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Background. Physical activity is a potential parameter to assess the severity or prognosis of lung disease. However, the differences in physical activity between healthy individuals and patients with lung disease remain unclear. Methods. The analyses in this report are a combined analysis of four cohorts, including a healthy control cohort, in a prospective study designed to evaluate wearable device-estimated physical activity in three cohorts: the lung cancer cohort, the interstitial pneumonia cohort, and the COPD cohort (UMIN000047834). In this report, physical activity in the lung disease cohort was compared with that in the healthy cohort. Subgroup analyses were performed based on age, sex, duration of wearable device use, and lung disease subtype. Results. A total of 238 cases were analyzed, including 216 patients with lung disease and 22 healthy cases. Distance walked and number of steps were significantly lower in the patient group compared to the healthy control group. ROC analysis for the diagnostic value of lung disease by mean distance walked and mean number of steps showed AUC of 0.764 (95%CI, 0.673 to 0.856) and 0.822 (95%CI, 0.740 to 0.905), respectively. There was a significant difference in physical activity by age, but not by gender nor by duration based on the threshold of 7 days of wearing the device. Conclusions. Lung disease decreases physical activity compared to healthy subjects, and aging may bias the estimation of physical activity. The distance walked or number of steps is recommended as a measure of physical activity, with a period of approximately one week and adjusted for age for future investigation.

Yoichi Nishii,1 Kazuki Furuhashi,1 Saki Nakamura,1 Miho Nishio,1 Yuki Nakamura,1 Kengo Ushiro,1 Kentaro Ito,1 Tadashi Sakaguchi,1 Yuta Suzuki,1 Kentaro Fujiwara,1 Taro Yasuma,2 Tetsu Kobayashi,3 Corina D’Alessandro-Gabazza,2 Esteban C Gabazza,2 Osamu Taguchi,1 Osamu Hataji1 1Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Mie, Japan; 2Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Tsu-city, Mie, Japan; 3Department of Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Tsu-city, Mie, JapanCorrespondence: Esteban C GabazzaDepartment of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu-city, Mie, 514-8507, JapanTel +81 59 231 5017Fax +81 59 231 5225Email gabazza@doc.medic.mie-u.ac.jpIntroduction: Many patients with nontuberculous mycobacteria pulmonary disease are asymptomatic. The disease diagnosis is confirmed in only a small proportion of patients with radiological findings suspicious for nontuberculous mycobacteria pulmonary disease. Thus, many patients remained undiagnosed. Here, we evaluated the diagnostic value of digital polymerase chain reaction (PCR) in nontuberculous mycobacteria pulmonary disease.Methods: We prospectively evaluated 123 patients with radiological findings suspicious for nontuberculous mycobacteria pulmonary disease. Digital PCR was performed using bronchial lavage fluid, sputum, saliva, blood, and urine.Results: The culture of bronchial washing fluid was positive for nontuberculous mycobacteria in 53 patients and negative in 70. The positive detection rate of nontuberculous mycobacteria by digital PCR in patients with positive culture (n = 53) was as follows: bronchial lavage fluid 100%, sputum 62.9%, saliva 41.5%, blood 7.5%, and urine 3.8%. All patients with two or more positive partitions for nontuberculous mycobacteria in the digital PCR of bronchial lavage fluid showed nontuberculous mycobacteria growth in the bronchial lavage fluid culture. The digital PCR analysis of the bronchial lavage fluid showed a high sensitivity (100%), specificity (85.7%), positive predictive value (84.1%), negative predictive value (100%), and a high concordance rate (91.9%) with the bronchial lavage fluid culture results. In addition, the culture of bronchial lavage fluid was positive for nontuberculous mycobacteria in patients with two or more positive partitions in the digital PCR of sputum and saliva with a combined positive predictive value of 81.1%.Conclusion: Digital PCR analysis of nontuberculous mycobacteria in bronchial lavage fluid shows a high concordance rate with the bronchial lavage fluid culture results and a high positive predictive value using both sputum and saliva, suggesting the potential usefulness of dPCR for diagnosis of nontuberculous mycobacteria pulmonary disease in clinical practice.Keywords: digital PCR, nontuberculous mycobacteria pulmonary disease, diagnosis, bronchial lavage fluid culture, bronchoscopy

