Search

Objective: We investigated immediate/late endoleaks and long-term patency following stent-graft placement for treatment of intracranial aneurysms located within the distal internal carotid artery (ICA) or vertebral artery (VA).Methods: Forty-five aneurysms in 41 patients receiving covered stents in three centres were followed. Outcome measures included aneurysm occlusion rate, endoleaks, late in-stent stenosis rate, clinical improvement, neurological deficiencies and death.Results: Total aneurysm exclusion was achieved in 69.2% (n = 27), with 30.8% (n = 12) experiencing immediate residual endoleaks. Angiographic follow-up (mean 43.5 ± 14.3 months) revealed that 87.2% (n = 34) were completely occluded with only 12.8% (n = 5) showing residual endoleaks. Predictors of immediate endoleaks in our patient group were stent number (P = 0.023) and stent diameter (P = 0.022), while predictors of late endoleaks in our patient group were stent diameter (P = 0.035) and stent angulation (P = 0.021). Late in-stent stenosis rates were 18.0 ± 13.3 and 29.0 ± 18.5% compared with the period immediately following implantation at 2- and 6-year follow-ups respectively. Smoking (P = 0.017) and stent angulation (P = 0.020) were predictors of late in-stent stenosis.Conclusion: Treating intracranial aneurysms with Willis stent-grafts has an acceptable immediate and late occlusion rate and long-term stented artery patency rate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical value of unenhanced magnetic resonance angiography (MRA) at 3.0 T for the diagnosis and therapeutic planning of patients with subarachnoid haemorrhage (SAH).Methods: A total of 165 patients with SAH were referred for three-dimensional time-of-flight MRA (3D-TOF-MRA) before digital subtraction angiography (DSA). For each aneurysm, 3D-TOF-MRA was used to determine whether the aneurysm was suitable for coil placement with or without balloon/stent-assisted coiling, surgical clipping or conservative treatment. Treatment planning with 3D-TOF-MRA was compared with actual treatment decisions or treatment that had been carried out in each aneurysm decided using DSA.Results: The aneurysm-based evaluation yielded accuracy of 96.9%, sensitivity of 97.6%, specificity of 93.1%, positive predictive value (PPV) of 98.8% and negative predictive value (NPV) of 87.1%, in the detection of intracranial aneurysms. Treatment planning could be correctly made on the basis of aneurysm anatomy and working view by volume rendering (VR) 3D-TOF-MRA with accuracy, sensitivity, specificity, PPV and NPV of 94.9%, 94.0%, 100%, 100% and 74.4%, respectively, on a per aneurysm-based evaluation.Conclusions: VR 3D-TOF-MRA offers high diagnostic accuracy in the detection of ruptured intracranial aneurysms, and appears to be an effective treatment planning tool for most patients with SAH.Key Points: VR 3D-TOF-MRA offers high diagnostic accuracy for detecting ruptured intracranial aneurysms. • VR 3D-TOF-MRA helps treatment planning for patients with subarachnoid haemorrhage. • 3D-TOF-MRA is non-invasive and avoids using ionising radiation or contrast agents. [ABSTRACT FROM AUTHOR]

To evaluate whether Willis covered stent implantation yielded angiographic and clinical results were better than those with coil embolization. Eighty-nine patients with cranial internal carotid artery (CICA) aneurysms were treated nonrandomly with covered stents (n = 43, group A) or coil embolization (n = 46, group B). Data on the technical success, procedure time, initial and final angiographic results, and final clinical outcomes were collected and analyzed at >6 months post-procedure. Covered stent placement and coil embolization were successful in all patients, except for one patient in group A. The initial angiographic results showed complete occlusion in 34 group-A patients (80.9%; 95% CI: 69%, 93%) and 24 group-B patients (52.2%; 95% CI: 37%, 67%) (P = 0.004). The final angiographic results indicated complete occlusion in 39 group A patients (39/41, 95.1%; 95% CI: 88%, 102%) and 22 group B patients (48.9%; 95% CI: 34%, 64%) (P < 0.001). The average procedure time was shorter in group A than that in group B (P < 0.001). CICA aneurysm treatment with covered stents yielded better intermediate-term angiographic outcome than those with the recommended approach of coil embolization. (ClinicalTrials.gov number, NCT01029938). [ABSTRACT FROM AUTHOR]

Objective: We designed a carotid siphon (CS) aneurysm model in dogs to test a new stent graft (the Willis covered stent) and compared tissue reaction over 12-month follow-up versus a comparison group with stents implanted in straight vessels.Methods: Twenty-four saccular sidewall aneurysms (group A) and 12 CS aneurysms (group B) were created surgically. A Willis stent graft was implanted in each aneurysm. Angiography was performed immediately and at 1-, 3-, 6- and 12-month post-implantation to investigate aneurysm isolation, endoleak, stent angulation, parent artery (PA) patency and restenosis. Light and scanning electron microscopy were used to identify aneurysmal sac thrombi, intima hyperplasia and endothelial progress.Results: Immediate angiography demonstrated mild endoleak in two aneurysms and three stent angulations in group B. Follow-up at 12 months revealed resolved endoleaks, occlusion in one PA and mild stenosis in three in group B. In group A, occlusion occurred in one PA and mild stenosis in two. Light microscopy revealed new intima, and all aneurysm sacs were filled with thrombi. In group B, endothelial progress was complete at 12 months, and closely correlated with haemodynamic changes.Conclusions: Application of a Willis stent graft is a feasible method of treating CS aneurysms, and it exhibits a prolonged endothelial progress compared with that in straight vessels. [ABSTRACT FROM AUTHOR]

Metal-oxo clusters show great promise in lithium ion battery applications as anode materials by virtue of their native nature of well-defined nanostructures and multielectron redox activities. However, their intrinsic unsatisfactory electrical conductivity and tendency to aggregation make them difficult to fully utilize. Herein, a well-dispersed Mn 12 O 12 (CH 3 COO) 16 (H 2 O) 4 (denoted as Mn 12 ) cluster is constructed by rationally adopting carbon dots (CDs) with nanosize and high conductivity as stabilizers. Thanks to the fully exposed redox sites of Mn 12 clusters and additional interfacial energy storage mechanism, the optimized Mn 12 /CDs-1:20 anode delivers a high specific capacity of 1643 mAh g -1 at 0.2 A g -1 (0.25 C) and exhibits outstanding rate and cycling capabilities. This paper provides a green and efficient paradigm to synthesize well-dispersed manganese-oxo clusters for the first time and builds a new platform for cluster-based energy storage.

Background and Purpose: Despite the superior dose conformity of proton therapy, the dose distribution is sensitive to daily anatomical changes, which can affect treatment accuracy. This study evaluated the dose recalculation accuracy of two synthetic computed tomography (sCT) generation algorithms in a commercial treatment planning system., Materials and Methods: The evaluation was conducted for head-and-neck, thorax-and-abdomen, and pelvis sites treated with proton therapy. Thirty patients with two cone-beam computed tomography (CBCT) scans each were selected. The sCT images were generated from CBCT scans using two algorithms, Corrected CBCT (corrCBCT) and Virtual CT (vCT). Dose recalculations were performed based on these images for comparison with "ground truth" deformed CTs., Results: The choice of algorithm influenced dose recalculation accuracy, particularly in high dose regions. For head-and-neck cases, the corrCBCT method showed closer agreement with the "ground truth", while for thorax-and-abdomen and pelvis cases, the vCT algorithm yielded better results (mean percentage dose discrepancy of 0.6 %, 1.3 % and 0.5 % for the three sites, respectively, in the high dose region). Head-and-neck and pelvis cases exhibited excellent agreement in high dose regions (2 %/2 mm gamma passing rate >98 %), while thorax-and-abdomen cases exhibited the largest differences, suggesting caution in sCT algorithm usage for this site. Significant systematic differences were observed in the clinical target volume and organ-at-risk doses in head-and-neck and pelvis cases, highlighting the importance of using the correct algorithm., Conclusions: This study provided treatment site-specific recommendations for sCT algorithm selection in proton therapy. The findings offered insights for proton beam centers implementing adaptive radiotherapy workflows., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

This study investigated the effect of 4 days low energy availability (LEA) on physiological markers and mood states in male endurance runners. Twelve participants (mean (standard deviation); age: 25.8 (3.8) years; fat-free mass (FFM): 52.8 (5.5) kg) completed three 4-day conditions: adequate energy availability (AEA): 45 kcal/kg FFM/day; LEA1: 30 kcal/kg FFM/day; and LEA2: 15 kcal/kg FFM/day, in a randomized order. Participants ran on a treadmill at 65% of V̇O 2 max until they expended 15 kcal/kg FFM/day of energy. Energy intake was adjusted to achieve the desired energy availability. Pre- and post-measurements of bone turnover, metabolism, testosterone and estradiol (plasma), resting metabolic rate (indirect calorimetry), and mood states (Brunel Mood Scale) were assessed. The results reported a significant decrease in testosterone (condition × time interaction, p  = 0.03) occurred on LEA2 (Pre: 23.8 (7.0) nmol/L vs. Post: 20.3 (7.7) nmol/L) compared with AEA (Pre: 22.9 (5.5) nmol/L vs. Post: 23.3 (6.1) nmol/L) or LEA1 (Pre: 23.6 (8.6) nmol/L vs. Post: 20.9 (8.8) nmol/L). Fatigue level significantly increased (condition × time interaction, p  = 0.02) in LEA2 (Pre: 3.5 (1.7) vs. Post: 6.5 (2.9)) but did not change in AEA (Pre: 2.8 (1.5) vs. Post: 2.5 (2.7)) or LEA1 (Pre: 2.8(2.4) vs. Post: 2.9 (2.0)). Other measures were unaffected by the interventions. In conclusion, this study suggests that testosterone and fatigue may serve as early indicators of LEA in male runners. However, other physiological markers and mood states appeared largely unaffected, aligning with existing literature indicating minimal disruption of physiological functions during acute LEA in male athletes. Study registration: Australian New Zealand Clinical Trials Registry (Trial No.: 381278)., Competing Interests: The authors declare there are no competing interests.

