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Purpose: Angiogenesis inhibitors are known to modify tumor immunity. Combination of angiogenesis inhibitors with immune checkpoint inhibitors (ICIs) has shown efficacy against many types of cancers, including non-small cell lung cancer (NSCLC). We investigated the feasibility of neoadjuvant therapy with pembrolizumab and ramucirumab, a vascular endothelial growth factor (VEGF) receptor-2 antagonist for patients with PD-L1-positive NSCLC and its influence on the tumor microenvironment (TME)., Patients and Methods: Patients with pathologically proven NSCLC with PD-L1-positive, clinical stage IB-IIIA were eligible. Patients received two cycles of pembrolizumab (200 mg/body) and ramucirumab (10 mg/kg) every three weeks. Surgery was scheduled 4 to 8 weeks after the last dose. The primary endpoint was the major pathologic response (MPR) rate by a blinded independent pathology review. The sample size was 24 patients. Exploratory endpoints were evaluated to elucidate the effects of neoadjuvant therapy on TME., Results: The 24 eligible patients were enrolled between July 2019 and April 2022. The MPR rate was 50.0% (90% confidence interval, 31.9-68.1%). Six patients showed pathological complete response. Grade 3 adverse events (AEs) occurred in 9 patients (37.5%), including 3 immune-related AEs (acute tubulointerstitial nephritis in 2 cases and polymyalgia rheumatica in one). There were no grade 4 or 5 AEs. The transcriptome and multiplexed immunohistochemistry results suggested that tumors with greater CD8+ T-cell infiltration and higher expression of effector molecules at the baseline could show better sensitivity to treatment., Conclusions: This new neoadjuvant combination of pembrolizumab plus ramucirumab was feasible and anti-VEGF agents may enhance the effects of ICIs.

The analysis of microplastics is crucial due to their widespread occurrence and significant impact as environmental pollutants. Appropriate extraction and analytical techniques are necessary to evaluate the abundance, dispersal, and effects of microplastics. In this context, the filtration step to extract microplastics from solution media is indispensable for quantifying microplastics accurately. Usually, a pretreatment procedure such as density separation or solvent extraction is employed before filtration. Nevertheless, the adsorption of microplastic particles onto the glassware surface is known to occur and careful rinsing is inevitable for a suitable recovery rate. The study presents a novel filtration device developed for easy use to increase microplastic recovery from liquid samples. Fluorescent polyethylene (PE) particles were used to examine recovery by optical microscopy and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The conventional filtration system (CFS) exhibited lower microplastic recovery (45.1 ± 7.9%, n = 10) due to the adsorption of microplastics onto the inner surface and the bottom edge of the upper glass funnel. In contrast, the newly developed modified filtration system (MFS) enables fast suction of liquid samples by removing the glass frit with the upper glass funnel and filter being spatially separated. The significantly improved recovery rates using MFS for PE particles were 100% ( n = 5) and 93.4 ± 3.4% ( n = 10), respectively, confirming the feasibility of the newly developed filtration system to analyze microplastics using Py-GC/MS. The study highlights the importance of filtration processing in establishing analytical standards for assessing and managing microplastics by suggesting MFS as an advanced filtration system.

Vacuum residue (VR) was copyrolysed with polyethylene (PE) or polystyrene (PS) in a batch reactor to investigate the corresponding synergistic pyrolytic interactions. The synergistic interactions between VR and plastic pyrolysates enhanced liquid and gas production while reducing coke formation, as compared with VR-only and plastic-only pyrolysis. The pyrolysis of 9:1 w/w VR: PE 3M (PE with M w = 3 MDa) and 9:1 w/w VR/PS 350K (PS with M w ≈ 350 kDa) mixtures produced oil in yields of 28.6 and 38.4 wt%, respectively, which exceeded those expected in the absence of synergistic interactions 1.12- and 1.29-fold, respectively. The corresponding coke yields were ~ 0.9 times lower than those expected in the absence of synergistic interactions. Moreover, copyrolysis synergistically increased the yields of oil-phase paraffins and olefins while decreasing that of aromatic compounds and was therefore concluded to enable effective VR utilisation and plastic recycling by enhancing liquid and gas production., (© 2024. The Author(s).)

Background: Chemoradiotherapy (CRT) modulates the tumor immune microenvironment of multiple cancer types, including esophageal cancer, which potentially induces both immunogenicity and immunosuppression by upregulating the presentation of tumor-specific antigens and immune checkpoint molecules in tumors, respectively. The prognostic effects of immune modification by CRT in esophageal squamous cell carcinoma (ESCC) remain controversial because of the lack of detailed immunological analyses using paired clinical specimens before and after CRT. We aimed to clarify the immunological changes in the tumor microenvironment caused by CRT and elucidate the predictive importance of clinical response and prognosis and the rationale for the necessity of subsequent programmed cell death protein 1 (PD-1) inhibitor treatment., Methods: In this study, we performed a comprehensive immunological analysis of paired biopsy specimens using multiplex immunohistochemistry before and after CRT in patients with unresectable locally advanced ESCC., Results: CRT significantly increased the intra-tumoral infiltration and PD-1 expression of CD8 + T cells and conventional CD4 + T cells but decreased those of regulatory T cells and the accumulation of tumor-associated macrophages. Multivariate analysis of tumor-infiltrating T-cell phenotypes revealed that the density of PD-1 + CD8 + T cells in the tumor after CRT could predict a confirmed complete response and favorable survival., Conclusions: This study showed that CRT improved the immunological characteristics of unresectable locally advanced ESCC and identified the density of PD-1 + CD8 + T cells as a predictive factor for prognosis. This finding supports the rationale for the necessity of subsequent PD-1 inhibitor treatment., (© 2024. Japanese Society of Gastroenterology.)

Pyrolytic synergistic interactions, in which the production of pyrolyzates is enhanced or inhibited, commonly occur during the co-pyrolysis of different polymeric materials, such as plastics and biomass. Although these interactions can increase the yield of desired pyrolysis products under controlled degradation conditions, the desired compounds must be separated from complex pyrolyzates and further purified. To balance these dual effects, this study was aimed at examining pyrolytic synergistic interactions during slow heating co-pyrolysis of biodegradable plastics including polylactic acid (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyhexaoate) (PHBH) and petroleum-based plastics including high-density polyethylene (HDPE), polypropylene (PP), and polystyrene (PS). Comprehensive investigations based on thermogravimetric analysis, pyrolysis-gas chromatography/mass spectrometry, and evolved gas analysis-mass spectrometry revealed that PLA and PHBH decompose at lower temperatures (273-378 °C) than HDPE, PP, and PS (386-499 °C), with each polymer undergoing independent decomposition without any pyrolytic interactions. Thus, the independent pyrolysis of biodegradable plastics, such as PLA and PHBH, with common plastics, such as HDPE, PP, and PS, can theoretically be realized through temperature control, enabling the selective recovery of their pyrolyzates in different temperature ranges. Thus, pyrolytic approaches can facilitate the treatment of mixed biodegradable and common plastics., (© 2024. The Author(s).)

Accumulating evidence indicates that aberrant signalling stemming from genetic abnormalities in cancer cells has a fundamental role in their evasion of antitumour immunity. Immune escape mechanisms include enhanced expression of immunosuppressive molecules, such as immune-checkpoint proteins, and the accumulation of immunosuppressive cells, including regulatory T (T reg ) cells, in the tumour microenvironment. Therefore, T reg cells are key targets for cancer immunotherapy. Given that therapies targeting molecules predominantly expressed by T reg cells, such as CD25 or GITR, have thus far had limited antitumour efficacy, elucidating how certain characteristics of cancer, particularly genetic abnormalities, influence T reg cells is necessary to develop novel immunotherapeutic strategies. Hence, T reg cell-targeted strategies based on the particular characteristics of cancer in each patient, such as the combination of immune-checkpoint inhibitors with molecularly targeted agents that disrupt the immunosuppressive networks mediating T reg cell recruitment and/or activation, could become a new paradigm of cancer therapy. In this Review, we discuss new insights on the mechanisms by which cancers generate immunosuppressive networks that attenuate antitumour immunity and how these networks confer resistance to cancer immunotherapy, with a focus on T reg cells. These insights lead us to propose the concept of 'immuno-genomic precision medicine' based on specific characteristics of cancer, especially genetic profiles, that correlate with particular mechanisms of tumour immune escape and might, therefore, inform the optimal choice of immunotherapy for individual patients., (© 2024. Springer Nature Limited.)