Clinical Practice Points • Immune checkpoint inhibitor (ICI) therapy could exacerbate preexisting active autoimmune diseases (AIDs), and the presence of preexisting AIDs might be associated with a greater risk of developing new immune-related adverse events (irAEs). • The safety of ICIs for patients with Lambert-Eaton myasthenic syndrome (LEMS), a neuromuscular autoimmune disease known as a paraneoplastic syndrome mainly associated with small-cell lung cancer (SCLC), is fully unknown. • We experienced an extensive-stage (ES)-SCLC patient with LEMS successfully treated with chemotherapy in combination with ICI without a flare-up of LEMS. • Phase III trials have shown that ICIs in combination with platinum doublet therapy significantly improved the overall survival of patients with ES-SCLC in first-line settings, therefore, patients diagnosed with ES-SCLC with the complication of LEMS have the widespread opportunity to receive ICIs as standard care. This report suggests that treatment using ICIs may be a treatment option to consider for ES-SCLC patients with LEMS.

Background Consolidation therapy with durvalumab after concurrent chemoradiotherapy has been reported to significantly prolong progression‐free survival and overall survival in patients with stage III unresectable non‐small cell lung cancer (NSCLC). However, which chemotherapy regimen should be selected for consolidation therapy with durvalumab is currently unknown. Methods We retrospectively reviewed consecutive patients with unresectable stage III NSCLC who received concurrent definitive chemoradiotherapy with platinum‐based chemotherapy. We reviewed the timing and severity of radiation pneumonitis by assessing chemotherapy regimens and histology. Results A total of 103 patients were identified. Fourteen patients (13.6%) developed grade 2 or greater radiation pneumonitis within 42 days after chemoradiotherapy. No adenocarcinoma patients treated with a regimen of cisplatin plus pemetrexed developed grade 2 or greater radiation pneumonitis within 42 days; however, 20% of patients who were treated with carboplatin plus paclitaxel developed grade 2 or greater radiation pneumonitis. Furthermore, the objective response rates and disease control rates of cisplatin plus pemetrexed were equal to or greater than those of carboplatin plus paclitaxel in adenocarcinoma patients. Conclusion Cisplatin plus pemetrexed regimen may be a preferable option to consider for subsequent consolidation therapy with durvalumab in patients with unresectable stage III adenocarcinoma., Among a total of 103 patients with unresectable stage III NSCLC who received concurrent definitive chemoradiotherapy, 13.6% of patients developed grade 2 or greater radiation pneumonitis within 42 days after chemoradiotherapy. No adenocarcinoma patients treated with cisplatin plus pemetrexed developed grade 2 or greater radiation pneumonitis within 42 days; however, 20% of patients treated with carboplatin plus paclitaxel developed grade 2 or greater radiation pneumonitis.

Background Next-generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide targeted therapy; however, little is known about the performance of the Oncomine Dx Target Test compared with conventional single gene tests for detecting EGFR mutations. The objective of this study was to evaluate the performance of the Oncomine Dx Target Test compared with a PNA-LNA PCR clamp test to detect EGFR mutations. Methods We retrospectively reviewed consecutive patients with non-small cell lung cancer (NSCLC) from whom FFPE samples were simultaneously submitted for the Oncomine Dx Target Test, and a PNA-LNA PCR clamp test using the same specimen. We subsequently compared the analysis success rates and detection rates between the two tests. Results A total of 116 samples were identified. The success rates and detection rates of EGFR mutations in the total number of samples were 90% and 28%, respectively for the Oncomine Dx Target Test, and 100% and 35% for the PNA-LNA PCR clamp test. The Oncomine Dx Target Test was unable to analyze three samples (2%) due to the samples not passing the nucleic acid concentration threshold, and nine (8%) samples had invalid results. The exon 19 deletion was not detected by the Oncomine Dx Target Test in four cases (4%). Conclusions The analytical performance of the Oncomine Dx Target Test analysis for EGFR mutations may not be comparable with conventional single gene tests due to both invalid and false-negative results. Key points Significant findings of the study The success rate of the Oncomine Dx Target Test was significantly lower than the PNA-LNA PCR clamp test. Among the samples successfully analyzed, four exon 19 deletions were not detected by the Oncomine Dx Target Test. What this study adds The analytical performance of the Oncomine Dx Target Test may not be comparable with conventional single gene tests. We should revise the sampling procedures, and review the sample quality assessment methods, to improve the analytical performance.

