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Byung Chull An,1 Yeo-Sang Yoon,1 Ho Jin Park,1 Sangkyun Park,1 Tai Yeub Kim,1 Jun Young Ahn,1 Daebeom Kwon,1 Oksik Choi,1 Jin Young Heo,1 Yongku Ryu,1 Joong-Hyun Kim,2 Heejong Eom,2 Myung Jun Chung1 1R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea; 2Laboratory Animal Center, Osong Medical Innovation Foundation, Chungbuk, Cheongju, 28160, KoreaCorrespondence: Myung Jun Chung Tel +82-31-987-6205Fax +82-31-987-6216Email ceo@cellbiotech.comPurpose: This study aimed to toxicological evaluate a probiotics-based delivery system for p8 protein as an anti-colorectal cancer drug.Introduction: Lactic acid bacteria (LAB) have been widely ingested for many years and are regarded as very safe. Recently, a Pediococcus pentosaceus SL4 (PP) strain that secretes the probiotic-derived anti-cancer protein P8 (PP-P8) has been developed as an anti-colorectal cancer (CRC) biologic by Cell Biotech. We initially identified a Lactobacillus rhamnosus (LR)-derived anti-cancer protein, P8, that suppresses CRC growth. We also showed that P8 penetrates specifically into CRC cells (DLD-1 cells) through endocytosis. We then confirmed the efficacy of PP-P8, showing that oral administration of this agent significantly decreased tumor mass (∼ 42%) relative to controls in a mouse CRC xenograft model. In terms of molecular mechanism, PP-P8 induces cell-cycle arrest in G2 phase through down-regulation of Cyclin B1 and Cdk1. In this study, we performed in vivo toxicology profiling to obtain evidence that PP-P8 is safe, with the goal of receiving approval for an investigational new drug application (IND).Methods: Based on gene therapy guidelines of the Ministry of Food and Drug Safety (MFDS) of Korea, the potential undesirable effects of PP-P8 had to be investigated in intact small rodent or marmoset models prior to first-in-human (FIH) administration. The estimated doses of PP-P8 for FIH are 1.0× 1010 – 1.0× 1011 CFU/person (60 kg). Therefore, to perform toxicological investigations in non-clinical animal models, we orally administered PP-P8 at doses of 3.375 × 1011, 6.75 × 1011, and 13.5× 1011 CFU/kg/day; thus the maximum dose was 800– 8000-fold higher than the estimated dose for FIH.Results: In our animal models, we observed no adverse effects of PP-P8 on clinicopathologic findings, relative organ weight, or tissue pathology. In addition, we observed no inflammation or ulceration during pathological necropsy.Conclusion: These non-clinical toxicology studies could be used to furnish valuable data for the safety certification of PP-P8.Keywords: biologics, therapeutic protein, probiotics derived anti-cancer protein P8, Pediococcus pentosaceus SL4, Lactobacillus rhamnosus, colorectal cancer, drug delivery system, protein secretion system, oral administration, non-clinical trial, toxicology finding

Moonkyoo Kong,1 Yu Jin Lim,1 Youngkyong Kim,1 Mi Joo Chung,2 Soonki Min,1 Dong Oh Shin,1 Weonkuu Chung21Department of Radiation Oncology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 2Department of Radiation Oncology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Republic of KoreaPurpose: We evaluated the effects of diabetes mellitus (DM) and DM-related serologic factors (HbA1c and fasting glucose) on the development of radiation pneumonitis in patients with lung cancer.Methods: We retrospectively analyzed the clinical data of 123 patients with lung cancer treated with radiotherapy. Radiation pneumonitis was scored according to the toxicity criteria of the Radiation Therapy Oncology Group. We used binary logistic regression analysis to find significant predictive factors for the development of grade ≥3 radiation pneumonitis.Results: On univariable analysis, V20, mean lung dose, DM, HbA1c, and fasting glucose level were significantly associated with the development of grade ≥3 radiation pneumonitis. On multivariable analysis, V20, mean lung dose, DM, HbA1c, and fasting glucose level remained significant predictive factors for grade ≥3 radiation pneumonitis. The incidence of grade ≥3 radiation pneumonitis was 44.4% in patients with DM and 20.7% in patients without DM. The incidence of grade ≥3 radiation pneumonitis was 12.7% for HbA1c level ≤6.15% and 41.5% for HbA1c level >6.15%. The incidence of grade ≥3 radiation pneumonitis was 17.2% for fasting glucose level ≤121 mg/dL and 35.5% for fasting glucose level >121 mg/dL.Conclusion: DM, HbA1c, and fasting glucose level are significant predictive factors for the development of grade ≥3 radiation pneumonitis in patients with lung cancer. Patients with DM, patients who have HbA1c >6.15%, and patients who have fasting glucose >121 mg/dL should be treated with greater caution.Keywords: lung cancer, radiotherapy, radiation pneumonitis, diabetes mellitus

