Comparative analysis of molecular fingerprints in prediction of drug combination effects

bbab291Application of machine and deep learning methods in drug discovery and cancer research has gained a considerable amount of attention in the past years. As the field grows, it becomes crucial to systematically evaluate the performance of novel computational solutions in relation to established techniques. To this end, we compare rule-based and data-driven molecular representations in prediction of drug combination sensitivity and drug synergy scores using standardized results of 14 high-throughput screening studies, comprising 64 200 unique combinations of 4153 molecules tested in 112 cancer cell lines. We evaluate the clustering performance of molecular representations and quantify their similarity by adapting the Centered Kernel Alignment metric. Our work demonstrates that to identify an optimal molecular representation type, it is necessary to supplement quantitative benchmark results with qualitative considerations, such as model interpretability and robustness, which may vary between and throughout preclinical drug development projects.Peer reviewe

Is anticoagulant therapy necessary after hospitalization with COVID-19 pneumonia?

The coronavirus disease 2019 (COVID-19) pandemic is associated with high virulence, mortality and healthcare burden around the world. One of its features is procoagulant activity, which leads to a high incidence of thromboembolic events in the lungs and other organs. Therefore, from the very onset of the moderate COVID-19, low molecular weight heparins began to be used as anticoagulants, which proved to have a beneficial effect on mortality and the disease course and were included in all guidelines. However, the question on anticoagulant therapy need after discharge from the hospital is controversial. The opinions of various medical professional communities on this issue are divided. In particular, some of them, including the Russian Ministry of Health guidelines recommend 30-45day anticoagulation using novel oral anticoagulants (dabigatran, rivaroxaban, apixaban), but other sources do not provide such recommendations. This review discusses the effectiveness of anticoagulant therapy after COVID-19, as well as the need to use stratification scales to assess this therapy

Преобразование кардиологических палат интенсивной терапии в кардиологическую реанимацию. Пятилетняя эволюция

The article highlights the key elements and results of the restructuring of emergency care for patients with acute myocardial infarction, the core of which is the teamwork of surgeons, anesthesiologist-intensivists and cardiologists of the department. The restructuring included a change in ideology, personnel changes, updating and expanding the range of equipment, development of inner protocols and their implementation. It took two years to transform the intensive care unit for patients with acute myocardial infarction into the cardiac intensive care unit, where patients with acute cardiac pathologies of various etiologies are treated and preoperative preparation and postoperative nursing are carried out.В статье освещаются ключевые элементы и результаты реструктуризации неотложной помощи пациентам с острым инфрактом миокарда, ядром которой является командная работа хирургов, анестезиологов-реаниматологов и кардиологов в отделении. Реструктуризация включала в себя изменение идеологии, кадровые перестановки, обновление и увеличение номенклатуры оборудования. Трансформация отделения интенсивной терапии для пациентов с острым инфарктом миокарда в отделение кардиореанимации, где проходят лечение пациенты с острой кардиальной патологией разной этиологии и проводится предоперационная подготовка и послеоперационное выхаживание, заняла два года

Место фиксированной комбинации будесонид / формотерол в лечении хронической обструктивной болезни легких стабильного течения. Заключение совета экспертов Приволжского федерального округа Российской Федерации

Late diagnosis of chronic obstructive pulmonary disease (COPD) at advanced stage, high risk of exacerbations, low compliance of patients, and adverse effects of treatment have been still unresolved problems in the treatment of COPD despite the development of new drugs. The personalized medicine rneeds distinct indications and predictors of efficacy and safety of treatment. Budesonide/formoterol fixed combination is recommended for patients with asthma – COPD overlap syndrome and bronchitis phenotype, blood eosinophilia > 300 cells/mm3, if other causes were excluded, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 50% pred.; and ≥ 2 exacerbations or ≥ 1 hospitalization related to exacerbation during the previous year. Budesonide/formoterol fixed combination is not recommended for regular use in patients with emphysema phenotype of COPD and rare exacerbations (< 2 exacerbations and without hospitalizations in the previous year).Несмотря на появление новых препаратов для лечения пациентов с хронической обструктивной болезнью легких (ХОБЛ), в настоящее время нерешенными проблемами в терапии этого заболевания остаются поздняя диагностика и выявление ХОБЛ уже на стадии тяжело протекающего заболевания, высокий риск обострений, низкая комплаентность пациентов, побочное действие лекарственных средств. Персонализированная медицина требует четких показаний, предикторов эффективности и безопасности лечения. Терапия фиксированной комбинацией будесонид / формотерол рекомендована пациентам с сочетанием бронхиальной астмы (БА) и ХОБЛ; высоким уровнем эозинофилов в периферической крови (> 300 клеток в 1 мкл крови) при исключении других причин (гельминты, лямблии и т. п.) и с постбронходилатационным объемом форсированного выдоха за 1-ю секунду (ОФВ1) < 50 %долж.; бронхитическим фенотипом; ≥ 2 обострениями в предшествующий год; ≥ 1 госпитализацией по поводу обострения в течение 1 года при наличии постбронходилатационного ОФВ1 < 50 %долж. Фиксированная комбинация будесонид / формотерол не рекомендуется к регулярному назначению при эмфизематозном фенотипе ХОБЛ у больных с редкими обострениями (< 2 / без госпитализаций за предшествующий год)

NEURAL NETWORK MODEL FOR DIAGNOSING MYOCARDIAL INFARCTION

Body surface potential mapping (BSPM) is a non-invasive and effective method for diagnosing coronary heart disease (CHD) and acute myocardial infarction (AMI). However, most existing systems of BSPM are unable to create standard diagnostic criteria. Aim. To develop the neural network model (NNM) for diagnosing Q-wave AMI and to assess the model effectiveness. Material and methods. The BSPM method in 90 leads was used in 96 controls, 35 patients with anterior Q-wave AMI, 43 with posterior Q-wave AMI, 14 with inferior Q-wave AMI, and 21 with lateral Q-wave AMI. The input NNM layer was decomposed into five subsets corresponding to horizontal levels of registered signals, using amplitudes of Q, R, S, and T waves and the ST segment. The output layer produced the probability of the norm (controls) and different AMI locations. Results. Exploring the NNM performance in controls and AMI patients, sensitivity of 100% and specificity of 97,4% was observed. Sensitivity reached 100% for anterior Q-wave AMI, 94,4% for posterior Q-wave AMI, 85,7% for inferior Q-wave AMI, and 83,3% for lateral Q-wave AMI. Conclusion. Our data have demonstrated the effectiveness of NNM in AMI diagnostics

DABIGATRAN – THE NEW APPROACH FOR DEEP VENOUS TROMBOSIS PROPHYLAXIS

The amount of total joint replacement is more than 1.5 mln world wide and requirement is increasing each year. Nevertheless one of the most dramatic complication after orthopedic manipulations are deep venous trombosis. As known, two aspects of prophylaxis are most important: duration of treatment and the doses of drags. The aim of study was to analys the influence of dabigatran for the risk of postop complications with the short time patients treatment complains. Treatment combination with dabigatran was clinically effective and the rate of adversing events was low. Thus we can conclude that treatment complains of dabigatran significantly higher then traditional injections of low molecular weight heparins