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown etiology; however, apoptosis of lung alveolar epithelial cells plays a role in disease progression. This intractable disease is associated with increased abundance of Staphylococcus and Streptococcus in the lungs, yet their roles in disease pathogenesis remain elusive. Here, we report that Staphylococcus nepalensis releases corisin, a peptide conserved in diverse staphylococci, to induce apoptosis of lung epithelial cells. The disease in mice exhibits acute exacerbation after intrapulmonary instillation of corisin or after lung infection with corisin-harboring S. nepalensis compared to untreated mice or mice infected with bacteria lacking corisin. Correspondingly, the lung corisin levels are significantly increased in human IPF patients with acute exacerbation compared to patients without disease exacerbation. Our results suggest that bacteria shedding corisin are involved in acute exacerbation of IPF, yielding insights to the molecular basis for the elevation of staphylococci in pulmonary fibrosis., Idiopathic pulmonary fibrosis is associated with increased abundance of Staphylococcus and Streptococcus in the lungs. Here, the authors identify a Staphylococcus nepalensis-derived peptide, named corisin, to induce apoptosis of lung epithelial cells and exacerbation of pulmonary fibrosis in mice.

Lead halide perovskites are promising materials for various optoelectronic device applications such as solar cells, light-emitting diodes, and lasers. Three-dimensional perovskites, for example, CH...

Summary Introduction Testicular torsion (TT), as per the reported incidences in children and preadolescents, is an emergency medical condition that requires prompt surgical treatment. In cases of TT, early and accurate diagnosis of acute scrotum (AS) is important to preserve testicular fertility. In this study, the authors aimed to determine the incidence, clinical examination, etiology, clinical predictors, and treatment of patients with AS and TT. Material and methods The authors retrospectively reviewed all children (age, ≤15 years) with AS who visited their hospital between January 2012 and June 2019. Data on age and diagnosis, clinical findings, mode of treatment, and blood examination results were collected. Results The authors examined 165 children aged between 0 days and 15 years (mean age, 9.4 years). Final diagnosis identified 72 patients with torsion of the appendix testis, 44 patients with epididymitis, and 38 patients with TT. Testes were salvaged in 23 of the 38 patients with TT (60.5%). Statistically significant variables revealed that the risk factors of TT were age (older than 12 years), white blood cell (WBC) count (>12,000 cells/mm3), and laterality (left side). The level of C-reactive protein (CRP), duration of symptoms, and degree of torsion were significantly higher in the non-salvageable testis group than in the salvageable testis group. Furthermore, the significant predictive factor for non-salvageable testis was the level of CRP >1.0 mg/dl. Conclusion The study results indicates that age, WBC count, and laterality are key factors to distinguish TT from AS. Salvageability largely depended on the duration of symptoms and the degree of TT. The salvage rate of the testis can be improved by educating pediatricians, parents, patients, and medical staff about the early diagnosis and treatment of torsion. Table 1 . Details of patients with AS (n = 165). Age (yrs) 9.4 ± 0.6 Final diagnosis Surgical treatment Conservative treatment Torsion of the appendix testis 72 (43.6%) 51 21 Epididymitis 44 (26.7%) 19 25 TT 38 (23.0%) 38 0 Torsion of the appendix epididymis 5 (3.0%) 5 0 Scrotal dermatitis 2 (1.2%) 0 2 Torsion of the epididymis 1 (0.6%) 1 0 Tumor of the spermatic cord 1 (0.6%) 1 0 Acute hydrocele 1 (0.6%) 0 1 Trauma 1 (0.6%) 0 1 Total 165 (100%) 115 50 Laterality Right side 66 (40.0%) Left side 93 (56.4%) Both sides 6 (3.6%) First diagnosis TT Not TT Final diagnosis TT 38 0 Not TT 23 127 Sensitivity 38/38 (100%) Specificity 127/150 (84.7%)

