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PloS One 2020Assessing algorithms of artificial pancreas systems is critical in developing automated and fault-tolerant solutions that work outside clinical settings. The development...
BACKGROUND AND AIMS
Assessing algorithms of artificial pancreas systems is critical in developing automated and fault-tolerant solutions that work outside clinical settings. The development and evaluation of algorithms can be facilitated with a platform that conducts virtual clinical trials. We present in this paper a clinically validated cloud-based distributed platform that supports the development and comprehensive testing of single and dual-hormone algorithms for type 1 diabetes mellitus (T1DM).
METHODS
The platform is built on principles of object-oriented design and runs user algorithms in real-time virtual clinical trials utilizing a multi-threaded environment enabled by concurrent execution over a cloud infrastructure. The platform architecture isolates user algorithms located on personal machines from proprietary patient data running on the cloud. Users import a plugin into their algorithms (Matlab, Python, or Java) to connect to the platform. Once connected, users interact with a graphical interface to design experimental protocols for their trials. Protocols include trial duration in days, mealtimes and amounts, variability in mealtimes and amounts, carbohydrate counting errors, snacks, and onboard insulin levels.
RESULTS
The platform facilitates development by solving the ODE model in the cloud on large CPU-optimized machines, providing a 62% improvement in memory, speed and CPU utilization. Users can easily debug & modify code, test multiple strategies, and generate detailed clinical performance reports. We validated and integrated into the platform a glucoregulatory system of ordinary differential equations (ODEs) parameterized with clinical data to mimic the inter and intra-day variability of glucose responses of 15 T1DM patients.
CONCLUSION
The platform utilizes the validated patient model to conduct virtual clinical trials for the rapid development and testing of closed-loop algorithms for T1DM.
Topics: Algorithms; Artificial Organs; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Insulin; Models, Biological; Pancreas
PubMed: 33332411
DOI: 10.1371/journal.pone.0243139 -
BMC Gastroenterology Jul 2022The objectives of this study were to evaluate the relationship between ductal morphometry and ramification patterns in the submandibular gland and pancreas in order to...
BACKGROUND
The objectives of this study were to evaluate the relationship between ductal morphometry and ramification patterns in the submandibular gland and pancreas in order to validate their common fractal dimension.
METHODS
X-ray ductography with software-aided morphometry were obtained by injecting barium sulphate in the ducts of post-mortem submandibular gland and pancreas specimens harvested from 42 adult individuals.
RESULTS
Three cases were excluded from the study because of underlying pathology. There was a significant correlation between the length of the main pancreatic duct (MPD) and the intraglandular portion of the right submandibular duct (SMD) (r = 0.3616; p = 0.028), and left SMD (r = 0.595; p < 0.01), respectively, but their maximal diameters did not correlate (r = 0.139-0.311; p > 0.05). Both dimensions of the SMD showed a significant right-left correlation (p < 0.05). The number of MPD side branches (mean = 37) correlated with the number of side branches of left SMD, but not with the right one (mean = 9). Tortuosity was observed in 54% of the MPD, 32% of the right SMD, and 24% of the left SMD, with mutual association only between the two salivary glands.
CONCLUSIONS
Although the length of intraglandular SMD and MPD correlate, other morphometric ductal features do not, thus suggesting a more complex relationship between the two digestive glands.
Topics: Adult; Head; Humans; Pancreas; Pancreatic Ducts; Salivary Ducts; Submandibular Gland
PubMed: 35906544
DOI: 10.1186/s12876-022-02443-2 -
Magyar Onkologia Oct 2021Modern imaging procedures, including CT and MR diagnostics, play a significant role in recognizing, characterizing, determining the extent of pancreatic tumor lesions,... (Review)
Review
Modern imaging procedures, including CT and MR diagnostics, play a significant role in recognizing, characterizing, determining the extent of pancreatic tumor lesions, assessing their operability, and evaluating response to treatment and patient follow-up. This article reviews the conventional imaging modalities used in the modern diagnosis of pancreatic tumors, conventional and contrast-enhanced abdominal ultrasound, standard protocols using the latest research results from CT and MRI scans, and their location and diagnostic value in the treatment of solid and cystic neoplasia. In addition, it briefly discusses the additional possibilities of artificial intelligence-based processing of digital imaging data, which is under strong development and is expected to be incorporated into clinical practice in the future.
