Porphyromonas (P.) gingivalis lipopolysaccharide (Pg-LPS) in mouse diabetic nephropathy.The overexpression of sodium-glucose cotransporter 2 (SGLT2) in diabetic kidneys has been reported. It has also been established that the diabetic glomerular endothelium expresses the toll-like receptors TLR2 and TLR4. The present study aims to examine the renal SGLT2 induction by the TLR2/4 ligand Immunohistochemical study and tissue RT-PCR analyses were performed on mouse kidneys in streptozotocin (STZ)-induced diabetic ICR mice (STZ-ICR), in healthy ICR mice administered Pg-LPS (LPS-ICR), and in diabetic ICR mouse kidneys with Pg-LPS-induced nephropathy (LPS-STZ).In the quantitative analysis of blood sugar levels, the mean time to reach 600 mg/dl was shorter in the LPS-STZ than in the STZ-ICR kidneys. The rise in blood glucose levels was significantly steeper in the LPS-STZ than in the STZ-ICR kidneys. According to these data the LPS-STZ model suggests a marked glucose intolerance. The expression of SGLT2 was significantly stronger in the whole of the renal parenchyma of the LPS-STZ than in the LPS-ICR or in the STZ-ICR. The expression of SGLT2 was observed both in the renal tubules and around the renal tubules, and in the glomeruli of the LPS-STZ kidneys. In the analysis by tissue real-time PCR and cell ELISA, the expression of the SGLT2 gene and protein was significantly stronger in the LPS-STZ than in the LPS-ICR or in the STZ-ICR. There were no differences in the renal SGLT2 production in the LPS-ICR and the STZ-ICR kidneys.P. gingivalis LPS. Periodontitis may be an exacerbating factor in diabetic nephropathy as well as in diabetes.Abnormally high renal expression of SGLT2 occurs in diabetic kidneys with  Porphyromonas (P.) gingivalis LPS (Pg-LPS) induces the production of inflammatory agents by host defense systems recognizing lipid A and co-existing molecules of TLR2 and TLR4 [The pathological mechanisms which cause individual differences in the progression of diabetes and in the accompanying complications are not fully elucidated. Diabetic glomerulosclerosis exhibits characteristics such as: diffuse lesions due to increased mesangial matrix including type I collagen by the production of several different cytokines through the recognition of advanced glycation end products (AGE) in a hyperglycemic environment ; nodularand TLR4 –20. The and TLR4 , 22. It and TLR4 –25. Inteand TLR4 –27.P. gingivalis in diabetic kidneys. The present study aims to examine the expression of SGLT2 in mouse kidneys with Pg-LPS-induced diabetic nephropathy.We recently reported that the glomerular endothelium expresses TLR2 and TLR4 in streptozotocin (STZ)-induced diabetic mice , and than = 8 per group) which is the smallest number that makes it possible to achieve statistically reliable results: the healthy control ICR mice without any treatment (data not shown), control ICR mice treated with Pg-LPS , control ICR mice treated with STZ , and ICR mice treated with Pg-LPS and STZ . At the end of the designated period of the experiments, all mice were euthanized, and tissue was collected.All processes for the upkeep of animals and experiments were conducted in the Fukuoka Dental College Animal Center following the conditions and procedures described elsewhere . This stThe immunohistochemical investigation was performed by the method described elsewhere . BrieflyThe analysis was as described elsewhere . ImmediaThe analysis was performed by modifying the cell ELISA for tissue, and is as described elsewhere . Normal P < 0.01) was determined by one-way ANOVA and two-tailed unpaired Student’s t test with STATVIEW 4.51 software . The corresponding author was fully aware of the group allocation at the different stages of the experiments. The data analysis and assessments were performed by all co-authors.Animal experiments were performed with 32 mice in 4 groups (8 mice in each group) as described above. All experiments for immunohistochemistry, RT-PCR and ELISA were repeated five times. Data were expressed as the mean + SD and mean values were calculated with standard deviations. The statistical significance of the differences , LPS-ICR, and STZ-ICR specimens and strongly in the whole of the renal parenchyma and in the glomeruli of the LPS-STZ specimens Fig. . There wP. gingivalis infection is the cause of the renal overexpression of SGLT2 under diabetic conditions, and that the SGLT2 overexpression does not occur only with one of diabetes or Pg-LPS. Since the glucose reabsorption by the overexpressed SGLT2 in the renal tubules is thought to be an important factor in exacerbating diabetes [Glomerulosclerosis is well-known as a serious complication which causes diabetic nephropathy in diabetes mellitus. We have recently reported that Pg-LPS exacerbates mouse diabetic nephropathy, and that diabetic nephropathic mice show glomerulosclerosis with the renal accumulation of type 1 collagen –30. Therdiabetes –33, thesP. gingivalis in diabetic kidneys increase the glucose reabsorption.In this study the expression of SGLT2 was much stronger throughout the renal parenchyma of the LPS-STZ than in kidneys of ICR (not shown), STZ-ICR, and LPS-ICR Fig. . It was E. coli could also be present. Such intestinal microorganisms and the LPS enter the liver via the enterohepatic circulation and are immediately sterilized, however, oral bacteria enter the systemic circulation directly without detoxification. This is the anatomical reason why head and neck infections spread to the whole body and reaction products accumulate in the kidneys [P. gingivalis LPS is a cause of glomerulosclerosis in diabetic mice with the accumulation of type 1 collagen and inflammatory cytokines in the glomeruli [P. gingivalis like the TLR recognition induce the production of inflammatory cytokines and progressively accelerate the abnormal expression of SGLT2 in glomeruli, renal proximal tubules, intertubular spaces of the renal parenchyma, and in the peritubular capillaries. Altogether this could suggest that the periodontal pathogen Pg-LPS causes the nephropathy in diabetic patients via TLR expressed by glomerular vascular endothelial cells. Further, the production of inflammatory cytokines by Pg-LPS may increase the SGLT2 expression in renal tubules and exacerbate diabetes.Commonly occurring intestinal inhabitants like  kidneys –27. We rlomeruli –30. As nlomeruli –41. Sinclomeruli –34. It mP. gingivalis like TLR recognition induce the production of inflammatory cytokines and progressively accelerate the inflammatory overexpression of SGLT2 in the renal proximal tubules under diabetic conditions. Our results suggest that periodontitis could be an exacerbating factor in both diabetic nephropathy as well as in diabetes.The results here suggest that renal inflammatory events by


The viral capsid plays a key role in HIV-1 reverse transcription. Recent studies have demonstrated that the small molecule IP6 dramatically enhances reverse transcription in vitro by stabilizing the viral capsid. Reverse transcription results in marked changes in the biophysical properties of the capsid, ultimately resulting in its breakage and disassembly. Here we review the research leading to these advances and describe hypotheses for capsid-dependent HIV-1 reverse transcription and a model for reverse transcription-primed HIV-1 uncoating. During infection by retroviruses, including the human immunodeficiency virus type 1 (HIV-1), the positive-sense viral RNA genome is copied into double-strand DNA by reverse transcription. This reaction is catalyzed by the viral reverse transcriptase enzyme (RT), which synthesizes both the negative and positive-sense DNA strands and generates the DNA sequence elements required for integration and subsequent expression of the integrated provirus. Reverse transcription is an essential step in HIV-1 infection, a major antiviral target, and a biological process of great interest. Research during the past 20 years has revealed that the viral capsid plays an essential role in reverse transcription, yet the mechanism for this is unknown. Moreover, reverse transcription appears to induce structural changes in the capsid. Here we describe the research toward an understanding of the role of the capsid in reverse transcription and highlight recent advances in this field.lentiviridae genus of retroviruses to which HIV-1 belongs. Although the capsid morphology is different in other retrovirus genera, the basic geometric principles of capsid structure (lattice of hexamers with 12 pentamers) is conserved among retroviruses. The particular distribution of the pentamers is what determines the shape of the particular viral capsid.Human immunodeficiency virus type 1 (HIV-1) particles contain a nucleoprotein core surrounded by a lipid membrane  The capsid may serve as a molecular reaction vessel for reverse transcription. The capsid is a closed volume composed of ~ 1200 molecules of CA. By contrast, it is estimated that ~ 50 molecules of active RT are present within the virion  with a fosing RT .Recent biochemical studies have strengthened the conclusion that the viral capsid plays a direct role in HIV-1 reverse transcription. For decades, researchers noted that HIV-1 reverse transcription is inefficient in vitro. Endogenous reverse transcription (ERT) assays were performed by incubating virions with dNTPs in the presence of detergents to permeabilize the viral membrane. In these reactions, only a fraction of viral genomes is copied into DNA, and the reactions produce few if any full-length DNA molecules. By contrast, ERT reactions with murine and avian retroviruses can efficiently generate full-length DNA molecules capable of producing a spreading infection upon transfection of permissive host cells –46. Thes. Furthermore, addition of IP6 to purified recombinant CA protein resulted in a dramatic enhancement of CA assembly yielding high quantities of cone-shaped capsids resembling native HIV-1 cores [As mentioned previously, recent attention has been focused on the small molecule IP6, an abundant eukaryotic cell metabolite. IP6 is synthesized from phosphatidylinositol 4,5)-bisphosphate in a series of reactions by host enzymes including the inositol polyphosphate multikinase (IPMK) and inositol pentakisphosphate 2-kinase (IPPK) (reviewed in ). IP6 pl,5-bispho-1 cores . The res-1 cores , an effe-1 cores , 53.Recently, Christensen and coworkers identified reaction conditions in which HIV-1 particles undergo efficient ERT . The autDespite the strong requirement for IP6 observed in ERT reactions, depletion of IP6 and its precursor IP5 from target cells resulted in little to no reduction in the early steps of HIV-1 infection. Mallery and coworkers disrupted the IPMK gene in 293T cells and evaluated the consequences for HIV-1 infection . BecauseThe observation that capsid stabilization by IP6 permits efficient reverse transcription seems likely to lead to a greater understanding of HIV-1 reverse transcription in the natural context of the viral core. In the Christensen study, the ERT reaction was associated