Cadherin-17 (CDH17) is a transmembrane protein that mediates cell-cell adhesion and is frequently expressed in adenocarcinomas, including gastric cancer. CDH17 may be an effective diagnostic marker for the staging of gastric cancer. Here, we developed an In-labeled anti-CDH17 monoclonal antibody (Mab) as an imaging tracer and performed biodistribution and single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies using mice with CDH17-positive gastric cancer xenografts. CDH17 expression in gastric cancer specimens was also analyzed.

Purpose To report the sequelae of and preventive strategies for selected lower urinary tract (LUT) complications, i.e., posterior urethral diverticulum (PUD), intraoperative LUT injuries, postoperative dysuria, and fistula recurrence in male imperforate anus (IA) with rectourethral/rectovesical (RU/RV) fistula after laparoscopy-assisted anorectoplasty (LAARP) or posterior sagittal anorectoplasty (PSARP). Methods 153 boys with IA and RU/RV fistula treated 1986–2019 by LAARP (n = 56) or PSARP (n = 97) at two unrelated institutes were studied retrospectively. Results After mean follow-up of 17.0 years (range: 36.5 days-32.0 years), the overall incidences of LUT complications were: LAARP (6/56; 10.7%); PSARP (7/97; 7.2%); p = 0.55, comprising PUD: LAARP (n = 5), PSARP (n = 0); p = 0.006; injuries: LAARP (n = 0), PSARP (n = 5); p = 0.16; dysuria: LAARP (n = 1), PSARP (n = 1); p>0.999; and recurrence: LAARP (n = 0), PSARP (n = 1); p>0.999. Mean onset of PUD was 5.1 years (range: 1.0–15.1 years). Treatment: PUD: surgery (n = 2/5), conservative (n = 3/5); injuries: intraoperative repair (n = 5/5); dysuria: conservative (n = 2/2), and recurrence: redo PSARP (n = 1/1). Conclusions Strategies devised to improve dissection accuracy resolved the specific technical issues causing LUT complications (remnant RU fistula dissection in LAARP and blind posterior access in PSARP). Currently, the incidence of new cases of PUD and LUT injuries is zero. Level of Evidence: Level III

There are cases of peripheral lung nodules that are difficult to approach despite using ancillary diagnostic devices during multimodal bronchoscopy. The use of ultrathin bronchoscopes has shown superiority over standard thin bronchoscopes. We retrospectively evaluated whether substitution of the thin-bronchoscope by the ultrathin device during multimodal bronchoscopy improves lesion ultrasound visualization and diagnostic yield in patients with difficult-to-approach pulmonary lesions. The study comprised 44 out of 338 patients that underwent multimodal bronchoscopy at Matsusaka Municipal Hospital. The thin-bronchoscope with an external diameter of 4 mm was substituted by the ultrathin-bronchoscope with an external diameter of 3 mm when the radial endobronchial ultrasound showed that the probe position was not within the target lesion. The median diameter of the pulmonary tumors was 17.5 mm (range: 6.0–5.2.0 mm). The endobronchial ultrasound showed the probe's position adjacent to the lesion in 12 cases and no visible lesion in 32 cases using a thin-bronchoscope. However, the endobronchial ultrasound views changed from adjacent to the lesion to within the lesion in nine cases, from no visible lesion to within the lesion in 17 cases, and from no visible lesion to adjacent to the lesion in nine cases after bronchoscope substitution. After substitution, the diagnostic yield was 80.8% in cases with the radial probe within the target lesion, 72.7% in cases with the probe adjacent to the target lesion, and 0% in cases with no visible lesion. The overall diagnostic yield was 65.9% after bronchoscope substitution. The substitution of the thin bronchoscope by the ultrathin device on a need basis improves the position of the radial endobronchial ultrasound probe and diagnostic yield of pulmonary lesions during multimodal diagnostic bronchoscopy.

