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Purpose: Radiation-induced lymphopenia (RIL) is associated with poor prognosis in patients with locally advanced pancreatic cancers. However, there are no reports comparing the effects of carbon ion radiation therapy (CIRT) and photon beam radiation therapy (RT) on the development of RIL. Differences in RIL after CIRT or photon beam RT and predictive factors for RIL in patients with locally advanced pancreatic cancer were investigated., Materials and Methods: This retrospective study cohort included 834 patients who received concurrent chemoradiotherapy (CCRT) in 2 separate institutions: 337 and 497 in the CIRT and photon beam RT groups, respectively. Severe RIL was defined as an absolute lymphocyte count (ALC) <0.5 × 10 9 cells/L. A 1:1 propensity score-matching analysis was performed between the CIRT and photon beam RT groups. Patients were categorized into 3 groups according to the development of recovery from severe RIL: no severe RIL (Group A), recovery from severe RIL (Group B), and no recovery from severe RIL (Group C). Logistic regression analysis was performed to identify the predictive value of severe RIL. The prognostic factors of overall survival (OS) were determined using Cox regression analysis., Results: After propensity score matching, the baseline ALC and planning target volume of the CIRT and photon beam RT groups were comparable. During CCRT, the ALC of the entire cohort decreased and was significantly lower in the photon beam RT group than in the CIRT group (P < .001). Multivariate logistic regression analysis showed that CIRT reduced severe RIL more than photon beam RT. After adjusting for other factors, the RT modality and RIL were significantly associated with OS. Photon beam RT showed a significantly worse OS than CIRT, and Group C showed a significantly worse OS than Group A., Conclusions: CIRT seems to reduce the development of severe RIL. The RT modality and development/recovery from severe RIL were associated with OS in patients who received CCRT for locally advanced pancreatic cancer. The reduction of severe RIL through optimized RT may be essential for improving treatment outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As the relationship between the gut microbiome and allergies becomes better understood, targeted strategies to prevent and treat allergies through gut microbiome modulation are being increasingly developed. In the study presented herein, we screened various probiotics for their ability to inhibit mast cell degranulation and identified Lactiplatibacillus plantarum HD02 and MD159 as effective candidates. The two strains significantly attenuated vascular permeability induced by mast cell degranulation in a passive cutaneous anaphylaxis (PCA) model and, in the MC903-induced murine atopic dermatitis (AD) model, demonstrated comparable preventive effects against allergies, reducing blood levels of MCPT-1 (mast cell protease-1) and total IgE. In the house dust mite (HDM)-induced murine AD model, both L. plantarum HD02 and MD159 showed therapeutic effects, with L. plantarum HD02 demonstrating superior efficacy. Nevertheless, L. plantarum MD159 better suppressed transepidermal water loss (TEWL). Furthermore, L. plantarum HD02 and MD159 significantly increased the number of splenic Foxp3 + regulatory T cells, with L. plantarum MD159 having a more pronounced effect. However, only L. plantarum HD02 achieved a reduction in immune cells in the draining lymph nodes. Our findings highlight L. plantarum HD02 and MD159 as promising candidates for the prevention and treatment of allergies, demonstrating significant efficacy in suppressing mast cell degranulation, reducing the number of allergy biomarkers, and modulating immune responses in experimental models of AD. Their distinct mechanisms of action suggest potential complementary roles in addressing allergic diseases, underscoring their therapeutic promise in clinical applications.

