Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. PATIENTS AND METHODS: Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy's effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. RESULTS: A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295-4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV-H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). CONCLUSIONS: The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. TRIAL REGISTRATION: Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228).

Predicting lung cancer survival prognosis based on the conditional survival bayesian network.

Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.

Effect of NLRP3 Inflammasome on Lung Cancer Immune Microenvironment Activation and Its Mechanism.

Objective: The NLRP3 inflammasome plays a dual role in the occurrence and development of tumors, and its role in lung cancer remains unclear. This study aims to investigate the impact of NLRP3 inflammasome activation on the proliferation and migration of lung cancer cells. Methods: Data from the GEPIA, TCGA, and HPA databases were utilized to analyze the expression of NLRP3 in lung adenocarcinoma and its microenvironment. GO/KEGG enrichment analysis and GSEA analysis were employed to annotate the functions of differentially expressed genes related to NLRP3. The impact of NLRP3 inflammasome activation on the proliferation and migration of lung cancer cells was further investigated by CCK-8 assay and scratch assay. The effects of blocking NLRP3 inflammasome activation with IL-1RA and IL-18BP on the proliferation and migration of lung cancer cells were further assessed. Survival analysis was conducted to analyze the impact of NLRP3 expression on the prognosis of patients with lung adenocarcinoma. Results: The expression of NLRP3 in lung cancer was lower than in normal tissues, with notably higher expression observed in macrophages compared to other cells. Patients with higher NLRP3 expression exhibit increased infiltration of M2 macrophages. Activation of the NLRP3 inflammasome using LPS+ATP promotes the proliferation and migration of A549 cells. Simultaneous use of IL-1RA and IL-18BP reverses the promoting effect of NLRP3 inflammasome activation on cell proliferation and migration. Survival analysis results indicate that patients with high NLRP3 expression have a poorer prognosis compared to those with low NLRP3 expression (Hazzard Ratio =1.44; 95% Confidence Interval: 1.21-1.71). Conclusions: The activation of the NLRP3 inflammasome promotes the proliferation and migration of A549 cells through secretion of IL-1ß and IL-18, potentially influencing patient prognosis. Simultaneously blocking IL-1ß and IL-18 can reverse the pro-proliferative and migration-promoting effects.

Simultaneous three-dimensional deformation measurement using tri-wavelength and monochrome camera imaging with a pyramid prism.

What we believe to be a new electronic speckle pattern interferometry (ESPI) configuration is being developed for simultaneous three-dimensional deformation measurements. In this ESPI system, two pairs of symmetrical illuminating arrangement with dual-wavelength lights were used to independently sense two in-plane deformation components, one Michelson interferometer-based set illuminating with the other wavelength light was utilized to measure out-of-plane deformation. The color speckle interferogram was split into four sub-patterns by a prism, three of them were filtered by three different bandpass dichroic filters and recorded by one monochrome camera. Micro-rotation testing work firstly verifies the validation of the proposed phase-shifting device. Three-dimensional deformation information was simultaneous obtained by using temporal phase-shift method. All strain components related to the specimen surface deformation were further determined by numerical differential. The experimental results of a tested specimen were excellently consistent with those of FEM simulation, which verified the validation and feasibility of the proposed ESPI system for measuring 3D deformation.

In-plane ESPI with unlimited angle of view for multi-object rotation angle determination.

The in-plane electronic speckle pattern interferometry (ESPI), implemented in a Michelson stellar interferometer-like configuration, offers high sensitivity and dynamic measurement. However, its limited angle of view (AOV) remains a major challenge for the rotation angle determination of multiple objects. In this Letter, we analyze the main factors that influence the AOV of the in-plane ESPI and propose an "image transmitting" approach to enlarge the AOV. With the aid of a folded dual-telescope imaging system, we develop an AOV-unlimited interferometer that can determine multi-object rotation angles in real time. The practicability of the interferometer is demonstrated by the application in real-time measuring of the rotation angles of the disks within a 2D granular system.

HGT: A Hierarchical GCN-Based Transformer for Multimodal Periprosthetic Joint Infection Diagnosis Using Computed Tomography Images and Text.

