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Lithium niobate Mach–Zehnder modulators (MZMs) with compact footprint and fast electro-optics (EO) responses are highly demanded for the next-generation optical interconnect systems. Here, we demonstrate slow-light (SL) effect using a coupled Bragg resonator structure on the thin-film lithium niobate (TFLN) platform, and an ultra-compact SL-MZM with length L of ∼370 μm is also constructed. The fabricated SL waveguides show a large optical passband width of ∼8 nm, an insertion loss of 2.9 dB, and a maximal optical group index of 7.50, corresponding to 3.4 times as large as that of regular TFLN rib waveguide. The fabricated SL-MZM exhibits a large EO bandwidth of >50 GHz in an operating wavelength band of ∼8 nm as well. High-speed OOK transmissions at data rates of 64 Gbit/s and 80 Gbit/s are successfully achieved. To our best knowledge, it is first time to build SL waveguides and compact SL-MZMs with large EO bandwidths of >50 GHz on the monolithic TFLN platform.

Background Stroke is one of the major public health problems affecting human health in current. Longitudinal check up data has accumulated a large amount of health information. However, the utilization rate of the longitudinal check up data is low and important information has not been fully extracted due to many problems such as missing data and small sample size, which brings difficulties to the effective prevention and control of common chronic diseases. Objective To explore the risk factors of stroke in check-up population based on Bayesian multivariate joint model, so as to provide a new approach for the analysis of risk factors for chronic diseases. Methods In this study, the data were collected from the Center for Health and Medicine, Xijing Hospital, Air Force Military Medical University from 2008 to 2015. Follow-up status: the follow up was conducted with the first occurrence of stroke as the outcome event and stopped at the occurrence of outcome event or ended when the collection of medical examination information was completed by 2015 if the outcome event did not occur. The interval between physical examinations was 1 year. The participants were divided into the stroke group and the non-stroke group according to whether stroke occurred during follow-up. Longitudinal variables observed in this study included total cholesterol (TC) , triglyceride (TG) , low density lipoprotein cholesterol (LDL-C) , high density lipoprotein cholesterol (HDL-C) , body mass index (BMI) and systolic blood pressure (SBP) . Multivariate Cox regression model was used to analyze the influence of baseline conditions on stroke outcome events. Bayesian multivariate joint model was used for analyzing the effect of longitudinal trajectory of TC, TG, LDL-C, HDL-C, BMI and SBP on the incidence of stroke during follow-up. Results A total of 234 subjects with 1 581 longitudinal follow-up records were included in this study, with the mean follow-up time of (7.4±1.2) years, of which 70 cases (29.9%) developed stroke during the follow-up. The results of multivariate Cox proportional hazards model showed that there was no effect of baseline values including TC, TG, LDL-C, HDL-C, BMI and SBP on the incidence of stroke (P>0.05) . The results of Bayesian multivariate joint model showed that the risk of stroke was 1.863 times higher for per longitudinal increase of 1 mmol/L TG level 〔95%CI (1.018, 3.294) , P=0.042〕 and 1.347 times higher for per longitudinal increase of 1 mmol/L LDL-C level〔95%CI (1.045, 1.863) , P=0.046〕. Conclusion The longitudinal increase of TG and LDL-C levels over time is a risk factor for stroke in check-up population. Bayesian multivariate joint model can be used to explore the risk factors of chronic diseases in check-up population.

In many regions across the world, hepatitis B virus (HBV) infection is still endemic and the transmission rate is much greater than majority of the known epidemic diseases. Numerous mathematical models (utilizing various differential operators) have been put forth over the past 20 years to understand the transmission mechanism of HBV in various nations and geographical areas. In this manuscript, an epidemic model with various novelties for capturing the dynamic of HBV while utilizing Caputo–Fabrizio fractional differential operator with asymptomatic carriers and vaccination effects is introduced. Initially, the model is formulated by using the ordinary derivative, and afterward, the fractional differential operator is applied to transform the model into arbitrary-ordered derivative. A few basic mathematical properties for the proposed integer-ordered model is presented. The existence of solution to the problem and its uniqueness of the fractional order model are established by transforming the problem into integral equations and then applying the standard results of fixed point theory. For boundedness and positivity of model’ solution is elaborated utilizing the techniques of fractional calculus. It is too much important to validate the theoretical findings through simulations; therefore, the solution curves of the model under consideration are displayed by using the well-known approach called the Mittag-Leffler. To show the behavior of the order of the operator on the dynamics of the disease, various graphical illustrations are presented at the end of the manuscript. By comparing the findings of the present study with the available literature, it is observed that fractional derivative is better to use than integer-order operator for capturing the realistic scenario of the disease.

