Uncovering the potential of APOD as a biomarker in gastric cancer: A retrospective and multi-center study.

Gastric cancer (GC) poses a significant health challenge worldwide, necessitating the identification of predictive biomarkers to improve prognosis. Dysregulated lipid metabolism is a well-recognized hallmark of tumorigenesis, prompting investigation into apolipoproteins (APOs). In this study, we focused on apolipoprotein D (APOD) following comprehensive analyses of APOs in pan-cancer. Utilizing data from the TCGA-STAD and GSE62254 cohorts, we elucidated associations between APOD expression and multiple facets of GC, including prognosis, tumor microenvironment (TME), cancer biomarkers, mutations, and immunotherapy response, and identified potential anti-GC drugs. Single-cell analyses and immunohistochemical staining confirmed APOD expression in fibroblasts within the GC microenvironment. Additionally, we independently validated the prognostic significance of APOD in the ZN-GC cohort. Our comprehensive analyses revealed that high APOD expression in GC patients was notably associated with unfavorable clinical outcomes, reduced microsatellite instability and tumor mutation burden, alterations in the TME, and diminished response to immunotherapy. These findings provide valuable insights into the potential prognostic and therapeutic implications of APOD in GC.

Cone beam CT-based adaptive intensity modulated proton therapy assessment using automated planning for head-and-neck cancer.

BACKGROUND: To assess the feasibility of CBCT-based adaptive intensity modulated proton therapy (IMPT) using automated planning for treatment of head and neck (HN) cancers. METHODS: Twenty HN cancer patients who received radiotherapy and had pretreatment CBCTs were included in this study. Initial IMPT plans were created using automated planning software for all patients. Synthetic CTs (sCT) were then created by deforming the planning CT (pCT) to the pretreatment CBCTs. To assess dose calculation accuracy on sCTs, repeat CTs (rCTs) were deformed to the pretreatment CBCT obtained on the same day to create deformed rCT (rCTdef), serving as gold standard. The dose recalculated on sCT and on rCTdef were compared by using Gamma analysis. The accuracy of DIR generated contours was also assessed. To explore the potential benefits of adaptive IMPT, two sets of plans were created for each patient, a non-adapted IMPT plan and an adapted IMPT plan calculated on weekly sCT images. The weekly doses for non-adaptive and adaptive IMPT plans were accumulated on the pCT, and the accumulated dosimetric parameters of two sets were compared. RESULTS: Gamma analysis of the dose recalculated on sCT and rCTdef resulted in a passing rate of 97.9% ± 1.7% using 3 mm/3% criteria. With the physician-corrected contours on the sCT, the dose deviation range of using sCT to estimate mean dose for the most organ at risk (OARs) can be reduced to (- 2.37%, 2.19%) as compared to rCTdef, while for V95 of primary or secondary CTVs, the deviation can be controlled within (- 1.09%, 0.29%). Comparison of the accumulated doses from the adaptive planning against the non-adaptive plans reduced mean dose to constrictors (- 1.42 Gy ± 2.79 Gy) and larynx (- 2.58 Gy ± 3.09 Gy). The reductions result in statistically significant reductions in the normal tissue complication probability (NTCP) of larynx edema by 7.52% ± 13.59%. 4.5% of primary CTVs, 4.1% of secondary CTVs, and 26.8% tertiary CTVs didn't meet the V95 > 95% constraint on non-adapted IMPT plans. All adaptive plans were able to meet the coverage constraint. CONCLUSION: sCTs can be a useful tool for accurate proton dose calculation. Adaptive IMPT resulted in better CTV coverage, OAR sparing and lower NTCP for some OARs as compared with non-adaptive IMPT.

Application of oral inorganic iodine in the treatment of Graves' disease.

Iodine is a crucial trace element for the human body and the basic raw material for the synthesis of thyroid hormones. Oral inorganic iodine includes dietary iodine and therapeutic iodine, both of which are closely associated with thyroid immunity and metabolism. Graves' disease (GD), also known as diffuse toxic goiter, is characterized by hyperthyroidism and high iodine metabolism. Clinically, patients diagnosed with GD are often asked to limit iodine intake or even avoid iodine in their diet. The latest research has demonstrated that the interference of dietary iodine with antithyroid drugs (ATDs) treatment may be overestimated. In addition, as a medication for GD treatment, the administration of inorganic iodine has shown positive results in patients with mild hyperthyroidism, a low thyroid autoantibody concentration, a small thyroid volume, a high iodine diet and so on. Inorganic iodine may also be used as an alternative when patients experience side effects with traditional ATDs and for those who still prefer conservative treatment. Due to its low teratogenicity, blood toxicity and bone marrow toxicity, inorganic iodine plays a unique role in special populations, such as pregnant or lactating patients and patients receiving tumor radiotherapy or chemotherapy. In this review, the research progress, biological function, doses and effects, applicable populations and specific applications of dietary iodine and therapeutic iodine are summarized to provide references for the diagnosis and treatment of GD, thus improving the quality of life of GD patients.

