A comprehensive pre-clinical treatment quality assurance program using unique spot patterns for proton pencil beam scanning FLASH radiotherapy.

BACKGROUND: Quality assurance (QA) for ultra-high dose rate (UHDR) irradiation is a crucial aspect in the emerging field of FLASH radiotherapy (FLASH-RT). This innovative treatment approach delivers radiation at UHDR, demanding careful adoption of QA protocols and procedures. A comprehensive understanding of beam properties and dosimetry consistency is vital to ensure the safe and effective delivery of FLASH-RT. PURPOSE: To develop a comprehensive pre-treatment QA program for cyclotron-based proton pencil beam scanning (PBS) FLASH-RT. Establish appropriate tolerances for QA items based on this study's outcomes and TG-224 recommendations. METHODS: A 250 MeV proton spot pattern was designed and implemented using UHDR with a 215nA nozzle beam current. The QA pattern that covers a central uniform field area, various spot spacings, spot delivery modes and scanning directions, and enabling the assessment of absolute, relative and temporal dosimetry QA parameters. A strip ionization chamber array (SICA) and an Advanced Markus chamber were utilized in conjunction with a 2 cm polyethylene slab and a range (R80) verification wedge. The data have been monitored for over 3 months. RESULTS: The relative dosimetries were compliant with TG-224. The variations of temporal dosimetry for scanning speed, spot dwell time, and spot transition time were within ± 1 mm/ms, ± 0.2 ms, and ± 0.2 ms, respectively. While the beam-to-beam absolute output on the same day reached up to 2.14%, the day-to-day variation was as high as 9.69%. High correlation between the absolute dose and dose rate fluctuations were identified. The dose rate of the central 5 × 5 cm2 field exhibited variations within 5% of the baseline value (155 Gy/s) during an experimental session. CONCLUSIONS: A comprehensive QA program for FLASH-RT was developed and effectively assesses the performance of a UHDR delivery system. Establishing tolerances to unify standards and offering direction for future advancements in the evolving FLASH-RT field.

Validation and reproducibility of in vivo dosimetry for pencil beam scanned FLASH proton treatment in mice.

PURPOSE: To investigate quality assurance (QA) techniques for in vivo dosimetry and establish its routine uses for proton FLASH small animal experiments with a saturated monitor chamber. METHODS AND MATERIALS: 227 mice were irradiated at FLASH or conventional (CONV) dose rates with a 250 MeV FLASH-capable proton beamline using pencil beam scanning to characterize the proton FLASH effect on abdominal irradiation and examining various endpoints. A 2D strip ionization chamber array (SICA) detector was positioned upstream of collimation and used for in vivo dose monitoring during irradiation. Before each irradiation series, SICA signal was correlated with the isocenter dose at each delivered dose rate. Dose, dose rate, and 2D dose distribution for each mouse were monitored with the SICA detector. RESULTS: Calibration curves between the upstream SICA detector signal and the delivered dose at isocenter had good linearity with minimal R2 values of 0.991 (FLASH) and 0.985 (CONV), and slopes were consistent for each modality. After reassigning mice, standard deviations were less than 1.85 % (FLASH) and 0.83 % (CONV) for all dose levels, with no individual subject dose falling outside a ±â€¯3.6 % range of the designated dose. FLASH fields had a field-averaged dose rate of 79.0 ±â€¯0.8 Gy/s and mean local average dose rate of 160.6 ±â€¯3.0 Gy/s. In vivo dosimetry allowed for the accurate detection of variation between the delivered and the planned dose. CONCLUSION: In vivo dosimetry benefits FLASH experiments through enabling real-time dose and dose rate monitoring allowing mouse cohort regrouping when beam fluctuation causes delivered dose to vary from planned dose.

A deep learning model, NAFNet, predicts adverse pathology and recurrence in prostate cancer using MRIs.

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification.

Construction of a high-density genetic map and mapping of a spike length locus for rye.

