Postoperative ctDNA in indicating the recurrence risk and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer (NSCLC). METHODS: We enrolled 58 NSCLC patients in a real-world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related and ultra-deep targeted NGS covering 338 genes, respectively. RESULTS: ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease-free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy. CONCLUSION: Postoperative ctDNA is a prognostic marker, and ctDNA-detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.

Scale-adaptive three-dimensional imaging using Risley-prism-based coherent lidar.

We present a scale-adaptive three-dimensional (3D) imaging architecture for coherent light detection and ranging (lidar) that incorporates Risley-prism-based beam scanning. An inverse design paradigm from beam steering to prism rotation is developed for demand-oriented beam scan pattern generation and prism motion law formulation, which allows the lidar to perform 3D imaging with adaptive scale and configurable resolution. By combining flexible beam manipulation with simultaneous distance and velocity measurement, the proposed architecture can achieve both large-scale scene reconstruction for situational awareness and small-scale object identification against long range. The experiment results demonstrate that our architecture enables the lidar to recover a 3D scene in a ±30° field of view and also focus on distant objects at over 500 m with spatial resolution up to 1.1 cm.

Multiview three-dimensional imaging using a Risley-prism-based spatially adaptive virtual camera field.

We present a three-dimensional (3D) imaging system that incorporates a stationary camera and Risley prisms. By planning prism rotation to generate a spatially adaptive virtual camera field, the system allows multiple virtual cameras in the field to capture any object from different perspectives for 3D reconstruction. An automatic virtual camera calibration method based on perspective projection and geometric optics is developed to enable virtual camera field construction and characterization. Moreover, a 3D computational reconstruction framework is proposed for multiview information fusion using the virtual camera field. This framework combines nonlinear distortion correction with epipolar geometry computation to efficiently perform image rectification and stereo matching, which can further facilitate 3D object reconstruction through multiview triangulation. The experiments on synthetic and real data validate the feasibility and flexibility of our 3D imaging technique.

Exosomal mir-625-3p derived from hypoxic lung cancer cells facilitates metastasis by targeting SCAI.

BACKGROUND: Tumor hypoxia is a feature of tumor micro-environment (TME), which provides a suitable environment for tumor cells migration and invasion. However, up to now, the function of exosomes derived from hypoxic tumor cells is still not fully understood. The present study is aimed to explore the underlying mechanisms of lung cancer-secreted exosomes-mediated tumor metastasis under hypoxia. METHODS & RESULTS: Exosomes were isolated from normoxic or hypoxic NCI-H446 cells. Some characteristic proteins were detected by western blots. Levels of CD63, CD 9 and CD 81 proteins were up-regulated on the membrane of exosomes secreted by hypoxic NCI-H446 cells. Basing on the results from miRNA sequencing, qRT-PCR and wound healing assay, hsa-miR-625-3p was discovered to be accumulated inside hypoxic exosomes and responsible for the metastasis of lung cancer cell. Further experiments from luciferase reporter gene assay demonstrated hsa-miR-625-3p could directly inhibit SCAI expression through binding with its 3'UTR, which suggested the mechanisms by which exosomal hsa-miR-625-3p suppressed tumor cells migration. CONCLUSIONS: Exosomal miR-625-3p derived from hypoxic small lung cancer cells accelerated tumor cells migration through inhibiting SCAI directly.

Improved LDTW Algorithm Based on the Alternating Matrix and the Evolutionary Chain Tree.

Dynamic time warping under limited warping path length (LDTW) is a state-of-the-art time series similarity evaluation method. However, it suffers from high space-time complexity, which makes some large-scale series evaluations impossible. In this paper, an alternating matrix with a concise structure is proposed to replace the complex three-dimensional matrix in LDTW and reduce the high complexity. Furthermore, an evolutionary chain tree is proposed to represent the warping paths and ensure an effective retrieval of the optimal one. Experiments using the benchmark platform offered by the University of California-Riverside show that our method uses 1.33% of the space, 82.7% of the time used by LDTW on average, which proves the efficiency of the proposed method.

Construction of a prognostic model for non-small-cell lung cancer based on ferroptosis-related genes.

