An end-to-end geometry-based pipeline for automatic preoperative surgical planning of pelvic fracture reduction and fixation.

Computer-assisted preoperative planning of pelvic fracture reduction surgery has the potential to increase the accuracy of the surgery and to reduce complications. However, the diversity of the pelvic fractures and the disturbance of small fracture fragments present a great challenge to perform reliable automatic preoperative planning. In this paper, we present a comprehensive and automatic preoperative planning pipeline for pelvic fracture surgery. It includes pelvic fracture labeling, reduction planning of the fracture, and customized screw implantation. First, automatic bone fracture labeling is performed based on the separation of the fracture sections. Then, fracture reduction planning is performed based on automatic extraction and pairing of the fracture surfaces. Finally, screw implantation is planned using the adjoint fracture surfaces. The proposed pipeline was tested on different types of pelvic fracture in 14 clinical cases. Our method achieved a translational and rotational accuracy of 2.56 mm and 3.31° in reduction planning. For fixation planning, a clinical acceptance rate of 86.7% was achieved. The results demonstrate the feasibility of the clinical application of our method. Our method has shown accuracy and reliability for complex multi-body bone fractures, which may provide effective clinical preoperative guidance and may improve the accuracy of pelvic fracture reduction surgery.

Lifetime History of Low Birth Weight Delivery and Cognitive Function in Middle-Aged Parous Women.

BACKGROUND AND OBJECTIVES: Pregnancy outcomes such as low birth weight (LBW) delivery may reflect vascular or metabolic dysfunction in mothers and presage future cognitive impairment and dementia. However, the evidence is currently limited. Our objective was to examine the extent to which a lifetime history of LBW delivery was associated with cognitive function in parous middle-aged women. METHODS: We studied participants from the Nurses' Health Study II, an ongoing longitudinal cohort of female nurses enrolled in 1989. In 2009, participants completed a reproductive history questionnaire. Participants who completed at least one of 2 post-traumatic stress disorder questionnaires were invited to participate in a cognition substudy with 2 waves of baseline data collection (2014 or 2018). We restricted the analysis to participants with one valid cognitive assessment who reported ≥1 birth at 18 years and older. We defined LBW delivery history as having delivered offspring with a birth weight <2,500 g (<5.5 lbs) in any pregnancy. The outcome was a single assessment of cognitive function evaluated with the self-administered Cogstate Brief Battery. The battery comprises 4 tasks, which we used to create 2 composite z-scores measuring psychomotor speed/attention and learning/working memory (higher z-scores = better cognitive function). We used multivariable linear regression models. RESULTS: The analysis included 15,323 participants with a mean age of 62 (standard deviation: 4.9 years) at cognitive assessment. Among them, 1,224 (8%) had a history of LBW delivery. After adjusting for age at cognitive assessment, race, and ethnicity, participants' education, wave of baseline cognitive assessment, socioeconomic status, and prepregnancy characteristics, women with a history of LBW delivery had lower z-scores in the psychomotor speed/attention (ß, -0.06; 95% CI -0.12 to -0.01) and learning/working memory (ß, -0.05; 95% CI -0.09 to -0.01) composites than parous women without a history of LBW delivery. We observed a gradient of lower z-scores with an increasing number of LBW deliveries. DISCUSSION: History of LBW delivery may be marker of future poorer cognition. If confirmed, our findings support future investigations into the value of early preventive efforts targeting women with a history of LBW delivery to reduce the burden of cognitive impairment in women.

R2D2-GAN: Robust Dual Discriminator Generative Adversarial Network for Microscopy Hyperspectral Image Super-Resolution.

