Highly Horizontal Oriented Tricomponent Exciplex Host with Multiple Reverse Intersystem Crossing Channels for High-Performance Narrowband Electroluminescence and Eye-Protection White Organic Light-Emitting Diodes.

Despite multiple-resonance thermally activated delayed fluorescence (MR-TADF) emitters with small full-width at half maximum are attractive for wide color-gamut display and eye-protection lighting applications, their inefficient reverse intersystem crossing (RISC) process and long exciton lifetime induce serious efficiency roll-off, which significantly limits their development. Herein, a novel device concept of building highly efficient tricomponent exciplex with multiple RISC channels is proposed to realize reduced exciton quenching and enhanced upconversion of nonradiative triplet excitons, and subsequently used as a host for high-performance MR-TADF organic light-emitting diodes (OLEDs). Compared with traditional binary exciplex, the tricomponent exciplex exhibits obviously improved photoluminescence quantum yield, emitting dipole orientation and RISC rate constant, and a record-breaking external quantum efficiency (EQE) of 30.4% is achieved for tricomponent exciplex p-PhBCzPh: PO-T2T: DspiroAc-TRZ (50: 20: 30) based OLED. Remarkably, maximum EQEs of 36.2% and 40.3% and ultralow efficiency roll-off with EQEs of 26.1% and 30.0% at 1000 cd m-2 are respectively achieved for its sky-blue and pure-green MR-TADF doped OLEDs. Additionally, the blue emission unit hosted by tricomponent exciplex is combined with an orange-red TADF emission unit to achieve a double-emission-layer blue-hazard-free warm white OLED with an EQEmax of 30.3% and stable electroluminescence spectra over a wide brightness range.

Boosted Sacrificial-Agent-Free Selective Photoreduction of CO2 to CH3OH by Rhenium Atomically Dispersed on Indium Oxide.

Solar-energy-driven photoreduction of CO2 is promising in alleviating environment burden, but suffers from low efficiency and over-reliance on sacrificial agents. Herein, rhenium (Re) is atomically dispersed in In2O3 to fabricate a 2Re-In2O3 photocatalyst. In sacrificial-agent-free photoreduction of CO2 with H2O, 2Re-In2O3 shows a long-term stable efficiency which is enhanced by 3.5 times than that of pure In2O3 and is also higher than those on Au-In2O3, Ag-In2O3, Cu-In2O3, Ir-In2O3, Ru-In2O3, Rh-In2O3 and Pt-In2O3 photocatalysts. Moreover, carbon-based product of the photoreduction overturns from CO on pure In2O3 to CH3OH on 2Re-In2O3. Re promotes charge separation, H2O dissociation and CO2 activation, thus enhancing photoreduction efficiency of CO2 on 2Re-In2O3. During the photoreduction, CO is a key intermediate. CO prefers to desorption rather than hydrogenation on pure In2O3, as CO binds to pure In2O3 very weakly. Re strengthens the interaction of CO with 2Re-In2O3 by 5.0 times, thus limiting CO desorption but enhancing CO hydrogenation to CH3OH. This could be the origin for photoreduction product overturn from CO on pure In2O3 to CH3OH on 2Re-In2O3. The present work opens a new way to boost sacrificial-agent-free photoreduction of CO2.

miR-622 Increases miR-30a Expression through Inhibition of Hypoxia-Inducible Factor 1α to Improve Metastasis and Chemoresistance in Human Invasive Breast Cancer Cells.

Hypoxia-inducible factor 1α (HIF-1α) plays a pivotal role in the survival, metastasis, and response to treatment of solid tumors. Autophagy serves as a mechanism for tumor cells to eliminate misfolded proteins and damaged organelles, thus promoting invasiveness, metastasis, and resistance to treatment under hypoxic conditions. MicroRNA (miRNA) research underscores the significance of these non-coding molecules in regulating cancer-related protein synthesis across diverse contexts. However, there is limited reporting on miRNA-mediated gene expression studies, especially with respect to epithelial-mesenchymal transition (EMT) and autophagy in the context of hypoxic breast cancer. Our study reveals decreased levels of miRNA-622 (miR-622) and miRNA-30a (miR-30a) in invasive breast cancer cells compared to their non-invasive counterparts. Inducing miR-622 suppresses HIF-1α protein expression, subsequently activating miR-30a transcription. This cascade results in reduced invasiveness and migration of breast cancer cells by inhibiting EMT markers, such as Snail, Slug, and vimentin. Furthermore, miR-30a negatively regulates beclin 1, ATG5, and LC3-II and inhibits Akt protein phosphorylation. Consequently, this improves the sensitivity of invasive MDA-MB-231 cells to docetaxel treatment. In conclusion, our study highlights the therapeutic potential of inducing miR-622 to promote miR-30a expression and thus disrupt HIF-1α-associated EMT and autophagy pathways. This innovative strategy presents a promising approach to the treatment of aggressive breast cancer.

