estimates from dust measurements are not consistent with the ones derived from CO(1-0) and thus have to be taken with caution. The multiplicity fraction of single-dish DSFGs is higher than that of the field. Moreover, two extreme concentrations of ALMA sources were found on the outskirts of the Spiderweb protocluster, with an excess of more than 12 times that of the general fields. These results indicate that the ALMA-detected DSFGs are supplied through gas accretion along filaments and are triggered by intense star formation by accretion shocks before falling into the cluster center. The identified two galaxy groups are likely falling into the protocluster center and will trigger new merger events eventually, as indicated in simulations.

Exploring the dynamical evolution of Cepheid multiplicity in star clusters and its implications for B-star multiplicity at birth

Classical Cepheid variable stars provide a unique probe of binary evolution in intermediate-mass stars over the course of several tens to hundreds of Myr. In addition, understanding binary evolution with the inclusion of cluster dynamics is desirable for obtaining a more complete picture of these stars, especially as they play a vital role in distance determinations. We studied the binary and multiple properties of Cepheids, assuming that all mid-B stars form in binaries inside star clusters. We also estimated the birth multiplicity of mid-B stars by comparing the observed multiplicity statistics of Cepheids with models based on particular assumptions. The clusters were modelled with the code, including synthetic stellar and binary evolutionary tracks. The Cepheids were identified from their position on the Hertzsprung-Russell diagram. The dynamical cluster environment results in a higher binary fraction among the Cepheids that remain in star clusters ($ 60$<!PCT!>) than among the Cepheids which have escaped to the field ($ 35$<!PCT!>). The fraction of Cepheids in triples ($ 30$<!PCT!> and $ 10$<!PCT!> in clusters and field, respectively) follows the same trend. In clusters, the binary, triple, and multiple fraction decreases with increasing cluster mass. More massive clusters have binaries of shorter orbital periods than lower mass clusters and field Cepheids. Mergers are very common with $ 30$<!PCT!> of mid-B stars not evolving to Cepheids because of the interaction with their companion. Approximately $40$ <!PCT!> of Cepheids have merged with their companion, and the merger event impacts stellar evolution, so that $ 25$<!PCT!> of all Cepheids occur at an age by more than $40$<!PCT!> different than what would be expected from their mass and the current cluster age; the expected age of Cepheids can differ from the age of their host cluster. Our models predict that one in five Cepheids is the result of a merger between stars with mass below the lower mass limit for Cepheids; in clusters, these objects occur substantially later than expected from their mass. Approximately $10$<!PCT!> of binary Cepheids have a different companion from the zero-age main sequence (ZAMS) one, and $ 3$ to $5$<!PCT!> of all Cepheids have a compact companion ($ 0.15$ <!PCT!> of all Cepheids are accompanied by a black hole). The binary fraction derived from our simulations (42<!PCT!>) underestimates the observed binary Cepheid fraction by approximately a factor of 2. This suggests that the true multiplicity fraction of B-stars at birth could be substantially larger than unity and, thus, that mid-B stars may typically form in triple and higher order systems.

Fractionated photoimmunotherapy stimulates an anti-tumour immune response: an integrated mathematical and in vitro study

BackgroundAdvanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery.MethodsWe use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction. The model outputs were used to calculate how photoimmunotherapy could be utilised for tumour control.ResultsIn vitro measurements of PIT dose responses revealed that although low light doses (<10 J/cm2) lead to limited tumour cell killing they also increased proliferation of anti-tumour immune effector cells. Model simulations demonstrated that breaking up a larger light dose into multiple lower dose fractions (vis-à-vis fractionated radiotherapy) could be utilised to effect tumour control via stimulation of an anti-tumour immune response.ConclusionsThere is promise for applying fractionated PIT in the setting of EOC. However, recommending specific fractionated PIT dosimetry and timing will require appropriate model calibration on tumour-immune interaction data in human patients and subsequent validation of model predictions in prospective clinical trials.