Optimization of carrier extraction and/or transport layers is an important factor for the development of perovskite semiconductor devices. In particular, tin dioxide, SnO2, is being frequently used as an electron transport layer (ETL) in perovskite solar cells. However, a systematic study on preparation and characterization of the SnO2-ETL is still lacking, and thus, morphological and electronic-functional roles are not fully understood. In this paper, we systematically investigate the SnO2-ETL prepared on fluorine-doped tin oxide (FTO) substrates by a spin-coating technique. Using microscopic observations, we morphologically study how the SnO2 film covers the FTO surface with large unevenness. Optical characterizations are employed for investigating an electronic band alignment of the perovskite/SnO2 interface varied with the SnO2 concentration in a solution. Furthermore, we systematically evaluate photovoltaic properties of FTO-based solar cell devices. A major finding from these investigations is the fact that while the SnO2-ETL prepared at the adequate condition exhibits an ideal band alignment, the excessive SnO2 deposition causes a poor electron extraction and device performance degradation. Furthermore, we show that the spin-coated SnO2-ETL can cover the FTO surface as an ultrathin wrapping layer. These results highlight the importance of the SnO2-ETL and pave the way for optoelectronic device applications of perovskite materials.

We report a trial of the valence control for mixed valence iron triangular oxide YbFe2O4 in order to develop an effective technique to control the frustration of charges in strongly correlated electron systems. The electro-chemical doping of Li + into YbFe2O4 was examined on the cell type sample similar to the Li-ion secondary battery cell. Systematic change of the lattice constant, Fe–Fe and Fe–Yb distance were observed with Li doping. Maximum value of the doping was over 300 mAh/g. An EXAFS experiment indicated that Li positioned between Yb octahedron layer (U-layer) and Fe-bipyramidal layer (W-layer). However, detailed change of iron valence state of YbFe2O4was not clearly observed because of the superimpose of the signal from iron metal nano particles in XANES observation. We discuss that the uncertainty might arise from the inhomogeneous distribution of the sample particle size, which might prevent the homogeneous doping of Li because the doping occurs on the surface of each nano-particles.

Background Next‐generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide targeted therapy; however, little is known about the performance of the Oncomine Dx Target Test compared with conventional single gene tests for detecting EGFR mutations. The objective of this study was to evaluate the performance of the Oncomine Dx Target Test compared with a PNA‐LNA PCR clamp test to detect EGFR mutations. Methods We retrospectively reviewed consecutive patients with non‐small cell lung cancer (NSCLC) from whom FFPE samples were simultaneously submitted for the Oncomine Dx Target Test, and a PNA‐LNA PCR clamp test using the same specimen. We subsequently compared the analysis success rates and detection rates between the two tests. Results A total of 116 samples were identified. The success rates and detection rates of EGFR mutations in the total number of samples were 90% and 28%, respectively for the Oncomine Dx Target Test, and 100% and 35% for the PNA‐LNA PCR clamp test. The Oncomine Dx Target Test was unable to analyze three samples (2%) due to the samples not passing the nucleic acid concentration threshold, and nine (8%) samples had invalid results. The exon 19 deletion was not detected by the Oncomine Dx Target Test in four cases (4%). Conclusions The analytical performance of the Oncomine Dx Target Test analysis for EGFR mutations may not be comparable with conventional single gene tests due to both invalid and false‐negative results. Key points Significant findings of the study The success rate of the Oncomine Dx Target Test was significantly lower than the PNA‐LNA PCR clamp test.Among the samples successfully analyzed, four exon 19 deletions were not detected by the Oncomine Dx Target Test. What this study adds The analytical performance of the Oncomine Dx Target Test may not be comparable with conventional single gene tests.We should revise the sampling procedures, and review the sample quality assessment methods, to improve the analytical performance., There have been few studies on the performance of the Oncomine Dx Target Test compared with a PNA‐LNA PCR clamp test. Here, we reviewed 116 samples and compared the success and detection rates of EGFR mutations. The rates of the Oncomine Dx Target Test were numerically lower than the PNA‐LNA PCR clamp test, and analytical performance between the two tests may therefore not be comparable.