A novel edge gradient distance metric for automated evaluation of deformable image registration quality.

PURPOSE: To develop a new registration quality metric, based on the distance between image edges, for automated evaluation and comparison of DIR algorithms. METHODS: Canny filter is used to create binary gradient images from input images to be compared. A small subregion of one binary image is translated relative to the other. The translational distance maximizing overlap of edges in the subregion is the local edge gradient distance to agreement (EGDTA); repeating over all subregions provides an EGDTA map. The method was tested on phantom and pelvic CT images, by applying a known deformable vector field (DVF). The method was then applied to evaluate two DIR algorithms (SICLE and Demons) for pelvic CTs from five patients. Three SICLE variants were used: Grayscale-driven (G), Contour-driven (C), and Grayscale + Contour-driven (G + C). For each patient, a planning CT was registered to three repeat CTs using the above DIR algorithms. Mean EGDTA values in concentric ring regions of interest close to and far away from the pelvic organ contours were compared. RESULTS: EGDTA maps and imposed DVF deformations on phantom and CT images demonstrated agreement. In comparison of the three variants of SICLE: C had lower EGDTA values close to the pelvic organs, while G showed much better performance in the regions distant from the organs compared to C; and G + C registration exhibited the lowest or comparable EGDTA value among three variants. Demons achieved the lowest EGDTA values. CONCLUSIONS: The EGDTA metric shows potential as an automated means of evaluating and comparing DIR algorithms.

Assessment of IMPT versus VMAT plans using different uncertainty scenarios for prostate cancer.

BACKGROUND: To assess the impact of systematic setup and range uncertainties for robustly optimized (RO) intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans in patients with localized prostate cancer. METHODS: Twenty-six localized prostate patients previously treated with VMAT (CTV to PTV expansion of 3-5 mm) were re-planned with RO-IMPT with 3 mm and 5 mm geometrical uncertainties coupled with 3% range uncertainties. Robust evaluations (RE) accounting for the geometrical uncertainties of 3 and 5 mm were evaluated for the IMPT and VMAT plans. Clinical target volume (CTV), anorectum, and bladder dose metrics were analyzed between the nominal plans and their uncertainty perturbations. RESULTS: With geometric uncertainties of 5 mm and accounting for potential inter-fractional perturbations, RO-IMPT provided statistically significant (p < 0.05) sparing at intermediate doses (V4000cGy) to the anorectum and bladder and high dose sparring (V8000cGy) to the bladder compared to VMAT. Decreasing the RO and RE parameters to 3 mm improved IMPT sparing over VMAT at all OAR dose levels investigated while maintaining equivalent coverage to the CTV. CONCLUSIONS: For localized prostate treatments, if geometric uncertainties can be maintained at or below 3 mm, RO-IMPT provides clear dosimetric advantages in anorectum and bladder sparing compared to VMAT. This advantage remains even under uncertainty scenarios. As geometric uncertainties increase to 5 mm, RO-IMPT still provides dosimetric advantages, but to a smaller magnitude.

A Novel Credible Carbon Footprint Traceability System for Low Carbon Economy Using Blockchain Technology.

To achieve the goal of carbon neutrality, many countries have established regional carbon emission trading markets and tried to build a low-carbon economic system. At present, the implementation of carbon emission trading and low-carbon economic systems faces many challenges such as manipulation, corruption, opacity, lack of trust, and lack of data tracking means. The application of blockchain technology can perfectly solve the above problems. However, the data recorded on a blockchain are often multi-type and heterogeneous, and users at different levels such as regulators, enterprises, and consumers have different requirements for data types and granularity. This requires a quick and trustworthy method for monitoring the carbon footprint of enterprises and products. In this paper, the carbon footprint traceability of enterprises and products is taken as an application scenario, and the distributed traceability concept of "traceability off the chain and verification on the chain" is adopted. By reconstructing the pointer of the file structure of the distributed storage, an interactive traceability structure supporting type filtering is constructed, which enables fast retrieval and locating of carbon emission data in the mixed data on the chain. The experimental results show that using the interactive traceability structure that supports type filtering for traceability not only releases the computing power of full nodes but also greatly improves the traceability efficiency of the long-span transaction chain. The proposed carbon footprint traceability system can rapidly trace and track data on an enterprise's and a product's carbon footprint, as well as meet the needs of users at all levels for traceability. It also offers more advantages when handling large amounts of data requests.

