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PURPOSE: Quantitative digital subtraction angiography (qDSA) has been proposed to quantify blood velocity for monitoring treatment progress during blood flow altering interventions. The method requires high frame rate imaging [~ 30 frame per second (fps)] to capture temporal dynamics. This work investigates performance of qDSA in low radiation dose acquisitions to facilitate clinical translation. MATERIALS AND METHODS: Velocity quantification accuracy was evaluated at five radiation dose rates in vitro and in vivo. Angiographic technique ranged from 30 fps digital subtraction angiography ( 29.3 ± 1.7 mGy / s at the interventional reference point) down to a 30 fps protocol at 23% higher radiation dose per frame than fluoroscopy ( 1.1 ± 0.2 mGy / s ). The in vitro setup consisted of a 3D-printed model of a swine hepatic arterial tree connected to a pulsatile displacement pump. Five different flow rates (3.5-8.8 mL/s) were investigated in vitro. Angiography-based fluid velocity measurements were compared across dose rates using ANOVA and Bland-Altman analysis. The experiment was then repeated in a swine study (n = 4). RESULTS: Radiation dose rate reductions for the lowest dose protocol were 99% and 96% for the phantom and swine study, respectively. No significant difference was found between angiography-based velocity measurements at different dose rates in vitro or in vivo. Bland-Altman analysis found little bias for all lower-dose protocols (range: [- 0.1, 0.1] cm/s), with the widest limits of agreement ([- 3.3, 3.5] cm/s) occurring at the lowest dose protocol. CONCLUSIONS: This study demonstrates the feasibility of quantitative blood velocity measurements from angiographic images acquired at reduced radiation dose rates.
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Angiografia Digital , Doses de Radiação , Animais , Angiografia Digital/métodos , Suínos , Velocidade do Fluxo Sanguíneo , Artéria Hepática/diagnóstico por imagem , Imagens de FantasmasRESUMO
PURPOSE: To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an ex vivo swine model. METHODS: An ex vivo model was created to simulate histotripsy treatment of solid organs through gas-filled bowel. Spherical 2.5 cm histotripsy treatments were performed in agar phantoms for each of five treatment groups: 1) control with no overlying bowel (n = 6), 2) bowel 0 cm above phantom (n = 6), 3) bowel 1 cm above phantom (n = 6), 4) bowel 2 cm above phantom (n = 6), and 5) bowel 0 cm above the phantom with increased treatment amplitude (n = 6). Bowel was inspected for gross and microscopic damage, and treatment zones were measured. A ray-tracing simulation estimated the percentage of therapeutic beam path blockage by bowel in each scenario. RESULTS: All histotripsy treatments through partial blockage were successful (24/24). No visible or microscopic damage was observed to intervening bowel. Partial blockage resulted in a small increase in treatment volume compared to controls (p = 0.002 and p = 0.036 for groups with bowel 0 cm above the phantom, p > 0.3 for bowel 1 cm and 2 cm above the phantom). Gas-filled bowel was estimated to have blocked 49.6%, 35.0%, and 27.3% of the therapeutic beam at 0, 1, and 2 cm, respectively. CONCLUSION: Histotripsy has the potential to be applied through partial gas blockage of the therapeutic beam path, as shown by this ex vivo small bowel model. Further work in an in vivo survival model appears indicated.