Background: Recently developed digital tomosynthesis has shown improved detection of pulmonary lesions with a radiation dose comparable to conventional CR but with a much lower radiation dose than CT. Purpose: To compare the diagnostic performance of digital tomosynthesis (DT) with that of chest radiography (CR) for the detection of aortic arch calcification (AAC). Material and Methods: The study included 100 patients who underwent multidetector computed tomography (MDCT), DT, and CR (DT and CR were obtained within one week of CT examination). We evaluated and compared the diagnostic performances of DT and CR for the detection of AAC with MDCT as the reference standard. The extent (four grades 0-3) of AAC on DT and CR was also compared with CT calcium score. Inter-observer agreement was analyzed by using kappa statistics. Results: On DT, overall accuracy for AAC was superior to that of CR (94% and 71%, respectively, P < 0.01). Inter-observer agreement was good with DT and CR (kappa values = 0.74 and 0.62, respectively) for the presence of AAC, and good with DT and moderate with CR (kappa value = 0.64 and 0.53, respectively) for AAC grading. The overall correlation coefficient on AAC grading between DT and CT (calcium score) was superior to that between CR and CT (0.90 and 0.60, respectively). Conclusion: DT is superior to CR for detection and extent evaluation of AAC. [ABSTRACT FROM AUTHOR]

Background: Solitary pulmonary nodule (SPN) evaluation based on analyses of combined wash-in (WI) and washout (WO) values obtained by helical dynamic CT (HDCT) scanning is useful for malignant SPN characterization, because this method has higher specificity and accuracy than that based on analyses of WI values only. However, increased specificity results in reduced sensitivity and the missing of malignant SPNs. Thus, the purpose of this study was to seek the most effective method for SPN characterization during HDCT scanning. Methods: After obtaining unenhanced CT scans, dynamic CT scanning was performed using a helical technique (images were obtained at 30, 60, 90, and 120 s, and at 5 and 15 min after the initiation of IV contrast administration) in 486 patients with a solid or partly solid SPN. Diagnostic efficacies were compared for three approaches involving considerations of WI values (in Housfield units [HU]) only, both WI and WO HU values, and WI HU values and morphologic characteristics. Results: Considering WI values only (> or = 25 HU), sensitivity, specificity, and accuracy for malignancy were 98% (233 of 237 nodules), 46% (114 of 249 nodules), and 71% (347 of 486 nodules), respectively. Using both a WI value of > or = 25 HU and a WO value of 5 to 36 HU, the corresponding values were 89% (212 of 237 nodules), 79% (197 of 249 nodules), and 84% (409 of 486 nodules), respectively; for a WI value of > or = 25 HU and a malignant morphology, the corresponding values were 92% (219 of 237 nodules), 79% (197 of 249 nodules), and 86% (416 of 486 nodules), respectively (these values were significantly different between the WI-only group and the other two groups; p = 0.001). Conclusions: The efficacy of SPN evaluation based on analyses of WI values plus morphologic features during HDCT scanning appears to be equivalent to that based on analyses of WI plus WO values, thus obviating the need for WO scans, which saves time and reduces radiation exposure of the patient. [ABSTRACT FROM AUTHOR]

In-sensor computing has gained attention as a solution to overcome the von Neumann computing bottlenecks inherent in conventional sensory systems. This attention is due to the ability of sensor elements to directly extract meaningful information from external signals, thereby simplifying complex data. The advantage of in-sensor computing can be maximized with the sampling principle of a restricted Boltzmann machine (RBM) to extract significant features. In this study, a stochastic photo-responsive neuron is developed using a TiN/In-Ga-Zn-O/TiN optoelectronic memristor and an Ag/HfO 2 /Pt threshold-switching memristor, which can be configured as an input neuron in an in-sensor RBM. It demonstrates a sigmoidal switching probability depending on light intensity. The stochastic properties allow for the simultaneous exploration of various neuron states within the network, making identifying optimal features in complex images easier. Based on semi-empirical simulations, high recognition accuracies of 90.9% and 95.5% are achieved using handwritten digit and face image datasets, respectively. In addition, the in-sensor RBM effectively reconstructs abnormal face images, indicating that integrating in-sensor computing with probabilistic neural networks can lead to reliable and efficient image recognition under unpredictable real-world conditions.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus , has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness. Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2 , along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

Introduction: This study aimed to compare the long-term effects of neoadjuvant therapy and upfront surgery on overall survival (OS) and progression-free survival (PFS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC)., Methods: We retrospectively analyzed 202 patients, including 167 who had upfront surgery and 35 who received neoadjuvant therapy followed by surgery. Surgical outcomes and survival rates were compared using propensity score matching to minimize selection bias., Results: Neoadjuvant therapy showed significantly longer 75% OS (72.7 months vs. 28.3 months, p = 0.032) and PFS (29.6 months vs. 13.2 months, p < 0.001) compared to upfront surgery. Additionally, neoadjuvant therapy demonstrated significant improvements in surgical outcomes, including higher R0 resection rates (74.3% vs. 49.5%, p = 0.034), reduced tumor size (22.0 mm vs. 28.0 mm, p = 0.001), and decreased lymphovascular invasion (20.0% vs. 52.4%, p = 0.001)., Conclusion: Our study demonstrates the potential benefits of neoadjuvant therapy for resectable PDAC. The improved survival rates, delayed disease progression, and enhanced surgical outcomes underscore the potential of neoadjuvant therapy in addressing this aggressive disease. Despite limitations such as the retrospective design and small sample size, these findings support the effectiveness of neoadjuvant therapy in improving treatment outcomes for PDAC patients in real-world settings. Further prospective studies are required to validate these results., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

BRCA genes have well-known associations with breast and ovarian cancers. However, variations in the BRCA gene, especially germline variations, have also been reported in colorectal cancer (CRC). We present the case of a rectal cancer with a germline BRCA1 variation inherited from the paternal side. A 39-year-old male was admitted with rectal cancer. The patient underwent surgical resection and the pathologic diagnosis was adenocarcinoma. Next-generation sequencing was performed and a BRCA1 variant was detected. Reviewing the public database and considering the young age of the patient, the variant was suggested to be germline. The patient's father had had prostate cancer and next-generation sequencing testing revealed an identical BRCA1 variant. In the BRCA cancer group, there is relatively little attention paid to male cancers. The accumulation of male CRC cases linked to BRCA variations may help clarify the potential pathological relationship between the two.

