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In this paper we present how the process modeling and execution tools iPM and iPE can be used to model and execute biological processes. The main focus of this paper is on the flexibility of iPM and iPE with respect to the customization to the biological application domain. We will demonstrate the flexibility of our modeling methodology by giving two examples: Modeling the invocation semantics of web services used in the biological application domain and the processing of streamed data.

Purpose: Avoidant restrictive food intake disorder (ARFID) was recently characterized, according to the DSM-5 classification, as a feeding and eating disorder (FED). However, ARFID remains poorly known by most pediatricians, but also by psychiatrists and primary care professionals. Despite the fact that patients with ARFID generally have a higher BMI than patients with anorexia nervosa, our purpose was to highlight the fact that they may present severe nutritional deficiencies and major somatic complications when the diagnosis is delayed., Method: We describe here a case of a 16-year-old boy who presented with severe undernutrition (BMI = 11.5) leading to Ogilvie's syndrome, which resolved with enteral refeeding. Because of undernutrition, very bad dental condition, and encopresis, some physicians wrongly suspected child neglect, but retrospective analysis of his personal history revealed a long-term FED and sensory specificities that led to the final diagnosis of an ARFID-autism spectrum disorder (ASD) association. A literature review was conducted on the ARFID somatic complications., Conclusion: The training of health professionals in the clinical forms of pediatric FED, including ARFID, is necessary, to promote early diagnosis and prevent poor nutritional outcomes. In this case the association of ARFID-ASD and the delay in access to specialized care favored by the disadvantaged social environment led to severe gastrointestinal complications., Level of Evidence: V, descriptive study., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: To evaluate dual-energy CT (DE) and dedicated metal artifact reduction algorithms (iMAR) during CT-guided biopsy in comparison to single-energy CT (SE)., Methods: A trocar was placed in the liver of six pigs. CT acquisitions were performed with SE and dose equivalent DE at four dose levels(1.7-13.5mGy). Iterative reconstructions were performed with and without iMAR. ROIs were placed in four positions e.g. at the trocar tip(TROCAR) and liver parenchyma adjacent to the trocar tip(LIVER-1) by two independent observers for quantitative analysis using CT numbers, noise, SNR and CNR. Qualitative image analysis was performed regarding overall image quality and artifacts generated by iMAR., Results: There were no significant differences in CT numbers between DE and SE at TROCAR and LIVER-1 irrespective of iMAR. iMAR significantly reduced metal artifacts at LIVER-1 for all exposure settings for DE and SE(p = 0.02-0.04), but not at TROCAR. SNR, CNR and noise were comparable for DE and SE. SNR was best for high dose levels of 6.7/13.5mGy. Mean difference in the Blant-Altman analysis was -8.43 to 0.36. Cohen's kappa for qualitative interreader-agreement was 0.901., Conclusions: iMAR independently reduced metal artifacts more effectively and efficiently than CT acquisition in DE at any dose setting and its application is feasible during CT-guided liver biopsy., Competing Interests: The authors have declared that no competing interests exist.

Introduction: To explore the feasibility, safety, and efficiency of ethiodized oil tumor marking combined with irreversible electroporation (IRE) for small hepatocellular carcinomas (HCCs) that were invisible on unenhanced computed tomography (CT)., Methods: A retrospective analysis of the institutional database was performed from January 2018 to September 2018. Patients undergoing ethiodized oil tumor marking to improve target-HCC visualization in subsequent CT-guided IRE were retrieved. Target-HCC visualization after marking was assessed, and the signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNR) were compared between pre-marking and post-marking CT images using the paired t -test. Standard IRE reports, adverse events, therapeutic endpoints, and survival were summarized and assessed., Results: Nine patients with 11 target-HCCs (11.1-18.8 mm) were included. After marking, all target-HCCs demonstrated complete visualization in post-marking CT, which were invisible in pre-marking CT. Quantitatively, the SNR of the target-HCCs significantly increased after marking (11.07 ± 4.23 vs. 3.36 ± 1.79, p = 0.006), as did the CNR (4.32 ± 3.31 vs. 0.43 ± 0.28, p = 0.023). In sequential IRE procedures, the average current was 30.1 ± 5.3 A, and both the delta ampere and percentage were positive with the mean values of 5.8 ± 2.1 A and 23.8 ± 6.3%, respectively. All procedures were technically successful without any adverse events. In the follow-up, no residual unablated tumor (endpoint-1) was observed. The half-year, one-year, and two-year local tumor progression (endpoint-2) rate was 0%, 9.1%, and 27.3%. The two-year overall survival rate was 100%., Conclusions: Ethiodized oil tumor marking enables to demarcate small HCCs that were invisible on unenhanced CT. It potentially allows a safe and complete ablation in subsequent CT-guided IRE.

