Statistical Verification of Anomaly in Chiral Angle Distribution of Air-Suspended Carbon Nanotubes.

Single-walled carbon nanotubes (SWCNT) have long attracted attention due to their distinct physical properties, depending on their chiral structures (chiralities). Clarifying their growth mechanism is important toward perfect chirality-controlled bulk synthesis. Although a correlation between the chirality distribution and the carbon atom configuration at an open tube edge has been predicted theoretically, lack of sufficient statistical data on metallic and semiconducting SWCNTs prohibited its verification. Here, we report statistical verification of the chirality distribution of 413 as-grown individual air-suspended SWCNTs with a length of over 20 µm using broadband Rayleigh spectroscopy. After excluding the impact of the difference in the number of possible SWCNT structures per chiral angle interval, the abundance profile with chiral angle exhibits an increasing trend with a distinct anomaly at a chiral angle of approximately 20°. These results are well explained considering the growth rate depending on armchair-shaped site configurations at the catalyst-nanotube interface.

Real-world evaluation of second line chemotherapy for patients with advanced non-small cell lung cancer harboring preexisting interstitial lung disease.

BACKGROUND: The optimal second and subsequent lines of chemotherapy for patients with non-small cell lung cancer (NSCLC) who have preexisting interstitial lung disease (ILD) are unclear. Hence, we examined the clinical efficacy and safety of second-line chemotherapy in such patients, including any exacerbation of preexisting ILD. METHODS: The medical records of patients with NSCLC and preexisting ILD who received both first- and second-line chemotherapy were retrospectively reviewed. RESULTS: Twenty-four patients with a median age of 71 years who were treated between April 2013 and March 2021 were included. The response rate after second-line chemotherapy with S-1 (n = 13), docetaxel (n = 8), pemetrexed (n = 2), or docetaxel plus ramucirumab (n = 1) was 12.5%, with a median progression-free survival (2nd line PFS) of 3.8 months. The overall survival from a start of first-line chemotherapy (1st line OS) and post-progression survival (PPS) post-first-line chemotherapy were 18.7 and 9.7 months, respectively. Spearman rank correlation and linear regression analyses showed that PPS was strongly correlated with 1st line OS (R = 0.85, P < 0.00001). Importantly, the 2nd line PFS was also significantly correlated with 1st line OS (R = 0.71, P = 0.0001). While second-line chemotherapy-related acute exacerbation of ILD was observed in 7 patients (29.2%), there were no treatment-related fatalities. Conslusions. Second-line chemotherapy has a strong positive impact on the OS of patients with NSCLC who have preexisting ILD. Given the findings of this study, second-line chemotherapy may be valuable in terms of prolonging long-term OS.

Simultaneous serodetection of major rat infectious pathogens by a multiplex immunochromatographic assay.

Rapid and simple serologic tests that require only a small amount of blood without the euthanization of animals are valuable for microbial control in colonies of laboratory animals. In this study, we developed a multiplex immunochromatographic assay (ICA) for detection of antibodies to Sendai virus (also known as hemagglutinating virus of Japan), hantavirus, and sialodacryoadenitis virus, which are causative agents of major infectious diseases in rats. For this assay, an ICA strip was placed into a microtube containing 150 µl PBS and either 0.75 µl of rat serum or 1.5 µl of whole blood. Binding antibodies were visualized by using anti-rat IgG antibody-conjugated colloidal gold. Under these conditions, the multiplex ICA simultaneously and specifically detected antibodies to multiple antigens. Positive serum samples for each infectious disease were used to evaluate the sensitivity and specificity of the multiplex ICA. The sensitivities of the multiplex ICA for Sendai virus, hantavirus, and sialodacryoadenitis virus were 100%, 100%, and 81%, respectively. No nonspecific reactions were observed in any of the 52 positive sera against heterologous antigens. In addition, 10 samples of uninfected sera did not show any bands except for the control line. These observations indicate high specificity of the multiplex ICA. Moreover, the multiplex ICA could be applied to diluted blood. These results indicate that the multiplex ICA is appropriate for rapid and simple serological testing of laboratory rats.

Creation of an experimental rearing environment for microbiome animal research using an individually ventilated cage system and bioBUBBLE enclosure.