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Intestino Delgado , Animais , Suínos , GasesRESUMO
BACKGROUND: The learning curve in minimally invasive surgery (MIS) is lengthened compared to open surgery. It has been reported that structured feedback and training in teams of two trainees improves MIS training and MIS performance. Annotation of surgical images and videos may prove beneficial for surgical training. This study investigated whether structured feedback and video debriefing, including annotation of critical view of safety (CVS), have beneficial learning effects in a predefined, multi-modal MIS training curriculum in teams of two trainees. METHODS: This randomized-controlled single-center study included medical students without MIS experience (n = 80). The participants first completed a standardized and structured multi-modal MIS training curriculum. They were then randomly divided into two groups (n = 40 each), and four laparoscopic cholecystectomies (LCs) were performed on ex-vivo porcine livers each. Students in the intervention group received structured feedback after each LC, consisting of LC performance evaluations through tutor-trainee joint video debriefing and CVS video annotation. Performance was evaluated using global and LC-specific Objective Structured Assessments of Technical Skills (OSATS) and Global Operative Assessment of Laparoscopic Skills (GOALS) scores. RESULTS: The participants in the intervention group had higher global and LC-specific OSATS as well as global and LC-specific GOALS scores than the participants in the control group (25.5 ± 7.3 vs. 23.4 ± 5.1, p = 0.003; 47.6 ± 12.9 vs. 36 ± 12.8, p < 0.001; 17.5 ± 4.4 vs. 16 ± 3.8, p < 0.001; 6.6 ± 2.3 vs. 5.9 ± 2.1, p = 0.005). The intervention group achieved CVS more often than the control group (1. LC: 20 vs. 10 participants, p = 0.037, 2. LC: 24 vs. 8, p = 0.001, 3. LC: 31 vs. 8, p < 0.001, 4. LC: 31 vs. 10, p < 0.001). CONCLUSIONS: Structured feedback and video debriefing with CVS annotation improves CVS achievement and ex-vivo porcine LC training performance based on OSATS and GOALS scores.
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Colecistectomia Laparoscópica , Competência Clínica , Gravação em Vídeo , Colecistectomia Laparoscópica/educação , Humanos , Suínos , Animais , Feminino , Masculino , Curva de Aprendizado , Currículo , Adulto , Estudantes de Medicina , Feedback Formativo , Adulto Jovem , RetroalimentaçãoRESUMO
Plastics are complex chemical mixtures of polymers and various intentionally and nonintentionally added substances. Despite the well-established links between certain plastic chemicals (bisphenols and phthalates) and adverse health effects, the composition and toxicity of real-world mixtures of plastic chemicals are not well understood. To assess both, we analyzed the chemicals from 36 plastic food contact articles from five countries using nontarget high-resolution mass spectrometry and reporter-gene assays for four nuclear receptors that represent key components of the endocrine and metabolic system. We found that chemicals activating the pregnane X receptor (PXR), peroxisome proliferator receptor γ (PPARγ), estrogen receptor α (ERα), and inhibiting the androgen receptor (AR) are prevalent in plastic packaging. We detected up to 9936 chemical features in a single product and found that each product had a rather unique chemical fingerprint. To tackle this chemical complexity, we used stepwise partial least-squares regressions and prioritized and tentatively identified the chemical features associated with receptor activity. Our findings demonstrate that most plastic food packaging contains endocrine- and metabolism-disrupting chemicals. Since samples with fewer chemical features induce less toxicity, chemical simplification is key to producing safer plastic packaging.
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Disruptores Endócrinos , Embalagem de Alimentos , Polímeros , Disruptores Endócrinos/química , Disruptores Endócrinos/farmacologia , PlásticosRESUMO
G protein-coupled receptors (GPCRs) are central mediators of cell signaling and physiological function. Despite their biological significance, GPCRs have not been widely studied in the field of toxicology. Herein, we investigated these receptors as novel targets of plastic chemicals using a high-throughput drug screening assay with 126 human non-olfactory GPCRs. In a first-pass screen, we tested the activity of triphenol phosphate, bisphenol A, and diethyl phthalate, as well as three real-world mixtures of chemicals extracted from plastic food packaging covering all major polymer types. We found 11 GPCR-chemical interactions, of which the chemical mixtures exhibited the most robust activity at adenosine receptor 1 (ADORA1) and melatonin receptor 1 (MTNR1A). We further confirm that polyvinyl chloride and polyurethane products contain ADORA1 or MTNRA1 agonists using a confirmatory secondary screen and pharmacological knockdown experiments. Finally, an analysis of the associated gene ontology terms suggests that ADORA1 and MTNR1A activation may be linked to downstream effects on circadian and metabolic processes. This work highlights that signaling disruption caused by plastic chemicals is broader than that previously believed and demonstrates the relevance of nongenomic pathways, which have, thus far, remained unexplored.