Background: Executive functions (EF) are often impaired in autism spectrum disorder (ASD). Such dysfunctions are associated with anxiety, depression, and a lack of autonomy. Transcranial direct current stimulation (tDCS) has been shown to enhance EF in healthy adults and clinical populations and to improve working memory - a component of the EF - in adults with high-functioning ASD (HF-ASD). We hypothesized that tDCS could improve the EF of HF-ASD patients. Such enhancement could improve their adaptive behaviors., Method: Eight patients with HF-ASD received 10 consecutive cathodal tDCS sessions (2 mA) over the left dorsolateral prefrontal cortex (F3) for 15 min each in an open trial. EF (with the Stroop test, Trail Making Test [TMT] A and B, Modified Wisconsin Card Sorting Test [mWCST], and Verbal Fluency Test) and behavioral dysexecutive syndrome (with the Behavioral Dysexecutive Syndrome Inventory and the Repetitive and Restricted Behaviour scale) were assessed before and 10 days after treatment., Results: This study showed significant improvement in initiation (TMT-A time: p = 0.018) and cognitive flexibility (TMT-B time: p = 0.009; letter Verbal Fluency Test: p = 0.017; mWCST total errors: p = 0.028) after tDCS. Regarding behavior, the hypoactivity of the patients improved, as well as their repetitive and restrictive behaviors. In addition, this noninvasive neurostimulation technique was well tolerated., Conclusions: Flexibility and initiation are the most impaired EF in autism. These are promising results which justify a randomized and placebo-controlled study in a wider population. If these results were confirmed by a randomized controlled trial, tDCS could be an easy and well-tolerated adjunctive treatment aiming to improve the quality of life and the autonomy of ASD patients., (© 2019 S. Karger AG, Basel.)

Background: The aim of this study was to evaluate the effect of 2nd generation argon plasma coagulation (VIO APC) with respect to the tissue destruction capacity, and to compare it with standard APC and Nd:YAG laser., Methods: 2nd generation APC (VIO APC2, Erbe, Germany), standard APC (APC 300/Erbotom ICC 200, Erbe) and Nd:YAG laser (KTP/YAG XP 800; Laserscope, San Jose, California) were applied in 35 porcine livers. Using APC, power settings (30-120 W), application time (2 and 5 sec) and gas flow (1 and 2 l/min) were varied. Using Nd:YAG laser, 30-60 W were applied (flow 21/min). Diameter and depth of tissue coagulation were evaluated., Results: Using VIO APC, maximum coagulation depth was 6 mm (maximum diameter 15 mm). In comparison to standard APC, the coagulation effect was significantly higher (p < 0.001). There was no significant difference in the mean depth achieved by VIO APC and Nd:YAG laser using 30- 60 W and an application time of 2 sec (p < 0.05). Using maximum energy available for the 2 systems, maximum depth achieved by VIO APC (6 mm) was higher than the one caused by Nd:YAG laser (4 mm)., Conclusions: VIO APC was more effective than standard APC. Using medium power and a limited application time, it was as effective as Nd:YAG laser. The high effectiveness of VIO APC should be a topic of clinical education.

