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Hybrid spin-mechanical systems offer a promising platform for advancing quantum science and technology. However, practical implementation of applications within these hybrid quantum systems demands the seamless integration of supplementary physical components. In this context, we present a proposal for a multi-mode spin-mechanical setup, featuring the utilization of three-mode coupling nanomechanical carbon nanotube (CNT) resonators. These resonators interact with each other via a phase-dependent phonon-exchange mechanism, which is coupled to the same nitrogen vacancy (NV) centers in diamond. Based on the modulation of the phonon–phonon coupling phase and leveraging the triple Fano-like resonance phenomenon, a tripling of electromagnetically induced transparency (EIT) becomes achievable within the system. This tripling is accompanied by swift dispersion, leading to a subtle advancement or delay in outcomes. The phenomenon of triple Fano-like resonance, alongside the resulting triple EIT, engenders noteworthy slow-to-fast and fast-to-slow light effects, which is theoretically demonstrated in CNT resonators, with both identical and distinct frequencies. The findings underscore that CNT resonators with varying frequencies can evoke a more pronounced transition in the slow–fast–slow and fast–slow–fast light effects. This study lays the foundation for the application of phonon-mediated optical information storage and processing. [ABSTRACT FROM AUTHOR]

We theoretically propose a loop-coupled multimode optomechanical system (OMS) with a single-mode cavity, a two-level system (TLS), and a mechanical resonator, which are coupled to each other. With controlled coupling parameters, the loop-coupled multimode OMS can flexibly transform into different OMSs (e.g. cavity OMSs, cavity quantum electrodynamic systems). By simultaneously driving the single-mode cavity using pump and probe fields, we investigate the coherent optical response and transmission spectra for the transparent window and absorption dips. Additionally, the transparent window and absorption dips that induce coherent light propagation were demonstrated. Our findings demonstrate that the transparent window and absorption dips can generate slow (fast) light, and that the control of coupling parameters can modulate optical fields in different OMSs. With further weaving of these coupling parameters, the loop-coupled multimode OMS can be a quantum information processing platform for chip-scale applications. [ABSTRACT FROM AUTHOR]

Key Clinical Message: One Kirsten Ras (KRAS) G12C mutated non‐small cell lung cancer (NSCLC) patient had improved poor performance status and obtained mixed response with the first‐line KRAS‐targeted treatment of sotorasib. After disease progression, partial response was achieved with chemotherapy plus immunotherapy. KRAS G12C mutated immunoenvironment in NSCLC may favor the immunotherapy. KRAS is one of the most commonly mutated genes, which used to be untargetable. The phase II CodeBreak 100 trial revealed 6.8‐month median progress‐free survival (PFS) and 12.5‐month overall survival (OS) in previously treated KRAS G12C‐mutant NSCLC patients treated with KRAS inhibitor, sotorasib. The specimens of the brain, lymph node (LN), and blood from the patient were analyzed by next‐generation sequencing. Hematoxylin and eosin staining and immunohistochemistry were performed for pathological characterization. Computed tomography (CT) and magnetic resonance imaging (MRI) scan were used for treatment response evaluation. The patient was diagnosed in a bad Eastern Cooperative Oncology Group performance status (ECOG‐PS) with metastatic KRAS G12C‐mutated lung adenocarcinoma who had achieved mixed response to sotorasib as the first‐line treatment. Although 5‐month PFS of the treatment with sotorasib was not surprising, the patient achieved significantly improved ECOG‐PS score from 4 to 1. Subsequently, partial response (PR) was achieved with the treatment of pemetrexed plus pembrolizumab. This case highlights superior efficacy of first‐line treatment with sotorasib for the advance untreated KRAS G12C‐mutant patients. The high efficacy of the treatment with chemotherapy plus immunotherapy revealed that immunoenvironment of KRAS G12C‐mutated patient may favor the immunotherapy. [ABSTRACT FROM AUTHOR]

This article discusses a study that examines the genetic and molecular characteristics of lung cancer patients who have transformed from one type of lung cancer to another. The study identifies two distinct subtypes based on the RB1 gene status of the patients. The findings suggest that RB1 and SMAD4 alterations are important factors in this transformation, and patients with RB1 mutations tend to have a longer time before the transformation occurs. The article highlights the importance of understanding the heterogeneity within this patient population in order to develop new treatments and improve outcomes. Additionally, the study develops a predictive model to assess the risk of transformation in patients with specific gene mutations. Overall, this research provides valuable insights into the biology of transformed lung cancer and potential targets for therapy. [Extracted from the article]

