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Purpose: ERBB2 exon 20 insertions (20ins) have been identified as oncogenic drivers in lung cancers. Lung cancer patients with 20ins benefit from afatinib. However, response heterogeneity was observed in patients harboring different 20ins subtypes. In this study, we interrogated clinical characteristics in ERBB2-mutated Chinese lung cancer and investigated the clinical outcomes of specific ERBB2 20ins in response to afatinib. Experimental design: In this study, we retrospectively collected genomic profiling data of 7,520 lung cancer patients sequenced using next-generation sequencing in a Clinical Laboratory Improvement Amendments-certified laboratory. We analyzed the clinical and molecular features of patients harboring ERBB2 20ins and evaluated clinical outcomes of 19 patients with clinical records after afatinib treatment. Results: ERBB2 20ins were identified in 2.27% (171/7,520) of this lung cancer cohort. It occurred with a high proportion in females with adenocarcinoma histology. ERBB2 20ins was mutually exclusive with other well-established lung cancer oncogenic driver mutations. The most frequently appearing subtype was Y772_A775dup (69.6%) and several novel insertion subtypes were also identified. The correlations of specific 20ins subtypes and survival were investigated. The presence of a glycine at position 778 in ERBB2 was suggested to be a common feature of drug sensitivity mutations. Patients harboring G778_P780dup (G778) subtype achieved longer median progression-free survival and median overall survival than other 20ins (non-G778) subtypes (median progression-free survival, 10 vs 3.3 months, P=0.32; median overall survival, 19.7 vs 7 months, P=0.16). Moreover, we presented the first clinical case of a lung squamous cell carcinoma patient harboring ERBB2 20ins who achieved partial response to afatinib. Conclusion: This study interrogated the characteristics of ERBB2 20ins in a large cohort from single ethnicity and demonstrated the response heterogeneity to afatinib among different ERBB2 20ins subtypes. Further studies in a larger cohort are needed to investigate the underlying molecular mechanisms and clinical response of different ERBB2 20ins subtypes. [ABSTRACT FROM AUTHOR]

Abstract: Immune checkpoint blockade‐related pneumonitis is a rare but potentially life‐threatening adverse effect, but its risk factors are not completely understood. This case‐control study was conducted to identify pneumonitis risk factors in patients treated with anti‐PD1 monoclonal antibodies (mAbs), including all the patients who developed pneumonitis after anti‐PD‐1 mAbs treatment in the Cancer Center of the Chinese People's Liberation Army from September 2015 to September 2017. Two controls per case were matched according to a propensity‐score matching algorithm to account for confounding effects caused by individual baseline variables. Demographic and clinical information was obtained from medical records. In total, 55 cases and 110 controls were included in the study. No association was observed between smoking status or primary lung cancer and risk of pneumonitis. Significant risk factors for pneumonitis related to anti‐PD‐1 mAbs were prior thoracic radiotherapy, prior lung disease and combination therapy with odds ratios of 3.34 (1.51‐7.39), 2.86 (1.45‐5.64) and 2.73 (1.40‐5.31), respectively. The associations remained significant in the multivariable logistic regression model. The risk of pneumonitis induced by anti‐PD‐1 mAbs is associated with prior thoracic radiotherapy, prior lung disease, and combination therapy. Clinicians should monitor these features in patients receiving anti‐PD‐1 therapy to optimize clinical safety and efficacy. [ABSTRACT FROM AUTHOR]

The effects of rhenium (Re) and high-angle grain boundaries upon the elemental distribution and microstructure of as-cast Ni-based single-crystal superalloy blades are investigated herein. The addition of Re reduces the coarsening of the γ dendrite and γ' phases. Further, the degree of partitioning of the element Al in the γ' phase decreases with Re addition, while that of the elements Ta, Ti, Ni, and Mo increases. The addition of Re greatly decreases the concentration gradient, and greatly increases the diffusion distance, of the alloying elements in the region close to the γ/γ' phase boundary. As the grain boundary angle increases from 35° to 45°, a Re -enriched σ phase is directly precipitated from the γ' phase at the grain boundary. In addition, both the amount of σ phase and the concentration of Re in that phase increase with increasing grain boundary angle. • Interactive effect of Re addition on elements distribution are studied. • Re changes elements diffusion from short- to long-distance at γ/γ' phase boundary. • Effect of HAGs on elements distribution and microstructure formation is studied. • Increasing Re is observed at grain boundary with increasing HAGs' angle. • With increasing HAGs' angle, increasing σ phases are precipitated from γ' phase. [ABSTRACT FROM AUTHOR]