Metabolic heterogeneity in clear cell renal cell carcinoma revealed by single-cell RNA sequencing and spatial transcriptomics.

BACKGROUND: Clear cell renal cell carcinoma is a prototypical tumor characterized by metabolic reprogramming, which extends beyond tumor cells to encompass diverse cell types within the tumor microenvironment. Nonetheless, current research on metabolic reprogramming in renal cell carcinoma mostly focuses on either tumor cells alone or conducts analyses of all cells within the tumor microenvironment as a mixture, thereby failing to precisely identify metabolic changes in different cell types within the tumor microenvironment. METHODS: Gathering 9 major single-cell RNA sequencing databases of clear cell renal cell carcinoma, encompassing 195 samples. Spatial transcriptomics data were selected to conduct metabolic activity analysis with spatial localization. Developing scMet program to convert RNA-seq data into scRNA-seq data for downstream analysis. RESULTS: Diverse cellular entities within the tumor microenvironment exhibit distinct infiltration preferences across varying histological grades and tissue origins. Higher-grade tumors manifest pronounced immunosuppressive traits. The identification of tumor cells in the RNA splicing state reveals an association between the enrichment of this particular cellular population and an unfavorable prognostic outcome. The energy metabolism of CD8+ T cells is pivotal not only for their cytotoxic effector functions but also as a marker of impending cellular exhaustion. Sphingolipid metabolism evinces a correlation with diverse macrophage-specific traits, particularly M2 polarization. The tumor epicenter is characterized by heightened metabolic activity, prominently marked by elevated tricarboxylic acid cycle and glycolysis while the pericapsular milieu showcases a conspicuous enrichment of attributes associated with vasculogenesis, inflammatory responses, and epithelial-mesenchymal transition. The scMet facilitates the transformation of RNA sequencing datasets sourced from TCGA into scRNA sequencing data, maintaining a substantial degree of correlation. CONCLUSIONS: The tumor microenvironment of clear cell renal cell carcinoma demonstrates significant metabolic heterogeneity across various cell types and spatial dimensions. scMet exhibits a notable capability to transform RNA sequencing data into scRNA sequencing data with a high degree of correlation.

Genetic insights into carbohydrate sulfotransferase 8 and its impact on the immunotherapy efficacy of cancer.

Immune checkpoint blockade (ICB) is a promising therapy for solid tumors, but its effectiveness depends on biomarkers that are not precise. Here, we utilized genome-wide association study to investigate the association between genetic variants and tumor mutation burden to interpret ICB response. We identified 16 variants (p < 5 × 10-8) probed to 17 genes on 9 chromosomes. Subsequent analysis of one of the most significant loci in 19q13.11 suggested that the rs111308825 locus at the enhancer is causal, as its A allele impairs KLF2 binding, leading to lower carbohydrate sulfotransferase 8 (CHST8) expression. Breast cancer cells expressing CHST8 suppress T cell activation, and Chst8 loss attenuates tumor growth in a syngeneic mouse model. Further investigation revealed that programmed death-ligand 1 (PD-L1) and its homologs could be sulfated by CHST8, resulting in M2-like macrophage enrichment in the tumor microenvironment. Finally, we confirmed that low-CHST8 tumors have better ICB response, supporting the genetic effect and clinical value of rs111308825 for ICB efficacy prediction.

In situ DRIFTS and DFT study of CO2 hydrogenation over the In2O3 catalyst.

The pressure dependent reaction mechanism of CO2 hydrogenation over In2O3 was investigated. CO2 hydrogenation on In2O3 can produce methanol only at high pressure, while the atmospheric pressure operation leads to the formation of CO. The conversion from HCOO* to H3CO* is accelerated at high pressure, leading to the formation of methanol with the formate route (CO2* → HCOO* → H3CO* → H3COH).

