Study on Calculation Method of Bending Performance of Concrete Sandwich Composite Slab.

In order to explore the flexural behavior of a concrete sandwich panel under concentrated boundary conditions, based on Kirachhoff's elastic thin plate theory in this paper, the geometric deformation, physical conditions, and equilibrium relationship of a sandwich panel are deduced by constructing the layered analysis model of the sandwich panel, the basic differential equation of the flexural deformation of the concrete sandwich thin plate is obtained, and the mathematical expression of the internal force and displacement under the boundary condition of concentrated support is given. Combined with an engineering example, the proposed calculation method is verified. The results show that, in the arrangement of reliable connectors for concrete sandwich panels, the concrete wythes bear the load while the contribution of the core layer to the bending capacity of the structure can be ignored. When subjected to a laterally distributed load, the sandwich panel mainly experiences out-of-plane bending deformation, and the bending normal stress in the concrete panel layer shows a linear non-uniform distribution along the thickness direction of the panel. The bending deformation performance and bearing efficiency of a concrete sandwich slab with the change in concentrated support position have significant effects, and the load transfer efficiency can be improved by optimizing the arrangement of supports. Except for small local areas near the supports, the bending stress distribution and deformation behavior of the concrete sandwich panel can be accurately analyzed by the calculation method established in this paper.

Investigation of dosimetric effect of beam current fluctuations in synchrotron-based proton PBS continuous scanning.

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 1mm/1% Gamma passing rate was 100% for all plans. Less than 0.2% root mean square error (RMSE) was observed in the PTV DVH. 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 MU deviations at each spot level, the overall impact on the dose distribution is minimal. .

Deformable anthropomorphic pelvis phantom for dose accumulation verification.

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.

Real-time gated proton therapy with a reduced source to imager distance: Commissioning and quality assurance.

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 mm2 Gold AnchorTM gave the best tracking results with visibility up to 30 g/cm2. 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.

The rise of baobab trees in Madagascar.

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.

Clinicopathological Analysis of Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma of the Spleen: A Case Report.

OBJECTIVE: The present study aims to explore the clinicopathological characteristics of Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (IFDCS; EBV+ IFDCS). CASE REPORT: The case involved a 32-year-old woman who underwent surgical resection of a splenic nodule. Histological examination and immunohistochemistry were performed using cluster of differentiation (CD) markers, and in-situ hybridization was conducted to detect EBV-encoded RNA (EBER). RESULTS: A microscopic analysis revealed neoplastic cells with various morphologies, including round, ovoid, or spindled shapes, dispersed within a prominent lymphoplasmacytic infiltrate. The tumor cells exhibited nuclear atypia, with some resembling Reed-Sternberg cells. The immunohistochemistry demonstrated focal positivity for follicular dendritic cell markers, such as CD21, CD23 and CD35, and focal negativity for other markers, including CD3, CD34, CD20, CD79a, myeloperoxidase and HMB45. Additionally, the EBER staining showed strongly positive results. The patient showed no local recurrence or metastasis during the 13-month follow-up. CONCLUSION: A comprehensive understanding of EBV+IFDCS, including its clinicopathological features and immunohistochemical characteristics, is crucial for accurate diagnosis and differential diagnosis of this rare tumor.

Cervical Sagittal Alignment and Related Factor Analysis and Prediction Model in Patients Undergoing Revision Surgery After Anterior Cervical Fusion.