Background: Some studies of dual-targeted therapy (DTT) targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Consequently, patient management following DTT resistance has gained significance. However, the underlying resistance mechanisms and clinical outcomes in these patients remain unclear. Objectives: This study aimed to delineate the molecular characteristics and survival outcomes of patients with NSCLC harboring EGFR mutations and acquired MET amplification after developing resistance to DTT. Design: We conducted a retrospective analysis of patients with NSCLC with EGFR mutations and acquired MET amplification who exhibited resistance to EGFR/MET DTT. Methods: Next-generation sequencing (NGS) was performed on patients with available tissue samples before and/or after the development of resistance to DTT. Stratified analyses were carried out based on data sources and subsequent salvage treatments. Univariate/multivariate Cox regression models and survival analyses were employed to explore potential independent prognostic factors. Results: The study included 77 NSCLC patients, with NGS conducted on 19 patients. We observed many resistance mechanisms, including EGFR-dependent pathways (4/19, 21.1%), MET-dependent pathways (2/19, 10.5%), EGFR/MET co-dependent pathways (2/19, 10.5%), and EGFR/MET-independent resistance mechanisms (11/19, 57.9%). Post-progression progression-free survival (pPFS) and post-progression overall survival (pOS) significantly varied among patients who received the best supportive care (BSC), targeted therapy, or chemotherapy (CT), with median pPFS of 1.5, 3.9, and 4.9 months, respectively (p = 0.003). Median pOS were 2.3, 7.7, and 9.2 months, respectively (p < 0.001). The number of treatment lines following DTT resistance and the Eastern Cooperative Oncology Group performance status emerged as the independent prognostic factors. Conclusion: This study revealed a heterogeneous landscape of resistance mechanisms to EGFR/MET DTT, with a similar prevalence of on- and off-target mechanisms. Targeted therapy or CT, as compared to BSC, exhibited the potential to improve survival outcomes for patients with advanced NSCLC following resistance to DTT. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal–epithelial transition (MET) amplification is a crucial oncogenic driver and a resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) of non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection. However, it is inapplicable when tissue samples are unavailable. Objective: This study assessed the performance of plasma droplet digital polymerase chain reaction (ddPCR) in MET amplification detection in NSCLC patients. Design and methods: A total of 87 NSCLC patients were enrolled, and 94 paired tissue and plasma samples were analyzed for the concordance between FISH and plasma ddPCR/tissue next-generation sequencing (NGS) in detecting MET amplification. In addition, the efficacy of patients with MET amplification using different detection methods who were treated with MET-TKIs was evaluated. Results: Plasma ddPCR showed substantial concordance with FISH (74.1% sensitivity, 92.5% specificity, and 87.2% accuracy with a kappa value of 0.68) and outperformed tissue NGS (kappa value of 0.64) in MET amplification detection. Combined plasma ddPCR and tissue NGS showed substantial concordance with FISH (92.3% sensitivity, 89.2% specificity, and an accuracy of 90.1% with a kappa value of 0.77). The efficacy is comparable in these NSCLC patients with MET amplification detected by FISH and plasma ddPCR who were treated with MET-TKIs. Conclusion: Plasma ddPCR is a potentially reliable method for detecting MET amplification in advanced NSCLC patients. Combined plasma ddPCR and tissue NGS might be an alternative or complementary method to MET amplification detection. [ABSTRACT FROM AUTHOR]

Aims: To evaluate microstructural impairment in the thalamus and thalamocortical connectivity using neurite orientation dispersion and density imaging (NODDI) in amyotrophic lateral sclerosis (ALS). Methods: This study included 47 healthy controls and 43 ALS patients, whose structural and diffusion‐weighted data were collected. We used state‐of‐the‐art parallel transport tractography to identify thalamocortical pathways in individual spaces. Thalamus was then parcellated into six subregions based on its connectivity pattern with the priori defined cortical (i.e., prefrontal/motor/somatosensory/temporal/posterior‐parietal/occipital) regions. For each of the thalamic and cortical subregions and thalamo‐cortical tracts, we compared the following NODDI metrics between groups: orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (ISO). We also used these metrics to conduct receiver operating characteristic curve (ROC) analyses and Spearman correlation. Results: In ALS patients, we found decreased ODI and increased ISO in the thalamic subregion connecting the left motor cortex and other extramotor (e.g., somatosensory and occipital) cortex (Bonferroni‐corrected p < 0.05). NDI decreased in the bilateral thalamo‐motor and thalamo‐somatosensory tracts and in the right thalamo‐posterior‐parietal and thalamo‐occipital tracts (Bonferroni‐corrected p < 0.05). NDI reduction in the bilateral thalamo‐motor tract (p = 0.017 and 0.009) and left thalamo‐somatosensory tract (p = 0.029) was correlated with disease severity. In thalamo‐cortical tracts, NDI yielded a higher effect size during between‐group comparisons and a greater area under ROC (p < 0.05) compared with conventional diffusion tensor imaging metrics. Conclusions: Microstructural impairment in the thalamus and thalamocortical connectivity is the hallmark of ALS. NODDI improved the detection of disrupted thalamo‐cortical connectivity in ALS. [ABSTRACT FROM AUTHOR]