Outcomes of covered vs bare metal stents for the treatment of aortoiliac occlusive disease.

OBJECTIVE: We retrospectively compared the clinical outcomes of self-expanding covered stents (CSs) and bare metal stents (BMSs) in the treatment of aortoiliac occlusive disease (AIOD) at a single center between 2016 and 2022. METHODS: All patients with AIOD receiving endovascular therapy at a single center from January 2016 to October 2022 were continuously analyzed, including patients with lesions of all classes according to the Trans-Atlantic Inter-Society Consensus II (TASC-II). Relevant clinical and baseline data were collected, and propensity score matching was performed to compare CSs and BMSs in terms of baseline characteristics, surgical factors, 30-day outcomes, 5-year primary patency, and limb salvage. The follow-up results were analyzed by Kaplan-Meier curves. Cox proportional hazard models were used to identify predictors of primary patency. RESULTS: A total of 209 patients with AIOD were enrolled in the study, including 135 patients (64.6%) in the CS group and 74 patients (35.4%) in the BMS group. Surgical success rates (100% vs 100%; P = 1.00), early (<30-day) mortality rates (0% vs 0%; P = 1.00), cumulative surgical complication rate (12.0% vs 8.0%; P = .891), 5-year primary patency rate (83.4% vs 86.9%; P = .330), secondary patency rate (96% vs 100%; P = .570), and limb salvage rate (100% vs 100%; P = 1.00) did not exhibit significant differences between the two groups. Patients in the CS group had a lower preoperative ankle-brachial index (0.48 ± 0.26 vs 0.52 ± 0.19; P = .032), more cases of complex AIOD (especially TASC D) (47.4% vs 9.5%; P < .001), more chronic total occlusive lesions (77.0% vs 31.1%; P < .001), and more severe calcification (20.7% vs 14.9%; P < .036). After propensity score matching, 50 patients (25 with CS and 25 with BMS) were selected. The results showed that only severe calcification (32.0% vs 8.0%; P = .034) and ankle-brachial index increase (0.45 ± 0.15 vs 0.41 ± 0.22; P = .038) were significantly different between the groups. In terms of surgical factors, patients in the CS group had more use of bilateral femoral or combined brachial artery percutaneous access (60.0% vs 12.0%; P < .001), more number of stents used (2.3 ± 1.2 vs 1.3 ± 0.7; P < .001), longer mean stent length (9.3 ± 3.3 vs 5.8 ± 2.6 cm; P < .001), and more catheter-directed thrombolysis treatment (32.0% vs 4.0%; P = .009). Multivariate Cox survival analysis showed that severe calcification (hazard ratio, 1.32; 95% confidence interval, 1.04-1.85; P = .048) was the only independent predictor of the primary patency rate. CONCLUSIONS: All patients with AIOD who underwent endovascular therapy were included and achieved good outcomes with both CSs and BMSs. The influence of confounding factors in the two groups was minimized by propensity score matching, and the 5-year patency rates were generally similar in the unmatched and matched cohorts. Postoperative hemodynamic improvement was more obvious in patients in the CS group. For more complex lesions, CS is recommended to be preferred. Especially for severe calcification lesions, which is the only independent predictor of primary patency, CS showed obvious advantages. Further studies with more samples are needed to investigate the role of stent types in AIOD treatment.

Identification of hub gene and lncRNA signature related to entotic cell death in cutaneous melanoma for prognostic and immune prediction.