INTRODUCTION: Patients with myelopathy or radiculopathy commonly undergo anterior cervical fusion surgery (ACFS), which has a notable failure rate on occasion. The goal of this study was to compare revision and nonrevision surgery patients in cervical sagittal alignment (CSA) subsequent to ACFS; additionally, to identify the best CSA parameters for predicting clinical outcome after ACFS; and furthermore, to create an equation model to assist surgeons in making decisions on patients undergoing ACFS. METHODS: The data of 99 patients with symptomatic cervical myelopathy/radiculopathy who underwent ACFS were analyzed. Patients were divided into group A (underwent revision surgery after the first surgery failed) and group B (underwent only the first surgery). We measured and analyzed both preoperative and postoperative CSA parameters, including C2 slope, T1 slope, cervical lordosis C2-C7 (CL), C2-C7 sagittal vertical axis (C2C7 SVA), occiput-C2 lordosis angle (C0-C2), and chin brow vertical angle, and we further computed the correlation between the CSA parameters and created a prediction model. RESULTS: The (T1S-CL)-C2S mismatch differed significantly between groups A and B ([9.95 ± 9.95] 0 , [3.79 ± 6.58] 0 , P < 0.05, respectively). A significant correlation was observed between C2 slope and T1CL in group B relative to group A postoperatively (R 2 = 0.42 versus R 2 = 0.09, respectively). Compared with group B, patients in group A had significantly higher C2C7SVA values, more levels of fusion, and more smokers. The sensitivity, specificity, accuracy, and discrimination of the model were, respectively, 73.5%, 84%, 78.8%, and 85.65%. CONCLUSION: The causes of revision surgery in cervical myelopathic patients after anterior cervical corpectomy and fusion/anterior cervical diskectomy and fusion are multifactorial. (T1S-CL)-C2S mismatch and high C2C7SVA are the best cervical sagittal parameters that increase the odds of revision surgery, and the effect is more enhanced when comorbidities such as smoking, low bone-mineral density, and increased levels of fusion are taken into account.

Utilizing the Subunit Concept to Achieve Better Outcomes in Lower Limb Reconstruction: A Clinical Experience in an Asian Population.

Background: The goals of reconstruction have progressed from filling a defect to enhancing function and aesthetic appearance. We aimed to achieve better aesthetic and functional outcomes in terms of shoe fitting and mobility. This is accomplished via a classification of the subunits and aesthetic considerations of the lower limb. Methods: Between April 2017 and December 2021, 66 cases of lower extremity free fasciocutaneous flap reconstruction cases were included in this retrospective study. Data parameters include age, sex, comorbidities, etiology of lower limb wounds, choice of free flap reconstruction, recipient arterial vessels, complications of flap reconstruction, and need for secondary debulking procedures. Physiotherapy records were also examined to determine the time to independent ambulation. Results: In total, 66 subjects were identified. The mean age was 48.6. An estimated 74.2% (n = 49) were men, 50% (n = 33) had diabetes, and 16.6% (n = 11) had peripheral vascular disease. Of the total wounds, 65.1% (n = 43) were caused by infection, whereas the remaining 34.9% (n = 23) were due to trauma. Of the cases, 72.7% (n = 48) had free anterolateral thigh flap reconstruction, 25.8% (n = 17) were reconstructed with superficial circumflex iliac artery perforator flaps, and 1.5% (n = 1) was reconstructed with medial sural artery perforator flaps. Cases that required secondary debulking procedures comprised 7.6% (n = 5). Conclusions: Free fasciocutaneous flaps are useful in lower extremity reconstruction. Based on the subunit principle and aesthetic considerations for lower limb reconstruction, it can aid in optimizing functional rehabilitation and decreasing secondary procedures.

Repurposing DailyQA3 for an efficient and spot position sensitive daily quality assurance tool for proton therapy.

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.

[Pollution Characteristics, Source Apportionment, and Meteorological Response of Water-soluble Ions in PM2.5 in Xinxiang, North China].