During the energy-based seismic design procedure for structures, structural members need to be designed based on hysteretic energy demand, and understanding the effects of the loading history and reinforcement conditions on energy dissipation capacity of structural members is the basis for this step. In this paper, deterioration characteristics of energy dissipation capacity for 22 reinforced concrete beam specimens with different stirrup ratios and reinforcement ratios under various displacement reversals were investigated. The results show that, under the constant amplitude displacement cycles, increasing stirrup ratio of beams can delay the energy dissipation capacity deterioration, and the delay rate is decreased with cyclic amplitude. The effect of reinforcement ratio on deterioration characteristics of energy dissipation capacity lacks regularity. Relative to the stirrup ratio and reinforcement ratio, cyclic amplitude effect is more obvious and more regular. The smaller cyclic amplitude would lead to the faster decay process of deterioration and the greater residual energy dissipation capacity. Under the variable-amplitude displacement cycles, the remaining energy dissipation capacity in a forthcoming displacement cycle is dependent on both the relative relationship between the maximal displacement cycle and the energy dissipated along the completed displacement path. Plastic energy dissipation capacity of reinforced concrete beams are both displacement path dependent and cumulative hysteretic energy dependent. Based on this double-dependency rule, a method was developed in order to predict the energy dissipation capacity of reinforced concrete beams subjected to random variable amplitude displacement cycles simulating severe seismic excitations. [ABSTRACT FROM AUTHOR]

Flexible ultraviolet (UV) light detection technology has important applications in wearable devices, smart sensors, and other fields and attracts much attention in recent years. However, for most semiconductor‐based UV detectors, the elastic modulus between rigid semiconductors and flexible substrates is mismatched, which makes it difficult to fabricate UV detectors that meet the needs of wearable devices. Herein, a fully flexible, large‐scale, skin‐friendly UV photodetector component centered on photo‐responsive worm‐like polymer nanoparticles (NPs) is developed, and the resulting device can quantitatively detect UV illumination. Skin‐friendly poly(vinyl alcohol) (PVA), amphiphilic azobenzene‐containing polymer NPs (AzNPs), and water‐soluble ionic liquids (IL) are formed into (AzNPs‐IL)/PVA fabrics by electrospinning. There are interactions such as hydrogen bonding among PVA, AzNPs, and IL, which make the material system stable. The UV detector made of the fabric realizes UV sensing through the illuminance–mechanical stress–electrical signal conversion mechanism. It is capable of achieving a response time of 9 s, a detection range of 10–150 mW cm−2, and stability for 1000 cycle tests upon 365 nm UV irradiation. Moreover, it has good skin affinity, and the water contact angle of the fabric is only 23.57°, which holds great promise for wearable smart devices. [ABSTRACT FROM AUTHOR]

Background: The migration of lymphocytes shares many similarities in mode and mechanism with the metastasis of lung cancer tumor cells. But changes in the expression of lymphocyte migration regulation related proteins in urine exosomes remain unclear. This study is to investigate the expression changes of lymphocyte migration regulation related proteins in urine exosomes of lung cancer patients, and further verify their correlation with the development and progression of lung cancer. Methods: Urine exosomes were collected from lung cancer patients and healthy people aged 15–79 years. Mass spectrometry was used to screen and explore the expression changes of lymphocyte migration regulation related proteins in healthy people of different ages. Enzyme-linked immunosorbent assay and western blotting were used to detect the expression changes of lymphocyte migration regulation related proteins in lung cancer patients. Results: Analyzing the data of urine exosome proteomics, a total of 12 lymphocyte related proteins were identified, 5 of which were lymphocyte migration regulation related proteins. Among these proteins, WASL and STK10 proteins showed a gradual decrease in expression with age, and WNK1 protein showed a gradual increase. Lung cancer patients had reduced expression of WASL and increased expression of STK10 and WNK1 proteins in urine exosomes compared to normal people. Urine exosome WASL, STK10, and WNK1 were diagnosed with lung cancer, with a combined AUC of 0.760. Conclusions: Lymphocyte migration regulation related proteins were differentially expressed in the urine exosome of lung cancer patients, and WASL, STK10 and WNK1 may serve as potential biomarkers for lung cancer diagnosis. [ABSTRACT FROM AUTHOR]