Osteoblasts originate from mesenchymal stem cells (MSCs) and their maturation is regulated by numerous genes. However, specific genes that play decisive roles in osteoblast maturation are not completely understood. Herein, we propose a new algorithm called SGCAL to identify sensitive gene combinations during osteoblast development and decode the regulatory roles of sensitive gene combinations in cell development. In contrast to conventional gene identification algorithms, the SGCAL algorithm, which is based on a combination of ARNN-LNE iterative cycles, quantitatively evaluates the sensitivity of genes by analyzing the average network entropy before and after gene perturbation. We verified that osteoblast development is fundamentally regulated by an overall sensitive network formed by specific genes. Moreover, we explored the roles of these sensitive genes and their combinations in the transition time point of the initial state of network change. Our algorithm was validated on two independent mouse osteoblast development datasets, successfully identifying sensitive genes and their combinations in both datasets and revealing that gene combinations containing Col1a1 can exhibit significant sensitivity. This study demonstrated the universality of cell fate and network regulation, offering new insights and a theoretical basis for the treatment and repair of bone diseases An algorithm called SGCAL is proposed to check effectively the sensitive genes and their combination during osteoblast development. The gene combinations containing Col1a1 can exhibit significant sensitivity for the process of Osteoblasts. We perturb expression data to discern the sensitivity of the maker gene by measuring the network entropy. [ABSTRACT FROM AUTHOR]

The formation of spatial patterns is an important issue in reaction–diffusion systems. Previous studies have mainly focused on the spatial patterns in reaction–diffusion models equipped with symmetric diffusion (such as normal or fractional Laplace diffusion), namely, assuming that spatial environments of the systems are homogeneous. However, the complexity and heterogeneity of spatial environments of biochemical reactions in vivo can lead to asymmetric diffusion of reactants. Naturally, there arises an open question of how the asymmetric diffusion affects dynamical behaviors of biochemical reaction systems. To answer this, we build a general asymmetric Lévy diffusion model based on the theory of a continuous time random walk. In addition, we investigate the two-species Brusselator model with asymmetric Lévy diffusion, and obtain a general condition for the formation of Turing and wave patterns. More interestingly, we find that even though the Brusselator model with symmetric diffusion cannot produce steady spatial patterns for some parameters, the asymmetry of Lévy diffusion for this model can produce wave patterns. This is different from the previous result that wave instability requires at least a three-species model. In addition, the asymmetry of Lévy diffusion can significantly affect the amplitude and frequency of the spatial patterns. Our results enrich our knowledge of the mechanisms of pattern formation. [ABSTRACT FROM AUTHOR]

Background: In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. Methods: This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60–65 Gy in 25–28 fractions to primary lesions and positive lymph nodes; 50–50.4 Gy in 25–28 fractions to the pelvis) or intensity-modulated radiotherapy (50–50.4 Gy in 25–28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. Discussion: Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. Trial registration: The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024). [ABSTRACT FROM AUTHOR]

The use of proton therapy (PT) in early-stage non-small cell lung cancer (ES-NSCLC) remains controversial, with insufficient evidence to determine its superiority over photon therapy (XRT). We conducted a systematic review of PT trials in ES-NSCLC, analyzing dosimetry, efficacy, and safety across to inform clinical decision-making. Our study showed that PT reduced lung and heart dosimetric parameters compared to XRT, with significant differences in lung V5, lung V10 and mean heart dose (MHD). In terms of efficacy, there were no significant differences in 1-year OS, 3-year OS and 3-year PFS between PT and XRT. For toxicity, no significant difference was observed in treatment-related adverse events (TRAEs) and radiation pneumonitis (RP). Single-arm analysis of PT found that V5, V10, V20 of lung and heart V5 were 13.4%, 11.3%, 7.9% and 0.7%, respectively. The mean lung dose and MHD were 4.15 Gy and 0.17 Gy, respectively. The single-arm pooled 1-, 2-, 3- and 5-year OS rates for PT were 95.3%, 82.5%, 81.3% and 69.3%, respectively. PFS rate and local control rate at 3 years were 68.1% and 91.2%, respectively. The rates of TRAEs of grade ≥ 3 and grade ≥ 2 were 2.8% and 19.8%, respectively. The grade ≥ 2 RP occurred at a rate of 8.7%. In conclusion, PT had acceptable efficacy and safety, and was better at protecting organs at risk than XRT in ES-NSCLC. However, the survival and safety benefit of PT was not significant compared to XRT. [ABSTRACT FROM AUTHOR]