High-resolution microscopy hyperspectral (HS) images can provide highly detailed spatial and spectral information, enabling the identification and analysis of biological tissues at a microscale level. Recently, significant efforts have been devoted to enhancing the resolution of HS images by leveraging high spatial resolution multispectral (MS) images. However, the inherent hardware constraints lead to a significant distribution gap between HS and MS images, posing challenges for image super-resolution within biomedical domains. This discrepancy may arise from various factors, including variations in camera imaging principles (e.g., snapshot and push-broom imaging), shooting positions, and the presence of noise interference. To address these challenges, we introduced a unique unsupervised super-resolution framework named R2D2-GAN. This framework utilizes a generative adversarial network (GAN) to efficiently merge the two data modalities and improve the resolution of microscopy HS images. Traditionally, supervised approaches have relied on intuitive and sensitive loss functions, such as mean squared error (MSE). Our method, trained in a real-world unsupervised setting, benefits from exploiting consistent information across the two modalities. It employs a game-theoretic strategy and dynamic adversarial loss, rather than relying solely on fixed training strategies for reconstruction loss. Furthermore, we have augmented our proposed model with a central consistency regularization (CCR) module, aiming to further enhance the robustness of the R2D2-GAN. Our experimental results show that the proposed method is accurate and robust for super-resolution images. We specifically tested our proposed method on both a real and a synthetic dataset, obtaining promising results in comparison to other state-of-the-art methods. Our code and datasets are accessible through Multimedia Content.

Hepatic arterial infusion chemotherapy with implantable arterial access port for advanced-stage hepatocellular carcinoma: a case report.

Background: Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy characterized by high incidence rates and a poor prognosis. Common treatment modalities include surgery, ablation, and transarterial chemoembolization (TACE). Hepatic arterial infusion chemotherapy (HAIC) has long been used in the treatment of unresectable liver cancer. In recent years, the combination of anti-angiogenesis therapy and immune checkpoint inhibitors has shown significant advances in the treatment of middle- and advanced-stage liver cancer. This report presents a case of HCC in which sustained benefits are achieved through a combination of HAIC of infusional oxaliplatin, leucovorin, and fluorouracil (FOLFOX), targeted therapy, and immunotherapy. Main body: A 64-year-old male patient was diagnosed with a parenchymal mass in the liver by a three-dimensional color ultrasound one month before admission, prompting consideration of liver cancer. Subsequently, computed tomography (CT) imaging performed at our hospital identified mass shadows in the right lobe of the liver and diffuse nodules throughout the liver, suggesting malignant lesions. Upon admission, the patient presented poor general health and baseline indicators. Following symptomatic treatment, the patient underwent a therapeutic regimen that combined transarterial infusion port FOLFOX-HAIC with Lenvatinib and Sintilimab. This combined treatment resulted in significant liver tumor necrosis and effectively managed the patient's condition. Conclusion: The combined approach of using FOLFO-HAIC transarterial infusion alongside anti-angiogenesis therapy and immune checkpoint inhibitors has shown promising results that provide substantial benefits. This combined regimen has demonstrated the potential to improve treatment compliance among certain patients. Given these encouraging outcomes, further investigation into this combination therapy regimen is warranted to understand better its efficacy and potential broader applications in clinical settings.

Heart and great vessels segmentation in congenital heart disease via CNN and conditioned energy function postprocessing.

PURPOSE: The segmentation of the heart and great vessels in CT images of congenital heart disease (CHD) is critical for the clinical assessment of cardiac anomalies and the diagnosis of CHD. However, the diverse types and abnormalities inherent in CHD present significant challenges to comprehensive heart segmentation. METHODS: We proposed a novel two-stage segmentation approach, integrating a Convolutional Neural Network (CNN) with a postprocessing method with conditioned energy function for pulmonary and aorta. The initial stage employs a CNN enhanced by a gated self-attention mechanism for the segmentation of five primary heart structures and two major vessels. Subsequently, the second stage utilizes a conditioned energy function specifically tailored to refine the segmentation of the pulmonary artery and aorta, ensuring vascular continuity. RESULTS: Our method was evaluated on a public dataset including 110 3D CT volumes, encompassing 16 CHD variants. Compared to prevailing segmentation techniques (U-Net, V-Net, Unetr, dynUnet), our approach demonstrated improvements of 1.02, 1.04, and 1.41% in Dice Coefficient (DSC), Intersection over Union (IOU), and the 95th percentile Hausdorff Distance (HD95), respectively, for heart structure segmentation. For the two great vessels, the enhancements were 1.05, 1.07, and 1.42% in these metrics. CONCLUSION: The outcomes on the public dataset affirm the efficacy of our proposed segmentation method. Precise segmentation of the entire heart and great vessels can significantly aid in the diagnosis and treatment of CHD, underscoring the clinical relevance of our findings.

