Search Results
Photodynamic Opening of the Blood–Brain Barrier and the Meningeal Lymphatic System: The New Niche in Immunotherapy for Brain Tumors
2022, Semyachkina-Glushkovskaya, Oxana, Terskov, Andrey, Khorovodov, Alexander, Telnova, Valeria, Blokhina, Inna, Saranceva, Elena, Kurths, Jürgen
Photodynamic therapy (PDT) is a promising add-on therapy to the current standard of care for patients with glioblastoma (GBM). The traditional explanation of the anti-cancer PDT effects involves the PDT-induced generation of a singlet oxygen in the GBM cells, which causes tumor cell death and microvasculature collapse. Recently, new vascular mechanisms of PDT associated with opening of the blood–brain barrier (OBBB) and the activation of functions of the meningeal lymphatic vessels have been discovered. In this review, we highlight the emerging trends and future promises of immunotherapy for brain tumors and discuss PDT-OBBB as a new niche and an important informative platform for the development of innovative pharmacological strategies for the modulation of brain tumor immunity and the improvement of immunotherapy for GBM.
Basins of attraction of chimera states on networks
2022, Li, Qiang, Larosz, Kelly C., Han, Dingding, Ji, Peng, Kurths, Jürgen
Networks of identical coupled oscillators display a remarkable spatiotemporal pattern, the chimera state, where coherent oscillations coexist with incoherent ones. In this paper we show quantitatively in terms of basin stability that stable and breathing chimera states in the original two coupled networks typically have very small basins of attraction. In fact, the original system is dominated by periodic and quasi-periodic chimera states, in strong contrast to the model after reduction, which can not be uncovered by the Ott-Antonsen ansatz. Moreover, we demonstrate that the curve of the basin stability behaves bimodally after the system being subjected to even large perturbations. Finally, we investigate the emergence of chimera states in brain network, through inducing perturbations by stimulating brain regions. The emerged chimera states are quantified by Kuramoto order parameter and chimera index, and results show a weak and negative correlation between these two metrics.
Data-Driven Discovery of Stochastic Differential Equations
2022, Wang, Yasen, Fang, Huazhen, Jin, Junyang, Ma, Guijun, He, Xin, Dai, Xing, Yue, Zuogong, Cheng, Cheng, Zhang, Hai-Tao, Pu, Donglin, Wu, Dongrui, Yuan, Ye, Gonçalves, Jorge, Kurths, Jürgen, Ding, Han
Stochastic differential equations (SDEs) are mathematical models that are widely used to describe complex processes or phenomena perturbed by random noise from different sources. The identification of SDEs governing a system is often a challenge because of the inherent strong stochasticity of data and the complexity of the system's dynamics. The practical utility of existing parametric approaches for identifying SDEs is usually limited by insufficient data resources. This study presents a novel framework for identifying SDEs by leveraging the sparse Bayesian learning (SBL) technique to search for a parsimonious, yet physically necessary representation from the space of candidate basis functions. More importantly, we use the analytical tractability of SBL to develop an efficient way to formulate the linear regression problem for the discovery of SDEs that requires considerably less time-series data. The effectiveness of the proposed framework is demonstrated using real data on stock and oil prices, bearing variation, and wind speed, as well as simulated data on well-known stochastic dynamical systems, including the generalized Wiener process and Langevin equation. This framework aims to assist specialists in extracting stochastic mathematical models from random phenomena in the natural sciences, economics, and engineering fields for analysis, prediction, and decision making.
Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System
2022, Semyachkina-Glushkovskaya, Oxana, Shirokov, Alexander, Blokhina, Inna, Telnova, Valeria, Vodovozova, Elena, Alekseeva, Anna, Boldyrev, Ivan, Fedosov, Ivan, Dubrovsky, Alexander, Khorovodov, Alexandr, Terskov, Andrey, Evsukova, Arina, Elovenko, Daria, Adushkina, Viktoria, Tzoy, Maria, Agranovich, Ilana, Kurths, Jürgen, Rafailov, Edik
The blood–brain barrier (BBB) limits the delivery of majority of cancer drugs and thereby complicates brain tumor treatment. The nasal-brain-lymphatic system is discussed as a pathway for brain drug delivery overcoming the BBB. However, in most cases, this method is not sufficient to achieve a therapeutic effect due to brain drug delivery in a short distance. Therefore, it is necessary to develop technologies to overcome the obstacles facing nose-to-brain delivery of promising pharmaceuticals. In this study, we clearly demonstrate intranasal delivery of liposomes to the mouse brain reaching glioblastoma (GBM). In the experiments with ablation of the meningeal lymphatic network, we report an important role of meningeal pathway for intranasal delivery of liposomes to the brain. Our data revealed that GBM is characterized by a dramatic reduction of intranasal delivery of liposomes to the brain that was significantly improved by near-infrared (1267 nm) photostimulation of the lymphatic vessels in the area of the cribriform plate and the meninges. These results open new perspectives for non-invasive improvement of efficiency of intranasal delivery of cancer drugs to the brain tissues using nanocarriers and near-infrared laser-based therapeutic devices, which are commercially available and widely used in clinical practice.
