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Wei-Fan Ou,1 Pei-Ya Liao,1 Yu-Wei Hsu,2,3 Yen-Hsiang Huang,1,4– 6 Kuo-Hsuan Hsu,6,7 Jeng-Sen Tseng,1,4– 6,8 Gee-Chen Chang,4,9– 11 Tsung-Ying Yang1,6,12 1Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Cancer Prevention and Control Center, Taichung Veterans General Hospital, Taichung, Taiwan; 3Computer and Communications Center, Taichung Veterans General Hospital, Taichung, Taiwan; 4Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; 5College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 6Lung Cancer Comprehensive Care and Research Center, Taichung Veterans General Hospital, Taichung, Taiwan; 7Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 8Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 9Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 10School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 11Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 12Department of Life Sciences, National Chung Hsing University, Taichung, TaiwanCorrespondence: Jeng-Sen Tseng, Lung Cancer Comprehensive Care and Research Center, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung, 407, Taiwan, Tel +886-4-23592525 ext. 3232, Fax +886-4-23741320, Email tzeng64@gmail.comBackground: Antiangiogenetic therapy and lung cancer, per se, are associated with an increased risk of thromboembolic events (TE). We aim to evaluate the pattern and outcome of TE as well as its influence on survival time of advanced non-small cell lung cancer (NSCLC) patients receiving antiangiogenic therapy.Methods: This was a retrospective cohort study, which included advanced NSCLC patients receiving antiangiogenic therapy. All TE were confirmed by objective image studies. We disclosed the presentation and risk factors of TE and evaluated its influence on outcome.Results: A total of 427 patients were included. TE occurred in 43 patients (10.1%). Deep vein thrombosis (DVT) was the most common TE (n = 20). Up to 46.2% of DVT did not occur in the typical lower extremities. Two patients died of TE. Among patients with continuous use or reuse of antiangiogenetic therapy, 18.2% had recurrent TE events. At the occurrence of TE, 28 patients experienced progressive disease (TE with PD), while tumor status remained stable in another 15 patients (TE without PD). The post-TE survival of patients without and with PD were 8.9 months (95% CI 3.9– 13.9) vs 2.2 months (95% CI 0.1– 4.3), P = 0.012. As compared with patients without TE (31.4 months [95% CI 27.1– 35.7]), TE with PD patients experienced a significantly shorter overall survival (20.1 months [95% CI 15.5– 24.6]), but TE without PD patients had comparable survival time (32.7 months [95% CI 7.4– 28.1]) (P = 0006). The use of hormone analogue and proteinuria predicted the events among TE with PD group (aOR 2.79 [95% CI 1.13=6.92]; P = 0.027) and TE without PD group (aOR 4.30 [95% CI 1.13– 16.42]; P = 0.033), respectively.Conclusion: Owing to the different risk factors and influences on the survival time, TE with and without PD may be two different disease entities.Keywords: non-small cell lung cancer, NSCLC, antiangiogenesis, bevacizumab, ramucirumab, thromboembolism

RATIONALE: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas. OBJECTIVES: To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis. METHODS: We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with lung adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with lung adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression. MEASUREMENTS AND MAIN RESULTS: We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with lung adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.024, log-rank test) in an independent cohort of 67 patients with lung adenocarcinoma. Overexpression of CLDN1 inhibited cancer cell dissociation in time-lapse imaging of wound healing, and suppressed cancer cell migration, invasion, and metastasis. Knockdown CLDN1 expression increased cancer cell invasive and metastatic abilities. Affymetrix microarrays identified a panel of genes altered by CLDN1 overexpression. CLDN1 increased expressions of cancer invasion/metastasis suppressors (e.g., connective tissue growth factor [CTGF], thrombospondin 1 [THBS1], deleted in liver cancer 1 [DLC1], occludin [OCLN], zona occludens 1 [ZO-1]) and suppressed expressions of invasion/metastasis enhancers (e.g., secreted phosphoprotein 1 [SPP1], cut-like homeobox 1 [CUTL1], transforming growth factor alpha [TGF-alpha], solute carrier family 2 [faciliated glucose transporter] member 3 [SLC2A3], placental growth factor [PGF]), supporting a role for CLDN1 as an invasion and metastasis suppressor. CONCLUSIONS: CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Study Design: Needle tract seeding after biopsy has been reported by many authors. Since the procedure of needle insertion in vertebroplasty is the same as in biopsy, tumor metastasis along the tract of the needle in vertebroplasty should be possible. Objective: We report local metastases along the needle tract as a rare complication of percutaneous vertebroplasty in treating spinal metastases in a lung cancer patient. Summary Of Background Data: The true incidence of tumor implantation along the needle tract may be underestimated as many patients die before the metastases become clinically significant. Methods: A 76-year-old man diagnosed with adenocarcinoma of lung underwent percutaneous vertebroplasty at L1 and L3 vertebral levels due to painful spinal metastases. His condition worsened 3 months later, however, with recurrent back pain and weakness of both legs. Results: MRI of lumbar spine performed post-percutaneous vertebroplasty revealed new contrast-enhanced lesions at the posterior aspect of L1 vertebral body with extension to the adjacent anterior epidural space of L1 and posterior epidural space along T12 to L3 levels with compression of the adjacent dural sac and additional paraspinal involvement. Conclusion: To our knowledge, local metastasis after vertebroplasty in treating spinal metastases has not been reported in the literature. However, this may be a potential complication of vertebroplasty in treating spinal metastases as improvement in cancer treatments occurs with subsequent longer survival times. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: The results for 37 surgical interventions in 31 consecutive patients with non-small cell lung cancer (NSCLC) with symptomatic spinal cord compression were reviewed retrospectively. OBJECTIVES: To evaluate postoperative outcomes and survival rates of NSCLC patients surgically treated for symptomatic spinal metastasis. SUMMARY OF BACKGROUND DATA: For patients with spinal cord compression secondary to lung cancer, the prognosis is usually poor. However, with the development of new chemotherapeutic drugs and targeted therapeutic agents, the survival rate may be better. METHODS: From November 2000 to March 2005, 31 patients with symptomatic metastatic spinal cord compression secondary to NSCLC underwent palliative surgery using a posterolateral transpedicular approach (PTA) or combined posterior and anterior procedures. The indication for surgery was neurologic progression due to spinal cord compression. RESULTS: The patients ranged in age from 20 to 81 years (mean, 61.4 years). Twenty-eight patients (90%) underwent PTA, and 3 patients had combined posterior and anterior procedures. Neurologic improvement by at least one Frankel grade was noted in 25 of 31 cases (80%). Overall, 74% of patients (23 of 31) were able to walk after surgery. There was no case of intraoperative mortality, but two deaths occurred in the postoperative period. Median survival time was 8.8 months. CONCLUSIONS: Even though lung cancer is considered an aggressive tumor, it is justifiable to aggressively treat patients with symptomatic spinal cord compression. Surgery by PTA can lead to good results in these patients. [ABSTRACT FROM AUTHOR]