Purpose: Focal interstitial fibrosis (FIF) manifesting as a persistent part-solid nodule (PSN) has been mistakenly treated surgically due to similar imaging features to invasive adenocarcinoma (ADC). The purpose of this study was to observe predictive imaging features correlated with FIF through CT morphologic analysis., Materials and Methods: From January 2009 to December 2020, 44 patients with surgically proven FIF in a single institution were enrolled and compared with 88 ADC patients through propensity score matching. Patient characteristics and CT morphologic analysis of persistent PSNs were used to identify predictive imaging features of FIF. Receiver operating characteristic (ROC) curve analysis was used to quantify the performance of imaging features., Results: A total of 132 patients with 132 PSNs (44 FIF, 88 ADC; mean age, 67.7±7.58; 75 females) were involved in our analysis. Multivariable analysis demonstrated that preserved peritumoral vascular margin (preserved vascular margin), preserved secondary pulmonary lobule margin (preserved lobular margin), and lower coronal to axial ratio (C/A ratio; cutoff: 1.005) were significant independent predictors of FIF ( P< 0.05). ROC curve analysis to evaluate the predictive value of the logistic model based on the imaging features of FIF, and the AUC value was 0.881., Conclusion: CT imaging features of preserved vascular margin, preserved lobular margin, and lower C/A ratio (cutoff, <1.005) might be helpful imaging features in discriminating FIF over ADC among persistent PSN in clinical practice., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC., Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography (MRCP) with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events., Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p = 0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well-tolerated., Conclusions: HK-660S is well-tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis. (cris.nih.go.kr, Number KCT0006590).

Background: Approximately half of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) receive subsequent lines of chemotherapy. Recently, the liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) regimen is recommended as subsequent lines of chemotherapy. However, little is known about the predictive factors for the nal-IRI + 5-FU/LV regimen, especially in patients with previous irinotecan (IRI) exposure., Objectives: We investigated the predictive factors associated with nal-IRI + 5-FU/LV treatment in patients with PDAC., Design: Multicenter, retrospective cohort study., Methods: This study included patients with advanced PDAC who received the nal-IRI + 5-FU/LV regimen for palliative purposes., Results: Overall, 268 patients were treated with nal-IRI + 5-FU/LV. The median overall survival (OS) was 7.9 months (95% confidence interval (CI): 7.0-8.8), while the median progression-free survival (PFS) was 2.6 months (95% CI: 1.9-3.2). An albumin level of<4.0 g/dL, neutrophil-to-lymphocyte ratio (NLR) of ⩾3.5, liver or peritoneal metastasis, and a history of >3 lines of palliative chemotherapy were associated with worse OS. An NLR of ⩾3.5 and liver metastasis were significant predictive factors for worse PFS. Previous exposure to IRI was not a significant predictor. Patients without prior IRI (no-IRI) treatment showed relatively longer OS and PFS compared to IRI responders and nonresponders, but these differences were not significant when compared specifically to the responders (OS: 8.8 vs 8.1 months, p = 0.388; PFS: 3.6 vs 2.6 months, p = 0.126)., Conclusion: An NLR of ⩾3.5 and liver metastasis were associated with worse PFS. Prior IRI exposure was not a significant predictive factor for OS and PFS, especially in IRI responders., Competing Interests: Seungmin Bang received funding from Servier., (© The Author(s), 2024.)

Lagerstroemia speciosa L. (Banaba) has been used as a functional food because of its diuretic, decongestant, antipyretic, anti-hyperglycemic, and anti-adipogenic activities. Triterpene acids, including corosolic acid, oleanolic acid, and asiatic acid, are the principal phytochemicals in Banaba and are potentially anti-diabetic substances, owing to their effect on blood glucose concentration. Bioconversion of Banaba leaf extract (BLE) by Lactobacillus plantarum CBT-LP3 improved the glucose uptake, insulin secretion, and fat browning of this functional food. Furthermore, we identified asiatic acid, which was found to be increased by 3.8-fold during the L. plantarum CBT-LP3-mediated bioconversion process using metabolite profiling. Most previous studies have focused on corosolic acid, another triterpene acid that is a known anti-diabetic compound and is used to standardize BLE preparations. However, asiatic acid is the second most common of the triterpene acids and is also well known to have anti-diabetic properties. The present study has provided strong evidence that asiatic acid represents an alternative to corosolic acid as the most important active compound. These results suggest that the probiotic-mediated bioconversion of BLE may improve the anti-diabetic effects of this functional food. This implies that the consumption of a probiotic should be encouraged for people undergoing BLE treatment to improve its anti-diabetic effects.