Responsive photonic crystals (RPCs) assembled by monodisperse colloidal particles have attracted enormous interest recently due to their tremendous applications in smart devices. Their structural colors can be determined by particle sizes. However, the lack of a reliable way to tune the sizes in situ limits their development. Herein, we present an efficient route to solve this problem through the fabrication of spherical polymeric particles with light‐triggered reversible swelling behavior via surfactant‐free reversible addition‐fragmentation chain transfer (RAFT) emulsion polymerization‐induced self‐assembly (PISA). Amphiphilic macro‐RAFT agents containing azobenzene groups were synthesized and subsequently employed to mediate the polymerization of methyl methacrylate. Uniform submicron spheres were obtained by modulating solid contents and other parameters. Benefiting from the photoisomerization of azobenzene moieties, the particle sizes expanded and contracted upon alternative ultraviolet/visible‐light irradiation accordingly. This strategy will be a supplement to the emulsion PISA and especially give aid to the progress of the RPC materials. [ABSTRACT FROM AUTHOR]

• ICI-associated myocarditis starts early in the course of drug administration and progresses rapidly. • Approximately 1/3 patients with ICI-associated myocarditis develop MACE, which is associated with a higher mortality rate. • Troponin has good specificity and sensitivity for diagnosing the occurrence of MACE. • This study provides a safe signal to re-challenge immunotherapy in patients with advanced malignancies. Myocarditis related to immune checkpoint inhibitors (ICIs) treatment is a rare but potentially life-threatening adverse event. To gain insight into this condition, we analyzed the clinical characteristics and prognosis of patients with ICI-related myocarditis. Data on the clinical characteristics, management, and outcomes of patients diagnosed with ICI-related myocarditis between August 2018 and August 2023 in our institution were gathered retrospectively from medical records. Outcomes included the occurrence of major adverse cardiac events (MACE). Among 8875 patients who received ICI therapy, 31 patients experienced ICI-related myocarditis. These 31 patients had a mean age of 62 ± 12 years and included 24 (77.4 %) males and 19 patients (61.3 %) with at least one risk factor for cardiovascular disease. The median duration from ICI initiation to the onset of myocarditis symptoms was 6.3 weeks (interquartile range, 4.3–8.1 weeks). Twenty-one patients (67.7 %) developed grade 3–4 myocarditis. Thirteen patients (42 %) experienced MACE after myocarditis onset, and 15 patients (48.4 %) showed a troponin rise > 4 times the maximum limit of the standard range. On receiver operating characteristic curve analysis, troponin level could predict MACE in patients with ICI-related myocarditis with an area under the curve of 0.82 (95 % confidence interval [CI]: 0.66–0.98, p = 0.003). From Kaplan–Meier analysis, the occurrence of MACE (p = 0.002) was an independent influencing factor on patients' overall survival. ICI-related myocarditis frequently leads to MACE, which is associated with poor prognosis. Elevated troponin levels and electrocardiogram abnormalities in these patients may help predict the occurrence of MACE. [ABSTRACT FROM AUTHOR]

Background: Rationale exists for combining immune checkpoint inhibitors and PARP inhibitors (PARPi), and results of clinical trials in ovarian cancer are promising, but data in other cancers are limited. Method: Efficacy and safety of PARPi/anti-PD-1 in advanced solid tumors were retrospectively analyzed. The efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: This retrospective study included data from 40 patients. The ORR was 27.5% (95% CI, 13.0–42.0%), with a DCR of 85.0% (95% CI, 73.4–96.6%). Except four patients in first-line treatment (three with PR and one with SD), the ORR of ≥second-line treatment, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was 22.2%, 23.1% and 28.6%, and the DCR was 83.3%, 84.6% and 71.4%, separately. The median PFS of all patients, ≥second-line treatment, NSCLC and SCLC was 4.6 m, 4.2 m, 4.5 m and 3.7 m. The median OS was 9.4 m, 11.4 m, 12.7 m and 5.4 m, respectively. Multivariable analysis revealed that BRCA1/2 mutation was positively correlated with ORR (P = 0.008), and LDH≥250U/L was negatively correlated with lowered DCR (P = 0.018), while lymphocyte number, ECOG and LDH significantly influenced both PFS and OS. We found that the possible resistant mechanisms were sarcomatous degeneration and secondary mutation, including BRCA2 truncation mutation, A2M, JAK1,T790M, KEAP1 and mTOR mutation. 37.5% patients had ≥grade 3 adverse events. Conclusion: PARPi/anti-PD-1 is an effective and tolerable method for patients with advanced solid tumors, and BRCA1/2 is a potential biomarker. [ABSTRACT FROM AUTHOR]

Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated great promise for treating cancers with homologous recombination (HR) defects, such as germline BRCA1/2 mutation. Further studies suggest that PARP inhibitors (PARPi) can also exhibit efficacy in HR-competent cancers, by amplifying the DNA damage and inducing immunogenic cell death, and PARPi lead to increasing tumor neoantigen, upregulation of interferons and PD-L1, and modulation of the tumor microenvironment, which may facilitate a more profound antitumor immune response. Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 or CTLA-4 have achieved impressive success in the treatment of different malignancies. However, only a subset of populations derive clinical benefit, and the biomarkers and resistance mechanisms are not fully understood. Therefore, given that PARPi could potentiate the therapeutic effect of ICIs, PARPi combined with ICIs are becoming an alternative for patients who cannot benefit from ICI monotherapy. In this review, we focus on the mechanisms and immune role of PARPi and discuss the rationale and clinical studies of this combined regimen. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the clinical characteristics and outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with osimertinib, and focused on the resistance mechanism to osimertinib in a real-world setting. Data from 128 patients with advanced NSCLC who were treated with osimertinib between March 2015 and November 2018 at the Chinese People's Liberation Army General Hospital (Beijing, China) were retrospectively collected, and the associations between mutation types and survival were analysed. In patients treated with osimertinib, the objective response rate reached 60.9% (78/128) and the disease control rate reached 81.3% (104/128), with a median progression-free survival (PFS) time of 12.2 months. A number of complex mutations were identified in the re-analysis after the development of osimertinib resistance, including TP53, KRAS and PIK3CA mutations, epidermal growth factor receptor (EGFR) and MYC amplifications, and mutations associated with SCLC transformation, demonstrating that these mutations may account for osimertinib resistance. The median PFS time for patients with the EGFR T790M mutation (n=41) was significantly longer than that for patients with the T790M mutation and the aforementioned complex mutations (n=13) (16.7 vs. 10.8 months; P=0.001). Patients with a single EGFR mutation (n=87) had a longer median PFS time than those with an EGFR mutation and complex mutations (n=24) (14.63 vs. 6.63 months; P<0.0001). In conclusion, the present study analysed the effects of osimertinib in patients with advanced NSCLC with EGFR mutations, particularly T790M mutations. The results indicated that the efficacy of osimertinib was weakened when patients had complex mutations, suggesting that complex mutations may be responsible for resistance to osimertinib. [ABSTRACT FROM AUTHOR]

Background: ROS1 gene fusion represents a specific subtype of non‐small cell lung cancer (NSCLC). Crizotinib is recommended for ROS1‐positive NSCLC due to its favorable outcome in published clinical trials. However, due to the low incidence of ROS1‐positive NSCLC, there is limited information on real‐world clinical outcomes in patients treated with either crizotinib or platinum‐based doublet chemotherapy. Methods: Outcomes were recorded in 102 patients with stage Ⅲb or Ⅳ NSCLC who were treated at four Chinese hospitals between April, 2010 and June, 2019. Results: Of the 102 patients followed, 71.6% were females, 81.4% were non‐smokers, and 98.0% had adenocarcinoma. First‐line treatment with crizotinib achieved a significantly longer median progression‐free survival (PFS) compared with platinum‐based chemotherapy (14.9 months vs 8.5 months, respectively; P <.001). Next‐generation sequencing (NGS) identified 61 patients who had ROS1 fusion variants, including CD74 (n = 33) and non‐CD74 (n = 28) variants. In patients harboring CD74 fusion variants, the median PFS with first‐line crizotinib treatment was significantly longer than in those harboring non‐CD74 fusion variants (20.1 months vs 12.0 months, respectively; P =.046). However, in patients treated with platinum‐based chemotherapy, there was no significant difference in PFS between the CD74 and non‐CD74 variant groups (8.6 months vs 4.3 months, respectively; P =.115). Overall survival (OS) was not reached. Conclusions: First‐line therapy with crizotinib is more beneficial than platinum‐based chemotherapy in patients with advanced NSCLC with different ROS1 fusion variants. Patients harboring CD74 fusion variants appear to respond better to crizotinib. [ABSTRACT FROM AUTHOR]