Purpose: This study evaluated the impact and clinical utility of an auto-contouring system for radiation therapy treatments., Methods and Materials: The auto-contouring system was implemented in 2019. We evaluated data from 2428 patients who underwent adjuvant breast radiation therapy before and after the system's introduction. We collected the treatment's finalized contours, which were reviewed and revised by a multidisciplinary team. After implementation, the treatment contours underwent a finalization process that involved manual review and adjustment of the initial auto-contours. For the preimplementation group (n = 369), auto-contours were generated retrospectively. We compared the auto-contours and final contours using the Dice similarity coefficient (DSC) and the 95% Hausdorff distance (HD95)., Results: We analyzed 22,215 structures from final and corresponding auto-contours. The final contours were generally larger, encompassing more slices in the superior or inferior directions. Among organs at risk (OAR), the heart, esophagus, spinal cord, and contralateral breast demonstrated significantly increased DSC and decreased HD95 postimplementation (all P < .05), except for the lungs, which presented inaccurate segmentation. Among target volumes, CTVn&#95;L2, L3, L4, and the internal mammary node showed increased DSC and decreased HD95 postimplementation (all P < .05), although the increase was less pronounced than the OAR outcomes. The analysis also covered factors contributing to significant differences, pattern identification, and outlier detection., Conclusions: In our study, the adoption of an auto-contouring system was associated with an increased reliance on automated settings, underscoring its utility and the potential risk of automation bias. Given these findings, we underscore the importance of considering the integration of stringent risk assessments and quality management strategies as a precautionary measure for the optimal use of such systems., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: Stereotactic ablative radiotherapy (SABR) can extend survival and offers the potential for cure in some patients with oligometastatic disease (OMD). However, limited evidence exists regarding its use in oligometastatic hepatocellular carcinoma (HCC). We aimed to prospectively investigate the efficacy and safety of SABR in patients with oligometastatic HCC., Methods: We enrolled patients with controlled primary HCC and one to five metastatic lesions amenable to SABR. The primary endpoint was treatment efficacy defined as overall survival (OS) and progression-free survival (PFS). The secondary endpoints included time to local progression, objective response rate, disease control rate, toxicities, and quality of life (QOL), assessed using the EORTC QLQ-C30 before, and 0, 1, and 3 months after SABR., Results: Overall, 40 consecutive patients received SABR on 62 lesions between 2021 and 2022. The most common locations for OMD were the lungs (48.4%), lymph nodes (22.6%), and bone (17.7%). After a median follow-up of 15.5 months, the 2-year OS was 80%. Median PFS was 5.3 months, with 1- and 2-year PFS rates of 21.2% and 0%, respectively. A shorter time to OMD from the controlled primary independently correlated with PFS (p = 0.039, hazard ratio 2.127) alongside age, Child-Pugh class, and alpha-fetoprotein (p = 0.002, 0.004, 0.019, respectively). The 2-year time to local progression, objective response rate, and disease control rate were 91.1%, 75.8%, and 98.4%, respectively. Overall, 10% of patients experienced acute toxicity, and 7.5% experienced late toxicity, with no grade 3+ toxicity. All QOL scores remained stable, whereas the patients without systemic treatments had improved insomnia and social functioning scores., Conclusions: SABR is an effective and feasible option for oligometastatic HCC that leads to excellent local tumor control and improves survival without adversely affecting QOL., Impact and Implications: Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment approach capable of efficiently ablating the target lesion; however, neither the oligometastatic disease concept nor the potential benefits of SABR have been well-defined in hepatocellular carcinoma (HCC). According to this study, SABR is an effective and safe treatment option for oligometastatic HCC, yielding excellent local tumor control and survival improvement without worsening patients' quality of life, regardless of tumor sites. We also demonstrated that patients with a later presentation of OMD from the controlled primary and lower alpha-fetoprotein levels achieved better survival outcomes. This is the first prospective study of SABR in oligometastatic HCC, providing insights for the development of novel strategies to improve oncologic outcomes., Clinical Trial Number: NCT05173610., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Locoregional recurrence (LRR) is the predominant pattern of relapse after definitive breast cancer treatment. The present study aimed to develop machine learning (ML)-based radiomics models to predict LRR in patients with breast cancer by using preoperative magnetic resonance imaging (MRI) data. Data from patients with localized breast cancer that underwent preoperative MRI between January 2013 and December 2017 were collected. Propensity score matching (PSM) was performed to adjust for clinical factors between patients with and without LRR. Radiomics features were obtained from T2-weighted with and without fat-suppressed MRI and contrast-enhanced T1-weighted with fat-suppressed MRI. In the present study five ML models were designed, three base models (support vector machine, random forest, and logistic regression) and two ensemble models (voting model and stacking model) composed of the three base models, and the performance of each base model was compared with the stacking model. After PSM, 28 patients with LRR and 86 patients without LRR were included. Of these 114 patients, 80 patients were randomly selected to train the models, and the remaining 34 patients were used to evaluate the performance of the trained models. In total, 5,064 features were obtained from each patient, and 47-51 features were selected by applying variance threshold and least absolute shrinkage and selection operator. The stacking model demonstrated superior performance in area under the receiver operating characteristic curve (AUC), with an AUC of 0.78 compared to a range of 0.61 to 0.70 for the other models. An external validation study to investigate the efficacy of the stacking model of the present study was initiated and is still ongoing (Korean Radiation Oncology Group 2206)., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Lee et al.)