Genetic maps provide the foundation for QTL mapping of important traits of crops. As a valuable food and forage crop, rye (Secale cereale L., RR) is also one of the tertiary gene sources of wheat, especially wild rye, Secale cereale subsp. segetale, possessing remarkable stress tolerance, tillering capacity and numerous valuable traits. In this study, based on the technique of specific-locus amplified fragment sequencing (SLAF-seq), a high-density single nucleotide polymorphism (SNP) linkage map of the cross-pollinated (CP) hybrid population crossed by S. cereale L (female parent) and S. cereale subsp. segetale (male parent) was successfully constructed. Following preprocessing, the number of 1035.11 M reads were collected and 2425800 SNP were obtained, of which 409134 SNP were polymorphic. According to the screening process, 9811 SNP markers suitable for constructing linkage groups (LGs) were selected. Subsequently, all of the markers with MLOD values lower than 3 were filtered out. Finally, an integrated map was constructed with 4443 markers, including 1931 female mapping markers and 3006 male mapping markers. A major quantitative trait locus (QTL) linked with spike length (SL) was discovered at 73.882 cM on LG4, which explained 25.29% of phenotypic variation. Meanwhile two candidate genes for SL, ScWN4R01G329300 and ScWN4R01G329600, were detected. This research presents the first high-quality genetic map of rye, providing a substantial number of SNP marker loci that can be applied to marker-assisted breeding. Additionally, the finding could help to use SLAF marker mapping to identify certain QTL contributing to important agronomic traits. The QTL and the candidate genes identified through the high-density genetic map above may provide diverse potential gene resources for the genetic improvement of rye.

Si-Ni-San Ameliorates the Clinical Symptoms of Interstitial Cystitis/Bladder Pain Syndrome in Rats by Decreasing the Expression of Inflammatory Factors.

OBJECTIVE: To observe the therapeutic effect of Si-Ni-San (SNS) on interstitial cystitis/bladder pain syndrome (IC/BPS) in rats, and explore the possible regulatory mechanism of SNS on IC/BPS combined with transcriptome analysis. METHODS: An IC/BPS model of Sprague-Dawley (SD) rats was established with cyclophosphamide (CYP), and the SNS was extracted for treatment. The rats were divided into 4 groups (n = 10 in each group): Control group (blank), cyclophosphamide group (CYP group, CYP injection + normal saline gavage), lower-dose SNS group (LSNS group, CYP injection + 6 g/kg SNS gavage), and higher-dose SNS group (HSNS group, CYP injection + 12 g/kg SNS gavage). Urination, pain, and histological changes were observed in the rats after the experiment, and Western blotting (WB) and transcriptome analysis were performed on bladder tissues. RESULTS: Compared with the CYP group, the urination, pain and inflammation symptoms of the IC/BPS model rats in the SNS treatment groups (LSNS and HSNS) were significantly improved (p < 0.05). WB results showed that the expressions of inflammation-related proteins interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the SNS treatment groups were significantly decreased compared with those in the CYP group. Transcriptome results showed that SNS can affect the expression of inflammation-related genes and inflammatory signaling pathways. CONCLUSIONS: SNS can significantly alleviate the symptoms of inflammation and pain in IC/BPS rats, and its mechanism may be related to the down-regulation of inflammatory factors IL-6 and TNF-α through messenger RNA (mRNA) and long non-coding RNA (LncRNA) pathways.

VEGF-A in serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration.