Background: Data on the effect of cardiac arrest (CA), cardiogenic shock (CS), and their combination on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI) are limited. The present study sought to evaluate the clinical outcomes of STEMI complicated by CA and CS, and to identify the risk factors for CA or CS., Methods: This study included 7468 consecutive patients with STEMI in China. The patients were divided into 4 groups (CA + CS, CA only, CS only, and No CA or CS). The endpoints were 30-day all-cause death and major adverse cardiovascular events. A Cox proportional hazards regression analysis was performed., Results: CA, CS, and their combination were noted in 332 (4.4 %), 377 (5.0 %), and 117 (1.6 %) among all patients. During the 30-day follow-up, 817 (10.9 %) all-cause deaths and 964 (12.9 %) major adverse cardiovascular events occurred, and the incidence of all-cause mortality (3.6 %, 62.3 %, 74.1 %, 83.3 %) and major adverse cardiovascular events (5.4 %, 67.1 %, 75.0 %, and 87.2 %) significantly increased in the No CA or CS, CS only, CA only, and CA + CS groups, respectively. In the multivariate Cox regression models, compared with the No CA or CS group, the CA + CS, CA, and C S-only groups were associated with an increased risk of all-cause death and major adverse cardiovascular events. Patients with CA + CS had the highest risk of all-cause death (hazard ratio [HR], 25.259 [95 % confidence interval (CI) 19.221-33.195]) and major adverse cardiovascular events (HR 19.098, 95%CI 14.797-24.648)., Conclusions: CA, CS, and their combination were observed in approximately 11 % of Chinese patients with STEMI, and were associated with increased risk for 30-day mortality and major adverse cardiovascular events in Chinese patients with STEMI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction: Daily quality assurance is an integral part of a radiotherapy workflow to ensure the dose is delivered safely and accurately to the patient. It is performed before the first treatment of the day and needs to be time and cost efficient for a multiple gantries proton center. In this study, we introduced an efficient method to perform QA for output constancy, range verification, spot positioning accuracy and imaging and proton beam isocenter coincidence with DailyQA3., Methods: A stepped acrylic block of specific dimensions is fabricated and placed on top of the DailyQA3 device. Treatment plans comprising of two different spread-out Bragg peaks and five individual spots of 1.0 MU each are designed to be delivered to the device. A mathematical framework to measure the 2D distance between the detectors and individual spot is introduced and play an important role in realizing the spot positioning and centering QA. Lastly, a 5 months trends of the QA for two gantries are presented., Results: The outputs are monitored by two ion chambers in the DailyQA3 and a tolerance of ± 3 % $ \pm 3\% $ are used. The range of the SOBPs are monitored by the ratio of ion chamber signals and a tolerance of ± 1 mm $ \pm 1\ {\mathrm{mm}}$ is used. Four diodes at ± 10 cm $ \pm 10\ {\mathrm{cm}}$ from the central ion chambers are used for spot positioning QA, while the central ion chamber is used for imaging and proton beam isocenter coincidence QA. Using the framework, we determined the absolute signal threshold corresponding to the offset tolerance between the individual proton spot and the detector. A 1.5 mm $1.5\ {\mathrm{mm}}$ tolerances are used for both the positioning and centering QA. No violation of the tolerances is observed in the 5 months trends for both gantries., Conclusion: With the proposed approach, we can perform four QA items in the TG224 within 10 min., (© 2024 The Authors. Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

In current clinical practice, radiotherapy (RT) is prescribed as a pre-determined total dose divided over daily doses (fractions) given over several weeks. The treatment response is typically assessed months after the end of RT. However, the conventional one-dose-fits-all strategy may not achieve the desired outcome, owing to patient and tumor heterogeneity. Therefore, a treatment strategy that allows for RT dose personalization based on each individual response is preferred. Multiple strategies have been adopted to address this challenge. As an alternative to current known strategies, artificial intelligence (AI)-derived mechanism-independent small data phenotypic medicine (PM) platforms may be utilized for N-of-1 RT personalization. Unlike existing big data approaches, PM does not engage in model refining, training, and validation, and guides treatment by utilizing prospectively collected patient's own small datasets. With PM, clinicians may guide patients' RT dose recommendations using their responses in real-time and potentially avoid over-treatment in good responders and under-treatment in poor responders. In this paper, we discuss the potential of engaging PM to guide clinicians on upfront dose selections and ongoing adaptations during RT, as well as considerations and limitations for implementation. For practicing oncologists, clinical trialists, and researchers, PM can either be implemented as a standalone strategy or in complement with other existing RT personalizations. In addition, PM can either be used for monotherapeutic RT personalization, or in combination with other therapeutics (e.g. chemotherapy, targeted therapy). The potential of N-of-1 RT personalization with drugs will also be presented., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective. In proton pencil beam scanning (PBS) continuous delivery, the beam is continuously delivered without interruptions between spots. For synchrotron-based systems, the extracted beam current exhibits a spill structure, and recent publications on beam current measurements have demonstrated significant fluctuations around the nominal values. These fluctuations potentially lead to dose deviations from those calculated assuming a stable beam current. This study investigated the dosimetric implications of such beam current fluctuations during proton PBS continuous scanning. Approach. Using representative clinical proton PBS plans, we performed simulations to mimic a worst-case clinical delivery environment with beam current varies from 50% to 250% of the nominal values. The simulations used the beam delivery parameters optimized for the best beam delivery efficiency of the upcoming particle therapy system at Mayo Clinic Florida. We reconstructed the simulated delivered dose distributions and evaluated the dosimetric impact of beam current fluctuations. Main results. Despite significant beam current fluctuations resulting in deviations at each spot level, the overall dose distributions were nearly identical to those assuming a stable beam current. The 1 mm/1% Gamma passing rate was 100% for all plans. Less than 0.2% root mean square error was observed in the planning target volume dose-volume histogram. Minimal differences were observed in all dosimetric evaluation metrics. Significance. Our findings demonstrate that with our beam delivery system and clinical planning practice, while significant beam current fluctuations may result in large local move monitor unit deviations at each spot level, the overall impact on the dose distribution is minimal., (© 2024 Institute of Physics and Engineering in Medicine.)

Objective. The validation of deformable image registration (DIR) for contour propagation is often done using contour-based metrics. Meanwhile, dose accumulation requires evaluation of voxel mapping accuracy, which might not be accurately represented by contour-based metrics. By fabricating a deformable anthropomorphic pelvis phantom, we aim to (1) quantify the voxel mapping accuracy for various deformation scenarios, in high- and low-contrast regions, and (2) identify any correlation between dice similarity coefficient (DSC), a commonly used contour-based metric, and the voxel mapping accuracy for each organ. Approach . Four organs, i.e. pelvic bone, prostate, bladder and rectum (PBR), were 3D printed using PLA and a Polyjet digital material, and assembled. The latter three were implanted with glass bead and CT markers within or on their surfaces. Four deformation scenarios were simulated by varying the bladder and rectum volumes. For each scenario, nine DIRs with different parameters were performed on RayStation v10B. The voxel mapping accuracy was quantified by finding the discrepancy between true and mapped marker positions, termed the target registration error (TRE). Pearson correlation test was done between the DSC and mean TRE for each organ. Main results . For the first time, we fabricated a deformable phantom purely from 3D printing, which successfully reproduced realistic anatomical deformations. Overall, the voxel mapping accuracy dropped with increasing deformation magnitude, but improved when more organs were used to guide the DIR or limit the registration region. DSC was found to be a good indicator of voxel mapping accuracy for prostate and rectum, but a comparatively poorer one for bladder. DSC > 0.85/0.90 was established as the threshold of mean TRE ⩽ 0.3 cm for rectum/prostate. For bladder, extra metrics in addition to DSC should be considered. Significance . This work presented a 3D printed phantom, which enabled quantification of voxel mapping accuracy and evaluation of correlation between DSC and voxel mapping accuracy., (© 2024 Institute of Physics and Engineering in Medicine.)