Objective: This study aimed to update the possible clinical benefits of radiation therapy in recurrent ovarian cancer., Methods: The medical records of 495 patients with recurrent ovarian cancer after initially undergoing maximal cytoreductive surgery and adjuvant platinum-based chemotherapy based on the pathologic stage between January 2010 and December 2020 were analyzed: 309 and 186 patients were treated without and with involved-field radiation therapy, respectively. Involved-field radiation therapy is defined as radiation therapy only to the areas of the body involved by tumor. The prescribed doses were ≥45 Gy (equivalent dose in 2 Gy/fraction). Overall survival was compared between patients treated with and without involved-field radiation therapy. The favorable group was defined as patients who satisfied at least four of the following factors: good performance, no ascites, normal CA-125, platinum-sensitive tumor, and nodal recurrence., Results: The median age of the patients was 56 years (range 49-63) and median time to recurrence was 11.1 months (range 6.1-15.5). 217 patients (43.8%) were treated at a single site. Radiation therapy, performance status, CA-125, platinum sensitivity, residual disease, and ascites were all significant prognostic factors. The 3-year overall survival of all patients, patients treated without radiation therapy, and patients treated with radiation therapy was 54.0%, 44.8%, and 69.3%, respectively. Radiation therapy was associated with higher overall survival rates in the unfavorable and favorable patient groups. Patient characteristics showed higher rates of normal CA-125, lymph node metastasis only, lower platinum sensitivity, and higher rates of ascites in the radiation therapy group. After propensity score matching, the radiation therapy group showed superior overall survival to the non-radiation therapy group. Normal CA-125, good performance status, and platinum sensitivity were associated with a good prognosis in patients treated with radiation therapy., Conclusion: Our study showed that higher overall survival was observed in patients treated with radiation therapy in recurrent ovarian cancer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the effect of local ablative therapy (LAT) on overall survival in patients with lung metastases from colorectal cancer (CRC) compared with patients treated with systemic therapy., Summary Background Data: CRC affects approximately 1.4 million individuals worldwide every year. The lungs are commonly affected by CRC, and there is no treatment standard for a secondary lung metastasis from CRC., Methods: This longitudinal, retrospective cohort study (2010-2018) quantified the pulmonary and extrapulmonary tumor burden of 1143 patients by retrospectively reviewing computed tomography images captured at diagnosis. A comprehensive multidisciplinary approach informed how and when surgery and/or stereotactic body radiotherapy was administered., Results: Among 1143 patients, 473 patients (41%) received LAT, with surgery first (n = 421) or stereotactic ablative radiation therapy first (n = 52) either at the time of diagnosis (n = 288), within 1 year (n = 132), or after 1 year (n = 53). LAT was repeated in 158 patients (33.4%, 384 total sessions) when new lung metastases were detected. The 5- and 10-year survival rates for patients treated with LAT (71.2% and 64.0%, respectively) were significantly higher than those of patients treated with systemic therapy alone (14.2% and 10.0%, respectively; P <0.001). The overall survival of patients who received LAT intervention increased as the total tumor burden decreased., Conclusions: A high long-term survival rate was achievable in a significant portion of patients with lung metastasis from CRC by the timely administrations of LAT to standard systemic therapy. The tumor burden and LAT feasibility should be included in a discussion during the follow-up period., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The pulsed electric field (PEF) is a non-thermal food processing technology that induces electroporation of the cell membrane thus improving mass transfer through the cell membrane. In this study, the drying and rehydration kinetics, microstructure, and carotenoid content of carrot ( Daucus carota ) pretreated by PEF during convective drying at 50 °C were investigated. The PEF treatment was conducted with different field strengths (1.0-2.5 kV/cm) using a fixed pulse width of 20 µs and at a pulse frequency of 50 Hz. The PEF 2.5 kV/cm showed the shortest drying time, taking 180 min, whereas the control required 330 min for the same moisture ratio, indicating a 45% reduction in drying time. The rehydration ability also increased as the strengths of PEF increased. PEF 2.5 kV/cm resulted in 27.58% increase in moisture content compared to the control after rehydration (1 h). Three mathematical models were applied to the drying and rehydration data; the Page and Peleg models were selected as the most appropriate models to describe the drying and rehydration kinetics, respectively. The cutting force of the sample was decreased as the strength of PEF increased, and a more homogeneous cellular structure was observed in the PEF pretreatment group. The reduction in drying time by PEF was beneficial to the carotenoid content, and PEF 2.5 kV/cm showed the highest preservation content of carotenoid. Overall, these results suggested that the pretreatment of PEF and the drying and rehydration rate influence the quality of products, functional components, and cellular structure.

