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Background: There is a dearth of data on outcomes of postoperative chemotherapy after neoadjuvant therapy followed by surgery in patients with locally advanced non-small cell lung cancer (NSCLC). The objective of this study was to compare survival outcomes in patients who did and did not receive adjuvant chemotherapy. Methods: A retrospective chart review was performed using our multicenter database to identify patients who received neoadjuvant therapy followed by surgery for clinical T3 N0 or N1-N2 resectable NSCLC between 2009 and 2016. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. Propensity score matching (PSM) was used to control for selection bias in evaluation of overall survival (OS) and recurrence-free survival (RFS) by matching age, sex, smoking history, Charlson Comorbidity Index, histologic type, and pathologic nodal status and stage. Results: The participants were 156 patients with a median age of 65 years. The median RFS of the whole cohort was 66.3 months; OS was not reached. Before PSM, patients receiving adjuvant chemotherapy had significantly shorter RFS (hazard ratio [HR], 1.79; 95% CI, 1.13-2.82) and showed a trend for shorter OS (HR, 1.37; 95% CI, 0.78-2.39). After PSM, 50 patients were used for comparison in each group, and those receiving adjuvant chemotherapy did not have a more favorable RFS (HR, 1.33; 95% CI, 0.75-2.34) or OS (HR, 1.25; 95% CI, 0.62-2.51). Conclusions: Adjuvant chemotherapy was not associated with favorable survival outcomes in patients treated with surgery after neoadjuvant therapy for locally advanced NSCLC.

Abstract Production of D-amino acids (D-AAs) on a large-scale enables to provide precursors of peptide therapeutics. In this study, we designed a novel L-amino acid oxidase, HTAncLAAO2, by ancestral sequence reconstruction, exhibiting high thermostability and long-term stability. The crystal structure of HTAncLAAO2 was determined at 2.2 Å by X-ray crystallography, revealing that the enzyme has an octameric form like a “ninja-star” feature. Enzymatic property analysis demonstrated that HTAncLAAO2 exhibits three-order larger k cat/K m values towards four L-AAs (L-Phe, L-Leu, L-Met, and L-Ile) than that of L-Trp. Through screening the variants, we obtained the HTAncLAAO2(W220A) variant, which shows a > 6-fold increase in k cat value toward L-Trp compared to the original enzyme. This variant applies to synthesizing enantio-pure D-Trp derivatives from L- or rac-forms at a preparative scale. Given its excellent properties, HTAncLAAO2 would be a starting point for designing novel oxidases with high activity toward various amines and AAs.

Although osimertinib is a key drug in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, the safety in hemodialysis patients has not been established. A 76-year-old man was diagnosed with NSCLC with EGFR deletion mutation in exon 19. After treatment failure with first- and second-generation EGFR tyrosine kinase inhibitors, a T790M mutation was revealed by liquid biopsy. Hemodialysis was started three times a week because chronic renal failure worsened during treatment. Although the subsequent administration of osimertinib (80 mg daily) resulted in a tumor shrinkage and a gradual increase in the plasma concentration of osimertinib, which resulted in grade 3 general fatigue, reducing the dosage of osimertinib decreased its plasma concentration, leading to an improvement in his adverse event. Subsequently, with by adjusting the dosage while periodically measuring the plasma concentration of osimertinib, a stable therapeutic effect was sustained over the long term with no symptoms. Periodic plasma concentration measurements may be indispensable for successful treatment with osimertinib in hemodialysis patients.

Abstract Some rodlike organic molecules exhibit exceptionally high layered crystallinity when composed of a link between π‐conjugated backbone (head) and alkyl chain (tail). These molecules are aligned side‐by‐side unidirectionally to form self‐organized polar monomolecular layers, providing promising 2D materials and devices. However, their interlayer stacking arrangements have never been tunable, preventing the unidirectional arrangements of molecules in whole crystals. Here, it is demonstrated that polar/antipolar interlayer stacking can be systematically controlled by the alkyl carbon number n, when the molecules are designed to involve effectively weakened head‐to‐head affinity. They exhibit remarkable odd–even effect in the interlayer stacking: alternating head‐to‐head and tail‐to‐tail (antipolar) arrangement in odd‐n crystals, and uniform head‐to‐tail (polar) arrangement in even‐n crystals. The films show excellent field‐effect transistor characteristics presenting unique polar/antipolar dependence and considerably improved subthreshold swing in the polar films. Additionally, the polar films present enhanced second‐order nonlinear optical response along normal to the film plane. These findings are key for creating polarity‐controlled optoelectronic materials and devices.

