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Realization of the quantum spin Hall effect in graphene devices has remained an outstanding challenge dating back to the inception of the field of topological insulators. Graphene's exceptionally weak spin-orbit coupling-stemming from carbon's low mass-poses the primary obstacle. We experimentally and theoretically study artificially enhanced spin-orbit coupling in graphene via random decoration with dilute Bi2Te3 nanoparticles. Multiterminal resistance measurements suggest the presence of helical edge states characteristic of a quantum spin Hall phase; the magnetic field and temperature dependence of the resistance peaks, x-ray photoelectron spectra, scanning tunneling spectroscopy, and first-principles calculations further support this scenario. These observations highlight a pathway to spintronics and quantum information applications in graphene-based quantum spin Hall platforms.

The introduction of spin–orbit interactions (SOIs) and the subsequent appearance of a two-dimensional topological phase are crucial for voltage-controlled and zero-emission energy spintronic devices. In contrast, graphene basically lacks SOIs due to the small mass of the carbon atom, and appropriate experimental reports for SOIs are rare. Here, we control small-amount (cover ratios <8%) random decoration of heavy nanoparticles [platinum (Pt) or bismuth telluride (Bi2Te3)] onto monolayer graphene by developing an original nanoneedle method. X-ray photoelectron spectra support low-damage and low-contamination decoration of the nanoparticles, suggesting the presence of Bi–C and Te–C coupling orbitals. In the samples, we find particle-density-dependent non-local resistance (RNL) peaks, which are attributed to the (inverse) spin Hall effect arising from SOI with energies as large as ∼30 meV. This is a larger value than those in previous reports and supported by scanning tunneling spectroscopy. The present observation should lead to topological phases of graphene, which can be introduced by random decoration with controlled small amounts of heavy nanoparticles and their applications. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with a poor prognosis and unknown aetiology. We have recently clarified the prognostic value of the serum platelet-derived growth factor (PDGF) level in patients with IPF. Interleukin (IL)-11 is a member of the IL-6 family, and in vivo and in vitro studies have suggested that it has profibrotic effects in pulmonary fibrosis. In this study, we investigated the predictive value of the serum IL-11 level in patients with IPF for survival and occurrence of acute exacerbation (AE)., Methods: This retrospective study included 68 patients with IPF diagnosed according to the 2018 guideline. Serum PDGF levels were measured using the Bio-Plex method and serum IL-11 levels using enzyme-linked immune-sorbent assay. Cytokine production per lung volume was evaluated using the serum cytokine/percent predicted forced vital capacity (%FVC) value., Results: Forty-six patients were male and the median age was 67 years. The serum IL-11/%FVC value was significantly correlated with the percent predicted diffusing capacity of carbon monoxide (ρ=-0.518, P<0.001) and modified Medical Research Council score for shortness of breath (mMRC) (ρ=0.335, P=0.006) by Spearman's rank correlation analysis. Multivariate Cox proportional hazard regression analysis revealed that the serum IL-11/%FVC value was a significant prognostic factor after adjustment for the serum PDGF/%FVC value and other clinical parameters including mMRC and lymphocyte percentage in bronchoalveolar lavage [hazard ratio (HR): 88.540, 95% confidence interval (CI): 1.905-4,115.686, P=0.022]. IL-11/%FVC value was also a significant predictor of AE after adjustment for age and PDGF/%FVC (HR: 1,815.443, 95% CI: 10.49-314,109.219, P=0.004)., Conclusions: The serum IL-11/%FVC value was an independent predictor of prognosis and AE occurrence in patients with IPF, and the IL-11 level appeared to show pathophysiologic value in IPF., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-876/coif). YI is a consultant or steering/advisory committee member of Boehringer Ingelheim, Roche, SAVARA, and Taiho (not related to this study). YI has received lecture fees from Boehringer Ingelheim, Shionogi, Kyorin, Thermo Fisher, and GSK (not related to this study). TA has received lecture fees from Boehringer Ingelheim and Shionogi for activities not connected with the submitted work. TA received grant from JSPS KAKENHI (Grant No. JP17K09636) and grant from National Hospital Organization (Grant No. H28-NHO [Kokyu]-2). The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Idiopathic pulmonary fibrosis is a fibrotic disease of unknown aetiology and has a poor prognosis. Some patients experience episodes of rapid deterioration known as acute exacerbations (AEs), which are often fatal. This study aimed to clarify whether serum cytokine levels can predict the outcome of idiopathic pulmonary fibrosis., Methods: This retrospective study included 69 patients with idiopathic pulmonary fibrosis diagnosed according