Pollution variation, source characteristics, and meteorological effects of water-soluble inorganic ions (WSIIs) in PM2.5 were analyzed in Xinxiang city, Henan Province. PM2.5 samples and their chemical components were monitored online by using URG-9000 in four seasons:winter (January, 2022), spring (April, 2022), summer (July, 2022), and fall (October, 2022). The results showed that the TWSIIs had the same seasonal fluctuations as PM2.5. The average seasonal concentrations of WSIIs ranged from 19.62-72.15 µg·m-3, accounting for more than 60% of PM2.5, demonstrating that WSIIs were the major components of PM2.5. The annual concentration value of NO3-/SO42- was 2.11, which showed an increasing trend, suggesting predominantly mobile sources for secondary inorganic aerosols (SNA). Further, the molar concentration value [NH4+]/[NO3-] was 1.95, demonstrating that agriculture emissions were the dominant contributors to atmospheric nitrogen. Furthermore, the backward trajectory analysis showed that the concentrations of Ca2+ and Mg2+ were higher when the northeasterly wind prevailed and the wind speed was high. High values of SOR and NOR were correlated with low temperatures and high relative humidity (T < 8℃, RH > 60%), demonstrating that more gaseous precursors were converted into sulfate and nitrate. At high temperatures (T > 24℃), there was no apparent high NOR value like that for SOR, mainly due to the decomposition of NH4NO3 at high temperatures. Finally, backward trajectories associated with the PMF-resolved results were used to explore the regional transport characteristics. The results illustrated that dust sources in the study areas were mainly influenced by air trajectories originating from the northwest regions, whereas secondary sulfate, secondary nitrate, and biomass sources contributed more to WSIIs when wind speed and altitude air masses were low in the area surrounding the observation site.

Radiation therapy with phenotypic medicine: towards N-of-1 personalization.

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.

First clinical experience following the consensus guide for calibrating a proton stopping power ratio curve in a new proton centre.

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.

A Green High-k Dielectric from Modified Carboxymethyl Cellulose-Based with Dextrin.

Many crucial components inside electronic devices are made from non-renewable, non-biodegradable, and potentially toxic materials, leading to environmental damage. Finding alternative green dielectric materials is mandatory to align with global sustainable goals. Carboxymethyl cellulose (CMC) is a bio-polymer derived from cellulose and has outstanding properties. Herein, citric acid, dextrin, and CMC based hydrogels are prepared, which are biocompatible and biodegradable and exhibit rubber-like mechanical properties, with Young modulus values of 0.89 MPa. Hence, thin film CMC-based hydrogel is explored as a suitable green high-k dielectric candidate for operation at low voltages, demonstrating a high dielectric constant of up to 78. These fabricated transistors reveal stable high capacitance (2090 nF cm-2) for ≈±3 V operation. Using a polyelectrolyte-type approach and poly-(2-vinyl anthracene) (PVAn) surface modification, this study demonstrates a thin dielectric layer (d ≈30 nm) with a small voltage threshold (Vth ≈-0.8 V), moderate transconductance (gm ≈65 nS), and high ON-OFF ratio (≈105). Furthermore, the dielectric layer exhibits stable performance under bias stress of ± 3.5 V and 100 cycles of switching tests. The modified CMC-based hydrogel demonstrates desirable performance as a green dielectric for low-voltage operation, further highlighting its biocompatibility.

Predicting autism spectrum disorder using maternal risk factors: A multi-center machine learning study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex environmental etiology involving maternal risk factors, which have been combined with machine learning to predict ASD. However, limited studies have considered the factors throughout preconception, perinatal, and postnatal periods, and even fewer have been conducted in multi-center. In this study, five predictive models were developed using 57 maternal risk factors from a cohort across ten cities (ASD:1232, typically developing[TD]: 1090). The extreme gradient boosting model performed best, achieving an accuracy of 66.2 % on the external cohort from three cities (ASD:266, TD:353). The most important risk factors were identified as unstable emotions and lack of multivitamin supplementation using Shapley values. ASD risk scores were calculated based on predicted probabilities from the optimal model and divided into low, medium, and high-risk groups. The logistic analysis indicated that the high-risk group had a significantly increased risk of ASD compared to the low-risk group. Our study demonstrated the potential of machine learning models in predicting the risk for ASD based on maternal factors. The developed model provided insights into the maternal emotion and nutrition factors associated with ASD and highlighted the potential clinical applicability of the developed model in identifying high-risk populations.