Research on Laser Cleaning Technology for Aircraft Skin Surface Paint Layer.

In this study, a pulsed laser operating at a wavelength of 1064 nm and with a pulse width of 100 ns was utilized for the removal of paint from the surface of a 2024 aluminum alloy. The experimental investigation was conducted to analyze the influence of laser parameters on the efficacy of paint layer removal from the aircraft skin's surface and the subsequent evolution in the microstructure of the laser-treated aluminum alloy substrate. The mechanism underlying laser cleaning was explored through simulation. The findings revealed that power density and scanning speed significantly affected the quality of cleaning. Notably, there were discernible damage thresholds and optimal cleaning parameters in repetitive frequency, with a power density of 178.25 MW/cm2, scanning speed of 500 mm/s, and repetitive frequency of 40 kHz identified as the primary optimal settings for achieving the desired cleaning effect. Thermal ablation and thermal vibration were identified as the principal mechanisms of cleaning. Moreover, laser processing induced surface dislocations and concentrated stress, accompanied by grain refinement, on the aluminum substrate.

Delta-sigma modulation supporting the 4194304QAM dual polarization signal at the W-band transmission over a 4.6†km wireless distance.

In this Letter, we propose a dual-polarized coherent millimeter-wave system based on differential delta-sigma modulation (D-DSM) intended for long-distance wireless transmission in the W-band. The proposed system can transmit polarization-division-multiplexed (PDM) D-DSM signals with modulation orders up to 4194304QAM over a wireless channel for 4.6 km at a signal baud rate of 20 G. After 4.6 km of wireless transmission, we successfully achieve a bit error rate (BER) lower than the hard-decision forward error correction (HD-FEC) of 3.8 × 10-3 for 34.51 Gbit/s PDM-524288QAM and a BER lower than the soft-decision forward error correction (SD-FEC) of 4.2 × 10-2 for 32.23 Gbit/s PDM-4194304QAM.

The anti-PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel in first-line treatment of metastatic triple-negative breast cancer: a multicenter phase II trial.

This multicenter, phase II study (NCT03872791) aims to evaluate the efficacy and safety of the anti-PD-L1/CTLA-4 bispecific antibody KN046 combined with nab-paclitaxel in the first-line treatment of patients with metastatic triple-negative breast cancer (TNBC). The primary endpoints included objective response rate (ORR) and duration of response (DoR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) rate, safety, and the correlation of PD-L1 status with clinical efficacy. This trial met pre-specified endpoints. 27 female patients were enrolled sequentially to receive KN046 in two dose levels (3 mg/kg or 5 mg/kg). Among the 25 evaluable patients, the ORR achieved 44.0% (95% CI, 24.4% - 65.1%), and the median DoR was not mature. The median PFS reached 7.33 months (95%CI, 3.68 - 11.07 months), and the median OS was 30.92 months (95%CI, 14.75 - NE months). In PD-L1 positive patients, PFS was 8.61 months (versus 4.73 months) and the 2-year OS rate was 62.5% (versus 57.1%) compared to PD-L1 negative patients. Patients tolerated well the combination therapy. In general, KN046 combined with nab-paclitaxel showed favorable efficacy and survival benefits with tolerable toxicity in the first-line treatment of metastatic TNBC, especially PD-L1 positive, which is worth further investigation.

Strategies for the Construction of Benzobicyclo[3.2.1]octane in Natural Product Synthesis.

Benzobicyclo[3.2.1]octane is a cage-like unique motif containing a bicyclo[3.2.1]octane structure fused with at least one benzene ring. It is found in various natural products that exhibit structural complexities and important biological activities. The total synthesis of natural products possessing this challenging structure has received considerable attention, and great advances have been made in this field during the past 15 years. This review summarizes thus far achieved chemical syntheses and synthetic studies of natural compounds featuring the benzobicyclo[3.2.1]octane core. It focuses on strategic approaches constructing the bridged structure, aiming to provide a useful reference for inspiring further advancements in strategies and total syntheses of natural products with such a framework.