Activation of innate immunity in the brain is a prominent feature of Alzheimer's disease (AD). The present study investigated the regulation of innate immunity by wild-type serum injection in a transgenic AD mouse model. We found that treatment with wild-type mouse serum significantly reduced the number of neutrophils and microglial reactivity in the brains of APP/PS1 mice. Mimicking this effect, neutrophil depletion via Ly6G neutralizing antibodies resulted in improvements in AD brain functions. Serum proteomic analysis identified vascular endothelial growth factor-A (VEGF-A) and chemokine (C-X-C motif) ligand 1 (CXCL1) as factors enriched in serum samples, which are crucial for neutrophil migration and chemotaxis, leukocyte migration, and cell chemotaxis. Exogenous VEGF-A reversed amyloid ß (Aß)-induced decreases in cyclin-dependent kinase 5 (Cdk5) and increases in CXCL1 in vitro and blocked neutrophil infiltration into the AD brain. Endothelial Cdk5 overexpression conferred an inhibitory effect on CXCL1 and neutrophil infiltration, thereby restoring memory abilities in APP/PS1 mice. Our findings uncover a previously unknown link between blood-derived VEGF signaling and neutrophil infiltration and support targeting endothelial Cdk5 signaling as a potential therapeutic strategy for AD.

Implementation of novel measurement-based patient-specific QA for pencil beam scanning proton FLASH radiotherapy.

BACKGROUND: Several studies have shown pencil beam scanning (PBS) proton therapy is a feasible and safe modality to deliver conformal and ultra-high dose rate (UHDR) FLASH radiation therapy. However, it would be challenging and burdensome to conduct the quality assurance (QA) of the dose rate along with conventional patient-specific QA (psQA). PURPOSE: To demonstrate a novel measurement-based psQA program for UHDR PBS proton transmission FLASH radiotherapy (FLASH-RT) using a high spatiotemporal resolution 2D strip ionization chamber array (SICA). METHODS: The SICA is a newly designed open-air strip-segmented parallel plate ionization chamber, which is capable of measuring spot position and profile through 2 mm-spacing-strip electrodes at a 20 kHz sampling rate (50 µs per event) and has been characterized to exhibit excellent dose and dose rate linearity under UHDR conditions. A SICA-based delivery log was collected for each irradiation containing the measured position, size, dwell time, and delivered MU for each planned spot. Such spot-level information was compared with the corresponding quantities in the treatment planning system (TPS). The dose and dose rate distributions were reconstructed on patient CT using the measured SICA log and compared to the planned values in volume histograms and 3D gamma analysis. Furthermore, the 2D dose and dose rate measurements were compared with the TPS calculations of the same depth. In addition, simulations using different machine-delivery uncertainties were performed, and QA tolerances were deduced. RESULTS: A transmission proton plan of 250 MeV for a lung lesion was planned and measured in a dedicated ProBeam research beamline (Varian Medical System) with a nozzle beam current between 100 to 215 nA. The worst gamma passing rates for dose and dose rate of the 2D SICA measurements (four fields) compared to TPS prediction (3%/3 mm criterion) were 96.6% and 98.8%, respectively, whereas the SICA-log reconstructed 3D dose distribution achieved a gamma passing rate of 99.1% (2%/2 mm criterion) compared to TPS. The deviations between SICA measured log, and TPS were within 0.3 ms for spot dwell time with a mean difference of 0.069 ± 0.11 s, within 0.2 mm for spot position with a mean difference of -0.016 ± 0.03 mm in the x-direction, and -0.036 ± 0.059 mm in the y-direction, and within 3% for delivered spot MUs. Volume histogram metric of dose (D95) and dose rate (V40Gy/s ) showed minimal differences, within less than 1%. CONCLUSIONS: This work is the first to describe and validate an all-in-one measurement-based psQA framework that can fulfill the goals of validating the dose rate accuracy in addition to dosimetric accuracy for proton PBS transmission FLASH-RT. The successful implementation of this novel QA program can provide future clinical practice with more confidence in the FLASH application.

Lift enhancement of a butterfly-like flapping wing vehicle by reinforcement learning algorithm.