Entotic cell death (ECD), a cell death program observed in cancer cell competition, predominantly occurs in an autophagy protein-dependent, non-apoptotic manner. However, the relationship between cutaneous melanoma (CM) and ECD-associated genes and lncRNAs has remained unclear. This study aimed to elucidate the role and mechanism of ECD-associated genes in CM. To achieve this, 4 mechanism learning algorithms and integrated bioinformatic analyses were employed to identify the core ECD-associated genes and lncRNAs. Subsequently, 2 risk signatures based on ECD-associated genes and hub lncRNAs were constructed for CM patients. As a result, we observed significant differential expression of ECD-associated genes in CM, indicating their potential as valuable predictors for CM patients. Moreover, RHOA was identified as a core ECD-associated gene in CM, and its expression was found to be associated with patients' survival and immune infiltration, suggesting its relevance as a potential therapeutic target. Additionally, this study provided clarification on hub ECD-associated lncRNAs in CM, offering insights into their roles in the disease. Through bioinformatic analyses, we identified 2 risk signatures based on the expression of ECD-associated genes and hub ECD-associated lncRNAs, respectively. Both risk signatures were strongly linked to the prognosis and cancer growth of CM, underscoring their potential as valuable prognostic indicators. Furthermore, mechanistic analyses suggested a significant association between the risk signature and the immune microenvironment in CM, highlighting potential immune-related implications in disease progression. In conclusion, we propose that ECD-associated genes and lncRNAs hold promise as potential targets in CM. Moreover, our findings revealed a significant correlation between ECD and the immune microenvironment, providing crucial insights for guiding individualized treatment strategies in CM.

A Bayesian network meta-analysis for acute thrombosis after lower extremity artery endovascular treatment.

BACKGROUND: Various endovascular treatment devices have been widely used in the lower extremity arterial disease (LEAD). Their patency efficiency for target lesions has been well studied and reported. Comparison of the risk of acute thrombosis events between the different endovascular treatment devices is unclear. AIMS: To rank the risk of acute thrombosis events when bare metal stents (BMSs), covered stents (CSs), drug-eluting stents (DESs), drug-coated balloons (DCBs), and conventional percutaneous transluminal balloon angioplasty (PTA) are used to treat LEAD through Bayesian network meta-analysis. METHODS: We performed a network meta-analysis of randomized controlled trials comparing the risk of 1-year postoperative acute thrombosis between BMSs, CSs, DESs, DCBs, and PTA for treating LEAD. Bayesian random models were used for pooled endovascular treatment modality comparisons. We ranked these treatment modalities via the Bayesian method according to their surface under the cumulative ranking curve (SUCRA) and estimated probabilities. RESULTS: Nineteen studies (38 study arms; 2758 patients) were included. The Bayesian network ranking of treatments indicated that DCB had the lowest risk of acute thrombosis, PTA had the second-lowest risk of thrombosis, and CS, BMS, and DES had the highest risk of thrombosis. Regarding the treatment efficacy, the OR values of the loss of primary patency were significantly lower for DCB (OR = 0.44, 95% CI: 0.30-0.62), DES (OR = 0.36, 95% CI: 0.14-0.94), and CS (OR = 0.31, 95% CI: 0.18,0.56) than for PTA. When BMS was used as a reference, only the OR for CS was significantly lower (OR = 0.41, 95% CI = 0.21-0.82). Correspondingly, the Bayesian ranking of treatments from better to worse target lesion primary patency was CS, DES, DCB, BMS, and PTA. CONCLUSION: With the available research evidence and according to the network analysis ranking, DES appears to have the highest risk of acute thrombosis and DCB appears to have the lowest risk.

Genome-Wide Association Studies for Albuminuria of Nondiabetic Taiwanese Population.

INTRODUCTION: Chronic kidney disease, which is defined by a reduced estimated glomerular filtration rate and albuminuria, imposes a large health burden worldwide. Ethnicity-specific associations are frequently observed in genome-wide association studies (GWAS). This study conducts a GWAS of albuminuria in the nondiabetic population of Taiwan. METHODS: Nondiabetic individuals aged 30-70 years without a history of cancer were enrolled from the Taiwan Biobank. A total of 6,768 subjects were subjected to a spot urine examination. After quality control using PLINK and imputation using SHAPEIT and IMPUTE2, a total of 3,638,350 single-nucleotide polymorphisms (SNPs) remained for testing. SNPs with a minor allele frequency of less than 0.1% were excluded. Linear regression was used to determine the relationship between SNPs and log urine albumin-to-creatinine ratio. RESULTS: Six suggestive loci are identified in or near the FCRL3 (p = 2.56 × 10-6), TMEM161 (p = 4.43 × 10-6), EFCAB1 (p = 2.03 × 10-6), ELMOD1 (p = 2.97 × 10-6), RYR3 (p = 1.34 × 10-6), and PIEZO2 (p = 2.19 × 10-7). Genetic variants in the FCRL3 gene that encode a secretory IgA receptor are found to be associated with IgA nephropathy, which can manifest as proteinuria. The PIEZO2 gene encodes a sensor for mechanical forces in mesangial cells and renin-producing cells. Five SNPs with a p-value between 5 × 10-6 and 5 × 10-5 are also identified in five genes that may have a biological role in the development of albuminuria. CONCLUSION: Five new loci and one known suggestive locus for albuminuria are identified in the nondiabetic Taiwanese population.