Objective We previously reported In-labeled anti-cadherin17 (CDH17) IgG visualized CDH17-positive gastric cancer xenografts. Unfortunately, a long waiting time was required to obtain high-contrast images due to long blood retention (blood half-life: 26 h). To accelerate blood clearance, we have developed anti-CDH17 minibody (D2101 minibody) and evaluated the pharmacokinetics in gastric cancer mouse models. Methods Two different single chain Fvs (scFvs), D2101 mutant and D2111, were developed from each parental IgG. The binding ability to CDH17 and stability in plasma were evaluated. D2101 minibody, constructed based on D2101 mutant scFv, was labeled with Cu (Cu-D2101 minibody), and the in-vitro and in-vivo properties were evaluated by cell ELISA, biodistribution experiments, and PET imaging in mice bearing CDH17-positive AGS and CDH17-negative MKN74 tumors. Results D2101 mutant and D2111 scFvs showed similar affinities to CDH17. D2101 mutant scFv was more stable than D2111 scFv in plasma. No loss of binding affinity of the D2101 minibody by chelate conjugation and radiolabeling procedures was observed. The biodistribution of Cu-D2101 minibody showed high uptake in AGS tumors and low uptake in MKN74. The blood half-life of Cu-D2101 minibody was 6.5 h. Improved blood clearance of Cu-D2101 minibody provided high tumor-to-blood ratios compared with the previous results of parental IgG in AGS xenograft mice. PET studies showed consistent results with biodistribution studies. Conclusions Cu-D2101 minibody exhibited higher tumor-to-blood ratios at earlier time points than those of the radiolabeled parental IgG. Cu-D2101 minibody has potential as an immunoimaging agent for CDH17-positive tumors.

The phytoplanktonic production and prokaryotic consumption of organic matter significantly contribute to marine carbon cycling. Organic matter released from phytoplankton via three processes (exudation of living cells, cell disruption through grazing, and viral lysis) shows distinct chemical properties. We herein investigated the effects of phytoplanktonic whole-cell fractions (WF) (representing cell disruption by grazing) and extracellular fractions (EF) (representing exudates) prepared from Heterosigma akashiwo, a bloom-forming Raphidophyceae, on prokaryotic communities using culture-based experiments. We analyzed prokaryotic community changes for two weeks. The shift in cell abundance by both treatments showed similar dynamics, reaching the first peak (~4.1×106‍ ‍cells‍ ‍mL–1) on day 3 and second peak (~1.1×106‍ ‍cells‍ ‍mL–1) on day 13. We classified the sequences obtained into operational taxonomic units (OTUs). A Bray-Curtis dissimilarity analysis revealed that the OTU-level community structure changed distinctively with the two treatments. Ten and 13 OTUs were specifically abundant in the WF and EF treatments, respectively. These OTUs were assigned as heterotrophic bacteria mainly belonging to the Alteromonadales (Gammaproteobacteria) and Bacteroidetes clades and showed successive dynamics following the addition of organic matter. We also analyzed the dynamics of these OTUs in the ocean using publicly available metagenomic data from a natural coastal bloom in Monterey Bay, USA. At least two WF treatment OTUs showed co-occurrence with H. akashiwo, indicating that the blooms of H. akashiwo also affect these OTUs in the ocean. The present results strongly suggest that the thriving and dead cells of uninfected phytoplankton differentially influence the marine prokaryotic community.