Small vertebrate carcasses represent critical resources for many terrestrial organisms, including burying beetles, which rely on carcasses for survival and breeding. Carcass attributes can influence the reproduction of burying beetles, yet most studies on their breeding ecology have used laboratory-reared carcasses of limited sizes. We conducted breeding and feeding experiments using a wide size range of lab (laboratory mice) and wild carcasses (wild mammals, birds and reptiles) to investigate how carcass size, source and taxon affect various breeding outcomes (e.g. clutch size, brood size and brood mass) of the burying beetle Nicrophorus nepalensis . Our results reveal a hump-shaped relationship between carcass size and breeding performance, with optimal breeding outcomes occurring on medium-sized carcasses. Furthermore, despite the variation in carcass tissue nutritional composition, breeding outcomes and larval growth did not differ between the two carcass sources or among the three wild carcass taxa. Finally, we found a larval quality-quantity trade-off across the range of carcasses examined, with carcass size shaping the larval life-history traits. Overall, these results elucidate how carcass resources may influence the breeding performance of burying beetles. Importantly, our study provides solid evidence validating decades of research using lab carcasses to study the reproductive ecology of burying beetles., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Background: Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC)., Methods: In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR -mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review., Results: Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR -related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib., Conclusions: Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR -mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Bevacizumab is extensively used in the treatment of advanced non-small-cell lung cancer (NSCLC). Numerous clinical trials have proven the clinical efficacies of bevacizumab biosimilars (BB)., Objective: Our study aimed to compare the clinical outcomes between bevacizumab reference product (RP) and BB among advanced NSCLC patients in a real-world setting., Design: We retrospectively analyzed stage IV metastatic NSCLC patients who were treated with bevacizumab as part of a combination therapy. Patients were categorized into chemotherapy (CT) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) groups. We compared the patients' characteristics, treatment efficacy, and adverse events between RP and BB in the two treatment groups., Methods: From January 2020 to July 2022, a total of 171 patients who underwent combination therapy with bevacizumab were screened. Seventy-nine of these patients met the study's inclusion criteria and were enrolled in the final analysis. We utilized the Kaplan-Meier method to estimate progression-free survival (PFS) and the log-rank test to compare PFS between groups. The Cox proportional hazards model was used to identify predictors of PFS., Results: Within the CT cohort, 34 patients were treated with RP in combination with platinum and pemetrexed, and 25 patients received a combination regimen with BB. The median PFS was 6.9 months in the RP group and 8.9 months in the BB group ( p  = 0.255). Within the EGFR-TKI cohort, 20 patients with EGFR -mutant NSCLC received first-line treatment with EGFR-TKI plus bevacizumab. Of these patients, 9 were treated with a combination regimen that included RP, and 11 patients received EGFR-TKI in combination with BB. The median PFS was 18.4 months for the RP group and 13.6 months for the BB group ( p  = 0.363)., Conclusion: In our advanced NSCLC patients, we found no difference in clinical outcomes when receiving treatment with RP or BB. Given a combination regimen, BB was as effective as RP together with either CT or EGFR-TKIs., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background: The clinical outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced lung adenocarcinoma vary according to real-world data., Objective: In this study, we aimed to investigate the treatment discontinuation (TTD) and overall survival (OS) of patients with ALK+ advanced lung adenocarcinoma treated with first-line ALK-TKIs in Taiwan., Patients and Methods: This retrospective study evaluated all advanced lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2020 who had ALK rearrangement and received ALK-TKI treatment, using data from Taiwan's National Health Insurance Research Database (NHIRD). The TKI treatment sequences were classified into first generation (G1: crizotinib), second generation (G2: ceritinib, alectinib, brigatinib), and third generation (G3: lorlatinib)., Results: A total of 587 patients were analyzed, with a median age of 60.0 years, 91 (15.5%) aged ≥ 74 years, 293 (49.9%) female, 397 (67.6%) never smoked, and 534 (91.0%) with stage IV disease. Patients who received next-generation ALK-TKIs during the treatment course had longer median time to ALK-TKI TTD and OS. The TTD of the G1, G1+2, G1+2+3, G2, and G2+3 groups was 7.5 (5.4-11.1), 40.6 (29.4-not calculated (NC)), 50.3 (41.3-NC), 34.3 (29.2-43.0), and 36.3 (22.4-NC) months, respectively (p < 0.001). The median OS of the patients in the G1, G1+2, G1+2+3, G2, and G2+3 groups was 10.6 (7.5-14.6), not reached (NR) (NC-NC), NR (NC-NC), 43.0 (36.3-NC), and NR (30.3-NC) months, respectively (p < 0.001). Compared with treatment with crizotinib alone, the multivariate analysis revealed that treatment with next-generation TKIs was independently associated with longer TTD (G1+2 (hazard ratio (HR), 0.24; 95% CI 0.17-0.33; p < 0.001), G1+2+3 or G1+3 (HR, 0.17; 95% confidence interval (CI), 0.10-0.28; p < 0.001), G2 (HR, 0.26; 95% CI 0.19-0.36; p < 0.001), and G2+3 (HR, 0.25; 95% CI 0.14-0.44; p < 0.001)) and median OS (G12 (HR, 0.24; 95% CI 0.17-0.35; p < 0.001), G1+2+3 or G1+3 (HR, 0.09; 95% CI 0.04-0.21; p < 0.001), G2 (HR, 0.22; 95% CI 0.15-0.31; p < 0.001), and G2+3 (HR, 0.20; 95% CI 0.10-0.42; p < 0.001))., Conclusions: For patients with ALK+ NSCLC, treatments including next-generation ALK-TKIs were independently associated with longer survival outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

C-reactive protein (CRP) is a liver-derived acute phase reactant that is a clinical marker of inflammation associated with poor cancer prognosis. Elevated CRP levels are observed in many types of cancer and are associated with significantly increased risk of metastasis, suggesting that CRP could have pro-metastatic actions. Here, we reported that CRP promotes lung metastasis by dampening the anti-cancer capacity of pulmonary macrophages in breast cancer and melanoma. Deletion of CRP in mice inhibited lung metastasis of breast cancer and melanoma cells without significantly impacting tumor growth compared to wildtype mice. In addition, the lungs of CRP deficient mice were enriched for activated pulmonary macrophages, which could be reduced to the level of wildtype mice by systemic administration of human CRP. Mechanistically, CRP blocked the activation of pulmonary macrophages induced by commensal bacteria in a FcγR2B-dependent manner, thereby impairing macrophage-mediated immune surveillance to promote the formation of a pre-metastatic niche in the lungs of tumor-bearing mice. Accordingly, treatment with specific CRP inhibitors activated pulmonary macrophages and attenuated lung metastasis in vivo. These findings highlight the importance of CRP in lung metastasis, which may represent an effective therapeutic target for patients with advanced solid cancers in clinics.

