Data-driven stochastic model for cross-interacting processes with different time scales.

In this work, we propose a new data-driven method for modeling cross-interacting processes with different time scales represented by time series with different sampling steps. It is a generalization of a nonlinear stochastic model of an evolution operator based on neural networks and designed for the case of time series with a constant sampling step. The proposed model has a more complex structure. First, it describes each process by its own stochastic evolution operator with its own time step. Second, it takes into account possible nonlinear connections within each pair of processes in both directions. These connections are parameterized asymmetrically, depending on which process is faster and which process is slower. They make this model essentially different from the set of independent stochastic models constructed individually for each time scale. All evolution operators and connections are trained and optimized using the Bayesian framework, forming a multi-scale stochastic model. We demonstrate the performance of the model on two examples. The first example is a pair of coupled oscillators, with the couplings in both directions which can be turned on and off. Here, we show that inclusion of the connections into the model allows us to correctly reproduce observable effects related to coupling. The second example is a spatially distributed data generated by a global climate model running in the middle 19th century external conditions. In this case, the multi-scale model allows us to reproduce the coupling between the processes which exists in the observed data but is not captured by the model constructed individually for each process.

Applying interval stability concept to empirical model of middle Pleistocene transition.

Interval stability is a novel method for the study of complex dynamical systems, allowing for the estimation of their stability to strong perturbations. This method describes how large perturbation should be to disrupt the stable dynamical regime of the system (attractor). In our work, interval stability is used for the first time to study the properties of a real natural system: to analyze the stability of the earth's climate system during the last 2.6×106 years. The main abrupt shift in global climate during this period is the middle Pleistocene transition (MPT), which occurred about 1×106 years ago as a change of the periodicity of glacial cycles from 41 to 100 kyr. On the basis of the empirical nonlinear stochastic model proposed in our recent work, we demonstrate that the global climate stability to any perturbations decreases throughout the Pleistocene period (including the MPT), enhancing its response to fast (with a millennial scale or less) internal disturbances.

Forced signal and predictability in a prototype climate model: Implications for fingerprinting based detection in the presence of multidecadal natural variability.

Advanced numerical models used for climate prediction are known to exhibit biases in their simulated climate response to variable concentrations of the atmospheric greenhouse gases and aerosols that force a non-uniform, in space and time, secular global warming. We argue here that these biases can be particularly pronounced due to misrepresentation, in these models, of the multidecadal internal climate variability characterized by large-scale, hemispheric-to-global patterns. This point is illustrated through the development and analysis of a prototype climate model comprised of two damped linear oscillators, which mimic interannual and multidecadal internal climate dynamics and are set into motion via a combination of stochastic driving, representing weather noise, and deterministic external forcing inducing a secular climate change. The model time series are paired with pre-specified patterns in the physical space and form, conceptually, a spatially extended time series of the zonal-mean near-surface temperature, which is further contaminated by a spatiotemporal noise simulating the rest of climate variability. The choices of patterns and model parameters were informed by observations and climate-model simulations of the 20th century near-surface air temperature. Our main finding is that the intensity and spatial patterns of the internal multidecadal variability associated with the slow-oscillator model component greatly affect (i) the ability of modern pattern-recognition/fingerprinting methods to isolate the forced response of the climate system in the 20th century ensemble simulations and (ii) climate-system predictability, especially decadal predictability, as well as the estimates of this predictability using climate models in which the internal multidecadal variability is underestimated or otherwise misrepresented.

[Mathematical modeling of high-flow extra-intracranial bypass in the treatment of a complex cerebral aneurysm]. / Matematicheskoe modelirovanie obkhodnogo vysokopotochnogo ekstra-intrakranial'nogo shuntirovaniya pri lechenii slozhnoi tserebral'noi anevrizmy.

