Model Coupling and Integration via XML in theM3 Simulation

Complex real-world systems are currently developing into a decisive instrument for IT-supported problem solving for a great number of problems posed by science, economy and society. Like in many environmental simulation systems the Man Model Measurement (M3) Simulation (http://mmm.first.fraunhofer.de) contains numerous single scientifically founded models coupled to each other to reflect the complexity of our world. The unpredictable human factor is considered by actively involving real people into the simulation by a Virtual Reality framework. The evolution and enhancement of the M3 system will be provided by an open software API. This paper will focus on the control and the data communication between the distributed simulation models that are realized by specialized markup languages which employ the XML technology for easy extension and validation. The input and output data of the models is represented by an XML data model that includes also the physical and mathematical meaning of the transferred data so that different models can be easily coupled by connecting their XML formatted input and output streams, e.g. via sockets. The initialization parameters and the relevant output data of the models can be stored in an SQL database (MySQL) which can be accessed by a web interface or directly using JDBC. Legacy Code is included in the simulation system using wrapping technologies

Process Oriented Collaboration in Grid-Environments: A Case Study in the Construction Industry

This paper addresses the process-oriented collaboration based on a grid-based platform for the support of virtual organizations (VO), illustrated on the example of the construction industry. Distributed, organizational and IT-structures of teams involved in vintage complex projects cannot be managed with conventional methods in an appropriate manner. Both using a grid platform and grid-based services, in conjunction with semantic methods for consistency saving and goal-oriented process management can increase the efficiency of collaboration processes in large-scale projects. A hybrid grid- and web service-based architecture for the next generation of VO service and a gateway solution was developed integrating the process-oriented perspective and prototypically implemented. The problem, as well as the solution on the basis of the hybrid system architecture combing the benefits of the cutting-edge technologies, the methodical concept for modeling VO processes and their automated execution on a grid platform are discussed in detail

M3 Project - Actor Based Simulation in VirtualWorlds

M3 Simulation is a simulation approach that actively involves real human actors in a virtual reality environment based on multidisciplinary simulation models. This actor based concept aims at integrated simulation of complex processes belonging to heterogeneous levels of reality, paying specific attention to real human behavior. The entities of the real system under consideration are represented in a consistent object-oriented way by agents simulated by environmental models. This distributed network-capable implementation of the M3 system combines environmental modeling with the intuitive graphic representation, complex communication and interaction structures of virtual worlds in order to support the process of investigation of complex real world systems

Vascularization and biocompatibility of poly(ε-caprolactone) fiber mats for rotator cuff tear repair

Rotator cuff tear is the most frequent tendon injury in the adult population. Despite current improvements in surgical techniques and the development of grafts, failure rates following tendon reconstruction remain high. New therapies, which aim to restore the topology and functionality of the interface between muscle, tendon and bone, are essentially required. One of the key factors for a successful incorporation of tissue engineered constructs is a rapid ingrowth of cells and tissues, which is dependent on a fast vascularization. The dorsal skinfold chamber model in female BALB/cJZtm mice allows the observation of microhemodynamic parameters in repeated measurements in vivo and therefore the description of the vascularization of different implant materials. In order to promote vascularization of implant material, we compared a porous polymer patch (a commercially available porous polyurethane based scaffold from Biomerix™) with electrospun polycaprolactone (PCL) fiber mats and chitosan-graft-PCL coated electrospun PCL (CS-g-PCL) fiber mats in vivo. Using intravital fluorescence microscopy microcirculatory parameters were analyzed repetitively over 14 days. Vascularization was significantly increased in CS-g-PCL fiber mats at day 14 compared to the porous polymer patch and uncoated PCL fiber mats. Furthermore CS-g-PCL fiber mats showed also a reduced activation of immune cells. Clinically, these are important findings as they indicate that the CS-g-PCL improves the formation of vascularized tissue and the ingrowth of cells into electrospun PCL scaffolds. Especially the combination of enhanced vascularization and the reduction in immune cell activation at the later time points of our study points to an improved clinical outcome after rotator cuff tear repair. © 2020 Gniesmer 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

In vivo analysis of vascularization and biocompatibility of electrospun polycaprolactone fibre mats in the rat femur chamber

