Digital Twins for Industry 4.0 in the 6G Era

Having the Fifth Generation (5G) mobile communication system recently rolled out in many countries, the wireless community is now setting its eyes on the next era of Sixth Generation (6G). Inheriting from 5G its focus on industrial use cases, 6G is envisaged to become the infrastructural backbone of future intelligent industry. Especially, a combination of 6G and the emerging technologies of Digital Twins (DT) will give impetus to the next evolution of Industry 4.0 (I4.0) systems. This article provides a survey in the research area of 6G-empowered industrial DT system. With a novel vision of 6G industrial DT ecosystem, this survey discusses the ambitions and potential applications of industrial DT in the 6G era, identifying the emerging challenges as well as the key enabling technologies. The introduced ecosystem is supposed to bridge the gaps between humans, machines, and the data infrastructure, and therewith enable numerous novel application scenarios.Comment: Accepted for publication in IEEE Open Journal of Vehicular Technolog

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

Epidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling

The architecture of EGFR's basal complexes reveals autoinhibition mechanisms in dimers and oligomers

Our current understanding of epidermal growth factor receptor (EGFR) autoinhibition is based on X-ray structural data of monomer and dimer receptor fragments and does not explain how mutations achieve ligand-independent phosphorylation. Using a repertoire of imaging technologies and simulations we reveal an extracellular head-to-head interaction through which ligand-free receptor polymer chains of various lengths assemble. The architecture of the head-to-head interaction prevents kinase-mediated dimerisation. The latter, afforded by mutation or intracellular treatments, splits the autoinhibited head-to-head polymers to form stalk-to-stalk flexible non-extended dimers structurally coupled across the plasma membrane to active asymmetric tyrosine kinase dimers, and extended dimers coupled to inactive symmetric kinase dimers. Contrary to the previously proposed main autoinhibitory function of the inactive symmetric kinase dimer, our data suggest that only dysregulated species bear populations of symmetric and asymmetric kinase dimers that coexist in equilibrium at the plasma membrane under the modulation of the C-terminal domain

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Very late thrombosis after implantation of sirolimus eluting stent

Stent thrombosis after sirolimus eluting stent implantation has been reported to occur at six hours to 375 days after the procedure and usually within the two weeks after discontinuation of antiplatelet medication. A case is reported of very late stent thrombosis after 17 months of sirolimus eluting stent implantation and eight months after clopidogrel discontinuation despite aspirin continuation. This case underlines the possible need for long term antiplatelet medication among patients receiving sirolimus eluting stents

Hypocalcemic heart failure in thalassemic patients

Hypocalcemic cardiomyopathy in primary or secondary hypoparathyroidism is usually refractory to conventional treatment of cardiac failure. We report the case of a thalassemic patient with severe cardiac failure that might have been attributed to several factors, such as hemosiderosis, hypomagnesemia, and hypocalcemia, refractory to conventional cardiac therapy. Cardiac echocardiography showed impaired biventricular performance, and laboratory analyses revealed hypoparathyroidism due to hemosiderosis. When concomitant treatment of heart failure and calcium supplementation was initiated, correction of hypocalcemia resulted in clinical and laboratory improvement, providing strong evidence in support of our hypothesis about hypocalcemic myocardiopathy

Release of platelet activation markers during coronary angioplasty

Background Authors of several studies have reported that activation of platelets occurs during coronary angioplasty, but consistent results have not been obtained. Levels of serotonin in coronary circulation have been found to be elevated during percutaneous transluminal coronary angioplasty but greater than normal concentrations of beta-thromboglobulin and platelet factor 4 have not been detected. Objective To perform a serial analysis of platelet-activation markers with simultaneous measurements of revels of serotonin, beta-thromboglobulin and platelet factor 4 in blood samples from the coronary artery and coronary sinus of patients undergoing coronary angioplasty. Methods Twenty patients undergoing elective coronary angioplasty were studied. Measurements of levels of beta-thromboglobulin, platelet factor 4, and serotonin in samples from the ostium of the coronary artery and the coronary sinus were performed immediately before angioplasty and after the first balloon deflation. Results Concentrations of beta-thromboglobulin and platelet factor 4 in coronary artery and coronary sinus were elevated in all patients before dilatation, whereas concentrations of serotonin were elevated in 85% of the patients. Concentrations of all markers in coronary sinus decreased after the first inflation. The coronary-sinus: coronary-artery concentration ratios before dilatation for beta-thromboglobulin, platelet factor 4, and serotonin were >1 for the majority of patients, particularly for those with complex culprit lesions, indicating that coronary activation of platelets was occurring. Ratios remained unchanged or decreased after the first inflation, depending on initial values. Conclusions Both systemic and coronary activation occur in patients subjected to percutaneous transluminal coronary angioplasty before the onset of intervention. After balloon deflation the greater than normal baseline coronary-sinus: coronary-artery concentration ratios of ail markers (beta-thromboglobulin, platelet factor 4 and serotonin) tend to decline or remain unchanged, depending on the level of activation. Coron Artery Dis 11:391-398 (C) 2000 Lippincott Williams & Wilkins

Unusual association between increased bone resorption and presence of paroxysmal nocturnal hemoglobinuria phenotype in multiple myeloma

Paroxysmal nocturnal hemoglobinuria (PNH) clones deficient in glycosylphosphatidylinositol-anchored molecules, including CD55 and CD59, have been previously described in patients with multiple myeloma (MM). The aim of this study was to investigate the possible association between existence of the PNH phenotype and myeloma bone disease. Forty-three patients with newly diagnosed MM were the subjects of the study. Radiographic evaluation of the skeleton was performed in all patients at diagnosis. The following biochemical markers were measured: bone resorption markers (tartrate-resistant acid phosphatase isoform 5b [TRACP-5b]and N-terminal cross-linking telopeptide of type-I collagen [NTX]), bone formation markers (bone alkaline phosphatase [bALP] and osteocalcin [OC]), osteoprotegerin (OPG), soluble receptor activator of nuclear factor kappaB ligand (sRANKL), and interleukin 6 (IL-6). Detection of CD55- and/or CD59-deficient red cell populations was performed after diagnosis. Patients with MM had elevated mean baseline NTX, TRACP-5b, sRANKL, and IL-6 levels compared with controls, whereas the mean values of bALP, OC, and OPG were significantly decreased. Four patients had no osteolytic lesions, whereas 8 patients had 1 to 3 lytic lesions, and 31 patients had more than 3 lytic lesions and/or pathologic fractures in the skeletal survey. CD55- and/or CD59-deficient red cell populations were observed in 56% of patients with MM. There was a strong correlation between the presence of PNH-like erythrocytes and increased bone resorption, as measured by NTX, TRACP-5b, and sRANKL/OPG ratio (P <.03, P <.02, and P <.02, respectively). There was also a significant correlation between PNH phenotype and severe bone disease (P <.02). These results suggest that there is a possible link between PNH phenotype and increased osteoclastic activity in MM owing to a potential effect of myeloma microenvironment on a preexisting PNH clone. Further studies are required for clarifying this phenomenon and investigating possible mechanisms of this unusual association. (C) 2003 The Japanese Society of Hematology