Topics: Artificial Intelligence; Humans; Magnetic Resonance Imaging; Pancreas; Tomography, X-Ray Computed
PubMed: 34614045
DOI: No ID Found -
International Journal of Molecular... Oct 2019Adenosine regulates exocrine and endocrine secretions in the pancreas. Adenosine is considered to play a role in acini-to-duct signaling in the exocrine pancreas. To...
Adenosine regulates exocrine and endocrine secretions in the pancreas. Adenosine is considered to play a role in acini-to-duct signaling in the exocrine pancreas. To identify the molecular basis of functional adenosine receptors in the exocrine pancreas, immunohistochemical analysis was performed in the rat, mouse, and guinea pig pancreas, and the secretory rate and concentration of HCO in pancreatic juice from the rat pancreas were measured. The A adenosine receptor colocalized with ezrin, an A-kinase anchoring protein, in the luminal membrane of duct cells in the mouse and guinea pig pancreas. However, a strong signal ascribed to A adenosine receptors was detected in insulin-positive β cells in islets of Langerhans. The A adenosine receptor agonist 4-[2-[[6-Amino-9-(-ethyl-β-D-ribofuranuronamidosyl)-9-purin-2-yl]amino]ethyl]benzenepropanoic acid (CGS 21680) stimulated HCO-rich fluid secretion from the rat pancreas. These results indicate that A adenosine receptors may be, at least in part, involved in the exocrine secretion of pancreatic duct cells via acini-to-duct signaling. The adenosine receptors may be a potential therapeutic target for cancer as well as exocrine dysfunctions of the pancreas.
Topics: Animals; Bicarbonates; Cytoskeletal Proteins; Female; Guinea Pigs; Islets of Langerhans; Male; Mice; Pancreas; Pancreatic Ducts; Rats; Receptors, Purinergic P1; Rodentia
PubMed: 31717704
DOI: 10.3390/ijms20215329 -
HPB : the Official Journal of the... Jun 2023Anastomotic suturing is the Achilles heel of pancreatic surgery. Especially in laparoscopic and robotically assisted surgery, the pancreatic anastomosis should first be...
BACKGROUND
Anastomotic suturing is the Achilles heel of pancreatic surgery. Especially in laparoscopic and robotically assisted surgery, the pancreatic anastomosis should first be trained outside the operating room. Realistic training models are therefore needed.
METHODS
Models of the pancreas, small bowel, stomach, bile duct, and a realistic training torso were developed for training of anastomoses in pancreatic surgery. Pancreas models with soft and hard textures, small and large ducts were incrementally developed and evaluated. Experienced pancreatic surgeons (n = 44) evaluated haptic realism, rigidity, fragility of tissues, and realism of suturing and knot tying.
RESULTS
In the iterative development process the pancreas models showed high haptic realism and highest realism in suturing (4.6 ± 0.7 and 4.9 ± 0.5 on 1-5 Likert scale, soft pancreas). The small bowel model showed highest haptic realism (4.8 ± 0.4) and optimal wall thickness (0.1 ± 0.4 on -2 to +2 Likert scale) and suturing behavior (0.1 ± 0.4). The bile duct models showed optimal wall thickness (0.3 ± 0.8 and 0.4 ± 0.8 on -2 to +2 Likert scale) and optimal tissue fragility (0 ± 0.9 and 0.3 ± 0.7).
CONCLUSION
The biotissue training models showed high haptic realism and realistic suturing behavior. They are suitable for realistic training of anastomoses in pancreatic surgery which may improve patient outcomes.
Topics: Humans; Suture Techniques; Digestive System Surgical Procedures; Laparoscopy; Anastomosis, Surgical; Pancreas; Clinical Competence
PubMed: 36828741
DOI: 10.1016/j.hpb.2023.02.002 -
Developmental Cell Jun 2022Diabetic patients show elevated plasma IL18 concentrations. IL18 has two receptors: the IL18 receptor (IL18r) and the Na-Cl co-transporter (NCC). Here, we report that...