with partial capsid disassembly in vitro, providing an initial structural glimpse into the process of HIV-1 uncoating which is intimately connected to nuclear entry of the virus. Indeed, a recent imaging study shows that HIV-1 cores appear to enter the nucleus by penetrating nuclear pores in an intact or nearly intact state, after which they complete reverse transcription and undergo uncoating and integration . These fAs stated previously, early studies of endogenous reverse transcription in avian retroviruses indicated that these reactions could occur relatively efficiently in the absence of added host factors, raising the question as to how these reactions occur in the absence of capsid stabilization. Because the HIV-1 capsid has been studied more intensively than capsids of other retroviruses, the explanation for these apparent differences is not yet known. Capsid metastability may be a specific feature of lentiviruses, and it is possible that non-lentiviral capsids are inherently more stable. It is currently unknown whether the mature capsids of retroviruses of genera other than lentiviruses are also stabilized by cellular metabolites.Using approaches involving immunofluorescent imaging and escape from host restriction, the Hope lab has shown that reverse transcription drives HIV-1 capsid disassembly (uncoating) from the core in target cells . ConsistIn subsequent studies, we employed AFM to analyze the effects of ERT on the properties of HIV-1 cores. Reverse transcription induced an increase in core stiffness. High resolution mechanical mapping of the core surface revealed the appearance of a striated pattern suggestive of a coiled structure beneath the capsid surface. Subsequently, the coiled structure vanished and the stiffness of the capsid dropped to a level below its initial value. Extended incubation for several hours resulted in a softening of the core and its eventual disassembly . These rReverse transcription of retroviruses occurs in a series of stages (see  for a de. showing capsid opening and DNA emergence at a late stage of ERT [Recently we analyzed the effects of IP6 on the dynamics of HIV-1 core stiffness changes during ERT . Additioe of ERT .Fig. 2IlWhile the molecular basis for reverse transcription-induced uncoating is unknown, it seems plausible that the structural changes in the ribonucleoprotein complex within the capsid that must occur during reverse transcription result in direct forces on the viral capsid, potentially damaging the lattice. Such stress may result from changes in the structural state of the nucleic acid. Double-strand DNA is more rigid than RNA which adopts a relatively compact tertiary structure based on flexibility in base pairing. Stress on the capsid could also result from changes in internal pressure of the core owing to osmotic effects. During DNA synthesis, addition of a nucleotide releases pyrophosphate and incorporation of a nucleotide into the DNA chain, resulting in a net charge increase of − 1. Hydrolysis of pyrophosphate to phosphate would further increase the net negative charge in the core by − 2. This could lead to an influx of water and ions, transiently increasing the pressure within the capsid. While this model is speculative, it is consistent with the kinetics of stiffness spike formation during ERT and seems to account for the rapid reversal of capsid stiffness to baseline with each spike. Nonetheless, it does not explain why capsid stiffness does not remain elevated during the prolonged stage of full-length minus strand synthesis.The mechanical properties of the viral capsid are fascinating. The structure is variably curved and flexible, and it undergoes elastic deformation during reverse transcription. Moreover, addition of IP6 and the CA-targeting inhibitor PF74 stiffens the capsid. Using AFM operating in the ultrafast scanning mode, we have observed that capsid stiffening is associated with rounding of the core, which returns to an elongated shape upon relaxation . This suRecent studies involving ERT reactions have established the essential role of the capsid in HIV-1 reverse transcription, but the mechanisms by which the capsid performs its critical functions remain to be determined. Biophysical studies have also revealed punctuated effects on the mechanical properties of the core during reverse transcription in vitro. As a system to study reverse transcription within the viral capsid and the structural consequences thereof, studies utilizing the ERT reaction are likely to provide further interesting insights into the key processes of HIV-1 reverse transcription, uncoating, nuclear import, and integration.


We present a yet to be described association of SARS-CoV-2 infection with Kikuchi-Fujimoto disease.A 32-year-old physician with history of SARS-CoV-2 infection presented to the emergency department with 2 weeks of fever, chills, and right sided cervical lymphadenopathy. He was treated empirically for presumed folliculitis with worsening of symptoms leading to repeat presentation to the emergency department.Extensive workup was unrevealing of an infectious cause and needle biopsy of the lesion was unrevealing. An excisional lymph node biopsy revealed follicular hyperplasia with necrotic foci showing abundance of histiocytes at the edge of necrosis with CD8 predominance of T-cells. Final diagnosis was deemed to be Kikuchi-Fujimoto disease. Antibiotic therapy was discontinued, and the patient’s symptoms resolved with steroid therapy and expectant management.This is the first report of a patient developing Kikuchi-Fujimoto disease following SARS-CoV-2 infection. Clinicians should be aware of Kikuchi-Fujimoto disease as a possibility when approaching patients with hyper-inflammatory states who present with cervical lymphadenopathy. The World Health Organization declared COVID-19 a global pandemic in January of 2020 [A 32-year-old male physician of Indian descent with a history of hypertension, latent tuberculosis treated with 4 months of rifampin completed 1 month prior to presentation, and resolved symptomatic SARS-CoV-2 infection diagnosed 3 months prior and not requiring hospitalization presented to the Emergency Department. His chief complaints at this time were 2 weeks of fever, chills, and neck swelling which began after a haircut. He had completed a course of doxycycline followed by trimethoprim-sulfamethoxazole for presumed folliculitis without improvement. On presentation to the hospital the patient complained of right neck swelling, worsened fatigue, myalgias and fevers. A CT with contrast of the neck was obtained and the patient was discharged with a plan for outpatient biopsy  with plan for inflammation control. The patient had a favorable response to steroid treatment and since discontinuation has remained asymptomatic with resolution of all symptoms.SARS-CoV-2 infection has been declared a Public Health Emergency of International Concern by the WHO on January 30th, 2020. Since this time the risks of transmission to healthcare workers has been well documented. Our patient was a physician known to be infected with SARS-CoV-2 in March with resolution of symptoms in April. The repeat positive test in July may indicate a false positive, viral shedding, DNA presence without infectivity or a new SARS-CoV-2 infection. There are case reports of patients with persistent SARS-CoV-2 positive tests despite clinical recovery. These individuals are thought to be chronic shedders of virus despite the resolution of symptoms . The sigKikuchi-Fujimoto disease is a rare clinical entity known as histiocytic necrotizing lymphadenitis characterized most often by several weeks of tender lymphadenopathy  and fever in individuals of Asian descent under the age of 40. The patient described above meets this characterization as he is an Indian male below the age of forty who suffered with those exact symptoms. The etiology of KFD has been postulated to be either infectious or autoimmune in nature, but no study has identified a specific pathogen associated with the disease syndrome. Previous case reports have identified the disease in patients with other autoimmune conditions . The casThere is no specific test which is diagnostic for KFD. Pathology from lymph node specimens remain essential for diagnosis with excisional biopsy preferred as core biopsy samples are frequently non-diagnostic due to low sample yield. The differential diagnosis includes infectious lymphadenitis of different etiologies, autoimmune lymphadenopathy (primarily SLE lymphadenopathy), and non-Hodgkin lymphoma. SLE lymphadenopathy is the most difficult to resolve as it is histologically and immunohistochemically indistinguishable from KFD. Importantly, lymphoma must be ruled out as both entities share similar clinical presentations and at times histologic features .Yersinia enterocolitica can also present with paracortical expansion with necrosis and histiocytic infiltrate, thus mimicking KFD morphologically. Infectious mononucleosis usually shows marked follicular hyperplasia and paracortical expansion with an increase in immunoblasts and scattered Hodgkin- and Reed-Sternberg–like cells. Single-cell apoptosis and foci of necrosis are also commonly seen. Epstein-Barr virus–encoded RNA in situ hybridization is usually strongly and diffusely positive and resolves the diagnostic dilemma [Several infectious etiologies, including viruses, tuberculosis, histoplasmosis, leprosy, cat-scratch disease, and  dilemma . SpecialActive tuberculosis infection can present in a similar manner as this patient presented and given his history of latent tuberculosis it was important to rule this out as a causative factor. He was known to have completed a 4 month course of rifampin only 1 month earlier and was asymptomatic throughout treatment. The acid-fast bacilli blood cultures on admission to the hospital were negative. Lymph node excisional biopsy revealed no granulomas and no evidence of acid-fast bacilli. Additionally, there was no growth of acid-fast bacilli on culture of the patient’s tissue. Although there was a history of tuberculosis infection; there was no histologic or microbiologic evidence of extrapulmonary tuberculosis infection despite robust testing. Active tuberculosis infection as etiology of this patient’s symptoms was deemed to be less likely.The lymph node specimen was also tested for SARS-CoV-2 and was found to be undetectable. Experience in our laboratory shows that in known SARS-CoV-2 positive individuals there is often a failure to amplify the virus, via PCR, in tissues other than the lung or liver due to low viral load. The lack of detection within the lymph node specimen does not rule out that this patient had active SARS-CoV-2 infection, but makes the diagnosis of Kikuchi-Fujimoto disease possible.This is the first case report on a patient presented developed Kikuchi-Fujimoto disease following SARS-CoV-2 infection. Clinicians should be aware of Kikuchi-Fujimoto disease as a possibility when approaching patients after SARS-CoV-2 infection who present with cervical lymphadenopathy.