The CLIP1-LTK fusion was recently discovered as a novel oncogenic driver in non-small cell lung cancer (NSCLC). Lorlatinib, a third-generation ALK inhibitor, exhibited a dramatic clinical response in a NSCLC patient harboring CLIP1-LTK fusion. However, it is expected that acquired resistance will inevitably develop, particularly by LTK mutations, as observed in NSCLC induced by oncogenic tyrosine kinases treated with corresponding tyrosine kinase inhibitors (TKIs). In this study, we evaluate eight LTK mutations corresponding to ALK mutations that lead to on-target resistance to lorlatinib. All LTK mutations show resistance to lorlatinib with the L650F mutation being the highest. In vitro and in vivo analyses demonstrate that gilteritinib can overcome the L650F-mediated resistance to lorlatinib. In silico analysis suggests that introduction of the L650F mutation may attenuate lorlatinib-LTK binding. Our study provides preclinical evaluations of potential on-target resistance mutations to lorlatinib, and a novel strategy to overcome the resistance., (© 2024. The Author(s).)

This review investigates the latest trends in separation technologies regarding hard-to-recycle thin cables, specifically in the form of end-of-life wire harnesses (WHs). The cables in WHs mainly contain copper (Cu) and poly(vinyl chloride) (PVC), which is commonly used to insulate and sheath cables. This review reveals that most separation technologies prioritize the recovery of Cu and overlook that of PVC. The recovery of high-purity PVC is very important because of its incompatibility with other plastics or Cu during recycling treatments. Through this investigation, we confirm that physical treatments, such as stripping and chopping, are insufficient to recover high-purity PVC from thin cables. Instead, a combination of chemical (e.g., swelling of PVC insulation or sheathing of cables under a suitable solvent) and physical (e.g., ball or rod milling and mechanical agitation of swollen cables) treatments can be used to achieve the recovery of high-purity PVC and Cu both for recycling. We believe that recovering metals and plastics from end-of-life cables is vital for sustainable waste management, offering several environmental and economic benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cancer cells employ glycolysis for their survival and growth (the "Warburg effect"). Consequently, surrounding cells including immune cells in the tumor microenvironment (TME) are exposed to hypoglycemic, hypoxic, and low pH circumstances. Since effector T cells depend on the glycolysis for their survival and functions, the metabolically harsh TME established by cancer cells is unfavorable, resulting in the impairment of effective antitumor immune responses. By contrast, immunosuppressive cells such as regulatory T (Treg) cells can infiltrate, proliferate, survive, and exert immunosuppressive functions in the metabolically harsh TME, indicating the different metabolic dependance between effector T cells and Treg cells. Indeed, some metabolites that are harmful for effector T cells can be utilized by Treg cells; lactic acid, a harmful metabolite for effector T cells, is available for Treg cell proliferation and functions. Deficiency of amino acids such as tryptophan and glutamine in the TME impairs effector T cell activation but increases Treg cell populations. Furthermore, hypoxia upregulates fatty acid oxidation via hypoxia-inducible factor 1α (HIF-1α) and promotes Treg cell migration. Adenosine is induced by the ectonucleotidases CD39 and CD73, which are strongly induced by HIF-1α, and reportedly accelerates Treg cell development by upregulating Foxp3 expression in T cells via A2AR-mediated signals. Therefore, this review focuses on the current views of the unique metabolism of Treg cells dictated by cancer cells. In addition, potential cancer combination therapies with immunotherapy and metabolic molecularly targeted reagents that modulate Treg cells in the TME are discussed to develop "immune metabolism-based precision medicine"., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Plastic waste has emerged as a serious issue due to its impact on environmental degradation and resource scarcity. Plastic recycling, especially of halogen-containing plastics, presents challenges due to potential secondary pollution and lower-value implementations. Chemical recycling via pyrolysis is the most versatile and robust approach for combating plastic waste. In this Review, we present recent advancements in halogen-plastic pyrolysis for resource utilization and the potential pathways from "reducing to recycling to upcycling" halogens. We emphasize the advanced management of halogen-plastics through copyrolysis with solid wastes (waste polymers, biomass, coal, etc.), which is an efficient method for dealing with mixed wastes to obtain high-value products while reducing undesirable substances. Innovations in catalyst design and reaction configurations for catalytic pyrolysis are comprehensively evaluated. In particular, a tandem catalysis system is a promising route for halogen removal and selective conversion of targeted products. Furthermore, we propose novel insights regarding the utilization and upcycling of halogens from halogen-plastics. This includes the preparation of halogen-based sorbents for elemental mercury removal, the halogenation-vaporization process for metal recovery, and the development of halogen-doped functional materials for new materials and energy applications. The reutilization of halogens facilitates the upcycling of halogen-plastics, but many efforts are needed for mutually beneficial outcomes. Overall, future investigations in the development of copyrolysis and catalyst-driven technologies for upcycling halogen-plastics are highlighted.