Quartz enhanced low sampling trace gas detection

Abstract Dectection of the exhaled gas, which can effectively reflect human health status, analyze and predict diseases has become a research focus. Quartz enhanced photoacoustic spectroscopy (QEPAS) technology has the advantages of small volume, low cost, and high sensitivity, exhibiting great potential in exhaled gas detection. In this work, small volume fractions of CO were detected by QEPAS technology. Optimizing the structure based on finite element method and designing circuit, a detection system with adjustable photoacoustic cell pressure was established. Then, the corresponding relationship between gas volume fraction and response signal was calibrated by the detection of multiple volume fractions of CO. The system has shown a volume fraction detection limit of 531.2×10−9, with a normalized noise equivalent absorption coefficient of 2.86×10−8 cm−1/Hz1/2 and an average detection error of less than 0.8%. The results indicate that our QEPAS system could monitor the exhaled CO trace gas, showing broad application prospects.

1677: First late rectal bleeding biological NTCP model for multiple fractionation schedules

1677: First late rectal bleeding biological NTCP model for multiple fractionation schedules

Predicting the entire pyrolysis process of representative charring material infiltrated with kerosene using an improved artificial neural network

It is crucial to predict the entire pyrolysis process of charring materials infiltrated with flammable liquids to provide guidance for reducing the fire hazards and implementing numerical simulations of fire accidents caused by the leakage of flammable liquids. In the present study, pyrolysis data obtained from the thermogravimetric experiments were preprocessed using linear interpolation and data normalization methods. The processed data set was then used to train the artificial neural network (ANN) framework to predict the pyrolysis behaviors of typical charring material (Mongolian Scots pine) infiltrated with typical flammable liquid (kerosene) under three different conditions: (1) pyrolysis at a constant mass fraction of kerosene with multiple heating rates; (2) pyrolysis at multiple mass fractions of kerosene with a constant heating rate; and (3) pyrolysis at multiple mass fractions of kerosene and multiple heating rates. The ANN, with the double hidden layer structure (6−3), was capable to well predict the entire pyrolysis behaviors of Mongolian Scots pine under all the three scenarios. Besides, five data transformation function (multiplication, exponential function with base e, logarithmic function with base e, square root, and exponentiation function) were applied to the present three input variables (temperature, mass fraction of kerosene, and heating rate) to generate new input variables in order to extract more characteristics among the pyrolysis data. Therein, the ANN utilizing the data transformation functions of multiplication and exponential function with base e exhibited the best predictive ability. Among the three input variables in the ANN (temperature, mass fraction of kerosene, and heating rate), temperature was identified as the most sensitive one to the prediction performance, followed by mass fraction of kerosene, with heating rate being the least sensitive.

Re-treatment of bone metastases for pain control: 2023 ASTRO education panel.

Bone metastases are a common and debilitating consequence of advanced cancer, often necessitating palliative radiation therapy (RT) for pain relief. Reirradiation (reRT) of bone metastases is often considered after lack of pain relief following an initial course of RT, after a partial but unsatisfying pain response to an initial course of radiotherapy, or after pain recurrence following a complete or partial pain response to an initial course of RT. The NCIC CTG SC.20 trial, a landmark multicenter, randomized, non-blinded, controlled non-inferiority trial, addressed the critical question of optimal dose fractionation for reRT in this patient population. This trial compared the efficacy and toxicity of a single 8 Gy fraction to multiple fractions totaling 20 Gy in 850 patients with painful bone metastases requiring reRT. The primary endpoint was overall pain response at 2 months, with secondary endpoints of quality of life (QoL) measures, functional interference, and toxicity profiles assessed using patient-reported questionnaires and the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. The intention-to-treat analysis revealed no significant difference in pain response between the two arms, meeting the pre-specified non-inferiority criteria. The per-protocol analysis suggested a potential benefit for a subset of patients receiving multiple fractions, although this was not statistically robust. Acute toxicities were more prevalent in the multiple fractions arm, with implications for patient comfort and healthcare utilization. Importantly, responders to reRT reported significant improvements in functional interference and QoL. The trial's findings support the use of a patient-centric approach to palliative RT, highlighting the viability of a single 8 Gy fraction as a less toxic and more convenient treatment option, albeit with consideration for individual patient circumstances. These results have significant implications for clinical practice, potentially reducing healthcare burdens while optimizing patient convenience during palliative care for painful bone metastases.