Introduction: Real-time gated proton therapy (RGPT) is a motion management technique unique to the Hitachi particle therapy system. It uses pulsed fluoroscopy to track an implanted fiducial marker. There are currently no published guidelines on how to conduct the commissioning and quality assurance. In this work we reported on our centre's commissioning workflow and our daily and monthly QA procedures., Methods: Six commissioning measurements were designed for RGPT. The measurements include imaging qualities, fluoroscopic exposures, RGPT marker tracking accuracy, temporal gating latency, fiducial marker tracking fidelity and an end-to-end proton dosimetry measurement. Daily QA consists of one measurement on marker localization accuracy. Four months daily QA trends are presented. Monthly QA consists of three measurementson the gating latency, fluoroscopy imaging quality and dosimetry verification of gating operation with RGPT., Results: The RGPT was successfully commissioned in our centre. The air kerma rates were within 15 % from specifications and the marker tracking accuracies were within 0.245 mm. The gating latencies for turning the proton beam on and off were 119.5 and 50.0 ms respectively. The 0.4x10.0 mm 2 Gold Anchor TM gave the best tracking results with visibility up to 30 g/cm 2 . Gamma analysis showed that dose distribution of a moving and static detectors had a passing rate of more than 95 % at 3 %/3mm. The daily marker localization QA results were all less than 0.2 mm., Conclusion: This work could serve as a good reference for other upcoming Hitachi particle therapy centres who are interested to use RGPT as their motion management solution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Objective: This study investigated the association of circulating levels of 25-hydroxyvitamin D (25[OH]D) with the risk of metabolic syndrome (MetS) and its components in adults., Methods: This nationwide cohort involved 23,810 Chinese adults attending annual health evaluations. Serum 25(OH)D levels, MetS status, and covariates were determined at each examination. Among them, 8146, 3310, and 1971 completed two, three, and more than three evaluations, respectively. A hybrid mixed-effects and Cox regression model was employed to determine the cross-sectional and longitudinal relationships., Results: The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS were significantly lower in individuals within quartile 4 (vs. 1) of serum 25(OH)D for both between-individual (0.43 [0.35, 0.52]) and within-individual comparisons (0.60 [0.50, 0.73]), respectively (all p -trends < 0.001). Among the MetS components, the corresponding ORs (95% CI) in between- and within-individual comparisons were 0.40 (0.29, 0.54) and 0.26 (0.19, 0.36) for abdominal obesity, 0.49 (0.41, 0.58) and 0.78 (0.66, 0.93) for high triglycerides, 0.70 (0.59, 0.82) and 0.75 (0.64, 0.87) for hypertriglyceridemia, 0.48 (0.39, 0.59) and 0.87 (0.71, 1.07) for low HDL cholesterol, and 0.92 (0.76, 1.12) and 0.49 (0.41, 0.59) for hypertension, respectively. Decreased hazard ratios (95% CIs) in quartile 4 (vs. 1) of 25(OH)D were found for MetS (0.80 [0.65, 1.00]), high triglycerides (0.76 [0.62, 0.92]), abdominal obesity (0.77 [0.63, 0.96]), and low HDL cholesterol (0.64 [0.50, 0.81])., Conclusions: Decreased concentrations of serum 25(OH)D correlate significantly to a heightened MetS risk and specific components. Our findings underscore the potential preventive function of circulating vitamin D concerning metabolic disorders.

Background: Given the increasing attention to glycemic variability (GV) and its potential implications for cardiovascular outcomes. This study aimed to explore the impact of acute GV on short-term outcomes in Chinese patients with ST-segment elevation myocardial infarction (STEMI)., Methods: This study enrolled 7510 consecutive patients diagnosed with acute STEMI from 274 centers in China. GV was assessed using the coefficient of variation of blood glucose levels. Patients were categorized into three groups according to GV tertiles (GV1, GV2, and GV3). The primary outcome was 30-day all-cause death, and the secondary outcome was major adverse cardiovascular events (MACEs). Cox regression analyses were conducted to determine the independent correlation between GV and the outcomes., Results: A total of 7136 patients with STEMI were included. During 30-days follow-up, there was a significant increase in the incidence of all-cause death and MACEs with higher GV tertiles. The 30-days mortality rates were 7.4% for GV1, 8.7% for GV2 and 9.4% for GV3 (p = 0.004), while the MACEs incidence rates was 11.3%, 13.8% and 15.8% for the GV1, GV2 and GV3 groups respectively (p < 0.001). High GV levels during hospitalization were significantly associated with an increased risk of 30-day all-cause mortality and MACEs. When analyzed as a continuous variable, GV was independently associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.679, 95% confidence Interval [CI] 1.005-2.804) and MACEs (HR 2.064, 95% CI 1.386-3.074). Additionally, when analyzed as categorical variables, the GV3 group was found to predict an increased risk of MACEs, irrespective of the presence of diabetes mellitus (DM)., Conclusion: Our study findings indicate that a high GV during hospitalization was significantly associated with an increased risk of 30-day all-cause mortality and MACE in Chinese patients with STEMI. Moreover, acute GV emerged as an independent predictor of increased MACEs risk, regardless of DM status., (© 2024. The Author(s).)

Background and Purpose: This work introduces the first assessment of CT calibration following the ESTRO's consensus guidelines and validating the HLUT through the irradiation of biological material., Methods: Two electron density phantoms were scanned with two CT scanners using two CT scan energies. The stopping power ratio (SPR) and mass density (MD) HLUTs for different CT scan energies were derived using Schneider's and ESTRO's methods. The comparison metric in this work is based on the Water-Equivalent Thickness (WET) difference between the treatment planning system and biological irradiation measurement. The SPR HLUTs were compared between the two calibration methods. To assess the accuracy of using MD HLUT for dose calculation in the treatment planning system, MD vs SPR HLUT was compared. Lastly, the feasibility of using a single SPR HLUT to replace two different energy CT scans was explored., Results: The results show a WET difference of less than 3.5% except for the result in the Bone region between Schneider's and ESTRO's methods. Comparing MD and SPR HLUT, the results from MD HLUT show less than a 3.5% difference except for the Bone region. However, the SPR HLUT shows a lower mean absolute percentage difference as compared to MD HLUT between the measured and calculated WET difference. Lastly, it is possible to use a single SPR HLUT for two different CT scan energies since both WET differences are within 3.5%., Conclusion: This is the first report on calibrating an HLUT following the ESTRO's guidelines. While our result shows incremental improvement in range uncertainty using the ESTRO's guideline, the prescriptional approach of the guideline does promote harmonization of CT calibration protocols between different centres., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: High-density dental fillings pose a non-negligible impact on head and neck cancer treatment. For proton therapy, stopping power ratio (SPR) prediction will be significantly impaired by the associated image artifacts. Dose perturbation is also inevitable, compromising the treatment plan quality. While plenty of work has been done on metal or amalgam fillings, none has touched on composite resin (CR) and glass ionomer cement (GIC) which have seen an increasing usage. Hence, this work aims to provide a detailed characterisation of SPR and dose perturbation in proton therapy caused by CR and GIC., Materials and Methods: Four types of fillings were used: CR, Fuji Bulk (FB), Fuji II (FII) and Fuji IX (FIX). The latter three belong to GIC category. Measured SPR were compared with SPR predicted using single-energy computed tomography (SECT) and dual-energy computed tomography (DECT). Dose perturbation of proton beams with lower- and higher-energy levels was also quantified using Gafchromic films., Results: The measured SPR for CR, FB, FII and FIX were 1.68, 1.77, 1.77 and 1.76, respectively. Overall, DECT could predict SPR better than SECT. The lowest percentage error achieved by DECT was 19.7 %, demonstrating the challenge in estimating SPR, even for fillings with relatively lower densities. For both proton beam energies and all four fillings of about 4.5 mm thickness, the maximum dose perturbation was 3 %., Conclusion: This study showed that dose perturbation by CR and GIC was comparatively small. We have measured and recommended the SPR values for overriding the fillings in TPS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Tolerance limit is defined on pre-treatment patient specific quality assurance results to identify "out of the norm" dose discrepancy in plan. An out-of-tolerance plan during measurement can often cause treatment delays especially if replanning is required. In this study, we aim to develop an outlier detection model to identify out-of-tolerance plan early during treatment planning phase to mitigate the above-mentioned risks., Methods: Patient-specific quality assurance results with portal dosimetry for stereotactic body radiotherapy measured between January 2020 and December 2021 were used in this study. Data were divided into thorax and pelvis sites and gamma passing rates were recorded using 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria. Statistical process control method was used to determine six different site and criterion-specific tolerance and action limits. Using only the inliers identified with our determined tolerance limits, we trained three different outlier detection models using the plan complexity metrics extracted from each treatment field-robust covariance, isolation forest, and one class support vector machine. The hyperparameters were optimized using the F1-score calculated from both the inliers and validation outliers' data., Results: 308 pelvis and 200 thorax fields were used in this study. The tolerance (action) limits for 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria in the pelvis site are 99.1% (98.1%), 95.8% (91.1%), and 91.7% (86.1%), respectively. The tolerance (action) limits in the thorax site are 99.0% (98.7%), 97.0% (96.2%), and 91.5% (87.2%). One class support vector machine performs the best among all the algorithms. The best performing model in the thorax (pelvis) site achieves a precision of 0.56 (0.54), recall of 1.0 (1.0), and F1-score of 0.72 (0.70) when using the 2%/2 mm (2%/1 mm) criterion., Conclusion: The model will help the planner to identify an out-of-tolerance plan early so that they can refine the plan further during the planning stage without risking late discovery during measurement., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Importance: Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a need for host-targeted therapies against influenza to provide an effective alternative therapeutic target. Sec13 was identified as a novel host interactor of influenza. Endoplasmic reticulum-to-Golgi transport is an important pathway of influenza virus replication and viral export. Specifically, Sec13 has a functional role in influenza replication and virulence., Competing Interests: The authors declare no conflict of interest.