The cartilage-conduction hearing aid (CC-HA) is a new hearing device that is suitable for use in patients with conductive hearing loss. It has been 5 years since the introduction of the CC-HA. Although the number of users has increased, the CC-HA is not yet widely known. This study examines the effects of CC-HA on patients with conductive hearing loss and investigates factors that affect the willingness to use the device by comparing purchasers and non-purchasers of CC-HA in patients with unilateral conductive hearing loss. Eight patients had bilateral conductive hearing loss, and 35 had unilateral conductive hearing loss. Each patient underwent sound field tests and speech audiometry, and the effects of the CC-HA were compared with those of conventional bone conduction hearing aids (BC-HA). In patients with bilateral conductive hearing loss, the CC-HA was non-inferior to BC-HA. The CC-HA improved the hearing thresholds and speech recognition in patients with unilateral conductive hearing loss. Moreover, in patients with unilateral conductive hearing loss, experiencing the effect of wearing the CC-HA under conditions such as putting noise in the better ear could affect patients’ willingness to use the CC-HA.

Abstract Pleurectomy/decortication for malignant pleural mesothelioma is a relatively recent surgical approach for which there is a dearth of information on complications, especially in the late postoperative period. A 70‐year‐old man was diagnosed with right epithelioid malignant pleural mesothelioma and underwent pleurectomy/decortication. Computed tomography at 6 months after surgery revealed nodules on the surface of the right lung. These nodules gradually increased in size and were diagnosed as recurrent disease. Immunotherapy was started, but treatment was discontinued a few days after the first course due to pneumonitis. Subsequent oral prednisolone therapy for about 2 months ameliorated pneumonitis, but fistulous pyothorax developed. During attempted transbronchial occlusion of the responsible bronchus, some spigots penetrated the empyema cavity. Open window thoracotomy was performed on the following day. This case suggests that if there is no change in diameter between the proximal and distal parts of the responsible bronchus, transbronchial occlusion should not be chosen.

Selective syntheses of coumarin and benzofuran derivatives were achieved via HClO4-mediated intermolecular annulation using phenols and α-methoxy-β-ketoesters. Coumarins are formed under dehydrated conditions, whereas benzofurans are formed in the presence of water. In the synthetic process of benzofurans, α-methoxy-β-ketoesters are converted into α-methoxyacetophenones, and the methoxy group is an important element in the intermolecular annulation.

Summary: Pulmonary fibrosis is a process characterized by epithelial injury and fibroblast activation. It is also well recognized as a predisposition to lung cancer. Here, we present a protocol to establish an in vivo model to evaluate the dynamics of alveolar epithelial type 2 cells and lung cancer cells in the context of the lung fibrogenic microenvironment. Utilizing the cell transfer technique, we detail a basis for therapeutic approaches in pulmonary fibrosis and tools for precision medicine against lung cancer.For complete details on the use and execution of this protocol, please refer to Miyata et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Reports of cervical thymoma with myasthenia gravis are rare. In addition, 99mTc‐MIBI (methoxyisobutylisonitrile:sestamibi) scintigraphy is a useful diagnostic examination for enlarged parathyroid tumours; however, there are a few reports of its accumulation in thymoma. Among them, there are no reports of cervical thymomas with 99mTc‐MIBI accumulation complicated by myasthenia gravis. In this study, we performed surgery on a patient with preoperative myasthenic crisis accompanied by a cervical thymoma and a parathyroid tumour. Preoperatively, the cervical mass was determined to be a parathyroid tumour and was complicated by myasthenia gravis without thymic tumour. However, a pathological examination revealed that the cervical tumour with 99mTc‐MIBI accumulation was a Type B2 thymoma, and a parathyroid tumour was identified in the vicinity. We report a very rare case in which symptoms improved with surgery.

Summary: A mesenchymal cell activation is a hallmark event of pulmonary fibrosis. Alveolar type 2 (AT2) cells are progenitor cells that maintain alveolar homeostasis, and their damage is assumed to be an initiating event for pulmonary fibrosis. However, the interaction between the lung fibrogenic microenvironment and AT2 cell dynamics remains to be elucidated. Here, we report a unique role of the lung fibrogenic microenvironment, where cell type-specific tissue reconstruction is achieved by exogenous cell transplantation. We found that in the lung fibrogenic microenvironment the AT2 cell pool was depleted, whereas mesenchymal cells could promote intact AT2 cell proliferation in vitro. Furthermore, exogenously transplanted AT2 cells formed alveolar colonies and ameliorated pulmonary fibrosis. Exogenous tumor cells formed tumor nests with relevant histological and transcriptional properties. Human primary cells were adaptable to this microenvironment, facilitating epithelial cell-targeted therapy in pulmonary fibrosis and the establishment of patient-derived xenografts for precision medicine in lung cancer.