In order to enhance the take-off lift of a butterfly-like flapping wing vehicle (FWV), we implemented an integrated experimental platform and applied a reinforcement learning algorithm. The vehicle, which has a wingspan of 81 cm and is mounted on a stand with a force sensor, is driven by two servos that are powered and controlled wirelessly. To achieve the goal of enhancing take-off lift, we used a model-free, on-policy actor-critic proximal policy optimization algorithm. After 300 learning steps, the average aerodynamic lift force increased significantly from 0.044 N to 0.861 N. This enhanced lift force was sufficient to meet the take-off requirements of the vehicle without the need for any additional aids or airflow. Additionally, we observed a strong lift peak in the upstroke after analyzing the learning results. Further experiments showed that this lift peak is directly related to the elastic release of the wing twist and the opening and closing of the gap between the forewing and hindwing in the early stage of the upstroke. These findings were not easily predicted or discovered using traditional aerodynamic methods. This work provides valuable reinforcement learning experience for the future development of FWVs.

Targeting SMYD2 inhibits prostate cancer cell growth by regulating c-Myc signaling.

SMYD2 is a lysine histone methyl transferase involved in various cancers epigenetically via methylating histone H3K4, and H3K36. c-Myc is one of the major drivers of prostate cancer (PCa) initiation and progression. The roles of SMYD2 in PCa and the regulators of c-Myc activity in PCa are still under-researched. SMYD2 expression and survival outcomes in PCa cohorts were analyzed by bioinformatics analysis. SMYD2 protein levels were detected in PCa tissues by immunohistochemistry. SMYD2 knockdown cells were established to identify the effects of SMYD2 on cell growth in vitro and in vivo. GSEA and RNA sequencing were adopted to reconnoiter the signaling regulated by SMYD2 in PCa. The relationship between SMYD2 and c-Myc was examined by western blot analysis, qPCR, and immunohistochemistry. SMYD2 specific inhibitor-AZ505 was used to pharmacologically inhibit SMYD2 function in vitro and in vivo. SMYD2 expression increased in PCa tissues compared with benign prostate tissues and higher SMYD2 expression was associated with a higher risk of biochemical relapse after radical prostatectomy. SMYD2 knockdown inhibited the growth of PCa cells both in vitro and in vivo. Furthermore, high SMYD2 levels conduced to activated c-Myc signaling in PCa cells. Importantly, the pharmacological intervention of SMYD2 by AZ505 significantly repressed PCa cell growth both in vitro and in vivo. Our findings indicate that SMYD2 inhibition restrains PCa cell proliferation by regulating c-Myc signaling and provide evidence for the potential practice of SMYD2 targeting in the treatment of PCa.

Dual-Modal Image Reconstruction for Electrical Impedance Tomography With Overlapping Group Lasso and Laplacian Regularization.

OBJECTIVE: Electrical Impedance Tomography (EIT) is a promising biomedical imaging modality, yet EIT image reconstruction remains an open challenge due to its severe ill-posedness. High-quality EIT image reconstruction algorithms are desired. METHODS: This paper reports a segmentation-free dual-modal EIT image reconstruction algorithm that uses Overlapping Group Lasso and Laplacian (OGLL) regularization. An overlapping group lasso penalty is constructed based on conductivity change properties and encodes the imaging targets' structural information obtained from an auxiliary imaging modality that provides structural images of the sensing region. We introduce Laplacian regularization to alleviate the artifacts caused by group overlapping. RESULTS: The performance of OGLL is evaluated and compared with single-modal and dual-modal image reconstruction algorithms using simulation and real-world data. Quantitative metrics and visualized images confirm the superiority of the proposed method in terms of structure preservation, background artifact (BA) suppression, and conductivity contrast differentiation. CONCLUSION: This work proves the effectiveness of OGLL in improving EIT image quality. SIGNIFICANCE: This study demonstrates that EIT has the potential to be adopted in quantitative tissue analysis by using such dual-modal imaging approaches.

Crowdsourced Indoor Positioning with Scalable WiFi Augmentation.