The long survival of patients with primary cancer increases the chance of such patients developing second primary cancer (SPC). The development of SPC in cancer survivors exerts a large psychological, social and economic burden on patients and their families. The aim of the present study was to assess the risk of cancer survivors developing SPC. The study included patients who had been diagnosed with a first primary cancer in five organs (stomach, colorectum, lung, breast and thyroid), which are the five most common sites of cancer in patients from Korea, at the regional cancer center in Jeonbuk National University Hospital between January 2007 and December 2009. The standardized incidence ratio (SIR) of SPC according to sex and site was calculated from 5,209 patients who were followed up to September 2017. General incidence was acquired from the National Cancer Registry of Republic of Korea. SPC occurred in 6.2% (323/5,209) of patients, and the incidence of SPC among the five major types of cancer was in the order of breast (8.8%, 46/524), colorectum (8.6%, 86/1,003), gastric (6.6%, 89/1,358), thyroid (4.7%, 67/1,437) and lung cancer (3.9%, 35/887). When all SPC sites were included, the SIRs of SPC in patients with colorectal cancer and breast cancer were >1.0 (1.21 and 1.66, respectively). Breast cancer and thyroid cancer exhibited a high site relationship (P<0.05), and colorectal cancer had a high site relationship with gastric cancer (P<0.05). The present study analyzed the incidence and pattern of SPC in patients with cancer who were diagnosed with primary carcinoma in five organs. The results of the study may be useful for effective follow-up and early detection of SPC in patients with cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Sung et al.)

Background and Aims: Propofol, a widely used sedative in GI endoscopic procedures, is associated with cardiorespiratory suppression. Remimazolam is a novel ultrashort-acting benzodiazepine sedative with rapid onset and minimal cardiorespiratory depression. This study compared the safety and efficacy of remimazolam and propofol during EUS procedures., Methods: A multicenter randomized controlled study was conducted between October 2022 and March 2023 in patients who underwent EUS procedures. Patients were randomly assigned to receive either remimazolam or propofol as a sedative agent. The primary endpoint was cardiorespiratory adverse events (AEs) during the procedure, including desaturation, respiratory depression, hypotension, and tachycardia. Secondary endpoints were the time to achieve sedation, recovery time, quality of sedation, pain at the injection site, and satisfaction of both endoscopists and patients., Results: Four hundred patients enrolled in the study: 200 received remimazolam (10.8 ± 7.7 mg) and 200 received propofol (88.0 ± 49.1 mg). For cardiorespiratory AEs, the remimazolam group experienced fewer occurrences than the propofol group (8.5% vs 16%, P = .022). A nonsignificant trend was found toward less oxygen desaturation (1.0% vs 3.5%, P = .09), respiratory depression (.5% vs 1.5%, P = .62), hypotension (2.5% vs 5.5%, P = .12), and tachycardia (4.5% vs 5.5%, P = .68) with remimazolam than with propofol. Remimazolam showed a shorter induction time than propofol while maintaining comparable awakening and recovery times. Injection site pain was significantly lower in the remimazolam group than in the propofol group. The remimazolam group demonstrated a significantly higher quality of sedation and satisfaction scores than the propofol group, as evaluated by both endoscopists and patients., Conclusions: Remimazolam was superior to propofol in terms of safety and efficacy during EUS examinations. (Clinical trial registration number: KCT 0007643.)., Competing Interests: Disclosure All authors disclosed no financial relationships. Research support for this study was provided by a National Research Foundation of Korea grant funded by the Korean government (MSIT) (no. RS-2023-00243402), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea (no. HI22C0474), and the Hana Pharm Co, Ltd., (Copyright © 2024. Published by Elsevier Inc.)

Rationale: Adenomatous polyposis (AP) is a genetic disorder characterized by the occurrence of numerous adenomatous polyps in the colon and rectum and can be classified into classical AP and attenuated AP (AAP). AAP is diagnosed when the number of observed adenomas is between 10 and 99. The detection of AAP is significantly increasing mainly due to the improvement of the imaging technique and application of the screening program for colorectal cancer detection. Currently, the germline variations of the APC and MUTYH genes are reported as the main cause of classical AP. However, the underlying genetic basis of AAP is not well understood. In this study, we report 2 cases of AAP with MSH6 variations., Patient Concerns: Both patients visited the hospital after multiple polyps were detected during colonoscopies conducted as part of their health checkups., Diagnoses: The 2 patients were diagnosed with AAP through colonoscopic examination at our hospital., Interventions: The 2 received genetic consultation; and, for follow-up purposes, both patients agreed to be tested for an underlying genetic condition through next generation sequencing. And germline MSH6 variations were detected in both AAP patients., Outcomes: There was no recurrence for both patients for 3 years follow-up., Lessons: Minor portion of AAP can cause by genetic mutation in MSH6, and further research is needed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Importance: Meticulous postoperative flap monitoring is essential for preventing flap failure and achieving optimal results in free flap operations, for which physical examination has remained the criterion standard. Despite the high reliability of physical examination, the requirement of excessive use of clinician time has been considered a main drawback., Objective: To develop an automated free flap monitoring system using artificial intelligence (AI), minimizing human involvement while maintaining efficiency., Design, Setting, and Participants: In this prognostic study, the designed system involves a smartphone camera installed in a location with optimal flap visibility to capture photographs at regular intervals. The automated program identifies the flap area, checks for notable abnormalities in its appearance, and notifies medical staff if abnormalities are detected. Implementation requires 2 AI-based models: a segmentation model for automatic flap recognition in photographs and a grading model for evaluating the perfusion status of the identified flap. To develop this system, flap photographs captured for monitoring were collected from patients who underwent free flap-based reconstruction from March 1, 2020, to August 31, 2023. After the 2 models were developed, they were integrated to construct the system, which was applied in a clinical setting in November 2023., Exposure: Conducting the developed automated AI-based flap monitoring system., Main Outcomes and Measures: Accuracy of the developed models and feasibility of clinical application of the system., Results: Photographs were obtained from 305 patients (median age, 62 years [range, 8-86 years]; 178 [58.4%] were male). Based on 2068 photographs, the FS-net program (a customized model) was developed for flap segmentation, demonstrating a mean (SD) Dice similarity coefficient of 0.970 (0.001) with 5-fold cross-validation. For the flap grading system, 11 112 photographs from the 305 patients were used, encompassing 10 115 photographs with normal features and 997 with abnormal features. Tested on 5506 photographs, the DenseNet121 model demonstrated the highest performance with an area under the receiver operating characteristic curve of 0.960 (95% CI, 0.951-0.969). The sensitivity for detecting venous insufficiency was 97.5% and for arterial insufficiency was 92.8%. When applied to 10 patients, the system successfully conducted 143 automated monitoring sessions without significant issues., Conclusions and Relevance: The findings of this study suggest that a novel automated system may enable efficient flap monitoring with minimal use of clinician time. It may be anticipated to serve as an effective surveillance tool for postoperative free flap monitoring. Further studies are required to verify its reliability.

