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BACKGROUND: Stereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases. METHODS: Patients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15-24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life. DISCUSSION: Currently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure. TRIAL REGISTRATION: ClincalTrials.gov, trial registration number: NCT05346367 , trial registration date: 26 April 2022.

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Time-resolved femtosecond-stimulated Raman spectroscopy (FSRS) provides valuable information on the structural dynamics of biomolecules. However, FSRS has been applied mainly up to the nanoseconds regime and above 700 cm-1, which covers only part of the spectrum of biologically relevant time scales and Raman shifts. Here we report on a broadband (~200-2200 cm-1) dual transient visible absorption (visTA)/FSRS set-up that can accommodate time delays from a few femtoseconds to several hundreds of microseconds after illumination with an actinic pump. The extended time scale and wavenumber range allowed us to monitor the complete excited-state dynamics of the biological chromophore flavin mononucleotide (FMN), both free in solution and embedded in two variants of the bacterial light-oxygen-voltage (LOV) photoreceptor EL222. The observed lifetimes and intermediate states (singlet, triplet, and adduct) are in agreement with previous time-resolved infrared spectroscopy experiments. Importantly, we found evidence for additional dynamical events, particularly upon analysis of the low-frequency Raman region below 1000 cm-1. We show that fs-to-sub-ms visTA/FSRS with a broad wavenumber range is a useful tool to characterize short-lived conformationally excited states in flavoproteins and potentially other light-responsive proteins.

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INTRODUCTION: Suicidal thoughts are relatively common among college students in Iran. However, measures frequently used to assess suicidality or specific aspects of suicidal ideation in the United States have yet to be validated in Iran. Thus, the present study validated Farsi versions of the Depressive Symptom Inventory Suicidality Subscale (F-DSI-SS) and Suicide Rumination Scale (F-SRS) among Iranian college students. METHODS: College students (N = 1043; 88.1% women) completed the F-DSI-SS. Forty-six percent (n = 481) of participants reported the presence of suicidal thoughts and were eligible to fill out the F-SRS. Analyses focused on validating the factor structure, construct, and convergent validity of the F-DSI-SS and F-SRS among college students, as well as testing measurement invariance by gender of the F-DSI-SS. RESULTS: Confirmatory factor analysis (CFA) indicated that the F-DSI-SS and F-SRS had good fit to the data and each displayed a one-factor structure. Furthermore, the F-DSI-SS showed strong measurement invariance across genders. Internal consistency of the F-DSI-SS and F-SRS was good. Lastly, the F-DSI-SS and F-SRS's items and their total scores were intercorrelated and demonstrated good convergent validity. CONCLUSION: Findings suggest that the F-DSI-SS and F-SRS will enable researchers to examine suicidal thoughts and suicide-specific rumination in Iran.

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Background Stereotactic radiosurgery (SRS) or fractionated SRS (fSRS) are effective options for the treatment of brain metastases. When treating multiple metastases with a linear accelerator-based approach, a single isocenter allows for efficient treatment delivery. In this study, we present our findings comparing dosimetric parameters of Brainlab (Munich, Germany) Elements™ Multiple Brain Mets SRS (MME) software (version 1.5 versus version 2.0) for a variety of scenarios and patients. The impact of multileaf collimator design and function on plan quality within the software was also evaluated. Materials and methods Twenty previously treated patients with a total of 58 lesions (from one to seven lesions each) were replanned with an updated version of the multiple brain Mets software solution. For each plan, the mean conformity index (CI), mean gradient index (GI), the volume of normal brain receiving 12 Gy (V12), and mean brain dose were evaluated. Additionally, all v2.0 plans were further evaluated with jaw tracking for by Elekta (Stockholm, Sweden) and HD120™ multileaf collimator by Varian Medical Systems (Palo Alto, USA). Results The new software version demonstrated improvements for CI, GI and V12 (p <0.01). For the Elekta Agility™ multileaf collimator, jaw tracking improved all dosimetric parameters except for CI (p =0.178) and mean brain dose (p =0.93). For the Varian with HD120 multileaf collimator, all parameters improved. Conclusions The software enhancements in v2.0 of the software provided improvements in planning efficiency and dosimetric parameters. Differences in multileaf collimator design may provide an additional incremental benefit in a subset of clinical scenarios.