Prosthetic joint infection (PJI) is a prevalent and severe complication characterized by high diagnostic challenges. Currently, a unified diagnostic standard incorporating both computed tomography (CT) images and numerical text data for PJI remains unestablished, owing to the substantial noise in CT images and the disparity in data volume between CT images and text data. This study introduces a diagnostic method, HGT, based on deep learning and multimodal techniques. It effectively merges features from CT scan images and patients' numerical text data via a Unidirectional Selective Attention (USA) mechanism and a graph convolutional network (GCN)-based Feature Fusion network. We evaluated the proposed method on a custom-built multimodal PJI dataset, assessing its performance through ablation experiments and interpretability evaluations. Our method achieved an accuracy (ACC) of 91.4% and an area under the curve (AUC) of 95.9%, outperforming recent multimodal approaches by 2.9% in ACC and 2.2% in AUC, with a parameter count of only 68 M. Notably, the interpretability results highlighted our model's strong focus and localization capabilities at lesion sites. This proposed method could provide clinicians with additional diagnostic tools to enhance accuracy and efficiency in clinical practice.

MST1/2 inhibitor XMU-MP-1 alleviates the injury induced by ionizing radiation in haematopoietic and intestinal system.

The Hippo signalling pathway has been considered as potential therapeutic target in self-renewal and differentiation of stem and progenitor cells. Thus, mammalian Ste20-like kinase 1/2 (MST1/2) as the core serine-threonine kinases in the Hippo signalling pathway has been investigated for its role in immunological disease. However, little information of MST1/2 function in bone marrow suppression induced by ionizing radiation was fully investigated. Here, we reported that MST1/2 inhibitor XMU-MP-1 could rescue the impaired haematopoietic stem cells (HSCs) and progenitor cells (HPCs) function under oxidative stress condition. Also, XMU-MP-1 pretreatment markedly alleviated the small intestinal system injury caused by the total body irradiation 9 Gy and extended the average survival days of the mice exposed to the lethal dose radiation. Therefore, irradiation exposure causes the serious pathological changes of haematopoietic and intestinal system, and XMU-MP-1 could prevent the ROS production, the haematopoietic cells impairment and the intestinal injury. These detrimental effects may be associated with regulating NOX/ROS/P38MARK pathway by MST1/2.

Measurement of natural frequencies and mode shapes of transparent insect wings using common-path ESPI.

In this study, a common-path electronic speckle pattern interferometry system which upholds the natural property of transparency of insect's wings has been developed to measure the wings' natural frequencies and mode shapes for the first time. A novel base-exciting method was designed to enable the simultaneous application of sinusoidal and static forces to excite wings and introduce an additional phase. The moiré effect induced by the amplitude modulation was employed to accurately recognize the resonance state. Subsequently, the mode shapes were visualized by phase-shifting and real-time frame subtraction. Eight pairs of forewings from cicadas were investigated. The first three order natural frequencies of the wings are approximately 145 Hz, 272 Hz and 394 Hz, respectively, which are dispersed to prevent modal coupling. The cambered mode shapes exhibit a strongly spanwise-chordwise anisotropy flexural stiffness distribution, generally dominated by bending and twisting deformation. The details of the high-order mode shapes show that the tip exhibits distinct deformation, indicating more flexibility to cope with external impact load, and the nodal lines usually comply with the direction of the wing veins in higher modes, substantiating the fact that the veins play an important role as stiffeners of the membrane. The results are in excellent agreement with the dynamic performance of previous studies, which will potentially affect a broader community of optical measurement specialists and entomologists to enhance our understanding of time-averaged interferograms and insect flights.

Pyrotinib for HER2-amplified non-small cell lung cancer patient after progression to Afatinib: a case report.

Contrary to the success of antihuman epidermal growth factor receptor 2 (HER2) therapy in HER2-amplified breast cancer, the optimal targeted drug therapy for HER2-amplified lung cancer remains to be determined clinically. In this report, a nonsmoker, Chinese, old, male patient was diagnosed with cT2bN3M0 nonsmall cell lung cancer with genetic testing revealing HER2 amplification. Though the patient received successful microwave ablation, the results of reexamination after two cycles of afatinib monotherapy showed disease progression. Then the treatment regimen was switched to pan-HER inhibitor pyrotinib 400 mg daily, with which the patient remained with stable disease for 9 months. After computed tomography showed tumor enlargement in October 2021, anlotinib was added to the present treatment. This case suggests that pyrotinib may provide a novel effective treatment option for HER2-amplified lung cancer.