In recent years, crowdsourcing approaches have been proposed to record the WiFi signals annotated with the location of the reference points (RPs) extracted from the trajectories of common users to reduce the burden of constructing a fingerprint (FP) database for indoor positioning. However, crowdsourced data is usually sensitive to crowd density. The positioning accuracy degrades in some areas due to a lack of FPs or visitors. To improve the positioning performance, this paper proposes a scalable WiFi FP augmentation method with two major modules: virtual reference point generation (VRPG) and spatial WiFi signal modeling (SWSM). A globally self-adaptive (GS) and a locally self-adaptive (LS) approach are proposed in VRPG to determine the potential unsurveyed RPs. A multivariate Gaussian process regression (MGPR) model is designed to estimate the joint distribution of all WiFi signals and predicts the signals on unsurveyed RPs to generate more FPs. Evaluations are conducted on an open-source crowdsourced WiFi FP dataset based on a multi-floor building. The results show that combining GS and MGPR can improve the positioning accuracy by 5% to 20% from the benchmark, but with halved computation complexity compared to the conventional augmentation approach. Moreover, combining LS and MGPR can sharply reduce 90% of the computation complexity against the conventional approach while still providing moderate improvement in positioning accuracy from the benchmark.

Commissioning a 250 MeV research beamline for proton FLASH radiotherapy preclinical experiments.

BACKGROUND: The potential reduction of normal tissue toxicities during FLASH radiotherapy (FLASH-RT) has inspired many efforts to investigate its underlying mechanism and to translate it into the clinic. Such investigations require experimental platforms of FLASH-RT capabilities. PURPOSE: To commission and characterize a 250 MeV proton research beamline with a saturated nozzle monitor ionization chamber for proton FLASH-RT small animal experiments. METHODS: A 2D strip ionization chamber array (SICA) with high spatiotemporal resolution was used to measure spot dwell times under various beam currents and to quantify dose rates for various field sizes. An Advanced Markus chamber and a Faraday cup were irradiated with spot-scanned uniform fields and nozzle currents from 50 to 215 nA to investigate dose scaling relations. The SICA detector was set up upstream to establish a correlation between SICA signal and delivered dose at isocenter to serve as an in vivo dosimeter and monitor the delivered dose rate. Two off-the-shelf brass blocks were used as apertures to shape the dose laterally. Dose profiles in 2D were measured with an amorphous silicon detector array at a low current of 2 nA and validated with Gafchromic films EBT-XD at high currents of up to 215 nA. RESULTS: Spot dwell times become asymptotically constant as a function of the requested beam current at the nozzle of greater than 30 nA due to the saturation of monitor ionization chamber (MIC). With a saturated nozzle MIC, the delivered dose is always greater than the planned dose, but the desired dose can be achieved by scaling the MU of the field. The delivered doses exhibit excellent linearity with R 2 > 0.99 ${R^2} > 0.99$ with respect to MU, beam current, and the product of MU and beam current. If the total number of spots is less than 100 at a nozzle current of 215 nA, a field-averaged dose rate greater than 40 Gy/s can be achieved. The SICA-based in vivo dosimetry system achieved excellent estimates of the delivered dose with an average (maximum) deviation of 0.02 Gy (0.05 Gy) over a range of delivered doses from 3 to 44 Gy. Using brass aperture blocks reduced the 80%-20% penumbra by 64% from 7.55 to 2.75 mm. The 2D dose profiles measured by the Phoenix detector at 2 nA and the EBT-XD film at 215 nA showed great agreement, with a gamma passing rate of 95.99% using 1 mm/2% criterion. CONCLUSION: A 250 MeV proton research beamline was successfully commissioned and characterized. Challenges due to the saturated monitor ionization chamber were mitigated by scaling MU and using an in vivo dosimetry system. A simple aperture system was designed and validated to provide sharp dose fall-off for small animal experiments. This experience can serve as a foundation for other centers interested in implementing FLASH radiotherapy preclinical research, especially those equipped with a similar saturated MIC.

Impact of respiratory motion on proton pencil beam scanning FLASH radiotherapy: anin silicoand phantom measurement study.