In orthopaedic medicine, connective tissues are often affected by traumatic or degenerative injuries, and surgical intervention is required. Rotator cuff tears are a common cause of shoulder pain and disability among adults. The development of graft materials for bridging the gap between tendon and bone after chronic rotator cuff tears is essentially required. The limiting factor for the clinical success of a tissue engineering construct is a fast and complete vascularization of the construct. Otherwise, immigrating cells are not able to survive for a longer period of time, resulting in the failure of the graft material. The femur chamber allows the observation of microhaemodynamic parameters inside implants located in close vicinity to the femur in repeated measurements in vivo. We compared a porous polymer patch (a commercially available porous polyurethane-based scaffold from Biomerix™) with electrospun polycaprolactone (PCL) fibre mats and chitosan (CS)-graft-PCL modified electrospun PCL (CS-g-PCL) fibre mats in vivo. By means of intravital fluorescence microscopy, microhaemodynamic parameters were analysed repetitively over 20 days at intervals of 3 to 4 days. CS-g-PCL modified fibre mats showed a significantly increased vascularization at Day 10 compared with Day 6 and at Day 14 compared with the porous polymer patch and the unmodified PCL fibre mats at the same day. These results could be verified by histology. In conclusion, a clear improvement in terms of vascularization and biocompatibility is achieved by graft-copolymer modification compared with the unmodified material. © 2019 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Lt

Prognostic Relevance of Cardiopulmonary Exercise Testing for Patients with Chronic Thromboembolic Pulmonary Hypertension

Following acute pulmonary embolism (PE), a relevant number of patients experience decreased exercise capacity which can be associated with disturbed pulmonary perfusion. Cardiopulmonary exercise testing (CPET) shows several patterns typical for disturbed pulmonary perfusion. Research question: We aimed to examine whether CPET can also provide prognostic information in chronic thromboembolic pulmonary hypertension (CTEPH). Study Design and Methods: We performed a multicenter retrospective chart review in Germany between 2002 and 2020. Patients with CTEPH were included if they had 6 months of follow-up and complete CPET and hemodynamic data. Symptom-limited CPET was performed using a cycle ergometer (ramp or Jones protocol). The association of anthropometric data, comorbidities, symptoms, lung function, and echocardiographic, hemodynamic, and CPET parameters with survival was examined. Mortality prediction models were calculated by Cox regression with backward selection. Results: 345 patients (1532 person-years) were included; 138 underwent surgical treatment (pulmonary endarterectomy or balloon pulmonary angioplasty) and 207 received only non-surgical treatment. During follow-up (median 3.5 years), 78 patients died. The death rate per 1000 person-years was 24.9 and 74.2 in the surgical and non-surgical groups, respectively (p < 0.001). In age- and sex-adjusted Cox regression analyses, CPET parameters including peak oxygen uptake (VO2peak, reflecting cardiopulmonary exercise capacity) were prognostic in the non-surgical group but not in the surgical group. In mortality prediction models, age, sex, VO2peak (% predicted), and carbon monoxide transfer coefficient (% predicted) showed significant prognostic relevance in both the overall cohort and the non-surgical group. In the non-surgical group, Kaplan–Meier analysis showed that patients with VO2peak below 53.4% predicted (threshold identified by receiver operating characteristic analysis) had increased mortality (p = 0.007). Interpretation: The additional measurement of cardiopulmonary exercise capacity by CPET allows a more precise prognostic evaluation in patients with CTEPH. CPET might therefore be helpful for risk-adapted treatment of CTEPH

Evaluation of large language model-generated medical information on idiopathic pulmonary fibrosis