Diabetes mellitus secondary to growth hormone-secreting pituitary adenoma.

Growth hormone-secreting pituitary adenoma is a common intracranial benign tumor, characterized by excessive production of growth hormone, which leads to acromegaly or giant disease. An abnormal increase in growth hormone can induce glucose metabolism disorder, which is often diagnosed and treated as type 2 diabetes, because of uncontrollable hyperglycemia, delaying the treatment of the primary disease. This paper reports the diagnosis and treatment data of a patient with growth hormone-secreting pituitary adenoma who was first diagnosed as having diabetes, and reviews the related literature to facilitate a better understanding of the disease.

Assessment of CT to CBCT contour mapping for radiomic feature analysis in prostate cancer.

This study provides a quantitative assessment of the accuracy of a commercially available deformable image registration (DIR) algorithm to automatically generate prostate contours and additionally investigates the robustness of radiomic features to differing contours. Twenty-eight prostate cancer patients enrolled on an institutional review board (IRB) approved protocol were selected. Planning CTs (pCTs) were deformably registered to daily cone-beam CTs (CBCTs) to generate prostate contours (auto contours). The prostate contours were also manually drawn by a physician. Quantitative assessment of deformed versus manually drawn prostate contours on daily CBCT images was performed using Dice similarity coefficient (DSC), mean distance-to-agreement (MDA), difference in center-of-mass position (ΔCM) and difference in volume (ΔVol). Radiomic features from 6 classes were extracted from each contour. Lin's concordance correlation coefficient (CCC) and mean absolute percent difference in radiomic feature-derived data (mean |%Δ|RF) between auto and manual contours were calculated. The mean (± SD) DSC, MDA, ΔCM and ΔVol between the auto and manual prostate contours were 0.90 ± 0.04, 1.81 ± 0.47 mm, 2.17 ± 1.26 mm and 5.1 ± 4.1% respectively. Of the 1,010 fractions under consideration, 94.8% of DIRs were within TG-132 recommended tolerance. 30 radiomic features had a CCC > 0.90 and 21 had a mean |%∆|RF < 5%. Auto-propagation of prostate contours resulted in nearly 95% of DIRs within tolerance recommendations of TG-132, leading to the majority of features being regarded as acceptably robust. The use of auto contours for radiomic feature analysis is promising but must be done with caution.

Assessment of Knowledge-Based Planning for Prostate Intensity Modulated Proton Therapy.

PURPOSE: To assess the performance of a proton-specific knowledge based planning (KBPP) model in creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of patients with prostate cancer. MATERIALS AND METHODS: Forty-five patients with localized prostate cancer, who had previously been treated with volumetric modulated arc therapy, were selected and replanned with robustly optimized IMPT. A KBPP model was generated from the results of 30 of the patients, and the remaining 15 patient results were used for validation. The KBPP model quality and accuracy were evaluated with the model-provided organ-at-risk regression plots and metrics. The KBPP quality was also assessed through comparison of expert and KBPP-generated IMPT plans for target coverage and organ-at-risk sparing. RESULTS: The resulting R 2 (mean ± SD, 0.87 ± 0.07) between dosimetric and geometric features, as well as the χ2 test (1.17 ± 0.07) between the original and estimated data, showed the model had good quality. All the KBPP plans were clinically acceptable. Compared with the expert plans, the KBPP plans had marginally higher dose-volume indices for the rectum V65Gy (0.8% ± 2.94%), but delivered a lower dose to the bladder (-1.06% ± 2.9% for bladder V65Gy). In addition, KBPP plans achieved lower hotspot (-0.67Gy ± 2.17Gy) and lower integral dose (-0.09Gy ± 0.3Gy) than the expert plans did. Moreover, the KBPP generated better plans that demonstrated slightly greater clinical target volume V95 (0.1% ± 0.68%) and lower homogeneity index (-1.13 ± 2.34). CONCLUSIONS: The results demonstrated that robustly optimized IMPT plans created by the KBPP model are of high quality and are comparable to expert plans. Furthermore, the KBPP model can generate more-robust and more-homogenous plans compared with those of expert plans. More studies need to be done for the validation of the proton KBPP model at more-complicated treatment sites.