Early Experience of Online Adaptive Radiation Therapy for Definitive Radiation of Patients With Head and Neck Cancer.

Purpose: The advent of cone beam computed tomography-based online adaptive radiation therapy (oART) has dramatically reduced the barriers of adaptation. We present the first prospective oART experience data in radiation of head and neck cancers (HNC). Methods and Materials: Patients with HNC receiving definitive standard fractionation (chemo)radiation who underwent at least 1 oART session were enrolled in a prospective registry study. The frequency of adaptations was at the discretion of the treating physician. Physicians were given the option of delivering 1 of 2 plans during adaptation: the original radiation plan transposed onto the cone beam computed tomography with adapted contours (scheduled), and a new adapted plan generated from the updated contours (adapted). A paired t test was used to compare the mean doses between scheduled and adapted plans. Results: Twenty-one patients (15 oropharynx, 4 larynx/hypopharynx, 2 other) underwent 43 adaptation sessions (median, 2). The median ART process time was 23 minutes, median physician time at the console was 27 minutes, and median patient time in the vault was 43.5 minutes. The adapted plan was chosen 93% of the time. The mean volume in each planned target volume (PTV) receiving 100% of the prescription dose for the scheduled versus adapted plan for high-risk PTVs was 87.8% versus 95% (P < .01), intermediate-risk PTVs was 87.3% versus 97.9% (P < .01), and low-risk PTVs was 94% versus 97.8% (P < .01), respectively. The mean hotspot was also lower with adaptation: 108.8% versus 106.4% (P < .01). All but 1 organ at risk (11/12) saw a decrease in their dose with the adapted plans, with the mean ipsilateral parotid (P = .013), mean larynx (P < .01), maximum point spinal cord (P < .01), and maximum point brain stem (P = .035) reaching statistical significance. Conclusions: Online ART is feasible for HNC, with significant improvement in target coverage and homogeneity and a modest decrease in doses to several organs at risk.

Bony structure enhanced synthetic CT generation using Dixon sequences for pelvis MR-only radiotherapy.

BACKGROUND: MRI-only radiotherapy planning (MROP) is beneficial to patients by avoiding MRI/CT registration errors, simplifying the radiation treatment simulation workflow and reducing exposure to ionizing radiation. MRI is the primary imaging modality for soft tissue delineation. Treatment planning CTs (i.e., CT simulation scan) are redundant if a synthetic CT (sCT) can be generated from the MRI to provide the patient positioning and electron density information. Unsupervised deep learning (DL) models like CycleGAN are widely used in MR-to-sCT conversion, when paired patient CT and MR image datasets are not available for model training. However, compared to supervised DL models, they cannot guarantee anatomic consistency, especially around bone. PURPOSE: The purpose of this work was to improve the sCT accuracy generated from MRI around bone for MROP. METHODS: To generate more reliable bony structures on sCT images, we proposed to add bony structure constraints in the unsupervised CycleGAN model's loss function and leverage Dixon constructed fat and in-phase (IP) MR images. Dixon images provide better bone contrast than T2-weighted images as inputs to a modified multi-channel CycleGAN. A private dataset with a total of 31 prostate cancer patients were used for training (20) and testing (11). RESULTS: We compared model performance with and without bony structure constraints using single- and multi-channel inputs. Among all the models, multi-channel CycleGAN with bony structure constraints had the lowest mean absolute error, both inside the bone and whole body (50.7 and 145.2 HU). This approach also resulted in the highest Dice similarity coefficient (0.88) of all bony structures compared with the planning CT. CONCLUSION: Modified multi-channel CycleGAN with bony structure constraints, taking Dixon-constructed fat and IP images as inputs, can generate clinically suitable sCT images in both bone and soft tissue. The generated sCT images have the potential to be used for accurate dose calculation and patient positioning in MROP radiation therapy.

A single-centre protocol using low-dose urokinase for catheter-directed thrombolysis in the treatment of acute lower limb ischaemia.