Purpose: A daily quality assurance (QA) check in proton therapy is ensuring that the range of each proton beam energy in water is accurate to 1 mm. This is important for ensuring that the tumor is adequately irradiated while minimizing damage to surrounding healthy tissue. It is also important to verify the total charge collected against the beam model. This work proposes a time-efficient method for verifying the range and total charge of proton beams at different energies using a multilayer Faraday collector (MLFC)., Methods: We used an MLFC-128-250 MeV comprising 128 layers of thin copper foils separated by thin insulating Kapton TM layers. Protons passing through the collector induce a charge on the metallic foils, which is integrated and measured by a multichannel electrometer. The charge deposition on the foils provides information about the beam range., Results: Our results show that the proton beam range obtained using MLFC correlates closely with the range obtained from commissioning water tank measurements for all proton energies. Upon applying a range calibration factor, the maximum deviation is 0.4 g/cm 2 . The MLFC range showed no dependence on the number of monitor units and the source-to-surface distance. Range measurements collected over multiple weeks exhibited stability. The total charge collected agrees closely with the theoretical charge from the treatment planning system beam model for low- and mid-range energies., Conclusions: We have calibrated and commissioned the use of the MLFC to easily verify range and total charge of proton beams. This tool will improve the workflow efficiency of the proton QA., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Reasonably designing and constructing efficient artificial S-mechanism photocatalysts, expanding their application in the field of photocatalytic organic synthesis, have become a hot and challenging topic in the photocatalysis. Herein, a series of coral-like W 18 O 49 @TpPa-H (TpPa-H represents COFs generated by the reaction of 1,3,5-triformylphloroglucinol (Tp) and p-phenylenediamine (Pa-H)) composites were successfully prepared by using a simple in-situ encapsulation strategy. Given the internal electric field at the S-scheme interface, W 18 O 49 acts as an oxidative photocatalyst with sufficient positive valence band (VB) position and TpPa-H as a reductive one with enough negative conduction band (CB) position for the efficient amines oxidative coupling to imines. The resulting W 18 O 49 @TpPa-H-0.1 hybrid material shows both optimal benzylamine to imine conversion and selectivity exceeding 99 % within 4 h under 10 W 420 nm LED light irradiation, which is 9.9 and 2.8 fold greater than that of W 18 O 49 and TpPa-H, respectively. The photocatalytic activity is even extended to 740 nm. Furthermore, the photocatalytic mechanism research confirmed that a high efficiency S-scheme heterojunction was formed between W 18 O 49 and TpPa-H, and multiple active species, such as ·O 2 - , 1 O 2 , and h + , synergistically participated in the reaction, imparting its excellent photocatalytic performance. This work may open new avenues for the development of high-efficiency COFs-based S-scheme heterojunction for organic photosynthesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Developing highly efficient, stable, and cost-effective two-dimensional (2D) conjugated polymers (CPs) for overall water splitting (OWS) is critical for producing clean and renewable hydrogen energy, yet it remains a great challenge. Here, we designed eight 2D CPs through the topological assembly of diacetylene and benzene-derived molecular linkers that can offer active sites for hydrogen and oxygen evolution reactions, and explored their structural, electronic, optical, and photocatalytic OWS properties by performing first-principles computations. It is shown that incorporating benzo-heterocyclic rings into CPs can significantly modulate the electronic structures of CPs and broaden the spectral absorption, suitable for visible-light-driven OWS. Remarkably, through a range of screening criteria, including stability, electronic band structures, band edge alignments, and photocatalytic activity, we found that CP-4 based on diacetylene and benzotrifuran can spontaneously trigger the OWS in a neutral environment under its own light-induced bias, eliminating the need for sacrificial agents or cocatalysts. Specifically, the HER active site is primarily located at diacetylene moieties, while the OER active site is mainly concentrated on the benzo-heterocyclic rings. Moreover, the ideal STH efficiency for OWS on CP-4 was estimated to be 13.87%, highlighting its potential as a prospective photocatalyst for large-scale industrial OWS. Our findings open a door to the rational design of novel polymer photocatalysts for OWS.

Background: Bevacizumab is used in the treatment of radiation necrosis (RN), which is a debilitating toxicity following head and neck radiotherapy. However, there is no biomarker to predict if a patient would respond to bevacizumab., Purpose: We aimed to develop a cluster-based radiomics approach to characterize the spatial heterogeneity of RN and map their responses to bevacizumab., Methods: 118 consecutive nasopharyngeal carcinoma patients diagnosed with RN were enrolled. We divided 152 lesions from the patients into 101 for training, and 51 for validation. We extracted voxel-level radiomics features from each lesion segmented on T1-weighted+contrast and T2 FLAIR sequences of pre- and post-bevacizumab magnetic resonance images, followed by a three-step analysis involving individual- and population-level clustering, before delta-radiomics to derive five radiomics clusters within the lesions. We tested the association of each cluster with response to bevacizumab and developed a clinico-radiomics model using clinical predictors and cluster-specific features., Results: 71 (70.3%) and 34 (66.7%) lesions had responded to bevacizumab in the training and validation datasets, respectively. Two radiomics clusters were spatially mapped to the edema region, and the volume changes were significantly associated with bevacizumab response ( OR :11.12 [95% CI: 2.54-73.47], P  = 0.004; and 1.63[1.07-2.78], P  = 0.042). The combined clinico-radiomics model based on textural features extracted from the most significant cluster improved the prediction of bevacizumab response, compared with a clinical-only model (AUC:0.755 [0.645-0.865] to 0.852 [0.764-0.940], training; 0.708 [0.554-0.861] to 0.816 [0.699-0.933], validation)., Conclusion: Our radiomics approach yielded intralesional resolution, enabling a more refined feature selection for predicting bevacizumab efficacy in the treatment of RN., Competing Interests: The authors declare no direct conflict of interests. Melvin L.K. Chua reports personal fees from Astellas, Janssen, Bayer, Pfizer, MSD, Varian, Telix Pharmaceuticals, personal fees and non-financial support from AstraZeneca, personal fees and grants from Ferring, non-financial support from Decipher Biosciences, non-financial support from MedLever, consults for immunoSCAPE Inc., and is a co-inventor and co-owns the patent of a High Sensitivity Lateral Flow Immunoassay For Detection of Analyte in Sample (10202107837T), Singapore, outside the submitted work., (© 2023 The Authors.)