Water droplets sitting between wires are ubiquitous in nature and industry, often showing irregular  droplet shapes. To understand their topological singularity and evaporation mechanism, measuring volume changes of irregular water droplets is essential but highly challenging for small-volume water droplets. Here we experimentally explore topological heterogeneity and evaporation dynamics for irregular water droplets between wires with four-dimensional X-ray microtomography that directly provides images in three spatial dimensions as a function of time, enabling us to get three-dimensional structural and geometric information changes with time. We find that the topological heterogeneity of an irregular droplet is due to the local contact lines and the evaporation dynamics of an irregular droplet is governed by the effective contact radius. This study may offer an opportunity to understand how the topological heterogeneity contributes to the evaporation dynamics of irregular water droplets. To understand the wetting phenomena and the evaporation dynamics of irregular water droplets on wires, real-time and highly-precise visualization of small-volume water droplets is essential but difficult with conventional imaging techniques. The topological heterogeneity of the irregular droplet makes it challenging to acquire volume measurements unless one uses a precise and accurate mass balance, particularly for water droplets smaller than microliters. Visualizing the evaporation dynamics of irregular water droplets smaller than microliters and measuring their volume changes with time are highly challenging.Small-volume (g), e.g., A tiny droplet on a flat solid substrate usually has topological homogeneity when the contact lines are identical at all radial directions and the droplet size is smaller than the capillary length. The capillary length is defined as 19. The high-speed high-resolution 4D X-ray microtomography enables us to achieve the 3D images changing with time for microliter or nanoliter irregular water droplets during evaporation. From our observations, we demonstrate how irregular water droplets evaporate in the air and show unprecedented evaporation dynamics for the irregular microliter water droplets. This study may offer an opportunity to understand the topological heterogeneity and the evaporation dynamics of irregular water droplets.In this study, we experimentally explore the topological heterogeneity and the evaporation dynamics of irregular water droplets setting between crossing wires with four-dimensional (4D) X-ray microtomography that directly provides three-dimensional (3D) structural and geometric information that changes with time18. We made two crossing glass wires from thin borosilicate glass tubes pulled by a commercial puller . The thin glass tube was modified from the original tube  with an outer diameter and a thickness of 1.0 and 0.2 mm, respectively. The glass wires were fixed in a cross position and two distinct included angles at the crossing point were tested as 22.07To visualize evaporating irregular water droplets between two crossing glass wires, we utilized high-speed high-resolution 4D X-ray microtomography techniqueshttp://www.woorimtech.com/page/octopus411). After the reconstruction, the reconstructed images were loaded into Avizo software . We applied non-local means filter to reduce the noise and improve image quality. Segmentation of background, water droplet, and wires was possible based on their relatively high attenuation coefficient difference, which depends on the material density and the atomic number. Thanks to the high spatial resolution of 1.1 μm and the high temporal resolution of 5 ms, the errors of segmentation were negligible. Based on the gray-scale intensity histogram, the threshold segmentation was carried out into the two different labels of droplets and wires. By measuring all the voxels in the droplet labels, we were able to measure the droplet volumes. By measuring the intersections between droplets and wires, we measured the contact surface areas. Finally, the reconstructed 3D images taken from X-ray microtomography of the same water droplet could be monitored as a function of time.We used the 6C Biomedical Imaging (BMI) beamline in the Pohang Light Source II (PLS-II) that provided monochromatic synchrotron X-rays with 15 keV energy. The layout of the PLS-II 6C instrumentation included a scintillator (LuAG:Ce 50 μm), a 10X lens coupled with an sCMOS  camera, producing 2.222 cover glass substrate (Marienfeld) was also obtained. The droplet mass was measured every 1s and the mass-based experiments were repeated four times for each condition.Additionally, the electronic balance  was separately used to measure the evaporation dynamics of the irregular water droplets  measured by 4D X-ray microtomography show a proportionality, as described by 20, indicating that the water vapor flux would rapidly diverge at the contact lines as a kind of the edge effects23.We suppose that the evaporation rate would be proportional to the contact radius mentclass2pt{minimThe effective contact radius dependence of the evaporation rate or the We experimentally explore how the irregular small-volume water droplet evaporates. The topological heterogeneity of the irregular water droplet is essential in understanding the actual wettability and the evaporation behaviors of the irregular water droplet. To measure the volume changes, we use the 4D X-ray microtomography that directly provides three-dimensional structural and geometric information as a function of time for the single irregular water droplet. We find that the evaporation dynamics of the irregular droplet is governed mainly by the effective contact lines. This study taken with the 4D X-ray microtomography guides a feasible way to characterize the topological complexity of the small-volume irregular water droplets that would determine the irregular contact lines, which provides a better understanding of the evaporation of the ultrasmall irregular water droplets.


Q  of over unity was reached in the JT-60U [Fusion is an ideal clean energy for human beings in the future. Significant progress has been achieved on tokamak research after successful construction of many large tokamak facilities and many years of experiments, which have established a sound base for tokamak experimental reactors. More than 10 MW fusion power has been produced in the Tokamak Fusion Testing Reactor (TFTR)  tokamakse JT-60U  device de JT-60U  and Koree JT-60U  tokamaksQ = 10 lasting for 400 seconds. There are still some risks in meeting this goal. The frontier and the most important issues for the next 10 years are the control of off-normal events, confinement and transport physics of the burning plasma, high-power particle and heat flux exhaust on the divertor, energetic particle behavior, high-performance long pulse and steady-state operation, and tritium breeding and retention.The world tokamak community has confidence that ITER will be successfully constructed without obstruction; the target for this is 2025. The scientific goal of ITER is to demonstrate the feasibility of 500 MW fusion power with Transient events can release plasma energy in a very short time and could damage plasma-facing components easily. These phenomena include minor and major disruptions and very localized plasma edge instabilities. Any major disruption in ITER could easily destroy some of the plasma-facing components, and therefore it is essential to develop robust ways to avoid or mitigate disruptions to prevent plasma-facing material from being damaged, to allow achievement of high-performance plasma and to ensure continuous operation in ITER. An elevated effort is needed in theory, modeling and technology for more advanced control to achieve a reliable, disruption-free operation scenario with 99% reliability.In ITER, a burning plasma will be tested while the plasma is heated by fusion-born alpha particles. Energetic alpha particles from fusion reactions heat and sustain the burning plasma, but they also bring plasma instabilities. It is clear that a significant loss of alpha/fast ions may degrade the plasma heating and current drive efficiency and may lead to significant loss of plasma performance. Theory and modeling predictions of alpha particle control and reliable alpha particle diagnostics are needed to be explored with simple technical solutions in preparation for the ITER burning plasma physics experiments in the near future.High-performance steady-state H-mode operation with a fusion power of 500 MW over 400 s is the premier goal of ITER operation, which needs integrated control for many physical quantities from both the core and edge. To maintain high core plasma performance, efficient plasma heating and current drive in the H-mode scenario, high bootstrap current fraction and low impurity concentration are required simultaneously. In the edge and scrape-off layer regions, it is essential to have a controllable plasma surface interaction by using strong gas puffing to keep a low ion temperature to sustain low impurity generation and physical sputtering on the tungsten divertor. The current superconducting tokamak devices such as EAST and KSTAR should make continued effort on these problems and achieve steady-state high-performance plasmas.2 peak heat fluxes that nearly reach the present technological limit are foreseen and the ITER mono-block divertor solution is not sufficient for DEMO. The future DEMO divertor working conditions are very challenging and need both new physical (detached plasma and new divertor configuration) and technical (over 20 MW/m2 target heat load) solutions. Moreover, integrated experiment validation with a heat load between 10 to 20 MW/m2 on a long-pulse tokamak is also needed in the near future.In ITER, over 10 MW/mQ burning plasma operation and fusion material in its early phase of operation. Almost all DEMO-reactor-related issues will be tested in the late phase of experimental operation together with experiences from ITER Q = 10 operation results. The DEMO-like advanced and reliable steady-state operation scenario will be achieved by a combination of high bootstrap current and efficient auxiliary driven current. The goal of tritium self-sufficiency will be obtained with the techniques of high fuel burning rate (over 3%), advanced tritium breeding blankets and a large-scale tritium factory, together with an advanced safety operation for the burning plasma and material technology development. By conducting engineering test and DEMO validation experiments respectively on CFETR, tremendous leaps from the engineering test reactor to the DEMO reactor and eventually the prototype of a power plant will be achieved by the mid-2050s.There are still many scientific and technical difficulties for successful construction and operation of the future DEMO after ITER in terms of plasma performance, enabling technologies, material and component performance and safety issues. At present, China is leading the efforts towards a tokamak DEMO, and the development roadmap of Chinese tokamak fusion is shown in Fig. Tc magnets, advanced new Nb3Sn magnets, megawatt continuous wave gyrotron development, a steady-state negative neutral beam injection system, a remote handling (RH) system, a new DEMO divertor, advanced fusion materials and breeding blankets. Several testing facilities are needed for simulating future CFTER operation without a nuclear environment, such as a superconducting testing facility, a vacuum vessel for installation and removal by RH, a tritium exhaust testing facility, and a DT neutron system for blanket testing. With successful construction of these R&D and testing facilities, together with further engineering testing, large-scale simulation and modeling and tokamak experiments, a more solid basis will be established for the beginning of CFETR construction.Large-scale R&D that addresses the major challenges for CFETR should start as soon as possible, such as high-performance superconducting magnets including high-