Dynamic changes of Th1/Th2/Th17 cytokines and hBD-2/3 in erosive oral lichen planus patients saliva before and after prednisone acetate treatment.

Objective: This study aimed to investigate the expression of T helper 1 (Th1)/Th2/Th17- related cytokines and human beta defensins 2 and 3 (hBD-2 and -3) in the saliva of patients with erosive oral lichen planus (EOLP) and to explore their role in the pathogenesis of EOLP and the effects of glucocorticoids on EOLP. Methods: A total of 30 patients with EOLP and 20 age- and sex-matched healthy individuals were included in this study. The patients were treated with prednisone at a dose of 0.4 mg/(kg·d) for 1 week and examined before and after treatment. Unstimulated whole saliva samples were collected to determine the levels of cytokines (interleukin 1 beta [IL-1ß], tumour necrosis factor alpha [TNF]-α, interferon gamma [IFN-γ], IL-4, IL-6, IL-10 and IL-17) by cytometric bead array and those of hBD-2 and -3 b y enzyme-linked immunosorbent assay. In addition, oral rinse samples were collected to detect Candida load. Results: The levels of salivary IL-1ß, IL-6, hBD-2 and hBD-3 were higher and the IFN-γ/IL-4 and IL-1ß/IL-6 ratios were lower in patients with EOLP than in healthy individuals. In patients with EOLP, hBD-2 levels were positively correlated with IFN-γ levels and negatively correlated with IL-17 levels, whereas hBD-3 levels were negatively correlated with IL-17 and IL-10 levels. In addition, the prevalence of EOLP was positively correlated with IL-6 levels and negatively correlated with the IFN-γ/IL-4 ratio. The levels of IL-1ß, TNF-α, IFN-γ, IL-6, hBD-2 and hBD-3 and the IFN-γ/IL-4 ratio decreased after treatment with prednisone for 1 week. The levels of IL-6, hBD-2 and hBD-3 were significantly higher in EOLP patients than in healthy individuals; while TNF-α levels and the IFN-γ/IL-4 ratio were significantly lower in EOLP patients than in healthy individuals. Furthermore, the oral counts of Candida spp. (colony forming unit [CFU]) were negatively correlated with TNF-α levels. Numerical Rating Scale(NRS) and Sign scores decreased in EOLP patients after treatment. Approximately 80 % of patients were effectively treated. Salivary TNF-α levels were significantly higher in the treatment-ineffective group than in the treatment-effective group before treatment with prednisone, and differences in salivary IL-6 levels before and after treatment were significantly higher in the treatment-effective group than in the treatment-ineffective group. Conclusions: High expression of IL-1ß, IL-6, hBD-2 and Th1/Th2 imbalance in saliva may be associated with the pathogenesis of EOLP. IFN-γ/IL-4 balance may serve as a protective factor for EOLP. Glucocorticoids significantly alleviate the symptoms of EOLP and inhibit the expression of Th1/Th2 cytokines.

A kinetic model for solving a combination optimization problem in ab-initio Cryo-EM 3D reconstruction.

Cryo-Electron Microscopy (cryo-EM) is a widely used and effective method for determining the three-dimensional (3D) structure of biological molecules. For ab-initio Cryo-EM 3D reconstruction using single particle analysis (SPA), estimating the projection direction of the projection image is a crucial step. However, the existing SPA methods based on common lines are sensitive to noise. The error in common line detection will lead to a poor estimation of the projection directions and thus may greatly affect the final reconstruction results. To improve the reconstruction results, multiple candidate common lines are estimated for each pair of projection images. The key problem then becomes a combination optimization problem of selecting consistent common lines from multiple candidates. To solve the problem efficiently, a physics-inspired method based on a kinetic model is proposed in this work. More specifically, hypothetical attractive forces between each pair of candidate common lines are used to calculate a hypothetical torque exerted on each projection image in the 3D reconstruction space, and the rotation under the hypothetical torque is used to optimize the projection direction estimation of the projection image. This way, the consistent common lines along with the projection directions can be found directly without enumeration of all the combinations of the multiple candidate common lines. Compared with the traditional methods, the proposed method is shown to be able to produce more accurate 3D reconstruction results from high noise projection images. Besides the practical value, the proposed method also serves as a good reference for solving similar combinatorial optimization problems.