A comprehensive review on versatile microalga Tetraselmis: Potentials applications in wastewater remediation and bulk chemical production

Microalgae are considered sustainable resources for the production of biofuel, feed, and bioactive compounds. Among various microalgal genera, the Tetraselmis genus, containing predominantly marine microalgal species with wide tolerance to salinity and temperature, has a high potential for large-scale commercialization. Until now, Tetraselmis sp. are exploited at smaller levels for aquaculture hatcheries and bivalve production. However, its prolific growth rate leads to promising areal productivity and energy-dense biomass, so it is considered a viable source of third-generation biofuel. Also, microbial pathogens and contaminants are not generally associated with Tetraselmis sp. in outdoor conditions due to faster growth as well as dominance in the culture. Numerous studies revealed that the metabolite compositions of Tetraselmis could be altered favorably by changing the growth conditions, taking advantage of its acclimatization or adaptation ability in different conditions. Furthermore, the biorefinery approach produces multiple fractions that can be successfully upgraded into various value-added products along with biofuel. Overall, Tetraselmis sp. could be considered a potential strain for further algal biorefinery development under the circular bioeconomy framework. In this aspect, this review discusses the recent advancements in the cultivation and harvesting of Tetraselmis sp. for wider application in different sectors. Furthermore, this review highlights the key challenges associated with large-scale cultivation, biomass harvesting, and commercial applications for Tetraselmis sp.

Chronic e-cigarette use in young adults is associated with reduced cardiopulmonary function at rest and during exercise

E-cigarette aerosols produce contaminant particles that have the potential to impair cardiopulmonary function. However, the current understanding of the impact of e-cigarette use on cardiopulmonary function remains inconclusive. Exercise represents a stress on the cardiopulmonary system and may help identify cardiopulmonary dysfunction in chronic e-cigarette users. Consequently, the purpose of this study was to investigate if e-cigarette users exhibit cardiopulmonary abnormalities under physiological stress of exercise. To further investigate pulmonary vascular responses, the secondary purpose of the study was to examine how diffusing capacity (DLCO), pulmonary capillary blood volume (VC), and membrane diffusing capacity (DM) respond to positional changes, as the transition from the upright to supine position should increase DLCO, VC, and DM, secondarily to increased perfusion pressure. We hypothesized that e-cigarette users would exhibit impaired cardiopulmonary function during exercise and reduced pulmonary vascular responsiveness to postural changes. Six chronic e-cigarette (e-cig) users (age: 24±5yrs, 5±2 years of e-cigarette use) with &lt;5 pack years of traditional cigarette smoking history and six non-smoking controls who were age-, height-, and sex-matched completed two experimental trials. Day 1: Pulmonary function test and cardiopulmonary exercise test. Day 2: multiple fraction of inspired oxygen DLCO technique to quantify DLCO, VC, and DM at rest in the upright and supine positions. Resting pulmonary function was not significantly different between groups. The change in DLCO from upright to supine was significantly lower in e-cig users compared to controls (Control: 7.61±2.32 ml/min/mmHg vs. E-cig: 3.17±2.09 ml/min/mmHg; p=0.01), due to a smaller change in VC ( p=0.03), which suggests reduced pulmonary vascular distention in e-cig users. V̇O2peak was significantly lower in e-cig users compared to controls (Control: 4.4±1.2 L/min vs. E-cig: 2.6 ±0.7 L/min; p=0.01). E-cig users exhibited significantly elevated V̇E/ V̇CO2nadir ( p=0.02) indicating worse ventilatory effciency, and greater dyspnea relative to power output ( p=0.02) compared to controls. Preliminary findings suggest that e-cigarette use is associated with normal resting lung function but reduced pulmonary vascular distensibility. Further, e-cigarette users demonstrate ventilatory ineffciency and greater exertional dyspnea along with exercise intolerance. Canadian Institutes of Health Research. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ni2+ removal by ion exchange resins and activated carbon: a benchtop NMR study