Threonine is a biosynthetic precursor to dimethylpyrazine derivatives, but the pathway by which this occurs is not fully established. Here l-throenine-3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase together are shown to convert l-threonine to dimethylpyrazine derivatives as a byproduct of glycine metabolism.

Propolis is an aggregate of functional components found in plant resins and has been reported to exhibit valuable biological activities. This study investigated the components and antioxidant activity of propolis from Papua New Guinea. In component analysis, seven known compounds, 6-deoxyhaplopinol (1), 5-formylguaiacol (2), trans-caffeic acid (3), cis-caffeic acid (4), trans-ferulic acid (5), trans-p-coumaric acid (6), and L-kaempferitrin (7), were isolated and identified from Papua New Guinean propolis. The structure of 1 was confirmed by comparing the 13C NMR chemical shifts of the isolated and synthesized compounds. Based on component analysis, Papua New Guinean propolis may be a new type of propolis. The EtOH extracts of Papua New Guinean propolis exhibited antioxidant activity comparable to that of Baccharis and Populus propolis. This study demonstrated the potential of Papua New Guinean propolis in human health maintenance.

We revealed the plant origin of propolis from Lombok, Indonesia; its plant origin was Calophyllum inophyllum Linn. This was confirmed by observing the behavior of stingless bees and from the LC-MS analysis of the 70% ethanol extracts of the propolis and C. inophyllum resin. Furthermore, a new chromanone derivative, calophylloidic acid A (1), was isolated from the stem bark resin of C. inophyllum. The structure of 1 was elucidated using a combination method based on the IR, UV, HRESIMS, and 1D and 2D NMR analyses. The absolute structure of C-2 and C-3 positions of 1 was determined by electronic circular dichroism (ECD). This determination was supported by the time-dependent density functional theory (TD-DFT) and ECD calculations. Additionally, the C. inophyllum resin, propolis, and 1 exhibited significant antibacterial activity against Staphylococcus aureus and Escherichia coli.

Calendula officinalis is commonly known as marigold and its flowers are used in herbal medicines, cosmetics, perfumes, dyes, pharmaceutical preparations, and food products. However, the utility of its leaves has not been studied in depth. The purpose of the present study was to identify the major compounds in C. officinalis leaves and to determine the inhibitory properties of the isolated compounds toward human catechol-O-methyltransferase (COMT), a key neurotransmitter involved in Parkinson’s disease and depression. We isolated and identified ten compounds, including two phenylpropanoids and seven flavonoids, from C. officinalis leaf extracts, of which four flavonoids were identified from C. officinalis leaves for the first time. Eight compounds exhibited COMT inhibitory activities with IC50 values of less than 100 μM. Our results indicate that compounds in C. officinalis leaves are potentially effective for preventing Parkinson’s disease and depression. Thus, C. officinalis leaves may hold promise as dietary supplements.

Sarcoma caused by radiation therapy is called radiation-induced sarcoma (RIS). This rare pathology is being encountered with increasing frequency due to the longer survival time of patients after radiation therapy. We report a case of RIS in the anterior neck of an 82-year-old man who had achieved complete response from radiation therapy for subglottic cancer 11 years earlier. He presented to our facility with an enlarged anterior cervical tumor. Contrast-enhanced computed tomography (CT) indicated a massive tumor (27×34 × 45 mm) extending from the thyroid cartilage into the hyoid bone. Additional magnetic resonance imaging (MRI) showed a signal-hyperintense mass on T1-weighted imaging and signal heterogeneity on T2-weighted imaging, and contrast-enhanced MRI showed some enhancing effects in the tumor. Considering his history of radiation therapy and these imaging characteristics, RIS was suspected and complete resection of the tumor was performed. Dedifferentiated liposarcoma was diagnosed on histopathological examination. He has been followed-up for 6 months with no apparent recurrence.

Three new compounds, namely sulabiroins A (1) and B (2), and 2',3'-dihydro-3'-hydroxypapuanic acid (3), were isolated from the propolis of stingless bees (Tetragonula aff. biroi) collected on South Sulawesi, Indonesia. In addition, ten known compounds, (–)-papuanic acid (4), (–)-isocalolongic acid (5), isopapuanic acid (6), isocalopolyanic acid (7), glyasperin A (8), broussoflavonol F (9), (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone (10), isorhamnetin (11), (1'S)-2-trans,4-trans-abscisic acid (12), and (1'S)-2-cis,4-trans-abscisic acid (13) were identified. The structures of the new and known compounds were determined by spectroscopic analysis. The absolute configurations of sulabiroins A (1) and B (2) were determined by X-ray crystallography analysis and ECD calculation, respectively. The propolis from stingless bee (Tetragonula aff. biroi) collected on South Sulawesi contained compounds not present in propolis from other regions. Sulabiroin A (1) and isorhamnetin (11) were examined for xanthine oxidase (XO) inhibitory activity as one of biological activities; isorhamnetin (11) exhibited potent XO inhibitory activity, with an IC50 value of 3.9 µm.