Background: The progress of the cell cycle of yeast involves the regulatory relationships between genes and the interactions proteins. However, it is still obscure which type of protein plays a decisive role in regulation and how to identify the vital nodes in the regulatory network. To elucidate the sensitive node or gene in the progression of yeast, here, we select 8 crucial regulatory factors from the yeast cell cycle to decipher a specific network and propose a simple mixed K2 algorithm to identify effectively the sensitive nodes and genes in the evolution of yeast. Results: Considering the multivariate of cell cycle data, we first utilize the K2 algorithm limited to the stationary interval for the time series segmentation to measure the scores for refining the specific network. After that, we employ the network entropy to effectively screen the obtained specific network, and simulate the gene expression data by a normal distribution approximation and the screened specific network by the partial least squares method. We can conclude that the robustness of the specific network screened by network entropy is better than that of the specific network with the determined relationship by comparing the obtained specific network with the determined relationship. Finally, we can determine that the node CDH1 has the highest score in the specific network through a sensitivity score calculated by network entropy implying the gene CDH1 is the most sensitive regulatory factor. Conclusions: It is clearly of great potential value to reconstruct and visualize gene regulatory networks according to gene databases for life activities. Here, we present an available algorithm to achieve the network reconstruction by measuring the network entropy and identifying the vital nodes in the specific nodes. The results indicate that inhibiting or enhancing the expression of CDH1 can maximize the inhibition or enhancement of the yeast cell cycle. Although our algorithm is simple, it is also the first step in deciphering the profound mystery of gene regulation. [ABSTRACT FROM AUTHOR]

Considering the time delay originating from a certain incubation period or asymptomatic state, we propose a delayed epidemic system within the noisy environment of the hepatitis B virus to analyze the mechanism of disease transmission and elucidate how to control it by applying the strategy of vaccinating and treatment. Applying stochastic Lyapunov functional theory, we first construct an integral Lyapunov function coupling the time delay and stochastic fluctuation to investigate whether there exists a unique global solution to the model. Next, we yield the threshold condition for controlling disease extinction, and persistence, as well as its stationary distribution. Governed by these sufficient conditions, we study the existence of optimal control solutions in deterministic and stochastic scenarios to uncover how to accelerate disease extinction through vaccination and treatment. The results indicate that the time delay will prolong the duration of the disease for the original system but suppress the peak value of HBV in the controlled system. Finally, we verify the versatility of theoretical results by numerical simulations. These results will effectively decipher the importance of the time delay in the control of hepatitis B. [ABSTRACT FROM AUTHOR]

As ferroelectric materials, lithium tantalate and lithium niobate share similar material characteristics, such as a high Pockels effect and nonlinear optical coefficients. When compared to lithium niobate, lithium tantalate offers a higher optical damage threshold, a broader transparent window, and lower birefringence, making it a promising candidate for high-performance electro-optical photonic integrated devices. In this study, we design and successfully fabricate micro-ring resonators on an acoustic-grade lithium-tantalate-on-insulator wafer, demonstrating their tunability and dynamic modulation capabilities. Experimental results indicate that the achieved thin-film lithium tantalate based micro-ring resonator exhibits an intrinsic Q-factor of 8.4 × 105, corresponding to a waveguide propagation loss of 0.47 dB/cm and a tuning efficiency of 1.94 pm/V. More importantly, as compared to those based on thin-film lithium niobate, a much weaker photorefractive effect and drift phenomenon around the 1550 nm wavelength under a direct-current drive are observed in the present fabricated thin-film lithium tantalate micro-rings with a silicon oxide over-cladding and a tuning electrode on top. [ABSTRACT FROM AUTHOR]

Chemical reactions are embedded in spatiotemporal fluctuations instead of a constant environment. Here, we aimed to assess reaction–diffusion (RD) with dichotomous noise‐controlling system parameters in the Brusselator and examine the effect of these fluctuations on the dynamic behavior of chemical reactions. By performing a multiscale perturbation analysis, we demonstrated that the correlated noise can broaden the Turing region even if molecular memory (autocorrelation time) exists. However, for small noise, short‐term memory promotes Turing instability. The instability of the Brusselator is determined by the noise strength, which belongs to the optimal region if the diffusion coefficient is fixed. Turing pattern selection and stability are also governed by the dynamic character of the amplitude equation, and the entire Turing instability region shifts to the right in the phase space with noise perturbation. Finally, numerical simulations validate the theoretical derivation that correlated noise can amplify Turing pattern formation to maintain distinct patterns. [ABSTRACT FROM AUTHOR]

Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive soft tissue tumor that predominantly affects the abdominal and pelvic regions of adolescent males. This case report presents our clinical experience of treating a 33-year-old male with multifocal peritoneal DSRCT using fan beam computed tomography-guided adaptive radiotherapy (FBCT-gART). The patient presented with abdominal pain and was diagnosed with DSRCT following imaging and biopsy. Despite initial treatment with surgery, chemotherapy, and targeted therapy, the patient experienced multifocal peritoneal recurrence. Due to the considerable mobility of the abdominal tumors and the associated risks to adjacent critical organs, the patient underwent daily online FBCT-gART. The prescribed dose regimen was 54 Gy delivered in 27 fractions at 2 Gy per fraction; however, the patient ultimately received only 25 treatments for personal reasons. This case report evaluates the technical workflow of using FBCT-gART for DSRCT and discusses its dosimetric advantages over non-adaptive radiotherapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Wang et al.)

We present an electro-optic (EO) switch with ultralow DC drift on a thin-film lithium tantalate (TFLT) platform, even with SiO 2 cladding and without post-annealing processes. The flat V π and EO responses have been measured across various driving frequencies, input optical powers, and temperatures. Stable optical switching is achievable in the low-frequency range. The experiment also demonstrated superior long-term stability (up to 2 h) compared to thin-film lithium niobate optical switches under similar on-chip optical power conditions (around -8 dBm).

Thin-film lithium niobate (TFLN) is a promising integrated photonics platform but currently lacks a polarization-insensitive multimode interference (MMI) coupler, a crucial component for polarization-related optical communication applications such as polarization management, polarization-division multiplexing, and polarization-insensitive modulation systems. This paper presents a novel, to the best of our knowledge, approach by rotating the MMI structure on an anisotropic x-cut TFLN at specific angles to compensate for the difference in the beat length between the two polarizations. A polarization-insensitive 1 × 2 MMI coupler is experimentally achieved with measured transmittances of -2.5 to -4 dB for both output ports and polarization modes in the wavelength range of 1520-1580 nm.

The recent development of tough tissue adhesives has stimulated intense interests among material scientists and medical doctors. However, these adhesives have seldom been tested in clinically demanding surgeries. Here we demonstrate adhesive anastomosis in organ transplantation. Anastomosis is commonly conducted by dense sutures and takes a long time, during which all the vessels are occluded. Prolonged occlusion may damage organs and even cause death. We formulate a tough, biocompatible, bioabsorbable adhesive that can sustain tissue tension and pressurized flow. We expose the endothelial surface of vessels onto a gasket, press two endothelial surfaces to the adhesive using a pair of magnetic rings, and reopen the bloodstream immediately. The time for adhesive anastomosis is shortened compared to the time for sutured anastomosis. We have achieved adhesive anastomosis of a great vein in transplanting the liver of a pig. After the surgery, the adhesive is absorbed, the vein heals, and the pig lives for over one month., Competing Interests: The authors declare no competing financial interests., (© 2021 The Authors.)

Background: Effective traction and dissection of the esophagus are key steps during thoracoscopic esophagectomy. In traditional methods, a separate trocar for the traction instruments or thoracic punctures are adopted to externally retract the esophageal loop. However, both methods bring about chest wall damage that is associated with increased morbidity and mortality. The magnetic anchoring and traction system can not only achieve exposure and pulling multi-directional flexible but also reduce the number of transthoracic ports and trocars used, and then avoid the chopstick effect in surgery. We aimed to verify the feasibility and safety of a self-designed magnetic anchoring and traction system in assisted thoracoscopic esophagectomy., Methods: Ten healthy pigs were used as the experimental objects. A magnetic anchoring and traction system composed of an external unit and internal unit was designed, then the requirements and stress characteristics of esophageal pulling and exposure during thoracoscopic esophagectomy were analyzed. The internal unit was introduced through the 5th intercostal space port and was secured to the right wall of the esophagus, the external unit was placed on the surface of the chest wall to allow pairing with the internal unit. The external unit was moved on the chest wall to help exposing operative field., Results: Ten pigs underwent a 3-port thoracoscopic esophagectomy using a magnetic anchoring and traction technique, and all operations were successful. The system provided adequate traction force to pull the esophagus. The external unit could move freely outside the chest wall, enabling suitable positioning of the esophagus for dissection., Conclusions: The novel magnetic anchoring and traction system in thoracoscopic esophagectomy is safe and feasible, and has the potential for clinical application., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-5359). The authors report that this work was supported by the Fundamental Research Funds for the Central University of China (No. xzd012020026), the Funds for Key Research and Development Program Projects in Shaanxi Province, China (No. 2019SF-014), and Bethune Charitable Foundation (No. HZB-20181119-070). The authors have no other conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)