To avoid microbial contamination risk, vinyl film isolators are generally used in animal microbiome experiments involving germ-free (GF) mice and/or gnotobiotic (GB) mice. However, it can take several months to gain expertise in operating the isolator competently. Furthermore, sterilization and sterility testing, which are essential for isolator preparation, can take more than 20 days. Hence, we built an experimental rearing environment that combines an individual ventilation cage system and a bioBUBBLE clean room enclosure to easily set up an experimental animal microbiome environment for animal facilities. In this work, a three-step evaluation was conducted. First, we examined whether GF mice can be maintained in this rearing environment without bacterial contamination. Next, we examined whether GF and GB mice can be maintained without cross-contamination in one individual ventilation cage rack. Finally, we tested whether GF mice can be maintained in a biological safety cabinet controlled by negative pressure. In our series of experiments, no microbial contamination occurred over more than 3 months. These results indicated that our rearing system that combines the individual ventilation cage and bioBUBBLE systems can be used not only for experiments with GF mice but also for Biosafety Level 2 experiments that handle bacteria. Our system can mitigate various disadvantages of using vinyl film isolators. In conclusion, we established an experimental method with improved working time and efficiency compared with those of the previous vinyl isolator method.

Retraction Note: Living annulative π-extension polymerization for graphene nanoribbon synthesis.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1038/s41586-020-2950-0 .

Multiplex Immunochromatographic Assay for Serologic Diagnosis of Major Infectious Diseases in Laboratory Mice.

Serologic monitoring of infectious diseases is important for microbial control in colonies of laboratory mice. Rapid and simple tests that do not require killing animals are valuable for this purpose. In this study, we developed a multiplex immunochromatographic assay (ICA) for detection of antibodies to mouse hepatitis virus (MHV), Sendai virus (also known as hemagglutinating virus of Japan [HVJ]), and Clostridium piliforme (The pathogen that causes Tyzzer disease), which are major infectious diseases in mice. For this assay, an ICA strip was put into a microtube containing 150 µL PBS and either 0.75 µL mouse serum or 1.5 µL whole blood. Binding antibodies were visualized by using protein A-conjugated colloidal gold. Under these conditions, multiplex ICA simultaneously and specifically detected antibodies to multiple antigens. To evaluate the sensitivity and specificity of multiplex ICA, positive serum samples for each infectious disease were used. Sensitivities of the multiplex ICA test for MHV, HVJ, and C. piliforme were 100%, 100%, and 90%, respectively. No nonspecific reaction was observed in any of the 30 positive sera. In addition, 10 samples of uninfected sera did not show any bands except for the control line. These observations indicate high specificity of the multiplex ICA test. Moreover, the multiplex ICA could be applied to diluted blood. These results indicate that the multiplex ICA is appropriate for rapid, simple, and safe serologic testing of laboratory mice.

Strength of carbon nanotubes depends on their chemical structures.

Single-walled carbon nanotubes theoretically possess ultimate intrinsic tensile strengths in the 100-200 GPa range, among the highest in existing materials. However, all of the experimentally reported values are considerably lower and exhibit a considerable degree of scatter, with the lack of structural information inhibiting constraints on their associated mechanisms. Here, we report the first experimental measurements of the ultimate tensile strengths of individual structure-defined, single-walled carbon nanotubes. The strength depends on the chiral structure of the nanotube, with small-diameter, near-armchair nanotubes exhibiting the highest tensile strengths. This observed structural dependence is comprehensively understood via the intrinsic structure-dependent inter-atomic stress, with its concentration at structural defects inevitably existing in real nanotubes. These findings highlight the target nanotube structures that should be synthesized when attempting to fabricate the strongest materials.

Living annulative π-extension polymerization for graphene nanoribbon synthesis.

The properties of graphene nanoribbons (GNRs)1-5-such as conductivity or semiconductivity, charge mobility and on/off ratio-depend greatly on their width, length and edge structure. Existing bottom-up methods used to synthesize GNRs cannot achieve control over all three of these parameters simultaneously, and length control is particularly challenging because of the nature of step-growth polymerization6-18. Here we describe a living annulative π-extension (APEX)19 polymerization technique that enables rapid and modular synthesis of GNRs, as well as control over their width, edge structure and length. In the presence of palladium/silver salts, o-chloranil and an initiator (phenanthrene or diphenylacetylene), the benzonaphthosilole monomer polymerizes in an annulative manner to furnish fjord-type GNRs. The length of these GNRs can be controlled by simply changing the initiator-to-monomer ratio, achieving the synthesis of GNR block copolymers. This method represents a type of direct C-H arylation polymerization20 and ladder polymerization21, activating two C-H bonds of polycyclic aromatic hydrocarbons and constructing one fused aromatic ring per chain propagation step.

Real-world evaluation of carboplatin plus a weekly dose of nab-paclitaxel for patients with advanced non-small-cell lung cancer with interstitial lung disease.