The “Japan Nuclear Human Resource Development Network (JN-HRD Network)” was established in November 2010. It is a framework for nuclear HRD, consisting of the industry, the academia, and the government of Japan, to share information and to promote national HRD activities in a harmonized, integrated and strategic manner. 73 organizations are members of the JN-HRD Network at present. The HRD Roadmap was created by the JN-HRD Network in 2014, and the JN-HRD has performed various activities to achieve the common goal since its establishment.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3-4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibits lung fibrosis by direct administration into the lung by intranasal route. Pulmonary fibrosis was induced with bleomycin and RNA therapeutics was administered during both acute and chronic phases of the disease. The levels of periostin and transforming growth factor-β1 in airway fluid and lung tissue, the deposition of collagen in lung tissue and the lung fibrosis score were significantly reduced in mice treated with siRNA and antisense against periostin compared to control mice. These findings suggest that direct administration of siRNA or antisense oligonucleotides against periostin into the lungs is a promising alternative therapeutic approach for the management of pulmonary fibrosis.

Introduction Alectinib and crizotinib have been approved for the therapy of NSCLC caused by anaplastic lymphoma kinase gene (ALK) rearrangement. The effect of alectinib or crizotinib on overall survival (OS) in patients with ALK-rearranged NSCLC remains unknown. Methods A multicenter retrospective study was conducted to compare OS between patients receiving alectinib and crizotinib and between patients treated with alectinib and those treated sequentially with crizotinib and then alectinib after crizotinib failure. The time to treatment failure (TTF), progression-free survival (PFS), and OS were compared. Results Sixty-one patients with ALK-rearranged NSCLC were enrolled. Forty-six patients were treated with anaplastic lymphoma kinase (ALK) inhibitors (31 with crizotinib, 28 with alectinib, and 13 with both ALK inhibitors). The response rate was 66.7% for the crizotinib-treated group and 80.8% for the alectinib-treated group. Among all patients, TTF and PFS were significantly prolonged in the alectinib-treated group compared with in the crizotinib-treated group. Subgroup analyses revealed significantly prolonged TTF for alectinib compared with crizotinib therapy in the ALK inhibitor–naive population. OS was significantly longer in the alectinib-treated group than in the crizotinib-treated group. The TTF and OS of patients treated sequentially with crizotinib and then with alectinib after crizotinib failure tended to be longer than those of patients treated with alectinib alone. Conclusions Therapy with alectinib alone was significantly superior to therapy with crizotinib alone in terms of TTF, PFS, and OS, and sequential therapy with crizotinib and alectinib after crizotinib failure tended to provide a better OS benefit than did therapy with alectinib alone in patients with ALK-positive NSCLC. However, large-scale prospective studies are needed to confirm these observations.

Background Bronchial asthma is a chronic disease characterized by inflammation, obstruction, and hyperresponsiveness of the airways. There is currently no curative therapy for asthma. Type 2 helper T cell response plays a critical role in the pathogenesis of the disease. Protein S is a glycoprotein endowed with anticoagulant, anti-inflammatory, and anti-apoptotic properties. Whether protein S can suppress bronchial asthma and be useful for its therapy is unknown. Methods To address this question here we compared the development of allergen-associated bronchial asthma between wild type and protein S-overexpressing transgenic mice. Mice were sensitized and challenged with ovalbumin. We also evaluated the circulating levels of total and active protein S in patients with bronchial asthma and healthy controls. Results The circulating level of total protein S and of its active form was significantly decreased in patients with bronchial asthma compared to controls. Allergic protein S transgenic mice showed a significant reduction of airway hyperresponsiveness, lung tissue inflammatory cell infiltration, lung levels of Th2 cytokines and IgE compared to their wild-type counterparts. Administration of exogenous human protein S also decreased airway hyperresponsiveness and Th2-mediated lung inflammation in allergic wild-type mice compared with their untreated mouse counterparts. Human protein S significantly shifted the Th1/Th2 balance to Th1 and promoted the secretion of Th1 cytokines (IL-12, tumor necrosis factor-α) from dendritic cells. Conclusions These observations suggest the strong protective activity of protein S against the development of allergic bronchial asthma implicating its potential usefulness for the disease treatment.