Studies have established immunochemotherapy as the first-line treatment for advanced esophageal cancer. Chen et al. and Carrol et al. performed exploratory analysis of the JUPITER-06 and LUD2015-005 trials, respectively and identified biomarkers to predict therapy response based on immunogenomic analysis. These findings may optimize precise patient stratification in advanced esophageal cancer., Competing Interests: Declaration of interests S. Koyama reports receiving research funding from Otsuka Pharmaceutical and Chugai Pharmaceutical. K.S. reports receiving personal fees for advisory roles from Lilly, Bristol Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical, Merck Pharmaceutical, Taiho Pharmaceutical, Astellas, Novartis, AbbVie, GlaxoSmithKline, Daiichi Sankyo, Amgen, Boehringer Ingelheim, Guardant Health Japan, and Janssen; honoraria (lecture fees) from Takeda, Bristol-Myers Squibb, and Janssen; and research funding from Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai, Merck Pharmaceutical, Medi Science, Eisai, and Amgen., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although definitive chemoradiotherapy (CRT) is the standard therapy for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), poor survival has been reported. Although the complete response (CR) rate is strongly correlated with good prognosis, the predictive factors for CR have not been elucidated., Methods: This registry study aimed to identify predictors of CR to definitive CRT in patients with unresectable locally advanced ESCC. "Unresectable" was defined as the primary lesion invading unresectable adjacent structures such as the aorta, vertebral body, and trachea (T4b), or the regional and/or supraclavicular lymph nodes invading unresectable adjacent structures (LNT4b)., Results: Overall, 175 patients who started definitive CRT between January 2013 and March 2020 were included. The confirmed CR (cCR) rate was 24% (42/175). The 2-year progression-free survival (PFS) and overall survival (OS) rates of cCR cases vs. non-cCR cases were 59% vs. 2% (log-rank p < 0.001) and 90% vs. 31% (log-rank p < 0.001), with a median follow-up period of 18.5 and 40.5 months, respectively. Multivariate analysis of clinicopathological factors revealed that tumor length ≥ 6 cm [odds ratio (OR) 0.446; 95% CI 0.220-0.905; p = 0.025] was a predictor of cCR., Conclusions: Favorable PFS and OS rates were observed in patients with cCR. Tumor length was a predictive factor for cCR., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Low-carbon water production technologies are indispensable for achieving sustainable development goals and mitigating global climate change. However, at present, many advanced water treatment processes lack a systematic assessment of related greenhouse gas (GHG) emissions. Thus, quantifying their life-cycle GHG emissions and proposing strategies toward carbon neutrality is urgently needed. This case study focuses on electrodialysis (ED), an electricity-driven desalination technology. To analyze the carbon footprint of ED desalination in various applications, a life cycle assessment model was developed based on industrial-scale ED processes. For seawater desalination, the carbon footprint is 59.74 kg CO 2 -eq/metric ton removed salt, which is one order of magnitude lower than that of high-salinity wastewater treatment and organic solvent desalination. Meanwhile, the power consumption during operation is the main hotspot of GHG emissions. Power grid decarbonization and improved waste recycling in China are projected to reduce the carbon footprint up to 92%. Meanwhile, the contribution of operation power consumption is expected to reduce from 95.83% to 77.84% for organic solvent desalination. Through sensitivity analysis, significant non-linear impacts of process variables on the carbon footprint were determined. Therefore, it is recommended to optimize the process design and operation to reduce power consumption based on the current fossil-based grid. GHG reduction for module production and disposal should also be emphasized. This method can be extended to general water treatment or other industrial technologies for carbon footprint assessment and reducing GHG emission., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: EGFR exon 20 insertion mutations account for 5% to 10% of EGFR-mutated NSCLC. CLN-081 (formerly known as TAS6417), a novel covalent EGFR tyrosine kinase inhibitor, exhibits pan-mutation selective efficacy, including exon 20 insertions, in the clinical setting. Nevertheless, some patients may not respond to CLN-081 and resistance to CLN-081 may emerge over time in others., Methods: We exposed Ba/F3 cells transduced with EGFR exon 20 insertions (Y764&#95;V765 insHH or A767&#95;S768insSVD) to increasing concentrations of CLN-081 to generate resistant cells and then subjected their complementary DNA to sequencing to identify acquired mutations. We then evaluated effects of small molecules on engineered Ba/F3 cells on the basis of proliferation assays, Western blotting, and xenograft models., Results: All CLN-081 resistant clones harbored the EGFR C797S mutation. Ba/F3 cells with C797S (Ba/F3-C797S) were resistant to EGFR tyrosine kinase inhibitors targeting EGFR exon 20 insertion mutations, including CLN-081. Pimitespib, a selective heat shock protein 90 inhibitor, induced apoptosis in Ba/F3-C797S cells in vitro and inhibited growth of Ba/F3-C797S tumors in vivo. Ba/F3 cells with A763&#95;Y764insFQEA-C797S remained sensitive to erlotinib., Conclusions: We conclude that the EGFR C797S mutation confers resistance to CLN-081. Our preclinical data suggest a potential small molecule to overcome CLN-081 resistance, which may benefit patients with lung cancer with EGFR exon 20 insertions., (© 2023 The Authors.)

Regulatory T (T reg ) cells suppress effective antitumor immunity in tumor-bearing hosts, thereby becoming promising targets in cancer immunotherapy. Despite the importance of T reg cells in tumor immunity, little is known about their differentiation process and epigenetic profiles in the tumor microenvironment (TME). Here, we showed that T reg cells in the TME of human lung cancers harbored a completely different open chromatin profile compared with CD8 + T cells, conventional CD4 + T cells in the TME, and peripheral T reg cells. The integrative sequencing analyses including ATAC, single-cell RNA, and single-cell ATAC sequencing revealed that BATF, IRF4, NF-κB, and NR4A were important transcription factors for T reg cell differentiation in the TME. In particular, BATF was identified as a key regulator, which leveraged T reg cell differentiation through epigenetically controlling activation-associated gene expression, resulting in the robustness of T reg cells in the TME. The single-cell sequencing approaches also revealed that tissue-resident and tumor-infiltrating T reg cells followed a common pathway for differentiation and activation in a BATF-dependent manner heading toward T reg cells with the most differentiated and activated phenotypes in tissues and tumors. BATF deficiency in T reg cells remarkably inhibited tumor growth, and high BATF expression was associated with poor prognosis in lung cancer, kidney cancer, and melanoma. These findings indicate one of the specific chromatin remodeling and differentiation programs of T reg cells in the TME, which can be applied in the development of T reg cell-targeted therapies.

Immunophenotyping of tumor-infiltrating lymphocytes (TILs) by flow cytometry can predict clinical efficacy of immunotherapy. However, several obstacles need to be overcome for developing a flow cytometry assay starting from solid tumor specimens. Here, we show a detailed enzyme-based protocol to isolate TILs from human tumor tissues. The protocol was optimized to obtain enough viable TILs from a biopsy tissue specimen for flow cytometry-based TIL immunophenotyping. Additionally, tissue samples could be preserved for up to 72 h for subsequent characterization. For complete details on the use and execution of this protocol, please refer to Kumagai et al. (2020, 2022)., Competing Interests: Declaration of interests H.N. received research funding from BD Japan for this study and received research funding and honoraria from Ono Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, and MSD, and research funding from Taiho Pharmaceutical, Daiichi-Sankyo, Kyowa Kirin, Zenyaku Kogyo, Oncolys BioPharma, Debiopharma, Asahi-Kasei, Sysmex, FUJIFILM, SRL, Eisai, Astellas Pharmaceutical, and Sumitomo Dainippon Pharma outside of this study. H.N. is the primary inventor on pending patents PCT/JP2020/0059919 belonging to the National Cancer Center Japan and BD Biosciences. S. Koyama received honoraria from Bristol-Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical, and MSD, and received research funding outside the scope of this work from Bristol-Myers Squibb, Ono Pharmaceutical, and Otsuka Pharmaceutical. S. Kumagai declares no competing interests. T.K., R.D., and E.A. are employees of Becton, Dickinson and Company, which is in the business of selling flow cytometers and flow cytometry reagents., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