Background and Purpose: This study aimed to investigate the feasibility of safe-dose escalation to dominant intraprostatic lesions (DILs) and assess the clinical impact using dose-volume (DV) and biological metrics in photon and proton therapy. Biological parameters defined as late grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) derived from planned ( D P ) and accumulated dose ( D A ) were utilized., Materials and Methods: In total, 10 patients with high-risk prostate cancer with multiparametric MRI-defined DILs were investigated. Each patient had two plans with a focal boost to the DILs using intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT). Plans were optimized to obtain DIL coverage while respecting the mandatory organ-at-risk constraints. For the planning evaluation, DV metrics, tumor control probability (TCP) for the DILs and whole prostate excluding the DILs (prostate-DILs), and normal tissue complication probability (NTCP) for the rectum and bladder were calculated. Wilcoxon signed-rank test was used for analyzing TCP and NTCP data., Results: IMPT achieved a higher D mean for the DILs compared to VMAT (IMPT: 68.1 GyRBE vs. VMAT: 66.6 Gy, p < 0.05). Intermediate-high rectal and bladder doses were lower for IMPT ( p < 0.05), while the high-dose region (V60 Gy) remained comparable. IMPT-TCP for prostate-DIL were higher compared to VMAT (IMPT: 86%; α/β = 3, 94.3%; α/β = 1.5 vs. VMAT: 84.7%; α/β = 3, 93.9%; α/β = 1.5, p < 0.05). Likewise, IMPT obtained a moderately higher DIL TCP (IMPT: 97%; α/β = 3, 99.3%; α/β = 1.5 vs. VMAT: 95.9%; α/β = 3, 98.9%; α/β = 1.5, p < 0.05). Rectal D A -NTCP displayed the highest GI toxicity risk at 5.6%, and IMPT has a lower GI toxicity risk compared to VMAT-predicted Quantec-NTCP ( p < 0.05). Bladder D P -NTCP projected a higher GU toxicity than D A -NTCP, with VMAT having the highest risk ( p < 0.05)., Conclusion: Dose escalation using IMPT is able to achieve a high TCP for the DILs, with the lowest rectal and bladder DV doses at the intermediate-high-dose range. The reduction in physical dose was translated into a lower NTCP ( p < 0.05) for the bladder, although rectal toxicity remained equivalent., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ong, Knight, Panettieri, Dimmock, Tuan, Tan and Wright.)

Introduction . Dispersion in an accelerator quantifies the deviation of the proton trajectory when there is a momentum deviation. We present for the first time a safe method of measuring dispersion in the clinic, using a scintillator detector and the momentum deviations within a spill. This is an important accelerator quantity as we found that this is the reason behind the large dose fluctuation in our absolute dosimetry measurement. Methods . Dispersions are measured for nine energies in a Hitachi ProBeat system at three locations (isocenter and at two profile monitors) and at two gantry angles (0 and 90 degrees) by first measuring the spot position and momentum drift within a spill. The spot position drift is measured by the XRV-4000 at the isocenter, and by the two profile monitors located at 0.57 and 2.27 m from the isocenter. The momentum drift is calculated from the intra-spill range drift which is measured using the Ranger accessory. The dispersion at isocenter and its gradient are calculated using the weighted least square regression on the measured dispersions at the three locations. A constraint is formulated on the dispersion and its gradient to ensure minimal intra-spill spot position deviation around the isocenter. Results . The measured intra-spill range and spot positional drift at isocenter are less than0.25mmand0.7mmrespectively. The momentum spread calculated from the range drift are less than 0.08%. The dispersion at the isocenter ranged from0.50to4.30mand the zero-crossing happens upstream of isocenter for all energies. 2 of the 9 energies (168.0 and 187.5 MeV) violated the constraint and has an intra-spill spot positional deviation greater than1.0within5cmfrom the isocenter. Conclusion . This measurement is recommended as part of commissioning and annual quality assurance for accelerator monitoring and to ensure intra-spill spot deviations remain low., (© 2023 Institute of Physics and Engineering in Medicine.)

Background: Endovascular recanalization in patients with symptomatic nonacute intracranial large artery occlusion (ILAO) has been reported to be feasible, but technically challenging. This study aimed to determine the predictors of successful endovascular recanalization in patients with symptomatic nonacute ILAO., Methods: The outcomes of endovascular recanalization attempts performed in 70 consecutive patients showing symptomatic nonacute ILAO with hemodynamic cerebral ischemia between January 2016 to December 2022 were reviewed. Potential variables, including clinical and radiological characteristics related to technical success, were collected. Univariate analysis and multivariate logistic regression were performed to identify predictors of successful recanalization for nonacute ILAO., Results: Technically successful recanalization was achieved in 57 patients (81.4%). The periprocedural complication rate was 21.4% (15 of 70), and the overall 30-day morbidity and mortality rates were 7.1% (5 of 70) and 2.9% (2 of 70), respectively. Univariate analysis showed that successful recanalization was associated with occlusion duration, stump morphology, occlusion length, slow distal antegrade flow sign, and the presence of bridging collateral vessels. Multivariate analysis showed that occlusion duration ≤ 3 months (odds ratio [OR]: 22.529; 95% confidence interval [CI]: 1.636-310.141), tapered stump (OR: 7.498; 95% CI: 1.533-36.671), and occlusion length < 10 mm (OR: 7.049; 95% CI: 1.402-35.441) were independent predictive factors for technical success of recanalization., Conclusions: Occlusion duration ≤ 3 months, tapered stump, and occlusion length < 10 mm were independent positive predictors of technical success of endovascular recanalization for symptomatic nonacute ILAO. These findings may help predict the likelihood of successful recanalization in patients with symptomatic nonacute ILAO and also provide a reference for the selection of appropriate patients. Further prospective and multicenter studies are required to validate our findings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To assess large language models on their ability to accurately infer cancer disease response from free-text radiology reports., Materials and Methods: We assembled 10 602 computed tomography reports from cancer patients seen at a single institution. All reports were classified into: no evidence of disease, partial response, stable disease, or progressive disease. We applied transformer models, a bidirectional long short-term memory model, a convolutional neural network model, and conventional machine learning methods to this task. Data augmentation using sentence permutation with consistency loss as well as prompt-based fine-tuning were used on the best-performing models. Models were validated on a hold-out test set and an external validation set based on Response Evaluation Criteria in Solid Tumors (RECIST) classifications., Results: The best-performing model was the GatorTron transformer which achieved an accuracy of 0.8916 on the test set and 0.8919 on the RECIST validation set. Data augmentation further improved the accuracy to 0.8976. Prompt-based fine-tuning did not further improve accuracy but was able to reduce the number of training reports to 500 while still achieving good performance., Discussion: These models could be used by researchers to derive progression-free survival in large datasets. It may also serve as a decision support tool by providing clinicians an automated second opinion of disease response., Conclusions: Large clinical language models demonstrate potential to infer cancer disease response from radiology reports at scale. Data augmentation techniques are useful to further improve performance. Prompt-based fine-tuning can significantly reduce the size of the training dataset., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: The relationship between copeptin and the severity of circulatory dysfunction and systemic stress response in patients with chronic liver disease (CLD) has been established. Nevertheless, the potential of serum copeptin levels to predict the prognosis of CLD patients remains unclear., Aim: To conduct a systematic review and meta-analysis to investigate the correlation between serum copeptin and transplant-free survival (TFS) in this population., Methods: To achieve the objective of the meta-analysis, PubMed, Embase, the Cochrane Library, and the Web of Science were searched to identify observational studies with longitudinal follow-up. The Cochrane Q test was utilized to assess between-study heterogeneity, and the I 2 statistic was estimated. Random-effects models were employed to combine the outcomes, taking into account the potential influence of heterogeneity., Results: Ten datasets including 3133 patients were involved. The follow-up durations were 1 to 48 mo (mean: 12.5 mo). Overall, it was shown that a high level of serum copeptin was associated with a poor TFS [risk ratio (RR): 1.82, 95% confidence interval: 1.52-2.19, P < 0.001; I 2 = 0%]. In addition, sensitivity analysis by omitting one dataset at a time showed consistent results (RR: 1.73-2.00, P < 0.05). Finally, subgroup analyses according to study country, study design, patient diagnosis, cutoff of copeptin, follow-up duration, and study quality score also showed similar results ( P for subgroup difference all > 0.05)., Conclusion: Patients with CLD who have high serum copeptin concentrations may be associated with a poor clinical prognosis., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective . Automatic deformable image registration (DIR) is a critical step in adaptive radiotherapy. Manually delineated organs-at-risk (OARs) contours on planning CT (pCT) scans are deformably registered onto daily cone-beam CT (CBCT) scans for delivered dose accumulation. However, evaluation of registered contours requires human assessment, which is time-consuming and subjects to high inter-observer variability. This work proposes a deep learning model that allows accurate prediction of Dice similarity coefficients (DSC) of registered contours in prostate radiotherapy. Approach . Our dataset comprises 20 prostate cancer patients with 37-39 daily CBCT scans each. The pCT scans and planning contours were deformably registered to each corresponding CBCT scan to generate virtual CT (vCT) scans and registered contours. The DSC score, which is a common contour-based validation metric for registration quality, between the registered and manual contours were computed. A Siamese neural network was trained on the vCT-CBCT image pairs to predict DSC. To assess the performance of the model, the root mean squared error (RMSE) between the actual and predicted DSC were computed. Main results . The model showed promising results for predicting DSC, giving RMSE of 0.070, 0.079 and 0.118 for rectum, prostate, and bladder respectively on the holdout test set. Clinically, a low RMSE implies that the predicted DSC can be reliably used to determine if further DIR assessment from physicians is required. Considering the event where a registered contour is classified as poor if its DSC is below 0.6 and good otherwise, the model achieves an accuracy of 92% for the rectum. A sensitivity of 0.97 suggests that the model can correctly identify 97% of poorly registered contours, allowing manual assessment of DIR to be triggered. Significance . We propose a neural network capable of accurately predicting DSC of deformably registered OAR contours, which can be used to evaluate eligibility for plan adaptation., (Creative Commons Attribution license.)