The identification of the CD34 molecule, expressed almost exclusively on human hematopoietic stem cells and committed progenitors, and the development of CD34-specific monoclonal antibodies have made procurement of relatively pure populations of CD34+ marrow cells for autologous transplantation feasible. Characterization of the immunogenicity of CD34+ marrow cells may facilitate the design of successful strategies to use these cells for allogeneic transplantation. CD34+ marrow cells from normal volunteers were enriched to greater than 98% purity by immunoaffinity chromatography on column followed by fluorescence-activated cell sorting. Purified CD34+ cells were tested for expression of HLA-DR and other accessory molecules, and function in hematopoietic colony growth and mixed leukocyte culture (MLC) assays. Greater than 95% CD34+ cells were positive for HLA-DR and 74% +/- 10% were highly positive for CD18, the common beta-chain of a leukointegrin family. CD34+/CD18- cells were small, agranular lymphocytes which contained the majority of precursors for colony-forming cells detected in long-term cultures. They produced almost no stimulation of purified T cells from HLA-DR-incompatible individuals in bulk MLC or in limiting dilution assay. In contrast, CD34+/CD18+ cells were large, were enriched for cells forming mixed colonies in short- but not long-term assays, and were capable of stimulating allogeneic T cells. CD86, a natural ligand for the T-cell activation molecule CD28, was coexpressed with CD18 in 6% +/- 3% of CD34+ cells. CD34+/CD86+ cells, but not CD34+/CD86- cells, exhibited strong alloantigen presenting function. Thus, pluripotent hematopoietic activity and alloantigen presenting function are attributes of distinct subsets of CD34+ marrow cells. CD34+/CD18- or CD34+/CD86- cells may be more effective than either the whole CD34+ population or unseparated marrow in engrafting allogeneic recipients and may also facilitate induction of tolerance.

To evaluate differential gene expression in multiple sclerosis (MS) patients and control subjects, we used differential display to screen for messenger RNAs that are differentially expressed in peripheral blood mononuclear cells from monozygotic twins who are discordant for MS. We identified a 232-bp complementary DNA fragment, present only in material from the normal twin, that exhibited 100% identity with the inhibitory transcription factor Sp3. Oligonucleotide primers corresponding to Sp3 messenger RNA sequences amplified complementary DNA of appropriate size from 83% of control subjects but from only 21% of MS patients (p < 0.001). These results suggest that Sp3 gene transcription is suppressed in peripheral blood mononuclear cells from most MS patients and that other genes whose expression is normally suppressed by Sp3 in immune cells may consequently be overexpressed.

A recent study suggested that a significant portion of the oligoclonal IgG found in multiple sclerosis (MS) cerebrospinal fluid may be removed by absorption with simian virus 5 (SV5). We have now evaluated the proliferative responses to SV5 generated by peripheral blood mononuclear cells from normal adult subjects and from patients with MS. Positive responses were detected in 16 of 16 subjects in each group. The magnitude of the response was not significantly different in the two groups. There was no correlation between the level of response and the presence or absence of HLA-DR2. No cross-reactivity with SV5 was demonstrated by panels of human T cell clones directed against myelin basic protein or measles virus. More than 60% of normal individuals between 10 and 16 years of age also generated positive T cell proliferative responses to SV5, while fewer than 25% of subjects below the age of 6 generated positive responses. Intermediate percentages of positive responders were detected in subjects 6-9 years of age. We conclude that the adult human population has been widely exposed to this organism and that initial exposure generally occurs in the early to middle school-age years.

We sequenced the cDNAs of alpha and beta T-cell receptors (TCRs), including V, J, and CDR3 regions, expressed by 54 myelin basic protein (MBP)-specific T-cell clones generated from the peripheral blood of 15 multiple sclerosis (MS) patients and three normal controls. Thirteen V alpha gene segments, 18 V beta gene segments, 23 CDR3 alpha sequences, and 30 CDR3 beta sequences were represented among these clones. Some CDR3 motifs were common to several clones that shared epitope specificity, while other motifs were common to clones with diverse epitope specificities. The extensive heterogeneity of TCR gene expression in the human immune response to MBP indicates that therapeutic strategies aimed at blocking a limited number of TCRs are unlikely to fully suppress the T-cell response to MBP in vivo.

The measles-specific antibody responses of seronegative adolescents and young adults were evaluated after revaccination. Of 1650 previously vaccinated healthy volunteers between the ages of 10 and 30 years, 4.4% were found to be seronegative for measles antibodies and 9.9% had equivocal titers. Seronegative volunteers were revaccinated to measles and followed serially for development of measles-specific IgG. Of 43 subjects followed for at least 1 year, only 58% developed and maintained positive antibody titers; 12% never developed positive titers and 30% initially developed titers that fell below positive levels within 1 year. The peak titers achieved by those subjects who responded transiently were lower than those achieved by subjects who developed sustained responses. Thus even after the recommended two dose schedule of the current measles vaccine, some adolescents and young adults lack protective titers of measles-specific antibody.