Mismatch repair gene MSH6 correlates with the prognosis, immune status and immune checkpoint inhibitors response of endometrial cancer.

Objective: Many patients treated with immune checkpoint inhibitors (ICIs) developed primary or secondary drug resistance for unknown reasons. This study investigates whether mismatch repair (MMR) genes are responsible for this therapeutic restriction. Methods: We obtained the transcriptional, clinical and single nucleotide polymorphism data for endometrial cancer (EC) from The Cancer Genome Atlas and the immunophenoscore data of EC from The Cancer Immunome Atlas, then analyzed in R to evaluate the relationship between MMR genes and clinicopathological features, prognosis, immune infiltration, immune checkpoint expression and responsiveness to ICIs in EC. We used differentially expressed genes in the MSH6 high and low expression groups to conduct GO and KEGG analyses to explore the impact of MSH6 on the biological functions of EC. Finally, we verified the bioinformatics results with in vitro experiments. Results: Our analyses showed that compared with the high MSH6 expression group, the low MSH6 expression group had better survival outcomes and less aggressive clinicopathological features. In the multivariate Cox analysis, MSH6 was the only independent risk factor that could predict the prognosis of EC. Besides, the low MSH6 expression group also had a higher immune score, more active immune infiltration and higher immune checkpoint expression, resulting in better responsiveness to ICIs treatment, consistent with the enrichment of GO terms and KEGG pathways related to immune response in this group. Meanwhile, the GO and KEGG enrichment results of the MSH6 high expression group were associated with cell cycle, DNA damage repair and tumorigenesis. To exclude the influence of MSH6 mutations, we performed the previous analyses on the MSH6 wild-type tumor samples and obtained consistent results. In vitro experiments also confirmed that after knocking down MSH6 in endometrial cancer cells, their proliferation, migration and invasion abilities were weakened, while the expression levels of PD-L1 and PD-L2 were elevated. In comparison, overexpression of MSH6 showed an opposite trend. Conclusion: Reduced MSH6 expression could serve as a potential biomarker for predicting better prognosis, active immune status, higher immune checkpoint expression level and better responsiveness to ICIs treatment in EC. MSH6 may become a potential target for treating solid tumors.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway.

OBJECTIVE: Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. METHODS: A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). RESULTS: The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). CONCLUSION: Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

Isolated spinal artery aneurysm: etiology, clinical characteristics, and outcomes.

OBJECTIVE: Isolated spinal aneurysms (ISAs) are rare causes of subarachnoid hemorrhage (SAH), which encompass a highly heterogeneous group of clinical entities with multifarious pathogeneses, clinical characteristics, and treatment strategies. Therefore, knowledge about the ISAs remains inadequate. In this study, the authors present a comprehensive analysis of clinical data associated with ISAs at their institutions to enhance the understanding of this disease. METHODS: Patients with ISAs confirmed by spinal angiography or surgery at the authors' institutions between 2015 and 2022 were included. Data regarding clinical presentation, lesion location, aneurysm morphology, comorbidities, treatment results, and clinical outcomes were reviewed. RESULTS: Seven patients with ISAs were included in the study. Among them, 4 patients (57.1%) experienced severe headache, and 3 patients (42.9%) reported sudden-onset back pain. Additionally, lower-extremity weakness and urinary retention were observed in 2 of these patients (28.6%). Four of the aneurysms exhibited fusiform morphology, whereas the remaining were saccular. All saccular aneurysms in this series were attributed to hemodynamic factors. Conservative treatment was administered to 3 patients, 2 of whom underwent follow-up digital subtraction angiography, which showed spontaneous occlusion of both aneurysms. Four patients ultimately underwent invasive treatments, including 2 who underwent microsurgery and 2 who received endovascular embolization. One patient died of recurrent SAH, while the remaining 6 patients had a favorable prognosis at the latest follow-up assessment. CONCLUSIONS: The morphology of aneurysms may be associated with their etiology. Saccular ISAs are usually caused by pressure due to abnormally increased blood flow, whereas fusiform lesions may be more likely to be secondary to vessel wall damage. The authors found that a saccular spinal aneurysm in young patients with a significant dilated parent artery may be a vestige of spinal cord arteriovenous shunts. ISAs can be managed by surgical, endovascular, or conservative procedures, and the clinical outcome is generally favorable. However, the heterogeneous nature of the disease necessitates personalized treatment decision-making based on specific clinical features of each patient.