The volumes of tissue activated were then used to make voxel-wise and structural connectivity correlations with clinically observed tremor suppression. The volume of the tissue-activated analyses identified the optimal region of stimulation at the ventralis oralis posterior ventralis intermedius border intersecting with the dentato-rubro-thalamic tract. A regression model showed strong connectivity to the supplemental motor area was positively associated with tremor suppression (r = 0.66) in this cohort, whereas connectivity to the primary motor cortex was negatively associated with tremor suppression (r = −0.69), a finding opposite to that seen in ventralis intermedius deep brain stimulation for essential tremor. Comparing the structural connectivity to that of an essential tremor cohort revealed a distinct network that lies anterior to the essential tremor network. Overall, the volumes of tissue activated and connectivity observations converge to suggest that optimal suppression of multiple sclerosis tremor will likely be achieved by directing stimulation more anteriorly toward the ventralis oralis posterior and that a wide field of stimulation synergistically modulating the ventralis oralis posterior and ventralis intermedius nuclei may be more effective than traditional ventralis intermedius deep brain stimulation at suppressing the severe tremors commonly seen in complex tremor syndromes such as multiple sclerosis tremor.Tremor is a common symptom in multiple sclerosis and can present as a severe postural and action tremor, leading to significant disability. Owing to the diffuse and progressive nature of the disease, it has been challenging to characterize the pathophysiology underlying multiple sclerosis tremor. Deep brain stimulation of the ventralis intermedius and the ventralis oralis posterior thalamic nuclei has been used to treat medically refractory multiple sclerosis tremors with variable results. The aim of this study was to characterize multiple sclerosis tremor at the network level by applying modern connectomic techniques to data from a previously completed single-centre, randomized, single-blind prospective trial of 12 subjects who were treated with unilateral dual-lead  thalamic deep brain stimulation. Preoperative T et al. report that supplemental motor area connectivity was positively associated with tremor suppression, whereas primary motor cortex connectivity was negatively associated with tremor suppression in unilateral dual-lead thalamic deep brain stimulation for multiple sclerosis tremor. Optimal tremor involved neuromodulation of the ventralis oralis thalamic nucleus.Wong   There can also be associated dystonia, ataxia and/or other debilitating neurological manifestations.4 The pathophysiology underpinning MS tremor has been difficult to elucidate because the causal lesions tend to be multiple and diffuse, and the disease itself is variably progressive. Consequently, defining precise MS-related anatomic correlations has been challenging.5 In clinical practice, tremor in MS is one of the most difficult conditions to address with pharmacologic therapy alone.6 Deep brain stimulation (DBS) of the ventralis intermedius (VIM) nucleus of the thalamus, the ventralis oralis posterior (VOp) nucleus of the thalamus and/or the zone incerta have all been used in an effort to address medically refractory MS tremor.7–10 The degree of tremor suppression post-DBS has been documented to be highly variable with high recurrence rates. Additionally, the outcomes are frequently affected by disease progression.8Tremor is a common symptom in multiple sclerosis (MS) and is estimated to have a lifetime prevalence as high as 45–75%.11 The goal of the present study was to apply modern connectomic techniques to data from that study in an effort to better understand treatment outcomes and optimize future DBS surgical interventions.Recently, our group published an National Institutes of Health (NIH)-funded pilot trial of unilateral dual-lead (VIM + VOp) thalamic DBS to treat medically refractory MS tremors.11 Participants with MS and medically refractory tremor underwent dual-lead thalamic (VIM and VOp) DBS  for tremor suppression. Participants were randomized into two groups (VIM or VOp) for single-lead stimulation and optimization for the first three months following implantation. At the 3-month visit, both leads were activated, and programming optimization continued monthly until ∼6 months. The Fahn–Tolosa–Marin Tremor Rating Scale (TRS) was collected at 3- and 6-months post-DBS implantation in the DBS OFF and DBS ON states.12 The 3-month TRS score was obtained during single-lead stimulation, whereas the 6-month TRS score was obtained during dual-lead stimulation. The subsequent statistical analyses in this study used the motor score of the TRS.Data were drawn from a previously completed single-centre, randomized, single-blind prospective MS DBS trial conducted at the University of Florida . The study design, surgical procedure and programming protocol have previously been described.1-weighted MPRAGE) using a two-stage linear registration that was implemented in advanced normalization tools (ANTs).13 Preoperative and postoperative acquisitions were spatially normalized into MNI_ICBM_2009b_NLIN_ASYM template space using the symmetric normalization (SyN) registration approach as implemented in ANTs.14 Non-linear deformation into template space was achieved in five stages: after two linear (rigid followed by affine) steps, a non-linear (whole brain) SyN-registration stage was followed by two non-linear SyN registrations that consecutively focused on the area of interest which was defined by subcortical masks in Schoenecker et al.15 The DBS contacts on each lead were localized using the PaCER method within the lead DBS advanced imaging pipeline with manual verification and correction as needed.16–18 The volume of tissue activated (VTA) was estimated using finite-element modelling using the lead DBS system. An electric field was generated over a tetrahedral mesh head model that was defined as an isotropic volume with a symmetric conductivity of 0.14 S/m.19 An electric field threshold of 0.2 V/mm was used to define the VTA boundary.20The postoperative high-resolution CT head was co-registered to the preoperative MRI brain  for the improvement weighted VTAs were estimated using FSL’s COG function and reported in Montreal Neurological Institute (MNI) space. The VTAs were then visualized alongside the dentato-rubro-thalamic tract (DRTT) as defined by the DBS Tractography Atlas.26The VTAs were determined for each subject at 3- and 6-months post-DBS implantation based on the programming parameters documented at the start of the respective visit. A unique VTA was calculated for each activated lead at the two respective time points. The VTAs in the right brain hemisphere were non-linearly warped to the left hemisphere based on the MNI_ICBM_2009b_NLIN_ASYM template. Voxel-wise analysis utilizing FSL’s fslmaths function was then conducted based on previously published methods to determine the optimal stimulation location.27–29 Regions of interest (ROIs) at the cortex were defined using the Human Connectome Project Multi-modal parcellation (HCP-MMP) atlas and chosen from established structural connectivity-based segmentations of the thalamus for VIM DBS.31 Connectivity to six cortical regions were defined as follows: (i) primary visual cortex (PVC), HCP-MMP label V1; (ii) primary motor cortex (PMC), HCP-MMP label 4; (iii) Supplemental motor area (SMA), HCP-MMP label 6ma 6mp; (iv) temporal lobe (TL), HCP-MMP label PIT MT A1; (v) somatosensory complex (SSC), HCP-MMP label 1 2 3a; (vi) primary sensory cortex (PSC), HCP-MMP label 3b. Fibre tracking of each ROI was performed using 200 000 seeds and normalized to the total number of streamlines generated for each participant to define ‘connectivity’ to the ROI. Streamlines were generated via deterministic tractography in DSI Studio (http://dsi-studio.labsolver.org/).32 ROIs with a connectivity of 0 were discarded from further analysis. The connectivity was then analysed via linear regression to the % improvement in total TRS at 3- and 6-months post-DBS implantation. The Spearman’s rank correlation coefficient was calculated for each linear regression. Statistics were calculated using GraphPad Prism 9.1 .The VTAs were used as seeds to calculate structural connectivity using deterministic tractography. A group averaged diffusion MRI template of 1065 healthy adults from the Human Connectome Project was utilized.33–35 This method utilized previously published techniques to highlight fibre tracts that are predictive of positive outcomes for each respective cohort.36 Through this analysis, we are able to compare the spatial differences in fibre tracts between the two groups that correlated with tremor suppression. This allowed for exploration of neuromodulation at the network level for these two tremor syndromes and elucidation of the pathological network driving MS tremor. The clinical metric for comparison was the percent TRS motor score change from baseline pre-DBS to 6-months postimplantation. Lead localization and VTAs for the ET cohort were determined using a similar method as mentioned previously. A normative connectome of 32 healthy subjects from the Human Connectome Project was designated as the structural group connectome for this analysis.37 All VTAs were binarized and independently used as a seed to estimate structural connectivity within the normative connectome. After the structural connectome was generated, the fibre tracts were refined to only include tracts that traversed at least 20% of the VTAs but no greater than 80% of the VTAs. For each fibre track generated, a two-sample t-test was calculated to compare the difference in percent TRS motor score change in VTAs the track traverses through versus VTAs the track does not traverse through.34 The corresponding T-score labelled each fibre as either ‘favourable’ or ‘unfavourable’ and was used to colorize each fibre track. After iterating through each fibre tract, the resulting connectome was filtered to include only tracts with a positive T-score. This equated to a connection with VTAs that was associated with an improvement in TRS motor score, thus representing a ‘favourable fibres’ group. The favourable fibres in the MS tremor cohort were colorized as blue, whereas the favourable fibres in the ET cohort were colorized as orange. Cortical connectivity of the two fibre groups was visualized using the Surf Ice surface rendering tool (https://www.nitrc.org/projects/surfice).Discriminative fibre tract analysis was then conducted to compare the connectivity profile in this cohort with 83 essential tremor (ET) subjects treated with VIM DBS at University of Florida.The data supporting the findings of this study are available from the corresponding author upon reasonable request.Twelve participants  were analysed from the parent study. One participant was excluded due to hardware infection ultimately requiring DBS hardware removal. Participant demographics and surgical information are summarized in Improvement weighted VTAs of VIM and VOp stimulation at 3- and 6-months post-DBS implantation are summarized in A network level comparison of ‘favourable fibres’ between the MS cohort and ET cohort can be seen in Cortical connectivity relationships at 3- and 6-months post-DBS implantation can be observed in 38 One participant (Subject 8) experienced worsening of tremor at 6-months post-DBS implantation (−50% worsening) and was labelled a non-responder. Her connectivity profile demonstrated strong connectivity to the PMC (0.33) and weaker connectivity to the SMA (0.56). The non-responder VTAs have been summarized in Binarization of the improvement weighted VTAs were superimposed on the VIM and VOp as defined by the DBS Intrinsic Atlas (DISTAL), and these have been displayed in 26 The improvement weighted VTAs for the VIM and VOp leads are represented in The spatial relationship of the super-responder and non-responder VTAs for the VIM and VOp leads located within the  and non-decussating dentato-rubro-thalamic tract (ndDRTT) branches with the dDRTT generally lying more anterior within the ventral thalamus (VIM and VOp), whereas the ndDRTT is more posterior and medial (closely associated with the VIM).26 The DRTT depicted in et al.43 showed that modulation of the pallidothalamic tract was significantly associated with improvement in dystonic tremor but not in ET. Given the phenomenological complexity of MS tremor and the disseminated nature of lesion burden in MS, it is conceivable that multiple pathologic networks contribute to the overall tremor syndrome. The findings from our spatial and connectomic analyses may suggest that the pathology underpinning MS tremor may share similarities with dystonic tremor at the network level. The findings collectively suggest that although modulation of the cerebello-thalamo-cortical circuitry was associated with tremor suppression, there exists a distinct connectivity profile difference in optimal thalamic stimulation in MS tremor when compared with ET. Triangulation of the concordance between the VTA and connectivity observations highlights that this difference likely lies within the VOp nucleus. This hypothesis may explain the lack of robust outcomes in previous attempts to treat MS tremor with a single VIM lead.Analysis of the fibre tracts with proximity to the DRTT was associated with greater tremor suppression as displayed in post hoc analysis of a previously published NIH prospective clinical trial and thus was not designed or powered to detect connectivity differences between surgical targets. Additionally, the sample size for this study was small, and the follow-up period was limited to 6 months. We could not control for MS progression over the study period. Several technical assumptions were made as part of the imaging analysis. The brain was modelled as an isotropic medium with uniform conductivity used for the VTA modelling. Structural data were normalized into MNI template space and analysed at the group level with MNI-based atlases. The study also utilized normative connectome data as opposed to patient-specific data. Although the debate of normative versus patient-specific data is ongoing, many studies have revealed that normative data yields similar results to patient-specific data.44 We cannot, however, at this time draw this conclusion based on the data from this small cohort. Despite these limitations, important connectomic data were derived from our investigation.This study had several limitations. First, it was a In conclusion, the DRTT is a well-studied structure thought to be highly involved with tremor genesis. However, in complex tremor disorders such as MS tremor, there may be additional pathological circuitry involved and possibly multiple tremor oscillators. In the present study, we show that unilateral dual-lead thalamic DBS provided a greater volume of stimulation and that there was a negative correlation between PMC connectivity and tremor suppression in this MS tremor cohort, a finding opposite to that observed in the ET cohort. Our findings here suggest that more anterior thalamic stimulation (VOp), incorporating both the DRTT and pallidothalamic circuits (with connectivity to the supplementary motor area), may be important for improving the outcomes of DBS for MS tremor.


