Perspectives of an Enterprise Integration Plug-in System Architecture for Networked Manufacturing Systems

This paper is a part of a research project funded by the Science and Technology Development Fund (STDF), to create a product serving the digital transformation of Egyptian manufacturing companies. It allows a manufacturing company to be a member of a distributed manufacturing network. The resulting system can be plugged into any ERP system. In this work, the limitation of a centralized integration entity to satisfy loosely coupling of distributed systems is overcome. The SOA framework and the remote method invocation (RMI) are applied using SOAP-XML technology. Enterprise integration patterns (EIP) were used in the architecture design

Fully Automated Electrophysiological Model Personalisation Framework from CT Imaging

International audienceThere has been a recent growing interest for cardiac computed tomography (CT) imaging in the electrophysiological community. This imaging modality indeed allows to locate and assess post-infarct scar heterogeneity, allowing to predict zones of abnormal electrical activity and even personalise EP models. To this end, most of the literature uses manually segmented CT images where one fundamental information is extracted, the myocardial wall thickness. In this paper, we evaluate the impact of using an automated deep learning (DL) methodology to segment the left ventricular wall and extract relevant scar information on the resulting personalised models. Using CT images from 8 patients that were not used during the DL training, we show that the automated segmentation is very similar to the manual one (median Dice score: 0.9). Thickness information obtained this way is also very close to the manual one (median difference: 0.7 mm). A wavefront propagation model personalisation framework based on this thickness information does not show relevant differences in its output (median difference in local activation time: 2 ms), proving its robustness. Bipolar electrograms, simulated through a novel approach, do not differ significantly between manual and automated segmentations (Pearson's r: 0.99)

Order versus Disorder: in vivo bone formation within osteoconductive scaffolds

In modern biomaterial design the generation of an environment mimicking some of the extracellular matrix features is envisaged to support molecular cross-talk between cells and scaffolds during tissue formation/remodeling. In bone substitutes chemical biomimesis has been particularly exploited; conversely, the relevance of pre-determined scaffold architecture for regenerated bone outputs is still unclear. Thus we aimed to demonstrate that a different organization of collagen fibers within newly formed bone under unloading conditions can be generated by differently architectured scaffolds. An ordered and confined geometry of hydroxyapatite foams concentrated collagen fibers within the pores, and triggered their self-assembly in a cholesteric-banded pattern, resulting in compact lamellar bone. Conversely, when progenitor cells were loaded onto nanofibrous collagen-based sponges, new collagen fibers were distributed in a nematic phase, resulting mostly in woven isotropic bone. Thus specific biomaterial design relevantly contributes to properly drive collagen fibers assembly to target bone regeneration

The impact of clothing style on bone mineral density among post menopausal women in Morocco: a case-control study

BACKGROUND: The clothing style is an important factor that influences vitamin D production and thus bone mineral density. We performed a case-control study in order to evaluate the effect of veil wearing (concealing clothing) on bone mineral density in Moroccan post menopausal women. METHODS: The cases were osteoporotic women whose disease was assessed by bone mineral density measurement. Each patient was matched with a non osteoporotic woman for age, and body mass index. All our patients were without secondary causes or medications that might affect bone density. The veil was defined as a concealing clothing which covered most of the body including the arms, the legs and the head. This definition is this of the usual Moroccan traditional clothing style. RESULTS: 178 post menopausal osteoporotic patients and 178 controls were studied. The mean age of the cases and the controls was 63.2 years (SD 7) and the mean body mass index was 32.1 (SD 8). The results of crude Odds Ratios analyses indicated that wearing a veil was associated with a high risk of osteoporosis: OR 2.29 (95% CI, 1.38–3.82). Multiparity or a history of familial peripheral osteoporotic fractures had also a significant effect on increasing the osteoporosis risk (ORs: 1.87 (95% CI, 1.05–3.49) and 2.01 (95% CI, 1.20–3.38)). After a multiple regression analysis, wearing the veil and a history of familial osteoporotic fractures remained the both independent factors that increased the osteoporosis risk (ORs: 2.20 (95% CI, 1.22–3.9) and 2.19 (95% CI, 1.12–4.29) respectively). CONCLUSION: our study suggested that in Moroccan post menopausal women, wearing a traditional concealing clothing covering arms, legs and head increased the risk of osteoporosis. Further studies are required to evaluate the clinical impact of the above findings and to clarify the status of vitamin D among veiled women in Morocco

Candidate Genes for Expansion and Transformation of Hematopoietic Stem Cells by NUP98-HOX Fusion Genes