Polyfluorene Conjugated Polyelectrolytes-Covalently Modified Black Phosphorus Nanosheets for Bioinspired Electronics.

As some of the most promising candidates for constituting bioinspired electronics, polymer memristors with analog-type switching behavior exhibit great potential for synaptic mimicking and neuromorphic computing systems. By using highly soluble conjugated polyelectrolyte poly[9,9-bis(6-(3-methyl-1-imidazolium-yl)hexyl)fluorene]-covalently modified black phosphorus (BP) nanomaterial (BP-PF-NMI+Br-) as the active layer, an electronic device with the BP-PF-NMI+Br- film sandwiched between the aluminum and indium tin oxide electrodes is successfully fabricated. This device exhibits an excellent amount of electricity-dependent memristive performance at a small sweep voltage range of ±1 V. With increasing amount of electricity flowing through the device, the device resistance gradually decreased in a linear pattern. The changes in frequency, amplitude, and duration of voltage pulses do not affect the linear relationship between the amount of electricity passing through the device and the resistance value achieved after each state reached equilibrium at different numbers of the same voltage pulse stimulations. Both the synaptic potentiation/depression and learning/memorizing/forgetting functions of biological systems have been emulated. In contrast to BP-PF-NMI+Br-, the pure PF-NMI+Br--based device shows a write-once-read-many-times effect at the same scanning voltage range, while the BP:PF-NMI+Br- blends exhibit very unstable memristive performances.

Post-traumatic stress disorder symptom remission and cognition in a large cohort of civilian women.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with cognitive impairments. It is unclear whether problems persist after PTSD symptoms remit. METHODS: Data came from 12 270 trauma-exposed women in the Nurses' Health Study II. Trauma and PTSD symptoms were assessed using validated scales to determine PTSD status as of 2008 (trauma/no PTSD, remitted PTSD, unresolved PTSD) and symptom severity (lifetime and past-month). Starting in 2014, cognitive function was assessed using the Cogstate Brief Battery every 6 or 12 months for up to 24 months. PTSD associations with baseline cognition and longitudinal cognitive changes were estimated by covariate-adjusted linear regression and linear mixed-effects models, respectively. RESULTS: Compared to women with trauma/no PTSD, women with remitted PTSD symptoms had a similar cognitive function at baseline, while women with unresolved PTSD symptoms had worse psychomotor speed/attention and learning/working memory. In women with unresolved PTSD symptoms, past-month PTSD symptom severity was inversely associated with baseline cognition. Over follow-up, both women with remitted and unresolved PTSD symptoms in 2008, especially those with high levels of symptoms, had a faster decline in learning/working memory than women with trauma/no PTSD. In women with remitted PTSD symptoms, higher lifetime PTSD symptom severity was associated with a faster decline in learning/working memory. Results were robust to the adjustment for sociodemographic, biobehavioral, and health factors and were partially attenuated when adjusted for depression. CONCLUSION: Unresolved but not remitted PTSD was associated with worse cognitive function assessed six years later. Accelerated cognitive decline was observed among women with either unresolved or remitted PTSD symptoms.

Development and validation of a combined nomogram for predicting perineural invasion status in rectal cancer via computed tomography-based radiomics.