BackgroundIdiopathic Pulmonary Fibrosis (IPF) information from AI-powered large language models (LLMs) like ChatGPT-4 and Gemini 1.5 Pro is unexplored for quality, reliability, readability, and concordance with clinical guidelines.Research questionWhat is the quality, reliability, readability, and concordance to clinical guidelines of LLMs in medical and clinically IPF-related content?Study design and methodsChatGPT-4 and Gemini 1.5 Pro responses to 23 ATS/ERS/JRS/ALAT IPF guidelines questions were compared. Six independent raters evaluated responses for quality (DISCERN), reliability (JAMA Benchmark Criteria), readability (Flesch–Kincaid), and guideline concordance (0–4). Descriptive analysis, Intraclass Correlation Coefficient, Wilcoxon signed-rank test, and effect sizes (r) were calculated. Statistical significance was set at p &lt; 0.05.ResultsAccording to JAMA Benchmark, ChatGPT-4 and Gemini 1.5 Pro provided partially reliable responses; however, readability evaluations showed that both models were difficult to understand. The Gemini 1.5 Pro provided significantly better treatment information (DISCERN score: 56 versus 43, p &lt; 0.001). Gemini had considerably higher international IPF guidelines concordance than ChatGPT-4 (median 3.0 [3.0–3.5] vs. 3.0 [2.5–3.0], p = 0.0029).InterpretationBoth models gave useful medical insights, but their reliability is limited. Gemini 1.5 Pro gave greater quality information than ChatGPT-4 and was more compliant with worldwide IPF guidelines. Readability analyses found that AI-generated medical information was difficult to understand, stressing the need to refine it.What is already known on this topicRecent advancements in AI, especially large language models (LLMs) powered by natural language processing (NLP), have revolutionized the way medical information is retrieved and utilized.What this study addsThis study highlights the potential and limitations of ChatGPT-4 and Gemini 1.5 Pro in generating medical information on IPF. They provided partially reliable information in their responses; however, Gemini 1.5 Pro demonstrated superior quality in treatment-related content and greater concordance with clinical guidelines. Nevertheless, neither model provided answers in full concordance with established clinical guidelines, and their readability remained a major challenge.How this study might affect research, practice or policyThese findings highlight the need for AI model refinement as LLMs evolve as healthcare reference tools to help doctors and patients make evidence-based decisions

Diagnosis of Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis by Measurement of microRNA Abundance in Blood and Tissue

A solid process for diagnosis could have a substantial impact on the successful treatment of pancreatic cancer, for which currently mortality is nearly identical to incidence. Variations in the abundance of all microRNA molecules from peripheral blood cells and pancreas tissues were analyzed on microarrays and in part validated by real-time PCR assays. In total, 245 samples from two clinical centers were studied that were obtained from patients with pancreatic ductal adenocarcinoma or chronic pancreatitis and from healthy donors. Utilizing the minimally invasive blood test, receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC) analysis demonstrated very high sensitivity and specificity of a distinction between healthy people and patients with either cancer or chronic pancreatitis; respective AUC values of 0.973 and 0.950 were obtained. Confirmative and partly even more discriminative diagnosis could be performed on tissue samples with AUC values of 1.0 and 0.937, respectively. In addition, discrimination between cancer and chronic pancreatitis was achieved (AUC = 0.875). Also, several miRNAs were identified that exhibited abundance variations in both tissue and blood samples. The results could have an immediate diagnostic value for the evaluation of tumor reoccurrence in patients, who have undergone curative surgical resection, and for people with a familial risk of pancreatic cancer

Burden of Uncontrolled Severe Asthma With and Without Elevated Type-2 Inflammatory Biomarkers

Background: Many patients with asthma have type-2 airway inflammation, identified by the presence of biomarkers, including history of allergy, high blood eosinophil (EOS) count, and high fractional exhaled nitric oxide levels. Objective: To assess disease burden in relation to type-2 inflammatory biomarker status (history of allergy, blood EOS count, and fractional exhaled nitric oxide level) in patients with uncontrolled and controlled severe asthma in the NOVEL observational longiTudinal studY (NOVELTY) (NCT02760329). Methods: Asthma diagnosis and severity were physician-reported. Control was defined using Asthma Control Test score (uncontrolled = 20) and/or 1 or more severe physician-reported exacerbation in the previous year. Biomarker distribution (history of allergy, blood EOS count, and fractional exhaled nitric oxide level), symptom burden (Asthma Control Test score, modified Medical Research Council dyspnea scale), health status (St George's Respiratory Questionnaire score), exacerbations, and health care resource utilization were assessed. Results: Of 647 patients with severe asthma, 446 had uncontrolled and 123 had controlled asthma. Among those with uncontrolled asthma, 196 (44%) had 2 or more positive biomarkers, 187 (42%) had 1 positive biomarker, 325 (73%) had low blood EOS, and 63 (14%) were triple-negative. Disease burden was similarly high across uncontrolled subgroups, irrespective of biomarker status, with poor symptom control (Asthma Control Test score 14.9-16.6), impaired health status (St George's Respiratory Questionnaire total score 46.7-49.4), clinically important breathlessness (modified Medical Research Council grade >= 2 in 47.3%-57.1%), and 1 or more severe exacerbation (70.6%-76.2%). Conclusions: Type-2 inflammatory biomarkers did not differentiate disease burden in patients with severe asthma. Patients with low type-2 inflammatory biomarker levels have few biologic therapy options; their needs should be addressed