Heavy metal pollution in water is a critical environmental concern, demanding effective remediation techniques. Traditional methods, including ion exchange and adsorption, often rely on inductively coupled plasma (ICP) atomic emission spectroscopy/mass spectrometry (AES/MS) for the indirect and time-consuming measurement of residual metal concentrations. In contrast, this study employs innovative direct monitoring of nickel removal by benchtop NMR relaxometry using the paramagnetic properties of Ni2+. To prove the feasibility of the NMR follow-up of Ni2+ uptake, batch experiments were performed with Amberlite IR120, Amberlite IRC748, Dowex Marathon MSC, and activated carbon (AC), which were previously characterized by various techniques. The effect of contact time, pH, and Ni2+ concentration on removal efficiency were studied. Pseudo-first and pseudo-second order kinetic models were used. The Langmuir model effectively described the equilibrium isotherms. The longitudinal and transverse relaxation curves of the loaded resins were biexponential. For sulfonic resins, a strong correlation was observed between the relaxation rates of the fast-relaxing fraction and the Ni2+ content determined by ICP-AES/MS. For IRC748, the effect of Ni2+ loading on the relaxation rates was weaker because of Ni2+ complexation. The relaxation curves of loaded AC revealed multiple fractions. Centrifugation was employed to eliminate the contribution of intergranular water. The remaining intragranular water contribution was biexponential. For high Ni2+ loadings, the relaxation rates of the slow relaxing fraction increased with the AC Ni2+ content. These results mark the initial stage in developing a column experiment to monitor, in real-time, adsorbent loading by NMR relaxometry.

Motion compensated cone-beam CT reconstruction using an a priori motion model from CT simulation: a pilot study

Objective. To combat the motion artifacts present in traditional 4D-CBCT reconstruction, an iterative technique known as the motion-compensated simultaneous algebraic reconstruction technique (MC-SART) was previously developed. MC-SART employs a 4D-CBCT reconstruction to obtain an initial model, which suffers from a lack of sufficient projections in each bin. The purpose of this study is to demonstrate the feasibility of introducing a motion model acquired during CT simulation to MC-SART, coined model-based CBCT (MB-CBCT). Approach. For each of 5 patients, we acquired 5DCTs during simulation and pre-treatment CBCTs with a simultaneous breathing surrogate. We cross-calibrated the 5DCT and CBCT breathing waveforms by matching the diaphragms and employed the 5DCT motion model parameters for MC-SART. We introduced the Amplitude Reassignment Motion Modeling technique, which measures the ability of the model to control diaphragm sharpness by reassigning projection amplitudes with varying resolution. We evaluated the sharpness of tumors and compared them between MB-CBCT and 4D-CBCT. We quantified sharpness by fitting an error function across anatomical boundaries. Furthermore, we compared our MB-CBCT approach to the traditional MC-SART approach. We evaluated MB-CBCT’s robustness over time by reconstructing multiple fractions for each patient and measuring consistency in tumor centroid locations between 4D-CBCT and MB-CBCT. Main results. We found that the diaphragm sharpness rose consistently with increasing amplitude resolution for 4/5 patients. We observed consistently high image quality across multiple fractions, and observed stable tumor centroids with an average 0.74 ± 0.31 mm difference between the 4D-CBCT and MB-CBCT. Overall, vast improvements over 3D-CBCT and 4D-CBCT were demonstrated by our MB-CBCT technique in terms of both diaphragm sharpness and overall image quality. Significance. This work is an important extension of the MC-SART technique. We demonstrated the ability of a priori 5DCT models to provide motion compensation for CBCT reconstruction. We showed improvements in image quality over both 4D-CBCT and the traditional MC-SART approach.