AIM: This study aimed to create and validate a clinic-radiomics nomogram based on computed tomography (CT) imaging for predicting preoperative perineural invasion (PNI) of rectal cancer (RC). MATERIAL AND METHODS: This study enrolled 303 patients with RC who were divided into training (n = 242) and test datasets (n = 61) in an 8:2 ratio with all their clinical outcomes. A total of 3,296 radiomic features were extracted from CT images. Five machine learning (ML) models (logistic regression (LR)/K-nearest neighbor (KNN)/multilayer perceptron (MLP)/support vector machine (SVM)/light gradient boosting machine (LightGBM)) were developed using radiomic features derived from the arterial and venous phase images, and the model with the best diagnostic performance was selected. By combining the radiomics and clinical signatures, a fused nomogram model was constructed. RESULTS: After using the Mann-Whitney U-test and least absolute shrinkage and selection operator (LASSO) to remove redundant features, the MLP model proved to be the most efficient among the five ML models. The fusion nomogram based on MLP prediction probability further improves the ability to predict the PNI status. The area under the curve (AUC) of the training and test sets was 0.883 and 0.889, respectively, which were higher than those of the clinical (training set, AUC = 0.710; test set, AUC = 0.762) and radiomic models (training set, AUC = 0.840; test set, AUC = 0.834). CONCLUSIONS: The clinical-radiomics combined nomogram model based on enhanced CT images efficiently predicted the PNI status of patients with RC.

Improved Short-Circuit Current and Fill Factor in PM6:Y6 Organic Solar Cells through D18-Cl Doping.

Based on the PM6:Y6 binary system, a novel non-fullerene acceptor material, D18-Cl, was doped into the PM6:Y6 blend to fabricate the active layer. The effects of different doping ratios of D18-Cl on organic solar cells were investigated. The best-performing organic solar cell was achieved when the doping ratio of D18-Cl reached 20 wt%. It exhibited a short-circuit current of 28.13 mA/cm2, a fill factor of 70.25%, an open-circuit voltage (Voc) of 0.81 V, and a power conversion efficiency of 16.08%. The introduction of an appropriate amount of D18-Cl expanded the absorption spectrum of the active layer, improved the morphology of the active layer, reduced large molecular aggregation and defects, minimized bimolecular recombination, and optimized the collection efficiency of charge carriers. These results indicate the critical importance of selecting an appropriate third component in binary systems and optimizing the doping ratio to enhance the performance of ternary organic solar cells.

Combined RNAi of CTTN and FGF2 Modulates Cell Migration, Invasion and G1/S Transition of Hepatocellular Carcinoma through Ras/ERK Signaling Pathway.

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) die of rapid progression and distant metastasis. Gene therapy represents a promising choice for HCC treatment, but the effective targeted methods are still limited. OBJECTIVE: CTTN/cortactin plays a key role in actin polymerization and regulates cytoskeleton remodeling. However, the interaction network of CTTN in HCC is not well understood. METHODS: siRNA was designed for CTTN silencing and Affymetrix GeneChip sequencing was used to obtain the gene profile after CTTN knockdown in the HCC cell line SMMC-7721. Potential interacting genes of CTTN were identified using qRT-PCR. The inhibition on HCC by combined RNA interference (RNAi) of CTTN and fibroblast growth factor 2 (FGF2) was detected. RESULTS: A total of 1,717 significantly altered genes were screened out and 12 potential interacting genes of CTTN were identified. The interaction of CTTN and FGF2 was validated and combined RNAi of CTTN and FGF2 achieved a synergistic effect, leading to better inhibition of HCC cell migration, invasion and G1/S transition than single knockdown of CTTN or FGF2. Mechanistically, combined RNAi of CTTN and FGF2 modulated the Ras/ERK signaling pathway. In addition, the EMT epithelial marker E-cadherin was upregulated while the mesenchymal marker Vimentin and cell cycle protein Cyclin D1 were downregulated after combined RNAi of CTTN and FGF2. Additionally, qRT-PCR and immunohistochemical staining showed that both CTTN and FGF2 were highly expressed in metastatic HCC tissues. CONCLUSION: Combined RNAi of CTTN and FGF2 may be a novel and promising intervention strategy for HCC invasion and metastasis.

Eribulin combined with antiangiogenic agents in women with HER2-negative metastatic breast cancer: a retrospective multicenter study.

