We study the coupling of mode in time for non-Hermitian cavities. Using variational principle, we provide a self-consistent approach to study the mode hybridization in non-Hermitian cavities from the ...first-principle of Maxwell's equations. We first extend the reaction concept for time reversal adjoint system using the scalar inner product. We apply our theory to the non-Hermitian parity-time symmetric cavities, and obtain excellent agreement with results obtained by finite element fullwave simulations. In contrast, the conventional coupled mode theory using complex inner product fails to capture the bifurcation of the dispersion of parity-time symmetric cavities, as non-Hermicity increases. Our theory may have potential applications in non-Hermitian optical systems.
Bladder cancer is a fatal cancer that happens in the genitourinary tract with quite high morbidity and mortality annually. The high level of recurrence rate ranging from 50 to 80% makes bladder ...cancer one of the most challenging and costly diseases to manage. Faced with various problems in existing methods, a recently emerging concept for the measurement of imaging biomarkers and extraction of quantitative features called "radiomics" shows great potential in the application of detection, grading, and follow-up management of bladder cancer. Furthermore, machine-learning (ML) algorithms on the basis of "big data" are fueling the powers of radiomics for bladder cancer monitoring in the era of precision medicine. Currently, the usefulness of the novel combination of radiomics and ML has been demonstrated by a large number of successful cases. It possesses outstanding strengths including non-invasiveness, low cost, and high efficiency, which may serve as a revolution to tumor assessment and emancipate workforce. However, for the extensive clinical application in the future, more efforts should be made to break down the limitations caused by technology deficiencies, inherent problems during the process of radiomic analysis, as well as the quality of present studies.
Abstract Background TFE3 -rearranged renal cell carcinoma ( TFE3 -rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely ...undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates. Methods Thirty-eight patients with metastatic TFE3 -rRCC were enrolled. Main outcomes included progression-free survival (PFS), overall survival, objective response rate (ORR) and disease control rate. RNA sequencing was performed on 32 tumors. Results Patients receiving first-line immune checkpoint inhibitor (ICI) based combination therapy achieved longer PFS than those treated without ICI (median PFS: 11.5 vs. 5.1 months, P = 0.098). After stratification of fusion partners, the superior efficacy of first-line ICI based combination therapy was predominantly observed in ASPSCR1-TFE3 rRCC (median PFS: not reached vs. 6.5 months, P = 0.01; ORR: 67.5% vs. 10.0%, P = 0.019), but almost not in non- ASPSCR1-TFE3 rRCC. Transcriptomic data revealed enrichment of ECM and collagen-related signaling in ASPSCR1-TFE3 rRCC, which might interfere with the potential efficacy of anti-angiogenic monotherapy. Whereas angiogenesis and immune activities were exclusively enriched in ASPSCR1-TFE3 rRCC and promised the better clinical outcomes with ICI plus tyrosine kinase inhibitor combination therapy. Conclusions The current study represents the largest cohort comparing treatment outcomes and investigating molecular correlates of metastatic TFE3 -rRCC based on fusion partner stratification. ICI based combination therapy could serve as an effective first-line treatment option for metastatic ASPSCR1-TFE3 rRCC patients. Regarding with other fusion subtypes, further investigations should be performed to explore the molecular mechanisms to propose pointed therapeutic strategy accordingly.
Buildings play a crucial role in global electricity consumption, but their function is evolving. Rather than merely consuming energy, buildings have the potential to become energy producers through ...participating in flexibility services, which involve demand response and distributed energy supplies. However, the new technological and societal challenges that arise from temporal and spatial changes on both supply and demand sides make building services increasingly complex. This paper presents an opportunity for flexibility services offered by building energy systems via power-to-heat technology and discusses four key aspects: quantitative indicators based on thermal inertia, model predictive control for building flexibility, flexible system optimization for smart buildings, and applications of flexible services. Thermal inertia is a crucial factor that transcends technical constraints and serves as a bridge between the demand and supply sides. Demand-side response and data-driven cogeneration under model predictive control are essential for managing building flexibility. In addition, flexible system optimization is achieved through the combination of demand-side trading and disturbed system optimization. Applications of flexible services represent a combination of demand-side trading and disturbed system optimization in the fields of engineering and sociology. Finally, the paper explores the challenges, as well as the potential and models of building flexibility services technologies, including features that can facilitate automated operational decision-making on both the demand and supply sides.
Conflicting evidence exists regarding the effect of hypertension on the prognosis of metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). This study aimed ...to assess the predictive value of TKIs-induced hypertension in patients with mRCC.
This study was registered in PROSPERO (CRD42019129593). PubMed, Embase, Web of Science and the Cochrane Library database were searched with terms: "renal cell carcinoma", "hypertension", "blood pressure", "tyrosine kinase inhibitor", "sunitinib", "axitinib", "sorafenib" and "pazopanib" until March 21, 2019. Hazard Ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) or overall survival (OS) were extracted and analyzed with Stata 15.0 software. Heterogeneity was assessed using the I
value. Meta-regression, subgroup analysis and sensitivity analysis were also performed to explore heterogeneity. Publication bias was assessed with funnel plots and precisely assessed by Egger's and Begg's tests. The quality of evidence of outcomes was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
A total of 4661 patients from 22 studies were included in the study. The results showed that the increase of blood pressure was an effective predictor for longer PFS (HR = 0.59, 95% CI: 0.48-0.71, p < 0.001; I
= 77.3%) and OS (HR = 0.57, 95% CI: 0.45-0.70, p < 0.001; I
= 77.4%) of patients with mRCC. Subgroup analysis revealed that patients receiving sunitinib and pazopanib could have longer PFS and OS.