Objective. To investigate the effects of respiratory motion on the delivered dose in the context of proton pencil beam scanning (PBS) transmission FLASH radiotherapy (FLASH-RT) by simulation and phantom measurements.Approach. An in-house simulation code was employed to performin silicosimulation of 2D dose distributions for clinically relevant proton PBS transmission FLASH-RT treatments. A moving simulation grid was introduced to investigate the impacts of various respiratory motion and treatment delivery parameters on the dynamic PBS dose delivery. A strip-ionization chamber array detector and an IROC motion platform were employed to perform phantom measurements of the 2D dose distribution for treatment fields similar to those used for simulation.Main results. Clinically relevant respiratory motion and treatment delivery parameters resulted in degradation of the delivered dose compared to the static delivery as translation and distortion. Simulation showed that the gamma passing rates (2 mm/2% criterion) and target coverage could drop below 50% and 80%, respectively, for certain scenarios if no mitigation strategy was used. The gamma passing rates and target coverage could be restored to more than 95% and 98%, respectively, for short beams delivered at the maximal inhalation or exhalation phase. The simulation results were qualitatively confirmed in phantom measurements with the motion platform.Significance. Respiratory motion could cause dose quality degradation in a clinically relevant proton PBS transmission FLASH-RT treatment if no mitigation strategy is employed, or if an adequate margin is not given to the target. Besides breath-hold, gated delivery can be an alternative motion management strategy to ensure high consistency of the delivered dose while maintaining minimal dose to the surrounding normal tissues. To the best of our knowledge, this is the first study on motion impacts in the context of proton transmission FLASH radiotherapy.

LINC02489 with m6a modification increase paclitaxel sensitivity by inhibiting migration and invasion of ovarian cancer cells.

The long non-coding RNA LINC02489 has been shown to be significantly downregulated in advanced ovarian cancer (OC). However, the function of LINC02489 remains unknown. This study aims to explain the role and mechanism of LINC02489 in OC. The expression of LINC02489 was examined by qRT-PCR in primary OC tissues. Additionally, MTT, wound healing, transwell, and flow cytometry assays were used to analyze the function of LINC02489. The mechanism of LINC02489 in OC was investigated by high-throughput RNA-sequencing, qRT-PCR, western blot, and N6-methyladenosine (m6A) meRIP. A total of 1101 and 827 genes are significantly down-regulated and up-regulated in metastatic and chemoresistant OC tissues. The expression of LINC02489 is decreased in metastatic and chemoresistant OC tissues compared with the primary OC tissues (p < 0.05). Overexpression of LINC02489 inhibits proliferation, invasion, and migration of drug-resistant OC cells. In the LINC02489 overexpressed chemoresistant SKOV3 cells, the m6A modified LINC02489 is significantly up-regulated. Furthermore, the expression of PKNOX2 is increased during overexpression of LINC02489, while the expression of PTEN and mTOR plummets. This study demonstrates that LINC02489 can inhibit the invasion and migration of chemoresistant OC cells by increasing its m6A modification and up-regulating PKNOX2 expression. In addition, LINC02489 regulates the invasion ability of OC cells through the PTEN/mTOR signaling pathway, thereby regulating the sensitivity of SKOV3 cells to paclitaxel. This result provides a potential therapeutic target for chemoresistant OC.

MMV-Net: A Multiple Measurement Vector Network for Multifrequency Electrical Impedance Tomography.

Multifrequency electrical impedance tomography (mfEIT) is an emerging biomedical imaging modality to reveal frequency-dependent conductivity distributions in biomedical applications. Conventional model-based image reconstruction methods suffer from low spatial resolution, unconstrained frequency correlation, and high computational cost. Deep learning has been extensively applied in solving the EIT inverse problem in biomedical and industrial process imaging. However, most existing learning-based approaches deal with the single-frequency setup, which is inefficient and ineffective when extended to the multifrequency setup. This article presents a multiple measurement vector (MMV) model-based learning algorithm named MMV-Net to solve the mfEIT image reconstruction problem. MMV-Net considers the correlations between mfEIT images and unfolds the update steps of the Alternating Direction Method of Multipliers for the MMV problem (MMV-ADMM). The nonlinear shrinkage operator associated with the weighted l2,1 regularization term of MMV-ADMM is generalized in MMV-Net with a cascade of a Spatial Self-Attention module and a Convolutional Long Short-Term Memory (ConvLSTM) module to better capture intrafrequency and interfrequency dependencies. The proposed MMV-Net was validated on our Edinburgh mfEIT Dataset and a series of comprehensive experiments. The results show superior image quality, convergence performance, noise robustness, and computational efficiency against the conventional MMV-ADMM and the state-of-the-art deep learning methods.