OBJECTIVES: Catheter-directed thrombolysis is one of the main treatments for acute limb ischaemia. Urokinase is still a widely used thrombolytic drug in some regions. However, there needs to be a clear consensus on the protocol of continuous catheter-directed thrombolysis using urokinase for acute lower limb ischaemia. METHODS: A single-centre protocol of continuous catheter-directed thrombolysis with low-dose urokinase (20,000 IU/hour) lasting 48-72 h for acute lower limb ischaemia was proposed based on our previous experiences. A retrospective study from June 2016 to December 2020 was conducted to evaluate the efficacy and safety of this protocol. The target lesion revascularisation, amputation and death were also monitored during follow-up. The Kaplan-Meier estimator was used for the subgroup analysis, and univariate and multivariate Cox regression analysis was applied to identify risk factors for reinterventions and death. RESULTS: 90 lower limbs were involved, including 51 Rutherford Grade I, 35 Grade IIa and four Grade IIb. During a 60.8-h thrombolysis, 86 cases (95.5%) were considered effective according to the angiogram. No major bleeding complication occurred during thrombolysis, and one amputation occurred after. Freedom from target lesion revascularisation, amputation and death were 75.6%, 94.4% and 91.1% during a mean 27.5-month follow-up, respectively. According to the Kaplan-Meier estimator, aortoiliac lesions had lower reintervention rates than femoropopliteal lesions (Log-rank p = 0.010), and cases without narrowing atheromatous plaque had a lower reintervention rate (Log-rank p = 0.049). Age was an independent risk factor for death (p = 0.038, hazard ratio 1.076, 95% confidence interval 1.004-1.153). CONCLUSIONS: The single-centre protocol of catheter-directed thrombolysis we proposed for acute lower limb ischaemia was effective and safe. Strict blood pressure control during catheter-directed thrombolysis ensured safety. Aortoiliac lesions and cases without narrowing atheromatous plaque had lower reintervention rates during follow-up.

Perfusion pressure of elastase impacts the formation ratio and diameters of abdominal aortic aneurysms in rats.

Intra-arterial perfusion with elastase is a common method used to create abdominal aortic aneurysms (AAA) models. The present study aimed to explore the impact of porcine pancreatic elastase (PPE) perfusion pressure on the morphology of abdominal aortic aneurysms. A total of 40 male Sprague Dawley rats were randomized into four groups. The elastase was perfused at pressures in the aortic lumen of 300, 100 and 0 mmHg in three groups, respectively. Rats perfused with saline at 300 mmHg were used as controls. The maximum diameters of the AAA were monitored with ultrasound at 7, 14 and 28 days after the operation. Elastin degradation and inflammatory cell counts were determined using histochemical staining. All rats were successfully perfused at the scheduled pressure. After 7 days, the AAA formation ratio of PPE-300, PPE-100 and PPE-0 was 100, 50 and 0%, respectively. After 14 days, the AAA formation ratio in PPE-100 and PPE-0 reached 90 and 20%, respectively. After 28 days, the diameters of the isolated aorta in PPE-300, PPE-100, PPE-0 and NaCl-300 were (mean ± standard deviation) 7.34±1.81, 4.02±0.40, 2.92±0.32 and 2.49±0.07 mm, respectively, and the difference between groups was statistically significant (P<0.05). The formation ratio in PPE-300, PPE-100, PPE-0 and NaCl-300 was 100, 100, 20 and 0%, respectively. Elastase perfusion pressure could impact the AAA formation ratio at an early stage and the maximum diameter of the aneurysm without increasing animal mortality. Elastase perfusion with high pressure could accelerate aneurysm formation and represents a potential method for building large-size abdominal aortic aneurysms. However, the underlying mechanisms need further investigation.

Implementation and evaluation of an intelligent automatic treatment planning robot for prostate cancer stereotactic body radiation therapy.