DNA damage-inducible transcript 3 (DDIT3) is a well-known transcription factor that regulates the expression of apoptosis-related genes for promoting apoptosis during endoplasmic reticulum stress. Here, we report an unrecognized role of DDIT3 in facilitating necroptosis. DDIT3 directly binds and competitively prevents the p38 MAPK-MK2 interaction and thereby blocking MK2 activation while stimulating p38 MAPK activation. This blockage of MK2 activation initially prevents RIPK1 phosphorylation at Ser320 (inactivation), subsequently relieving its suppression of RIPK1 activation. Consequently, p38 MAPK facilitates RIPK1 phosphorylation at Ser166 (activation) through DDIT3 phosphorylation-related mechanisms, leading to necroptosis. Mechanistically, a 10-amino acid segment (Glu19-Val28) within DDIT3's N-terminus is identified to account for its pro-necroptotic function. In vivo studies demonstrate that forced expression of DDIT3 induces necroptosis, whereas deletion of DDIT3 alleviates necroptosis in mouse hearts under stress. These findings shed light on a novel regulatory mechanism by which DDIT3 promotes RIPK1 activation and subsequent necroptosis., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Acetylene semihydrogenation is an important process both theoretically and experimentally. Pure Pd catalysts usually suffer from limited selectivity for ethylene products and poor stability. Pd-Bi bimetallic compounds are synthesized and show not only excellent catalytic performance but also remarkable long-term stability. However, the detailed mechanism is still unclear. In this paper, the acetylene semihydrogenation mechanism on Pd(100), Pd 3 Bi 1 (100), and Pd 1 Bi 1 (100) is studied by density functional theory (DFT) calculation and microkinetic modeling. Adding Bi causes the surface d-band center (ε d ) to move to a lower energy, and the adsorption strength of the intermediate becomes weaker. Besides, ethylidyne (CCH 3 ) formation becomes more difficult on the Pd-Bi alloy due to the lack of continuous surface Pd atoms. As a spectator, CCH 3 deactivates the Pd and Pd-Bi alloys by a steric effect. However, the selectivity for ethylene on the Pd-Bi alloy is still high because of the weakly bonded ethylene. We found the relationship between ε d and the catalysts' activity and selectivity. This study may supply some clues for the design of selective hydrogenation catalysts.

Purpose: Tissue-based next-generation sequencing (NGS) analysis is highly recommended for patients with advanced/metastatic non-small cell lung cancer (NSCLC). We investigated a specific patient population with NSCLC that required tissue-based NGS analysis., Materials and Methods: We enrolled 500 patients with advanced/metastatic (1) epidermal growth factor receptor ( EGFR ) mutations or anaplastic large-cell lymphoma kinase ( ALK ) rearrangement-positive NSCLC who had failed at minimum one line of tyrosine kinase inhibitor (TKI) therapy, (2) EGFR-/ALK -negative nonsquamous, and (3) non- or light-smoker patients with squamous NSCLC who were treatment-naïve or had failed at maximum two lines of systemic treatment. These patients were divided into five cohorts. Comprehensive tissue-based NGS testing (ACTOnco+) was conducted., Results: Cohort 1: EGFR TKI-pretreated EGFR -mutated population (50.0%, n = 250), cohort 2: ALK inhibitor-pretreated ALK -positive population (1.6%, n = 8), cohort 3: treatment-naïve EGFR-/ALK -negative population (28.2%, n = 141), cohort 4: pretreated EGFR-/ALK -negative population (16.8%, n = 84), and cohort 5: squamous cell carcinoma (3.4%, n = 17). In cohort 1, 11.2% (28/250) of the patients had MET amplification, 32.4% (81/250) had been treated with osimertinib, and EGFR C797S was detected in 6.2% (5/81) of these patients. In cohort 2, resistance ALK mutation was detected in 37.5% (3/8) of the patients. In cohorts 3 and 4, targetable genetic alterations, including EGFR mutation (13.3%), ERBB2 mutation (9.3%), MET exon 14 skipping (5.3%), KRAS G12C mutation (4.4%), ROS1 fusion (2.7%), RET fusion (1.8%), and BRAF V600E mutation (1.3%), were detected. In cohort 5, MET exon 14 skipping was detected in 29.4% (5/17) of the patients., Conclusion: This multicenter registration study investigated tissue-based NGS for a specific patient population with NSCLC in Taiwan.