Modified robotic-assisted laparoscopic pyeloplasty in children for ureteropelvic junction obstruction with long proximal ureteral stricture: The "double-flap" technique.

Objective: The objective of this study is to introduce a novel technique of robotic-assisted laparoscopic pyeloplasty (RALP) for ureteropelvic junction obstruction (UPJO) with long proximal ureteral stricture in children. Materials and methods: Clinical information on patients who underwent a modified RALP between July 2018 and May 2019 in our center was collected retrospectively. Our surgical modifications mainly include "double-flap" tailoring of the renal pelvis and anastomosis of spatulate ureter with the double-flap. Demographic, perioperative, postoperative, and follow-up information was recorded in detail. Results: A total of 13 patients were included in the study. All the patients underwent a modified RALP without conversion to open surgery. They were followed up with a median time of 36 months. The anteroposterior diameter of the renal pelvis was 1.19 ± 0.21 at 6 months after the surgery, which was significantly lower than that on admission (3.93 ± 0.79). The split renal function of the children was also significantly improved from 0.37 ± 0.05) to 0.46 ± 0.02 at 6 months after surgery (p < 0.05). The diuretic renography revealed that all the patients have a T1/2 time less than 20 min postoperatively. The children were in good condition during the follow-up period. Conclusions: Modified RALP is an effective surgical treatment for children with UPJO with long proximal ureteral stricture. The success rate of this modification has been preliminarily confirmed.

Long non-coding RNA SNHG3 promotes prostate cancer progression by sponging microRNA-1827.

Long non-coding RNAs (lncRNAs) are important biological factors that contribute to the initiation and progression of different types of cancer, including gastric, bladder and colorectal cancer. Small nucleolar RNA host gene 3 (SNHG3) has been implicated in prostate cancer (PCa) progression. However, the expression pattern and function of SNHG3 in PCa remain unclear, impeding the development of novel treatment strategies for this cancer. The present study aimed to investigate a combination of molecular and biochemical approaches to determine the role of SNHG3 in patients at different stages of disease, and elucidate the pathway by which SNHG3 affects PCa progression. A Cell Counting Kit-8 assay was used to assess cell proliferation. Transwell assays were used to analyze cell migration and invasion. Reverse transcription-quantitative PCR and western blotting were used to evaluate the expression levels of RNAs and proteins, respectively. The results demonstrated that SNHG3 expression was upregulated in PCa tissues downloaded from The Cancer Genome Atlas database, which was associated with poor prognosis. Furthermore, cell proliferation, migration and invasion were significantly inhibited following SNHG3 knockdown in vitro, the effects of which were reversed following overexpression of SNHG3 in PCa cells. Bioinformatic analysis revealed that microRNA (miRNA/miR)-1827 was a downstream target of SNHG3. The direct interaction between SNHG3 and miR-1827 was validated via the dual-luciferase reporter and RNA immunoprecipitation assays. Pearson's correlation analysis demonstrated that SNHG3 expression was negatively correlated with miR-1827 expression at different stages of PCa. Furthermore, rescue assays indicated that cotransfection with small interfering-SNHG3 and miR-1827 inhibitor reversed the effects of SNHG3 knockdown on cell proliferation, migration and invasion. In addition, SNHG3 knockdown in vivo suppressed tumor growth. Notably, lncRNA SNHG3 promoted PCa progression through miR-1827 via the Wnt/AKT/mTOR pathway. Taken together, the results of the present study suggest that SNHG3 promotes PCa progression by sponging miR-1827, indicating that SNHG3 may be a promising diagnostic and therapeutic target of PCa.