PURPOSE: We previously developed a virtual treatment planner (VTP), an artificial intelligence robot, operating a treatment planning system (TPS). Using deep reinforcement learning guided by human knowledge, we trained the VTP to autonomously adjust relevant parameters in treatment plan optimization, similar to a human planner, to generate high-quality plans for prostate cancer stereotactic body radiation therapy (SBRT). This study describes the clinical implementation and evaluation of VTP. MATERIALS AND METHODS: We integrate VTP with Eclipse TPS using scripting Application Programming Interface. VTP observes dose-volume histograms of relevant structures, decides how to adjust dosimetric constraints, including doses, volumes, and weighting factors, and applies the adjustments to the TPS interface to launch the optimization engine. This process continues until a high-quality plan is achieved. We evaluated VTP's performance using the prostate SBRT case from the 2016 American Association of Medical Dosimetrist/Radiosurgery Society plan study with its plan scoring system, and compared to human-generated plans submitted to the challenge. Using the same scoring system, we also compared the plan quality of 36 prostate SBRT cases (20 planned with IMRT and 16 planned with VMAT) treated at our institution for both VTP and human-generated plans. RESULTS: In the plan study case, VTP achieved a score of 142.1/150.0, ranking the third in the competition (median 134.6). For the clinical cases, VTP achieved 110.6 ± 6.5 for 20 IMRT plans and 126.2 ± 4.7 for 16 VMAT plans, similar to scores of human-generated plans with 110.4 ± 7.0 for IMRT plans and 125.4 ± 4.4 for VMAT plans. The workflow, plan quality and planning time of VTP were reviewed to be satisfactory by experienced physicists. CONCLUSION: We successfully implemented VTP to operate a TPS for autonomous human-like treatment planning for prostate SBRT.

Midterm Outcomes of Kissing Covered Self-Expanding Stents for Reconstruction of Complex Aortoiliac Occlusive Disease.

BACKGROUND: We sought to investigate the midterm results of kissing self-expanding covered stents (SECSs) for the reconstruction of aortic bifurcation in complex aortoiliac occlusive disease. METHODS: Data of consecutive patients who had undergone endovascular treatment for aortoiliac occlusive disease were screened. Only patients with TransAtlantic Inter-Society Consensus (TASC) class C and D lesions treated by bilateral iliac kissing stents (KSs) were included. Midterm primary patency, risk factors, and limb salvage rates were analyzed. Follow-up results were analyzed using the Kaplan-Meier curves. Cox proportional hazards models were used to identify the predictors of primary patency. RESULTS: A total of 48 patients (95.8% men; mean age, 65.3 ± 10.2 years) were treated with kissing SECSs. Of them, 17 patients had TASC-II class C lesions and 31 had class D lesions. There were 38 total occlusive lesions, with a mean occlusive lesion length of 108.2 ± 57.3 mm. The overall mean lesion length was 140.3 ± 60.5 mm, and the mean length of implanted stents in the aortoiliac arteries was 141.9 ± 59.9 mm. The mean diameter of the deployed SECSs was 7.8 ± 0.5 mm. The mean follow-up time was 36.5 ± 15.8 months, and the follow-up rate was 95.8%. At 36 months, the overall primary patency, assisted primary patency, secondary patency, and limb salvage rates were 92.2%, 95.7%, 97.8%, and 100%, respectively. Univariate Cox regression analysis revealed that stent diameter ≤7 mm (hazard ratio [HR]: 9.53; 95% confidence interval [CI] 1.56-57.94, P = 0.014) and severe calcification (HR: 12.66; 95% CI 2.04-78.45, P = 0.006) were significantly associated with restenosis. Multivariate analysis showed severe calcification to be the only significant determinant of restenosis (HR: 12.66; 95% CI 2.04-78.45, P = 0.006). CONCLUSIONS: Kissing SECSs provide good midterm results for the treatment of aortoiliac occlusive disease. A stent diameter >7 mm is a potent protective factor against restenosis. Because severe calcification appears to be the only significant determinant of restenosis, patients with severe calcification require close follow-up.

Clinical experience on patient-specific quality assurance for CBCT-based online adaptive treatment plan.