One main challenge to utilize cellulose-based fibers as the precursor for carbon fibers is their inherently low carbon yield. This study aims to evaluate the use of keratin in chicken feathers, a byproduct of the poultry industry generated in large quantities, as a natural charring agent to improve the yield of cellulose-derived carbon fibers. Keratin-cellulose composite fibers are prepared through direct dissolution of the pulp and feather keratin in the ionic liquid 1,5-diazabicyclo[4.3.0]non-5-enium acetate ([DBNH]OAc) and subsequent dry jet wet spinning (so-called Ioncell process). Thermogravimetric analysis reveals that there is an increase in the carbon yield by ∼53 wt % with 30 wt % keratin incorporation. This increase is comparable to the one observed for lignin-cellulose composite fibers, in which lignin acts as a carbon booster due to its higher carbon content. Keratin, however, reduces the mechanical properties of cellulose precursor fibers to a lesser extent than lignin. Keratin introduces nitrogen and induces the formation of pores in the precursor fibers and the resulting carbon fibers. Carbon materials derived from the keratin-cellulose composite fiber show potential for applications where nitrogen doping and pores or voids in the carbon are desirable, for example, for low-cost bio-based carbons for energy harvest or storage., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Fast co-pyrolysis has been suggested as a promising technique to solve the environmental issues and simultaneously recover value-added products from polymer wastes. However, to date, no studies have focused on fast co-pyrolysis of printed circuit boards (PCB) and waste tire (WT). Therefore, we comprehensively investigated the fast co-pyrolysis of PCB and WT using pyrolysis-gas chromatography/mass spectrometry. The results show that an increase in temperature during fast pyrolysis improved the interactions between the PCB and WT pyrolyzates, increasing the formation of aliphatic and aromatic compounds. The formation of p-cymene was greatly induced by the isomerization and dehydrogenation reactions of D-limonene. Co-pyrolysis reduced the formation of brominated phenols and benzothiazole from PCB and WT pyrolysis, respectively, whereas promoted the interactions between Br- and S/N-containing radicals, concentrating them into heavy compounds. Increasing the temperature enhanced the release of heteroatom compounds. The findings suggest that debromination of PCB achieved via dehydrogenation of WT pyrolysis provoked secondary reactions of olefins and interactions of heteroatom radicals. The major products were accurately predicted by different fitting models using response surface methodology, indicating the synergistic interactions during co-pyrolysis. The results were beneficial for optimizing the experimental parameters to obtain the maximum yield of desired products., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Superior sulcus tumours (SSTs) are relatively uncommon and one of the most intractable lung cancers among non-small cell lung cancer (NSCLC). We planned a multicenter, single-arm confirmatory trial of new multidisciplinary treatment using immune-checkpoint inhibitor. The aim is to evaluate the safety and efficacy of new multidisciplinary treatment with perioperative durvalumab after chemoradiotherapy (CRT)., Methods: The primary endpoint is 3-year overall survival. Patients receive induction CRT with sequential two courses of durvalumab, followed by surgical resection for resectable SST. The regimen for CRT is two courses of cisplatin and S-1, and concurrent radiotherapy (66 Gy/33 Fr). After surgery, 22 courses of post-operative durvalumab therapy are administered. For unresectable SST, an additional 22 courses of durvalumab are administered after induction durvalumab., Results: In two cases as a safety cohort, the safety of intervention treatment up to 30 days after surgery was examined, and there were no special safety signals. Patient enrollment has now resumed in the main cohort., Conclusions: The results of this study may contribute to the establishment of a new standard of care for SST, which is an intractable NSCLC., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The balance of programmed death-1 (PD-1)-expressing CD8 + T cells and regulatory T (Treg) cells in the tumor microenvironment (TME) determines the clinical efficacy of PD-1 blockade therapy through the competition of their reactivation. However, factors that determine this balance remain unknown. Here, we show that Treg cells gain higher PD-1 expression than effector T cells in highly glycolytic tumors, including MYC-amplified tumors and liver tumors. Under low-glucose environments via glucose consumption by tumor cells, Treg cells actively absorbed lactic acid (LA) through monocarboxylate transporter 1 (MCT1), promoting NFAT1 translocation into the nucleus, thereby enhancing the expression of PD-1, whereas PD-1 expression by effector T cells was dampened. PD-1 blockade invigorated the PD-1-expressing Treg cells, resulting in treatment failure. We propose that LA in the highly glycolytic TME is an active checkpoint for the function of Treg cells in the TME via upregulation of PD-1 expression., Competing Interests: Declaration of interests H.Nishikawa received research funding from Ono Pharmaceutical for this work, research funding and honoraria from Chugai Pharmaceutical, Bristol-Myers Squibb and MSD, honoraria from Ono Pharmaceutical, and research funding from Taiho Pharmaceutical, Daiichi-Sankyo, Kyowa Kirin, Zenyaku Kogyo, Oncolys BioPharma, Debiopharma, Asahi-Kasei, Sysmex, Fujifilm, SRL, Astellas Pharmaceutical, Sumitomo Dainippon Pharma, and BD Japan outside of this study. H.Nishikawa is the primary inventor on pending patents PCT/JP2020/0059919 belonging to the National Cancer Center Japan and BD Biosciences. S.Koyama received research funding from Ono Pharmaceutical and Bristol-Myers Squibb outside this study. Y.Togashi received research grants from KOTAI Biotechnologies Inc., Daiichi-Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, and honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, Chugai Pharmaceutical, and MSD outside of this study. T.Yoshida received grants from Ono Pharmaceutical, AstraZeneca, AMGEN, Daiichi Sankyo, Bristol-Myers Squibb, MSD, Abbvie, and Takeda, and personal fees from Ono Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, MSD, Takeda, Chugai, Novartis, Lilly, Taiho, Archer DX, and Roche outside of this study. K.S. received paid consulting or advisory roles for Astellas, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono, MSD, Taiho, Novartis, AbbVie, GlaxoSmithKline, Daiichi Sankyo, Amgen, and Boehringer Ingelheim; honoraria from Novartis, AbbVie, and Yakult; and research funding from Astellas, Lilly, Ono Pharmaceutical, Sumoitomo Dainippon, Daiichi Sankyo, Taiho, Chugai, MSD, Medi Science, and Eisai outside of this study. Y.S. received research funding from Ono Pharmaceutical and Janssen Pharma and personal fees from AstraZeneca, Chugai, and Pfizer. N.Y. received personal fees from Ono Pharmaceutical, grants from Bristol-Myers Squibb, grants and personal fees from Novartis Pharma K.K., outside the submitted work. All other authors declare no competing financial interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Lung cancer is one of the most aggressive tumour types. Targeted therapies stratified by oncogenic drivers have substantially improved therapeutic outcomes in patients with non-small-cell lung cancer (NSCLC) 1 . However, such oncogenic drivers are not found in 25-40% of cases of lung adenocarcinoma, the most common histological subtype of NSCLC 2 . Here we identify a novel fusion transcript of CLIP1 and LTK using whole-transcriptome sequencing in a multi-institutional genome screening platform (LC-SCRUM-Asia, UMIN000036871). The CLIP1-LTK fusion was present in 0.4% of NSCLCs and was mutually exclusive with other known oncogenic drivers. We show that kinase activity of the CLIP1-LTK fusion protein is constitutively activated and has transformation potential. Treatment of Ba/F3 cells expressing CLIP1-LTK with lorlatinib, an ALK inhibitor, inhibited CLIP1-LTK kinase activity, suppressed proliferation and induced apoptosis. One patient with NSCLC harbouring the CLIP1-LTK fusion showed a good clinical response to lorlatinib treatment. To our knowledge, this is the first description of LTK alterations with oncogenic activity in cancers. These results identify the CLIP1-LTK fusion as a target in NSCLC that could be treated with lorlatinib., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

PD-1 blockade exerts antitumor effects by reinvigorating tumor antigen–specific CD8 + T cells. Whereas neoantigens arising from gene alterations in cancer cells comprise critical tumor antigens in antitumor immunity, a subset of non–small cell lung cancers (NSCLCs) harboring substantial tumor mutation burden (TMB) lack CD8 + T cells in the tumor microenvironment (TME), which results in resistance to PD-1 blockade therapy. To overcome this resistance, clarifying the mechanism(s) impairing antitumor immunity in highly mutated NSCLCs is an urgent issue. Here, we showed that activation of the WNT/β-catenin signaling pathway contributed to the development of a noninflamed TME in tumors with high TMB. NSCLCs that lacked immune cell infiltration into the TME despite high TMB preferentially up-regulated the WNT/β-catenin pathway. Immunologic assays revealed that those patients harbored neoantigen-specific CD8 + T cells in the peripheral blood but not in the TME, suggesting impaired T cell infiltration into the TME due to the activation of WNT/β-catenin signaling. In our animal models, the accumulation of gene mutations in cancer cells increased CD8 + T cell infiltration into the TME, thus slowing tumor growth. However, further accumulation of gene mutations blunted antitumor immunity by excluding CD8 + T cells from tumors in a WNT/β-catenin signaling-dependent manner. Combined treatment with PD-1 blockade and WNT/β-catenin signaling inhibitors induced better antitumor immunity than either treatment alone. Thus, we propose a mechanism-oriented combination therapy whereby immune checkpoint inhibitors can be combined with drugs that target cell-intrinsic oncogenic signaling pathways involved in tumor immune escape.