to the 2018 guideline. AE of idiopathic pulmonary fibrosis was diagnosed using the Japanese Respiratory Society criteria. Serum levels of 27 cytokines were measured using the Bio-Plex method. Cytokine production was estimated per lung volume using the serum cytokine level/percent predicted forced vital capacity (%FVC) value. The ability of the serum cytokine level and serum cytokine level/%FVC value to predict the prognosis and AE was examined in a univariate Cox proportional hazards regression model; significant factors were subjected to multivariate analysis with adjustment for significant clinical parameters, including the modified Medical Research Council score., Results: The study included 57 men and 12 women (median age, 67 years). The modified Medical Research Council score was ≤1 in 47 patients and ≥2 in 22. None of the serum cytokine levels measured could predict survival or AE; however, the serum platelet-derived growth factor/%FVC and interleukin-9/%FVC values were significant prognostic factors and the serum platelet-derived growth factor/%FVC and interleukin-13/%FVC values were significant predictors of AE. Serum platelet-derived growth factor/%FVC alone was a significant predictor of the prognosis and AE after adjustment for clinical parameters., Conclusions: The prognosis of idiopathic pulmonary fibrosis and AEs of the disease could be predicted by the serum platelet-derived growth factor/%FVC value., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1418/coif). YI is members of steering committees or advisor of Boehringer Ingelheim, Taiho, Roche, GALAPAGOS and SAVARA (not related to this study). YI has received lecture fees from Boehringer Ingelheim, Kyorin, GSK and Shionogi (not related to this study). YI has received supports of medical writing from Boehringer Ingelheim about other manuscripts related to other clinical trial (not related to this study). TA has received lecture fees from Boehringer Ingelheim and Shionogi for activities not connected with the submitted work. MH reports a grant from Japanese Society for the Promotion of Science (JSPS), but has no competing interest. The other authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Background: Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease characterized by the abnormal accumulation of surfactant-like material within the alveolar spaces and distal bronchioles. If high-resolution computed tomography (HRCT) indicates the presence of PAP, a definitive diagnosis of PAP is established when consistent pathological findings are obtained. Herein, we retrospectively studied the yield and safety of bronchofiberscopy in the diagnosis of PAP., Methods: One hundred and fifty consecutive patients with PAP were prospectively registered in the PAP cohort database of the National Hospital Organization Kinki-Chuo Chest Medical Center between January 1991 and December 2018. We examined 86 patients who underwent bronchofiberscopy with bronchoalveolar lavage (BAL) and transbronchial lung forceps biopsy (TBLB)., Results: The patients included 56 men and 30 women, with a median age of 57 years. All patients had autoimmune PAP, and the median level of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies was 42.8 μg/mL. The diagnostic yield was 90.7% (78/86) with BAL and 81.4% (70/86) with TBLB. The combination of BAL and TBLB increased the yield to 98.8%. Age, disease severity score, and frequency of traction bronchiectasis on HRCT were significantly different between the TBLB-positive and TBLB-negative groups. No patient developed serious complications due to bronchofiberscopy; TBLB-related complications included pneumothorax (3.5%) and minimal bleeding (7.0%)., Conclusions: Bronchofiberscopy, in combination with BAL and TBLB, is an effective and safe method for the diagnosis of PAP, with a yield of 98.8%., Competing Interests: Conflict of Interest YI received consulting and lecture fees from Boehringer Ingelheim, lecture fees from Shionogi & Co., Ltd., consulting fees from Taiho Pharmaceutical Co., Ltd., and Roche, which was not directly related to this study. YI is a member of the advisory board of SAVARA. TA received lecture fees from Boehringer Ingelheim and Shionogi Co., Ltd. for the activities outside the submitted works. There are no other conflicts of interest to report., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Acute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs., Methods: This study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse., Results: Univariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality., Conclusions: A higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome., Trial Registration Number: UMIN000014969., Competing Interests: Competing interests: HM, MH, HK, SY, YO, MM, KH, CS, KT and MA have no competing interests. YI is an advisor to Boehringer Ingelheim, Shionogi and Asahi Kasei. TA has received lecture fees from Boehringer Ingelheim and Shionogi for activities not connected with the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Anti-granulocyte-macrophage colony-stimulating factor autoantibody (GMAb) has been recognized as a diagnostic