Introduction: We aimed to investigate the significance of lymph node metastasis from hepatocellular carcinoma and the efficacy of local treatment., Methods: We included patients diagnosed hepatocellular carcinoma with lymph node metastasis. The pattern of lymph node metastasis was evaluated based on imaging examinations and stratified by three locations: regional (group A), beyond regional intra-abdomen (group B), and extra-abdomen (group C) lymph node metastasis., Results: Among 14,474 patients, 852 (5.8%) were identified as having lymph node metastasis. Regarding the location of presentation, group A showed the highest incidence, followed by groups B and C. The 1-year overall survival of patients was 31.7%. The survival significantly differed according to the location of lymph node metastasis. The 1-year overall survival rates were 39.8%, 25.5%, and 22.2% in groups A, B, and C, respectively. All patients underwent systemic treatment, with others receiving additional local treatment. Local treatment yielded superior overall survival compared with no local treatment. After propensity score matching, local treatment was associated with improved survival. Additionally, patients were stratified based on disease status at the time of diagnosis of lymph node metastasis: lymph node alone and combined extra-nodal metastasis. The survival benefits of local treatment were observed in both groups., Conclusions: Our findings demonstrated the clinical significance of lymph node metastasis from hepatocellular carcinoma, which was well discriminated according to location, favoring regional metastasis. In patients with hepatocellular carcinoma presenting lymph node metastasis, active application of local treatment for lymph node metastasis can improve oncologic outcomes., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel.)

Drilling mud is a multi-phase fluid that is used in the petroleum drilling process. Bentonite is the most important constituent of drilling mud; it endows the drilling mud with its rheological behaviors, such as viscosity, yield stress, and shear thinning. The process of manufacturing microscale bentonite at the nanoscale level is very promising for commercializing nano-based drilling mud. In contrast to the conventional method using the impeller, bentonite was manufactured in its nanoparticle state in the present work through ultrasonic and homogenizer processes in the solution state. In case of the ultrasonic process, the viscosity increase in the low shear rate region before and after processing of the 5 wt% bentonite-based mud and the rheological properties in the presence of polymer additive were compared. In case of the homogenizer process, the rheological properties of 3 wt% bentonite-based mud employed through the homogenizer process and 5 wt% mud prepared generally were compared. Both processes reported improvement of rheological properties, in which shear thinning behavior strongly occurred when particle size decreased through FE-SEM, TEM image analysis, and particle size analyzer. A regularized Herschel-Bulkley model suitable for rheological quantitative explanation of drilling mud including yield stress was selected. The homogenizer process has the potential to be applied in the petroleum drilling industry for large-scale production, and the mechanism was confirmed by numerical analyses. In conclusion, we presented a simple and easy-to-apply process to rapidly produce nano-based drilling mud., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: This study aimed to explore the possibility and clinical utility of existing artificial intelligence (AI)-based computer-aided detection (CAD) of lung nodules to identify pulmonary oligometastases., Patients and Methods: The chest computed tomography (CT) scans of patients with lung metastasis from colorectal cancer between March 2006 and November 2018 were analyzed. The patients were selected from a database of 1395 patients and studied in 2 cohorts. The first cohort included 50 patients, and the CT scans of these patients were independently evaluated for lung-nodule (≥3 mm) detection by a CAD-assisted radiation oncologist (CAD-RO) as well as by an expert radiologist. Interobserver variability by 2 additional radiation oncologists and 2 thoracic surgeons were also measured. In the second cohort of 305 patients, survival outcomes were evaluated based on the number of CAD-RO-detected nodules., Results: In the first cohort, the sensitivity and specificity of the CAD-RO for identifying oligometastatic disease (OMD) from varying criteria by ≤2 nodules, ≤3 nodules, ≤4 nodules, and ≤5 nodules were 71.9% and 88.9%, 82.9% and 93.3%, 97.1% and 73.3%, and 97.5% and 90.0%, respectively. The sensitivity of the CAD-RO in the nodule detection compared with the radiologist was 81.6%. The average (standard deviation) sensitivity in interobserver variability analysis was 80.0% (3.7%). In the second cohort, the 5-year survival rates of patients with 1, 2, 3, 4, or ≥5 metastatic nodules were 75.2%, 52.9%, 45.7%, 29.1%, and 22.7%, respectively., Conclusions: Proper identification of the pulmonary OMD and the correlation between the number of CAD-RO-detected nodules and survival suggest the potential practicality of AI in OMD recognition. Developing a deep learning-based model specific to the metastatic setting, which enables a quick estimation of disease burden and identification of OMD, is