The Physics of Indirect Estimators of Lyman Continuum Escape and their Application to High-Redshift JWST Galaxies

ABSTRACT Reliable indirect diagnostics of LyC photon escape from galaxies are required to understand which sources were the dominant contributors to reionization. While multiple LyC escape fraction (fesc) indicators have been proposed to trace favourable conditions for LyC leakage from the interstellar medium of low-redshift ‘analogue’ galaxies, it remains unclear whether these are applicable at high redshifts where LyC emission cannot be directly observed. Using a library of 14 120 mock spectra of star-forming galaxies with redshifts 4.64 ≤ z ≤ 10 from the SPHINX20 cosmological radiation hydrodynamics simulation, we develop a framework for the physics that leads to high fesc. We investigate LyC leakage from our galaxies based on the criteria that successful LyC escape diagnostics must (i) track a high-specific star formation rate, (ii) be sensitive to stellar population age in the range 3.5–10 Myr representing the times when supernova first explode to when LyC production significantly drops, and (iii) include a proxy for neutral gas content and gas density in the interstellar medium. O32, ΣSFR, MUV, and H β equivalent width select for one or fewer of our criteria, rendering them either necessary but insufficient or generally poor diagnostics. In contrast, UV slope (β), and E(B − V) match two or more of our criteria, rendering them good fesc diagnostics (albeit with significant scatter). Using our library, we build a quantitative model for predicting fesc based on direct observables. When applied to bright z &amp;gt; 6 Ly α emitters observed with JWST, we find that the majority of them have $f_{\rm esc} \lesssim 10~{{\ \rm per\ cent}}$.

Microwave-based removal of polyurethane and epoxy floor coatings

A new debonding technique based on microwave stimulation is being investigated in epoxy and polyurethane floor coatings by combining specific microwave absorbers with temperature-induced blowing agents. Current methods, including mechanical processes such as grinding, typically produce materials with multiple fractions, impeding recycling and the establishment of a circular economy. The microwave method facilitates mono-fraction materials and enhances accessibility to commonly used recycling techniques, particularly in solvolytic processes such as polyurethane recycling. Consequently, a standard two-layer coating system is used, consisting of an epoxy primer and a polyurethane overlay. Various microwave absorbers, such as carbon black and carbon fibres, as well as blowing agents based on thermally expanding particles are investigated. The influence of the additives on the thermo-mechanical properties is studied to identify suitable combinations. The modified materials are later evaluated for their mechanical properties. Two microwave antennas, operating at a frequency of 2.45 GHz and power of 1 kW, are used and compared to activate the modified coating systems. The technology has been successfully integrated into the formulation to allow mono-fraction recovery of the materials. No significant negative effects on material quality were observed. However, due to the extended processing time required for the debonding, further optimisation is necessary. Nevertheless, the feasibility of utilising a laboratory-based microwave approach has been substantiated.

Evaluation of the safety and efficacy of high-dose rate brachytherapy for radiorecurrent prostate cancer: asystematic review and meta-analysis.