Background: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups., Patients and Methods: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR)., Results: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]., Conclusions: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Eliciting host plant resistance using plant hormones such as jasmonates has the potential to protect seeds and seedlings against insect pests; however, several hurdles exist for adapting it for pest management. This includes determining a dose that promotes resistance without limiting plant growth, an application method that growers could use, and ensuring the plants are responsive in the abiotic conditions when the pest occurs. In laboratory and field assays, we tested if treating corn seeds with multiple concentrations of methyl jasmonate would reduce the preference of ovipositing seed corn maggot adults and the performance of larvae feeding on seeds., Results: We found that corn seeds soaked in aqueous 0.2 mM methyl jasmonate solution showed marginally lower seedling growth, but the adult oviposition preference was ~60% lower on these seeds compared to control water-soaked seeds. Seeds that were treated with methyl jasmonate using a conventional polymer-based seed coating showed no effect on seedling growth but reduced adult oviposition preference. In no-choice bioassays with adult flies, we found reduced oviposition on seeds soaked with aqueous methyl jasmonate compared to controls. Larval survival to pupation was also lower in methyl jasmonate-treated seeds. Lastly, the methyl jasmonate-induced resistance also occurred at the lower temperatures typical of the spring soil conditions when this fly is most damaging., Conclusion: Methyl jasmonate seed treatment in aqueous solution or using conventional polymer-based technology, has the potential to deter adult oviposition and reduce maggot performance in spring temperature conditions with minor effects on seed germination and growth. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Gonorrhea remains a significant burden in central Ohio, particularly in socially disadvantaged communities. This study evaluates gonorrhea case rates and changes from 2020 to 2021, focusing on geographic patterns associated with social vulnerability., Methods: We analyzed gonorrhea case data from the Columbus STD Surveillance Network (SSuN) for 2020 and 2021. Cases were linked to census tracts and categorized into low (0-0.66) or high (0.67-1.0) vulnerability groups based on the CDC/ATSDR social vulnerability index (SVI). We mapped gonorrhea case rates per 100,000 population, stratified by SVI group, and compared changes using Jenks natural breaks to determine cutpoints. High case rates were defined as ≥605 (2020) and ≥ 532 (2021). A change in case rates was defined as <154 (decrease/no change) or ≥ 154 (increase). Demographic factors were summarized for both years., Results: In 2020 and 2021, nearly half of high SVI tracts had high gonorrhea rates, compared to about 4-7% of low SVI tracts. Median rates in high SVI tracts were approximately five times higher than in low SVI tracts, with rates 546 and 598 per 100,000 in 2020 and 2021, compared to 98 and 104 per 100,000, respectively. Gonorrhea rates increased in 23 (9%) of low SVI tracts and 37 (25%) of high SVI tracts. Demographic characteristics remained consistent between the two years., Conclusions: Gonorrhea rates increased in central Ohio between 2020 and 2021, with higher burdens in high SVI census tracts. Understanding the dynamics of social vulnerability at the community level is crucial for targeting limited STD resources effectively., Competing Interests: Conflict of Interest Statement: none, (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Lorlatinib is a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-positive metastatic non-small cell lung cancer (NSCLC). In a global phase II study, patients who experience disease progression despite prior treatment with ALK tyrosine kinase inhibitors (TKIs) was assessed. Herein, we report real-world clinical outcomes of lorlatinib-treated patients with ALK-positive advanced NSCLC who were heavily pretreated and progressed on first- and second-generation ALK-TKIs, in a Taiwanese population under the lorlatinib expanded access program (EAP)., Methods: This multicenter observational study examined the effectiveness and safety of ALK-positive advanced NSCLC patients that progressed from previous second-generation ALK-TKI therapy and received lorlatinib treatment subsequently. Patients who received lorlatinib treatment under EAP between Jul 2017 and Sep 2019 were eligible. Patients were followed for at least one year from the first lorlatinib treatment until study completion., Results: Sixty-three patients were eligible for safety analysis (male: 46.0 %; median age: 52.8 [27.5-78.3] years; brain metastases: 81.0 %). Fifty-four patients with more than one-month lorlatinib treatment were included in the effectiveness analysis. Prior to lorlatinib treatment, 10 patients (18.5 %) received one ALK-TKI, 27 (50.0 %) received two ALK-TKIs, and 17 (31.5 %) received three or more ALK-TKIs. The overall median rwPFS was 9.2 months (95 % confidence interval: 5.3-21.1). The best overall response rate (n = 51) was 13.7 %, with a disease control rate of 80.4 %., Conclusion: Lorlatinib exhibits substantial activity and tolerability when used clinically in a later-line setting in a Taiwanese population with ALK-positive advanced NSCLC., Competing Interests: Declaration of competing interest A conflict of interest occurs when an individual's objectivity is potentially compromised by a desire for financial gain, prominence, professional advancement or a successful outcome. JFMA Editors strive to ensure that what is published in the Journal is as balanced, objective and evidence-based as possible. Since it can be difficult to distinguish between an actual conflict of interest and a perceived conflict of interest, the Journal requires authors to disclose all and any potential conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Four new lycoctonine-type C 19 -diterpenoid alkaloids kamaonensines H-K ( 1-4 ) have been isolated from the whole plants of Delphinium kamaonense , together with 12 known compounds ( 5-16 ). Interestingly, kamaonensines 1-3 contained a rare nitrone (immine N-oxide) moiety, respectively. Their structures were established by spectroscopic analyses. The active evaluation of compounds ( 1-16 ) by LPS induced RAW 264.7 macrophages showed that compounds 4 and 8 displayed strong anti-inflammatory activities. While compounds 11 and 12 also showed strong cytotoxicities by the RAW 264.7 cell viability assay.

Context: The mechanisms for the formation of the first C - C bond and lower olefins on methanol to olefins (MTO) conversion on H-ZSM-5 had been focused in dispute. In this paper, density functional theory has been used to study the reaction mechanisms of methanol to olefins on ZSM-5. The configurations of reactants, intermediates, products and transition state of the numerous reactions involved in such a process have been optimized, as well as the elementary reactions related to these configurations were determined by the calculation of corresponding activation energy barriers and reaction heats. Here, two different kinds of the mechanisms were proposed for the formation of dimethyl ether (DME), one involving an associative interaction of two methanol molecules with the zeolite Brønsted acid sites and the other occurring via a surface methoxy species and a methanol molecule. A critical intermediate of the methoxy methyl cation was theoretically verified by the reaction of the methoxy species and dimethyl ether. Besides, it was found that the first intermediates containing a C - C bond were 1,2-dimethoxyethane and 2-methoxy-ethanolare, in which the former was formed from methoxy species with dimethyl ether and the latter was formed from methanol by onium ions((CH 3 ) 2 O + CH 2 CH 2 OCH 3 ), respectively. For the whole reaction mechanism, the results in this paper indicated that the ethene formation is more favorable than propylene formation due to the low activation energy barrier for ethene formation (123.49 vs. 162.09 kJ.mol -1 ). From these calculations, it would be concluded that ethene is the first alkene product that induces the occurrence of the hydrocarbon pool mechanism., Methods: All the periodic density function theory (DFT) calculations were performed by the Vienna Ab Initio Simulation package (VASP). The interaction between nucleus and valence electron was described using the pseudopotentials found in the projector augmented wave (PAW) method. PBE-D3 was used in the whole DFT calculations and CI-NEB was used to locate transition state., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The vast extensional planes of two-dimensional (2D) nanomaterials are recognized as desirable ground for electrocatalytic reactions. However, they tend to exhibit catalytic inertia due to their surface-ordered coordination configurations. Herein, an in situ autoxidation strategy enables high-density grafting of ultrafine CeO 2 nanoclusters on 2D Co(OH) 2 . Affluent active units were activated at the inert interface of Co(OH) 2 via the formation of Co-O-Ce units. The optimized catalyst exhibits oxygen evolution reaction activity with an overpotential of 83 mV lower than that of Co(OH) 2 at 10 mA cm -2 . The cascade orbital coupling between Co (3d) and Ce (4f) in Co-O-Ce units drives electron transfer by unlocking a "d-f electron ladder". Meanwhile, the bond-order theorem analyses and the d-band center show that the occupancy of Co-3d- e g is optimized to balance the adsorption-desorption process of active sites to the key reaction intermediate *OOH, thereby making it easier to release oxygen. This work will drive the development of wider area electron modulation methods and provide guidance for the surface engineering of 2D nanomaterials.

Dry reforming of methane (DRM) reaction has great potential in reducing the greenhouse effect and solving energy problems. Herein, the DRM reaction mechanism and activity on Ni 16 /LaZrO 2 catalyst under electric fields were comprehensively investigated by combining density functional theory calculations with microkinetic modeling. The results showed that La doping increases the interaction between Ni and ZrO 2 by Ni cluster transfer of more electrons. The adsorption strength of species followed the order Ni 16 /ZrO 2 > Ni 16 /LaZrO 2 , which is consistent with the results for the d-band center but opposite to the metal-support interaction. The best DRM reaction path on Ni 16 /LaZrO 2 was the CH 2 -O pathway, which is different from the CH-O pathway on Ni(111) and Ni 16 /ZrO 2 . Both positive and negative electric fields of strong and weak metal-support interactions reduced the energy barrier of DRM reaction. Importantly, our results showed that the more dispersed and smaller Ni 12 /LaZrO 2 model by considering the dispersing effect induced by La doping, which displayed very different results from that of Ni 16 /LaZrO 2 : reduced the energy barrier for methane decomposition, thereby promoting DRM reaction activity. Microkinetic results showed that the carbon deposition behavior of DRM becomes weaker on Ni 16 /LaZrO 2 due to the suppression of methane decomposition in the presence of La doping compared to Ni 16 /ZrO 2 , but the opposite result is obtained on Ni 12 /LaZrO 2 . The order of DRM reactivity was Ni 16 /LaZrO 2 < Ni 16 /ZrO 2 < Ni 12 /LaZrO 2 , which is consistent with the experiment observations. The conversion of methane and CO 2 was higher in positive electric fields than in negative electric fields at low temperatures, but the results were opposite at high temperature. Negative electric fields can improve the carbon deposition resistance of Ni-based catalysts compared to positive electric fields. The degree of rate control analysis showed that CH x * oxidation also plays an important role in the DRM reaction. We envision that this study could provide a deeper understanding for guiding the widespread application of electric field catalysis.