The anti-inflammatory effects of supernatants produced from sprouted barley inoculated with Lactiplantibacillus plantarum KCTC3104 (Lp), Leuconostoc mesenteroides KCTC3530 (Lm), Latilactobacillus curvatus KCTC3767 (Lc), or a mixture of these lactic acid bacteria were investigated using RAW264.7 macrophages. BLp and BLc, the lyophilized supernatants of fermented sprouted barley inoculated with Lp and Lc, respectively, effectively reduced the nitric oxide (NO) levels hypersecreted by lipopolysaccharide (LPS)-stimulated RAW264.7 and LPS-stimulated Caco-2 cells. BLp and BLc effectively reduced the NO levels in LPS-stimulated RAW264.7 macrophages, and these effects tended to be concentration-dependent. BLc and BLp also exhibited strong DPPH radical scavenging activity and immunostimulatory effects. BLp and BLc significantly suppressed the levels of NO and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in LPS-stimulated RAW264.7 macrophages and LPS-stimulated Caco-2 cells, indicating their anti-inflammatory effects. These effects were greater than those of unfermented barley sprout (Bs). The functional components of Bs, BLp, and BLc were analyzed by HPLC, and it was found that lutonarin and saponarin were significantly increased in the fermented sprouted barley sample inoculated with Lp and Lc (BLp and BLc).

Males often strategically adjust the number of available sperm based on the social context (i.e. sperm priming response), but it remains unclear how environmental and genetic factors shape this adjustment. In freshwater ecosystems, high ambient temperatures often lead to isolated pools of hotter water in which inbreeding occurs. Higher water temperatures and inbreeding can impair fish development, potentially disrupting sperm production. We used guppies ( Poecilia reticulata ) to investigate how developmental temperature (26 °C, 30 °C) and male inbreeding status (inbred, outbred) influence their sperm priming response. We also tested if sperm priming was affected by whether the female was a relative (sister) and whether she was inbred or outbred. There was no effect of rearing temperature; male inbreeding status alone determined the number of available sperm in response to female presence, her inbreeding status, and her relatedness. Inbred males produced significantly more sperm in the presence of an unrelated, outbred female than when no female was present. Conversely, outbred males did not alter the number of sperm available in response to female presence or relatedness. Moreover, inbred males produced marginally more sperm when exposed to an unrelated female that was outbred rather than inbred, but there was no difference when exposed to an inbred female that was unrelated versus related. Together, a sperm priming response was only observed in inbred males when exposed to an outbred female. Outbred females in our study were larger than inbred females, suggesting that inbred males strategically allocated ejaculate resources toward females in better condition., Competing Interests: We declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology.)

Interstitial lung disease (ILD) is characterized by progressive pathological changes that require timely and accurate diagnosis. The early detection and progression assessment of ILD are important for effective management. This study introduces a novel quantitative evaluation method utilizing chest radiographs to analyze pixel-wise changes in ILD. Using a weakly supervised learning framework, the approach incorporates the contrastive unpaired translation model and a newly developed ILD extent scoring algorithm for more precise and objective quantification of disease changes than conventional visual assessments. The ILD extent score calculated through this method demonstrated a classification accuracy of 92.98% between ILD and normal classes. Additionally, using an ILD follow-up dataset for interval change analysis, this method assessed disease progression with an accuracy of 85.29%. These findings validate the reliability of the ILD extent score as a tool for ILD monitoring. The results of this study suggest that the proposed quantitative method may improve the monitoring and management of ILD.