This cohort study examines health care utilization patterns for patients with COVID-19 who were enrolled vs not enrolled in a home monitoring program. We assessed health care utilization patterns for patients enrolled in the HMP compared with similar patients who were not enrolled.Remote monitoring programs have been implemented for patients with suspected or confirmed COVID-192 or Fisher exact tests for categorical variables. Overlap propensity score weighting5 using all collected variables was then used to address baseline group differences in those enrolled vs not enrolled in the HMP. The 30-day and 90-day utilization outcomes, including hospitalizations (primary outcome) and ED and outpatient visits, were measured while excluding ED visits or hospitalizations that occurred within 24 hours of the positive SARS-Co-V-2 test result. Subgroup analyses were performed for patients with positive test results that were associated with hospitalization/ED or outpatient visits. This study was approved by the CCHS institutional review board as minimal risk; thus, consent was not required. The reporting follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. All statistical analyses were performed using the tidyverse and survey package with R software (R Foundation). Statistical significance was set at P < .05.We identified patients with positive test results for SARS-CO-V-2 in the CCHS  from March 1 to July 31, 2020, from the CCHS COVID-19 registry, which included demographic and clinical variables. Utilization in the year before the SARS-Co-V-2 test  was obtained from the electronic medical record (EMR). While all patients with COVID-19 were offered HMP enrollment to receive telephone outreach (a description of the HMP can be found in eAppendix 1 in the Baseline characteristics of the study population by HMP participation and subgroup are shown in 6 This study’s outcomes support the need for randomized clinical trials to evaluate HMPs and consideration of targeted resource allocation for home monitoring after COVID-19 diagnosis or to other opportunities to maintain the health of patients during the pandemic.The COVID-19 HMP was associated with lower odds of hospitalization, particularly for the posthospital or ED subgroup, with no significant association with ED utilization up to 90 days after diagnosis and with higher odds of subsequent outpatient utilization. Limitations include that these findings are from a single health system, and our analytic methods may not have adjusted for all confounders, specifically the choice for HMP enrollment. The COVID-19 pandemic has prompted resource distribution discussions and concern for missed opportunities for chronic disease management.


A 78-year-old, overweight woman with a severe individual history of the cardiovascular system was admitted in the intensive care unit with acute pulmonary edema. Despite appropriate emergency treatment, the patient did not show any clinical improvement and emergency intubation was decided. Post-intubation physical examination revealed dullness to percussion, absent breath sounds and reduced chest excursion of the right hemithorax combined with a gradual drop in blood pressure and oxygen saturation. An emergency chest X-ray showed opacification of the entire right lung and an ipsilateral shift of the mediastinum. Improvement of the patient’s respiratory and hemodynamic status was observed immediately after the partial withdrawal of the tube. Tube displacement is a relative frequent complication and concerns mainly the right main bronchus due to anatomical procedures. However, the above case is a rare case of tube displacement in the left main bronchus, which led to total atelectasis of the rightlung. The physical examination revealed dullness to percussion, absent breath sounds and reduced chest excursion of the right hemithorax. A suction test revealed no mucous or secretions. An emergency chest X-ray showed opacification of the entire right lung and an ipsilateral shift of the mediastinum  and hemodynamic status improved immediately after the partial (4 cm) withdrawal of the tube. A second chest X-ray demonstrated expansion of the right lung (A 78-year-old woman with a history of heart failure (LVEF = 50%), hypertension and Parkinson’s disease was admitted to ICU with acute pulmonary edema associated with new-onset slow-atrial fibrillation. A temporary pacemaker was implanted and intravenous diuretic treatment was started. The patient subsequently developed respiratory failure  and was iastinum . Patientght lung .Tube displacement is a relative frequent complication (~13%) in critically ill patients undergoing tracheal intubation who manifest obstructive atelectasis . Other causes include neoplasm, mucus plug or foreign body . Risk fa


The COVID-19 pandemic challenges international and national healthcare systems. In the field of thoracic surgery, procedures may be deferred due to mandatory constraints of the access to diagnostics, staff and follow-up facilities. There is a lack of prospective data on the management of benign and malignant thoracic conditions in the pandemic. Therefore, we derived recommendations from 14 thoracic societies to address key questions on the topic of COVID-19 in the field of thoracic surgery. Respective recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found to temporarily suspend non-critical elective procedures or procedures for benign conditions and to prioritize patients with symptomatic or advanced cancer. Prior to hospitalization, patients should be screened for respiratory symptoms indicating possible COVID-19 infection and most societies recommended to screen all patients for COVID-19 prior to admission. There was a weak consensus on the usage of serology tests and CT scans for COVID-19 diagnostics. Nearly all societies suggested to postpone elective procedures in patients with suspected or confirmed COVID-19 and recommended constant reevaluation of these patients. Additionally, we summarized recommendations focusing on precautions in the theater and the management of chest drains. This study provides a novel approach to informed guidance for thoracic surgeons during the COVID-19 pandemic in the absence of scientific evidence-based data. For more than a year, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has challenged healthcare providers worldwide . Strict Beginning in March 2020, recommendations of national and international thoracic surgery societies on COVID-19 were identified by an online search from official websites. Only recommendations published or referenced by thoracic surgery societies were considered. Societies with recommendations that were not publicly available were contacted by email. The acquired recommendations were pooled and examined by two independent researchers (TD and SK). Key statements were extracted and assigned to defined thematic areas. Statements were categorized and the degree of consensus was evaluated. Categories were defined as (a) does support (+), (b) does not support (-), (c) leaves the answer open/case-by-case decision (±) or (d) does not comment (n/a) [In a second step, extracted key statements were sent to all previously identified national and international thoracic surgery societies in order to achieve a comprehensive consensus of the recommendations. The key statements and responses of the societies were summarized. A score was calculated by subtracting the number of negative recommendations from the count of positive recommendations. Zero points were counted if the answer was left open or no statement was available. The society recommendation consensus (SRC) was classified as “strong recommendation” , “medium recommendation”  or “low recommendation” . Subsequently, the statements were discussed on the basis of existing literature. No study approval was necessary, as all information was publicly available, or if not online, provided by the societies.No statistical tests were used to reach consensus. The study did not compare strategies of different countries, nor was it used to draw causal conclusions. Nine society recommendation bulletins on thoracic surgery in the COVID-19 pandemic were identified as of 1st March 2021 : Australia/New Zealand (ANZSCTS/RACS), Brazil (SBCT), China (CSTCS), France (SFCTVCS), Germany (DGT), Italy (SICT), Spain (SECT), United Kingdom (SCTC/RCS), USA (AATS/ACS). The Austrian Society of Thoracic Surgeons (OGTC) had no published guidelines and referred to the guidelines of the DGT. The European Association of Cardio-Thoracic Surgeons (EACTS) and the European Society of Thoracic Surgeons (ESTS) referred to national guidelines of each European society. The World Health Organization (WHO) had no published recommendations for thoracic surgeons or patients on its website by 1st March 2021. General StatementsStaffPrecautions in the theaterDiagnosticsTreatmentChest drainsConforming with the information given on the individual websites , 27 recoFive societies replied to the statement proposal request (response rate 23%). Their assessments were taken into account in the consensus-building process.The guidelines and recommendations should be adapted according to the local prevalence of COVID-19 and the hospital’s resources (SRC A).The incidence of COVID-19 differs substantially around the world with various epicenters [2.All patients for whom the delay of surgical procedures is necessary should be tracked and their treatment should be prioritized. The usage of alternative treatment options should be considered and documented (SRC A).3.If standard care  is not available, an individual treatment plan should be made for each patient by a multidisciplinary team (SRC A).With increasing numbers of COVID-19 cases, elective surgical procedures may be halted by local, regional and state-based authorities. Thoracic surgery includes a variety and elective cases and emergencies. Therefore, a deliberate prioritization of surgical cases should be considered and stratified in emergency, urgent and elective procedures ,4. The l4.The attendance of patients in the hospital should be limited. Family visits should be reduced to one or no visitors (SRC A).Cancer patients located in an epicenter of a viral epidemic harbor a higher risk of SARS-CoV-2 infection compared with the community . Thus, p5.On arrival at the clinic, all patients should wear surgical masks (SRC A).6.Staff should wear surgical masks at any patient contact (SRC A).Strong agreement was detected with respect to surgical masks for hospital patients in general and that staff members should wear surgical masks when in contact with patients. Clear evidence on the effectiveness of surgical masks is still lacking and contradicting reports in the literature exist ,9,10. Re7.Staffing should be kept to a minimum. Virtual appointments/conferences and consultations should be preferred (SRC A).Decreasing interactions between staff members and workforce distribution can reduce the risk of transmission within the division ,10. Work8.Staff members should not be screened for SARS-CoV-2 (SRC C).Two societies recommended to screen all hospital staff for SARS-CoV-2 and four societies disagreed on the topic. Some societies recommended nasopharyngeal swab tests in staff presenting with typical symptoms of COVID-19. In such a condition, self-isolation at home needs to be started immediately. In case of a negative test result, staff should resume work . In rece9.All patients should be evaluated for respiratory symptoms before hospitalization (SRC A).10.All patients should be screened for SARS-CoV-2 by nasopharyngeal swabs (SRC C).Most societies agreed that patients’ previous medical history should be screened for typical COVID-19 symptoms and physical examination should be conducted ,19. HoweIf routine testing of patients is performed, the following procedure is recommended: (1) Testing at admission in the hospital, (2) isolation with appropriate protection until obtaining test results, (3) in case of emergency surgery, behavioral instructions for COVID-19-positive patients should be applied until confirmation of a negative result.11.Serology tests are generally recommended (SRC C).As of now, several antibody tests have been approved by the United States Food and Drug Administration and the European Union . The ado12.Preoperative CT scans should be conducted for all cancer surgery patients that require critical care (IMC/ICU) postoperatively (SRC C).It has been proposed that patients planned for intensive care monitoring after elective thoracic surgery receive a CT scan preoperatively . The aim13.A designated theater and scrub room should be used for suspected or proven COVID-19 patients. A preoperative COVID-19 checklist should be used for suspected and confirmed COVID-19 patients (SRC B).It has been proposed to establish a theater designated for proven or suspected COVID-19 cases in order to create a physical separation. Detailed guidelines and a preoperative checklist have been provided by the SCTS . 