The properties of nanopipettes largely rely on the materials introduced onto their inner walls, which allow for a vast extension of their sensing capabilities. The challenge of simultaneously enhancing the sensitivity and selectivity of nanopipettes for pH sensing remains, hindering their practical applications. Herein, we report insulin-modified nanopipettes with excellent pH response performances, which were prepared by introducing insulin onto their inner walls via a two-step reaction involving silanization and amidation. The pH response intensity based on ion current rectification was significantly enhanced by approximately 4.29 times when utilizing insulin-modified nanopipettes compared with bare ones, demonstrating a linear response within the pH range of 2.50 to 7.80. In addition, insulin-modified nanopipettes featured good reversibility and selectivity. The modification processes were monitored using the I-V curves, and the relevant mechanisms were discussed. The effects of solution pH and insulin concentration on the modification results were investigated to achieve optimal insulin introduction. This study showed that the pH response behavior of nanopipettes can be greatly improved by introducing versatile molecules onto the inner walls, thereby contributing to the development and utilization of pH-responsive nanopipettes.

Despite the widespread application of next-generation sequencing (NGS) in advanced lung adenocarcinoma, its impact on survival and the optimal timing for the examination remain uncertain. This cohort study included advanced lung adenocarcinoma patients who underwent NGS testing. We categorized patients into four groups: Group 1: treatment-naïve, upfront NGS; Group 2: Treatment-naïve, exclusionary EGFR / ALK / ROS1 ; Group 3: post-treatment, no known EGFR / ALK / ROS1 ; Group 4: known driver mutation and post-TKI treatment. A total of 424 patients were included. There were 128, 126, 90, and 80 patients in Groups 1, 2, 3, and 4, respectively. In Groups 1, 2, 3, and 4, targetable mutations were identified in 76.6%, 49.2%, 41.1%, and 33.3% of the patients, respectively ( p < 0.001). Mutation-targeted treatments were applied in 68.0%, 15.1%, 27.8%, and 22.5% of the patients, respectively ( p < 0.001). In the overall population, patients receiving mutation-targeted treatments exhibited significantly longer overall survival (OS) (aHR 0.54 [95% CI 0.37-0.79], p = 0.001). The most profound benefit was seen in the Group 1 patients (not reached vs. 40.4 months, p = 0.028). The median OS of patients with mutation-targeted treatments was also significantly longer among Group 2 patients. The median post-NGS survival of patients receiving mutation-targeted treatments was numerically longer in Group 3 and Group 4 patients. In conclusion, mutation-targeted therapy is associated with a favorable outcome. However, the opportunities of NGS-directed treatment and the survival benefits of mutation-targeted treatment were various among different populations., Competing Interests: The authors declare no conflicts of interest.

Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene-based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force-tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high-efficient movement, pre-orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high-orientation MXene-rich layer (orientation degree, f = 0.83) and a polymer-rich layer. The authors demonstrate that MXene-based nanocomposite hydrogels leverage their high-orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super-low MXene of 0.3 wt%, surpassing most hydrogels-based electromagnetic shielding materials. This versatile supergravity-steered strategy can be further extended to arbitrary nanosheets including MoS 2 , GO, and C 3 N 4 , offering a paradigm in the development of oriented nanocomposites., (© 2024 Wiley‐VCH GmbH.)

