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Naoko Katsurada,1 Motoko Tachihara,1 Yukihisa Hatakeyama,1 Kiyoko Koyama,1 Masako Yumura,1 Tatsunori Kiriu,1 Ryota Dokuni,1 Daisuke Hazama,1 Shuntaro Tokunaga,1 Daisuke Tamura,1 Kyosuke Nakata,1 Masatsugu Yamamoto,1 Hiroshi Kamiryo,1 Kazuyuki Kobayashi,1 Yugo Tanaka,2 Yoshimasa Maniwa,2 Yoshihiro Nishimura1 1Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; 2Division of General Theocratic Surgery, Kobe University Graduate School of Medicine, Kobe, JapanCorrespondence: Motoko TachiharaDivision of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanTel +81-78-382-5660Fax +81-78-382-5661Email mt0318@med.kobe-u.ac.jpPurpose: Adjuvant chemotherapy with cisplatin (CDDP) plus vinorelbine is the standard regimen for the treatment of non-small cell lung cancer (NSCLC). However, CDDP elicits severe toxic effects, including emesis, neurotoxicity, and renal damage; carboplatin (CBDCA) may be a feasible alternative for CDDP-unfit patients. CBDCA plus paclitaxel (PTX) adjuvant chemotherapy showed a survival benefit for patients with stage IB tumors > 4 cm in size, while CBDCA plus nanoparticle albumin-bound (nab)-PTX showed greater efficacy and lower neurotoxicity than CBDCA plus PTX in advanced NSCLC. Here, we investigated the feasibility of using CBDCA plus nab-PTX as adjuvant chemotherapy for NSCLC.Patients and Methods: Patients with completely resected stage II or III NSCLC, with an Eastern Cooperative Oncology Group performance status of 0– 1 and adequate kidney function, received four cycles of postoperative adjuvant chemotherapy with CBDCA (AUC=5 mg/mL/min, on day 1) and nab-PTX (100 mg/m2, on days 1, 8, and 15) administered every 4 weeks within 8 weeks after surgery. The study was designed as a prospective, single-center, Phase II study. The primary endpoint was the completion rate of chemotherapy; secondary endpoints were two-year relapse-free survival (RFS) and safety. The expected completion rate was 80%, with a 50% lower limit.Results: Of 21 enrolled patients, 18 (85.7%) were CDDP-unfit owing to age (≥ 75 years old [n=11, 52.4%]) or mild renal impairment (n=7, 33.3%). Nineteen of the 21 enrolled patients were assigned to the intervention. The most common grade 3 or 4 adverse events were neutropenia (n=15, 78.9%) and anemia (n=3, 15.8%). The completion rate for the four cycles was 63.2% (95% CI, 38.4– 83.7). Two-year RFS was 56.8% (95% CI, 29.7– 76.9).Conclusion: The completion rate for CBDCA plus nab-PTX as adjuvant chemotherapy for CDDP-unfit NSCLC patients did not reach treatment feasibility. Further dose modifications may be required in future studies.Keywords: nab-paclitaxel, carboplatin, adjuvant chemotherapy, non-small cell cancer

We report an electrical characterization of nanographite fibers (NGFs) by measuring current–voltage characteristics of the individual NGFs in air at room temperature in order to optimize the NGF mass production process. The NGFs were synthesized by thermal chemical vapor deposition with thermal annealing. The NGF contains many defects in comparison with a multiwalled carbon nanotube (MWNT) synthesized by arc discharge, which can be clearly confirmed in the current–voltage characteristic. The maximum current density, however, is typically 10[sup 8] A/cm[sup 2], which is comparable to that in the MWNT. The high-density current operation mechanism is inferred from the measured diameter dependence of the current-voltage characteristic in various diameter NGFs. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

A detailed study of static and dynamic magnetic behavior of Fe3O4 nanoparticles with average particle sizes ranging from 5 to 150nm is presented. Findings state that the static and dynamic properties can be understood by considering changes in the single- particle anisotropy energy Ea through the effect of interparticle interactions in these concentrated systems.