RNA-binding proteins (RBPs) control RNA metabolism to orchestrate gene expression and, when dysfunctional, underlie human diseases. Proteome-wide discovery efforts predict thousands of RBP candidates, many of which lack canonical RNA-binding domains (RBDs). Here, we present a hybrid ensemble RBP classifier (HydRA), which leverages information from both intermolecular protein interactions and internal protein sequence patterns to predict RNA-binding capacity with unparalleled specificity and sensitivity using support vector machines (SVMs), convolutional neural networks (CNNs), and Transformer-based protein language models. Occlusion mapping by HydRA robustly detects known RBDs and predicts hundreds of uncharacterized RNA-binding associated domains. Enhanced CLIP (eCLIP) for HydRA-predicted RBP candidates reveals transcriptome-wide RNA targets and confirms RNA-binding activity for HydRA-predicted RNA-binding associated domains. HydRA accelerates construction of a comprehensive RBP catalog and expands the diversity of RNA-binding associated domains., Competing Interests: Declaration of interests G.W.Y. is a co-founder, member of the Board of Directors, on the SAB, equity holder, and paid consultant for Locanabio and Eclipse BioInnovations. G.W.Y. is a visiting professor at the National University of Singapore. G.W.Y.’s interests have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies., (Copyright © 2023 University of California San Diego. Published by Elsevier Inc. All rights reserved.)

Background: Absolute dosimetry measurement is an integral part of Treatment Planning System (TPS) commissioning and it involves measuring the integrated absorbed dose to water for all energies in a pencil beam scanning delivery system. During the commissioning of Singapore's first proton therapy center, a uniform scanned field with an Advanced Markus chamber method was employed for this measurement, and a large dose fluctuation of at least 5% was observed for 10% of the energy layers during repeated measurements., Purpose: This study aims to understand the root cause of this fluctuation by relating the actual delivered spot information in the log file with the charge measurement by the ion chambers., Methods: A dedicated pencil beam dose algorithm was developed, taking into account the log file parameters, to calculate the dose for a single energy layer in a homogeneous water phantom. Three energies, 70.2, 182.7, and 228.7 MeV were used in this study, with the 182.7 MeV energy exhibiting large dose fluctuation. The dose fluctuation was investigated as a function of detector's sizes (pinpoint 3D, Advanced Markus, PTW 34070, and PTW 34089) and water depth (2 , 6, and 20 cm). Twelve ion chambers measurements were performed for each chamber and depth. The comparison of the theoretically predicted integrated dose and the charge measurement served as a validation of the algorithm., Results: About 5.9% and 9.6% dose fluctuation were observed in Advanced Markus and pinpoint 3D measurements at 2 cm depth for 182.7 MeV, while fluctuation of 1.6% and 1.1% were observed in Advanced Markus with 228.7 and 70.2 MeV at similar depth. Fluctuation of less than 0.1% was observed for PTW34070 and PTW 34089 for all energies. The fluctuation was found to diminish with larger spot size at 20 cm depth to 1.3% for 182.7 MeV. The theoretical and measured charge comparison showed a high linear correlation of R 2 > 0.80 ${R^2} &gt; 0.80$ for all datasets, indicating the fluctuation originated from the delivered spot characteristics. The cause of fluctuation was identified to be due to the spill change occurring close to the detector, and since the spot positional deviation profiles were different between two spills, this resulted in local hot spots between columns of spots. The actual position of spill change varies randomly during measurement, which led to a random occurrence of hot spot within the detector's sensitive volume and a fluctuating dose measurement., Conclusion: This is the first report of a dose fluctuation greater than 5% in absolute dosimetry measurement with a uniform scanned field and the cause of the fluctuation has been conclusively determined. It is important to choose the MU and scanning pattern carefully to avoid spill change happening when the spot delivery is near the detector., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Aims: The purpose of this research was to assess the effect of chlorogenic acid (CGA) in the diet on ileac structure, barrier function, immunological state, and microbial profile of broiler chickens in a high stocking density (HD) environment. Methods: Four hundred and seventy-six male AA broiler chickens were randomly split into four groups, two with a normal stocking density (ND) of fourteen birds per m 2 and two with a high stocking density of twenty-two birds per m 2 . Each of the treatments consisted of five replicates. One of the two ND and HD groups received the usual feed, while the other two were given at 1.5 g/kg CGA as part of their dietary regimen. Results: The ND CGA group showed a greater increase in villus height and villus height/crypt depth compared to the ND group at 35 and 42 days. The HD group experienced a greater elevation in villus height due to CGA supplementation than the HD group across days 28, 35, and 42. At day 42, the HD group saw a decline in OCLN and ZO-1 mRNA expression in the ileum, but CGA was able to restore them. The HD group experienced a greater rise in OCLN mRNA than the control HD group when supplemented with CGA. The expression of TNF-α, IL-1β , and IL-6 in the ileum was higher in the HD group, and CGA supplementation enhanced this effect. The HD group experienced a greater rise in IL-10 mRNA expression than the control group following the administration of CGA. The HD group showed reduced alpha diversity and an increase in detrimental microbes such as Turicibacter and Shigella in the gut compared to the ND group, while the HD CGA group saw a reduction in Turicibacter, Shigella , and other harmful microbes. These findings reveal that HD stress suppressed the growth of ileac villi, decreased the expression of tight-junction genes, amplified the expression of inflammatory genes, and disturbed the gut microbiota, ultimately leading to increased intestinal permeability. Conclusion: We conclude that when chickens are given dietary CGA, the disruption of the ileac barrier and increased oxidative damage and inflammation due to HD stress are reduced, which increases ileac integrity and the presence of beneficial intestinal bacteria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Zhang, Bai, Liu, He, Ito, Liu, Tan, Zhen, Zhang, Zhang and Ma.)

Spine stereotactic body radiation therapy (SBRT) uses high dose per fraction for palliative pain control. The treatment plans are often heavily modulated due to close proximity to spinal cord and this can lead to poor plan quality which are susceptible to dose delivery discrepancy. Therefore, we aim to assess the effectiveness of the monitor unit (MU) objective tool in Eclipse treatment planning systems in modulating the plan complexity to improve the plan quality in spine SBRT. Seven retrospective spine SBRT plans are re-optimized using the MU objective tool in Eclipse TPS v13.6 and were compared with the original plans. The dose metrics of the tumor PTV were compared using D 1cc. D 99%, D 95%, D 0.03cc , D 0.1cc , D 0.35cc and D 1cc, and that of cord PRV were compared using D 0.03cc , D 0.1cc , D 0.35cc . Four different plan complexities were also calculated for the original and re-optimized plans to quantify the impact of the tool on the modulation. Patient specific quality assurance measurements were performed with Stereophan and SRS MapCheck, and analyzed using the 1%/1-mm and 2%/2-mm criteria with gamma analysis. The dose metrics of the PTV and cord PRV of the re-optimized and original plans are similar and still meet the planning dose constraints. In particular, the PTV dose coverage has a small percentage difference of (0.15 ± 1.33)% and (0.01 ± 1.04)% for D 99% and D 95% , respectively. The 4 calculated plan complexity metrics consistently show that the re-optimized plans are quantitatively less complex than the original plan. The gamma passing rate of the re-optimized plans improved from (92.2 ± 2.0)% to (94.2 ± 1.6)% with the 1%/1-mm criterion, and (98.7 ± 1.0)% to (99.5 ± 0.3)% with the 2%/2-mm criterion. Overall, the re-optimized plans achieve at least a 10% MU reduction (11.7% to 24.6%). Our study shows that optimization with the MU objective tool can reduce plan complexity and improves dose delivery accuracy, while not compromising the dose distribution., (Copyright © 2022 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Objective: This work aims to use machine learning models to predict gamma passing rate of portal dosimetry quality assurance with log file derived features. This allows daily treatment monitoring for patients and reduce wear and tear on EPID detectors to save cost and prevent downtime., Methods: 578 VMAT trajectory log files selected from prostate, lung and spine SBRT were used in this work. Four machine learning models were explored to identify the best performing regression model for predicting gamma passing rate within each sub-site and the entire unstratified data. Predictors used in these models comprised of hand-crafted log file-derived features as well as modulation complexity score. Cross validation was used to evaluate the model performance in terms of R 2 and RMSE., Result: Using gamma passing rate of 1%/1mm criteria and entire dataset, LASSO regression has a R 2 of 0.121 ± 0.005 and RMSE of 4.794 ± 0.013%, SVM regression has a R 2 of 0.605 ± 0.036 and RMSE of 3.210 ± 0.145%, Random Forest regression has a R 2 of 0.940 ± 0.019 and RMSE of 1.233 ± 0.197%. XGBoost regression has the best performance with a R 2 and RMSE value of 0.981 ± 0.015 and 0.652 ± 0.276%, respectively., Conclusion: Log file-derived features can predict gamma passing rate of portal dosimetry with an average error of less than 2% using the 1%/1mm criteria. This model can potentially be applied to predict the patient specific QA results for every treatment fraction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lew, Chua, Koh, Lee, Park and Tan.)