Tidal flats provide critical habitat for migratory waterbird species; however, populations of migratory waterbirds have significantly declined due to tidal flat loss and degradation caused by human activities, particularly in Asia. Gochang getbol is one of tidal flats located on the southwest coast of South Korea and a center of clam production. Using bird monitoring data collected at five zones (zone1 to zone5) established across Gochang getbol and near coastal area, we examined distribution patterns of migratory bird diversity and conservation-related species along the coast of Gochang getbol. The intensity of human activity ‒ mudflat culture (mostly bivalve) and aquaculture was relatively high at zone2 and zone3, occupying > 30% of 2km circular area surrounding most sample points of these zones. Zone1 and particularly zone4 contained more natural/semi-natural habitats (less disturbed mudflats and wetlands) and zone5 had smallest mudflat than others. Shannon diversity, species richness, and abundance of migratory birds differed between zones (Anova test, P ≤ 0.02) except Shannon diversity in winter. In fall, all values were higher at zone4 than zone3 and zone5. In winter, zone1 showed greatest species richness and higher abundance than zone2, zone3, and zone5. In spring, while most differences were found between zone4 and zone5, abundance at zone4 was somewhat higher than zone2. The results from the fourth corner analysis indicated that abundance of species foraging at mudflat level was positively associated with zone1 (winter) but negatively with zone3 (fall). Sandpipers were positively associated with zone4. Abundance distribution maps of conservation-related species, created by inverse distance-weighted interpolation modeling, also showed high abundance of most conservation-related species at zone4 and 1. The findings of our study suggest the importance of natural/semi-natural habitat, and the possible link between human activity and distribution patterns of migratory birds in Gochang getbol. While we need further investigation on direct response of migratory birds to human activity, areas with low human activity with more natural/semi-natural habitat, e.g., zone4 and zone1 may be crucial for the conservation of migratory birds., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Osimertinib has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) in clinical trials. However, real-world data on its effectiveness remain scarce. Taiwanese patients with T790M-positive locally advanced or metastatic NSCLC and progressive disease following treatment with at least one EGFR tyrosine kinase inhibitor (TKI) were enrolled from the osimertinib early access program. Of the 419 patients (mean age, 63 years; female, 67%), 53% were heavily pretreated (≥ third-line [3L]), making osimertinib a fourth-line (4L) intervention. The median progression-free survival (PFS) was 10.5 months (95% confidence interval [CI]: 8.95-11.41); the 18-month PFS rate was 26.5%. The median overall survival (OS) was 19.0 months (95% CI: 16.30-20.95); the 24-month OS rate was 40.9%. The objective response rate was 32.46%, and the disease control rate was 86.38%. The median time to treatment discontinuation of osimertinib monotherapy was 11.9 months (95% CI: 10.49-13.11). Subgroup analyses of median PFS and OS in the chemotherapy combination group vs. the osimertinib monotherapy group yielded no difference. Central nervous system (CNS) metastasis, number of prior lines of therapy, and types of initial EGFR-TKIs did not significantly impact outcomes. The median PFS values were 9.0 (95% CI: 5.18-11.34) and 10.9 (95% CI: 9.18-11.90) months with and without CNS metastasis, respectively, and 10.8 (95% CI: 8.59-12.69), 13.6 (95% CI: 10.89-16.3), and 9.2 (95% CI: 7.8-10.62) months for second-line (2L), 3L, and ≥4L therapy, respectively. In patients who received osimertinib as 2L therapy, the median PFS values in response to prior afatinib, erlotinib and gefitinib treatment were 11.2 (95% CI: 4.85-4.79), 10.5 (95% CI: 8.59-20.26) and 8.7 (95% CI: 7.21-16.79) months, respectively. Overall, real-world data from Taiwan support the clinical benefits of osimertinib in EGFR T790M -positive NSCLC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The tumor microenvironment (TME) in renal cell carcinomas (RCC) is marked by substantial immunosuppression and immune resistance despite having extensive T-cell infiltration. Elucidation of the mechanisms underlying immune evasion could help identify therapeutic strategies to boost the efficacy of immune checkpoint blockade (ICB) in RCC. This study uncovered a mechanism wherein the polyadenylate-binding protein PABPC1L modulates indoleamine 2,3-dioxygenase 1 (IDO1), a prospective target for immunotherapy. PABPC1L was markedly upregulated in RCC, and high PABPC1L expression correlated with unfavorable prognosis and resistance to ICB. PABPC1L bolstered tryptophan metabolism by upregulating IDO1, inducing T-cell dysfunction and Treg infiltration. PABPC1L enhanced the stability of JAK2 mRNA, leading to increased JAK2-STAT1 signaling that induced IDO1 expression. Additionally, PABPC1L-induced activation of the JAK2-STAT1 axis created a positive feedback loop to promote PABPC1L transcription. Conversely, loss of PABPC1L diminished IDO1 expression, mitigated cytotoxic T-cell suppression, and enhanced responsiveness to anti-PD-1 therapy in patient-derived xenograft models. These findings reveal the crucial role of PABPC1L in facilitating immune evasion in RCC and indicate that inhibiting PABPC1L could be a potential immunotherapeutic approach in combination with ICB to improve patient outcomes., Significance: PABPC1L functions as a key factor in renal cell carcinoma immune evasion, enhancing IDO1 and impeding T-cell function, and represents a potential target to enhance the efficacy of immune checkpoint blockade therapy., (©2024 The Authors; Published by the American Association for Cancer Research.)

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with onset in infancy or early childhood. Mendelian randomization (MR) is a statistical method used to infer causal relationships between exposures and outcomes. This article summarizes MR studies related to ASD. Existing research supports a causal relationship between maternal inflammatory bowel disease in children with ASD, parental education levels, screen time exposure, obesity, insomnia, serum transferrin, decreased blood selenium, abnormal signals in brain functional MRI, interleukin-6, phosphodiesterase 2A, mitogen-activated protein kinase kinase 3, mitochondrial ribosomal protein L33, serotonin, and ASD. However, it does not support a causal relationship between parental rheumatoid arthritis, systemic lupus erythematosus, neonatal jaundice in children with ASD, cytomegalovirus infection, asthma, oral ulcers, vitamin D levels, and ASD. This article reviews the etiological factors related to ASD and MR studies, aiming to explore and deepen the understanding of the pathophysiology of ASD. It provides strong statistical support for the prevention, diagnosis, and treatment of ASD, and offers new methods and strategies for the etiological analysis of complex traits.

Objectives: Severe acute respiratory syndrome coronavirus 2 has been described as eliciting a powerful immune response. The association of coronavirus disease 2019 (COVID-19) infection with diseases requiring emergent or urgent colectomies may exacerbate the risk of surgical complications. We investigated the effect of preoperative COVID-19 infection on the clinical outcomes of patients who underwent a nonelective colectomy in 2021., Methods: We queried the American College of Surgeons National Surgical Quality Improvement Program Targeted Colectomy database for all of the patients who underwent a colectomy in 2021 and filtered for patients classified as "Urgent" or "Emergent." Two groups were created based on preoperative COVID-19 status: COVID + (n = 242) and COVID - cohorts (n = 11,049). Several clinical variables were compared., Results: Before filtering for urgent/emergent operations, a large percentage of COVID + patients were found to have undergone an urgent or emergency colectomy (68.36% vs 25.05%). Preoperatively, these patients were more likely to be taking steroids (21.49% vs 12.41%) or have a bleeding issue requiring a transfusion (19.42% vs 11.00%). A larger percentage of infected patients returned to the operating room (14.05% vs 8.13%) and had a hospital stay >30 days (18.18% vs 5.35%). COVID-19 infection was associated with a higher rate of mortality (14.05% vs 8.08%) but did not independently predict it (odds ratio 1.25, P = 0.233), with all P ≤ 0.001., Conclusions: Urgent or emergent colectomy patients who were COVID-19 + preoperatively were more likely to present with comorbidities, which, along with the recent viral infection, contributed to markedly worse clinical outcomes, including an increased rate of mortality.