There are numerous combinations of biomass, plastic, and co-pyrolysis conditions. The presence of synergies, which make pyrolyzate distribution more complex, has been supported by research. In this study, the potential of response surface methodology (RSM) to predict the pyrolyzate yields affected by synergies during co-pyrolysis (500-700 °C) of cellulose and polyethylene was investigated, beyond gas, oil, and char yields. The results indicated that co-pyrolysis promoted liquid and C 5-28 hydrocarbon production with increasing temperature. The quadratic model could predict the total gas, CO, CO 2 , and liquid yields, including the synergy. The cubic model could predict the levoglucosan and C 5-28 hydrocarbon yields due to various synergies under different conditions. The linear model was suitable for the char yield distribution without interaction. Thus, this study reveals that RSM has a significant potential to predict pyrolyzate yields, enabling co-pyrolysis condition setting to maximize the desired product recovery with the fewest experiments., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Polycarbonate (PC) is an engineering thermoplastic that is widely used in electrical and electronic equipment. This plastic often contains tetrabromobisphenol A (TBBA), the most common brominated flame retardant. Thermal degradation of the PC-TBBA leads to generation of numerous bromo-organic products in the pyrolytic oil, hindering its appropriate utilization, as well as corrosive hydrogen bromide gas. The purpose of this study was to experimentally investigate and compare the pyrolysis products of PC-TBBA and PC-TBBA + Cu 2 O at various temperatures, with an emphasis on the yield and distribution of brominated compounds. In pyrolysis of PC-TBBA + Cu 2 O, at the maximum degradation temperature (600 °C), as much as 86% of total Br was trapped in the residue, while 3% and 11% were distributed in the condensate and gas fractions, respectively. In contrast, the distribution of Br from non-catalytic pyrolysis of PC-TBBA (600 °C) was 0.5% residue, 40% condensate, and 60% gas. The results of this study revealed that in the presence of Cu 2 O, organo-bromine products were most likely involved in Ullman-type coupling reactions, leading to early cross-linking of the polymer network that efficiently hinders their vaporization. HBr in the gas fraction was suppressed due to effective fixation of bromine in residue in the form of CuBr., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pyrolysis of cellulose primarily produces 1,6-anhydro-β-d-glucopyranose (levoglucosan), which easily repolymerizes to form coke precursors in the heating zone of a pyrolysis reactor. This hinders the investigation of primary pyrolysis products as well as the elucidation of cellulose pyrolysis mechanisms, particularly because of the significant buildup of coke during slow pyrolysis. The present study discusses the applicability of a pyrolysis-gas chromatography/flame ionization detection (Py-GC/FID) system using naphthalene as the internal standard, with the aim of substantially improving the quantification of pyrolyzates during the slow pyrolysis of cellulose. This method achieved quantification of levoglucosan with a yield that was 14 times higher than that obtained from offline pyrolysis in a simple tube reactor. The high yield recovery of levoglucosan was attributed to the suppression of levoglucosan repolymerization in the Py-GC/FID system, owing to the rapid escape of levoglucosan from the heating zone, low concentration of levoglucosan in the gas phase, and rapid quenching of levoglucosan. Therefore, this method facilitated the improved quantification of primary pyrolysis products during the slow pyrolysis of cellulose, which can be beneficial for understanding the primary pyrolysis reaction mechanisms. This method can potentially be applied to other polymeric materials that produce reactive pyrolyzates., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Aberrant signalling of ERBB family members plays an important role in tumorigenesis and in the escape from antitumour immunity in multiple malignancies. Molecular-targeted agents against these signalling pathways exhibit robust clinical efficacy, but patients inevitably experience acquired resistance to these molecular-targeted therapies. Although cancer immunotherapies, including immune checkpoint inhibitors (ICIs), have shown durable antitumour response in a subset of the treated patients in multiple cancer types, clinical efficacy is limited in cancers harbouring activating gene alterations of ERBB family members. In particular, ICI treatment of patients with non-small cell lung cancers with epidermal growth factor receptor (EGFR) alterations and breast cancers with HER2 alterations failed to show clinical benefits, suggesting that EGFR and HER2 signalling may have an essential role in inhibiting antitumour immune responses. Here, we discuss the mechanisms by which the signalling of ERBB family members affects not only autonomous cancer hallmarks, such as uncontrolled cell proliferation, but also antitumour immune responses in the tumour microenvironment and the potential application of immune-genome precision medicine into immunotherapy and molecular-targeted therapy focusing on the signalling of ERBB family members.

Pyrolysis is considered to be a promising method for polymer characterization (in the field of analytical pyrolysis) and for chemical feedstock recovery from plastic wastes (in the field of applied pyrolysis) because it can decompose any polymeric material into smaller molecules by applying heat alone in an inert atmosphere. Pyrolysis-gas chromatography (Py-GC) involves pyrolyzing polymeric materials in a micropyrolyzer and a subsequent direct GC analysis of pyrolyzates. Py-GC has immense potential for applications in the fields of both analytical and applied pyrolysis, as it allows for rapid and accurate analysis of pyrolyzates. This is beneficial for elucidating microstructure and composition of polymers and for a rapid screening of pyrolysis conditions for designing feedstock recycling processes. In this review, we examined the latest research trends in Py-GC applications for polymer characterization, analysis of plastics in the environment, and chemical feedstock recovery from plastics.

Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) is a promising technique allowing the rapid characterization of the polymer structure and additives of microgram-scale plastics. However, the Py-GC/MS analysis of polymers with urethane bonds is challenging because they produce highly reactive pyrolyzates such as amines and isocyanates polymerizing in the GC column, which limits the efforts to elucidate the pyrolysis mechanism and plastic characterization by online GC analysis. Herein, a novel pyrolysis-gas-phase derivatization-GC/MS (Py-GPD-GC/MS) technique was developed, allowing the pyrolysis of polymers and the subsequent direct gas-phase derivatization of pyrolyzates, employing a modified tandem μ-reactor-GC/MS system. This work conducted the gas-phase trifluoroacetylation of 4,4'-methylenedianiline (MDA), which is one of the major polyurethane (PU) pyrolyzates, using N -methyl-bis-trifluoroacetamide (MBTFA) as a derivatization agent. The trifluoroacetylation gas-phase reaction was monitored by in situ GC/MS analysis and the effects of derivatization conditions were investigated. The highest MDA conversion observed was 65.6 area %. Furthermore, the sequential PU pyrolysis and direct trifluoroacetylation of PU pyrolyzates in the first μ-reactor and second μ-reactor, respectively, were successfully operated, achieving the inhibited polymerization and detection of trifluoroacetylated derivatives. Thus, the Py-GPD-GC/MS method has a significant potential to be applied for other combinations of pyrolyzates and derivatization reactions, enabling deeper characterization of plastics producing highly reactive pyrolyzates that cannot be accurately analyzed by conventional Py-GC/MS analysis.

Immune checkpoint blockade has provided a paradigm shift in cancer therapy, but the success of this approach is very variable; therefore, biomarkers predictive of clinical efficacy are urgently required. Here, we show that the frequency of PD-1 + CD8 + T cells relative to that of PD-1 + regulatory T (T reg ) cells in the tumor microenvironment can predict the clinical efficacy of programmed cell death protein 1 (PD-1) blockade therapies and is superior to other predictors, including PD ligand 1 (PD-L1) expression or tumor mutational burden. PD-1 expression by CD8 + T cells and T reg cells negatively impacts effector and immunosuppressive functions, respectively. PD-1 blockade induces both recovery of dysfunctional PD-1 + CD8 + T cells and enhanced PD-1 + T reg cell-mediated immunosuppression. A profound reactivation of effector PD-1 + CD8 + T cells rather than PD-1 + T reg cells by PD-1 blockade is necessary for tumor regression. These findings provide a promising predictive biomarker for PD-1 blockade therapies.

A low carbon yield is a major limitation for the use of cellulose-based filaments as carbon fiber precursors. The present study aims to investigate the use of an abundant biopolymer chitosan as a natural charring agent particularly on enhancing the carbon yield of the cellulose-derived carbon fiber. The ionic liquid 1,5-diazabicyclo[4.3.0]non-5-enium acetate ([DBNH]OAc) was used for direct dissolution of cellulose and chitosan and to spin cellulose-chitosan composite fibers through a dry-jet wet spinning process (Ioncell). The homogenous distribution and tight packing of cellulose and chitosan revealed by X-ray scattering experiments enable a synergistic interaction between the two polymers during the pyrolysis reaction, resulting in a substantial increase of the carbon yield and preservation of mechanical properties of cellulose fiber compared to other cobiopolymers such as lignin and xylan.