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AIMS AND BACKGROUND: There is scant data on the utility of repeated radiosurgery for management of locally recurrent brain metastases after upfront stereotactic radiosurgery (SRS). Most studies have used single-fraction SRS for repeated radiosurgery, and the use of fractionated stereotactic radiosurgery (f-SRS) in this setting has been poorly addressed. In this study, we assessed the utility of f-SRS for the management of locally recurrent brain metastases after failed upfront single-fraction SRS and report our single-center experience. METHODS AND STUDY DESIGN: A total of 30 patients receiving f-SRS for locally recurrent brain metastases after upfront single-fraction SRS at our department between September 2011 and September 2017 were retrospectively evaluated for local control (LC), toxicity, and overall survival outcomes. RESULTS: Median age and Karnofsky performance status were 57 (range: 38-78 years) and 80 (range: 70-100) at repeated radiosurgery (SRS2). The median time interval between the two radiosurgery applications was 13.5 months (range: 3.7-49 months). LC after SRS2 was 83.3%. Radionecrosis developed in 4 of the 30 lesions after SRS2, and total rate of radionecrosis was 13.3%. Statistical analysis revealed that the volume of planning target volume (PTV) at SRS2 was significantly associated with radionecrosis (P = 0.014). The volume of PTV was >13 cm3 at SRS2 in all patients with radionecrosis. CONCLUSION: A repeated course of radiosurgery in the form of f-SRS may be a viable therapeutic option for the management of locally recurrent brain metastases after failed upfront SRS with high LC rates and an acceptable toxicity profile despite the need for further supporting evidence.

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The effect of rotation of the stagnation surface on the nanoparticle deposition in the flame stabilizing on a rotating surface (FSRS) configuration was numerically assessed using CFD method. The deposition properties including particle trajectories, deposition time, temperature and surrounding O2 concentration between the flame and stagnation surface were examined. The results revealed that although flame position is insensitive to the surface rotation, the temperature and velocity fields are remarkably affected, and the deposition properties become asymmetric along the burner centerline when the surface rotates at a fast speed (rotational speed ω ≥ 300 rpm). Particles moving on the windward side have similar deposition properties when the surface rotates slowly, but the off-center particles on the leeward side have remarkable longer deposition time, lower deposition temperature, and lower surrounding O2 concentration, and they even never deposit on the surface when the surface rotates at a high speed. The rotation effect of the stagnation surface can be quantitatively described by an analogous Karlovitz number (Ka'), which is defined as the ratio of characteristic residence time of moving surface to the aerodynamics time induced by flame stretch. For high quality semiconducting metal oxide (SMO) films, it is suggested that Ka' ≥ 1 should be kept.

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OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm3 (range 2.4-31.3 cm3) and 7.0 cm3 (range 1.0-29.7 cm3). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm3 (range 0.1-23.1 cm3). The median change in volume compared with baseline was a decrease of 54.9% (range -98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3-7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively. CONCLUSIONS 2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS.

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Introduction Stereotactic radiosurgery (SRS) is increasingly used as an alternative to whole brain radiotherapy (WBRT) following surgical resection of brain metastases. We analyzed the outcomes of postoperative frameless fractionated stereotactic radiosurgery (fSRS) cases for surgically resected brain metastases at our institution. Materials and Methods We performed a retrospective review of 85 patients who underwent fSRS to 87 resection beds from 2006 - 2014 with a median follow-up of 6.4 months. Clinically relevant outcomes were assessed with analysis to determine predictors of these outcomes. Results The median target volume was 9.8 cm-3 (1.1 - 43.1 cm-3). The most frequently used fractionation scheme was 3,000 cGy in five fractions. The rates of local control (LC), distant brain failure (DBF), and overall survival (OS) at one-year were 87%, 52%, and 52%, respectively. Five patients (5.9%) experienced Grade >2 toxicity related to fSRS, including seizures (two), symptomatic radionecrosis (two), and potential treatment-related death (one). A multivariable analysis revealed that tumor volume (p < 0.001) and number of fractions (p < 0.001) were associated with LC, while recursive partitioning analysis (RPA) class (p < .0001), tumor volume (p = .0181), and the number of fractions (p = .0181) were associated with OS. Conclusions Postoperative fSRS for surgically resected brain metastases is well-tolerated and achieves durable LC. Further studies are needed to determine the optimal dose and fractionation for fSRS as well as to compare outcomes with WBRT.

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Time-resolved multi-pulse spectroscopic methods-pump-dump-probe (PDP) and femtosecond stimulated Raman spectroscopy-were used to investigate the excited state photodynamics of the carbonyl group containing carotenoid fucoxanthin (FX). PDP experiments show that S1 and ICT states in FX are strongly coupled and that the interstate equilibrium is rapidly (<5 ps) reestablished after one of the interacting states is deliberately depopulated. Femtosecond stimulated Raman scattering experiments indicate that S1 and ICT are vibrationally distinct species. Identification of the FSRS modes on the S1 and ICT potential energy surfaces allows us to predict a possible coupling channel for the state interaction.

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Ultrafast structural relaxation of photoexcited 2,2':5',2″:5″,2‴-quaterthiophene (4T) and 3,3‴-Dihexyl-2,2':5',2″:5″,2‴-quaterthiophene (DH4T) in solution were interrogated with femtosecond stimulated Raman spectroscopy (FSRS). Relaxation was observed through time-dependent evolution in frequencies and intensity ratios of out-of-phase (Z) and in-phase (Я) intraring C═C stretching features. Frequency shifts occurred on time scales of 0.4 and 0.86 ps, respectively, dominated by a blue shift in the Z mode (6.2 and 11.5 cm(-1) shifts for 4T and DH4T, respectively). Intensity ratios evolved on similar time scales due to correlated intensity decreases and increases of Z- and Я-mode features. Excited-state quantum-chemical calculations with bithiophene demonstrate that mode frequencies are coupled to the torsional dihedral, such that the spectral evolution observed reflects excited-state relaxation toward a planar conformation. This work demonstrates the power of ultrafast Raman spectroscopy for probing dynamics in photoexcited conjugated materials with structural detail given the parametric dependence of intraring vibrational modes on interring torsional dihedrals.