We wished to construct a prognostic model based on ferroptosis-related genes and to simultaneously evaluate the performance of the prognostic model and analyze differences between high-risk and low-risk groups at all levels. The gene-expression profiles and relevant clinical data of patients with non-small-cell lung cancer (NSCLC) were downloaded from public databases. Differentially expressed genes (DEGs) were obtained by analyzing differences between cancer tissues and paracancerous tissues, and common genes between DEGs and ferroptosis-related genes were identified as candidate ferroptosis-related genes. Next, a risk-score model was constructed using univariate Cox analysis and least absolute shrinkage and selection operator (Lasso) analysis. According to the median risk score, samples were divided into high-risk and low-risk groups, and a series of bioinformatics analyses were conducted to verify the predictive ability of the model. Single-sample gene set enrichment analysis (ssGSEA) was used to investigate differences in immune status between high-risk and low-risk groups, and differences in gene mutations between the two groups were investigated. A risk-score model was constructed based on 21 ferroptosis-related genes. A Kaplan-Meier curve and receiver operating characteristic curve showed that the model had good prediction ability. Univariate and multivariate Cox analyses revealed that ferroptosis-related genes associated with the prognosis may be used as independent prognostic factors for the overall survival time of NSCLC patients. The pathways enriched with DEGs in low-risk and high-risk groups were analyzed, and the enriched pathways were correlated significantly with immunosuppressive status.

Identification of genes and pathways involved in malignant pleural mesothelioma using bioinformatics methods.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare tumor in the pleura. This study was carried out to identify key genes and pathways that may be involved in MPM. METHODS: Microarray datasets GSE51024 and GSE2549 were analyzed for differentially expressed genes (DEGs) between normal and MPM tissues. The identified DEGs were subjected to functional analyses using bioinformatics tools. RESULTS: A total of 276 DEGs were identified, consisting of 187 downregulated and 79 upregulated genes. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis indicated that the DEGs were enriched in extracellular structure organization, extracellular matrix, and ECM-receptor interaction. Due to high degree of connectivity among 24 hub genes, EZH2 and HMMR are likely to play roles in the carcinogenesis and progression of MPM. The two genes were found over-expressed in MPM tissues. Patients with elevated EZH2 and HMMR expressions had poor overall survival. CONCLUSIONS: EZH2 and HMMR are identified to be the hub genes for MPM and they may be further characterized to better understand the molecular mechanisms underlying the carcinogenesis of MPM.

Non-Small Cell Lung Cancer in Young Patients: An Analysis of Clinical, Pathologic and TNM Stage Characteristics Compared to the Elderly.

PURPOSE: To compare clinicopathologic factors including tumor-node-metastasis (TNM) stage between young and elderly patients with non-small cell lung cancer (NSCLC). METHODS: This retrospective study compared the following characteristics between 52 young patients with NSCLC (<50 years of age) and 67 elderly patients with NSCLC (>60 years): duration of symptoms before medical consultation, smoking index, family history of cancer, Ki-67 index, and pTNM stage. A binary logistic regression analysis was used to identify factors predictive of greater stage NSCLC (stage III/IV compared to stage I/II) within each age group. RESULTS: The incidence of adenocarcinoma was higher in the young than in the elderly (P=0.006). Smoking index (P=0.002) and Ki-67 index (P<0.001) were lower in the young than in the elderly. In young patients with NSCLC, delayed treatment (greater duration from symptoms to medical consultation, P=0.050) and active tumor proliferation (higher Ki-67 index, P=0.003) were predictive of more advanced cancer stage (III/IV), with only symptom duration being predictive of stage III/IV NSCLC among elderly patients. Among young patients, cough (P=0.021) and chest congestion (P=0.040) were the most significant warning symptoms of advanced-stage NSCLC. CONCLUSION: High tumor proliferation and delayed treatment are predictive of advanced NSCLC on presentation among young individuals. Early diagnosis by imaging, such as with the use of low dose computed tomography (LDCT), for young individuals with coughing and chest congestion over 1 month might be effectiveto improve prognosis and outcomes.

Compact three-dimensional computational imaging using a dynamic virtual camera.

We present a three-dimensional (3D) computational imaging architecture based on the imaging principle of a dynamic virtual camera, which enables the spatial reconstruction using a single camera and a compact wedge prism device. By rotating the prism for camera boresight adjustment, the proposed system can capture an object from different viewpoints. Each captured image appears to be recorded directly with one virtual camera moving in a certain path, facilitating the computational process for stereo matching and profile reconstruction. The experimental results have demonstrated that our architecture allows a compact and flexible system to achieve 3D imaging performance competitive to conventional stereovision.