When males compete, sexual selection favors reproductive traits that increase their mating or fertilization success (pre- and postcopulatory sexual selection). It is assumed that males face a trade-off between these 2 types of sexual traits because they both draw from the same pool of resources. Consequently, allocation into mate acquisition or ejaculation should create similar trade-offs with other key life history traits. Tests of these assumptions are exceedingly rare. Males only ejaculate after they mate, and the costs of ejaculation are therefore highly confounded with those of mating effort. Consequently, little is known about how each component of reproductive allocation affects a male's future performance. Here, we ran an experiment using a novel technique to distinguish the life history costs of mating effort and ejaculation for mosquitofish (Gambusia holbrooki). We compared manipulated males (mate without ejaculation), control males (mate and ejaculate), and naïve males (neither mate nor ejaculate) continuously housed with a female and 2 rival males. We assessed their growth, somatic maintenance, mating and fighting behavior, and sperm traits after 8 and 16 weeks. Past mating effort significantly lowered a male's future mating effort and growth, but not his sperm production, while past sperm release significantly lowered a male's future ejaculate quantity, but not his mating effort. Immune response was the only trait impacted by both past mating effort and past ejaculation. These findings challenge the assumption that male reproductive allocation draws from a common pool of resources to generate similar life history costs later in life. Instead, we provide clear evidence that allocation into traits under pre- and postcopulatory sexual selection have different trait-specific effects on subsequent male reproductive performance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: Post-cholecystectomy biliary strictures can be treated surgically or nonsurgically. Although endoscopic or percutaneous treatments are the preferred approaches, these methods are not feasible in cases in which complete stricture occlusion prevents the successful passage of a guidewire. The utility of magnetic compression anastomosis (MCA) in patients with post-cholecystectomy complete biliary obstruction that cannot be treated conventionally was evaluated., Methods: MCA was performed in 10 patients with post-cholecystectomy biliary strictures that did not resolve with conventional endoscopic or percutaneous treatment. One magnet was delivered through the percutaneous transhepatic biliary drainage tract, and another was advanced via ERCP of the common bile duct. After magnet approximation and recanalization, a fully covered self-expandable metal stent (FCSEMS) was placed for 3 months and then replaced for an additional 3 months. Stricture resolution was evaluated after FCSEMS removal., Results: Among the 10 patients who underwent MCA for post-cholecystectomy biliary stricture, the biliary injury was Strasberg type B in 2, type C in 3, and type E in 5. Recanalization was successful in all patients (technical success rate, 100%). The mean follow-up period after recanalization was 50.2 months (range, 13.2-116.8 months). Partial restenosis after MCA occurred in 2 patients at 24.1 and 1.6 months after stent removal. ERCP with FCSEMS placement resolved the recurrent stenosis in both patients., Conclusions: MCA is a useful nonsurgical alternative treatment for complete biliary obstruction after cholecystectomy that cannot be resolved by use of conventional methods., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Male-male contests for access to females or breeding resources are critical in determining male reproductive success. Larger males and those with more effective weaponry are more likely to win fights. However, even after controlling for such predictors of fighting ability, studies have reported a winner-loser effect: previous winners are more likely to win subsequent contests, while losers often suffer repeated defeats. While the effect of winning-losing is well-documented for the outcome of future fights, its effect on other behaviors (e.g. mating) remains poorly investigated. Here, we test whether a winning versus losing experience influenced subsequent behaviors of male mosquitofish ( Gambusia holbrooki ) toward rivals and potential mates. We housed focal males with either a smaller or larger opponent for 24 h to manipulate their fighting experience to become winners or losers, respectively. The focal males then underwent tests that required them to enter and swim through a narrow corridor to reach females, bypassing a cylinder that contained either a larger rival male (competitive scenario), a juvenile or was empty (non-competitive scenarios). The tests were repeated after 1 wk. Winners were more likely to leave the start area and to reach the females, but only when a larger rival was presented, indicating higher levels of risk-taking behavior in aggressive interactions. This winner-loser effect persisted for at least 1 wk. We suggest that male mosquitofish adjust their assessment of their own and/or their rival's fighting ability following contests in ways whose detection by researchers depends on the social context., Competing Interests: We declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology.)

Objective: To evaluate the clinical and imaging characteristics of SARS-CoV-2 breakthrough infection in hospitalized immunocompromised patients in comparison with immunocompetent patients., Materials and Methods: This retrospective study analyzed consecutive adult patients hospitalized for COVID-19 who received at least one dose of the SARS-CoV-2 vaccine at two academic medical centers between June 2021 and December 2022. Immunocompromised patients (with active solid organ cancer, active hematologic cancer, active immune-mediated inflammatory disease, status post solid organ transplantation, or acquired immune deficiency syndrome) were compared with immunocompetent patients. Multivariable logistic regression analysis was performed to evaluate the effect of immune status on severe clinical outcomes (in-hospital death, mechanical ventilation, or intensive care unit admission), severe radiologic pneumonia (≥ 25% of lung involvement), and typical CT pneumonia., Results: Of 2218 patients (mean age, 69.5 ± 16.1 years), 274 (12.4%), and 1944 (87.6%) were immunocompromised an immunocompetent, respectively. Patients with active solid organ cancer and patients status post solid organ transplantation had significantly higher risks for severe clinical outcomes (adjusted odds ratio = 1.58 [95% confidence interval {CI}, 1.01-2.47], P = 0.042; and 3.12 [95% CI, 1.47-6.60], P = 0.003, respectively). Patient status post solid organ transplantation and patients with active hematologic cancer were associated with increased risks for severe pneumonia based on chest radiographs (2.96 [95% CI, 1.54-5.67], P = 0.001; and 2.87 [95% CI, 1.50-5.49], P = 0.001, respectively) and for typical CT pneumonia (9.03 [95% CI, 2.49-32.66], P < 0.001; and 4.18 [95% CI, 1.70-10.25], P = 0.002, respectively)., Conclusion: Immunocompromised patients with COVID-19 breakthrough infection showed an increased risk of severe clinical outcome, severe pneumonia based on chest radiographs, and typical CT pneumonia. In particular, patients status post solid organ transplantation was specifically found to be associated with a higher risk of all three outcomes than hospitalized immunocompetent patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Purpose To develop an artificial intelligence (AI) system for humeral tumor detection on chest radiographs (CRs) and evaluate the impact on reader performance. Materials and Methods In this retrospective study, 14 709 CRs (January 2000 to December 2021) were collected from 13 468 patients, including CT-proven normal ( n = 13 116) and humeral tumor ( n = 1593) cases. The data were divided into training and test groups. A novel training method called false-positive activation area reduction (FPAR) was introduced to enhance the diagnostic performance by focusing on the humeral region. The AI program and 10 radiologists were assessed using holdout test set 1, wherein the radiologists were tested twice (with and without AI test results). The performance of the AI system was evaluated using holdout test set 2, comprising 10 497 normal images. Receiver operating characteristic analyses were conducted for evaluating model performance. Results FPAR application in the AI program improved its performance compared with a conventional model based on the area under the receiver operating characteristic curve (0.87 vs 0.82, P = .04). The proposed AI system also demonstrated improved tumor localization accuracy (80% vs 57%, P < .001). In holdout test set 2, the proposed AI system exhibited a false-positive rate of 2%. AI assistance improved the radiologists' sensitivity, specificity, and accuracy by 8.9%, 1.2%, and 3.5%, respectively ( P < .05 for all). Conclusion The proposed AI tool incorporating FPAR improved humeral tumor detection on CRs and reduced false-positive results in tumor visualization. It may serve as a supportive diagnostic tool to alert radiologists about humeral abnormalities. Keywords: Artificial Intelligence, Conventional Radiography, Humerus, Machine Learning, Shoulder, Tumor Supplemental material is available for this article. © RSNA, 2024.