Regional hyperthermia therapy (RHT) is a treatment that applies moderate heat to tumours in an attempt to potentiate the effects of oncological treatments and improve responses. Although it has been used for many years, the mechanisms of action are not fully understood. Heterogenous practices, poor quality assurance, conflicting clinical evidence and lack of familiarity have hindered its use. Despite this, several centres recognise its potential and have adopted it in their standard treatment protocols. In recent times, significant technical improvements have been made and there is an increasing pool of evidence that could revolutionise its use. Our narrative review aims to summarise the recently published prospective trial evidence and present the clinical effects of RHT when added to standard cancer treatments. In total, 31 studies with higher-quality evidence across various subsites are discussed herein. Although not all of these studies are level 1 evidence, benefits of moderate RHT in improving local tumour control, survival outcomes and quality of life scores were observed across the different cancer subsites with minimal increase in toxicities. This paper may serve as a reference when considering this technique for specific indications.

This paper aims to review on fetal dose in radiotherapy and extends and updates on a previous work 1 to include proton therapy. Out-of-field doses, which are the doses received by regions outside of the treatment field, are unavoidable regardless of the treatment modalities used during radiotherapy. In the case of pregnant patients, fetal dose is a major concern as it has long been recognized that fetuses exposed to radiation have a higher probability of suffering from adverse effects such as anatomical malformations and even fetal death, especially when the 0.1Gy threshold is exceeded. In spite of the low occurrence of cancer during pregnancy, the radiotherapy team should be equipped with the necessary knowledge to deal with fetal dose. This is crucial so as to ensure that the fetus is adequately protected while not compromising the patient treatment outcomes. In this review paper, various aspects of fetal dose will be discussed ranging from biological, clinical to the physics aspects. Other than fetal dose resulting from conventional photon therapy, this paper will also extend the discussion to modern treatment modalities and techniques, namely proton therapy and image-guided radiotherapy, all of which have seen a significant increase in use in current radiotherapy. This review is expected to provide readers with a comprehensive understanding of fetal dose in radiotherapy, and to be fully aware of the steps to be taken in providing radiotherapy for pregnant patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Normal tissue complication probability (NTCP) parameters derived from traditional 3D plans may not be ideal in defining toxicity outcomes for modern radiotherapy techniques. This study aimed to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively scored clinical data for late gastrointestinal (GI) and genitourinary (GU) toxicities for high-risk prostate cancer patients treated using volumetric-modulated-arc-therapy (VMAT). Dose-volume-histograms (DVH) extracted from planned (D P ) and accumulated dose (D A ) were used., Material and Methods: D P and D A obtained from the DVH of 150 prostate cancer patients with pelvic-lymph-nodes irradiation treated using VMAT were used to generate LKB-NTCP parameters using maximum likelihood estimations. Defined GI and GU toxicities were recorded up to 3-years post RT follow-up. Model performance was measured using Hosmer-Lemeshow goodness of fit test and the mean area under the receiver operating characteristics curve (AUC). Bootstrapping method was used for internal validation., Results: For mild-severe (Grade ≥1) GI toxicity, the model generated similar parameters based on D A and D P DVH data (D A -D 50 :71.6 Gy vs D P -D 50 :73.4; D A -m:0.17 vs D P -m:0.19 and D A/P -n 0.04). The 95% CI for D A -D 50 was narrower and achieved an AUC of >0.6. For moderate-severe (Grade ≥2) GI toxicity, D A -D 50 parameter was higher and had a narrower 95% CI (D A -D 50 :77.9 Gy, 95% CI:76.4-79.6 Gy vs D P -D 50 :74.6, 95% CI:69.1-85.4 Gy) with good model performance (AUC>0.7). For Grade ≥1 late GU toxicity, D 50 and n parameters for D A and D P were similar (D A -D 50 : 58.8 Gy vs D P -D 50 : 59.5 Gy; D A -n: 0.21 vs D P -n: 0.19) with a low AUC of<0.6. For Grade ≥2 late GU toxicity, similar NTCP parameters were attained from D A and D P DVH data (D A -D 50 :81.7 Gy vs D P -D 50 :81.9 Gy; D A -n:0.12 vs D P -n:0.14) with an acceptable AUCs of >0.6., Conclusions: The achieved NTCP parameters using modern RT techniques and accounting for organ motion differs from QUANTEC reported parameters. D A -D 50 of 77.9 Gy for GI and D A /D P -D 50 of 81.7-81.9 Gy for GU demonstrated good predictability in determining the risk of Grade ≥2 toxicities especially for GI derived D 50 and are recommended to incorporate as part of the DV planning constraints to guide dose escalation strategies while minimising the risk of toxicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ong, Knight, Panettieri, Dimmock, Tuan, Tan and Wright.)

The present study aimed to evaluate sex-specific association between admission systolic blood pressure (SBP) and in-hospital prognosis in patients with acute decompensated heart failure (ADHF) admitted to intensive care unit (ICU). In this retrospective, observational study, 1268 ADHF patients requiring intensive care were consecutively enrolled and divided by sex. Patients were divided into three subgroups according to SBP tertiles: high (≥ 122 mmHg), moderate (104-121 mmHg) and low (< 104 mmHg). The primary endpoint was either all-cause mortality, cardiac arrest or utilization of mechanical support devices during hospitalization. Female patients were more likely to be older, have poorer renal function and higher ejection fractions (p < 0.001). The C statistics of SBP was 0.665 (95%CI 0.611-0.719, p < 0.001) for men and 0.548 (95% CI 0.461-0.634, p = 0.237) for women, respectively. Multivariate analysis demonstrated that admission SBP as either a continuous (OR = 0.984, 95% CI 0.973-0.996) or a categorical (low vs. high, OR = 3.293, 95% CI 1.610-6.732) variable was an independent predictor in male but the risk did not statistically differ between the moderate and high SBP strata (OR = 1.557, 95% CI 0.729-3.328). In female, neither low (OR = 1.135, 95% CI 0.328-3.924) nor moderate (OR = 0.989, 95% CI 0.277-3.531) SBP had a significant effect on primary endpoint compared with high SBP strata. No interaction was detected between left ventricular ejection fraction (LVEF) and SBP (p for interaction = 0.805). In ADHF patients admitted to ICU, SBP showed a sex-related prognostic effect on primary endpoint. In male, lower SBP was independently associated with an increased risk of primary endpoint. Conversely, in female, no relationship was observed., (© 2022. Springer Japan KK, part of Springer Nature.)

The brown planthopper (BPH) is the leading cause of insect damage to rice plants and BPH infestations have caused profound losses in rice production since the 1970's. There is an urgent need to discover new BPH resistance genes to ensure the successful production of rice. Here, a new BPH resistance source provided by SeedWorks International Pvt. Ltd., SWD10, was used for this purpose. QTL mapping using 232 F 2 progenies and 216 polymorphic markers revealed two dominant BPH resistance QTLs, BPH41 and BPH42, located on chromosome 4. BPH resistance mechanism test revealed that antibiosis and antixenosis mechanisms both play a role in BPH resistance conferred by these two QTLs. The QTLs were delimited between markers SWRm&#95;01617 and SWRm&#95;01522 for BPH41, and SWRm&#95;01695 and SWRm&#95;00328 for BPH42. Additionally, using RNA-seq data of lines containing the resistant QTLs, we shortlisted four and three gene candidates for BPH41 and BPH42, respectively. Differential gene expression analysis of lines containing the QTLs suggested that SWD10 BPH resistance is contributed by the plant's innate immunity and the candidate genes may be part of the rice innate immunity pathway. Currently, the newly identified QTLs are being utilized for breeding BPH resistant rice varieties and hybrids., (© 2022. The Author(s).)

