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BackgroundDue to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed therapy (MDT). There are two types of radiation based MDT applied when treating oligometastatic disease: (1) stereotactic body radiation therapy (SBRT) generally used for bone metastases; or (2) SBRT for isolated nodal oligometastases combined with prophylactic elective nodal radiotherapy. This review aims to summarize current evidence data, which may shed light on the optimal management of this heterogeneous group of patients.MethodsA systematic review of the Medline database through PubMed was performed according to PRISMA guidelines. All relevant studies published up to November 2020 were identified and screened. Fifty-six titles were included. Besides outcome parameters, different prognostic and predictive factors were assessed, including site of metastases, time between primary treatment and MDT, use of systemic therapies, hormone sensitivity, as well as pattern of recurrence.FindingsEvidence consists largely of retrospective case series and no consistent precise definition of oligometastasis exists, however, most investigators seem to acknowledge the need to distinguish between patients presenting with what is frequently called "synchronous" versus "metachronous" oligometastatic disease. Available data on radiotherapy as MDT demonstrate high local control rates and a small but relevant proportion of patients without progressive disease after 2 years. This holds true for both hormone sensitive and castration resistant prostate cancer diseases. The use of 68Ga-PSMA PET/CT for staging increased dramatically. Radiation doses and field sizes varied considerably among the studies. The search for relevant prognostic and predictive factors is ongoing.ConclusionsTo our best knowledge this review on oligometastatic prostate cancer included the largest number of original articles. It demonstrates the therapeutic potential and challenges of MDT for oligometastatic prostate cancer. Prospective studies are under way and will provide further high-level evidence.

Electro-osmotic flow (EOF) is a phenomenon where fluid motion occurs in porous materials or micro/nano-channels when an external electric field is applied. In the particular example of single-molecule electrophoresis using single nanopores, the role of EOF on the translocation velocity of the analyte molecule through the nanopore is not fully understood. The complexity arises from a combination of effects from hydrodynamics in restricted environments, electrostatics emanating from charge decorations and geometry of the pores. We address this fundamental issue using the Poisson–Nernst–Planck and Navier–Stokes (PNP–NS) equations for cylindrical solid-state nanopores and three representative protein nanopores (α-hemolysin, MspA, and CsgG). We present the velocity profiles inside the nanopores as a function of charge decoration and geometry of the pore and applied electric field. We report several unexpected results: (a) The apparent charges of the protein nanopores are different from their net charge and the surface charge of the whole protein geometry, and the net charge of inner surface is consistent with the apparent charge. (b) The fluid velocity depends non-monotonically on voltage. The three protein nanopores exhibit unique EOF and velocity–voltage relations, which cannot be simply deduced from their net charge. Furthermore, effective point mutations can significantly change both the direction and the magnitude of EOF. The present computational analysis offers an opportunity to further understand the origins of the speed of transport of charged macromolecules in restricted space and to design desirable nanopores for tuning the speed of macromolecules through nanopores. [ABSTRACT FROM AUTHOR]