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The ultrafast formation of bound charge pairs, or polaron pairs (PPs), in mixed-order aggregates of poly(3-hexylthiophene) was investigated using femtosecond stimulated Raman spectroscopy (FSRS). Spectral dynamics in the carbon-carbon stretching region reveal a significant photoinduced depletion in steady-state features associated with lamellar-stacked, ordered polymer regions upon 500 nm photoexcitation; this is followed by the appearance of red-shifted features attributable to PPs that is delayed by a few hundred femtoseconds. PP features decay with concomitant recovery of the steady-state Raman depletion over a few picoseconds. The vibrational spectrum of the PP obtained exhibits a modest red shift (<15 cm(-1)) and lower Raman activity relative to steady-state features in the C═C stretching region but similar features in other regions. In total, this work demonstrates the potential of time-resolved Raman as a morphologically selective and structurally sensitive probe for tracking ultrafast charge separation and recombination dynamics within polymer regions of conjugated materials.

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Raman scattering with stimulating femtosecond probe pulses (FSR) was used to observe vibrational activity of all-trans ß-carotene in n-hexane. The short-lived excited electronic state S2 was accessed in two ways: (i) by transient FSR after an actinic pulse to populate the S2 state, exploiting resonance from an Sx ← S2 transition, and (ii) by FSR without actinic excitation, using S2 ↔ S0 resonance exclusively and narrow-band Raman/broad-band femtosecond probe pulses only. The two approaches have nonlinear optical susceptibilities χ((5)) and χ((3)), respectively. Both methods show low-frequency bands of the S2 state at 200, 400, and ∼600 cm(-1), which are reported for the first time. With (ii) the intensities of low-frequency vibrational resonances in S2 are larger compared to those in S0, implying strong anharmonicities/mode mixing in the excited state. In principle, for short-lived electronic states, the χ((3)) method should allow the best characterization of low-frequency modes.

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BACKGROUND: Recent incorporation of simulation in surgical training necessitates developing validated platforms for training and assessment. A tool should fulfill the fundamental criteria of validation. OBJECTIVE: To report the ability of a simulation-based robotic training curriculum-Fundamental Skills of Robotic Surgery (FSRS)-to assess and distinguish between different performance levels of operator experience (construct validity). MATERIALS AND METHODS: This is a prospective multicenter observational study. Participants were classified as novice (0 robotic cases performed) and experts (>150 robotic cases performed). All participants were required to complete 4 key tasks in a previously validated FSRS curriculum: ball placement, coordinated tool control, fourth arm control, and needle handling and exchange. Using the metrics available in the simulator software, the performances of each group were compared to evaluate construct validation. RESULTS: A convenience cohort of 61 surgeons participated. Novice group (n = 49) consisted of 41 fellows/residents/medical students and 8 trained open/laparoscopic surgeons, whereas expert group consisted of 12 surgeons. The novice group had no previous robotic console experience, whereas the expert group had >150 prior robotic cases experience. An overall significant difference was observed in favor of the expert group in 4 skill sets (p < 0.05). Time to complete all 4 tasks was significantly shorter in the expert group (p < 0.001). The expert group displayed significantly lesser tool collision (p = 0.002) and reduced tissue damage (p < 0.001). In performing most tasks, the expert group's camera (p < 0.001) and clutch usage (p < 0.001) was significantly greater when compared with the novice group. CONCLUSION: The components of the FSRS curriculum showed construct validity. This validation would help in effectively implementing this curriculum for robot-assisted surgical training.

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Surface-enhanced Raman spectroscopy (SERS) and femtosecond stimulated Raman spectroscopy (FSRS) have revolutionized the Raman spectroscopy field. SERS provides spectroscopic detection of single molecules, and FSRS enables the acquisition of Raman spectra on the ultrafast time scale of molecular motion. Here, we present the first successful combination of these two techniques, demonstrating surface-enhanced femtosecond stimulated Raman spectroscopy (SE-FSRS) using gold nanoantennas with embedded reporter molecules. Using a picosecond Raman and femtosecond probe pulse, the time- and ensemble-averaged enhancement factor is estimated to be in the range of 10(4)-10(6). We report the line shapes, power dependence, and magnitude of the SE-FSRS signal and discuss contributions to sample degradation on the minute time scale. With these first successful proof-of-principle experiments, time-resolved SE-FSRS techniques can now be rationally attempted with the goals of investigating the dynamics of plasmonic materials as well as examining the contributions of environmental heterogeneities by probing more homogeneous molecular subsets.