BACKGROUND: The optimal chemotherapy regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remains unknown. Therefore, in this study, we investigated the real-world efficacy and safety of carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) as a first-line regimen for NSCLC patients with ILD. PATIENTS AND METHODS: We retrospectively reviewed advanced NSCLC patients with ILD who had received CBDCA plus nab-PTX as a first-line chemotherapy regimen between April 2013 and March 2018. Patients were diagnosed with ILD based on the findings of a pretreatment high-resolution computed tomography of the chest. RESULTS: The 34 patients enrolled in this study were included in the efficacy and safety analysis. Collagen vascular disease or a history of exposure to dust or asbestos was not reported for any patients. The median age of patients was 71 years (range, 59-83 years), and 32 patients had a performance status of 0 or 1. The overall response rate was 38.2%. The median progression-free survival and overall survival were 5.8 months and 12.7 months, respectively. Chemotherapy-related acute exacerbation of ILD was observed in two patients (5.7%). Other toxicities were feasible, and no treatment-related deaths occurred. CONCLUSION: CBDCA plus nab-PTX, as a first-line chemotherapy regimen for NSCLC, showed favorable efficacy and safety in patients with preexisting ILD.

Ultra-narrow-band near-infrared thermal exciton radiation in intrinsic one-dimensional semiconductors.

Thermal radiation is the most primitive light emission phenomenon of materials. Broadband radiation from red-hot materials is well known as the kick-starter phenomenon of modern quantum physics in the early twentieth century; even nowadays, its artificial control plays a central role in modern science and technology. Herein, we report the fundamental thermal radiation properties of intrinsic one-dimensional semiconductors and metals, which have not been elucidated because of significant technical challenges. We observed narrow-band near-infrared radiation from semiconducting single-walled carbon nanotubes at 1000-2000 K in contrast to its broadband metallic counterpart. We confirm that the ultra-narrow-band radiation is enabled by the thermal generation of excitons that are hydrogen-like neutral exotic atoms comprising mutually bound electrons and holes. Our findings uncover the robust quantum correlations in intrinsic one-dimensional semiconductors even at 2000 K; additionally, the findings provide an opportunity for excitonic optothermal engineering toward the realization of efficient thermophotovoltaic energy harvesting.

Intracranial Response to Nivolumab in a Patient with PD-L1-negative Lung Adenocarcinoma.

We herein report the case of a 52-year-old man with stage IV lung adenocarcinoma. The patient was negative for epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule-associated protein-like 4 (EML4) /anaplastic lymphoma kinase (ALK) rearrangement. He was treated with nivolumab as a third-line chemotherapy. After four cycles of nivolumab treatment, a partial response was observed in the brain and at the primary tumor site. Nivolumab treatment has been continued for 11 months without progression. Immunohistochemistry revealed that the programmed death-ligand 1 (PD-L1) expression was 0% (according to the tumor proportion score). Our case indicates that the efficacy of programmed cell death 1 inhibitors is not solely predicted by the PD-L1 status, and that immune checkpoint inhibitors might be effective for the treatment of central nervous system metastasis.

Phase I/II study of induction chemotherapy using carboplatin plus irinotecan and sequential thoracic radiotherapy (TRT) for elderly patients with limited-disease small-cell lung cancer (LD-SCLC): TORG 0604.

BACKGROUND: The role of irinotecan for elderly patients with LD-SCLC has been unclear, and the timing of TRT combined with chemotherapy has not been fully evaluated. METHODS: Patients aged > 70 years with untreated, measurable, LD-SCLC, performance status (PS) 0-2, and adequate organ function were eligible. Treatment consisted of induction with carboplatin on day 1 and irinotecan on days 1 and 8, every 21 days for 4 cycles, and sequential TRT (54Gy in 27 fractions). Carboplatin doses were based on AUC of 4 and 5 (levels 1 and 2, respectively), with a fixed irinotecan dose (50 mg/m2). Primary objective of the phase II study was overall responce rate. RESULTS: Forty-three patients were enrolled and forty-one were finally analyzed (median age: 75 years [range 70-86 years); males 31; PS 0/1/2, n = 22/18/1]. Two patients were excluded because of protocol violation (ascertained to be extensive disease). Twelve patients were accrued at phase I and the number of patients with carboplatin dose-limiting toxicities at levels-1 (n = 6) and -2 (n = 6) were 1(grade 3 hypertension) and 2 (grade 4 thrombocytopenia), respectively. The phase II trial was expanded to 29 additional patients receiving the level 1 carboplatin dose, total of 35 patients. The median number of chemotherapy cycles was 4 (range 1-4), and the median radiation dose was 54Gy (range 36-60). Toxicities were generally mild. There were 4 complete and 27 partial responses (response rate 88.6%). With a median follow-up of 52 months, the median progression-free and overall survival times of phase II were 11.2 and 27.1 months, respectively. CONCLUSIONS: Induction chemotherapy of carboplatin plus irinotecan and sequential TRT was well tolerated and effective for elderly patients with LD-SCLC. Additional confirmatory studies are warranted. TRIAL REGISTRATION: Trial registration number: UMIN000007352 Name of registry: UMIN. Date of registration: 1/Dec/2006. Date of enrolment of the first participant to the trial: 6/Feb/2007. Clinical trial registration date: 1/Feb/2006 (prospective).

