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Fabricating a robust interfacial layer on the lithium metal anode to isolate it from liquid electrolyte is vital to restrain the rapid degradation of a lithium metal battery. Here, we report that the solution-processed metal chloride perovskite thin film can be coated onto the lithium metal surface as a robust interfacial layer to shield the lithium metal from liquid electrolyte. Via phase analysis and density functional theory calculations, we demonstrate that the perovskite layer can allow fast lithium ion shuttle under a low energy barrier of 0.45 eV without the collapse of framework. Such perovskite modification can realize stable cycling of LiCoO 2 |Li cells with an areal capacity of 2.8 mAh cm −2 using thin lithium metal foil (50 μm) and limited electrolyte (20 μl mAh −1 ) for over 100 cycles at 0.5 C. The metal chloride perovskite protection strategy could open a promising avenue for advanced lithium metal batteries. Metal halide perovskite is well-known for the high absorption coefficient; however, its Li-ion transport property remains poorly explored. Here the authors coat an ion conducting metal chloride perovskite interfacial layer on the Li metal anode, enabling good battery performance.

Context.— Gastrointestinal (GI) and pancreatobiliary tracts contain a variety of neuroendocrine cells that constitute a diffuse endocrine system. Neuroendocrine tumors (NETs) from these organs are heterogeneous tumors with diverse clinical behaviors. Recent improvements in the understanding of NETs from the GI and pancreatobiliary tracts have led to more-refined definitions of the clinicopathologic characteristics of these tumors. Under the 2010 World Health Organization classification scheme, NETs are classified as grade (G) 1 NETs, G2 NETs, neuroendocrine carcinomas, and mixed adenoneuroendocrine carcinomas. Histologic grades are dependent on mitotic counts and the Ki-67 labeling index. Several new issues arose after implementation of the 2010 World Health Organization classification scheme, such as issues with well-differentiated NETs with G3 Ki-67 labeling index and the evaluation of mitotic counts and Ki-67 labeling. Hereditary syndromes, including multiple endocrine neoplasia type 1 syndrome, von Hippel-Lindau syndrome, neurofibromatosis 1, and tuberous sclerosis, are related to NETs of the GI and pancreatobiliary tracts. Several prognostic markers of GI and pancreatobiliary tract NETs have been introduced, but many of them require further validation. Objective.— To understand clinicopathologic characteristics of NETs from the GI and pancreatobiliary tracts. Data Sources.— PubMed (US National Library of Medicine) reports were reviewed. Conclusions.— In this review, we briefly summarize recent developments and issues related to NETs of the GI and pancreatobiliary tracts.

Inorganic superionic conductors possess high ionic conductivity and excellent thermal stability but their poor interfacial compatibility with lithium metal electrodes precludes application in all-solid-state lithium metal batteries 1 , 2 . Here we report a LaCl 3 -based lithium superionic conductor possessing excellent interfacial compatibility with lithium metal electrodes. In contrast to a Li 3 MCl 6 (M = Y, In, Sc and Ho) electrolyte lattice 3 – 6 , the UCl 3 -type LaCl 3 lattice has large, one-dimensional channels for rapid Li + conduction, interconnected by La vacancies via Ta doping and resulting in a three-dimensional Li + migration network. The optimized Li 0.388 Ta 0.238 La 0.475 Cl 3 electrolyte exhibits Li + conductivity of 3.02 mS cm −1 at 30 °C and a low activation energy of 0.197 eV. It also generates a gradient interfacial passivation layer to stabilize the Li metal electrode for long-term cycling of a Li–Li symmetric cell (1 mAh cm −2 ) for more than 5,000 h. When directly coupled with an uncoated LiNi 0.5 Co 0.2 Mn 0.3 O 2 cathode and bare Li metal anode, the Li 0.388 Ta 0.238 La 0.475 Cl 3 electrolyte enables a solid battery to run for more than 100 cycles with a cutoff voltage of 4.35 V and areal capacity of more than 1 mAh cm −2 . We also demonstrate rapid Li + conduction in lanthanide metal chlorides (LnCl 3 ; Ln = La, Ce, Nd, Sm and Gd), suggesting that the LnCl 3 solid electrolyte system could provide further developments in conductivity and utility. A LaCl 3 -based lithium superionic conductor is developed that has excellent interfacial compatibility with lithium metal electrodes, with its optimized Li 0.388 Ta 0.238 La 0.475 Cl 3 electrolyte exhibiting good Li + conductivity and low activation energy.

Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.

To investigate the applicability of ChatGPT, in answering conceptual and non-conceptual questions related to urodynamic quality control, including trace analysis and report interpretation. Utilizing a structured questioning approach, the study employs ChatGPT3.5 and ChatGPT4.0. Questions are mainly divided into conceptual questions and non-conceptual questions related to urodynamic quality control, and trace analysis. Evaluation criteria include alignment with the “Good Urodynamic Practice” guideline and literature. ChatGPT excels in delivering hierarchical responses to conceptual questions, providing comprehensive insights in a structured format. Challenges arise in offering specific references to published literature, with a 50% accuracy rate in 10 basic conceptual questions. For non-conceptual urodynamic quality control questions, ChatGPT achieves a 50% accuracy rate, accurately addressing various aspects. However, in both cases, we found no statistically significant difference in accuracy rate between conceptual questions and non-conceptual questions. However, challenges persist when questions are linked to recent literature, leading to misunderstandings and inaccurate responses. Regarding urodynamics trace interpretation, ChatGPT states its inability to directly analyze images, emphasizing reliance on qualified healthcare professionals for detailed clinical analysis. This study preliminarily demonstrates ChatGPT’s limited performance in answering conceptual and non-conceptual questions related to urodynamic quality control, without finding significant differences between the two kinds of questions. Additionally, ChatGPT’s capability to process image data for urodynamic trace analysis is non-existent. The study suggests that ChatGPT only has the potential to serve as an \"electronic dictionary” to aid urodynamic operators, but it should be noted that this study cannot prove ChatGPT’s ability to change the overall quality of urodynamic examinations.

ObjectivesTo identify CT features distinguishing neuroendocrine carcinomas (NECs) of pancreas from well-differentiated neuroendocrine tumors (NETs) according to the World Health Organization 2017 and 2019 classification systems.MethodsThis retrospective study included 69 patients with pathologically confirmed pancreatic neuroendocrine neoplasms who underwent dynamic CT (17, 17, 18, and 17 patients for well-differentiated grade 1, 2, 3 NET and NEC, respectively). CT was used to perform qualitative analysis (component, homogeneity, calcification, peripancreatic infiltration, main pancreatic ductal dilatation, bile duct dilatation, intraductal extension, and vascular invasion) and quantitative analysis (interface between tumor and parenchyma [delta], arterial enhancement ratio [AER], portal enhancement ratio [PER], and dynamic enhancement pattern). Uni- and multivariate logistic regression analyses were performed to identify features indicating NEC. Optimal cutoff values for enhancement ratios were determined.ResultsNECs demonstrated significantly higher frequencies of main pancreatic ductal dilatation, bile duct dilatation, vascular invasion, and significantly lower delta (i.e., lower conspicuity), AER, and PER than well-differentiated NET (p < 0.05). On multivariate analysis, PER was the only independent factor selected by the model for differentiation of NEC from well-differentiated NET (odds ratio, < 0.001; 95% confidence interval [CI], < 0.001–0.012). PER < 0.8 showed the sensitivity of 94.1% (95% CI, 71.3–99.9) and the specificity of 88.5% (95% CI, 76.6–95.6). When three significant CT features were combined, the sensitivity and specificity for diagnosing NEC were 88.2% and 88.5%, respectively.ConclusionsTumor-parenchyma enhancement ratio in portal phase is a useful CT feature to distinguish NECs from well-differentiated NETs. Combining qualitative and quantitative CT features may aid in achieving good diagnostic accuracy in the differentiation between NEC and well-differentiated NET.Key Points• Neuroendocrine carcinoma of the pancreas should be distinguished from well-differentiated neuroendocrine tumor in line with the revised grading and staging system.• Neuroendocrine carcinoma of the pancreas can be differentiated from well-differentiated neuroendocrine tumor on dynamic CT based on assessment of the portal enhancement ratio, arterial enhancement ratio, tumor conspicuity, dilatation of the main pancreatic duct or bile duct, and vascular invasion.• Tumor-parenchyma enhancement ratio in portal phase of dynamic CT is a useful feature, which may help to distinguish neuroendocrine carcinoma from well-differentiated neuroendocrine tumor of the pancreas.