[Trametenolic acid inhibits migration and invasion of hepatocellular carcinoma HepG2.2.15 cells via RhoC/ROCK1 pathway].

This study investigated the effect of trametenolic acid(TA) on the migration and invasion of human hepatocellular carcinoma HepG2.2.15 cells by using Ras homolog gene family member C(RhoC) as the target and probed into the mechanism, aiming to provide a basis for the utilization of TA. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of HepG2.2.15 cells exposed to TA, and scratch and Transwell assays to examine the cell migration and invasion. The pull down assay was employed to determine the impact of TA on RhoC GTPase activity. Western blot was employed to measure the effect of TA on the transport of RhoC from cytoplasm to cell membrane and the expression of RhoC/Rho-associated kinase 1(ROCK1)/myosin light chain(MLC)/matrix metalloprotease 2(MMP2)/MMP9 pathway-related proteins. RhoC was over-expressed by transient transfection of pcDNA3.1-RhoC. The changes of F-actin in the cytoskeleton were detected by Laser confocal microscopy. In addition, the changes of cell migration and invasion, expression of proteins in the RhoC/ROCK1/MLC/MMP2/MMP9 pathway, and RhoC GTPase activity were detected. The subcutaneously transplanted tumor model of BALB/c nude mice and the low-, medium-, and high-dose(40, 80, and 120 mg·kg~(-1), respectively) TA groups were established and sorafenib(20 mg·kg~(-1)) was used as the positive control. The tumor volume and weight in each group were measured, and the expression of related proteins in the tumor tissue was determined by Western blot. The results showed that TA inhibited the proliferation of HepG2.2.15 cells in a concentration-dependent manner, with the IC_(50) of 66.65 and 23.09 µmol·L~(-1) at the time points of 24 and 48 h, respectively. The drug administration groups had small tumors with low mass. The tumor inhibition rates of sorafenib and low-, medium-and high-dose TA were 62.23%, 26.48%, 55.45%, and 62.36%, respectively. TA reduced migrating and invading cells and inhibited RhoC protein expression and RhoC GTPase activity in a concentration-dependent manner, dramatically reducing RhoC and membrane-bound RhoC GTPase. The expression of ROCK1, MLC, p-MLC, MMP2, and MMP9 downstream of RhoC can be significantly inhibited by TA, as confirmed in both in vitro and in vivo experiments. After HepG2.2.15 cells were transfected with pcDNA3.1-RhoC to overexpress RhoC, TA down-regulated the protein levels of RhoC, ROCK1, MLC, p-MLC, MMP2, and MMP9 and decreased the activity of RhoC GTPase, with the inhibition level comparable to that before overexpression. In summary, TA can inhibit the migration and invasion of HepG2.2.15 cells. It can inhibit the RhoC/ROCK1/MLC/MMP2/MMP9 signaling pathway by suppressing RhoC GTPase activity and down-regulating RhoC expression. This study provides a new idea for the development of autophagy modulators targeting HSP90α to block the proliferation and inhibit the invasion and migration of hepatocellular carcinoma cells via multiple targets of active components in traditional Chinese medicines.

Effects of modern aesthetic dental fillings on proton therapy.

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.