Correlation between the efficacy of amrubicin and the previous chemotherapy regimen for relapsed small cell lung cancer.

Amrubicin has been demonstrated to be beneficial in the treatment of patients with relapsed small cell lung cancer (SCLC). The aim of the present study was to evaluate whether there is a significant difference in the efficacy of amrubicin between patients with relapsed SCLC who were previously treated with a platinum agent in combination with a topoisomerase I inhibitor, and those patients previously treated with a platinum agent in combination with a topoisomerase II inhibitor. The medical records of patients with SCLC, who were diagnosed as having relapsed following treatment with a platinum-based regimen and subsequently received amrubicin monotherapy, were retrospectively reviewed. Of a total of 48 patients with SCLC who were treated with amrubicin, the overall response rate, median progression-free survival (PFS) time and median survival time (MST) were determined to be 31.3%, 7.1 and 17.0 months, respectively. The response rate, PFS time and MST did not differ significantly between the patients treated previously with a platinum agent in combination with irinotecan, a topoisomerase I inhibitor, (36.4%, 5.7 and 11.4 months, respectively) and those treated previously with a platinum agent in combination with etoposide, a topoisomerase II inhibitor (30.0%, 4.7 and 14.8 months, respectively). The results indicate that amrubicin may be effective as a second-line chemotherapeutic agent for patients with SCLC, irrespective of which platinum agent and topoisomerase inhibitor-based chemotherapy regimen was previously administered.

[A Case Strongly Suspected of Being Pulmonary Toxocariasis Showing Multiple Pulmonary Nodules with a Disappearing and Reappearing Halo Sign].

We report herein on a case strongly suspected of being pulmonary toxocariasis. A 22-year-old Indonesian man referred to our hospital presented with abnormal chest shadows upon medical examination. He had no symptoms. He did not have any pets nor did he eat raw beef or chicken. Hematological examination revealed eosinophilia and elevation of IgE. Chest computed tomography revealed 3 pulmonary nodules with the halo sign. We suspected a parasite infection and performed antiparasite antibody testing. Ascaris suum was slightly positive on the screening test. As specific antibody against the larval excretory-secretory products of Toxocara canis, measured at the National Institute of Infectious Diseases, was positive (level 3 up to 8). Subsequently, the abnormal chest shadows disappeared. However, two months later, 2 pulmonary nodules with the halo sign reappeared in other places. Diagnostic therapy with albendazole was performed for 8 weeks. Mild hepatic impairment emerged during therapy, but it was within the allowed range. Thereafter, the results improved for the imaging findings, eosinophilia, serum IgE level, and specific antibody. The antibody level became negative two months after the treatment had ended. We should consider toxocariasis in the differential diagnosis of migratory nodular shadows with the halo sign on chest computed tomography, and immunoserological testing is useful for the diagnosis.

[Two Cases of Rapidly Progressive Community-acquired Pneumonia Due to Pseudomonas aeruginosa].

Pseudomonas aeruginosa is a significant causative bacterium in hospital-acquired pneumonia and nursing and healthcare-associated pneumonia, but it seems to be rare in community-acquired pneumonia (CAP). We report two cases of severe CAP due to P. aeruginosa. Case 1: A 52-year-old man was referred to our hospital for chest and back pain. He was being treated for diabetes mellitus and had a long history of smoking. Chest images showed consolidation in the right upper lobe. Soon after hospitalization, he developed sepsis shock and died seven hours later. Case 2: A 73-year-old man with a history of heavy smoking was referred to our hospital for right chest pain. Chest images showed right upper lobe pneumonia. Although wide-spectrum antimicrobial agents were administrated, he died ten hours after admission. In both cases, there was a rapid progression to death, despite administration of a broad spectrum of antibiotics and treatment for sepsis. In cases of CAP involving the right upper lobe, the possibility of bacteremia and rapid progress should be considered.