Several recent studies have reported that expression quantitative trait loci (eQTLs) may affect gene expression in a cell-dependent manner. In the current study, a genome-wide eQTL analysis was performed in whole blood samples collected from 76 Japanese subjects. RNA microarray analysis was performed for 3 independent sample groups that were genotyped in a genome-wide scan. The correlations between the genotypes of 534,404 autosomal single nucleotide polymorphisms (SNPs) and the expression levels of 30,465 probes were examined for each sample group. The SNP-probe pairs with combined correlation coefficients of all 3 sample groups corresponding to P

Background/Aim: The prognostic impact of adjuvant cytotoxic chemotherapy for patients with resectable locally advanced non-small cell lung cancer (NSCLC) who underwent surgery after neoadjuvant chemotherapy remains unclear. Patients and Methods: A retrospective chart review was performed to identify patients who underwent surgery following neoadjuvant therapy for clinical T3N0 or N1-N2 resectable NSCLC between 2011 and 2016 at our hospital. Survival outcomes were analyzed with the Kaplan–Meier method and a Cox proportional hazard model. Results: Thirty-eight patients were identified. The median recurrence-free survival (RFS) was 50.6 months and overall survival (OS) was 75.2 months. Patients who had undergone adjuvant chemotherapy were not associated with a favorable RFS (hazard ratio=1.01, p=0.98) or OS (hazard ratio=0.72, p=0.55), as compared with those who had not. However, subgroup analysis revealed that hazard ratio based on RFS and OS varied greatly between subgroups, suggesting that selected patients might benefit from adjuvant therapy, while others might be harmed by it. For example, in surgical-pathological stage III disease, adjuvant therapy showed a favorable RFS (HR=0.22, 95%CI=0.02-2.57, p=0.23) and OS (HR=0.36, 95%CI=0.03-4.01, p=0.40). Conversely, in surgical-pathological stage 0-II disease, adjuvant therapy showed an unfavorable RFS (HR=1.40, 95%CI=0.49-3.96, p=0.53) and OS (HR=0.95, 95%CI=0.29-3.12, p=0.93). Conclusion: Regardless of the negative findings in our overall patient cohort, our results may be beneficial in identifying patients who may likely benefit from adjuvant therapy. This contribution could assist the planning of large-scale prospective studies. [ABSTRACT FROM AUTHOR]

A new chromanone derivative, calophylloidic acid B (2), was isolated from Calophyllum inophyllum resin in Lombok, Indonesia. The structure of the new compound was elucidated as a structural isomer of calophylloidic acid A (1), which we had previously isolated from Indonesian C. inophyllum resin. It exhibited potent antibacterial activity against Staphylococcus aureus and Escherichia coli. [ABSTRACT FROM AUTHOR]

Background/Objective: Propolis, a resinous substance collected by honeybees from origin plants to protect their beehive, has been reported to have various biological activities and gained popularity as an alternative medicine in recent years.We have previously reported the plant origin, the chemical composition and some biological activities of native Thailand stingless bee propolis. In this study, we further elucidated its active components and their mode of action. Methods/Results: Among nine prenylated xanthones isolated from this propolis, α-mangostin and γ-mangostin were shown to strongly inhibit tube formation of human umbilical vein endothelial cells (HUVECs), an indication of antiangiogenic activity in vitro. Further investigation of their effects at a molecular level revealed that both mangostins inactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and activated p38 in tube-forming HUVECs in a concentration-dependent manner. Taken together, the two mangostins were shown to inhibit angiogenesis in vitro by inactivating angiogenic signal ERK1/2 and activating stress signal p38. Detailed comparison revealed that α-mangostin seemed to have a slightly stronger effect than γ-mangostin in these experiments. Combined with the fact that being the most abundant component among the nine prenylated xanthones tested, α-mangostin might be responsible for the antiangiogenic activity of this Thailand stingless bee propolis. Conclusion: These results indicate that α-mangostin isolated from Thailand stingless bee propolis may be a good candidate for future applications in the prevention of angiogenesis-related diseases. [ABSTRACT FROM AUTHOR]