Background: Bone marrow stromal cells (BMSCs) transplantation is a treatment strategy for ischemic stroke (IS) with great potential. However, the vitality, migration and adhesion of BMSCs are greatly impaired due to the harsh environment of the ischemic area, which affects the therapeutic effects. Herein, we aimed to investigate the roles of nerve growth factor (NGF) in regulating cell behaviors of BMSCs in IS., Methods: The mRNA and protein expressions were assessed using qRT-PCR and western blot, respectively. To simulate ischemic-like conditions in vitro, Brain microvascular (bEnd.3) cells were exposed to oxygen and glucose deprivation (OGD). Cell viability and cell proliferation were evaluated by MTT assay and BrdU assay, respectively. Transwell migration and cell adhesion assays were carried out to determine cell migration and adhesion of BMSCs, respectively, coupled with flow cytometry to evaluate cell apoptosis of bEnd.3 cells. Finally, angiogenesis assay was performed to assess the angiogenesis ability of bEnd.3 cells., Results: NGF overexpression resulted in increased cell vitality, adhesion and migration of BMSCs, while NGF knockdown presented the opposite effects. We subsequently discovered that TrkA was a receptor for NGF, and TrkA knockdown significantly inhibited the cell viability, migration and adhesion of BMSCs. Besides, Nrf2 was confirmed as the downstream target of NGF/TrkA to promote the viability, adhesion and migration of BMSC cells. Finally, NGF-silenced BMSCs could not effectively restore the OGD-induced brain microvascular cell damage., Conclusions: NGF/TrkA promoted the viability, migration and adhesion of BMSCs in IS via activating Nrf2 pathway., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: Significant dose deviations have been reported between planned (D P ) and accumulated (D A ) dose in prostate radiotherapy. This study aimed to develop multivariate analysis (MVA) models associating Grade 1 and 2 gastrointestinal (GI) toxicity with clinical and D P or D A dosimetric variables separately., Materials and Methods: Dose volume (DV) metrics were compared between D A and D P for 150 high-risk prostate cancer patients. MV models were generated from significant clinical and dosimetric variables (p < 0.05) at univariate level. Dose-based-region of interest (DB-ROI) metrics were included. Model performance was measured, and additional subgroup analysis were performed., Results: Rectal D A demonstrated a higher intermediate-high dose (V 30-65 Gy and DB-ROI at 15-50 mm) compared to D P . Conversely, at the very high dose region, rectal D A (V 75 Gy and DB-ROI at 5-10 mm) were significantly lower. In MVA, rectal DB-ROI at 10 mm was predictive for Grade ≥ 1 GI toxicity for D A and D P . Age, rectal D A for D 0.03 cc , and rectal D P for DB-ROI 10 mm were predictors for Grade 2 GI toxicity. Subgroup analysis revealed that patients ≥ 72 years old and a rectal D A of ≥ 78.2 Gy were highly predictive of Grade 2 GI toxicity., Conclusions: The dosimetric impact of a higher dose rectal dose in D A due to volumetric changes was minimal and was not predictive of detrimental clinical toxicity apart from rectal D 0.03 cc  ≥ 78.2 Gy for Grade 2 GI toxicity. The use of the DB-ROI method can provide equivalent predictive power as the DV method in toxicity prediction., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Four polyoxometalate (POM)-based organic-inorganic hybrid compounds, namely, (H 2 bimb) 6 H 8 [((Mn(H 2 O) 3 (μ-bimb)) 0.5 (Mn(H 2 O) 4 )(Mn(H 2 O) 5 ) 0.5 (AgP 5 W 30 O 110 )) 2 ]·29H 2 O ( 1 ), [(Cu(Hbimb)(H 2 O) 2 (μ-bimb)Cu(Hbimb)(H 2 O))(Cu(H 2 O) 2 (μ-bimb)Cu(H 2 O) 3 )((Cu(H 2 O) 2 ) 0.5 (μ-bimb)(Cu(H 2 O) 3 ) 0.5 )H 2 (AgP 5 W 30 O 110 )]·12.5H 2 O ( 2 ), (H 2 bimb) 2 H[(Zn(Hbimb)(H 2 O) 4 (Zn(Hbimb)(H 2 O) 2 ) 0.5 ) 2 (AgP 5 W 30 O 110 )]·12H 2 O ( 3 ), and (H 2 bimb) 3 H 2 [(Ag(H 2 O) 2 ) 0.5 (Ag(Hbimb)Ag(Hbimb)(μ-bimb)Ag)(Ag(H 2 O) 2 ) 0.5 (AgP 5 W 30 O 110 )]·7H 2 O ( 4 ) (bimb = 1,4-bis(1H-imidazol-1-yl)benzene), were hydrothermally synthesized using a silver-centered Preyssler-type POM K 14 [AgP 5 W 30 O 110 ]·18H 2 O (abbreviated as K-{AgP 5 W 30 }) as a precursor. In 1 - 4 , {AgP 5 W 30 } clusters integrating the merits of Ag + and {P 5 W 30 } units are modified by different transition metal (TM)-organic fragments to extend the structures into three-dimensional frameworks. As nonenzymatic electrochemical sensor materials, 1 - 4 show good electrocatalytic activity, high sensitivity, and a low detection limit for detecting hydrogen peroxide (H 2 O 2 ); 4 possesses the highest sensitivity of 195.47 μA·mM -1 ·cm -2 for H 2 O 2 detection. Most importantly, the average level of H 2 O 2 detection of these {AgP 5 W 30 }-based materials outperforms that of Na-centered Preyssler-type {NaP 5 W 30 } and most Keggin-type POM-based materials. The performances of such {AgP 5 W 30 } materials mainly stem from the unique advantage of high-negatively charged {AgP 5 W 30 } clusters together with the good synergistic effect between {AgP 5 W 30 } and TMs. This work expands on the research of high-efficiency POM-based nonenzymatic electrochemical H 2 O 2 sensors using Ag-containing POMs with high negative charges, which is also of great theoretical and practical significance to carry out health monitoring and environmental analysis.

Backgrounds: Respiratory gating is one of the motion management techniques that is used to deliver radiation dose to a tumor at a specific position under free breathing. However, due to the dynamic feedback process of this approach, regular equipment quality assurance (QA) and patient-specific QA checks need to be performed. This work proposes a new QA methodology using electronic portal imaging detector (EPID) to determine the target localization accuracy of phase gating., Methods: QA tools comprising 3D printed spherical tumor phantoms, programmable stages, and an EPID detector are characterized and assembled. Algorithms for predicting portal dose (PD) through moving phantoms are developed and verified using gamma analysis for two spherical tumor phantoms (2 cm and 4 cm), two different 6 MV volumetric modulated arc therapy plans, and two different gating windows (30%-70% and 40%-60%). Comparison between the two gating windows is then performed using the Wilcoxon signed-rank test. An optimizer routine, which is used to determine the optimal window, based on maximal gamma passing rate (GPR), was applied to an actual breathing curve and breathing plan. This was done to ascertain if our method yielded a similar result with the actual gating window., Results: High GPRs of more than 97% and 91% were observed when comparing the predicted PD with the measured PD in moving phantom at 2 mm/2% and 1 mm/1% levels, respectively. Analysis of gamma heatmaps shows an excellent agreement with the tumor phantom. The GPR of 40%-60% PD was significantly lower than that of the 30%-70% PD at the 1 mm/1% level (p = 0.0064). At the 2 mm/2% level, no significant differences were observed. The optimizer routine could accurately predict the center of the gating window to within a 10% range., Conclusion: We have successfully performed and verified a new method for QA with the use of a moving phantom with EPID for phase gating with real-time position management., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The NAR score, which takes into account the pathological tumour and nodal stage as well as clinical tumour stage, is a validated surrogate endpoint used for early determination of treatment response whereby a low NAR score (< 8) has been correlated with better outcomes and high NAR score (> 16) has been correlated with poorer outcomes. CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR > 16 and NAR < 8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR > 16 and NAR < 8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model. The most important clinical features are age and CEA for NAR > 16 and NAR < 8 models respectively, while the most significant clinical features are age, surgical margin and NAR score across all the four survival models., (© 2022. The Author(s).)

The dynamic regulation of alternative splicing requires coordinated participation of multiple RNA binding proteins (RBPs). Aberrant splicing caused by dysregulation of splicing regulatory RBPs is implicated in numerous cancers. Here, we reveal a frequently overexpressed cancer-associated protein, DAP3, as a splicing regulatory RBP in cancer. Mechanistically, DAP3 coordinates splicing regulatory networks, not only via mediating the formation of ribonucleoprotein complexes to induce substrate-specific splicing changes, but also via modulating splicing of numerous splicing factors to cause indirect effect on splicing. A pan-cancer analysis of alternative splicing across 33 TCGA cancer types identified DAP3-modulated mis-splicing events in multiple cancers, and some of which predict poor prognosis. Functional investigation of non-productive splicing of WSB1 provides evidence for establishing a causal relationship between DAP3-modulated mis-splicing and tumorigenesis. Together, our work provides critical mechanistic insights into the splicing regulatory roles of DAP3 in cancer development., (© 2022. The Author(s).)