14.During procedures with suspected or proven COVID-19 patients, no changes in staff should be made. Reduce personnel to a minimum. Non-essential personnel should be absent  (SRC B).A medium consensus was reached for this statement. In order to reduce the possibility of infection and to minimize transmission of aerosolized SARS-CoV-2, most societies recommend that staffing levels should remain constant through the surgery and these procedures should not be used for training purposes.15.Appropriate PPE (≥PPE2) should be used for all patients and in case of COVID-19-positive patients: PPE2/3 and goggles (SRC A).A strong recommendation was given to wear at least personal protective equipment (PPE) category 2 for all thoracic procedures. In case of COVID-19-positive patients, PPE2/3 and goggles should be used. The numbers indicate three different categories as defined by the European Union (Council Directive 89/686/EEC): “PPE1” refers to basic protective equipment with a simple design, whereas complex designs are included under “PPE3” . “PPE2” refers to all PPE not falling into categories 1 or 3. Due to the significant environmental contamination of SARS-CoV-2, appropriate protection is an absolute must . 16.The use of laminar airflow is recommended in the theater (SRC C).Low consensus was reached on this statement. A general recommendation to use ventilation techniques to reduce the risk of transmission of SARS-CoV-2 in operating or procedural rooms could not be given, mostly because of a lack of evidence . Still, 17.The routine use of low-dose CT scans instead of chest X-ray (CXR) is not recommended (SRC C).There is only a low consensus on the use of CT scans instead of CXRs as a routine diagnostic procedure. No evidence was found that in the COVID-19 pandemic should a CT scan be performed if the needed information can be provided by CXR . 18.Bronchoscopy should only be performed in patients who have no symptoms, contact or imaging suggestive of COVID-19 infection and postponed in patients with suspected or confirmed COVID-19 infections (SRC A).There is little evidence on the role of bronchoscopy during the COVID-19 pandemic . Most so19.Avoid high-flow nasal oxygen or aerosol-generating procedures (SRC A).There is a strong agreement on the avoidance of high-flow nasal oxygen (HFNO) and aerosol-generating procedures during diagnostic procedures due to fear of aerosol dispersion. However, recent evidence on aerosol generation associated with HFNO fails to establish a clear link between the use of HFNO and increased SARS-CoV-2 infection rates of healthcare workers ,47. In a20.Triage and surgical indications should be adapted according to the local prevalence of COVID-19 and the hospital’s resources (SRC A).All societies have strongly agreed to a three-phase triage approach. Depending on the national administrative structure, phase assessment should be conducted following a protocol with respect to the number of COVID-19 patients within the hospital (A), the availability of hospital resources (B) and the dynamic ratio between A and B. Since the course of the COVID-19 pandemic remains unclear, all societies point out that triage recommendations should not be considered as rigid guidelines. They should be applied individually to each patient, as the situation may change rapidly. All depicted societies embedded the proposed triage guidelines either directly or by reference in their recommendations  Figure . However21.Patients with symptomatic or more advanced cancers should be prioritized for surgery (SRC A).In particular, patients with a predicted decrease in survival are considered at risk and should be prioritized. This is supported by evidence from national cancer registries ,54. Addi22.Surgery for non-critical elective/benign conditions should be postponed  (SRC A).The decision on the treatment of elective/benign conditions should be made according to the national triage classification with close monitoring and reevaluation. However, it should be noted that these patients are at higher risk of acquiring infections, including COVID-19, due to their underlying disease or previous chemotherapies ,57. Thes23.In patients with proven COVID-19 infection, only essential and life-saving surgeries should be performed after a multidisciplinary decision (SRC B).Hospital-associated transmission is a relevant mechanism of COVID-19 infection of healthcare professionals (29%) and hospitalized patients (12.3%) . All non24.The use of a closed system connected to a bag instead of a water seal system is recommended in pleural effusions (SRC C).25.In pneumothorax with indication of thoracic drainage, it is recommended to connect to a conventional water seal system (SRC B).26.There is no benefit of digital drain systems (SRC B).Experts reached a low to medium consensus regarding the handling of chest tubes in the COVID-19 pandemic. The utilization of chest drains may be associated with a higher risk of aerosolization. There is still uncertainty about which chest drain system is best to avoid or decreases aerosol generation. Proper preparation, PPE, modified techniques and drainage maintenance are critical to minimizing exposure of healthcare personnel ,61. Ther27.Avoid early removal of chest drains placed in patients with COVID-19 infection and pneumothorax. Drains should be closed at least 24 hours before radiological confirmation and removal (SRC C).To prevent repetitive chest tube placements, three societies proposed performing a CXR after a 24 h interval of clamping before removal of chest tubes.Healthcare professionals are currently facing unprecedented challenges in handling the COVID-19 pandemic-induced healthcare crisis. Scientific evidence is scarce and thus strategies are mostly based on expert opinion rather than evidence. In the field of thoracic surgery, many questions remain unclear. Thoracic surgeons must deal directly with the clinical picture of the COVID-19 disease, and it is becoming more and more apparent, in particular the consequences for the rest of the patient population.The core findings were the following: Action plans can be based on these proposed recommendations and be adapted according to the local prevalence of COVID-19 and the hospital’s resources (SRC A). If standard care is not available, an individual treatment plan should be made for each patient with a multidisciplinary team (SRC A). All patients for whom the delay of surgical procedures is necessary should be tracked and prioritized later on with constant reevaluations (SRC A). When surgical therapies are delayed and access to medicine is limited, the implementation of prehabilitation programs (PREHAB) and enhanced recovery after surgery (ERAS) protocols for affected patients may help in overcoming the drawbacks of the pandemic . NutritiWith respect to staff and patient precautions, all societies agreed on reducing contact between patients and staff by implementation of video appointments (SRC A). Face masks should be worn as long as the pandemic continues by patients and hospital stuff at any contact (SRC A). Low consensus was found on screening all personnel and patients for SARS-CoV-2 (SRC C). It is worth mentioning that many societies have not updated their recommendations for some time and that screening of personnel and inpatients has now become standard practice due to the broad availability of tests and, therefore, this recommendation seems outdated.Additionally, it is recommended to have a separate operating room track for COVID-19 patients (SRC B) and procedures performed on patients with suspected or confirmed COVID-19 should be kept as short as possible. Albeit only a moderate consensus was found on the usage of closed chest tube systems or anti-viral filters (SRC B/C), more recent data and publications support the usage of closed systems to reduce aerosolization to a minimum and to use a specialized thoracostomy team ,62.Generating a “conventional” consensus usually requires existing data and is a very time-consuming process requiring repeated reevaluations and discussions. Since evidence and time are still lacking, we based our novel consensus-building approach on expert guidelines and focused on recommendations with definitive statements on the depicted topics. Our study can serve as a basis for future decision-making until evidence-based results become available. However, since we bypassed the elaborate consensus-building process, some relevant limitations need to be addressed. The first major limitation of this work is the distortion caused by interpretation and translation errors. Occasional re-interpretation of societal guidelines was necessary to confirm or dismiss the proposed key statements. Due to the lack of scientific evidence, the abovementioned consensus statements are based mostly on expert opinions as the retrieved information was not intended to serve as a basis for consensus recommendation. This limitation is aggravated by the low response rate of 23% after contacting thoracic surgery societies. By answering directly to our proposed statements, interpretation errors could have been avoided and more clear deductions would have been possible. Additionally, we primarily focused on definitive statements and some less clear statements were listed rather than counted in the recommendation-building process. Therefore, some of our statements may underestimate and other overestimate certain topics. Decision making in the pandemic is not always straightforward and there is rarely one right way. Each country, each region and each hospital has different pandemic situations and also different resources to deal with it. There is no “one size fits all” solution and some recommendations may apply well for some readers other may not. Another weakness of this work is its moderate timeliness. The pandemic situation changes weekly, and some recommendations may already be outdated at the time of publication or new aspects may not be taken into account . In addition, several societal recommendations have not been updated for months or adapted to recent scientific findings and the current pandemic situation. Consequently, all recommendations, even if supported by a high SRC, have to be classified as the lowest (scientific) evidence level and should be interpreted as such. Finally, this review is not a complete overview of all recommendations on the topic as similar societal recommendations from other disciplines  were not analyzed.In the quest for a rapid transition back to the field of evidence-based medicine, accurate documentation and publication of prospectively collected clinical data on COVID-19 in thoracic surgery patients are necessary. We suggest that these studies also should scrutinize the evidence of the abovementioned emphasized statements. In the meantime, our summary of expert recommendations in the field of thoracic surgery may help with decision making during this difficult time.