Introduction: For patients with unresectable, stage III non-small-cell lung cancer (NSCLC), current standard of care is concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab. However, earlier initiation of durvalumab simultaneously with cCRT may increase antitumor activity relative to initiation after cCRT. The phase 1 CLOVER study (NCT03509012) evaluated durvalumab combined with cCRT in patients with advanced solid tumors; we report findings from the NSCLC cohort., Methods: CLOVER comprised a dose-limiting toxicity (DLT) assessment part, followed by an expansion part. In the NSCLC cohort, patients with previously untreated, unresectable, stage III NSCLC were enrolled in three treatment arms: durvalumab every 4 weeks (Q4W) + cisplatin + etoposide + radiotherapy (Arm 1); durvalumab Q4W + carboplatin + paclitaxel + radiotherapy (Arm 2); or durvalumab Q4W + carboplatin or cisplatin + pemetrexed + radiotherapy (non-squamous histology only; Arm 3). Patients received durvalumab until disease progression or unacceptable toxicity. The primary endpoint was safety and tolerability., Results: Sixty-four patients were enrolled: 21, 22, and 21 in Arms 1, 2, and 3, respectively. One patient in Arm 1 had DLT (grade 3 aspartate aminotransferase increase and grade 4 alanine aminotransferase increase); no DLTs were observed in Arms 2 or 3. Grade 3/4 adverse events occurred in 76.6 % of patients overall; the most common were neutropenia (51.6 %), leukopenia (20.3 %), and anemia (17.2 %). In a post-hoc analysis, 7.8 % of patients had grade 3 pneumonitis/radiation pneumonitis (grouped term) events. Overall, the objective response rate was 60.9 % (95 % confidence interval [CI], 47.9-72.9); median duration of response was 15.8 months (95 % CI, 9.0-not estimable [NE]). Median progression-free survival was 13.4 months (95 % CI, 8.8-20.1) and median overall survival was not reached (95 % CI, 21.9-NE)., Conclusion: Durvalumab in combination with cCRT was well tolerated, with a manageable safety profile and showed encouraging antitumor activity in patients with unresectable, stage III NSCLC., Competing Interests: Declaration of competing interest Dong-Wan Kim reports research funding (to institution) from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer-Ingelheim, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, InnoN Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan, reports uncompensated consultation or advisory roles for Amgen, AstraZeneca, BMS/ONO Pharmaceuticals, Daiichi-Sankyo, GSK, Janssen, Meck, MSD, NoveltyNobility, Oncobix, Pfizer, SK Biopharm, and Takeda, and has received medical writing assistance from Amgen, AstraZeneca, Boehringer-Ingelheim, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Janssen, Merus, Mirati Therapeutics, MSD, Meck, Novartis, Pfizer, Roche, Takeda, and Yuhan. Byoung Chul Cho is an employee of Yonsei University Health System, reports stock/share ownership in TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., and J INTS BIO, reports advisory council or committee membership for KANAPH Therapeutic Inc, Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, and Oscotec Inc, is a member of the board of directors for Interpark Bio Convergence Corp., and J INTS BIO, is an invited speaker for ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, and Pfizer, is a consultant for Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus Therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Takeda, MSD, Janssen, Medpacto, Blueprint Medicines, RandBio, and Hanmi, reports grants or funds from MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, Abbvie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, and CHA Bundang Medical Center, reports royalties from Champions Oncology, Crown Bioscience, and Imagen, and is a founder of DAAN Biotherapeutics. Sang-We Kim reports advisory meeting participation for AstraZeneca, Amgen, Boehringer Ingelheim, Janssen, Novartis, Takeda, Therapex, and Yuhan, lecture fees from Boehringer Ingelheim, and research funding from Yuhan. Gee-Chen Chang reports honoraria from F. Hoffmann–La Roche, Ltd, Eli Lilly and Company Oncology, AstraZeneca, Novartis, Pfizer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Merck Sharp & Dohme. Myung-Ju Ahn reports advisory council or committee membership for AstraZeneca, YUHAN, Roche, Pfizer, Amgen, Merck, Takeda, Alpha Pharmaceutical, and VORONOI. Rosa Alvarez reports advisory council or committee membership for Astra Zeneca, Pharmamar, Boehringer Ingelheim, Novartis, Sanofi, and GSK, reports research funding (to institution) from PharmaMar, Astra Zeneca, Rain Therapeutics, GSK, Boehringer Ingelheim, Cebiotex, Roche, Philogen, MSD, Janssen, Pfizer, Daichii Sankyo, Gilead, and Seagen, speaker fees from Pharmamar, and travel support from Roche and Pharmamar. Chao-Hua Chiu reports honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, Shionogi, and Takeda. José Trigo reports consulting fees from AstraZeneca, MSD, Eisai, and BMS. Ana Estiva reports advisory council or committee membership for Takeda, Roche, and MSD, and honoraria from Pfizer, MSD, Roche, Takeda, Pharmamar, and GSK. Sana D. Karam reports grants or funds from AstraZeneca (clinical trial), Genentech (clinical trial), and Roche (preclinical). Cathy O’Brien is a contractor for AstraZeneca. Hema Gowda is an employee of AstraZeneca, and reports stock/share ownership in AstraZeneca and Incyte. Haiyi Jiang reports employment and stock/share ownership with AstraZeneca. Julie E. Bauman reports consulting fees from BluedotBio and Exelixis. Krishna Pachipala and Chih-Liang Wang do not have any competing interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Efficient clearance and degradation of apoptotic cardiomyocytes by macrophages (collectively termed efferocytosis) is critical for inflammation resolution and restoration of cardiac function after myocardial ischemia/reperfusion (I/R). Here, we define secreted and transmembrane protein 1a (Sectm1a), a cardiac macrophage-enriched gene, as a modulator of macrophage efferocytosis in I/R-injured hearts. Upon myocardial I/R, Sectm1a-KO mice exhibited impaired macrophage efferocytosis, leading to massive accumulation of apoptotic cardiomyocytes, cardiac inflammation, fibrosis, and consequently, exaggerated cardiac dysfunction. By contrast, therapeutic administration of recombinant SECTM1A protein significantly enhanced macrophage efferocytosis and improved cardiac function. Mechanistically, SECTM1A could elicit autocrine effects on the activation of glucocorticoid-induced TNF receptor (GITR) at the surface of macrophages, leading to the upregulation of liver X receptor α (LXRα) and its downstream efferocytosis-related genes and lysosomal enzyme genes. Our study suggests that Sectm1a-mediated activation of the Gitr/LXRα axis could be a promising approach to enhance macrophage efferocytosis for the treatment of myocardial I/R injury.

Background: Spodoptera frugiperda, a global agricultural pest, can be effectively controlled through the sterile insect technique. However, exposure to low-dose radiation below the sterilization threshold may induce hormetic effects. Here, the biphasic aspects of the fertile progeny population of S. frugiperda were analyzed using an age-stage, two-sex life table after dosing male and female pupae with 10-350 Gy gamma radiation., Results: The parental sterilizing dose for 6-day-old female and male pupae was 200 and 350 Gy, respectively. The total longevity, pre-adult survival rate, net reproduction rate, and intrinsic growth rate of the offspring population increased with decreasing radiation doses from 250 to 10 Gy. Offspring population of parents treated with low doses of 10-100 Gy showed better life table parameters compared to non-irradiated controls. Females and males fecundity irradiated with 10, 50, and 100 Gy and 10 Gy, respectively, exceeded controls, producing 2339.4, 2726.4, 2311, and 2369 eggs, as opposed to 1802.9 eggs produced by the controls. Males irradiated with 10 Gy displayed the highest intrinsic rates of increase and net reproduction rate, at 0.1709 and 682.3, respectively. Projections from the survival rate and fecundity indicated that female and male S. frugiperda populations after 10 Gy irradiation may grow considerably faster than the controls., Conclusion: This study explores the hormetic effects of low-dose radiation on S. frugiperda through life table analysis, while providing enhancements for utilizing substerilizing gamma dose in a modified F 1 sterility technique. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Objectives: To investigate the value of the human chorionic gonadotropin (hCG) stimulation test in the diagnosis of disorder of sexual development (DSD) in children., Methods: A retrospective analysis was conducted on 132 children with DSD. According to the karyotype, they were divided into three groups: 46,XX group ( n =10), 46,XY group ( n =87), and sex chromosome abnormality group ( n =35). The above groups were compared in terms of sex hormone levels before and after hCG stimulation test, and the morphological manifestation of the impact of testicular tissue on the results of the hCG stimulation test was analyzed., Results: There was no significant difference in the multiple increase of testosterone after stimulation among the three groups ( P> 0.05). In the 46,XY group, the children with 5α-reductase type 2 deficiency had a testosterone-to-dihydrotestosterone ratio higher than that of the 46,XY DSD children with other causes. Morphological analysis showed that DSD children with testicular tissue demonstrated a significantly higher multiple increase in testosterone after stimulation compared to children without testicular tissue ( P <0.05)., Conclusions: The hCG stimulation test has an important value in assessing the presence and function of testicular interstitial cells in children with different types of DSD, and it is recommended to perform the hCG stimulation test for DSD children with unclear gonadal type.