Diabetic patients show elevated plasma IL18 concentrations. IL18 has two receptors: the IL18 receptor (IL18r) and the Na-Cl co-transporter (NCC). Here, we report that IL18 is expressed on islet α cells, NCC on β cells, and IL18r on acinar cells in human and mouse pancreases. The deficiency of these receptors reduces islet size, β cell proliferation, and insulin secretion but increases β cell apoptosis and exocrine macrophage accumulation after diet-induced glucose intolerance or streptozotocin-induced hyperglycemia. Together with the glucagon-like peptide-1 (GLP1), IL18 uses the NCC and GLP1 receptors on β cells to trigger β cell development and insulin secretion. IL18 also uses the IL18r on acinar cells to block hyperglycemic pancreas macrophage expansion. The β cell-selective depletion of the NCC or acinar-cell-selective IL18r depletion reduces glucose tolerance and insulin sensitivity with impaired β cell proliferation, enhanced β cell apoptosis and macrophage expansion, and inflammation in mouse hyperglycemic pancreas. IL18 uses NCC, GLP1r, and IL18r to maintain islet β cell function and homeostasis.
Topics: Animals; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Interleukin-18; Mice; Pancreas
PubMed: 35675813
DOI: 10.1016/j.devcel.2022.05.013 -
Obesity Facts 2022Ectopic fat deposition in the pancreas is involved in the pathogenesis of metabolic sequelae following an attack of pancreatitis. However, its relationship with the...
INTRODUCTION
Ectopic fat deposition in the pancreas is involved in the pathogenesis of metabolic sequelae following an attack of pancreatitis. However, its relationship with the exocrine pancreas has never been explored in this setting. The aim was to investigate the associations between intra-pancreatic fat deposition (IPFD), pancreas size, and pancreatic enzymes.
METHODS
This cross-sectional study recruited individuals with a history of acute pancreatitis and healthy controls. All participants underwent 3T magnetic resonance imaging, from which IPFD, total pancreas volume (TPV), and pancreas diameters (across the head, body, and tail) were measured independently by 2 raters in a blinded fashion. Circulating levels of pancreatic amylase, pancreatic lipase, and chymotrypsin were measured in a fasted state. A series of linear regression analyses was conducted, accounting for possible confounders.
RESULTS
A total of 108 individuals with pancreatitis and 60 healthy controls were studied. There was a statistically significant difference in IPFD (p < 0.001), but not in TPV (p = 0.389), between the groups. In the post-pancreatitis group, IPFD was significantly inversely associated with pancreas tail diameter (β = -0.736, p = 0.036 in the most adjusted model). In the control group, IPFD was significantly inversely associated with TPV (β = -3.557, p = 0.026 in the most adjusted model). Levels of pancreatic amylase were significantly directly associated with pancreas tail diameter in the post-pancreatitis group (β = 3.891, p = 0.042 in the most adjusted model), whereas levels of pancreatic lipase were significantly inversely associated with TPV in the control group (β = -10.533, p = 0.024 in the most adjusted model).
CONCLUSION
Increased IPFD in individuals after an attack of pancreatitis is associated with reduced pancreas tail diameter, which is in turn associated with reduced circulating levels of pancreatic amylase. The relationship between IPFD and the exocrine pancreas warrants further investigations.
Topics: Acute Disease; Cross-Sectional Studies; Humans; Magnetic Resonance Imaging; Pancreas; Pancreatitis
PubMed: 34753126
DOI: 10.1159/000519621 -
Theranostics 2023Pancreatic lineage specification follows the formation of tripotent pancreatic progenitors (PPs). Current protocols rebuilding PPs have an endocrine lineage bias and...