Financial bubbles are a result of aggregate irrational behavior and cannot be explained by standard economic pricing theory. Research in neuroeconomics can improve our understanding of their causes. We conducted an experiment in which 28 healthy subjects traded in a simulated market bubble, while scalp EEG was recorded using a low-cost, BCI-friendly desktop device with 14 electrodes. Independent component (IC) analysis was performed to decompose brain signals and the obtained scalp topography was used to cluster the ICs. We computed single-trial time-frequency power relative to the onset of stock price display and estimated the correlation between EEG power and stock price across trials using a general linear model. We found that delta band (1–4 Hz) EEG power within the left frontal region negatively correlated with the trial-by-trial stock prices including the financial bubble. We interpreted the result as stimulus-preceding negativity (SPN) occurring as a dis-inhibition of the resting state network. We conclude that the combination between the desktop-BCI-friendly EEG, the simulated financial bubble and advanced signal processing and statistical approaches could successfully identify the neural correlate of the financial bubble. We add to the neuroeconomics literature a complementary EEG neurometric as a bubble predictor, which can further be explored in future decision-making experiments. Crashes of financial bubbles have had severe negative impacts on society. Bubbles are deviations from the market equilibrium for which standard asset pricing theory does not apply, and they form when prices are significantly increased above a fundamental intrinsic value ,2. Theirkeyhole hypothesis ).


Results suggest that such a device is feasible and might inherently possess some features that simplify its control. Brake engagement timing and elastic tendon stiffness values determine the level of exoskeleton assistance. Our study affirms that timing of assistive torque is crucial, especially the timing of assistance termination which is determined by brake disengagement timing. Insights acquired by this study should serve as a basis for designing an experimental device and conducting studies on effects of AN-EXTRA-Push in humans.Regaining efficient push-off is a crucial step in restitution of walking ability in impaired individuals. Inspired by the elastic nature of ankle plantarflexor muscle-tendon complex, we propose a novel rehabilitation device: Ankle Exoskeleton using Treadmill Actuation for Push-off assistance (AN-EXTRA-Push). Using a brake and an elastic tendon, it harnesses energy of a moving treadmill during stance phase, then releases it during push-off to aid with plantarflexion torque generation. We studied the feasibility of such a device and explored some key design and control parameters. A parameter sweep of three key parameters  was conducted  Walking is the primary mode of human locomotion. A major contributor to walking capacity is the ability of the ankle-foot complex to produce positive work, accelerating the body’s center of mass and facilitating step to step transitions . In healIndividuals suffering from neuromuscular impairments (e.g. post stroke) have reduced propulsion generating capabilities due to muscle weakness and loss of voluntary muscle control and coordination . Modern In recent years a new research field of ankle exoskeletons focused specifically on the gait subtask of propulsion has emerged. The common feature of these exoskeletons is that they provide positive mechanical work at the ankle joint, thereby reducing the demand for biologically produced work and ideally lowering the metabolic cost of transport for the wearer. Ankle exoskeletons can be classified as either passive or active. Passive ankle exoskeletons  store enAn untapped readily available source of energy that could potentially be used to power an ankle exoskeleton is a treadmill. Treadmills are already parts of clinical rehabilitation setups and are necessary for any tethered ankle exoskeleton’s operation. Inspired by the elastic nature of the ankle plantarflexor muscle-tendon complex , we propin-silico study that investigates the feasibility of our novel approach and gives insights into key design and control parameters of AN-EXTRA-Push.The device we propose is called Ankle Exoskeleton using Treadmill Actuation for Push-off assistance (AN-EXTRA-Push). It operates by harnessing energy of a moving treadmill in elastic structures during stance phase, then releasing it during push-off to aid with plantarflexion torque generation. In this paper, we present an AN-EXTRA-Push consists of an orthosis [element (A) in When the brake is engaged, the constant force spring ceases to have effect on the elastic tendon and the comparatively stiffer elastic tendon can start to stretch. This should be done in early to mid-stance  after wein-silico design space exploration to determine the ranges of feasible values for key parameters. These can then serve as a base for designing an experimental device and an a protocol for testing in humans.The main parameters shaping the ankle torque assistance profile provided by AN-EXTRA-Push are elastic tendon stiffness and brake engagement and disengagement timings. Previous research has shown the importance of optimal assistance power and timing in ankle exoskeleton-based rehabilitation . ExperimWe developed a dynamic walking model and used it to investigate the effects of AN-EXTRA-Push system on gait kinematics and kinetics. All modeling and simulations were done in MATLAB and Simulink , making extensive use of the Simscape Multibody library. We decided on a 2D model constrained to the sagittal plane. The model consisted of 10 rigid segments  connected by rotary joints as shown in A simplified AN-EXTRA-Push was modeled. The elastic tendon was modeled as an ideal unilateral spring. Forces created by the constant force spring and transient phenomena after brake engagements/disengagements were not considered. Modeled inertiae of the shank and foot segments of the right leg were adjusted to account for an estimated total of 0.8 kg of additional mass representing the orthosis.Gait kinematics from a public dataset of healthy human walking  were useFirst, normal gait without the exoskeleton (referred to as NO-EXO) was simulated. A stable and physiologically adequate gait pattern was produced. Then AN-EXTRA-Push model was added to the walking model. When forces and torques were exerted by AN-EXTRA-Push onto the body, a slight adjustment of reference kinematics was necessitated. An optimization problem with the goal of creating new reference kinematics for the hip, knee and ankle joints that resulted in stable and physiological gait was formulated. The lumbo-sacral joint was not included in the optimization. Rather, a simple feedback loop that ensured the upright position of the HAT segment was implemented. Genetic algorithm was used to solve the optimization problem. Reference kinematics of the NO-EXO condition were used as the initial guess. The fitness function consisted of a weighted sum of five criteria: time until the fall, distance traveled compared to NO-EXO condition, ground reaction force impulse at heel-strike, total absolute joint power and similarity of torque profiles to NO-EXO condition  and absent (NO-EXO) condition of AN-EXTRA-Push in To produce an example of AN-EXTRA-Push assisted walking . Joint kinematics remained almost unchanged across the entire sweep. A detailed figure of the parameter sweep results that includes graphs of joint angles, torques, powers and ground reaction forces can be found in the A reduction in positive biological ankle torque and power needed for push-off was observed across all experiments with the active assistance of AN-EXTRA-Push. In the example shown in In R2 = 0.94, p = 3.18*10–4). The earlier the brake was engaged, the more energy was stored and subsequently released by the elastic tendon. Joint kinematics remained almost unchanged across the entire sweep. A detailed figure of the parameter sweep that includes graphs of joint angles, torques, powers and ground reaction forces can be found in the A reduction in positive biological ankle torque and power needed for push-off was observed across all experiments with the active assistance of AN-EXTRA-Push. In the example shown in In Three distinct groups of simulations were identified based on the brake disengagement timings. If the brake was disengaged at 50% of the stride or earlier, the energy stored in the elastic tendon was lost before it could be used to assist the push-off. In cases of brake disengagement timings of 44% and 47%, less than 5% of the positive ankle work needed for push-off was saved compared to NO-EXO condition. Approximately 11% of positive ankle work needed for push-off was saved if the brake disengagement timing was at 50% of stride. These simulations formed the “premature” group. No peak biological ankle plantarflexion torque reduction was observed in this group. The brake disengagement timings from 51% to 55% of stride were considered “on-time”. Simulations with brake disengagement timings of 56% of stride and later formed the “overdue” group. In these simulations all or nearly all energy stored by the elastic tendon was returned to the leg. Even after push-off was completed, the force remaining in the elastic tendon exerted external plantarflexion moment onto the ankle joint, creating a need for biological dorsiflexion moment to prevent a change in kinematics. After all stored energy was spent and the swinging leg reached a position, where the elastic tendon was no longer elongated, further delays in brake disengagement timing ceased to have any effect. In our case, this happened after 58% of stride.R2 = 0.98, p = 1.10*10–3). Within this group, positive ankle work also appeared to be more sensitive to the brake disengagement timing (trend line slope of 9.05) compared to the sensitivity to brake engagement timing (trend line slope of -2.63). A detailed figure of the parameter sweep that includes graphs of joint angles, torques, powers and ground reaction forces can be found in the If the “on-time” group was considered alone, there was a strong linear correlation between the brake disengagement timing and positive ankle work reduction  was conducted