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Receptores Acoplados a Proteínas G , Transdução de Sinais , Humanos , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Ensaios de Triagem em Larga Escala , PolímerosRESUMO
Data on MP in aquatic environments have low resolution in space and time. Scaling up sampling and increasing analysis throughput are the main bottlenecks. We combined two approaches: an uncrewed surface vehicle (USV) and near infrared hyperspectral imaging (NIR-HSI) for sampling and analysis of MP > 300 µm. We collected 35 water samples over 4 d in a coastal area. Samples were analyzed using NIR-HSI and Fourier transform infrared spectroscopy (FTIR). Spiked samples were used to determine recovery. We conclude that using a USV can mitigate issues of traditional trawls like scalability, repeatability, and contamination. NIR-HSI detects more polyethylene but less polypropylene than FTIR analysis and reduces analysis time significantly. Highly variable concentrations were found at both sampling locations, with mean MP concentration of 0.28 and 0.01 MP m-3 for location A and B respectively. USV sampling in tandem with NIR-HSI is an effective analytical pipeline for MP monitoring.
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Microplásticos , Poluentes Químicos da Água , Microplásticos/análise , Plásticos , Imageamento Hiperespectral , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodosRESUMO
BACKGROUND: MAR algorithms have not been productized in interventional imaging because they are too time-consuming. Application of a beam hardening filter can mitigate metal artifacts and doesn't increase computational burden. We evaluate the ability to reduce metal artifacts of a 0.5 mm silver (Ag) additional filter in a Multidetector Computed Tomography (MDCT) scanner during CT-guided biopsy procedures. METHODS: A biopsy needle was positioned inside the lung field of an anthropomorphic phantom (Lungman, Kyoto Kagaku, Kyoto, Japan). CT acquisitions were performed with beam energies of 100 kV, 120 kV, 135 kV, and 120 kV with the Ag filter and reconstructed using a filtered back projection algorithm. For each measurement, the CTDIvol was kept constant at 1 mGy. Quantitative profiles placed in three regions of the artifact (needle, needle tip, and trajectory artifacts) were used to obtain metrics (FWHM, FWTM, width at - 100 HU, and absolute error in HU) to evaluate the blooming artifact, artifact width, change in CT number, and artifact range. An image quality analysis was carried out through image noise measurement. A one-way analysis of variance (ANOVA) test was used to find significant differences between the conventional CT beam energies and the Ag filtered 120 kV beam. RESULTS: The 120 kV-Ag is shown to have the shortest range of artifacts compared to the other beam energies. For needle tip and trajectory artifacts, a significant reduction of - 53.6% (p < 0.001) and - 48.7% (p < 0.001) in the drop of the CT number was found, respectively, in comparison with the reference beam of 120 kV as well as a significant decrease of up to - 34.7% in the artifact width (width at - 100 HU, p < 0.001). Also, a significant reduction in the blooming artifact of - 14.2% (FWHM, p < 0.001) and - 53.3% (FWTM, p < 0.001) was found in the needle artifact. No significant changes (p > 0.05) in image noise between the conventional energies and the 120 kV-Ag were found. CONCLUSIONS: A 0.5 mm Ag additional MDCT filter demonstrated consistent metal artifact reduction generated by the biopsy needle. This reduction may lead to a better depiction of the target and surrounding structures while maintaining image quality.