Only a small percentage of patients afflicted with gastric cancer (GC) respond to immune checkpoint blockade (ICB). To study the mechanisms underlying this resistance, we examined the immune landscape of GC. A subset of these tumors was characterized by high frequencies of regulatory T (Treg) cells and low numbers of effector T cells. Genomic analyses revealed that these tumors bore mutations in RHOA that are known to drive tumor progression. RHOA mutations in cancer cells activated the PI3K-AKT-mTOR signaling pathway, increasing production of free fatty acids that are more effectively consumed by Treg cells than effector T cells. RHOA mutant tumors were resistant to PD-1 blockade but responded to combination of PD-1 blockade with inhibitors of the PI3K pathway or therapies targeting Treg cells. We propose that the metabolic advantage conferred by RHOA mutations enables Treg cell accumulation within GC tumors, generating an immunosuppressive TME that underlies resistance to ICB., Competing Interests: Declaration of interests Y.T. has received honoraria from Bristol-Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim GmbH, MSD, and AstraZeneca and has received research funding from KOTAI biotechnologies outside of this work. T. Kuwata. has received research funding from Ono Pharmaceutical and has received honoraria from Chugai Pharmaceutical outside of this work. H.M. has served as a member of the scientific advisory board for Chugai Pharmaceutical and has received research funding from Ono Pharmaceutical outside of this work. K.S. has served as a member of the scientific advisory board for Ono Pharmaceutical, Eli Lilly, Bristol-Myers Squibb, Astellas Pharmaceutical, Takeda Pharmaceutical, and Pfizer; has received research funding from Ono Pharmaceutical, Eli Lilly, Sumitomo Dainippon Pharmaceutical, Daiichi-Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, and MSD; and has received honoraria from Novartis Pharma, AbbVie GK, and Yakult Pharmaceutical Industry outside of this work. H.N. received research funding from Ono Pharmaceutical for this work, honoraria and research funding from Chugai Pharmaceutical and Bristol-Myers Squibb, honoraria from Ono Pharmaceutical and MSD, and research funding from Taiho Pharmaceutical, Daiichi-Sankyo, Kyowa Kirin, Zenyaku Kogyo, Oncolys BioPharma, Debiopharma, Asahi-Kasei, Astellas Pharmaceutical, Sumitomo Dainippon Pharmaceutical, Sysmex, and BD Japan outside this study. All the other authors declare that they have no competing financial interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Poly(vinyl chloride) (PVC) swelling coupled with ball milling was employed for the simultaneous recovery of high-purity Cu and PVC from waste wire harness under ambient conditions. The experimentally determined performances of 15 organic solvents for PVC swelling and phthalate plasticiser extraction were compared with those predicted considering Hansen solubility parameters. As a result, n-butyl acetate and acetone were identified as the two best solvents for adequate PVC swelling without PVC dissolution and almost complete plasticiser extraction within 60 min. The swelling was concluded to contribute to the control of phthalate plasticisers, the use of which in wire harness has recently been limited by the Restriction of Hazardous Substances (RoHS) directive. Cables swollen with n-butyl acetate or acetone were subjected to dry ball milling for ~ 60 min to completely separate PVC and Cu and achieve the quantitative recovery of these components from 20-cm-long cables. Thus, this work unveils the high potential of recycling the otherwise non-recyclable long and non-uniform waste wire harness cables and is expected to impact the related (e.g., automotive, electrical, and electronics) industries, contributing to the establishment of a more sustainable society.

To avoid the formation of undesired Cl compounds during polyvinyl chloride (PVC) wastes treatment and facilitate the recycling of valuable NaCl and dechlorinated hydrocarbons as feedstocks, advanced dechlorination (de-Cl) process should be developed. Here, an up-scale ball mill reactor was established for the de-Cl of real PVC wastes, including sealing strips from waste refrigerators and crushed cable coverings from waste cables. The effects of NaOH on de-Cl were validated with lab-scale studies and the influences of mechanical conditions were innovatively investigated. A maximum de-Cl degree of 99% was obtained with 1 M NaOH in ethylene glycol for sealing strips, whereas a maximum de-Cl degree of 92% was obtained with Φ1.27 cm stainless steel balls at a moderate rotation speed for cable coverings. The remaining Cl content in the sample residues was small and decreased with decreasing residue size, resulting in minimum contents of 0.49% and 0.61% for sealing strips and cable coverings, respectively. The de-Cl behavior was consistent with a shrinking-core model and the meaning of kinetic parameters was illustrated. The ball milling process was simulated by discrete element method (DEM). A positive correlation was observed between the apparent rate constant of the experimental de-Cl process and the specific impact energy calculated using DEM simulations. The combined experimental and simulation approach suggested that the surface of PVC is first dechlorinated and then crushed into fine particles by ball milling to expose the inner unreacted surface. For industrial application, the balance of chemical and mechanical conditions should be optimized., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In consideration of the toxicity and high migration capacity of plasticizers, the possibility to obtain flexible PVC via chemical modification of PVC was investigated for feedstock recycling. In this work, some Cl atoms of PVC were substituted with fragments of the common plasticizer DINP (diisononyl phthalate) in the presence of K 2 CO 3 (potassium carbonate) or DIEA ( N , N -diisopropylethylamine), and the simultaneous elimination of PVC was suppressed. 1 H NMR ( 1 H nuclear magnetic resonance spectroscopy) and 1 H- 1 H COSY ( 1 H- 1 H correlation spectroscopy) were used to evaluate the substitution while a novel method of calculating the substitution and elimination ratios was developed using a combination of 1 H NMR and elemental analysis. A maximum substitution rate of 35.7% was achieved using thiophenol as a nucleophile in the presence of DIEA, while the corresponding elimination of HCl was just 4.4%. In addition, the thermal stability of the modified PVCs was very close to that of pure PVC, which suggested that the main characteristics of PVC were preserved. Moreover, the T g values of all the modified PVCs were less than that of PVC, which means it is feasible to improve the plasticity of PVC via substituting some Cl on PVC with DINP moieties. Therefore, an alternative approach for feedstock recycling of PVC by chemical modification was developed in this work., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In this study, a high-accuracy separation process is proposed for recycling pure polyvinyl chloride (PVC) and Cu from the thin electric cables of electrical, electronic, and automotive wastes by PVC swelling and mechanical agitation in hydrophobic organic solvent mixed with water. The high stirring speed and low blade height combined with proper blade type and reactor tank shape ensure a separation rate of over 98%. By conducting computational fluid dynamic and discrete element model simulations, quantitative force, fluid velocity, and data visualization analyses were performed. The obtained separation rate exhibited strong positive correlations with the resultant, drag, and centripetal forces at various stirring speeds and blade heights. Using the experimental and simulation data, a plausible separation mechanism was suggested. It was found that Cu pieces could slip out from swollen PVC covers under the action of external forces, while the stirring speed should be high enough to apply sufficient external forces to cables via either blade-to-cable collisions or fluid drag. Furthermore, the vertical motion of cables induced by the low blade height was essential because the rotation in the bottom reactor part inhibited the slipping of Cu pieces., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Waste electric cables from end-of-life vehicles and electronic and electrical equipment present a significant problem in terms of environmental protection and resource recycling. Herein we detail a novel recycling method for thin waste electric cables, by combining polyvinyl chloride (PVC) swelling and centrifugal separation to simultaneously recover PVC and high-purity copper. PVC coverings were swollen in an organic solvent at ambient temperatures, which creates a gap between the covering and the copper wire and facilitates centrifugal separation. Electric cables (12 g) were 100% separated, and more than 95% of the plasticizer was extracted by stirring in 100-mL acetone or ethyl acetate that facilitated the separate recovery of copper, the PVC covering, and the plasticizer. In contrast, >97% separation, with <10% extraction of the plasticizer, was achieved with a mixture of 10 mL butyl acetate and 90 mL water. High-purity copper and PVC with controlled plasticizer content were recovered, which is highly advantageous for recycling both copper and PVC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study elucidated complex interactions during the chloride volatilization of heavy metals (Pb, Cu, Zn, Mn, and Cr) from municipal solid waste fly ash by combining thermodynamic and kinetic approaches. Chloride volatilization tests under HCl flow at 900 °C and subsequent rinsing with water achieved almost complete removal of Pb, Zn, and Mn. In contrast, almost 100 % of Cr and ∼40 % of Cu were not removed by either volatilization or rinsing processes. Kinetics indicated that the chlorination of Pb, Zn, and Mn followed a pseudo second order reaction and their apparent activation energies were 96.3, 89.2, and 43.5 kJ/mol, respectively. Further thermodynamic calculation revealed that the components contained in fly ash greatly influenced the chlorination of each heavy metal. Unburned carbon facilitated the chlorination of Pb, Zn, and Mn, while it inhibited Cu chlorination. MgO immobilized Cr and inhibited chlorination. KCl and NaCl promoted Zn and Mn chlorination, respectively. The revealed chloride volatilization behavior and effects of co-existing elements could be useful in the design of high-efficiency recovery process of heavy metals from fly ash and the utilization of residues as raw materials for cement. Furthermore, these findings could guide the realization of a recycling-oriented society in terms of reducing waste disposal., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: In patients with non-HIV Pneumocystis jirovecii pneumonia (PjP), computed tomography imaging reveals ground grass opacities (GGO). Previous reports show that some patients with non-HIV PjP exhibit GGO with crazy paving. However, there have been no studies on the association between crazy paving GGO and non-HIV PjP clinical outcomes. Here, at the diagnosis of non-HIV PjP, we reviewed high-resolution computed tomography (HRCT) findings that included GGO types and evaluated the prognostic impact of crazy paving GGO on the clinical outcomes of non-HIV PjP immunocompromised patients., Methods: We retrospectively reviewed the clinical information including the HRCT findings of patients diagnosed with non-HIV PjP from five institutions between 2006 and 2015. The GGO types included those with or without crazy paving. The associations between clinical factors such as HRCT findings and in-hospital mortality were assessed using the Cox regression model., Results: Sixty-one patients were included in our study. Nineteen patients died at a hospital. All patients exhibited GGO on HRCT imaging at diagnosis of non-HIV PjP. The HRCT findings included crazy paving GGO (29 patients, 47.5%), consolidations (23 patients, 37.7%), bronchiectasis (14 patients, 23.0%), and centrilobular small nodules (30 patients, 49.2%). Cysts were not observed in any patient. Multivariate analysis revealed that crazy paving GGO and low serum albumin levels were independent risk factors for mortality., Conclusions: At the diagnosis of non-HIV PjP, patients with crazy paving GGO on HRCT imaging and low serum albumin levels may have a poor prognosis.