Introduction: Pancreatic cancer cells generally accumulate large numbers of lipid droplets (LDs), which regulate lipid storage. To promote rapid diagnosis, an automatic pancreatic cancer cell recognition system based on a deep convolutional neural network was proposed in this study using quantitative images of LDs from stain-free cytologic samples by optical diffraction tomography., Methods: We retrieved 3D refractive index tomograms and reconstructed 37 optical images of one cell. From the four cell lines, the obtained fields were separated into training and test datasets with 10,397 and 3,478 images, respectively. Furthermore, we adopted several machine learning techniques based on a single image-based prediction model to improve the performance of the computer-aided diagnostic system., Results: Pancreatic cancer cells had a significantly lower total cell volume and dry mass than did normal pancreatic cells and were accompanied by greater numbers of lipid droplets (LDs). When evaluating multitask learning techniques utilizing the EfficientNet-b3 model through confusion matrices, the overall 2-category accuracy for cancer classification reached 96.7 %. Simultaneously, the overall 4-category accuracy for individual cell line classification achieved a high accuracy of 96.2 %. Furthermore, when we added the core techniques one by one, the overall performance of the proposed technique significantly improved, reaching an area under the curve (AUC) of 0.997 and an accuracy of 97.06 %. Finally, the AUC reached 0.998 through the ablation study with the score fusion technique., Discussion: Our novel training strategy has significant potential for automating and promoting rapid recognition of pancreatic cancer cells. In the near future, deep learning-embedded medical devices will substitute laborious manual cytopathologic examinations for sustainable economic potential., Competing Interests: Declaration of competing interest The authors declare no conflict of interest relevant to this work, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Conventional surgical site infection (SSI) surveillance is labour-intensive. We aimed to develop machine learning (ML) models for the surveillance of SSIs for colon surgery and to assess whether the ML could improve surveillance process efficiency., Methods: This study included cases who underwent colon surgery at a tertiary center between 2013 and 2014. Logistic regression and four ML algorithms including random forest (RF), gradient boosting (GB), and neural networks (NNs) with or without recursive feature elimination (RFE) were first trained on the entire cohort, and then re-trained on cases selected based on a previous rule-based algorithm. We assessed model performance based on the area under the curve (AUC), sensitivity, and positive predictive value (PPV). The estimated proportion of reduction in workload for chart review based on the ML models was evaluated and compared with the conventional method., Results: At a sensitivity of 95%, the NN with RFE using 29 variables had the best performance with an AUC of 0.963 and PPV of 21.1%. When combining both the rule-based algorithm and ML algorithms, the NN with RFE using 19 variables had a higher PPV (28.9%) than with the ML algorithm alone, which could decrease the number of cases requiring chart review by 83.9% compared with the conventional method., Conclusion: We demonstrated that ML can improve the efficiency of SSI surveillance for colon surgery by decreasing the burden of chart review while providing high sensitivity. In particular, the hybrid approach of ML with a rule-based algorithm showed the best performance in terms of PPV., (Copyright © 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: SMARCA4-deficient non-small cell lung carcinoma (SD-NSCLC) is a relatively rare tumor, which occurs in 5-10% of NSCLC. Based on World Health Organization thoracic tumor classification system, SMARCA4-deficient undifferentiated tumor (SD-UT) is recognized as a separate entity from SD-NSCLC. Differentiation between SD-NSCLC and SD-UT is often difficult due to shared biological continuum, but often required for choosing appropriate treatment regimen. Therefore, the aim of our study was to identify the clinicopathologic, computed tomography (CT), and positron emission tomography (PET)-CT imaging features of SD-NSCLC., Methods: Nine patients of pathologically confirmed SD-NSCLC were included in our analysis. We reviewed electronic medical records for clinical information, demographic features, CT, and PET-CT imaging features were analyzed., Results: Smoking history and male predominance are observed in all patients with SD-NSCLC (n=9). On CT, SD-NSCLC appeared as relatively well-defined masses with lobulated contour (n=8) and peripheral location (n=7). Invasion of adjacent pleura or chest wall (n=7) were frequently observed, regardless of small tumor size. Four cases showed lymph node metastases. Among nine patients, three patients showed multiple bone metastases, and one patient showed lung-to-lung metastases., Conclusions: In patient with SD-NSCLC, there was tendency for male smokers, peripheral location and invasion of adjacent pleural or chest wall invasion regardless of small tumor size, when compared to SD-UT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1606/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC., Methods: TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application., Results: Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001)., Conclusion: TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure., (© 2024. The Author(s).)

ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD + )-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer., (© 2024. The Author(s).)

Background : This study evaluated the effectiveness of short fully covered self-expanding metal stents (FCSEMS) with an anti-migration design in treating benign biliary strictures (BBS) not related to living donor liver transplantation (LDLT). Methods : A retrospective analysis was conducted on 75 patients who underwent FCSEMS insertion for BBS management. Stents were initially kept for 3 months and exchanged every 3 months until stricture resolution. Adverse events and stricture recurrence after FCSEMS removal were assessed during follow-up. Results : The study outcomes were technical success, stenosis resolution, and treatment failure. Technical success was 100%, with stricture resolution in 99% of patients. The mean onset time of BBS post-surgery was 4.4 years, with an average stent indwelling period of 5.5 months. Stricture recurrence occurred in 20% of patients, mostly approximately 18.8 months after stent removal. Early cholangitis and stent migration were noted in 3% and 4% of patients, respectively. Conclusions : This study concludes that short FCSEMS demonstrate high efficacy in the treatment of non-LDLT-related BBS, with a low incidence of interventions and complications. Although this is a single-center, retrospective study with a limited sample size, the findings provide preliminary evidence supporting the use of short FCSEMS as a primary treatment modality for BBS. To substantiate these findings, further research involving multicenter studies is recommended to provide additional validation and a broader perspective.

To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age < 60 years, presence of lymph node metastasis, and no adjuvant chemotherapy were significantly associated with early recurrence (all P < 0.05). The proportion of patients with high S100A2 expression (H-score > 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score < 5 (41.5% vs. 63.3%, P = 0.012). The median overall survival of patients with higher S100A2 expression was longer than those with lower S100A2 expression (median 30.1 months vs. 24.2 months, P = 0.003). High-risk factors for early recurrence after surgery for pancreatic cancer include young age, lymph node metastasis, and no adjuvant therapy. Neoadjuvant treatment or intensive adjuvant therapy after surgery may improve the prognosis of patients with high-risk signatures. In patients who receive adjuvant therapy, high S100A2 expression is a good predictor., (© 2024. The Author(s).)

Background and Aims: Pancreatic steatosis (PS) may be a risk factor for acute pancreatitis. Whether it is also a risk factor for post-ERCP pancreatitis (PEP) has not been evaluated. This study aimed to determine the impact of PS on PEP development., Methods: This multicenter prospective trial enrolled 786 consecutive patients who underwent contrast-enhanced abdominal CT and subsequent first-time ERCP. PS was evaluated based on pancreatic attenuation on unenhanced CT images. The risk of PS for the development of PEP was evaluated using a logistic regression model., Results: Of 527 patients included in the study, 157 (29.8%) had PS and 370 (70.2%) did not. At 24 hours after ERCP, there was a significant difference in the PEP identified in 22 patients (14.0%) in the PS group and 23 patients (6.2%) in the "no PS" (NPS) group (P = .017). Diabetes and hypertension were more common in the PS group than in the NPS group; no differences in dyslipidemia were found. Patients with PS had a higher risk for the development of PEP than those with NPS (odds ratio, 2.09; 95% confidence interval, 1.08-4.03). No other variables were identified as risk factors for PEP., Conclusions: PS is a significant risk factor for PEP for which preventive measures should be considered. Standardized measurement protocols to assess PS by CT are needed. (Clinical trial registration number: KCT0006068.)., Competing Interests: Disclosure All authors disclosed no financial relationships. Research support for this study was provided by a National Research Foundation of Korea grant funded by the Korean government (Ministry of Science and ICT, no. 2022R1C1C1006242)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity., Methods: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples., Results: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep&#95;VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep&#95;VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data., Conclusions: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets., (© 2024. The Author(s).)

We propose a hybrid technique that employs artificial intelligence (AI)-based segmentation and machine learning classification using multiple features extracted from the foveal avascular zone (FAZ)-a retinal biomarker for Alzheimer's disease-to improve the disease diagnostic performance. Imaging data of optical coherence tomography angiography from 37 patients with Alzheimer's disease and 48 healthy controls were investigated. The presence or absence of brain amyloids was confirmed using amyloid positron emission tomography. In the superficial capillary plexus of the angiography scans, the FAZ was automatically segmented using an AI method to extract multiple biomarkers (area, solidity, compactness, roundness, and eccentricity), which were paired with clinical data (age and sex) as common correction variables. We used a light-gradient boosting machine (a light-gradient boosting machine is a machine learning algorithm based on trees utilizing gradient boosting) to diagnose Alzheimer's disease by integrating the corresponding multiple radiomic biomarkers. Fivefold cross-validation was applied for analysis, and the diagnostic performance for Alzheimer's disease was determined by the area under the curve. The proposed hybrid technique achieved an area under the curve of [Formula: see text]%, outperforming the existing single-feature (area) criteria by over 13%. Furthermore, in the holdout test set, the proposed technique exhibited a 14% improvement compared to single features, achieving an area under the curve of 72.0± 4.8%. Based on these facts, we have demonstrated the effectiveness of our technology in achieving significant performance improvements in FAZ-based Alzheimer's diagnosis research through the use of multiple radiomic biomarkers (area, solidity, compactness, roundness, and eccentricity)., (© 2024. The Author(s).)