Pancreatic lineage specification follows the formation of tripotent pancreatic progenitors (PPs). Current protocols rebuilding PPs have an endocrine lineage bias and are mostly based on PDX1/NKX6-1 coexpression neglecting other markers decisive for PP heterogeneity and lineage potential. However, true tripotent PPs are of utmost interest to study also exocrine disorders such as pancreatic cancer and to simultaneously generate all three pancreatic lineages from the same ancestor. Here, we performed a comprehensive compound testing to advance the generation of multipotent progenitors, which were further characterized for their trilineage potential and . The heterogeneity and cell-cell communication across the PP subpopulations were analyzed via single-cell transcriptomics. We introduce a novel PP differentiation platform based on a comprehensive compound screening with an advanced computing tool to reduce impurities and to increase Glycoprotein-2 expression and subsequent trilineage potential. Superior PP tripotency was proven by the generation of acinar, endocrine, and ductal cells as well as upon orthotopic transplantation revealing all three lineages at fetal maturation level. GP2 expression levels at PP stage ascribed varying pancreatic lineage potential. Intermediate and high GP2 levels were superior in generating endocrine and duct-like organoids (PDLO). FACS-based purification of the GP2 PPs allowed the generation of pancreatic acinar-like organoids (PALO) with proper morphology and expression of digestive enzymes. scRNA-seq confirmed multipotent identity, positioned the GP2/PDX1/NKX6-1 population next to human fetal tip and trunk progenitors and identified novel ligand-receptor (LR) interactions in distinct PP subpopulations. LR validation experiments licensed midkine and VEGF signaling to increase markers labelling the single cell clusters with high GP2 expression. In this study, we guide human pluripotent stem cells into multipotent pancreatic progenitors. This common precursor population, which has the ability to mature into acinar, ductal and functional β-cells, serves as a basis for studying developmental processes and deciphering early cancer formation in a cell type-specific context. Using single-cell RNA sequencing and subsequent validation studies, we were able to dissect PP heterogeneity and specific cell-cell communication signals.
Topics: Humans; Pancreas; Cell Differentiation; Pluripotent Stem Cells; Insulin-Secreting Cells; Organoids
PubMed: 37064874
DOI: 10.7150/thno.78323 -
The British Journal of Radiology Feb 2021Interventional radiology (IR) provides minimally invasive therapeutic and palliative options for the treatment of pancreatic cancer depending on the stage of the... (Review)
Review
Interventional radiology (IR) provides minimally invasive therapeutic and palliative options for the treatment of pancreatic cancer depending on the stage of the disease. IR plays a critical, and also a very effective role, in both pre- and post-operative care of the patients with early stage resectable disease and also in palliative treatment of the patients with locally advanced or metastatic disease. In this article, we aimed to present the capability and the limitations of IR procedures including: local treatment options of primary and metastatic pancreatic cancer, palliation of biliary and intestinal obstructions, minimally invasive treatment of post-operative complications, and pain management.
Topics: Humans; Minimally Invasive Surgical Procedures; Pain; Pain Management; Palliative Care; Pancreas; Pancreatic Neoplasms; Radiology, Interventional
PubMed: 33156695
DOI: 10.1259/bjr.20200702 -
Frontiers in Endocrinology 2022Diabetes mellitus, a disease that affects nearly 536.6 million people worldwide, is characterized by the death or dysfunction of insulin-producing beta cells of the... (Review)
Review
Diabetes mellitus, a disease that affects nearly 536.6 million people worldwide, is characterized by the death or dysfunction of insulin-producing beta cells of the pancreas. The beta cells are found within the islets of Langerhans, which are composed of multiple hormone-producing endocrine cells including the alpha (glucagon), delta (somatostatin), PP (pancreatic polypeptide), and epsilon (ghrelin) cells. There is direct evidence that physical and paracrine interactions between the cells in the islet facilitate and support beta cell function. However, communication between endocrine and exocrine cells in the pancreas may also directly impact beta cell growth and function. Herein we review literature that contributes to the view that "crosstalk" between neighboring cells within the pancreas influences beta cell growth and function and the maintenance of beta cell health.
Topics: Diabetes Mellitus; Endocrine Cells; Glucagon; Humans; Insulin-Secreting Cells; Pancreas
PubMed: 35769082
DOI: 10.3389/fendo.2022.904004