Accurate estimation of tumor mutational burden (TMB) as a predictor of responsiveness to immune checkpoint inhibitors in gene panel assays requires an adequate panel size. The current calculations of TMB only consider coding regions, while most of gene panel assays interrogate non-coding regions. Leveraging the non-coding regions is a potential solution to address this panel size limitation. However, the impact of including non-coding regions on the accuracy of TMB estimates remains unclear. This study investigated the validity of leveraging non-coding regions to supplement panel size using the OncoGuide NCC Oncopanel System (NOP). The aim of this study was to evaluate test performance against orthogonal assays and the association with responsiveness to immune checkpoint inhibitors was not included in the evaluation. We compared TMB status and values between TMB calculated only from coding regions (NOP-coding) and from both coding and non-coding regions (NOP-overall) using whole exome sequencing (WES) and FoundationOne®CDx (F1CDx) assay. Our findings revealed that NOP-overall significantly improved the overall percent agreement (OPA) with TMB status compared with NOP-coding for both WES (OPA: 96.7% vs. 73.3%, n = 30) and F1CDx (OPA: 90.0% vs. 73.3%). Additionally, the mean difference in TMB values compared with WES was lower for NOP-overall (3.55 [95% CI: 0.98-6.13]) than for NOP-coding (6.22 [95% CI: 3.73-8.70]). These results exemplify the utility of incorporating non-coding regions to maintain accurate TMB estimates in small-sized panels., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Even with recent advances in pathobiology and treatment options, chronic obstructive pulmonary disease (COPD) remains a major contributor to morbidity and mortality. To develop new ways of combating this disease, breakthroughs in our understanding of its mechanisms are sorely needed. Investigating the involvement of underanalyzed lung cell types, such as endothelial cells (ECs), is one way to further our understanding of COPD. JCAD is a junctional protein in endothelial cells (ECs) arising from the KIAA1462 gene, and a mutation in this gene has been implicated in the risk of developing COPD. In our study, we induced inflammation and emphysema in mice via the global knockout of KIAA1462/JCAD (JCAD-KO) and confirmed it in HPMECs and A549 to examine how the loss of JCAD could affect COPD development. We found that KIAA1462/JCAD loss reduced acute lung inflammation after elastase treatment. Even after 3 weeks of elastase, JCAD-KO mice demonstrated a preserved lung parenchymal structure and vasculature. In vitro, after KIAA1462 expression is silenced, both endothelial and epithelial cells showed alterations in pro-inflammatory gene expression after TNF-α treatment. We concluded that JCAD loss could ameliorate COPD through its anti-inflammatory and anti-angiogenic effects, and that KIAA1462/JCAD could be a novel target for COPD therapy.

High-flow nasal cannulas (HFNCs) have become common devices for patients with respiratory failure who are treated in general wards. Few reports have been published on in-hospital mortality associated with the ratio of oxygen saturation (ROX) index, measured by pulse oximetry/fraction of inspired oxygen to respiratory rate, in patients treated with HFNCs. We aimed to examine in-hospital mortality and associated factors in patients who initiated HFNC use in a general ward. Sixty patients who initiated HFNC use in general wards at Kobe University Hospital between December 2016 and October 2020 were retrospectively enrolled. We assessed in-hospital mortality, comorbidities, and ROX index. The in-hospital mortality was 48.3%, and ROX index values were significantly lower in patients who died than in those who did not (at HFNC oxygen therapy initiation; 6.93 [2.73-18.5] vs. 9.01 [4.62-18.1], p = 0.00861). Although the difference was not statistically significant, the change in ROX index values between HFNC initiation and 12 hours after initiation tended to be greater in the patients who died in the hospital (0.732 [-2.84-3.5] vs. -0.35[-4.3-2.6], p = 0.0536). Lower ROX index values may be associated with the in-hospital death of patients who are treated with HFNCs in general wards.

Background: Bronchoscopy can be a distress for the patient. There have been few studies on the combination of sedatives and opioids. The aim of this study was to demonstrate the usefulness and safety of administration of the combination of midazolam and pethidine during bronchoscopy., Methods: In this prospective randomized single (patient)-blind study, we randomly assigned 100 patients who were scheduled to undergo bronchoscopy biopsy to receive treatment with either the midazolam/pethidine combination (combination group) or midazolam alone (midazolam group) during examinations. After the end of bronchoscopy, patients completed a questionnaire and the visual analogue scale was measured. The primary outcome was the patients' acceptance of re-examination assessed by visual analogue scale. We also assessed pain levels, vital signs, midazolam use, xylocaine use, and adverse events. Univariate analyses were performed using Fisher's exact test for categorical data, and the t-test or Mann-Whitney test was carried out for analysis of numeric data. All P-values were two-sided, and values < 0.05 were considered statistically significant., Results: We analyzed 47 patients in the combination group and 49 patients in the midazolam group. The primary outcome was a good trend in the combination group, but not significantly different (3.82 ± 2.3 in combination group versus 4.17 ± 2.75 in midazolam alone, P = 0.400). In the combination group, the visual analog scale score for pain during bronchoscopy was significantly lower (1.10 ± 1.88 versus 2.13 ± 2.42, P = 0.022), and the sedation level score per the modified observer's assessment of alertness/sedation scale was significantly deeper (3.49 ± 0.98 versus 3.94 ± 1.03, P = 0.031). Maximal systolic blood pressure during testing was significantly lower (162.39 ± 23.45 mmHg versus 178.24 ± 30.24 mmHg, P = 0.005), and the number of additional administrations of midazolam was significantly lower (2.06 ± 1.45 versus 2.63 ± 1.35, P = 0.049). There were also significantly fewer adverse events (30 versus 41, P = 0.036)., Conclusions: The combination uses of midazolam and pethidine for sedation resulted in significant improvements in the pain, blood pressure, additional use of midazolam, and safety during bronchoscopy among patients., Trial Registration: This study was registered in the University Medical Hospital Information Network in Japan (UMINCTR Registration number: UMIN000032230 , Registered: 13/April/2018)., (© 2022. The Author(s).)