Wavelength locking in a large-smile diode-laser array using dual-beam transformation systems.

Dual-beam transformation systems (dual BTSs) are used to obtain a wide wavelength-locking range for high-power large-smile diode-laser arrays. The collimating residual divergence angle can be reduced from 9 mrad to less than 6.5 mrad using a set of two angled BTSs that are located in front of a diode-laser array with about a 2 µm smile. Due to the reduced collimating residual divergence angle, the external cavity with a set of two angled BTSs and a volume Bragg grating achieved a wide wavelength-locking range for temperatures ranging from 20°C to 30°C. In addition, the side-mode suppression ratio exceeds 30 dB.

Risley-prism-based tracking model for fast locating a target using imaging feedback.

Fast imaging tracking technology exhibits attractive application prospects in the emerging fields of target tracking and recognition. Smart and compact tracking model with fast and flexible tracking strategy can play a decisive role in improving system performance. In this paper, an effective imaging tracking model from a target to a rotation Risley prism pair embedded with a camera is derived by the beam vector propagation method. A boresight adjustment strategy using the inverse ray tracing and iterative refinement method is established to accomplish the function of fast locating a target. The influence of system parameters on boresight adjustment accuracy and even the dynamic characteristics of the tracking system are investigated to reveal the coupling mechanisms between prism rotation and imaging feedback. The root-mean-square tracking error is below 4.5 pixels by just once adjustment in the static target experiment, while the error in the dynamic experiment is below 8.5 pixels for a target moving at the speed of 50 mm/s, which validates the feasibility of the proposed method for fast imaging tracking applications.

Easy method to measure the packaging-induced stress of a semiconductor laser diode by lasing wavelength shifting.

In this paper, the packaging-induced stresses are theoretically calculated by modeling multilayered structures for different packaging structures. We report a method to measure the packaging-induced stress of a laser diode array (LDA) by comparing the emission wavelength of the single emitter located in the middle of a laser bar before and after packaging. The wavelength is tested under a low duty cycle (50 µs/10 Hz, DC 0.05%) to eliminate the thermal effect to wavelength shifting. Experimental calculation results for the packaging-induced stress of LDAs are in good agreement with the theoretical calculations and simulation results. For a GaAs laser bar, we find the packaging stresses are compression stresses, which make the emission wavelength blue-shift in terms of 1.09×10-2 nm/MPa. We propose a mapping of packaging-induced stress distribution in laser bars on a microscopic scale by considering the emission spectra of each emitter in a laser bar. Compared to single-emitter resolved photo-current or micro-photoluminescence measurements, as proposed by other authors, we offer a much easier tool to test and map the distribution of packaging-induced stress in laser bars.

Three-dimensional thermal model of high-power semiconductor lasers.

In this paper, 3-D, steady-state, analytical thermal models of high-power single-emitter semiconductor lasers (SEs) and laser diode arrays (LDAs) are derived, considering the heat conduction in multi-layered laser structures. Heat flow in the laser chips for an epi-down bonded SE and LDA is described using this model, and it is observed that the laser chips contribute to 8% and 6% of total heat dissipation for the SE and LDA, respectively. The submount size requirement for this model is discussed by revealing the heat flow in the submount. Through finite element simulations, the solution accuracy for the lasers with non-ideal submounts is confirmed. Finally, the performance of our proposed analytical models is verified by finite element simulations and experimental measurements based on the wavelength shift method.

Thermal hydraulic performance of a microchannel heat sink for cooling a high-power diode laser bar.

Numerical and analytical methods are employed to investigate the thermal and fluid flow performance of a microchannel heat sink for cooling a high-power diode laser bar. Heat transfer characteristics and pressure drop in the microchannel under different flow rates are studied. A thermal resistance network, which is proved to have less than 5.4% error, is proposed to characterize the resistance components for the microchannel heat sink. Both numerical modeling and thermal resistance network analysis are verified by experimental results based on the wavelength shift method. Two new heat sinks with more uniform temperature distribution for laser emitters compared with the existing design are presented, and their performance is validated by numerical modeling and spatially resolved spectrum measurements.

Prelocation image stitching method based on flexible and precise boresight adjustment using Risley prisms.