BACKGROUND: Intracranial aneurysms (IAs) pose a high risk of spontaneous subarachnoid hemorrhage. In the most complex cases, the only way to exclude the aneurysm from the circulation is to perform a high-flow extracranial-to-intracranial bypass, thus creating a new bloodstream. This avoids severe ischemic complications; however, it requires careful consideration of individual anatomy and hemodynamic parameters. Computational fluid dynamics (CFD) can be of great help in planning such a surgery by creating 3D patient-specific models of cerebral circulation. OBJECTIVE: Assessment of the perspectivity of high-flow extracranial-to-intracranial bypass planning using computational modeling. MATERIAL AND METHODS: In this research work, we have applied the CFD methods to a patient with a giant thrombosed IA of the internal carotid artery (ICA). Preoperative CTA images and Gamma Multivox workstation were used to create a 3D model with current geometry and three additional models: Normal anatomy (no IA), Occlusion (with ligated ICA), Virtual bypass (with bypass and ligated ICA). The postoperative data were also available. Boundary conditions were based on PC-MRI measurements. Calculation of hemodynamics was conducted with a finite element package ANSYS Workbench 19. RESULTS: The results demonstrated an increase in the blood flow on the affected side by more than 70% after the virtual surgery and uniformity of flow distribution between the affected and contralateral sides, indicating that the treatment is likely to be efficient. Later, postoperative data confirmed that. CONCLUSION: The study showed that virtual preoperative CFD modeling could significantly simplify and improve surgical planning.

Evaluation of the Fractional Flow Reserve by Computer Tomography Data: Comparison of the Calculated Parameters with the Results of Invasive Measurements.

Aim      To create a three-dimensional mathematical model of coronary flow in patients with ischemic heart disease based on findings of computed tomography angiography (CTA) with subsequent calculation of the fractional flow reserve (FFRCTA) and comparison of estimated FFRCTA with FFR reference values measured by coronary angiography (CAG).Material and methods  The study included 10 patients with borderline stenosis (50-75 %) as determined by CTA performed with a 640­slice CT-scanner. Based on CTA findings, three-dimensional mathematical models were constructed for further calculation of FFRCTA. Later, an invasive measurement of FFR (FFRINV) was performed for all patients. FFR values <0.8 indicated the hemodynamic significance of stenosis.Results FFRCTA and FFRINV values differed insignificantly in most cases (n=9) and exceeded 5% in only one case. The regression analysis showed a close correlation between estimated and invasively measured FFR values.Conclusion      Preliminary results showed a good consistency of calculated and measured FFR values. Therefore, further development of the method for mathematical modeling of three-dimensional blood flow by CTA findings is promising. Noninvasive evaluation of FFR is particularly relevant for analysis of hemodynamic significance of borderline (50-75 %) coronary stenoses.

[Falcine chondrosarcoma (case report and literature review)]. / Redkoe nablyudenie fal'ks-khondrosarkomy (klinicheskii primer i obzor literatury).

Chondrosarcoma is a rare malignancy composed of transformed cells of cartilage. This cancer is characterized by slow growth. Almost 75% of intracranial chondrosarcomas are observed on the skull base and grow from bone synchondrosis. Other rarer localizations of tumor are cerebral falx, tentorium cerebelli, vascular plexuses of the ventricles, fourth ventricle, convexital surface of the brain, etc. In this manuscript, we report treatment of patient with falcine chondrosarcoma.

The Role of Liquid-Liquid Phase Separation in the Compartmentalization of Cell Nucleus and Spatial Genome Organization.

Functional compartmentalization of the cell nucleus plays an important role in the regulation of genome activity by providing accumulation of enzymes and auxiliary factors in the reaction centers, such as transcription factories, Cajal bodies, speckles, etc. The mechanisms behind the nucleus functional compartmentalization are still poorly understood. There are reasons to believe that the key role in the nucleus compartmentalization belongs to the process of liquid-liquid phase separation. In this brief review, we analyze results of experimental studies demonstrating that liquid-liquid phase separation not only governs functional compartmentalization of the cell nucleus but also contributes to the formation of the 3D genomic architecture.

Analysis of 20th century surface air temperature using linear dynamical modes.

