Abstract Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic ...malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.
Non-reciprocal devices, which allow non-reciprocal signal routing, serve as fundamental elements in photonic and microwave circuits and are crucial in both classical and quantum information ...processing. The radiation-pressure-induced coupling between light and mechanical motion in travelling-wave resonators has been exploited to break the Lorentz reciprocity, enabling non-reciprocal devices without magnetic materials. Here, we experimentally demonstrate a reconfigurable non-reciprocal device with alternative functions as either a circulator or a directional amplifier via optomechanically induced coherent photon-phonon conversion or gain. The demonstrated device exhibits considerable flexibility and offers exciting opportunities for combining reconfigurability, non-reciprocity and active properties in single photonic devices, which can also be generalized to microwave and acoustic circuits.
Autophagy is a genetically well-controlled cellular process that is tightly controlled by a set of core genes, including the family of autophagy-related genes (ATG). Autophagy is a "double-edged ...sword" in tumors. It can promote or suppress tumor development, which depends on the cell and tissue types and the stages of tumor. At present, tumor immunotherapy is a promising treatment strategy against tumors. Recent studies have shown that autophagy significantly controls immune responses by modulating the functions of immune cells and the production of cytokines. Conversely, some cytokines and immune cells have a great effect on the function of autophagy. Therapies aiming at autophagy to enhance the immune responses and anti-tumor effects of immunotherapy have become the prospective strategy, with enhanced antigen presentation and higher sensitivity to CTLs. However, the induction of autophagy may also benefit tumor cells escape from immune surveillance and result in intrinsic resistance against anti-tumor immunotherapy. Increasing studies have proven the optimal use of either ATG inducers or inhibitors can restrain tumor growth and progression by enhancing anti-tumor immune responses and overcoming the anti-tumor immune resistance in combination with several immunotherapeutic strategies, indicating that induction or inhibition of autophagy might show us a prospective therapeutic strategy when combined with immunotherapy. In this article, the possible mechanisms of autophagy regulating immune system, and the potential applications of autophagy in tumor immunotherapy will be discussed.
Background
Positron emission tomography (PET)/MRI biomarkers have been shown to have prognostic significance in patients with cervical cancer. Their associations with progression‐free survival (PFS) ...and overall survival (OS) merit further investigation.
Purpose
To evaluate the association between PET/MRI biomarkers and tumor stage, PFS, and OS in patients with cervical cancer.
Study Type
Prospective cohort study.
Population
In all, 54 patients with newly diagnosed cervical cancer and measurable tumors (>1 cm) were included in the image analysis.
Field Strength/Sequence
3.0T integrated PET/MRI including diffusion‐weighted echo‐planar imaging (b = 50 and 1000 s/mm2) and 18Ffluorodeoxyglucose PET.
Assessment
Two radiologists measured the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors.
Statistical Tests
A Mann–Whitney U‐test was used to evaluate the association between the imaging biomarkers and tumor stage. A Cox proportional hazards model was used to assess the relationships between the imaging biomarkers and survival.
Results
In advanced tumors (T ≥ 1b2, M1, stage ≥ IB3), ADCmin was significantly lower and MTV, TLG, MTV/ADCmin, and TLG/ADCmin were significantly higher (P values between <0.001 and 0.036). In N1 tumors, ADCmin was significantly lower and MTV and MTV/ADCmin were significantly higher (P values between 0.005 and 0.016). In survival analysis, SUVmax was an independent predictor of PFS (hazard ratio HR = 4.57, P < 0.05), and ADCmin was an independent predictor of OS (HR = 0.02, P < 0.05). In subgroup analysis of patients with different stages, MTV/ADCmin was a predictor of PFS in stage I disease (P = 0.003), ADCmin (P = 0.038), and MTV (P = 0.020) in stage II, SUVmax (P = 0.006), and TLG (P = 0.006) in stage IV; and ADCmin was a predictor of OS in stage III disease (P = 0.008).
Data Conclusion
PET/MRI biomarkers of cervical cancer are associated with tumor stage and survival. SUVmax and ADCmin are independent predictors of PFS and OS, respectively.
Level of Evidence
1
Technical Efficacy
3
Non-reciprocal devices, such as circulators and isolators, are indispensable components in classical and quantum information processing in integrated photonic circuits. Aside from these applications, ...the non-reciprocal phase shift is of fundamental interest for exploring exotic topological photonics, such as the realization of chiral edge states and topological protection. However, incorporating low-optical-loss magnetic materials into a photonic chip is technically challenging. In this study we experimentally demonstrate non-magnetic non-reciprocity using optomechanical interactions in a whispering gallery microresonator, as proposed in a previous work. Optomechanically induced non-reciprocal transparency and amplification are observed and a non-reciprocal phase shift of up to 40 degree is also demonstrated. The underlying mechanism of optomechanically induced non-reciprocity has great potential for all-optical controllable isolators and circulators, as well as non-reciprocal phase shifters in integrated photonic chips.