Tri-wavelength simultaneous ESPI for 3D micro-deformation field measurement.

Electronic speckle pattern interferometry (ESPI), a well-established technique for micro-deformation measurement, can be used to determine both in-plane and out-of-plane displacement components. Although many works in ESPI have been reported for three-dimensional (3D) displacement measurement, few works have focused on the simultaneous measurement of 3D deformation fields. Here we present an ESPI system that consists of three sub-interferometers for simultaneous measurement of all three displacement components and in-plane strain fields. A 3CCD color camera, a specially designed shifting stage, and three lasers with optimal wavelengths are used in this system. The lasers and 3CCD camera provide independent interferograms with different color signals, while the shifting stage allows the sub-interferometers to achieve simultaneous phase shifting. The results of color separation and experimental measurement demonstrate the utility of the system.

Binocular camera calibration based on timing correction.

Camera calibration is crucial to the application of binocular measurement. However, many of the calibrations are carried out manually, so shaking of the calibration plate cannot be avoided. When the cameras are not synchronized or the exposure time is inconsistent, the image acquisition time of different cameras does not correspond strictly, which will introduce inevitable calibration errors. In this paper, two consecutive frames are collected instead of one frame, and the calibration data are corrected by the image acquisition time value returned by the camera. Experiments show that the proposed method can greatly reduce the re-projection error of calibration, and achieve higher calibration accuracy and less image quantity dependence.

WITHDRAWN: A deep learning framework for diagnosing periprosthetic joint infections using X-ray images: a discovery and validation study.

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Point-Wise Phase Estimation Method in Fringe Projection Profilometry under Non-Sinusoidal Distortion.

In fringe projection profilometry, high-order harmonics information of distorted fringe will lead to errors in the phase estimation. In order to solve this problem, a point-wise phase estimation method based on a neural network (PWPE-NN) is proposed in this paper. The complex nonlinear mapping relationship between the gray values and the phase under non-sinusoidal distortion is constructed by using the simple neural network model. It establishes a novel implicit expression for phase solution without complicated measurement operations. Compared with the previous method of combining local image information, it can accurately calculate each phase value by point. The comparison results show that the traditional method is with periodic phase errors, while the proposed method can effectively eliminate phase errors caused by non-sinusoidal phase shifting.

Heterologous-coating antigen enhancing the sensitivity of enzyme-linked immunosorbent assay for detection of mebendazole residues.

The heterologous strategy could improve the sensitivity of competitive enzyme-linked immunosorbent assay (ELISA) for detection of chemical contaminants in food samples. In this study, the heterologous coating antigen ELISA was developed to evaluate its sensitivity for mebendazole (MBZ). Results showed that the heterologous ELISA had a linear range of (IC20-IC80) 0.34-10.54 ng/mL, an IC50 value of 1.83 ng/mL, and a limit of detection (LOD) of 0.13 ng/mL, in which the sensitivity of ELISA improved 1.7- and 2-fold (IC50 value dropping from 7.41 and 3.65 ng/mL to 4.27 and 1.83 ng/mL) than that of rabbit IgG- and chicken IgY-based homologous ELISA for MBZ, respectively. The heterologous coating antigen ELISA showed negligible cross reactivity (<0.2%) with its structural analogues, including hydroxy-MBZ, albendazole, oxfendazole, fenbendazole, and flubendazole, except the value of 72.6% for amino-MBZ. The average recoveries of MBZ spiked in pork and chicken muscle samples by the assay ranged from 83.7% to 109.8% and agreed well with those of high-performance liquid chromatography. The results suggested that using heterologous coating antigen could distinctly improve the sensitivity of ELISA for routine screening of MBZ residues in food samples.

SMARCA2 deficiency in NSCLC: a clinicopathologic and immunohistochemical analysis of a large series from a single institution.