High-dose-rate brachytherapy (HDR-BT) plays an important role in the treatment of locally recurrent prostate cancer after definitive treatment. The objective of this study is to summarize the efficacy and toxicity of HDR-BT in these patients. We performed asystematic review of PubMed and EMBASE from inception to July 2023. The primary endpoint was relapse-free survival (RFS) in different subgroups, and the secondary endpoint was gastrointestinal (GI) and genitourinary (GU) toxicity. Asemi-automated tool (WebPlotDigitizer) and anew Shiny application combined with Rsoftware (R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria; https://www.R-project.org/ ) helped to reconstruct survival curves. Twenty-six studies met the inclusion criteria for quantitative analysis, including 1447 patients. Atotal of 761 patients from 13studies were included in survival reconstruction, and the median RFS time was 61.2 months (57.6-72.0months). The estimated 2‑, 3‑, and 5‑year rates were 75.9% (95% confidence interval [CI] 72.8 ~ 79.2%), 66.7% (95% CI 63.0 ~ 70.5%), and 52.3% (95% CI 47.5 ~ 57.4%), respectively. Whole-gland irradiation with multiple fractions (≥ 2F) resulted in better RFS compared with focal gland irradiation with fewer fractions (1F mostly; hazard ratio [HR]: 0.60, 95% CI 0.47-0.77, p < 0.0001). According to the different median time from primary treatment to salvage therapy (TRS) and median age at recurrence, short median TRS (56-67.2 months vs. 70-120 months; HR 0.52, 95% CI 0.68-0.40; p < 0.0001) and younger median age (60-70years vs. 71-75years; HR 0.58, 95% CI 0.46-0.74; p < 0.0001) were positive factors for RFS. The cumulative incidences estimated for grade ≥ 3 acute and late GU toxicities were 1% (95% CI 0 ~ 1%) and 5% (95% CI 4 ~ 7%), respectively. Three patients (3/992) experienced grade ≥ 3 late GI toxicity, and no cases of grade ≥ 3 acute GI toxicity were reported. HDR-BT has ahigh safety profile and good RFS benefit for salvage treatment of radiorecurrent prostate cancer. In terms of RFS, whole-gland irradiation with multiple fractions seems to be better than focal gland irradiation with fewer fractions, while short TRS and younger age are good prognostic factors. In view of the low level of evidence in the included studies and the large heterogeneity of each study, these conclusions still need to be confirmed by randomized controlled trials.

Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET

BackgroundRadiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience.MethodsThis study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival.DiscussionThis study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone.Trial registrationClinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

Goodbye to Chi by Eye: A Bayesian Analysis of Photometric Binaries in Six Open Clusters

We present a robust methodology for identifying photometric binaries in star clusters. Using Gaia DR3, Pan-STARRS, and Two Micron All Sky Survey data, we self-consistently define the cluster parameters and binary demographics for the open clusters (OCs) NGC 2168 (M35), NGC 7789, NGC 6819, NGC 2682 (M67), NGC 188, and NGC 6791. These clusters span in age from ∼200 Myr (NGC 2168) to more than ∼8 Gyr (NGC 6791) and have all been extensively studied in the literature. We use the Bayesian Analysis of Stellar Evolution software suite to derive the age, distance, reddening, metallicity, binary fraction, and binary mass-ratio posterior distributions for each cluster. We perform a careful analysis of our completeness and also compare our results to previous spectroscopic surveys. For our sample of main-sequence stars with masses between 0.6 and 1 M ⊙, we find that these OCs have similar binary fractions that are also broadly consistent with the field multiplicity fraction. Within the clusters, the binary fraction increases dramatically toward the cluster centers, likely a result of mass segregation. Furthermore nearly all clusters show evidence of mass segregation within the single and binary populations. The OC binary fraction increases significantly with cluster age in our sample, possibly due to a combination of mass-segregation and cluster-dissolution processes. We also find a hint of an anticorrelation between binary fraction and cluster central density as well as total cluster mass, possibly due to an increasing frequency of higher-energy close stellar encounters that inhibit long-period binary survival and/or formation.