Knowledge-Based Planning for Robustly Optimized Intensity-Modulated Proton Therapy of Head and Neck Cancer Patients.

PURPOSE: To assess the performance of a proton-specific knowledge-based planning (KBP) model in the creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of advanced head and neck (HN) cancer patients. METHODS: Seventy-three patients diagnosed with advanced HN cancer previously treated with volumetric modulated arc therapy (VMAT) were selected and replanned with robustly optimized IMPT. A proton-specific KBP model, RapidPlanPT (RPP), was generated using 53 patients (20 unilateral cases and 33 bilateral cases). The remaining 20 patients (10 unilateral and 10 bilateral cases) were used for model validation. The model was validated by comparing the target coverage and organ at risk (OAR) sparing in the RPP-generated IMPT plans with those in the expert plans. To account for the robustness of the plan, all uncertainty scenarios were included in the analysis. RESULTS: All the RPP plans generated were clinically acceptable. For unilateral cases, RPP plans had higher CTV_primary V100 (1.59% ± 1.24%) but higher homogeneity index (HI) (0.7 ± 0.73) than had the expert plans. In addition, the RPP plans had better ipsilateral cochlea Dmean (-5.76 ± 6.11 Gy), with marginal to no significant difference between RPP plans and expert plans for all other OAR dosimetric indices. For the bilateral cases, the V100 for all clinical target volumes (CTVs) was higher for the RPP plans than for the expert plans, especially the CTV_primary V100 (5.08% ± 3.02%), with no significant difference in the HI. With respect to OAR sparing, RPP plans had a lower spinal cord Dmax (-5.74 ± 5.72 Gy), lower cochlea Dmean (left, -6.05 ± 4.33 Gy; right, -4.84 ± 4.66 Gy), lower left and right parotid V20Gy (left, -6.45% ± 5.32%; right, -6.92% ± 3.45%), and a lower integral dose (-0.19 ± 0.19 Gy). However, RPP plans increased the Dmax in the body outside of CTV (body-CTV) (1.2 ± 1.43 Gy), indicating a slightly higher hotspot produced by the RPP plans. CONCLUSION: IMPT plans generated by a broad-scope RPP model have a quality that is, at minimum, comparable with, and at times superior to, that of the expert plans. The RPP plans demonstrated a greater robustness for CTV coverage and better sparing for several OARs.

CBCT-Based Adaptive Assessment Workflow for Intensity Modulated Proton Therapy for Head and Neck Cancer.

PURPOSE: Anatomical changes and patient setup uncertainties during intensity modulated proton therapy (IMPT) of head and neck (HN) cancers demand frequent evaluation of delivered dose. This work investigated a cone-beam computed tomography (CBCT) and deformable image registration based therapy workflow to demonstrate the feasibility of proton dose calculation on synthetic computed tomography (sCT) for adaptive IMPT treatment of HN cancer. MATERIALS AND METHODS: Twenty-one patients with HN cancer were enrolled in this study, a retrospective institutional review board protocol. They had previously been treated with volumetric modulated arc therapy and had daily iterative CBCT. For each patient, robust optimization (RO) IMPT plans were generated using ±3 mm patient setup and ±3% proton range uncertainties. The sCTs were created and the weekly delivered dose was recalculated using an adaptive dose accumulation workflow in which the planning computed tomography (CT) was deformably registered to CBCTs and Hounsfield units transferred from the planning CT. Accumulated doses from ±3 mm/±3% RO-IMPT plans were evaluated using clinical dose-volume constraints for targets (clinical target volume, or CTV) and organs at risk. RESULTS: Evaluation of weekly recalculated dose on sCTs showed that most of the patient plans maintained target dose coverage. The primary CTV remained covered by the V95 > 95% (95% of the volume receiving more than 95% of the prescription dose) worst-case scenario for 84.5% of the weekly fractions. The oral cavity accumulated mean dose remained lower than the worst-case scenario for all patients. Parotid accumulated mean dose remained within the uncertainty bands for 18 of the 21 patients, and all were kept lower than RO-IMPT worst-case scenario for 88.7% and 84.5% for left and right parotids, respectively. CONCLUSION: This study demonstrated that RO-IMPT plans account for most setup and anatomical uncertainties, except for large weight-loss changes that need to be tracked throughout the treatment course. We showed that sCTs could be a powerful decision tool for adaptation of these cases in order to reduce workload when using repeat CTs.