PURPOSE: Ethos CBCT-based adaptive radiotherapy (ART) system can generate an online adaptive plan by re-optimizing the initial reference plan based on the patient anatomy at the treatment. The optimization process is fully automated without any room for human intervention. Due to the change in anatomy, the ART plan can be significantly different from the initial plan in terms of plan parameters such as the aperture shapes and number of monitor units (MUs). In this study, we investigated the feasibility of using calculation-based patient specific QA for ART plans in conjunction with measurement-based and calculation-based QA for initial plans to establish an action level for the online ART patient-specific QA. METHODS: A cohort of 98 cases treated on CBCT-based ART system were collected for this study. We performed measurement-based QA using ArcCheck and calculation-based QA using Mobius for both the initial plan and the ART plan for analysis. For online the ART plan, Mobius calculation was conducted prior to the delivery, while ArcCheck measurement was delivered on the same day after the treatment. We first investigated the modulation factors (MFs) and MU numbers of the initial plans and ART plans, respectively. The γ passing rates of initial and ART plan QA were analyzed. Then action limits were derived for QA calculation and measurement for both initial and online ART plans, respectively, from 30 randomly selected patient cases, and were evaluated using the other 68 patient cases. RESULTS: The difference in MF between initial plan and ART-plan was 12.9% ± 12.7% which demonstrates their significant difference in plan parameters. Based on the patient QA results, pre-treatment calculation and measurement results are generally well aligned with ArcCheck measurement results for online ART plans, illustrating their feasibility as an indicator of failure in online ART QA measurements. Furthermore, using 30 randomly selected patient cases, the γ analysis action limit derived for initial plans and ART plans are 89.6% and 90.4% in ArcCheck QA (2%/2 mm) and are 92.4% and 93.6% in Mobius QA(3%/2 mm), respectively. According to the calculated action limits, the ArcCheck measurements for all the initial and ART plans passed QA successfully while the Mobius calculation action limits flagged seven and four failure cases respectively for initial plans and ART plans, respectively. CONCLUSION: An ART plan can be substantially different from the initial plan, and therefore a separate session of ART plan QA is needed to ensure treatment safety and quality. The pre-treatment QA calculation via Mobius can serve as a reliable indicator of failure in online ART plan QA. However, given that Ethos ART system is still relatively new, ArcCheck measurement of initial plan is still in practice. It may be skipped as we gain more experience and have better understanding of the system.

Iatrogenic arteriovenous fistula after lumbar discectomy surgery: a case report.

Iatrogenic arteriovenous fistula (IAVF) is an unusual and potentially fatal complication of lumbar spinal surgery. A 62-year-old patient presented with a history of dyspnea, left lower limb edema and coughing. A physical exam showed bilateral basal rales in the lungs, abdominal bruit and bilateral lower limb pitting edema. A computed tomography angiograph revealed an arteriovenous communication between the right internal iliac artery and the left common iliac vein. The patient was diagnosed with an IAVF, which developed post-lumbar disc surgery. The patient underwent a successful endovascular treatment by using covered stent at the common iliac artery with embolism of lumbar artery. The patient's symptoms were relieved 2 months after surgery.

Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.

Dual- and multi-energy CT for particle stopping-power estimation: current state, challenges and potential.

Range uncertainty has been a key factor preventing particle radiotherapy from reaching its full physical potential. One of the main contributing sources is the uncertainty in estimating particle stopping power (ρs) within patients. Currently, theρsdistribution in a patient is derived from a single-energy CT (SECT) scan acquired for treatment planning by converting CT number expressed in Hounsfield units (HU) of each voxel toρsusing a Hounsfield look-up table (HLUT), also known as the CT calibration curve. HU andρsshare a linear relationship with electron density but differ in their additional dependence on elemental composition through different physical properties, i.e. effective atomic number and mean excitation energy, respectively. Because of that, the HLUT approach is particularly sensitive to differences in elemental composition between real human tissues and tissue surrogates as well as tissue variations within and among individual patients. The use of dual-energy CT (DECT) forρsprediction has been shown to be effective in reducing the uncertainty inρsestimation compared to SECT. The acquisition of CT data over different x-ray spectra yields additional information on the material elemental composition. Recently, multi-energy CT (MECT) has been explored to deduct material-specific information with higher dimensionality, which has the potential to further improve the accuracy ofρsestimation. Even though various DECT and MECT methods have been proposed and evaluated over the years, these approaches are still only scarcely implemented in routine clinical practice. In this topical review, we aim at accelerating this translation process by providing: (1) a comprehensive review of the existing DECT/MECT methods forρsestimation with their respective strengths and weaknesses; (2) a general review of uncertainties associated with DECT/MECT methods; (3) a general review of different aspects related to clinical implementation of DECT/MECT methods; (4) other potential advanced DECT/MECT applications beyondρsestimation.