BACKGROUND: SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 2) is an important ATPase catalytic subunit in the switch-sucrose nonfermenting (SWI/SNF) complex. However, its relationship with the pathological features of NSCLC and its prognosis remain unclear. METHODS: We retrospectively reviewed 2390 patients with surgically resected NSCLC, constructed tissue microarrays (TMAs) and performed immunohistochemical assays. We analyzed the correlation of SAMRCA2 with clinicopathological features and evaluated its prognostic value. RESULTS: Among 2390 NSCLC cases, the negative expression ratios of SAMRCA2, SMARCA4, ARID1A, ARID1B and INI1 were 9.3%, 1.8%, 1.2%, 0.4% and 0%, respectively. In NSCLC, male sex, T3 and T4 stage, moderate and poor differentiation, tumor ≥ 2 cm, Ki67 ≥ 15%, SOX-2 negative expression, middle lobe lesion and adenocarcinoma were relative risk factors affecting SMARCA2-negative expression. In lung adenocarcinomas, high-grade nuclei, histological morphology of acinar and papillary, solid and micropapillary and TTF-1-negative expression were relative risk factors affecting SMARCA2-negative expression. Kaplan-Meier survival analysis showed that the OS was shorter in the SMARCA2-negative group. Multivariate survival analysis revealed that SMARCA2-negative expression was an independent factor correlated with a poor prognosis in NSCLC. CONCLUSION: In conclusion, SMARCA2-negative expression is an independent predictor of a poor outcome of NSCLC and is a potential target for NSCLC treatment.

Generalized 2-step phase-shifting algorithm for fringe projection.

Fringe projection profilometry using the phase-shifting technique enables high-precision, high-speed and flexible measurements. Among them, the two-step phase-shifting method has become an important approach to coordinate the accuracy and measurement speed; methods especially based on the amount of phase-shift of π/2, π or 3π/2 can improve time efficiency by reducing steps in unique way. In this paper, a phase iterative technique is proposed and established for two-step phase-shifting with arbitrary phase shift. The general mathematical scheme and parameters linear and nonlinear optimization of the proposed method are described in detail. The simulational and experimental results show that the proposed technique is an effective and precise phase detection method for two-step phase-shifting profilometry.

Efficient ESPI method to identify vibration characteristics of transparent films.

Electronic speckle pattern interferometry (ESPI) has been frequently used to study vibration characteristics of engineering structures. However, efficient ESPI methods for identifying the vibration characteristics of transparent membranes are rarely reported. A convenient approach to determine the resonant frequencies and the vibration modes of transparent films is proposed. A quasi-common-path ESPI (QCP-ESPI) is developed to detect out-of-plane deformation and visualize vibrational modes of a vibrating transparent diaphragm. An amplitude-modulation-based method is proposed for quick and accurate determining resonance of oscillating objects during frequency scanning. Experimental performances demonstrate the feasibility and efficiency of the QCP-ESPI and amplitude-modulation-based methods for determining the resonant frequency and vibration modes of transparent objects.

Geometry constrained correlation adjustment for stereo reconstruction in 3D optical deformation measurements.

Recovering the geometric shape of deformable objects from images is essential to optical three-dimensional (3D) deformation measurements and is also actively pursued by researchers. Most of the existing techniques retrieve the shape data with triangulation based on pre-estimated stereo correspondences. In this paper, we instead propose to recover depth information directly from images of a binocular vision system for 3D deformation estimation. Given a calibrated geometry of the system, the reprojection error is parameterized by the depth and then described with local intensity dissimilarity between a stereo pair in considering spatial deformation. Afterward, a correlation adjustment model is formulated to estimate the depth parameter by minimizing the error. As a solving strategy, we show the Gauss-Newton linearization of the proposed model and its initialization. 3D displacement estimation based on depth information is also presented. Experiments, including rigid translation and bending deformation measurements, are conducted to verify the performance of the proposed method. Results show that the proposed method is accurate yet precise in 3D deformation estimations. Other underlying developments are underway.

Panoramic dual-directional shearography assisted by a bi-mirror.

A panoramic dual-directional shearography system is proposed to simultaneously determine out-of-plane deformation derivatives in two directions and globally inspect the object to be tested. A dichroic filter (DF), a 3CCD camera, and dual-wavelength light are used in the proposed shearography configuration. The dual-wavelength light coupled with the corresponding imaging sensors of the 3CCD camera provides independent color signals and shearograms. Through adjustment of the tilted stereo-angle of the DF, which offers a second wavelength-dependent measurement, an additional independent image-shearing can be introduced into the setup. The auxiliary bi-mirror surrounding the object helps to fully illuminate the object surface and capture it in a single shot. Theoretical analysis and experimental results demonstrated the utility of the system.

Design, synthesis, and biological evaluation of novel substituted thiourea derivatives as potential anticancer agents for NSCLC by blocking K-Ras protein-effectors interactions.

Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01-TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 µM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.