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PURPOSE: Histotripsy is a nonionizing, noninvasive, and nonthermal focal tumor therapy. Cone-beam computed tomography (CBCT) guidance was developed for targeting tumors not visible on ultrasound. This approach assumes cavitation is formed at the geometrical focal point of the therapy transducer. In practice, the exact location might vary slightly between transducers. In this study, we present a phantom with an embedded target to evaluate CBCT-guided histotripsy accuracy and assess the completeness of treatments. METHODS: Spherical (2.8 cm) targets with alternating layers of agar and radiopaque barium were embedded in larger phantoms with similar layers. The layer geometry was designed so that targets were visible on pre-treatment CBCT scans. The actual histotripsy treatment zone was visualized via the mixing of adjacent barium and agar layers in post-treatment CBCT images. CBCT-guided histotripsy treatments of the targets were performed in six phantoms. Offsets between planned and actual treatment zones were measured and used for calibration refinement. To measure targeting accuracy after calibration refinement, six additional phantoms were treated. In a separate investigation, two groups (N = 3) of phantoms were treated to assess visualization of incomplete treatments ("undertreatment" group: 2 cm treatment within 2.8 cm tumor, "mistarget" group: 2.8 cm treatment intentionally shifted laterally). Treatment zones were segmented (3D Slicer 5.0.3), and the centroid distance between the prescribed target and actual treatment zones was quantified. RESULTS: In the calibration refinement group, a 2 mm offset in the direction of ultrasound propagation (Z) was measured. After calibration refinement, the centroid-to-centroid distance between prescribed and actual treatment volumes was 0.5 ± 0.2 mm. Average difference between the prescribed and measured treatment sizes in the incomplete treatment groups was 0.5 ± 0.7 mm. In the mistarget group, the distance between prescribed and measured shifts was 0.2 ± 0.1 mm. CONCLUSION: The proposed prototype phantom allowed for accurate measurement of treatment size and location, and the CBCT visible target provided a simple way to detect misalignments for preliminary quality assurance of CBCT-guided histotripsy.
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Tomografia Computadorizada de Feixe Cônico , Imagens de Fantasmas , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapiaRESUMO
At the central workplace of the surgeon the digitalization of the operating room has particular consequences for the surgical work. Starting with intraoperative cross-sectional imaging and sonography, through functional imaging, minimally invasive and robot-assisted surgery up to digital surgical and anesthesiological documentation, the vast majority of operating rooms are now at least partially digitalized. The increasing digitalization of the whole process chain enables not only for the collection but also the analysis of big data. Current research focuses on artificial intelligence for the analysis of intraoperative data as the prerequisite for assistance systems that support surgical decision making or warn of risks; however, these technologies raise new ethical questions for the surgical community that affect the core of surgical work.
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Inteligência Artificial , Salas Cirúrgicas , Humanos , Cirurgia Assistida por Computador/ética , Cirurgia Assistida por Computador/métodos , Cirurgia Assistida por Computador/instrumentação , Procedimentos Cirúrgicos Robóticos/éticaRESUMO
OBJECTIVE: Evaluation of the benefits of a virtual reality (VR) environment with a head-mounted display (HMD) for decision-making in liver surgery. BACKGROUND: Training in liver surgery involves appraising radiologic images and considering the patient's clinical information. Accurate assessment of 2D-tomography images is complex and requires considerable experience, and often the images are divorced from the clinical information. We present a comprehensive and interactive tool for visualizing operation planning data in a VR environment using a head-mounted-display and compare it to 3D visualization and 2D-tomography. METHODS: Ninety medical students were randomized into three groups (1:1:1 ratio). All participants analyzed three liver surgery patient cases with increasing difficulty. The cases were analyzed using 2D-tomography data (group "2D"), a 3D visualization on a 2D display (group "3D") or within a VR environment (group "VR"). The VR environment was displayed using the "Oculus Rift ™" HMD technology. Participants answered 11 questions on anatomy, tumor involvement and surgical decision-making and 18 evaluative questions (Likert scale). RESULTS: Sum of correct answers were significantly higher in the 3D (7.1 ± 1.4, p < 0.001) and VR (7.1 ± 1.4, p < 0.001) groups than the 2D group (5.4 ± 1.4) while there was no difference between 3D and VR (p = 0.987). Times to answer in the 3D (6:44 ± 02:22 min, p < 0.001) and VR (6:24 ± 02:43 min, p < 0.001) groups were significantly faster than the 2D group (09:13 ± 03:10 min) while there was no difference between 3D and VR (p = 0.419). The VR environment was evaluated as most useful for identification of anatomic anomalies, risk and target structures and for the transfer of anatomical and pathological information to the intraoperative situation in the questionnaire. CONCLUSIONS: A VR environment with 3D visualization using a HMD is useful as a surgical training tool to accurately and quickly determine liver anatomy and tumor involvement in surgery.