Background/aim: Annexin A10 (ANXA10) is a member of the annexin family and a calcium-dependent phospholipid-binding protein. The aim of this study was to clarify the clinical significance of ANXA10 expression in lung adenocarcinoma., Materials and Methods: ANXA10 expression was immunohistochemically examined in surgical specimens of lung adenocarcinoma obtained from 74 consecutive patients who underwent complete resection from January 2014 to December 2014. Expression of ANXA10 was down-regulated in A549 cells via siRNA transfection and the effect of ANXA10 on cell migration was assessed by the wound healing assay. Expression of ANXA10 was examined by immunocytochemistry and polymerase chain reaction., Results: High ANXA10 expression was significantly correlated with poor overall survival (p=0.00705). Multivariate analysis with the Cox proportional hazard model demonstrated that ANXA10 expression was an independent prognostic factor. Cell migration was suppressed in ANXA10-down-regulated A549 cell lines., Conclusion: ANXA10 has a role in cancer cell migration and high ANXA10 expression is a novel prognostic marker in lung adenocarcinoma., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A seventy‒year‒old man complaining of left arm weakness and gait disturbance was diagnosed with multiple tumors and severe edema in the brain as well as right lung mass lesion, suggesting brain metastases. He started whole brain radiation therapy but had to discontinue it since his neurological symptoms were worsened including paralysis, aphasia, and coma. These symptoms made it difficult to perform tumor biopsy for cancer diagnosis as well as oncogene mutations. Liquid biopsy, which examines EGFR gene mutations in plasma sample, revealed EGFR L858R point mutation. Treatment with osimertinib improved his symptoms, resulting in discharge to home. Even a patient severely ill with metastatic brain tumors can benefit from the molecular‒targeted therapy using liquid biopsy to diagnose EGFR‒mutated lung cancer, suggesting an important differential diagnosis in such patients.

We report an approach to fabricate high conductivity graphite sheets based on a heat-and-current treatment of filtrated, exfoliated graphite flakes. This treatment combines heating (~ 900 °C) and in-plane electrical current flow (550 A·cm -2 ) to improve electrical conductivity through the reduction of crystalline defects. This process was shown to require only a 1-min treatment time, which resulted in a 2.1-fold increase in electrical conductivity (from 1088 ± 72 to 2275 ± 50 S·cm -1 ). Structural characterization by Raman spectroscopy and X-ray diffraction indicated that the improvement electrical conductivity originated from a 30-fold improvement in the crystallinity (Raman G/D ratio increase from 2.8 to 85.3) with no other observable structural transformations. Significantly, this treatment was found to act uniformly across a macroscopic (10 mm) sheet surface indicating it is on the development of applications, such as electrodes for energy generation and storage and electromagnetic shielding, as well as on the potential for the development of large-scale treatment technologies.

In recent years, multitarget drugs for neurological diseases such as Alzheimer's disease have been developed and well researched. Many studies have revealed that multitarget drugs are also useful for lung cancer and respiratory diseases. Pemetrexed is a multitargeted antifolate with strong antitumor activity against mesothelioma and lung adenocarcinoma. Crizotinib is an ATP-competitive tyrosine kinase inhibitor that targets c-MET , ROS1, and ALK . Alectinib is known as an ALK inhibitor but also targets LTK , CHEK2 , FLT3 , PHKG2, and RET . Sorafenib is a tyrosine kinase inhibitor that targets RAF kinase, KIT , VEGFR , PDGFR1β , FLT3 , and RET . Nintedanib is a multiple tyrosine kinase inhibitor that targets FGFR , PDGFR, and VEGFR . In this review, we summarize the mechanisms of action of multitarget therapies and report the results of the latest clinical trials.

We describe a case of microscopic polyangiitis manifested as pleuritis confirmed by thoracoscopic biopsy. An 80-year-old man presented with a three-day history of shortness of breath and cough. Chest radiography revealed patchy opacities in the lower fields of the bilateral lung and right-sided pleural effusion. Thoracentesis revealed lymphocytic pleural exudates. Thoracoscopic biopsy specimens were compatible with fibrotic pleuritis. He developed rapidly progressive glomerulonephritis with elevated myeloperoxidase anti-neutrophil cytoplasmic antibody titer in blood and pleural effusion. Although the patient was resistant to two weekly courses of pulse steroid therapy, he was successfully treated with a five-day course of intravenous immunoglobulin.