biomarker for autoimmune pulmonary alveolar proteinosis (aPAP). The aims of this study were to know the incidence of increased level of serum GMAb in granulomatous lung diseases (sarcoidosis and hypersensitivity pneumonitis [HP]) and to clarify the role of GMAb. Consecutive individuals diagnosed with sarcoidosis (n = 92) and HP (n = 45) at National Hospital Organization Kinki-Chuo Chest Medical Center were retrospectively analyzed. We measured serum GMAb levels at the diagnosis. Cut-off values of GMAb discriminating aPAP (n = 110) from healthy controls (n = 31) were determined by receiver operating characteristic (ROC) curve analysis. We compared the clinical features of sarcoidosis and HP patients with GMAb levels above the cut-off value ("Elevated-GMAb") with those of patients whose GMAb levels below the cut-off value ("Low-GMAb"). Radiological and pathological findings in elevated-GMAb patients were re-evaluated to elucidate the role of GMAb in granulomatous lung diseases., Results: Analysis of ROC indicated a sensitivity and specificity of 100% at GMAb level of 3.33 μg/mL for discriminating aPAP from healthy controls (area under curve = 1.000, p < 0.0001). The percentages of elevated-GMAb sarcoidosis and HP patients were 5.4% (n = 5) and 11.1% (n = 5), respectively. The number of comorbid sarcoidosis and HP patients with aPAP was two and one, respectively. Elevated-GMAb sarcoidosis patients presented with significantly higher serum levels of Krebs von den Lungen (KL)-6, surfactant protein-D (SP-D), lactate dehydrogenase, and the requirement of systemic corticosteroid therapy. Elevated-GMAb HP patients demonstrated older age, higher serum KL-6, SP-D, carcinoembryonic antigen, and cytokeratin fragment 21-1 levels, and a higher percentage of lymphocytes in bronchoalveolar lavage than low-GMAb patients. A subset of patients presented with radiological and pathological findings characteristic of aPAP., Conclusions: We demonstrated the percentage of elevated-GMAb sarcoidosis and HP patients who presented with several features suggestive of aPAP. Elevated-GMAb sarcoidosis and HP patients without definitive aPAP diagnosis may have subclinical or early-stage aPAP and may not necessarily indicate false positives. Upon diagnosis of sarcoidosis or HP, measurement of GMAb may be useful in detecting possible comorbidity of subclinical or early-onset aPAP.

Introduction: Semi-solid nutrition with high viscosity has the advantage of reducing gastroesophageal reflux and diarrhea and shortens the duration of administration compared with liquid nutrition. This is the first report describing the administration of semi-solid nutrition with high viscosity via a nasogastric tube, which achieved a remarkable improvement in the patient's nutritional state., Case Presentation: A 67-year-old man (mongoloid race, Japanese) with tuberculosis, a pressure ulcer and malnutrition was admitted to our hospital. He also had right hemiplegia, dysphagia and aphasia as sequelae of a cerebral hemorrhage. Before his admission, he had been treated at another hospital with 600 kcal/day of liquid nutrition via a nasogastric tube, which was insufficient and induced severe malnutrition. After he was admitted to our hospital, we increased the quantity of his liquid nutrition without success because of complications, specifically diarrhea and gastroesophageal reflux. As it was difficult to confirm whether or not he would accept gastrostomy feeding, we administered semi-solid nutrition with high viscosity (20,000 mPa x s) via a large-bore nasogastric tube (18 French). Soon after he was started on semi-solid nutrition, his pressure ulcer and malnutrition improved without diarrhea or complications accompanying the large-bore nasogastric tube., Conclusion: When patients have problems with liquid nutrition, such as diarrhea or gastroesophageal reflux, semi-solid nutrition via a nasogastric tube is a useful method of achieving improvements in nutritional state in a short period of time.

Human endometrium had potent peroxidase activity and an antimicrobial effect. Relationships which existed between the human endometrial peroxidase and antimicrobial effect were studied. Human endometrial peroxidase activity was measured by the modified method of Himmelhoch. In the normal menstrual cycle, the peroxidase activity in the secretory phase was higher than in the proliferative phase. The peroxidase activity in endometrial carcinoma was remarkably higher than in the normal menstrual cycle. The organisms (E.coli, S.aureus) and peroxidase extract were incubated for 60 min at 37 degrees C. Bacterial viability was determined by the plate culture method. The viable cell count was decreased. Endometrial peroxidase had an antimicrobial effect on E.coli and S.aureus. But the antimicrobial effect on clinically isolated S.aureus exerted by the peroxidase was not effective. Although the peroxidase activity in the endometrial carcinoma was higher than in the normal endometrium, there was no detectable antimicrobial effect. Peroxidase of endometrial carcinoma was suspected of having some different characteristics from normal endometrium.