A Bayesian Linear Dynamical Mode (LDM) decomposition method is applied to isolate robust modes of climate variability in the observed surface air temperature (SAT) field. This decomposition finds the optimal number of internal modes characterized by their own time scales, which enter the cost function through a specific choice of prior probabilities. The forced climate response, with time dependence estimated from state-of-the-art climate-model simulations, is also incorporated in the present LDM decomposition and shown to increase its optimality from a Bayesian standpoint. On top of the forced signal, the decomposition identifies five distinct LDMs of internal climate variability. The first three modes exhibit multidecadal scales, while the remaining two modes are attributable to interannual-to-decadal variability associated with El Niño-Southern oscillation; all of these modes contribute to the secular climate signal-the so-called global stadium wave-missing in the climate-model simulations. One of the multidecadal LDMs is associated with Atlantic multidecadal oscillation. The two remaining slow modes have secular time scales and patterns exhibiting regional-to-global similarities to the forced-signal pattern. These patterns have a global scale and contribute significantly to SAT variability over the Southern and Pacific Oceans. In combination with low-frequency modulation of the fast LDMs, they explain the vast majority of the variability associated with interdecadal Pacific oscillation. The global teleconnectivity of the secular climate modes and their possible crucial role in shaping the forced climate response are the two key dynamical questions brought about by the present analysis.

[Echocardiography in the Assessment of Intraventricular Flows and Pressure Gradients in Obstructive Hypertrophic Cardiomyopathy].

Aim      To evaluate results of myomectomy by intraventricular pressure gradients (IVPG) and blood flows in patients with obstructive hypertrophic cardiomyopathy (OHCMP).Material and methods  The study included a total of 76 subjects, 42 patients with OHCMP (mean age, 39±7 years) and 34 healthy volunteers (mean age, 41±3 years). Prior to and after myomectomy, transthoracic echocardiography was performed and followed by digital image processing and calculation of IVPG and left ventricular (LV) vortex flows. Vector analysis was used to estimate the myocardial displacement rate (V), vortex flows, and LV apex-to-base pressure gradients.Results The study showed a dynamic decrease in the LV apex-to-outflow IVPG by more than 50% and recovery of myocardial contraction velocity in the septal area (р<0.001). The decrease in LV cavity pressure gradient serves as an index for evaluating the effectiveness of OHCMP correction. Myomectomy reduces the load on the myocardium and abolishes mitral valve regurgitation with improvement of LV blood flows as also evidenced by the dynamics of long axis velocity change during the cardiac cycle (dL / dt) and the myocardial contraction velocity (V).Conclusion      Effectiveness of the surgical correction of OHCMP is based on the dynamics of myocardial contraction velocities, vortex blood flows, and a decrease in LV apex-to-base IVPG.

[Analysis of local hemodynamics in complex aneurysms: an effect of the vessel arising from the dome or the neck]. / Issledovanie lokal'noi gemodinamiki v slozhnykh anevrizmakh: vliyanie sosuda, otkhodyashchego ot kupola ili sheiki.

BACKGROUND: Assessment of rupture risk for intracranial aneurysms (IA) is a particular challenge in cases of so-called complex aneurysms due to their variable morphometric characteristics. Arterial branch arising from the dome or the neck of IA is one of the least explored features of complex aneurysms. The methods of computational fluid dynamics may be valuable to determine the influence of arterial branches of IA on local hemodynamics. OBJECTIVE: To analyze local hemodynamics in IA with arterial branch arising from the cupola or the neck depending on the structure of the aneurysm and blood flow rate in the parent vessel. MATERIAL AND METHODS: CT angiography data of 4 patients with IA were estimated in this study. Modifications of the baseline 3D models of the aneurysms resulted 12 patient-specific models included into analysis. Hemodynamic calculations were made by using of ANSYS Workbench 19 software package. RESULTS: Wall shear stress (WSS) was characterized by the most significant variability, especially in case of sidewall aneurysms. Small cross-sectional area of additional branch in relation to the neck of IA was not followed by considerable changes of blood flow patterns inside IA after «virtual¼ removal of the vessel. Otherwise, the intensity of flows was drastically reduced. Simulation of high inlet flows demonstrated substantial variation of WSS in the area of jet. CONCLUSION: Additional arterial branch arising from the dome or the neck of IA significantly influences local hemodynamics. This influence depends on the localization of IA in relation to the parent vessel and the diameter of additional arterial branch.

[3D Genomics].

The development of new research methods significantly changed our views on the role that the 3D organization of the genome plays in its functional activity. It was found that the genome is subdivided into structural-functional units that restrict the area of enhancer action at the level of spatial organization. Spatial reconfiguration of an extended genomic fragment was identified as a potential mechanism that activates or represses various genes. Accordingly, a distorted spatial organization of the genome often causes various diseases, including cancer. All these observations contributed to the emergence of 3D genomics as a new avenue of research. The review summarizes the most important discoveries in the field of 3D genomics and discusses the directions of its further development.

[Advanced skull defect repair]. / Rekonstruktsiia obshirnogo kombinirovannogo defekta cherepa.

It is presented case report of successful repair of advanced combined defect of parietal-temporal-occipital scalp over one-half of skull vault with an excellent cosmetic result. To do this, the authors used a staged expander dermal tension, i.e. repeated stretching of the remaining scalp tissues combined with cranioplasty using mesh titanium implant.

[Giant thrombosed aneurysm of the pericallosal artery: clinical observation, literature review]. / Gigantskaia trombirovannaia anevrizma perikalleznoi arterii: klinicheskoe nabliudenie i obzor literatury.

Are characterized by Distal giant aneurysms of the anterior cerebral artery are an extremely rare pathology. There are less than 40 cases of this disease described in literature. OBJECTIVE: The aim of the article is to present the clinical observation of a successfully treated giant aneurysm of the pericallosal artery in a 58-year-old man, and also analyze the publications on distal cerebral aneurysms. MATERIAL AND METHODS: The data of a patient hospitalized with a suspected tumor of the left brain hemisphere spreading to the left lateral ventricle is presented. Repeated MRI suggests a giant subtotal thrombotic aneurysm of the left perical artery, which was confirmed by SCT angiography. The patient underwent aneurysm treping-cliping with dissection of the aneurysm sac. In the analysis of the literature it was shown that the frequency of perical artery aneurysms varies from 5.3-6.0%, and giant aneurysms of this localization are extremely rare and occur in 1-4.5% of all perical artery aneurysms. Unlike distal anterior cerebral artery aneurysms of small and medium size, giant aneurysms are characterized by pseudotumorrhagic symptoms, which causes diagnostic difficulties. CONCLUSION: It is necessary to remember about the diagnostic difficulties caused by the pseudotumorrhosis of the giant aneurysms of the pericallosal artery and the frequent negative angiography data due to total thrombosis of the aneurysmal sac. The gold standard is microsurgical clipping with excision of the aneurysmal sac. The prognosis for this group of patients is favorable.

[Vector mapping of deformation and blood flows in patients with ascending aortic aneurysm]. / Vektornoe kartirovanie deformatsii i potokov krovi u patsientov s anevrizmoi voskhodiashchei aorty.

The authors performed clinical studies based on modelling of an ascending aortic aneurysm in 37 patients and 10 apparently healthy subjects. Echocardiography was carried out in the B-mode using the Vivid E9 device (USA, GE). The linear dimensions of the aorta were assessed at three points - in the immediate vicinity of the valves, in the area of the maximum dilatation and in the area of decreased dilatation with registration of blood flow velocity in the aorta. The aortic walls were contoured with the division of equal intervals into 4 portions in order to obtain longitudinal shear deformation velocity during the cardiac cycle. We worked out a system of assessing the velocity vector fields with the help of transthoracic echocardiography in patients with an ascending aortic aneurysm, based on registration of blood flows, which made it possible to obtain the components of velocity. We also determined an optimal method of assessing turbulence in the aorta taking into account the direction of the vectors. Obtained were the numerical data of aortic wall deformation velocity in the longitudinal direction and calculation of the weighting function with the distinction between pathology and the norm. Based on the deformation, the distance between the registered points, and the movement of the vascular wall, we determined the reference values of blood flow velocity inside the aorta and immediately close to its walls.

[CSF shunting surgery in patients with post-traumatic hydrocephalus in the vegetative status and minimally conscious state: analysis of its efficacy and safety]. / Likvoroshuntiruiushchie operatsii u patsientov s posttravmaticheskoi gidrotsefaliei v vegetativnom statuse i sostoianii minimal'nogo soznaniia: analiz éffektivnosti i bezopasnosti.

The development of post-traumatic hydrocephalus (PTH) after severe traumatic brain injury can cause, in some cases, severe impairment of consciousness and prevent rehabilitation of patients. The influence of cerebrospinal fluid (CSF) circulation disorders on processes of consciousness recovery is a fundamental problem that requires in-depth research. The issues of differential diagnosis, results of surgical treatment of PTH, and its complications in patients in the vegetative status (VS) and minimally conscious state (MCS) remain poorly covered. MATERIAL AND METHODS: We performed a retrospective analysis of the long-term outcomes of surgical treatment in 82 PTH patients in the VS (38 cases) and MCS (44 cases). RESULTS: A significant clinical improvement occurred in 60.6% of VS patients and in 65.9% of MCS patients. The rate of shunt infection was high and amounted to 21.05% in the group of VS patients and 20.4% in the group of MCS patients. The rate of shunt system dysfunction was 26.05% in the first group and 20.4% in the second group. Postoperative mortality (associated directly with treatment complications) was 3.6%. Total mortality was 10.9%. DISCUSSION: The positive effect of shunting surgery in patients with gross impairment of consciousness was associated with transition to higher levels of consciousness. The high rate of complications, especially infections, was due to a serious condition of patients and comorbidities, in particular chronic infection foci. Shunt system dysfunction was not a factor of the adverse outcome of surgical treatment because rarely led to irreversible consequences, but required repeated surgery. Mortality after shunting surgery was significantly higher in patients with gross impairment of consciousness than in other groups of patients. We found a correlation between deaths in VS patients and shunt infection in the postoperative period. CONCLUSION: CSF shunting surgery is an important step in surgical rehabilitation of PTH patients. To assess the contribution of various risk factors to the development of shunt infection and to develop measures reducing its rate, further prospective studies are needed.

Structural-Functional Domains of the Eukaryotic Genome.

It is well known that DNA folding in the eukaryotic cell nucleus is tightly coupled with the operation of epigenetic mechanisms defining the repertoires of the genes expressed in different types of cells. To understand these mechanisms, it is important to know how DNA is packaged in chromatin. About 30 years ago a hypothesis was formulated, according to which epigenetic mechanisms operate not at the level of individual genes, but rather groups of genes localized in structurally and functionally isolated genomic segments that were called structural and functional domains. The question of what exactly these domains constitute has been re-examined multiple times as our knowledge of principles of chromatin folding has changed. In this review, we discuss structural and functional genomic domains in light of the current model of interphase chromosome organization based on the results of analysis of spatial proximity between remote genomic elements.

[Phenomenological Regularities of Assessment of Left Ventricle Function in Mitral Valve Insufficiency].

OBJECTIVE: to examine relationship between anatomical changes of the left ventricle (LV), dynamics of velocity of its volume modification, and blood flows in the LV in patients with mitral regurgitation (MR) before and after surgical treatment. MATERIALS AND METHODS: We included into this study 58 patients with severe 3-4 degree MR (38 men, 20 women aged 24-69 [mean age 51±9] years) in sinus rhythm (96 %) or atrial fibrillation (4 %). The control group included 86 healthy volunteers, mean age 39±7 years. Transthoracic echocardiographic studies were performed in both groups by standard technique at rest using a high-quality echocardiograph Vivid E9, equipped with a 3.5-4.6 MHz multi frequency transducer (in patients before and after surgical repair - mitral valve [MV] replacement and MV reconstruction with annuloplasty ring). The analysis of files recorded was performed off-line by vector analysis technique including estimation of myocardial deformation velocities and dynamics of LV volume modification, construction of "flow-volume" diagram, calculation of the expended kinetic energy, and registration of intraventricular blood flows. RESULTS: End diastolic volume (EDV), end systolic volume (ESV) and total stroke volume (TSV) (effective + retrograde) were significantly increased in patients with severe LV volume overload before surgery in comparison with the control group (p.

[Modern diagnostics and treatment of posttraumatic hydrocephalus]. / Sovremennaia diagnostika i lechenie posttravmaticheskoi gidrotsefalii.

One of the frequent consequences of severe traumatic brain injury is posttraumatic hydrocephalus that not only hampers the processes of consciousness recovery, rehabilitation, and social adaptation of patients but also is the cause of disability. Pathological processes underlying the clinical picture of posttraumatic hydrocephalus and the relationship between CSF circulation disorders and structural changes in the brain substance have not been adequately studied. Of particular importance are patients in the chronic vegetative or minimally conscious state, recovery from which is blocked by posttraumatic hydrocephalus. The question of reversibility of impaired consciousness depending on the disease duration has remained open. High risks of purulent-inflammatory complications of shunting surgery are especially important in patients with chronic infection foci (tracheostomy, gastrostomy, epicystostomy, prolonged bladder catheterization, pressure ulcers, etc.), but their actual effect on the shunting outcomes has not been revealed. Posttraumatic hydrocephalus remains a topical neurosurgical problem requiring clarification of its diagnostic criteria, differentiation from atrophy-related ventriculomegaly, and comprehensive development of pathogenetic and therapeutic aspects.

[Li-Fraumeni syndrome in a patient with multiple anaplastic oligodendrogliomas of the brain (a case report and literature review)]. / Sindrom Li-Fraumeni u patsienta so mnozhestvennymi anaplasticheskimi oligodendrogliomami golovnogo mozga (klinicheskoe nabliudenie i obzor literatury).

Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous hereditary syndrome with predominantly oncological manifestations, which is associated with mutations in the TP53, MDM2, and CHEK2 genes. The most common variant is a TP53 mutation. OBJECTIVE: To analyze the literature and present a clinical case of a patient with Li-Fraumeni syndrome and multiple anaplastic oligodendrogliomas of the brain. CLINICAL CASE: A 42-year-old male patient presented with complaints of headaches, word finding difficulty, memory loss, right hemianopsia, and generalized convulsive attacks. For 10 years, he underwent multiple interventions and chemotherapy courses for colon adenocarcinoma and recurrent B-cell lymphoma. MRI revealed multiple space-occupying lesions of the cerebraln hemispheres, which were located in the left temporo-occipital and right frontal regions. RESULTS: The patient underwent resection of multiple space-occupying lesions of the left temporo-occipital and right frontal regions. The postoperative period proceeded without complications. The histological diagnosis was WHO grade III anaplastic oligodendroglioma. The patient and one of his sons were detected with a R248W missense mutation in the TP53 gene. The patient underwent six courses of temozolomide chemotherapy. At a follow-up examination 20 months after surgery and chemotherapy, the patient's condition was satisfactory; he returned to work. Control MRI of the brain revealed no signs of continued tumor growth. CONCLUSION: An analysis of the literature and the clinical case indicate the success of multiple surgical interventions and chemotherapy courses performed for a long time in the patient with Li-Fraumeni syndrome manifested by colon adenocarcinoma, recurrent B-cell lymphoma, and multiple anaplastic oligodendroglioma of the brain. The patient had a good quality of life and returned to professional activity.

[Progressive pulmonary hypertension in a patient with type 1 Gaucher disease]. / Progressiruiushchaia legochnaia gipertenziia u patsienta s bolezn'iu Goshe I tipa.

Gaucher disease is the most common form of hereditary enzymopathies combined into a group of lysosomal storage diseases. The basis for the disease is a hereditary deficiency of the activity of acid ß-glucosidase, a lysosomal enzyme involved in the catabolism of lipids, which results in the accumulation of nonutilized cellular metabolism products in the macrophage lysosomes. The main clinical manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and splenomegaly, and bone lesion. One of the atypical clinical manifestations of Gaucher disease is damage to the lungs with the development of pulmonary hypertension, which is usually considered within the underlying disease - the development of pneumosclerosis due to macrophage dysfunction. The paper describes a case of progressive pulmonary hypertension in a patient with type 1 Gaucher disease.