A 2D strip ionization chamber array with high spatiotemporal resolution for proton pencil beam scanning FLASH radiotherapy.

PURPOSE: Experimental measurements of two-dimensional (2D) dose rate distributions in proton pencil beam scanning (PBS) FLASH radiation therapy (RT) are currently lacking. In this study, we characterize a newly designed 2D strip-segmented ionization chamber array (SICA) with high spatial and temporal resolution and demonstrate its applications in a modern proton PBS delivery system at both conventional and ultrahigh dose rates. METHODS: A dedicated research beamline of the Varian ProBeam system was employed to deliver a 250-MeV proton PBS beam with nozzle currents up to 215 nA. In the research and clinical beamlines, the spatial, temporal, and dosimetric performances of the SICA were characterized and compared with measurements using parallel-plate ion chambers (IBA PPC05 and PTW Advanced Markus chamber), a 2D scintillator camera (IBA Lynx), Gafchromic films (EBT-XD), and a Faraday cup. A novel reconstruction approach was proposed to enable the measurement of 2D dose and dose rate distributions using such a strip-type detector. RESULTS: The SICA demonstrated a position accuracy of 0.12 ± 0.02 mm at a 20-kHz sampling rate (50 µs per event) and a linearity of R2  > 0.99 for both dose and dose rate with nozzle beam currents ranging from 1 to 215 nA. The 2D dose comparison to the film measurement resulted in a gamma passing rate of 99.8% (2 mm/2%). A measurement-based proton PBS 2D FLASH dose rate distribution was compared to simulation results and showed a gamma passing rate of 97.3% (2 mm/2%). CONCLUSIONS: The newly designed SICA demonstrated excellent spatial, temporal, and dosimetric performances and is well suited for commissioning, quality assurance, and a wide range of clinical applications in proton PBS clinical and FLASH-RT.

Presence of CD133-positive circulating tumor cells predicts worse progression-free survival in patients with metastatic castration-sensitive prostate cancer.

OBJECTIVE: To investigate the clinical significance of the expression of the stemness marker CD133 in circulating tumor cells of newly diagnosed metastatic castration-sensitive prostate cancer patients. METHODS: For this study, 104 metastatic castration-sensitive prostate cancer patients treated at the Fudan University Shanghai Cancer Center from September 2015 to February 2017 were considered. After enrollment, the patients received androgen deprivation therapy (bicalutamide + goserelin). Circulating tumor cells were isolated and identified using the CanPatrol system, which can identify not only traditional epithelial markers but also mesenchymal markers in cells that have undergone epithelial mesenchymal transition. CD133 was used to characterize the circulating tumor cells. The primary endpoint of this research was to evaluate progression to castration resistance. RESULTS: Among the 104 patients enrolled, 89 patients were circulating tumor cell positive at baseline, and the median circulating tumor cell count was four. The median follow-up was 24 months, and at the end of follow-up, the proportion of patients who progressed to castration-resistant prostate cancer in the CTC+CD133+ group was 93.3%, which was significantly higher than that of the circulating tumor cell negative group (73.3%) and the CTC+CD133- group (75.0%), with P = 0.043. After follow-up, progression-free survival for CTC+CD133+, CTC+CD133-, and circulating tumor cell patients was 10.0, 13.0, and 14.0 months, respectively, with P = 0.022. Univariate and multivariate analyses also confirmed that the characterization of circulating tumor cells using CD133 can independently predict progression-free survival in metastatic castration-sensitive prostate cancer patients after receiving androgen deprivation therapy (P = 0.042; hazard ratio 1.396). CONCLUSION: Baseline CTC+CD133+ was a poor independent prognostic factor for metastatic castration-sensitive prostate cancer patients to progress to castration-resistant prostate cancer after receiving androgen deprivation therapy.

Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer.

The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.