Assessment of daily dose accumulation for robustly optimized intensity modulated proton therapy treatment of prostate cancer.

PURPOSE: To implement a daily CBCT based dose accumulation technique in order to assess ideal robust optimization (RO) parameters for IMPT treatment of prostate cancer. METHODS: Ten prostate cancer patients previously treated with VMAT and having daily CBCT were included. First, RO-IMPT plans were created with ± 3 mm and ± 5 mm patient setup and ± 3% proton range uncertainties, respectively. Second, the planning CT (pCT) was deformably registered to the CBCT to create a synthetic CT (sCT). Both daily and weekly sampling strategies were employed to determine optimal dose accumulation frequency. Doses were recalculated on sCTs for both ± 3 mm/±3% and ± 5 mm/±3% uncertainties and were accumulated back to the pCT. Accumulated doses generated from ± 3 mm/±3% and ± 5 mm/±3% RO-IMPT plans were evaluated using the clinical dose volume constraints for CTV, bladder, and rectum. RESULTS: Daily accumulated dose based on both ± 3mm/±3% and ±5 mm/±3% uncertainties for RO-IMPT plans resulted in satisfactory CTV coverage (RO-IMPT3mm/3% CTVV95 = 99.01 ± 0.87% vs. RO-IMPT5mm/3% CTVV95 = 99.81 ± 0.2%, P = 0.002). However, the accumulated dose based on ± 3 mm/3% RO-IMPT plans consistently provided greater OAR sparing than ±5 mm/±3% RO-IMPT plans (RO-IMPT3mm/3% rectumV65Gy = 2.93 ± 2.39% vs. RO-IMPT5mm/3% rectumV65Gy = 4.38 ± 3%, P < 0.01; RO-IMPT3mm/3% bladderV65Gy = 5.2 ± 7.12% vs. RO-IMPT5mm/3% bladderV65Gy = 7.12 ± 9.59%, P < 0.01). The gamma analysis showed high dosimetric agreement between weekly and daily accumulated dose distributions. CONCLUSIONS: This study demonstrated that for RO-IMPT optimization, ±3mm/±3% uncertainty is sufficient to create plans that meet desired CTV coverage while achieving superior sparing to OARs when compared with ± 5 mm/±3% uncertainty. Furthermore, weekly dose accumulation can accurately estimate the overall dose delivered to prostate cancer patients.

Margin verification for hypofractionated prostate radiotherapy using a novel dose accumulation workflow and iterative CBCT.

PURPOSE: Hypofractionated radiotherapy for prostate cancer reduces the inconvenience of an extended treatment course but the appropriate treatment margin to ensure tumor control while minimizing toxicity is not standardized. Using a novel dose accumulation workflow with iterative CBCT (iCBCT) images, we were able to validate treatment margins. METHODS: Sixteen patients treated to the prostate on a hypofractionated clinical trial were selected. Prescription dose was 3625 cGy to > 95% of the PTV in 5 fractions with a boost to 4000 cGy to the high risk GTV (if applicable). PTV margin expansion was 5 mm isotropic except 3 mm posterior, no margin for the GTV. Daily iCBCT images were obtained while practicing strict bladder and rectal filling protocols. Using a novel adaptive dose accumulation workflow, synthetic CTs were created and the daily delivered dose was recalculated. The daily dose distributions were accumulated and target coverage and organ dose were assessed. RESULTS: Although the PTV coverage dropped for the accumulated dose, the prostate coverage was not compromised. The differences in bladder and anorectum dose were not significantly different. Four patients received a boost to the GTV and a significant decrease in coverage was noted in the accumulated dose. CONCLUSIONS: The novel dose accumulation workflow demonstrated that daily iCBCT images can be used for dose accumulation. We found that our clinical treatment margins resulted in adequate dose to the prostate while sparing OARs. If the goal is to deliver the full dose to an intra-prostatic GTV, a margin may be appropriate.

All-solid microstructured fibers with double cross linear arrays.

An all-solid microstructured fiber containing a pure silica core and the double cross linear arrays of high refractive index dielectric rods imbedded in the silica serving as the cladding is proposed. The bandgap and confinement loss (CL) are numerically investigated. The fiber has a lowest loss of 3.37 dB/km that can be achieved in the first-order photonic bandgap (PBG) and the bandwidth with transmission loss less than <0.05 dB/m is up to 550 nm. The effects of refractive index difference and geometric structure are discussed on the CL in the first-order PBG. The minimal attenuation can be reduced to 0.14 dB/km by choosing appropriate parameters. The bending property is also presented.