Metabolic disorders are prevalent worldwide and have recently become public health problems recently. Previous studies have proposed different body composition indices for predicting future ...cardiovascular risks. We hypothesized an association among fat-to-muscle ratio (FMR), metabolic syndrome (MetS), hypertension (HTN), prediabetes, type 2 diabetes mellitus (DM), and cardiovascular risk in an adult population. A total of 66829 eligible subjects composed of 34182 males and 32647 females aged 20 years or older were obtained from health examinations in the Tri-Service General Hospital from 2011 to 2017. The body composition indices included fat and muscle mass measured by bioelectrical impedance analysis. A multivariable regression model was performed in a large population-based cross-sectional study. FMR was significantly associated with MetS, prediabetes, DM and HTN in all models of both genders. Based on quartile analysis, higher FMR had higher predictive ability for adverse health outcomes. The association between different definitions of MetS and the Framingham risk score was analyzed, and FMR-incorporated MetS was more useful for predicting higher Framingham risk scores than traditional definitions. FMR was a useful indicator for the presence of adverse cardiometabolic risks. Compared to traditional definition of MetS, FMR-incorporated MetS had a greater ability to predict incident cardiovascular risks. FMR seemed to be a simple and effective index for the early prevention and management of cardiometabolic events.
We propose an approach for face image generation of virtual people with disentangled, precisely-controllable latent representations for identity of non-existing people, expression, pose, and ...illumination. We embed 3D priors into adversarial learning and train the network to imitate the image formation of an analytic 3D face deformation and rendering process. To deal with the generation freedom induced by the domain gap between real and rendered faces, we further introduce contrastive learning to promote disentanglement by comparing pairs of generated images. Experiments show that through our imitative-contrastive learning, the factor variations are very well disentangled and the properties of a generated face can be precisely controlled. We also analyze the learned latent space and present several meaningful properties supporting factor disentanglement. Our method can also be used to embed real images into the disentangled latent space. We hope our method could provide new understandings of the relationship between physical properties and deep image synthesis.
Autophagy dysfunctions are involved in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) in the ...inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal and cellular models. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment significantly induced mouse movement disorder and decreased the protein level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and dopamine (DA) content in striatum. Along with the dopamine neuron injury, we observed significant upregulations of microtubule-associated light chain-3 II (LC3-II) and α-synuclein as well as a downregulation of P62 in MPTP-treated mice. These changes could be restored by IGF-1 pretreatment. Cotreatment with IGF-1R antagonist JB-1 or GPER antagonist G15 could block the neuroprotective effects of IGF-1. 1-Methy-4-phenylpyridinium (MPP
) treatment could also excessively activate autophagy along with the reduction of cell viability in SH-SY5Y cells. IGF-1 could inhibit the neurotoxicity through promoting the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which could also be antagonized by JB-1 or G15. These data suggest that IGF-1 inhibits MPTP/MPP
-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER.
In this paper we propose a novel image representation called face X-ray for detecting forgery in face images. The face X-ray of an input face image is a greyscale image that reveals whether the input ...image can be decomposed into the blending of two images from different sources. It does so by showing the blending boundary for a forged image and the absence of blending for a real image. We observe that most existing face manipulation methods share a common step: blending the altered face into an existing background image. For this reason, face X-ray provides an effective way for detecting forgery generated by most existing face manipulation algorithms. Face X-ray is general in the sense that it only assumes the existence of a blending step and does not rely on any knowledge of the artifacts associated with a specific face manipulation technique. Indeed, the algorithm for computing face X-ray can be trained without fake images generated by any of the state-of-the-art face manipulation methods. Extensive experiments show that face X-ray remains effective when applied to forgery generated by unseen face manipulation techniques, while most existing face forgery detection or deepfake detection algorithms experience a significant performance drop.
Coronavirus disease 2019 (COVID-19) has recently emerged as a global threat. Understanding workers' knowledge, attitudes, and practices (KAP) regarding this new infectious disease is crucial to ...preventing and controlling it. This study aimed to assess KAP regarding COVID-19 during the outbreak among workers in China. The present study was part of a cross-sectional online survey study conducted based on a large labor-intensive factory, which has 180,000 workers from various Chinese provinces, from 2 February 2020 to 7 February 2020. KAP related to COVID-19 were measured by 32 items, each item was measured with an agree/disagree/unclear format, and only correct responses were given 1 point. KAP regarding COVID-19 were measured with 20 items, 6 items and 6 items, respectively. A total of 123,768 valid responses (68.8%) were included in the analysis. Generally, the levels of knowledge (mean: 16.3 out of 20 points), attitudes (mean: 4.5 out of 6 points), and practices (mean: 5.8 out of 6 points) related to COVID-19 were high. Only 36,373 respondents (29.4%) disagreed that gargling with salt water is effective in protecting against COVID-19. Moreover, older respondents had decreased levels of knowledge and practices related to COVID-19 (both P values for the trend <0.001), while better-educated respondents had increased levels of knowledge and practices related to COVID-19 (both P values for the trend <0.001). These results suggest that Chinese workers are highly aware of COVID-19, but health authorities still need to provide correct information on COVID-19 prevention and strengthen health interventions, particularly for older and less-educated workers.
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