Background: The relative lack of specifically targeted agents for HER2-negative metastatic breast cancer (MBC) makes the need for new agents or combination therapies to maximize clinical benefit while reducing toxicity critical. Objectives: To retrospectively analyze the efficacy and safety of eribulin combined with antiangiogenic drugs in the treatment of Chinese women with HER2-negative MBC. Methods: A total of 85 consecutive MBC patients with HER2-negative who were treated with eribulin + antiangiogenic agents between October 2020 and April 2023 in four institutions were retrospectively included in this study. Patients received eribulin 1.4 mg/m2 (day 1 and 8) plus bevacizumab 7.5 mg/kg (day 1, 64 patients) or anlotinib 10 mg daily (day 1-14, 16 patients) or apatinib 250 mg daily (5 patients) on a 21-day cycle until progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS), according to Response Evaluation Criteria in Solid tumors (RECIST) 1.1. Secondary end-points included toxicities, objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The study included 85 HER2-negative MBC patients, with 41 patients (48.2%) in the first to second line group and 44 patients (51.8%) in the greater than or equal to third line group. The median age was 54.0 years. Thirty patients in the first to second line group and 14 patients in the greater than or equal to third line group had triple-negative breast cancer (TNBC). The ORR and DCR were 34.1% (29/85) and 75.3% (64/85). The median PFS (mPFS) of total population was 6.0 months (95% CI: 4.3-7.7), and median OS (mOS) was immature. The mPFS was 7.7 and 4.3 months in the first to second and greater than or equal to third line treatment (p = 0.003), respectively. TNBC patients in first to second line therapy showed a significantly longer PFS (6.5 months versus 2.0 months, p = 0.021) compared to greater than or equal to third line. The incidences of cardiovascular toxicity were 29.4% in grades 1-2 and no grades 3-4. Hematologic toxicity (leukopenia and neutropenia) was the most common grade ⩾3 AEs, and AEs were more common in patients in greater than or equal to third line. Conclusion: The results suggest that eribulin combined with antiangiogenic therapy has a meaningful clinical activity and an acceptable safety profile in HER2-negative MBC.

High quality stealth dicing of sapphire with a picosecond Bessel beam by controlling the polarization direction.

Sapphire is an important substrate material in optoelectronic devices, and it is also widely used as a touch screen panel. In order to achieve high quality cutting of sapphire, the stealth dicing of 500 µm thick sapphire by a picosecond Bessel beam is studied in this paper. The influences of laser polarization direction and process parameters on cutting section roughness were studied. By controlling the laser polarization direction, different crack propagation morphologies were obtained. When the polarization direction was vertical to the cutting path, the crack propagation path was straighter, and the sapphire had better cutting quality. The laser processing parameters, including burst mode, hole spacing, and pulse energy, had a significant impact on the cutting section roughness. When the polarization direction was vertical to the cutting path under the optimal process parameters, the cutting section was uniform and flat, with no recondensable particles, no ripples, and no chamfer, and an 89.7 nm average roughness of the cutting section could be obtained.

PDM-OFDM 1-bit DSM 1024QAM/4096QAM signals at W-band transmission over 4.6-km wireless distance.

In this Letter, we propose the application of delta-sigma modulation (DSM) higher-order quadrature amplitude modulation (QAM) technology in long-distance transmission of W-band wireless communication, and demonstrate, for the first time to the best of our knowledge, the wireless transmission of millimeter wave signals in the W-band based on 1-bit DSM quantization using polarization-division-multiplexed orthogonal frequency division multiplexing (PDM-OFDM) 1024QAM/4096QAM for 4.6 km. We successfully achieved a bit error rate (BER) of 40-Gbit/s PDM-OFDM 1024QAM and 48-Gbit/s PDM-OFDM 4096QAM after 4.6-km wireless transmission, both lower than the soft decision forward error correction (SD-FEC) of 4.2 × 10-2. To the best of our knowledge, this is the first time that up to 4096QAM signals have been quantized and transmitted based on 1-bit DSM in a 4.6-km-long distance W-band millimeter wave system.