underway., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: Metabolic parameters evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) are known as prognostic markers in various cancers. We aimed to validate the predictive value of mid-radiotherapy (RT) FDG PET/CT parameters in esophageal cancer., Materials and Methods: Eighty-three patients treated with RT with or without chemotherapy between 2015 and 2020 were included. PET parameters including metabolic tumor volume (MTV), total lesion glycolysis, and mean (SUV mean ) and maximum standardized uptake value (SUV max ) were analyzed. Locoregional recurrence-free rate (LRFR) and distant metastasis-free rate (DMFR) were analyzed., Results: The median follow-up period was 10.5 months. Mid-RT SUV max was significantly associated with LRFR (HR 1.07, p = 0.009) and DMFR (HR 1.13, p = 0.047) while mid-RT MTV was associated with DMFR (HR 1.06, p = 0.007). Treatment response after RT was associated with overall survival (HR, 1.52, p = 0.025). Further, treatment response was significantly associated with mid-RT SUV max . The optimal cutoff value for mid-RT SUV max in predicting LRFR and DMFR was 11 while cutoff value for mid-RT MTV was 15. The patients with mid-RT SUV max  ≤ 11 showed superior LRFR and DMFR compared to SUV max  > 11 (1-year LRFR; 73.4% vs. 48.4%, p = 0.028, 1-year DMFR; 74.6% vs. 40.7%, p = 0.007). The 1-year DMFR was significantly different between patients with mid-RT MTV ≤ 15 and >15 (1-year DMFR; 78.2% vs. 31.9%, p = 0.002)., Conclusion: Tumor metabolism changes during RT can be a useful predictive tool for treatment response and recurrence in patients with esophageal cancer. Clinicians may consider early response evaluation with PET during RT for predicting prognosis information about prognosis., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To investigate whether radiotherapy (RT) dose escalation would improve treatment outcomes without increasing severe toxicity in locally advanced pancreatic cancer patients., Methods: From 2005 to 2015, 497 locally advanced pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) were included. Patients were divided according to the total dose (TD). Overall survival (OS), progression-free survival (PFS), local failure-free rate (LFFR), distant failure-free rate (DFFR), and toxicity rates were compared between <61Gy (n=345) and ≥61Gy groups (n=152). Additionally, propensity score matching was performed., Results: At a median follow-up of 19.3months (range, 4.8-128.5months), the 1-year OS, PFS, LFFR, and DFFR were significantly higher in the ≥61Gy group. After multivariate analysis, a TD of ≥61Gy remained a significant favorable factor for OS (p=0.019), PFS (p=0.001), LFFR (p=0.004), and DFFR (p=0.008). After propensity score matching, the ≥61Gy group still showed higher OS, PFS, and LFFR, but not DFFR (p=0.205). The acute and late toxicity rates showed no significant difference between the two groups., Conclusion: Patients who received a higher RT dose showed not only improved PFS and LFFR, but also improved OS without an increase in severe toxicity. Dose-escalated CCRT can be a favorable treatment option in locally advanced pancreatic cancer patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Enhancing and/or modulating innate and adaptive immunity by cytokines appears to be greatly useful to provide effective protective immunity against infectious diseases. However, an effective delivery system for mass administration in livestock industry is needed because of limitations such as cost, labor, time, and protein stability. Here the immunomodulatory functions of swine interleukine-18 (swIL-18), known as IFN-γ-inducing factor (IGIF), were evaluated in a vaccination model of pseudorabies virus (PrV) using attenuated Salmonella enterica serovar Typhimurium as the oral delivery system. The oral administration of S. enterica serovar Typhimurium expressing swIL-18 prior to vaccination with inactivated PrV vaccine induced enhanced levels of serum PrV-specific IgG and its IgG2 isotype, compared to administration of S. enterica serovar Typhimurium harboring the empty vector. Furthermore, S. enterica serovar Typhimurium expressing swIL-18 mounted Th1-biased cellular immune responses against PrV antigen, as evaluated by the production of IFN-γ and IL-4 from peripheral blood mononuclear cells of piglets. Subsequently, Th1-biased immunity induced by S. enterica serovar Typhimurium expressing swIL-18 showed rapid response and rendered piglets displayed more alleviated clinical signs following the virulent PrV challenge. Also, this alleviation of clinical signs was further confirmed by the reduction of nasal excretion of PrV after challenge. The present study demonstrates the extended use of immunomodulatory functions of swIL-18 orally delivered by attenuated S. enterica serovar Typhimurium., (Copyright © 2011 Elsevier B.V. All rights reserved.)

While N-(2-nitrobenzylidene)anilines produced mixtures of 2,1-benzisoxazoles and 3-anilino-2-aryl-2H-indazoles in the presence of indium and iodine in MeOH, N-(2-nitrobenzylidene)anilines were transformed into 3-anilino-2-aryl-2H-indazoles as the predominant major product through the change of the solvent from protic MeOH to aprotic THF. In an indium-mediated one-pot reductive reaction, 2-benzaldehydes and anilines in THF were also successfully transformed into the corresponding indazoles.