In the last decade, silicon carbide (SiC) has emerged as a potential material for high-frequency electronics and optoelectronics applications that may require elevated temperature processing. SiC exists in more than 200 different crystallographic forms, referred to as polytypes. Based on their remarkable physical and electrical characteristics, such as better thermal and electrical conductivities, 3C-SiC, 4H-SiC, and 6H-SiC are considered as the most distinguished polytypes of SiC. In this article, physical device simulation of a light-emitting diode (LED) based on the unique structural configuration of 4H-SiC and 6H-SiC layers has been performed which corresponds to a novel material joining technique, called diffusion welding/bonding. The proposed single quantum well (SQW) edge-emitting SiC-based LED has been simulated using a commercially available semiconductor device simulator, SILVACO TCAD. Moreover, by varying different design parameters, the current-voltage characteristics, luminous power, and power spectral density have been calculated. Our proposed LED device exhibited promising results in terms of luminous power efficiency and external quantum efficiency (EQE). The device numerically achieved a luminous efficiency of 25% and EQE of 16.43%, which is at par performance for a SQW LED. The resultant LED structure can be customized by choosing appropriate materials of varying bandgaps to extract the light emission spectrum in the desired wavelength range. It is anticipated that the physical fabrication of our proposed LED by direct bonding of SiC-SiC wafers will pave the way for the future development of efficient and cost-effective SiC-based LEDs. The phenomenon of electroluminescence was observed for the very first time in the crystal of silicon carbide (SiC) in 1907. At that time of earlier development stages, the light emission process through semiconductors was not well understood . In receSiC is a wide bandgap compound semiconductor material that is highly suitable for optoelectronic applications involving operations at higher temperatures. It possesses high thermal stability, enhanced electric field maintenance, and a remarkable physical strength compared to that of Silicon (Si). It is also highly suitable for light-emitting applications. SiC exists in several polytypic forms among which 4H-SiC and 6H-SiC have gained attention due to their attractive physical and electronics attributes . In receMoreover, SiC is an extraordinary candidate for high-power optoelectronic applications. Its light emission characteristics have several attractive attributes such as higher efficiency, higher electrical conductivity, longer lifetime, and higher output electrical power compared to that of the conventional LEDs. In conventional LEDs, for high-power applications, heat dissipation becomes a crucial challenge that must be overcome. There are many other factors such as current crowding, Auger recombination, electron leakage, and the polarization effect that degrade the performance of the device in terms of efficiency . OverheaThe motivation of our research is to contribute to the theoretical research by investigating the fabrication feasibility of SiC-based LEDs using a novel technique; called diffusion bonding/welding. For this purpose, a SiC-based edge-emitting LED has been simulated in this work via a novel technique of diffusion welding. The edge-emitting LEDs have been primarily used as a light source in fiber optic communication links. The diffusion welding or diffusion bonding method is used to join dissimilar materials . The working principle is based on the solid-state diffusion process in which atoms diffuse from a higher concentration to a lower concentration. This method has several economic advantages over state-of-the-art epitaxial techniques. This process reduces the fabrication complexity, processing time, and allows high material utilization . This meFor the purpose of analysis and attaining the fabrication feasibility, the prototype device’s performance parameters are first optimized by employing simulators before the commencement of the physical fabrication process. In this work, the fabrication feasibility of our proposed LED structure has been investigated using a commercially available semiconductor device simulator (SILVACO TCAD) via the diffusion welding approach. This technique has been successfully used to fabricate metallic contacts for SiC-based power electronics devices. However, it has rarely been used for the fabrication of SiC-SiC based heterostructures due to the extreme hardness of SiC wafers and their ability to withstand higher temperatures. Physical fabrication of SiC-SiC heterostructures using our proposed technique could be a breakthrough in semiconductor processing technology . Our resIt is pertinent to mention that the fabrication of our proposed/simulated device may need wafer surface treatment so that the surface may appear smooth and homogenous. The optimized temperature and pressure required to bond the wafer successfully need to be investigated for prospective physical fabrication of our proposed device. As far as the epitaxial growth of 6H-SiC is concerned, it has been reported in the literature. Epi-layer growth of 6H-SiC on 6H-SiC substrate has been performed via chemical vapor deposition in the past . SatoshiIn this article, a novel design of SiC-SiC based double hetero-structure edge-emitting LED has been proposed using the diffusion welding process. In the SILVACO TCAD simulator, a thin active layer of intrinsic 6H-SiC has been sandwiched between heavily doped P-type and N-type 4H-SiC to make a single quantum-well (SQW) double hetero-structure 4H-SiC/6H-SiC/4H-SiC LED. To the best of our knowledge, this configuration of SiC LED with our proposed technique has not been reported yet in the literature. Physical fabrication of the proposed LED structure with diffusion welding/bonding will simplify the fabrication process and reduce the device fabrication cost (as the diffusion welding process is simple with a low running cost).2 has been defined in SILVACO TCAD  characteristics, luminous power, and power spectral density as a function of wavelength have been presented. The plots are generated through SILVACO TCAD Software using TONYPLOT . TONYPLOT is a graphical user interface that is used with all SILVACO simulators to generate graphs. A comprehensive detail about this graphical user interface can be found at this reference .2 at approximately 6 V as shown in Energy band profile as a function of LED depth has been shown in s). Luminous power output as a function of current density has been given in 2, and luminous power at this point is 4 × 10−05 W/cm, which is quite low. Current density of simulated LED gradually increases after turn-on voltage. At bias voltage of 6 V, the current density reached its maximum value, as shown in 2 current density, luminous power is 0.00028 W/cm. Although it is a SQW LED, still the luminous power is not so low. If we add multiple quantum wells (MQW) in this structure, this would definitely increase the luminous power output of the device. Because LED devices based on periodic MQW have high luminous power due to several reasons.A voltage bias of 0 to 6 V has been applied at the anode of the simulated LED. To analyze the luminous power output of the simulated LED, we need to know the current density  in TCAD. Emitted power spectral density of the simulated LED has been extracted using the TONYPLOT module of TCAD and shown in bias = 6 V. After that, the radiative recombination rate and total recombination have been measured at the current density of 39 kA/cm2 using the TONYPLOT module. To calculate the percentage luminous efficiency of simulated LED, radiative recombination rate (r) has been divided with total recombination (T) and percentage luminous efficiency has been calculated, as given in 2 using the TONYPLOT module. Then this flux spectral density is multiplied with charge q, where q = 1.602 × 10−19 Coulombs. Finally, this value is divided by bias current density to obtain external quantum efficiency. All these calculations and values have been given in The performance of LED is evaluated on the basis of percentage luminous efficiency and percentage external quantum efficiency (EQE). For these calculations, the simulated LED structure is fixed biased at VIn this section, the luminous and external quantum efficiencies of simulated SiC LED have been compared with the similar LED structure reported in the literature. Epitaxial growth of SiC polytypes is extremely difficult and costly due to its ability to resist extremely high temperatures. Therefore, to avoid complications of the fabrication process and reduce the cost caused by the epitaxial growth techniques, a single QW has been used in our proposed LED structure. As we opt for the fabrication of SiC-based LED with a novel technique, called diffusion welding which is a cheap and simple fabrication technique. The comparison of luminous and external quantum efficiencies of our simulated SQW SiC LED has been done with the similar structure of GaN MQW LED reported in the literature. Despite the presence of SQW, our device exhibited impressive luminous and external quantum efficiencies compared to that of the MQW LED device reported in the literature . The comIn this article, a novel design of SiC-based edge-emitting LED has been simulated by realizing a novel technique; diffusion welding/bonding. We proposed a unique combination of SiC-SiC polytype-based heterostructure LED by direct bonding of SiC wafers. This type of SiC-based LED has not yet been reported in the existing literature since it is extremely challenging to join SiC wafers directly due to their ability to resist even extremely elevated temperatures. Considering the research gap, the comparative performance analysis of the devised LED structure has been carried out with GaN-based LED reported in the literature. However, it is noteworthy that comparative LED possesses the attributes of MQW, whereas our device has been realized with SQW. Moreover, we delineated a novel direct bonding technique for joining SiC-SiC wafers to reduce the complexity and fabrication cost. Our simulated LED device exhibited promising results in terms of luminous efficiency and external quantum efficiency. The simulated device achieved 25% luminous efficiency and 16.43% external quantum efficiency with only one quantum-well formed by the active layer of 6H-SiC. Prospective fabrication of our proposed device with diffusion welding will dramatically reduce the device cost since diffusion welding techniques has several economic advantages over state-of-the-art epitaxial techniques. This process is very simple and allows high material utilization. It reduces the fabrication complexity and processing time. The characteristics of our proposed LED device can be customized by choosing appropriate materials with varying bandgaps to obtain the wavelength of emitted light in the desired wavelength range. Catalytic etching has been proposed for polishing of 4H-SiC wafers to get a flatter surface at the atomic level in order to improve the bonding capability of SiC wafers for the prospective physical fabrication of the device.