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Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Realidade Virtual , Humanos , Tomografia Computadorizada por Raios X/métodos , Feminino , Masculino , Hepatectomia/métodos , Hepatectomia/educação , Adulto , Adulto Jovem , Tomada de Decisão Clínica , Interface Usuário-Computador , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/diagnóstico por imagemRESUMO
Plastic ingestion in birds is a widespread phenomenon of increasing concern. However, little is known about how exposure to microplastics (MP) affects the health of birds. In other organisms, MP exposure alters lipid metabolism and composition. If also true in birds, this could affect their fitness, especially since birds heavily rely on lipids during migration and egg production. Therefore, the aim of this study was to determine if ingestion of MP (polypropylene and polyethylene collected in nature) in two size ranges, large (3 mm) and small (<125 µm), affects lipid metabolism in the Japanese quail (Coturnix japonica). We orally exposed 55 one-week-old quail during 5 weeks to a total of 600 mg of MP in sizes of either large, small, or a mixture of both. After the exposure period, females fed small MP had higher liver masses compared to control females (on average ± SD, 8.95 ± 2.3 g vs. 6.34 ± 1.0 g), while liver lipid content did not differ in either males or females. The levels of monounsaturated fatty acids were lower in females exposed to large MP and the mixture of both MP sizes compared to controls. Females exposed to MP also had different levels of oleic- (18:1) and palmitoleic (16:1) acid compared to controls dependent on MP size. Exposure to small MP increased levels of palmitic- (16:0) and palmitoleic (16:1) acid in both males and females suggesting a possible increase in de novo fatty acid synthesis. Taken together, our results point towards a sex-specific sensitivity to MP as well as size-dependent MP effects on lipid metabolism in birds. Disruption of fatty acid composition could affect important life stages in female birds, such as migration and egg-laying. We stress the importance of further research focused on determining the mechanisms of action of MP on lipid metabolism.
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Coturnix , Ácidos Graxos , Animais , Masculino , Feminino , Ácidos Graxos/metabolismo , Microplásticos/metabolismo , Plásticos/toxicidade , Plásticos/metabolismo , Tamanho da PartículaRESUMO
PURPOSE: For the modeling, execution, and control of complex, non-standardized intraoperative processes, a modeling language is needed that reflects the variability of interventions. As the established Business Process Model and Notation (BPMN) reaches its limits in terms of flexibility, the Case Management Model and Notation (CMMN) was considered as it addresses weakly structured processes. METHODS: To analyze the suitability of the modeling languages, BPMN and CMMN models of a Robot-Assisted Minimally Invasive Esophagectomy and Cochlea Implantation were derived and integrated into a situation recognition workflow. Test cases were used to contrast the differences and compare the advantages and disadvantages of the models concerning modeling, execution, and control. Furthermore, the impact on transferability was investigated. RESULTS: Compared to BPMN, CMMN allows flexibility for modeling intraoperative processes while remaining understandable. Although more effort and process knowledge are needed for execution and control within a situation recognition system, CMMN enables better transferability of the models and therefore the system. Concluding, CMMN should be chosen as a supplement to BPMN for flexible process parts that can only be covered insufficiently by BPMN, or otherwise as a replacement for the entire process. CONCLUSION: CMMN offers the flexibility for variable, weakly structured process parts, and is thus suitable for surgical interventions. A combination of both notations could allow optimal use of their advantages and support the transferability of the situation recognition system.
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Administração de Caso , Humanos , Fluxo de TrabalhoRESUMO
PURPOSE: To evaluate the concordance between lung biopsy puncture pathways determined by artificial intelligence (AI) and those determined by expert physicians. MATERIALS AND METHODS: An AI algorithm was created to choose optimal lung biopsy pathways based on segmented thoracic anatomy and emphysema in volumetric lung computed tomography (CT) scans combined with rules derived from the medical literature. The algorithm was validated using pathways generated from CT scans of randomly selected patients (n = 48) who had received percutaneous lung biopsies and had noncontrast CT scans of 1.25-mm thickness available in picture archiving and communication system (PACS) (n = 28, mean age, 68.4 years ± 9.2; 12 women, 16 men). The algorithm generated 5 potential pathways per scan, including the computer-selected best pathway and 4 random pathways (n = 140). Four experienced physicians rated each pathway on a 1-5 scale, where scores of 1-3 were considered safe and 4-5 were considered unsafe. Concordance between computer and physician ratings was assessed using Cohen's κ. RESULTS: The algorithm ratings were statistically equivalent to the physician ratings (safe vs unsafe: κ¯=0.73; ordinal scale: κ¯=0.62). The computer and physician ratings were identical in 57.9% (81/140) of cases and differed by a median of 0 points. All least-cost "best" pathways generated by the algorithm were considered safe by both computer and physicians (28/28) and were judged by physicians to be ideal or near ideal. CONCLUSIONS: AI-generated lung biopsy puncture paths were concordant with expert physician reviewers and considered safe. A prospective comparison between computer- and physician-selected puncture paths appears indicated in addition to expansion to other anatomic locations and procedures.
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BACKGROUND: With Surgomics, we aim for personalized prediction of the patient's surgical outcome using machine-learning (ML) on multimodal intraoperative data to extract surgomic features as surgical process characteristics. As high-quality annotations by medical experts are crucial, but still a bottleneck, we prospectively investigate active learning (AL) to reduce annotation effort and present automatic recognition of surgomic features. METHODS: To establish a process for development of surgomic features, ten video-based features related to bleeding, as highly relevant intraoperative complication, were chosen. They comprise the amount of blood and smoke in the surgical field, six instruments, and two anatomic structures. Annotation of selected frames from robot-assisted minimally invasive esophagectomies was performed by at least three independent medical experts. To test whether AL reduces annotation effort, we performed a prospective annotation study comparing AL with equidistant sampling (EQS) for frame selection. Multiple Bayesian ResNet18 architectures were trained on a multicentric dataset, consisting of 22 videos from two centers. RESULTS: In total, 14,004 frames were tag annotated. A mean F1-score of 0.75 ± 0.16 was achieved for all features. The highest F1-score was achieved for the instruments (mean 0.80 ± 0.17). This result is also reflected in the inter-rater-agreement (1-rater-kappa > 0.82). Compared to EQS, AL showed better recognition results for the instruments with a significant difference in the McNemar test comparing correctness of predictions. Moreover, in contrast to EQS, AL selected more frames of the four less common instruments (1512 vs. 607 frames) and achieved higher F1-scores for common instruments while requiring less training frames. CONCLUSION: We presented ten surgomic features relevant for bleeding events in esophageal surgery automatically extracted from surgical video using ML. AL showed the potential to reduce annotation effort while keeping ML performance high for selected features. The source code and the trained models are published open source.