Recycling wood/plastic composites in municipal and industrial wastes currently represents a challenge which needs to be overcome. In this work, we considered the concept of independent pyrolysis of wood and plastic in wood/plastic mixtures for enabling a versatile catalytic process design which is capable of producing recoverable final products from both components. In order to reveal the influence of plastic on wood pyrolysis, the pyrolysis of beech wood (BW, wood material) in a polyethylene (PE) melt (polyolefin material) was performed at 350 °C. The combined use of thermogravimetric analysis, product recovery studies, in situ radical characterisations, and microscopic analysis revealed the influence of the PE melt on the BW pyrolysis. More specifically, a physical prevention of the intermolecular condensation and hydrogen abstraction from PE pyrolysates in the liquid/solid phase was observed. These interactions enhanced the production of levoglucosan and methoxyphenols by factors of 1.7 and 1.4, respectively, during the BW pyrolysis in the PE melt. Based on these results, we concluded that the observed synergistic effects could potentially control the yield and quality of useful products, as well as the utilisation of mixed wood/plastic wastes, which cannot be effectively recycled otherwise.

Objectives: High-resolution computed tomography (HRCT) parenchymal patterns have been used to predict prognosis in patients with interstitial lung disease (ILD). In idiopathic pulmonary fibrosis, the fibrosis score (i.e. the combined extent of reticulation and honeycombing) has been associated with worse survival. This study aimed to identify HRCT patterns and patient characteristics that can predict poor prognosis in rheumatoid arthritis-related ILD (RA-ILD)., Methods: We retrospectively analysed 65 patients with newly diagnosed RA-ILD from 2007 to 2016 at Kurashiki Central hospital. Using univariate and bivariate Cox regression analysis, associations with mortality, were identified., Results: During a median follow-up of 56.5 months, 16/65 (24.6%) patients died. Univariate analysis identified six significant poor prognostic factors: lower baseline % predicted forced vital capacity, total interstitial disease score, reticulation score, traction bronchiectasis score, fibrosis score, and definite UIP pattern. Fibrosis score remained to be an independently significant poor prognostic factor of survival on bivariate analysis. Patients with a fibrosis score >20% had higher mortality (HR, 9.019; 95% CI, 2.87-28.35; p < .05)., Conclusion: This study showed that fibrosis score is strongly associated with worse survival in RA-ILD, and patients with fibrosis score >20% had a 9.019-fold increased risk of mortality.

Background: Most patients with acute eosinophilic pneumonia (AEP) show rapid improvement. However, some cases of AEP prove fatal. The aims of this study were to determine the clinical, radiographic, and pathologic characteristics of patients in whom AEP has a fatal outcome and to identify predictors of a poor prognosis., Methods: We retrospectively identified the medical records of all patients diagnosed with AEP at our institution in Japan from July 2005 to July 2013., Results: There were four deaths among 41 patients diagnosed to have AEP during the study period. All the patients who died were male; three cases were idiopathic and one was medication-related. The median bronchoalveolar lavage eosinophil differential count was 59%. An autopsy was performed on the patient with medication-related AEP who died and the pathologic finding was diffuse alveolar damage with eosinophilic infiltration. Diffuse ground-glass attenuation and traction bronchiectasis (TBE) were identified on high-resolution computed tomography in the four patients with fatal AEP. TBE was observed in six patients (five with idiopathic AEP, one with medication-related AEP), and 67% of these patients died. None of the patients with smoking-related AEP had TBE; all these patients had better responses to treatment and survived., Conclusions: We observed the characteristics of patients with fatal AEP who did not respond to treatment. TBE was observed in all fatal cases and may be associated with a poor prognosis., (Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

There is increasing demand in the electronics recycling industry for an effective method to separate polyvinyl chloride (PVC) and Cu from thin electric cable waste. Herein, a novel separation technique involving PVC embrittlement via plasticizer extraction and crushing by ball milling is proposed. The method was developed by varying the size, quantity, and hardness of the cables, as well as the size and quantity of the milling balls, to determine a combination that resulted in complete separation of PVC and high-purity Cu (>99.9%) from thin electric cables. The experimental crushing behavior was demonstrated via a sphere-to-cylinder discrete element model combined with a statistical approach. The mechanism of PVC crushing generated cracks from the edge to the center of the cable via ball impacts that were strong enough to overcome the elastic repulsion force of the PVC. The resulting method was found to be effective at separating PVC and high-purity Cu (>99.9%) from de-plasticized thin electric cables with diameters of 1.5-2.7 mm., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The pyrolysis of bisphenol A (BPA), an essential process ingredient used in industry and many everyday life products, helps produce low-industrial-demand chemicals such as isopropenyl- and isopropyl-phenols (IPP and iPrP). In this study, tandem micro-reactor gas chromatography/mass spectrometry combined with an H 2 generator (H 2 -TR-GC/MS) was employed for the first time to investigate the selective recovery of phenol via simultaneous hydrogenation/dealkylation of IPP and iPrP. After investigating the iPrP dealkylation performances of several zeolites, we obtained full iPrP conversion with over 99% phenol selectivity using the Y-zeolite at 350 °C. In contrast, when applied to IPP, the zeolite acid centres caused IPP polymerisation and subsequent IPP-polymer cracking, resulting in many byproducts and reduced phenol selectivity. This challenge was overcome by the addition of 0.3 wt% Ni on the Y-zeolite (0.3Ni/Y), which enabled the hydrogenation of IPP into iPrP and subsequent dealkylation into phenol (full IPP conversion with 92% phenol selectivity). Moreover, the catalyst deactivation and product distribution over repetitive catalytic use were successfully monitored using the H 2 -TR-GC/MS system. We believe that the findings presented herein could allow the recovery of phenol-rich products from polymeric waste with BPA macro skeleton.