Impact of Smoking History on the Efficacy of Gefitinib in Patients with Non-Small Cell Lung Cancer Harboring Activating Epidermal Growth Factor Receptor Mutations.

BACKGROUND: Gefitinib treatment has come to be recognized as the standard therapy for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. However, resistance to gefitinib has been observed in certain subpopulations of these patients. The purpose of this study was to evaluate the impact of smoking status on the efficacy of gefitinib in patients with NSCLC harboring EGFR mutations. METHODS: The records of NSCLC patients harboring EGFR mutations who were treated with gefitinib at Kitasato University Hospital were retrospectively reviewed, and the treatment outcomes were evaluated. RESULTS: In 153 patients with NSCLC harboring EGFR mutations, the overall response rate and progression-free survival (PFS) were 66.7% and 9.0 months, respectively. PFS differed significantly among the current smokers and never-smokers/former light smokers (10.7 vs. 5.4 months, p=0.0002), and the response rate was significantly higher in the never-smokers/former light smokers than in the current smokers (72.3 vs. 55.8%, p=0.04). Multivariate analysis identified smoking status as an independent predictor of PFS. CONCLUSION: The clinical data obtained in this study provide a valuable rationale for considering smoking status as a predictor of the efficacy of gefitinib in patients with NSCLC harboring activating EGFR mutations.

Phase I and pharmacokinetic study of erlotinib administered in combination with amrubicin in patients with previously treated, advanced non-small cell lung cancer.

OBJECTIVES: We conducted a phase I trial of erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with amrubicin, a topoisomerase II inhibitor. The aim was to determine the maximum tolerated dose, the dose-limiting toxicities (DLTs), and the pharmacokinetics of this combination in patients with non-small cell lung cancer who had received previous chemotherapy. METHODS: A total of 9 patients with stage IV disease were treated at 3-week intervals with erlotinib once daily on days 1 through 21 plus a 5-minute intravenous injection of amrubicin on days 1 through 3. RESULTS: The dose levels evaluated were erlotinib (mg/body)/amrubicin (mg/m): 100/30 (n=3), 100/35 (n=3), and 150/30 (n=3). The maximum tolerated dose of erlotinib and amrubicin was 100 mg/body and 35 mg/m because 2 of the 3 patients experienced DLTs during the first cycle of treatment at the third dose level of 150 mg/body and 30 mg/m. Cessation of erlotinib administration for 8 days because of grade 3 leukopenia and grade 3 skin infection (erysipelas) were the DLTs. No drug-drug interactions between erlotinib and amrubicin were observed in this study. The overall response rate was 33%, including 3 partial responses, in the 9 patients. The median progression-free survival for all patients was quite long, 11.3 months, and the median overall survival has not yet been reached. CONCLUSIONS: Combined erlotinib plus amrubicin therapy seems to be highly effective, with acceptable toxicity, against non-small cell lung cancer. The recommended dose for phase II studies was erlotinib 100 mg once daily on days 1 through 21, and amrubicin 35 mg/m on days 1 through 3 administered every 21 days.

Aminophylline increases respiratory muscle activity during hypercapnia in humans.

BACKGROUND: Theophylline is an old drug traditionally used as a bronchodilator, although it was recently shown to possess anti-inflammatory properties, enhance the actions of corticosteroid actions, and stimulate the respiratory neuronal network. Theophylline has been recognized as an important drug for not only asthma but also corticosteroid-insensitive chronic obstructive pulmonary disease (COPD). To clarify the role of theophylline in hypercapnic ventilatory responses in humans, we analyzed the effects of aminophylline administered at the usual clinical therapeutic doses on ventilation and augmentation of respiratory muscle contractility in room air and under 3 conditions of hypercapnia. STUDY DESIGN: We performed electromyography (EMG) of the parasternal intercostal muscle (PARA) and transversus abdominis muscle (TA) in 7 healthy subjects and recorded both ventilatory parameters and EMG data in room air and under 3 conditions of hypercapnia before (control) and during aminophylline administration. RESULTS: Before aminophylline administration (control), hypercapnic stimulation elicited ventilatory augmentation in a hypercapnia intensity-dependent manner. Ventilatory parameters (tidal volume, frequency of respiration, and minute ventilation) showed significant increases from lower PaCO2 levels during aminophylline administration when compared with the corresponding values before aminophylline administration. EMG activity of both PARA and TA increased significantly at each level of hypercapnia, and those augmentations were shown from lower PaCO2 levels during aminophylline administration. CONCLUSION: Aminophylline administered at the usual clinical therapeutic dose increases ventilation and EMG activity of both inspiratory and expiratory muscles during hypercapnia in healthy humans.