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Esofagectomia , Robótica , Humanos , Teorema de Bayes , Esofagectomia/métodos , Aprendizado de Máquina , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos ProspectivosRESUMO
BACKGROUND AND AIMS: Development of pancreatic ductal adenocarcinoma (PDAC) is a multistep process intensively studied; however, precocious diagnosis and effective therapy still remain unsatisfactory. The role for Notch signaling in PDAC has been discussed controversially, as both cancer-promoting and cancer-antagonizing functions have been described. Thus, an improved understanding of the underlying molecular mechanisms is necessary. Here, we focused on RBPJ, the receiving transcription factor in the Notch pathway, examined its expression pattern in PDAC, and characterized its function in mouse models of pancreatic cancer development and in the regeneration process after acute pancreatitis. METHODS: Conditional transgenic mouse models were used for functional analysis of RBPJ in the adult pancreas, initiation of PDAC precursor lesions, and pancreatic regeneration. Pancreata and primary acinar cells were tested for acinar-to-ductal metaplasia together with immunohistology and comprehensive transcriptional profiling by RNA sequencing. RESULTS: We identified reduced RBPJ expression in a subset of human PDAC specimens. Ptf1α-CreERT-driven depletion of RBPJ in transgenic mice revealed that its function is dispensable for the homeostasis and maintenance of adult acinar cells. However, primary RBPJ-deficient acinar cells underwent acinar-to-ductal differentiation in ex vivo. Importantly, oncogenic KRAS expression in the context of RBPJ deficiency facilitated the development of pancreatic intraepithelial neoplasia lesions with massive fibrotic stroma formation. Interestingly, RNA-sequencing data revealed a transcriptional profile associated with the cytokine/chemokine and extracellular matrix changes. In addition, lack of RBPJ delays the course of acute pancreatitis and critically impairs it in the context of KRASG12D expression. CONCLUSIONS: Our findings imply that downregulation of RBPJ in PDAC patients derepresses Notch targets and promotes KRAS-mediated pancreatic acinar cells transformation and desmoplasia development.
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Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatite , Animais , Humanos , Camundongos , Células Acinares/metabolismo , Doença Aguda , Carcinoma in Situ/metabolismo , Carcinoma Ductal Pancreático/patologia , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Camundongos Transgênicos , Neoplasias Pancreáticas/patologia , Pancreatite/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias PancreáticasRESUMO
BACKGROUND: Surgery generates a vast amount of data from each procedure. Particularly video data provides significant value for surgical research, clinical outcome assessment, quality control, and education. The data lifecycle is influenced by various factors, including data structure, acquisition, storage, and sharing; data use and exploration, and finally data governance, which encompasses all ethical and legal regulations associated with the data. There is a universal need among stakeholders in surgical data science to establish standardized frameworks that address all aspects of this lifecycle to ensure data quality and purpose. METHODS: Working groups were formed, among 48 representatives from academia and industry, including clinicians, computer scientists and industry representatives. These working groups focused on: Data Use, Data Structure, Data Exploration, and Data Governance. After working group and panel discussions, a modified Delphi process was conducted. RESULTS: The resulting Delphi consensus provides conceptualized and structured recommendations for each domain related to surgical video data. We identified the key stakeholders within the data lifecycle and formulated comprehensive, easily understandable, and widely applicable guidelines for data utilization. Standardization of data structure should encompass format and quality, data sources, documentation, metadata, and account for biases within the data. To foster scientific data exploration, datasets should reflect diversity and remain adaptable to future applications. Data governance must be transparent to all stakeholders, addressing legal and ethical considerations surrounding the data. CONCLUSION: This consensus presents essential recommendations around the generation of standardized and diverse surgical video databanks, accounting for multiple stakeholders involved in data generation and use throughout its lifecycle. Following the SAGES annotation framework, we lay the foundation for standardization of data use, structure, and exploration. A detailed exploration of requirements for adequate data governance will follow.
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Inteligência Artificial , Melhoria de Qualidade , Humanos , Consenso , Coleta de DadosRESUMO
Within the European-funded Coordination and Support Action MicrobiomeSupport (https://www.microbiomesupport.eu/), the Workshop 'Education in Food Systems Microbiome Related Sciences: Needs for Universities, Industry and Public Health Systems' brought together over 70 researchers, public health and industry partners from all over the world to work on elaborating microbiome-related educational needs in food systems. This publication provides a summary of discussions held during and after the workshop and the resulting recommendations.