Although venous invasion (VI) is a poor prognostic factor for patients with pancreatobiliary tract cancers, its histopathologic characteristics have not been well described. We evaluated the patterns of VI and the added benefit provided by CD31, desmin, and dual CD31‒desmin immunolabeling for identification of VI. We included 120 surgically resected pancreatobiliary tract cancer cases—59 cases as a test set with known VI and 61 cases as a validation set without information of VI. VI was classified into three patterns: intraepithelial neoplasia-like (IN-like), conventional, and destructive. Hematoxylin and eosin (H&E) staining and CD31, desmin, and dual CD31‒desmin immunolabeling were performed. Foci number and patterns of VI were compared with the test and validation sets. More foci of VI were detected by single CD31 ( P = 0.022) than H&E staining in the test set. CD31 immunolabeling detected more foci of the conventional pattern of VI, and desmin immunolabeling detected more foci of the destructive pattern (all, P < 0.001). Dual CD31‒desmin immunolabeling identified more foci of VI ( P = 0.012) and specifically detected more foci of IN-like ( P = 0.045) and destructive patterns ( P < 0.001) than H&E staining in the validation set. However, dual CD31‒desmin immunolabeling was not helpful for detecting the conventional pattern of VI in the validation set. Patients with VI detected by dual CD31‒desmin immunolabeling had shorter disease-free survival ( P <0.001) than those without VI. VI detected by dual CD31‒desmin immunolabeling was a worse prognostic indicator ( P = 0.009). More foci of VI could be detected with additional single CD31 or dual CD31‒desmin immunolabeling. The precise evaluation of VI with dual CD31‒desmin immunolabeling can provide additional prognostic information for patients with surgically resected pancreatobiliary tract cancers.

The diagnosis and management of pancreatic neuroendocrine neoplasms (NENs) have evolved significantly in recent years. There are several diagnostic and therapeutic challenges and controversies regarding the management of these lesions. In this review, we focus on the recent significant changes and controversial issues regarding the diagnosis and management of NENs and discuss the role of imaging in the multidisciplinary team approach.

Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration.

BackgroundCancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) contribute to an impaired functionality of natural killer (NK) cells that have emerged as a promising therapeutic modality. The interaction between CAFs and NK cells within the TME exerts major inhibitory effects on immune responses, indicating CAF-targeted therapies as potential targets for effective NK-mediated cancer killing.MethodsTo overcome CAF-induced NK dysfunction, we selected an antifibrotic drug, nintedanib, for synergistic therapeutic combination. To evaluate synergistic therapeutic efficacy, we established an in vitro 3D Capan2/patient-derived CAF spheroid model or in vivo mixed Capan2/CAF tumor xenograft model. The molecular mechanism of NK-mediated synergistic therapeutic combination with nintedanib was revealed through in vitro experiments. In vivo therapeutic combination efficacy was subsequently evaluated. Additionally, the expression score of target proteins was measured in patient-derived tumor sections by the immunohistochemical method.ResultsNintedanib blocked the platelet-derived growth factor receptor β (PDGFRβ) signaling pathway and diminished the activation and growth of CAFs, markedly reducing CAF-secreted IL-6. Moreover, coadministration of nintedanib improved the mesothelin (MSLN) targeting chimeric antigen receptor-NK-mediated tumor killing abilities in CAF/tumor spheroids or a xenograft model. The synergistic combination resulted in intense NK infiltration in vivo. Nintedanib alone exerted no effects, whereas blockade of IL-6 trans-signaling ameliorated the function of NK cells. The combination of the expression of MSLN and the PDGFRβ+-CAF population area, a potential prognostic/therapeutic marker, was associated with inferior clinical outcomes.ConclusionOur strategy against PDGFRβ+-CAF-containing pancreatic cancer allows improvements in the therapy of pancreatic ductal adenocarcinoma.