A prelocation image stitching method is proposed for the scan imaging system using Risley prisms. By confining the feature-based stitching procedure to several prelocated overlap areas in multiple subregion images, the proposed method reduces the computational complexity of feature extraction and image registration. Experiment results and analysis have validated the feasibility and robustness of the overlap prelocation algorithm, which can enhance the image stitching efficiency by 21.89% at least and by 39.38% at most. In addition, the composite image obtained from the prelocation stitching procedure can achieve a large field of view while maintaining high resolution.

Double-wedge prism imaging tracking device based on the adaptive boresight adjustment principle.

A double-wedge prism device has been used in various imaging detection applications due to its high precision and strong anti-disturbance capability. In this paper, a self-adaptation double-wedge prism boresight adjustment principle suitable for both far-field and near-field target tracking is proposed. In order to realize this application, an adaptive variable boresight imaging tracking device is designed specifically. Then a tracking error model is established, and dynamic simulation, error evaluation, and sensitivity analysis are carried out according to the design objective. The experimental results show that the pitch angle deviation and azimuth angle deviation of the device are less than 6', and the blind zone can be eliminated by adding a third wedge prism, thus achieving high-precision boresight adjustment and tracking.

Rotation double prisms steered by noncircular gear pairs to scan specified nonlinear trajectories.

In order to scan some specified nonlinear motion trajectories with high accuracy, simple control process, and good stability, we propose a method to design the drive mechanism of the rotation double-prism scanner, which can transfer the nonlinear motor control to the profile design of corresponding noncircular gear pairs. Given a nonlinear target trajectory, this method can successfully change the complicated nonlinear motion of the motor to the more operative uniform rotation. The simulation and experiment results show that the tracking error is less than 0.981 mm in the distance of 500 mm between the actual tracking trajectory and the original one. The proposed drive mechanical setup offers a perfect alternative to the nonlinear control design of the rotation double-prism scanner.

Investigation of scan errors in the three-element Risley prism pair.

In this paper, the error analysis model for the three-element Risley-prism scan system (TRSS) is established, and categories of error sources are redefined. The impact of each error on the pointing accuracy is graphically presented with analytical and numerical results. The analysis method can be implemented to any Risley-prism beam scan system. For thin prisms, an error compensation algorithm for the TRSS is developed to accomplish high-accuracy beam scanning, which can be referred to the error calibration of the TRSS.

Effect of submount thickness on near-field bowing of laser diode arrays.

Near-field bowing a laser diode bar (i.e., the "SMILE" effect) degrades the laser beam brightness, adversely affecting optical coupling and beam shaping. Due to thermally induced stress during the bonding process, the emitters in a laser diode array (LDA) are vertically displaced, which causes the SMILE effect. The mismatch between the coefficients of thermal expansion of an LDA (GaAs with 6.4 ppm/K) and a heat sink (Cu with 16.4 ppm/K) is a large obstacle in the LDA bonding process, because it provokes thermal stress and a large SMILE value, resulting in a larger divergence angle and a wider line after focusing and collimation. In this paper, the changes in stress and strain (SMILE value) and their effects on the laser bar as a function of the copper-tungsten (CuW) submount thickness were theoretically and experimentally studied. The finite element modeling simulations and experimental results show that the compression stress on the laser bar decreases with increasing CuW submount thickness because the CuW submount works as a buffer layer and can absorb stress. However, the laser bar out-of-plane strain (SMILE value) is approximately zero when the LDA is directly bonded onto the heat sink without a submount; the SMILE value is maximized when the CuW submount thickness is increased to approximately one half or 44% of the heat sink. Beyond that, the SMILE value decreases with increasing CuW submount thickness.

Three-dimensional thermal model of a high-power diode laser bar.

An analytical, three-dimensional, steady-state thermal model of a high-power diode laser bar is presented in this paper. The heat spreading angle in a laser bar heat sink, subjected to several convective conditions on the bottom-side, was calculated with this model. Thermal design curves for the heat sink and submount are also presented. Special discussion is presented for two kinds of our conduction-cooled laser bars. Finite element simulation and experimental results based on the wavelength shift method are compared with this analytical solution. The familiar 45° angle in thermal design for a commercial hard solder conduction-cooled laser bar was found to lead to a 12% increase in thermal resistance relative to a free lateral diffusion heat sink.