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The analysis of microplastics (MP) is time-consuming which limits our capacity to monitor and mitigate plastic pollution. Here, near infrared (1000-2500 nm) hyperspectral imaging (NIR-HSI) offers an advantage over other spectroscopic techniques because it can rapidly image large areas relative to other systems. While NIR-HSI can successfully detect MP, accuracy and limitations of the method have not been fully explored. In addition, lack of open databases and analysis pipelines increases the barrier to use. In this work, we developed a spectral database containing preproduction pellets, consumer products and marine plastic debris, imaged using a Hyspex SWIR-320me imager. A SIMCA model identified four polymer types: polypropylene, polyethylene, polyethylene terephthalate and polystyrene (PP, PE, PET, PS) to identify MP in hyperspectral images. We determined the accuracy of size estimates for PS MP > 1000 µm using fluorescence microscopy and tested the impact of photooxidation on detection of plastics by NIR-HSI (PE, PP, PS, PET) and subsequent prediction by the SIMCA model. The model performed well across all polymers as shown by high specificity, sensitivity, and accuracy for internal cross validation (>88%), and sensitivity >80% for external validation. PS MP < 500 µm Feret diameter were not consistently detected by NIR-HSI when compared with fluorescence microscopy. However, estimates for Feret diameter were consistent for PS MP > 1000 µm. Analysis by NIR-HSI showed no spectral changes and SIMCA showed no decreased precision with increased photooxidation across polymer types. Recall varied across polymer type and photooxidation stage with no clear trends. This study shows that NIR-HSI is a rapid method which can accurately identify MP of the four most relevant polymer types, precluding the need to analyze particles one at a time. NIR-HSI can be a key technology for environmental monitoring of plastic debris where rapid analysis of multiple samples is required.
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Plásticos , Poluentes Químicos da Água , Plásticos/análise , Microplásticos , Imageamento Hiperespectral , Fluxo de Trabalho , Polímeros , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análiseRESUMO
The expression of viral antigens in chronic hepatitis B virus (HBV) infection drives continuous liver inflammation, one of the main risk factors to develop liver cancer. HBV developed immune-suppressive functions to escape from the host immune system, but their link to liver tumor development is not well understood. Here, we analyzed if and how HBV surface antigen (HBs) expression in combined hepatocellular-cholangiocarcinoma (cHCC/iCCA) cells influences their antigenicity for CD8 T cells. We randomly isolated liver tumor tissues from AlfpCre+-Trp53fl/fl/Alb-HBs+ tg mice and established primary carcinoma cell lines (pCCL) that showed a bilineal (CK7+/HNF4α+) cHCC/iCCA phenotype. These pCCL uniformly expressed HBs (HBshi), and low levels of MHC-I (MHC-Ilo), and were transiently convertible to a high antigenicity (MHC-Ihi) phenotype by IFN-γ treatment. HBshi/pCCL induced HBs/(Kb/S190-197)-specific CD8 T cells and developed slow-growing tumors in subcutaneously transplanted C57Bl/6J (B6) mice. Interestingly, pCCL-ex cells, established from HBshi/pCCL-induced and re-explanted tumors in B6 but not those in immune-deficient Rag1-/- mice showed major alterations, like an MHC-Ihi phenotype, a prominent growth-biased gene expression signature, a significantly decreased HBs expression (HBslo) and a switch to fast-growing tumors in re-transplanted B6 or PD-1-/- hosts with an unlocked PD-1/PD-L1 control system. CD8 T cell-mediated elimination of HBshi/pCCL, together with the attenuation of the negative restraints of HBs in the tumor cells, like ER-stress, reveals a novel mechanism to unleash highly aggressive HBslo/pCCL-ex immune-escape variants. Under certain conditions, HBs-specific CD8 T-cell responses thus potentiate tumor growth, an aspect that should be considered for therapeutic vaccination strategies against chronic HBV infection and liver tumors.