This study indicated that TKIs-induced hypertension may be a good predictor for better prognosis of patients with mRCC receiving TKIs treatment, especially using sunitinib or pazopanib.
This study aimed to develop and internally validate computed tomography (CT)-based radiomic models to predict the lesion-level short-term response to tyrosine kinase inhibitors (TKIs) in patients ...with advanced renal cell carcinoma (RCC).
This retrospective study included consecutive patients with RCC that were treated using TKIs as the first-line treatment. Radiomic features were extracted from noncontrast (NC) and arterial-phase (AP) CT images. The model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).
A total of 36 patients with 131 measurable lesions were enrolled (training: validation = 91: 40). The model with five delta features achieved the best discrimination capability with AUC values of 0.940 (95% CI, 0.890‒0.990) in the training cohort and 0.916 (95% CI, 0.828‒1.000) in the validation cohort. Only the delta model was well calibrated. The DCA showed that the net benefit of the delta model was greater than that of the other radiomic models, as well as that of the treat-all and treat-none criteria.
Models based on CT delta radiomic features may help predict the short-term response to TKIs in patients with advanced RCC and aid in lesion stratification for potential treatments.
Optical Kerr solitons generation based on microresonators is essential in nonlinear optics. Among various soliton generation processes, the single soliton generation plays a pivotal role since it ...ensures rigorous mode-locking on each comb line whose interval equals the free spectral range (FSR) of the microresonator. Current studies show that single soliton generation is challenging due to cavity instability. Here, we propose a new method to greatly improve single soliton generation probalility in the anomalous group velocity dispersion (GVD) regime in a micro-ring resonator based on silicon nitride. The improvement is realized by introducing mode depletion through an integrated coupled filter. It is convenient to introduce controllable single mode depletion in a micro-ring resonator by adjusting the response function of a coupled filter. We show that spectral mode depletion (SMD) can significantly boost the single soliton generation probability. The effect of SMD on the dynamics of optical Kerr solitons generation are also discussed. The proposed method offers a straightforward and simple way to facilitate robust single soliton generation, and will have an impact on the research development in optical Kerr soliton generation and on-chip optical frequency mode manipulation.
Objectives
To develop and validate a predictive model based on clinical features and multiparametric magnetic resonance imaging (mpMRI) to reduce unnecessary systematic biopsies (SBs) in biopsy-naïve ...patients with suspected prostate cancer (PCa).
Methods
A total of 274 patients who underwent combined cognitive MRI-targeted biopsy (MRTB) with SB were retrospectively enrolled and temporally split into development (
n
= 201) and validation (
n
= 73) cohorts. Multivariable logistic regression analyses were used to determine independent predictors of clinically significant PCa (csPCa) on cognitive MRTB, and the clinical, MRI, and combined models were established respectively. Area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses were assessed.
Results
Prostate imaging data and reporting system (PI-RADS) score, index lesion (IL) on the peripheral zone, age, and prostate-specific antigen density (PSAD) were independent predictors and included in the combined model. The combined model achieved the best discrimination (AUC 0.88) as compared to both the MRI model incorporated by PI-RADS score, IL level, and zone (AUC 0.86) and the clinical model incorporated by age and PSAD (AUC 0.70). The combined model also showed good calibration and enabled great net benefit. Applying the combined model as a reference for performing MRTB alone with a cutoff of 60% would reduce 43.8% of additional SB, while missing 2.9% csPCa.
Conclusions
The combined model based on clinical and mpMRI findings improved csPCa prediction and might be useful in making a decision about which patient could safely avoid unnecessary SB in addition to MRTB in biopsy-naïve patients.
Critical relevance statement
The combined model based on clinical and mpMRI findings improved csPCa prediction and might be useful in making a decision about which patient could safely avoid unnecessary SB in addition to MRTB in biopsy-naïve patients.
Key points
• Age, PSAD, PI-RADS score, and peripheral index lesion were independent predictors of csPCa.
• Risk models were used to predict the probability of detecting csPCa on cognitive MRTB.
• The combined model might reduce 43.8% of unnecessary SBs, while missing 2.9% csPCa.
Graphical Abstract
Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between ...metastatic and primary lesions are still unclear.
In this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions.
Paired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrent NF2 mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci.
Overall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.
Integrated optical filters based on microring resonators play a critical role in many applications, ranging from wavelength division multiplexing and switching to channel routing. Bandwidth tunable ...filters are capable of meeting the on-demand flexible operations in complex situations, due to their advantages of scalability, multi-functionality, and being energy-saving. Recent studies have investigated how parity-time (PT) symmetry coupled-resonant systems can be applied to the bandwidth-tunable filters. However, due to the trade-off between the bandwidth-tunable contrast ratio and insertion loss of the system, the bandwidth-tunable contrast ratio of this method is severely limited. Here, the bandwidth-tunable contrast ratio is defined as the maximum bandwidth divided by the minimum bandwidth. In this work, we show that a high bandwidth-tunable contrast ratio and low insertion loss of the system can be achieved simultaneously by increasing the coupling strength between the input port and the resonant. Theoretical analysis under different coupling states reveals that the low insertion loss can be obtained when the system initially operates at the over-coupling condition. A high bandwidth-tunable contrast ratio PT-symmetry band-pass filter with moderate insertion loss is shown on the Silicon platform. Our scheme provides an effective method to reduce the insertion loss of on-chip tunable filters, which is also applicable to the high-order cascaded microring systems.
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