Acute lung injury is a fatal disease characterized by inflammatory cell infiltration, alveolar-capillary barrier disruption, protein-rich edema, and impairment of gas exchange. Protein S is a vitamin K-dependent glycoprotein that exerts anticoagulant, immunomodulatory, anti-inflammatory, anti-apoptotic, and neuroprotective effects. The aim of this study was to evaluate whether human protein S inhibits cell apoptosis in acute lung injury. Acute lung injury in human protein S transgenic and wild-type mice was induced by intratracheal instillation of lipopolysaccharide. The effect of human protein S on apoptosis of lung tissue cells was evaluated by Western blotting. Inflammatory cell infiltration, alveolar wall thickening, myeloperoxidase activity, and the expression of inflammatory cytokines were reduced in human protein S transgenic mice compared to the wild-type mice after lipopolysaccharide instillation. Apoptotic cells and caspase-3 activity were reduced while phosphorylation of extracellular signal-regulated kinase was enhanced in the lung tissue from human protein S transgenic mice compared to wild-type mice after lipopolysaccharide instillation. The results of this study suggest that human protein S is protective in lipopolysaccharide-induced acute lung injury by inhibiting apoptosis of lung cells.

The tandem architecture of solar cells is expected to be one of the promising strategies for further improving the performance of photovoltaic devices. While a dry-wet hybrid deposition method is highly promising for fabricating perovskite top cells on textured silicon bottom cells, the bandgap tunability of this deposition method has not been investigated in detail. Here, we show the systematic investigation on mixed-halide perovskite films fabricated by the dry-wet hybrid deposition method on a PbBr2 underlayer. The thermally deposited PbBr2 underlayer is demonstrated to be beneficial for promoting reaction with an organic halide precursor solution, resulting in a dense morphology with large perovskite grains. Furthermore, the hybrid deposition method is also shown to be a straightforward way for wide-range bandgap tuning as it can facilitate halogen mixing. These findings provide useful guidelines for further improving the power conversion efficiency of multijunction tandem solar cell devices.

We previously reported that radioimmunotherapy (RIT) using 90Y-labeled anti-ROBO1 IgG (90Y-B5209B) achieved significant anti-tumor effects against small-cell lung cancer (SCLC) xenografts. However, subsequent tumor regrowth suggested the necessity for more effective therapy. Here, we evaluated the efficacy of combination 90Y-B5209B and cisplatin therapy in NCI-H69 SCLC xenograft mice. Mice were divided into four therapeutic groups: saline, cisplatin only, RIT only, or combination therapy. Either saline or cisplatin was administered by injection one day prior to the administration of either saline or 90Y-B5209B. Tumor volume, body weight, and blood cell counts were monitored. The pathological analysis was performed on day seven post injection of 90Y-B5209B. The survival duration of the combination therapy group was significantly longer than that of the group treated with RIT alone. No significant survival benefit was observed following the isolated administration of cisplatin (relative to saline). Pathological changes following combination therapy were more significant than those following the isolated administration of RIT. Although combination therapy was associated with an increase of several adverse effects such as weight loss and pancytopenia, these were transient. Thus, cisplatin pre-treatment can potentially enhance the efficacy of 90Y-B5209B, making it a promising therapeutic strategy for SCLC.

We previously reported that radioimmunotherapy (RIT) using Y-labeled anti-ROBO1 IgG (Y-B5209B) achieved significant anti-tumor effects against small-cell lung cancer (SCLC) xenografts. However, subsequent tumor regrowth suggested the necessity for more effective therapy. Here, we evaluated the efficacy of combination Y-B5209B and cisplatin therapy in NCI-H69 SCLC xenograft mice. Mice were divided into four therapeutic groups: saline, cisplatin only, RIT only, or combination therapy. Either saline or cisplatin was administered by injection one day prior to the administration of either saline or Y-B5209B. Tumor volume, body weight, and blood cell counts were monitored. The pathological analysis was performed on day seven post injection of Y-B5209B. The survival duration of the combination therapy group was significantly longer than that of the group treated with RIT alone. No significant survival benefit was observed following the isolated administration of cisplatin (relative to saline). Pathological changes following combination therapy were more significant than those following the isolated administration of RIT. Although combination therapy was associated with an increase of several adverse effects such as weight loss and pancytopenia, these were transient. Thus, cisplatin pre-treatment can potentially enhance the efficacy of Y-B5209B, making it a promising therapeutic strategy for SCLC.