Background: The number of patients with pulmonary nontuberculous mycobacterial disease complicated by chronic pulmonary aspergillosis (CPA) has been increasing. Additionally, CPA is reportedly associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). In the present study, we aimed to identify risk factors for developing CPA and stratify the risk for CPA development in patients with MAC-LD., Methods: We retrospectively examined 361 patients newly diagnosed with MAC-LD. Risk factors for CPA development were examined using multivariate Cox proportional hazards regression analyses. A risk stratification system was established using the risk factors and receiver operating characteristic curve analyses., Results: CPA developed in 20 (5.5%) of the 361 patients. Independent risk factors for CPA development included the presence of pulmonary emphysema, baseline steroid use, a serum albumin level <3.5 g/dL, and the presence of MAC-LD cavities. A 4-point scoring system was established to stratify patients into low-risk (0-1 point) and high-risk (2-4 points) groups. The 5-year incidence rates of CPA were 2.2% and 31% in the low- and high-risk groups, respectively (P < 0.001)., Conclusions: We identified independent predictors of CPA development and established a simple risk stratification system for identifying patients with MAC-LD who were at a high risk of developing CPA., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Nitrate-intercalated MgAl layered double hydroxide (LDH) was successfully delaminated in water by a facile and effective method upon reflux at 120 °C for 24 h followed by sonication at 40 °C for 5 h. This process is environmentally friendly since water is the only solvent used. The delaminated nanosheets were characterized by microscopic, spectroscopic, and particle size analyses. The delamination process successfully produced octahedron-shaped single-layer nanosheets 50-150 nm in size. X-ray photoelectron spectroscopy (XPS) data confirmed that the surface elements and their chemical status are consistent with the basic layer of MgAl LDH. The delaminated nanosheets displayed higher adsorption capacity for removing heavy metals from waste water than the original powdered LDH. After treating the waste water, a sharp and intense peak in the X-ray powder diffraction (XRD) pattern of the precipitate confirms the restacking of the LDH nanosheets., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Objective: Interstitial lung disease (ILD) is a common pulmonary manifestation of systemic sclerosis (SSc). It is unknown whether radiographic fibrosis score predicts mortality in SSc-associated ILD (SSc-ILD). We retrospectively analysed patients with SSc-ILD to evaluate whether radiographic fibrosis score was a useful predictor of mortality., Methods: We identified SSc-ILD patients evaluated at Kurashiki Central Hospital (Japan) from 2006 to 2016, and radiographic fibrosis scores based on the extent of reticulation and honeycombing on high-resolution computed tomography (HRCT) scanning were calculated by manually tracing around each fibrotic area. Independent predictors of overall survival were determined using the Cox proportional hazards model., Results: The study included 48 patients, of whom 19 had usual interstitial pneumonia on HRCT. The median follow-up period was 56.6 months, and over the follow-up period 15 patients died. The 5-year survival was 72.4%. In the multivariate analysis, radiographic fibrosis score, age, being male and forced vital capacity were independently associated with an increased risk of death, while HRCT pattern was not., Conclusion: A high radiographic fibrosis score was a poor prognostic factor in SSc-ILD. More widespread fibrosis was associated with an increased risk of death, independent of HRCT pattern., (© 2017 Asian Pacific Society of Respirology.)

The treatment of cesium-contaminated wastewater has become one of the biggest issues. The selective Cs + removal from wastewater containing competitive alkali metal ions such as Na + is desired to reduce the volume of sludge. Therefore, the present work focused on water-soluble calix[4]arene-bis-crown-6 (W-BisC6) to selectively capture Cs + . For characterization of the complex, UV-vis spectroscopy is commonly used, however, due to the limited availability of information it can be hard to quickly identify the specific structures of some complexes. In this work, the electrospray ionization time of flight spectrometry (ESI-TOF-MS) is successfully utilized to identify the number and type of cations in W-BisC6-cation complexes. ESI-TOF-MS accurately recognized 4 types of complex (W-BisC6-Na + , W-BisC6-Cs + , W-BisC6-2Na + , W-BisC6-Na + -Cs + ), and the experimental and simulated results were almost perfectly matched. It also revealed the difficulty of W-BisC6-2Cs + complex formation under the present conditions. Thus, this technique is significantly helpful for rapid identification of the specific structures of complexes during Cs + -contaminated wastewater treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Herein, we introduce a combination of plasticizer extraction from polyvinyl chloride (PVC) and ball milling for the simultaneous, effective recovery of PVC and copper (Cu) from thin electric cables. PVC coverings typically contain plasticizers for flexibility. As such, PVC cables become brittle after plasticizer extraction, causing them to be easily crushed by physical impact. Hence, we extracted the plasticizers from the PVC coverings of electric cables using organic solvents, and then crushed the obtained cable samples by ball milling. The influences of the plasticizer extraction yield and PVC morphologies before and after extraction on separation by ball milling were investigated. After a series of treatments to PVC coverings including quantitatively de-plasticizing for 5 h by Soxhlet-extraction in diethyl ether, 6 h ball milling and 1 h shaking in the sieve shaker, a maximum separation rate of 77% was achieved and the purity of the obtained separated Cu reached >99.8%., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: Pneumococcal pneumonia causes high morbidity and mortality among adults. This study aimed to identify risk factors for bacteremic pneumococcal pneumonia, and to construct a prediction model for the development of bacteremia in patients with community-acquired pneumococcal pneumonia., Methods: We retrospectively analyzed data from patients hospitalized with community-acquired pneumococcal pneumonia between April 2007 and August 2015. Logistic regression models were applied to detect risk factors for pneumococcal bacteremia, and a receiver operating characteristic curve was used to devise a prediction model., Results: Based on the results of sputum cultures, urine antigen tests, and/or blood cultures, 389 patients were diagnosed with pneumococcal pneumonia, 46 of whom had bacteremia. In the multivariate analysis, age < 65 years, serum albumin level < 3.0 g/dL, need for intensive respiratory or vasopressor support (IRVS), and C-reactive protein level > 20 mg/dL were identified as independent risk factors for the development of pneumococcal bacteremia. The bacteremia prediction score based on receiver operating characteristic curve analysis had a sensitivity of 0.74 and a specificity of 0.78 in patients with two risk factors. The area under the receiver operating characteristic curve was 0.77 (95% confidence interval (CI), 0.70-0.85)., Conclusions: Age < 65 years, hypoalbuminemia, IRVS, and high C-reactive protein level on admission are independent risk factors for the development of bacteremia in patients with community-acquired pneumococcal pneumonia. A prediction model based on these four risk factors could help to identify patients with community-acquired pneumococcal pneumonia at high risk of developing bacteremia; this can be used to guide antibiotic choices., Trial Registration: UMIN-CTR UMIN 000004353 . Registered 7 October 2010. Retrospectively registered.

IgA vasculitis (IgAV) commonly occurs in young children, who present with a tetrad of purpura, abdominal pain, arthralgia and nephritis. Diffuse alveolar hemorrhage (DAH) is a rare complication of IgAV. We herein report an adult case of IgAV with a presentation of DAH and nephritis (pulmonary renal syndrome, PRS), but without other typical manifestations, such as purpura, abdominal pain and arthralgia. A 33-year-old man presented with hemoptysis and a low-grade fever and was diagnosed to have IgAV based on the results of a renal biopsy. Treatment with corticosteroids, cyclophosphamide, and plasmapheresis was effective. IgAV should therefore be considered in the differential diagnosis of adult PRS.