Predicting the data structure prior to extreme events from passive observables using echo state network
2022, Banerjee, Abhirup, Mishra, Arindam, Dana, Syamal K., Hens, Chittaranjan, Kapitaniak, Tomasz, Kurths, Jürgen, Marwan, Norbert
Extreme events are defined as events that largely deviate from the nominal state of the system as observed in a time series. Due to the rarity and uncertainty of their occurrence, predicting extreme events has been challenging. In real life, some variables (passive variables) often encode significant information about the occurrence of extreme events manifested in another variable (active variable). For example, observables such as temperature, pressure, etc., act as passive variables in case of extreme precipitation events. These passive variables do not show any large excursion from the nominal condition yet carry the fingerprint of the extreme events. In this study, we propose a reservoir computation-based framework that can predict the preceding structure or pattern in the time evolution of the active variable that leads to an extreme event using information from the passive variable. An appropriate threshold height of events is a prerequisite for detecting extreme events and improving the skill of their prediction. We demonstrate that the magnitude of extreme events and the appearance of a coherent pattern before the arrival of the extreme event in a time series affect the prediction skill. Quantitatively, we confirm this using a metric describing the mean phase difference between the input time signals, which decreases when the magnitude of the extreme event is relatively higher, thereby increasing the predictability skill.
Interconnection between the Indian and the East Asian summer monsoon: Spatial synchronization patterns of extreme rainfall events
2022, Gupta, Shraddha, Su, Zhen, Boers, Niklas, Kurths, Jürgen, Marwan, Norbert, Pappenberger, Florian
A deeper understanding of the intricate relationship between the two components of the Asian summer monsoon (ASM)—the Indian summer monsoon (ISM) and the East Asian summer monsoon (EASM)—is crucial to improve the subseasonal forecasting of extreme precipitation events. Using an innovative complex network-based approach, we identify two dominant synchronization pathways between ISM and EASM—a southern mode between the Arabian Sea and southeastern China occurring in June, and a northern mode between the core ISM zone and northern China which peaks in July—and their associated large-scale atmospheric circulation patterns. Furthermore, we discover that certain phases of the Madden–Julian oscillation and the lower frequency mode of the boreal summer intraseasonal oscillation (BSISO) seem to favour the overall synchronization of extreme rainfall events between ISM and EASM while the higher-frequency mode of the BSISO is likely to support the shifting between the modes of ISM–EASM connection.
Music improves the therapeutic effects of bevacizumab in rats with glioblastoma: Modulation of drug distribution to the brain
2022, Semyachkina-Glushkovskaya, Oxana, Diduk, Sergey, Anna, Eroshova, Elina, Dosadina, Artem, Kruglov, Khorovodov, Alexander, Shirokov, Alexander, Fedosov, Ivan, Dubrovsky, Alexander, Blokhina, Inna, Terskov, Andrey, Navolokin, Nikita, Evsukova, Arina, Elovenko, Daria, Adushkina, Viktoria, Kurths, Jürgen
Background: The development of new methods for modulation of drug distribution across to the brain is a crucial step in the effective therapies for glioblastoma (GBM). In our previous work, we discovered the phenomenon of music-induced opening of the blood-brain barrier (OBBB) in healthy rodents. In this pilot study on rats, we clearly demonstrate that music-induced BBB opening improves the therapeutic effects of bevacizumab (BZM) in rats with GBM via increasing BZM distribution to the brain along the cerebral vessels. Methods: The experiments were performed on Wistar male rats (200-250 g, n=161) using transfected C6-TagRFP cell line and the loud rock music for OBBB. The OBBB was assessed by spectrofluorometric assay of Evans Blue (EB) extravasation and confocal imaging of fluorescent BZM (fBZM) delivery into the brain. Additionally, distribution of fBZM and Omniscan in the brain was studied using fluorescent and magnetic resonance imaging (MRI), respectively. To analyze the therapeutic effects of BZM on the GBM growth in rats without and with OBBB, the GBM volume (MRI scans), as well as immunohistochemistry assay of proliferation (Ki67 marker) and apoptosis (Bax marker) in the GBM cells were studied. The Mann-Whitney-Wilcoxon test was used for all analysis, the significance level was p < 0.05, n=7 in each group. Results: Our finding clearly demonstrates that music-induced OBBB increases the delivery of EB into the brain tissues and the extravasation of BZM into the brain around the cerebral vessels of rats with GBM. Music significantly increases distribution of tracers (fBZM and Omniscan) in the rat brain through the pathways of brain drainage system (perivascular and lymphatic), which are an important route of drug delivery into the brain. The music-induced OBBB improves the suppressive effects of BZM on the GBM volume and the cellular mechanisms of tumor progression that was accompanied by higher survival among rats in the GBM+BZM+Music group vs. other groups. Conclusion: We hypothesized that music improves the therapeutic effects of BZM via OBBB in the normal cerebral vessels and lymphatic drainage of the brain tissues. This contributes better distribution of BZM in the brain fluids and among the normal cerebral vessels, which are used by GBM for invasion and co-opt existing vessels as a satellite tumor form. These results open the new perspectives for an improvement of therapeutic effects of BZM via the music-induced OBBB for BZM in the normal cerebral vessels, which are used by GBM for migration and progression.