Postnatal development of mouse spermatogonial stem cells as determined by immunophenotype, regenerative capacity, and long-term culture-initiating ability: a model for practical applications

Spermatogonial stem cells (SSCs) are the foundation of life-long spermatogenesis. While SSC research has advanced greatly over the past two decades, characterization of SSCs during postnatal development has not been well documented. Using the mouse as a model, in this study, we defined the immunophenotypic profiles of testis cells during the course of postnatal development using multi-parameter flow cytometry with up to five cell-surface antigens. We found that the profiles progress over time in a manner specific to developmental stages. We then isolated multiple cell fractions at different developmental stages using fluorescent-activated cell sorting (FACS) and identified specific cell populations with prominent capacities to regenerate spermatogenesis upon transplantation and to initiate long-term SSC culture. The data indicated that the cell fraction with the highest level of regeneration capacity exhibited the most prominent potential to initiate SSC culture, regardless of age. Interestingly, refinement of cell fractionation using GFRA1 and KIT did not lead to further enrichment of regenerative and culture-initiating stem cells, suggesting that when a high degree of SSC enrichment is achieved, standard markers of SSC self-renewal or commitment may lose their effectiveness to distinguish cells at the stem cell state from committed progenitors. This study provides a significant information resource for future studies and practical applications of mammalian SSCs.

Single versus multiple fraction stereotactic radiosurgery for medium-sized brain metastases (4-14 cc in volume): reducing or fractionating the radiosurgery dose?

Stereotactic radiosurgery (SRS) of brain metastases (BM) and resection cavities is a widely used and effective treatment modality. Based on target lesion size and anatomical location, single fraction SRS (SF-SRS) or multiple fraction SRS (MF-SRS) are applied. Current clinical recommendations conditionally recommend either reduced dose SF-SRS or MF-SRS for medium-sized BM (2-2.9 cm in diameter). Despite excellent local control rates, SRS carries the risk of radionecrosis (RN). The purpose of this study was to assess the 12-months local control (LC) rate and 12-months RN rate of this specific patient population. This single-center retrospective study included 54 patients with medium-sized intact BM (n=28) or resection cavities (n=30) treated with either SF-SRS or MF-SRS. Follow-up MRI was used to determine LC and RN using a modification of the "Brain Tumor Reporting and Data System" (BT-RADS) scoring system. The 12-month LC rate following treatment of intact BM was 66.7% for SF-SRS and 60.0% for MF-SRS (p=1.000). For resection cavities, the 12-month LC rate was 92.9%% after SF-SRS and 46.2% after MF-SRS (p=0.013). For intact BM, RN rate was 17.6% for SF-SRS and 20.0% for MF-SRS (p=1.000). For resection cavities, RN rate was 28.6% for SF-SRS and 20.0% for MF-SRS (p=1.000). Patients with intact BM showed no statistically significant differences in 12-months LC and RN rate following SF-SRS or MF-SRS. In patients with resection cavities the 12-months LC rate was significantly better following SF-SRS, with no increase in the RNFS.

2V-CBCT: Two-Orthogonal-Projection based CBCT Reconstruction and Dose Calculation for Radiation Therapy using Real Projection Data.

This work demonstrates the feasibility of two-orthogonal-projection-based CBCT (2V-CBCT) reconstruction and dose calculation for radiation therapy (RT) using real projection data, which is the first 2V-CBCT feasibility study with real projection data, to the best of our knowledge. RT treatments are often delivered in multiple fractions, for which on-board CBCT is desirable to calculate the delivered dose per fraction for the purpose of RT delivery quality assurance and adaptive RT. However, not all RT treatments/fractions have CBCT acquired, but two orthogonal projections are always available. The question to be addressed in this work is the feasibility of 2V-CBCT for the purpose of RT dose calculation. 2V-CBCT is a severely ill-posed inverse problem for which we propose a coarse-to-fine learning strategy. First, a 3D deep neural network that can extract and exploit the inter-slice and intra-slice information is adopted to predict the initial 3D volumes. Then, a 2D deep neural network is utilized to fine-tune the initial 3D volumes slice-by-slice. During the fine-tuning stage, a perceptual loss based on multi-frequency features is employed to enhance the image reconstruction. Dose calculation results from both photon and proton RT demonstrate that 2V-CBCT provides comparable accuracy with full-view CBCT based on real projection data.