BACKGROUND: Hox genes are implicated in hematopoietic stem cell (HSC) regulation as well as in leukemia development through translocation with the nucleoporin gene NUP98. Interestingly, an engineered NUP98-HOXA10 (NA10) fusion can induce a several hundred-fold expansion of HSCs in vitro and NA10 and the AML-associated fusion gene NUP98-HOXD13 (ND13) have a virtually indistinguishable ability to transform myeloid progenitor cells in vitro and to induce leukemia in collaboration with MEIS1 in vivo. METHODOLOGY/PRINCIPAL FINDINGS: These findings provided a potentially powerful approach to identify key pathways mediating Hox-induced expansion and transformation of HSCs by identifying gene expression changes commonly induced by ND13 and NA10 but not by a NUP98-Hox fusion with a non-DNA binding homedomain mutation (N51S). The gene expression repertoire of purified murine bone marrow Sca-1+Lin- cells transduced with retroviral vectors encoding for these genes was established using the Affymetrix GeneChip MOE430A. Approximately seventy genes were differentially expressed in ND13 and NA10 cells that were significantly changed by both compared to the ND13(N51S) mutant. Intriguingly, several of these potential Hox target genes have been implicated in HSC expansion and self-renewal, including the tyrosine kinase receptor Flt3, the prion protein, Prnp, hepatic leukemia factor, Hlf and Jagged-2, Jag2. Consistent with these results, FLT3, HLF and JAG2 expression correlated with HOX A cluster gene expression in human leukemia samples. CONCLUSIONS: In conclusion this study has identified several novel Hox downstream target genes and provides important new leads to key regulators of the expansion and transformation of hematopoietic stem cells by Hox

Acute diverticulitis in immunocompromised patients: evidence from an international multicenter observational registry (Web-based International Register of Emergency Surgery and Trauma, Wires-T)

Background: Immunocompromised patients with acute diverticulitis are at increased risk of morbidity and mortality. The aim of this study was to compare clinical presentations, types of treatment, and outcomes between immunocompromised and immunocompetent patients with acute diverticulitis. Methods: We compared the data of patients with acute diverticulitis extracted from the Web-based International Registry of Emergency Surgery and Trauma (WIRES-T) from January 2018 to December 2021. First, two groups were identified: medical therapy (A) and surgical therapy (B). Each group was divided into three subgroups: nonimmunocompromised (grade 0), mildly to moderately (grade 1), and severely immunocompromised (grade 2). Results: Data from 482 patients were analyzed—229 patients (47.5%) [M:F = 1:1; median age: 60 (24–95) years] in group A and 253 patients (52.5%) [M:F = 1:1; median age: 71 (26–94) years] in group B. There was a significant difference between the two groups in grade distribution: 69.9% versus 38.3% for grade 0, 26.6% versus 51% for grade 1, and 3.5% versus 10.7% for grade 2 (p < 0.00001). In group A, severe sepsis (p = 0.027) was more common in higher grades of immunodeficiency. Patients with grade 2 needed longer hospitalization (p = 0.005). In group B, a similar condition was found in terms of severe sepsis (p = 0.002), quick Sequential Organ Failure Assessment score > 2 (p = 0.0002), and Mannheim Peritonitis Index (p = 0.010). A Hartmann’s procedure is mainly performed in grades 1–2 (p < 0.0001). Major complications increased significantly after a Hartmann’s procedure (p = 0.047). Mortality was higher in the immunocompromised patients (p = 0.002). Conclusions: Immunocompromised patients with acute diverticulitis present with a more severe clinical picture. When surgery is required, immunocompromised patients mainly undergo a Hartmann’s procedure. Postoperative morbidity and mortality are, however, higher in immunocompromised patients, who also require a longer hospital stay

IL-6-Dependent PGE2 Secretion by Mesenchymal Stem Cells Inhibits Local Inflammation in Experimental Arthritis

BACKGROUND: Based on their capacity to suppress immune responses, multipotent mesenchymal stromal cells (MSC) are intensively studied for various clinical applications. Although it has been shown in vitro that the immunomodulatory effect of MSCs mainly occurs through the secretion of soluble mediators, the mechanism is still not completely understood. The aim of the present study was to better understand the mechanisms underlying the suppressive effect of MSCs in vivo, using cells isolated from mice deficient in the production of inducible nitric oxide synthase (iNOS) or interleukin (IL)-6 in the murine model of collagen-induced arthritis. PRINCIPAL FINDINGS: In the present study, we show that primary murine MSCs from various strains of mice or isolated from mice deficient for iNOS or IL-6 exhibit different immunosuppressive potential. The immunomodulatory function of MSCs was mainly attributed to IL-6-dependent secretion of prostaglandin E2 (PGE2) with a minor role for NO. To address the role of these molecules in vivo, we used the collagen-induced arthritis as an experimental model of immune-mediated disorder. MSCs effectively inhibited collagen-induced inflammation during a narrow therapeutic window. In contrast to wild type MSCs, IL-6-deficient MSCs and to a lesser extent iNOS-deficient MSCs were not able to reduce the clinical signs of arthritis. Finally, we show that, independently of NO or IL-6 secretion or Treg cell induction, MSCs modulate the host response by inducing a switch to a Th2 immune response. SIGNIFICANCE: Our data indicate that mscs mediate their immunosuppressive effect via two modes of action: locally, they reduce inflammation through the secretion of anti-proliferative mediators, such as NO and mainly PGE2, and systemically they switch the host response from a Th1/Th17 towards a Th2 immune profile

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Purpose: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality