Deep learning risk assessment models for predicting progression of radiographic medial joint space loss over a 48-MONTH follow-up period.

OBJECTIVE: To develop and evaluate deep learning (DL) risk assessment models for predicting the progression of radiographic medial joint space loss using baseline knee X-rays. METHODS: Knees from the Osteoarthritis Initiative without and with progression of radiographic joint space loss (defined as ≥ 0.7 mm decrease in medial joint space width measurement between baseline and 48-month follow-up X-rays) were randomly stratified into training (1400 knees) and hold-out testing (400 knees) datasets. A DL network was trained to predict the progression of radiographic joint space loss using the baseline knee X-rays. An artificial neural network was used to develop a traditional model for predicting progression utilizing demographic and radiographic risk factors. A combined joint training model was developed using a DL network to extract information from baseline knee X-rays as a feature vector, which was further concatenated with the risk factor data vector. Area under the curve (AUC) analysis was performed using the hold-out test dataset to evaluate model performance. RESULTS: The traditional model had an AUC of 0.660 (61.5% sensitivity and 64.0% specificity) for predicting progression. The DL model had an AUC of 0.799 (78.0% sensitivity and 75.5% specificity), which was significantly higher (P < 0.001) than the traditional model. The combined model had an AUC of 0.863 (80.5% sensitivity and specificity), which was significantly higher than the DL (P = 0.015) and traditional (P < 0.001) models. CONCLUSION: DL models using baseline knee X-rays had higher diagnostic performance for predicting the progression of radiographic joint space loss than the traditional model using demographic and radiographic risk factors.

Laser-driven vacuum breakdown waves.

It is demonstrated by three-dimensional quantum electrodynamics - particle-in-cell (QED-PIC) simulations that vacuum breakdown wave in the form of QED cascade front can propagate in an extremely intense plane electromagnetic wave. The result disproves the statement that the self-sustained cascading is not possible in a plane wave configuration. In the simulations the cascade is initiated during laser-foil interaction in the light sail regime. As a result, a constantly growing electron-positron plasma cushion is formed between the foil and laser radiation. The cushion plasma efficiently absorbs the laser energy and decouples the radiation from the moving foil thereby interrupting the ion acceleration. The models describing propagation of the cascade front and electrodynamics of the cushion plasma are presented and their predictions are in a qualitative agreement with the results of numerical simulations.

Efficacy and safety of the use of rebamipide in the scheme of triple eradication therapy of Helicobacter pylori infection: a prospective randomized comparative study.

AIM: To evaluate the effectiveness and safety of the use of rebamipide as part of the triple eradication therapy (ET) scheme of Helicobacter pylori infection. MATERIALS AND METHODS: A prospective, randomized comparative study included 94 patients with uncomplicated H. pylori-associated stomach / duodenal ulcer. In the process of randomization, patients are divided into three groups depending on the intended therapy. The first group (n=36) received a classical triple scheme of the first-line ET (omeprazole 20 mg twice a day, amoxicillin 1000 mg twice a day, clarithromycin 500 mg twice a day) for 10 days. Patients of the second group (n=33) were assigned a classical triple scheme of ET with the inclusion of rebamipide (omeprazole 20 mg twice a day, amoxicillin 1000 mg twice a day, clarithromycin 500 mg twice a day, rebamipide 100 mg 3 times a day day) for 10 days. Patients of the third group (n=25) were assigned a classical triple scheme of ET with the inclusion of rebamipide (omeprazole 20 mg twice a day, amoxicillin 1000 mg twice a day, clarithromycin 500 mg twice a day, rebamipide 100 mg 3 times a day) in for 10 days, with the prolongation of the administration of rebamipide for the next 20 days. The effectiveness of ET was determined by the respiratory test after 6 weeks after the end of treatment. Adverse events were recorded by patients in specially developed diaries. All patients with gastric ulcer at the 6th week underwent a histological examination of the biopsy specimens of the antrum and the body of the stomach, assessing the inflammatory activity of the process on a point system in accordance with the updated Sydney system. RESULTS: Efficiency of H. pylori eradication in the first group was 77.7% (ITT), 82.3% (PP), in the second group - 81.8% (ITT), 84.4% (PP), and in the third group - 84% (ITT), 87.5% (PP). The use of rebamipide in the triple ET regimen was associated with an increase in H. pylori eradication efficiency, both with simultaneous use with the scheme [odds ratio (OR) 1.16; 95% confidence interval (CI) 0.32-4.24], and with subsequent prolonged admission (OR 1.5, 95% CI 0.34-6.7). A somewhat more pronounced dynamics of the epithelization of erosive and ulcerative changes in the mucous membrane of the stomach and duodenum to the 21st and 28th days in the third group of patients was noted. The incidence of adverse events between the groups was comparable: 22.2% in the first group, 24.2% in the second group and 20% in the third group. In the pathomorphological evaluation of biopsy specimens of patients with gastric ulcer at the 6th week after the treatment, significant differences were revealed between the first and third groups in terms of the inflammatory activity in the antrum stomach (2±0.63 vs. 1.4±0.52; p=0,0399). CONCLUSION: The inclusion of rebamipide in the classical triple scheme of H. pylori ET increases the effectiveness of treatment and does not affect the safety profile. In the post-eradication period, it is advisable to continue the use of rebamipide to potentiate the repair of the gastric mucosa and regress the inflammatory processes.

[Numerical Analysis of Particle Trajectories in Living Cells under Uncertainty Conditions].

We have developed a numerical method for the analysis of particle trajectories in living cells, where a type of movement is determined by Akaike's information criterion, while model parameters are identified by a weighted least squares method. The method is realized in computer software, written in the Java programming language, that enables us to automatically conduct the analysis of trajectories. The method is tested on synthetic trajectories with known parameters, and applied to the analysis of replication complexes in cells, infected with hepatitis C virus. Results of the analysis are in agreement with available data on the movement of biological objects along microtubules.

[MENETRIER DISEASE].

Menetrier disease (MD) is a very rare stomach pathology of unknown etiology characterized by manifest hypertrophy of gastric mucosa. The main causes of MD are believed to be Helicobacter pylori and cytomegalovirus infections. The most frequent symptom is epigastric pain. Also common are peripheral oedema due to hypoalbuminemia and increased permeability of gastric mucosa. The main diagnostic signs of MD include diffusive enhancement of mucosal folds, foveolar hyperplasia and glandular atrophy with a decrease in the number of main and parietal cells, hypoalbuminemia and peripheral oedema. MD being a very rare condition, the optimal methodfor its treatment is unknown.

[The dynamics of feed-forward loop depends on regulator type in indirect pathway].

Gene networks contain a recurring motif, called the feed-forward loop, in which a transcription factor regulates target expression directly and indirectly via the second regulator. Here we present the results of mathematical modeling of feed-forward loops with either the transcription factor or miRNA as a repressor in the indirect pathway. We showed that the substitution of the transcription factor with miRNA changes the dynamic behavior of the feed-forward loop and lends new properties critical for biological system functioning.

[Method of Entirely Parallel Differential Evolution for Model Adaptation in Systems Biology].

We developed a method of entirely parallel differential evolution for identification of unknown parameters of mathematical models by minimization of the objective function that describes the discrepancy of the model solution and the experimental data. The method is implemented in the free and open source software available on the Internet. The method demonstrated a good performance comparable to the top three methods from CEC-2014 and was successfully applied to several biological problems.

[Pharmacoeconomic evaluation of treatment in patients with Helicobacter pylori-associated diseases].

AIM: To estimate the pharmacoeconomic parameters of treatment in patients with Helicobacter pylori-associated diseases when using 6 eradication therapy (ET) regimens. SUBJECTS AND METHODS: The investigation enrolled a total of 231 patients who received anti-Helicobacter pylori therapy according to the intention-to-treat (ITT) principle, including 229 patients who met the protocol requirements, i.e. who completed the prescribed per-protocol (PP) treatment: 106 patients with duodenal bulb ulcer disease, 2 with gastric ulcer, 90 with erosive gastritis, and 31 patients with non-atrophic gastritis. In an outpatient setting, the patients received one of the 6 ET regimens: OAC, RBMA, RBCA, EBCA, sequential OACM therapy, and modified sequential OACMB therapy (O--omeprazole; A--amoxicillin; C--clarithromycin; B--bismuth tripotassium dicitrate, R--rabeprazole; M--metronidazole; E--esomeprazole). Treatment costs were calculated only from direct drug expenditures. The effective cost coefficient (K(eff)) was determined from the cost/ treatment efficiency ratio: K(eff) = cos/eff, where the cost was the average total costs; the eff was efficiency (%). RESULTS: The modified sequential OACMB therapy has proven to be more cost-efficient than the other regimens as it has a lower K(eff), (14). The RBMA regimens can overcome an 80% ET barrier (82.4%); however, in this case the K(eff) is 21.5. the sequential OACM therapy can also overcome an 80% ET barrier (84.8%); the K(eff) being 10.8. Incorporation of the bismuth preparation can achieve a more noticeable therapeutic effect up to 95.4%. The EBCA regimen has turned out to be most expensive with the highest K(eff) of 36.9. The RBCA regimen is most effective with the least K(eff) of 29; the therapeutic effect is 96.7%. CONCLUSION: The clinical cost-efficiency of ET is enhanced by the incorporation of the bismuth preparation for the treatment of patients with H. pylori-associated diseases. The modified sequential OACMB therapy can overcome resistance to clarithromycin and metronidazole with a good cost-efficiency.

Cross-relaxation imaging of human patellar cartilage in vivo at 3.0T.

OBJECTIVE: To compare quantitative magnetization transfer (qMT) parameters of patellar cartilage measured using cross-relaxation imaging (CRI) in asymptomatic volunteers and patients with osteoarthritis. DESIGN: The study was performed with Institutional Review Board approval and with all subjects signing informed consent. CRI of the knee joint was performed at 3.0T on 20 asymptomatic volunteers and 11 patients with osteoarthritis. The fraction of macromolecular bound protons (f), the exchange rate constant between macromolecular bound protons and free water protons (k), and the T2 relaxation time of macromolecular bound protons (T2(B)) of patellar cartilage were measured. Mann-Whitney-Wilcoxon rank-sum tests were used to compare qMT parameters between asymptomatic volunteers and patients with osteoarthritis. RESULTS: Average f, k, and T2(B) of patellar cartilage was 12.46%, 7.22 s(-1), and 6.49 µs respectively for asymptomatic volunteers and 12.80%, 6.13 s(-1), and 6.80 µs respectively for patients with osteoarthritis. There were statistically significant differences between groups of subjects for k (P < 0.01) and T2(B) (P < 0.0001) but not f (P = 0.38) of patellar cartilage. CONCLUSION: Patients with osteoarthritis had significantly lower k and significantly higher T2(B) of patellar cartilage than asymptomatic volunteers which suggests that qMT parameters can detect changes in the macromolecular matrix of degenerative cartilage.

[Drug interaction of proton pump inhibitors and clopidogrel taken together].

Current clinical practice lays special emphasis on drug interactions. High rates of cardiovascular morbidity and acid-dependent diseases dictates the necessity of antiaggregation and antisecretory therapy. The former uses a variety of medicines with acetylsalicylic acid (ASA) and clopidogrel being the most popular ones. Therapy using drugs with different mechanisms of action on the thrombocytic component of homeostasis appears to be especially promising as having synergic antiplatelet effect. The most common variant of antiplatelet therapy is a combination of ASA and clopidogrel usually referred to as double antiplatelet therapy (DAP). Current consensus recommends intake of proton pump inhibitors (PPI) during DAP to reduce the risk of gastrointestinal complications. However, recent studies showed that this approach is fraught with severe cardiovascular disorders, such as myocardial infarction, stroke, unstable angina, necessity of repeat coronary interventions, and coronary death. Hence, the importance of differential application of PPI in patients treated with ASA and clopidogrel. A comprehensive review of this problem is presented along with results of investigations of PPI action on clinical outcome of clopidrogel therapy.

[Current recommendations for the diagnosis of chronic pancreatitis in general clinical practice].

The paper gives practical recommendations based on the provisions of a number of foreign national guidelines for the diagnosis of chronic pancreatitis (CP). There is virtually no evidence for Class I database for its diagnosis. Despite an inadequate scientific rationale, the review of these international guidelines has brought together the basic available data in the context of the current global standards for the diagnosis of CP.

[The role of respiratory tests in diagnostics of Helicobacter pylori infection].

The clinical significance and potential of respiratory tests for diagnostics of Helicobacter pylori infection was estimated in 76 patients. Results of 13C and 14C-urease tests were in especially good agreement with those oh histological studies. The 13C-urease test should be preferred in the examination of both in-patients and out-patients whereas NH3-urease test is much inferior to 13C and 14C-urease tests in terms of informative value.

[Difficulties and errors in the management tactics of patients with chronic pancreatitis].

The paper deals with the difficulties and errors that are most commonly used in clinical practice to manage patients with chronic pancreatitis (CP). The higher interest in CP is inspired by the wide prevalence of this disease with its constant upward trend. At the same time, a variety of the etiological forms of CP, from generically determined to infectious and autoimmune ones, in combination with a weak theoretical basis in a number of practitioners gives rise to a broad spectrum of tactical errors in the management of patients with CP. The paper summarizes and analyzes the most common defects and errors in the management tactics of patients with this nosological entity, including the aspects of diagnosis and medical treatment. Ways to solve the set optimization problems in management protocols for patients with CP are proposed in the context of evidence-based medicine.

[Replication of the subgenomic hepatitis C virus replicon in the presence of the NS3 protease inhibitors: a stochastic model].

The hepatitis C virus (HCV) belongs to Flaviviridae family and causes hazardous liver diseases leading frequently to cirrhosis and hepatocellular carcinoma. HCV is able to rapidly acquire drug resistance and for this reason there is currently no effective anti-HCV therapy in spite of appearance of new potential drugs. Mathematical models are relevant to predict the efficacy of potential drugs against virus or host targets. One of the promising targets for development of new drugs is the viral NS3 protease. Here we developed a stochastic model of the subgenomic HCV replicon replication in Huh-7 cells and in the presence of the NS3 protease inhibitors. Along with consideration of the stochastic nature of the subgenomic HCV replicon replication the model takes into account the existence and generation of main NS3 protease drug resistant mutants, namely BILN-2061 (A156T, D168V, R155Q), VX-950 (A156S, A156T, T54A) and SCH-503034 (A156T, A156S, T54A). The model reproduces well the viral RNA kinetics in the cell from the moment of the subgenomic HCV replicon transfection to steady state, as well as the viral RNA suppression kinetics in the presence of NS3 protease inhibitors BILN-2061, VX-950 and SCH-503034. We showed that the resistant mutants should be taken into account for the correct description of biphasic kinetics of the viral RNA suppression. The mutants selected in the presence of different inhibitor concentrations have maximal replication capacity in the given inhibitor concentration range. Our model can be used to interpret the results of the new anti-HCV drug testing in replicon systems, as well as to predict the efficacy of new potential drugs and optimize the regimen of their use.

[Clinical significance of Helicobacter pylori infection].

This article deals with modern concepts of H. pylori infection and its role in the development of gastric and extragastic pathology. The currently available algorithms of diagnostics and treatment of this infection are presented Recommendations of recent Maastricht consensuses (7MC-3, 2005; MC-4, 2010) on diagnostics and treatment of H. pylori infection are considered. The data on resistance of H .pylori to antibiotics, mechanisms of its development and methods of control are summarized.

Local immobilization of particles in mass transfer described by a Jeffreys-type equation.

We consider the Jeffreys-type equation as the foundation in three different models of mass transfer, namely, the Jeffreys-type and two-phase models and the D(1) approximation to the linear Boltzmann equation. We study two classic (1+1)-dimensional problems in the framework of each model. The first problem is the transfer of a substance initially confined at a point. The second problem is the transfer of a substance from a stationary point source. We calculate the mean-square displacement (MSD) for the solutions of the first problem. The temporal behavior of the MSD in the framework of the first and third models is found to be the same as that in the Brownian motion described by the standard Langevin equation. In addition, we find a remarkable phenomenon when a portion of the substance does not move.

Delayed uncoupled continuous-time random walks do not provide a model for the telegraph equation.

It has been alleged in several papers that the so-called delayed continuous-time random walks (DCTRWs) provide a model for the one-dimensional telegraph equation at microscopic level. This conclusion, being widespread now, is strange, since the telegraph equation describes phenomena with finite propagation speed, while the velocity of the motion of particles in the DCTRWs is infinite. In this paper we investigate the accuracy of the approximations to the DCTRWs provided by the telegraph equation. We show that the diffusion equation, being the correct limit of the DCTRWs, gives better approximations in L(2) norm to the DCTRWs than the telegraph equation. We conclude, therefore, that first, the DCTRWs do not provide any correct microscopic interpretation of the one-dimensional telegraph equation, and second, the kinetic (exact) model of the telegraph equation is different from the model based on the DCTRWs.

[Prostate biopsy in the outpatient setting].

The article describes the methodology of transrectal diagnostic prostate biopsy under ultrasound guidance with regard to settings of municipal polyclinic; existing complications are listed. The analysis of the results of 876 biopsies performed within 3 years is presented. The distribution of the results of histological examination depending on the level of total PSA, ratio of free and total PSA, and PSA density was followed-up. Relationship between PC detection rate using standard biopsy and prostate volume is shown. The analysis of the degree of PC differentiation (Gleason score) depending on the level of total PSA, the ratio of free and total PSA, and PSA density was performed. Practical recommendations to improvement of PC detection rate are presented. Based on the analysis, it was concluded that the screening for prostate cancer for the purpose of its earlier diagnosis is reasonable.

[Helicobacter pylori: what schemes of eradication are essential today?].

Current approaches to treatment of Helicobacter pylori infection, basic international recommendations, problems of growing H. pylori resistance to antibiotics are reviewed. Much attention is given to prospects of new eradication schemes, for example combinations based on bismuth tripotassium dicitrate and successive treatment schedules.