The chemisorbed oxygen usually promotes the CH bond activation over less active metals like IB group metals but has no effect or even an inhibition effect over more active metals like Pd based on the static electronic structure study. However, the understanding in terms of dynamics knowledge is far from complete. In the present work, methane dissociation on the oxygen-preadsorbed transition metals including Au, Cu, Ni, Pt, and Pd is systemically studied by reactive force field (ReaxFF). The ReaxFF simulation results indicate that CH 4 molecules mainly undergo the direct dissociation on Ni, Pt, and Pd surfaces, while undergo the oxygen-assisted dissociation on Au and Cu surfaces. Additionally, the ab initio molecular dynamics (AIMD) simulations with the umbrella sampling are employed to study the free-energy changes of CH 4 dissociation, and the results further support the CH 4 dissociation pathway during the ReaxFF simulations. The present results based on ReaxFF and AIMD will provide a deeper dynamic understanding of the effects of pre-adsorbed oxygen species on the CH bond activation compared to that of static DFT., (© 2023 Wiley Periodicals LLC.)

Background: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer., Methods: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ 2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing., Findings: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis., Interpretation: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer., Funding: Ministry of Health and Welfare of Taiwan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC). These two chronic inflammatory conditions can differ in severity, presentation, and anatomical localization, and can greatly affect quality of life if not managed properly. Given the many healthcare challenges during the coronavirus disease 2019 pandemic, we studied the effects of the pandemic and corresponding changes to medical resources on surgical outcomes for patients with IBD., Methods: Deidentified data from patients who underwent a colectomy for CD or UC were collected from the National Surgical Quality Improvement Program database of the American College of Surgeons. We analyzed clinical factors and surgical outcomes between 2019 and 2020., Results: Patients with IBD were more likely to have lost >10% of their body mass before the operation in 2020. Operations for patients with UC were significantly shorter in the first year of the pandemic. Patients with CD were less likely to have a urinary tract infection or sepsis postoperatively in 2020, whereas patients with UC were more likely to require a repeat operation. Interestingly, both patient populations were less likely to undergo an emergency operation in 2020 than in 2019., Conclusions: Colectomy outcomes for patients with CD in 2020 were similar or improved in comparison with those seen in 2019, whereas colectomies for UC saw a statistically but not clinically significant increase in the rate of repeat operations. Overall, these patients seem to have been well managed despite the coronavirus disease 2019 pandemic-induced strain on the healthcare system.

Abstract: Extracellular vesicles (EVs) are a new revelation in cross-kingdom communication, with increasing evidence showing the diverse roles of bacterial EVs (BEVs) in mammalian cells and host-microbe interactions. Bacterial EVs include outer membrane vesicles released by gram-negative bacteria and membrane vesicles generated from gram-positive bacteria. Recently, BEVs have drawn attention for their potential as biomarkers and therapeutic tools because they are nano-sized and can deliver bacterial cargo into host cells. Importantly, exposure to BEVs significantly affects various physiological and pathological responses in mammalian cells. Herein, we provide a comprehensive overview of the various effects of BEVs on host cells (i.e., immune cells, endothelial cells, and epithelial cells) and inflammatory/infectious diseases. First, the biogenesis and purification methods of BEVs are summarized. Next, the mechanisms and pathways identified by BEVs that stimulate either proinflammatory or anti-inflammatory responses are highlighted. In addition, we discuss the mechanisms by which BEVs regulate host-microbe interactions and their effects on the immune system. Finally, this review focuses on the contribution of BEVs to the pathogenesis of sepsis/septic shock and their therapeutic potential for the treatment of sepsis., Competing Interests: The authors report no conflicts of interests., (Copyright © 2023 by the Shock Society.)

Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA. Method: We used pooled genetic data from the UK Biobank for ALM(n = 450,243), left-hand grip strength (n = 461,026), right-hand grip strength (n = 461,089) and usual walking pace (n = 459,915). Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA (n = 826,690), hand OA (n = 303,7782), hip OA (n = 353,388) and knee OA (n = 396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted p values ( P FDR ). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses. Results: We discovered ALM (odds ratio (OR) = 1.103, 95% confidence interval (CI) = 1.052-1.156, P FDR = 2.87E-04), hand grip strength (left, IVW OR = 0.823, 95% CI = 0.712 to 0.952, P FDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, P FDR = 0.020), and usual walking pace (OR = 0.339, 95% CI = 0.204 to 0.564, P FDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (β = -0.258, 95% CI = -0.369 to 0.146, P FDR = 0.6.07E-06), grip strength (left, β = -0.064, 95% CI = -0.104 to 0.024, P FDR = 0.002; right, β = -0.055, 95% CI = -0.095 to 0.014, P FDR = 0.008), and usual walking pace (β = -0.104, 95% CI = -0.147 to 0.061, P FDR = 1.61E-05). Conclusion: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jia, Deng, Su, Shi, Qin, Yu, Yin, Liu and Shi.)

Biomass-coal blending combustion is an effective method for utilizing biomass; however, its pollutant emission requires attention. Herein, the effect of biomass-coal blending combustion on lead (Pb) transformation was explored. Combustion experiments were conducted in a fixed-bed reactor, using coal, corn stalk, rice stalk, bamboo flour and their mixtures as fuels, at 1000, 1100, 1200 and 1300 °C. The Pb release ratios were determined by measuring its content in the fuels and solid-phase combustion products. The distribution of Pb forms was analyzed using sequential chemical extraction. The results indicate that blending combustion significantly enhanced the release of Pb. At blending ratio 1:1, the release ratios increased by 1.54-27.2%, 5.30-15.6%, and 2.31-7.76% at 1000, 1100, and 1200 °C, respectively. The potassium (K) components in biomass, mainly KCl and K 2 CO 3 , had a significant promoting effect on Pb release. K compounds facilitated the release of residual Pb through reactions with aluminosilicates. The promotion effect weakened as the temperature increased due to the faster evaporation rate of K. When the mass fractions of K in the fuels were equal, K 2 CO 3 exhibited a stronger promoting effect. HCl had minimal impact on the transformation of Pb. The results are helpful for optimizing the combination of biomass and coal to control Pb emission from the blending combustion source., 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 Elsevier B.V. All rights reserved.)