[Objective] This study aims to investigate the physical properties of electroosmotic flow in protein nanopores using numerical simulations, particularly under varying electric field strengths and solution salt concentrations. This research is remarkable because electroosmosis is an efficient and controllable method for liquid transport, which is widely utilized in microfluidics, biomedical detection, chemical analysis, soil remediation, and water treatment, especially in high-throughput gene sequencing. By systematically examining the physical properties of nanoconfined electroosmotic flow, these applications can be optimized to enhance their performance and efficiency. However, owing to the challenges associated with nanoscale research, it is extremely difficult to directly measure the properties of electroosmotic flow in experiments. Therefore, employing theoretical and numerical simulation methods has emerged as an effective approach to address this issue. This study aims to gain a deeper understanding of the dynamic characteristics of electroosmotic flow in protein nanopores through numerical simulations, offering theoretical support and technical guidance for molecular separation and biomedical detection. [Methods] This study employed a coupled model of the Poisson-Nernst-Planck and Navier-Stokes equations to numerically simulate the electroosmotic flow in protein nanopores using the finite element method. This research focused on charged protein nanopores, considering the effects of varying electric field strengths and solution salt concentrations. The model was established by coupling the Poisson-Nernst-Planck and Navier-Stokes equations to obtain a mathematical representation of the nanopore system. The proposed model includes charged nanopores, electrolyte solutions containing free ions and water molecules, and external electric fields applied to both sides of the nanopore. [Results] The distribution of electroosmotic velocity and electric field strength within protein nanopores is highly uneven and substantially influenced by external potential and solution salt concentration. The specific findings are as follows: 1) Electroosmotic flow velocity distribution: in environments with high salt concentrations, the electroosmotic flow velocity considerably increases, particularly in the central region of the nanopores. The velocity profile of the electroosmotic flow along the z-axis exhibits nonlinear characteristics, with the velocity varying from the center to both ends of the nanopore. 2) Electric field intensity distribution: The electric field intensity is highest in the central region of the nanopore and shows notable nonuniformity in the surrounding areas. The electric field strength gradient greatly influences the distribution of electroosmotic flow velocity, with an increase in electric field strength leading to a substantial increase in the electroosmotic flow velocity in the central nanopore. 3) Salt concentration effect: As the salt concentration in the solution increases, the electroosmotic flow rate rises remarkably, and the velocity curve becomes steeper, particularly in the central nanopores, indicating that the electroosmotic flow rate is directly related to the ionic strength of the solution, with high salt concentrations promoting the passage of more ions through the nanopores under the influence of an electric field and enhancing electroosmotic flow. These findings deepen our understanding of the dynamics of electroosmotic flow at the nanoscale and provide a theoretical foundation for optimizing the performance of nanopore-based sensing and separation devices. [Conclusions] This study systematically investigated the electroosmotic characteristics of protein nanopores under varying potentials and salt concentrations using numerical simulations. Results indicate that the nonuniformity of electroosmotic flow velocity and electric field distribution is a key factor in determining electroosmotic flow characteristics. The electric field strength and solution salt concentration considerably affect the electroosmotic flow rate, with high salt concentration and electric field strength leading to a substantial increase in the flow rate within nanopores. By precisely controlling the electric field strength and distribution, the behavior of the electroosmotic flow can be effectively manipulated, which is crucial for optimizing the performance of nanopores in molecular separation and biomedical detection. These research findings offer deeper insights into the electrical properties within nanopores and underscore their potential applications in molecular separation and biomedical detection. In summary, this study offers theoretical support and methodological guidance for optimizing nanopore-based technologies, demonstrating notable application value. Future research can further explore the relationship between the structural characteristics and electroosmotic behavior of different protein nanopores, expanding their applications across various fields. [ABSTRACT FROM AUTHOR]

On-ramp control is an effective approach for alleviating traffic congestion on highways. However, there is still a lack of on-ramp control approaches applicable to large regional highway networks. Here, we develop a targeted on-ramp control approach applicable to regional highway networks by taking advantage of the vehicle source information, which pinpoints the on-ramps contributing major traffic flow to the highway bottleneck. Furthermore, a combined and tunable controlling index is proposed to enhance the equity of the generated traffic control scheme. The proposed on-ramp control approach is validated on an actual large highway network using actual travel demand data. Results indicate that the proposed approach can well mitigate the traffic congestion of highway bottleneck while at the same time enhancing the equity and practicability of the generated traffic control scheme. [ABSTRACT FROM AUTHOR]

On-ramp control is an effective way to mitigate traffic congestion in freeways. In this study, a traffic control approach is developed based on the OD data of a regional freeway to alleviate the traffic overload in freeway bottlenecks. We first locate the major driver sources of the freeway bottlenecks and identify the on-ramps for implementing the traffic control schemes. Next, the differential evolution algorithm is employed to calculate the optimal control time at each traffic control on-ramp. The results indicate that the major driver sources of the freeway bottlenecks are limited. Traffic congestion in the freeway bottlenecks can be effectively mitigated by adaptively controlling the waiting time of vehicles at the on-ramps of their major driver sources., Author(s): Minglun Li [1]; Hu Yang [1]; Bao Guo [1]; Jianjun Dai [2]; Pu Wang (corresponding author) [1] 1. Introduction In the past few decades, freeway congestion has become a [...]