Recommender systems in antiviral drug discovery

Recommender systems (RSs), which underwent rapid development and had an enormous impact on e-commerce, have the potential to become useful tools for drug discovery. In this paper, we applied RS methods for the prediction of the antiviral activity class (active/inactive) for compounds extracted from ChEMBL. Two main RS approaches were applied: Collaborative filtering (Surprise implementation) and content-based filtering (sparse-group inductive matrix completion (SGIMC) method). The effectiveness of RS approaches was investigated for prediction of antiviral activity classes ("interactions") for compounds and viruses, for which some of their interactions with other viruses or compounds are known, and for prediction of interaction profiles for new compounds. Both approaches achieved relatively good prediction quality for binary classification of individual interactions and compound profiles, as quantified by cross-validation and external validation receiver operating characteristic (ROC) score >0.9. Thus, even simple recommender systems may serve as an effective tool in antiviral drug discovery

Cognitive functions and patterns of brain activity in patients after simultaneous coronary and carotid artery revascularization

BackgroundOn-pump coronary artery bypass grafting (CABG) is associated with a high risk of neurological complications in patients with severe carotid stenosis. Moreover, early postoperative cognitive dysfunction (POCD) incidence remains high in patients undergoing simultaneous coronary and carotid surgery. Recent studies have shown that even moderate carotid stenosis (≥50%) is associated with postoperative cognitive decline after CABG. Data on brain health in the postoperative period of simultaneous coronary and carotid surgery are limited.ObjectivesThis study aimed to analyze early postoperative changes in the cognitive function and patterns of brain electrical activity in patients after simultaneous coronary and carotid artery revascularization.Materials and methodsBetween January 2017 and December 2020, consecutive patients were assigned to on-pump CABG with or without carotid endarterectomy (CEA) according to clinical indications. An extended neuropsychological and electroencephalographic (EEG) assessment was performed before surgery and at 7–10 days after CABG or CABG + CEA.ResultsA total of 100 patients were included [median age 59 (55; 65), 95% men, MMSE 27 (26; 28)], and among these, 46 underwent CEA. POCD was diagnosed in 29 (63.0%) patients with CABG + CEA and in 32 (59.0%) patients with isolated CABG. All patients presented with a postoperative theta power increase. However, patients with CABG + right-sided CEA demonstrated the most pronounced theta power increase compared to patients with isolated CABG.ConclusionThe findings of our study show that patients with CABG + CEA and isolated CABG have comparable POCD incidence; however, patients with CABG + right-sided CEA presented with lower brain activity

Влияние предоперационного когнитивного расстройства на изменения электрической активности головного мозга у пациентов, перенесших одномоментное вмешательство на каротидных и коронарных артериях

HighlightsThe presence of preoperative mild cognitive impairment (MCI) in patients undergoing combined carotid endarterectomy and coronary artery bypass grafting is associated with an increased theta activity at the frontal and parieto-occipital regions of both hemispheres after surgery. AbstractAim. To study the impact of preoperative cognitive impairment on changes in electrical activity of the brain in patients undergoing combined carotid endarterectomy and coronary artery bypass grafting.Methods. Sixty-three patients undergoing combined carotid endarterectomy (CAE) and coronary artery bypass grafting (CABG) were included in the study. The patients were divided into three groups, depending on the preoperative cognitive functions: without cognitive impairment (n = 17), with MCI (n = 29), and with severe cognitive impairment (n = 17). High-resolution electroencephalography (EEG) (62 channels, bandpass filtered between 0.1–50.0 Hz, sampling rate of 1000 Hz) was performed 3–5 days before and 7–10 days after surgery.Results. Patients with severe cognitive impairment at baseline presented with higher theta activity at the frontal region of the left hemisphere compared to patients without cognitive impairment and patients with MCI (p = 0.048). At the same time, patients with MCI showed the most pronounced theta activity increase after surgery compared to preoperative levels at the frontal and parieto-occipital cortical regions of both the left and right hemispheres (p≤0.05). Postoperative changes of theta activity in patients with severe cognitive impairment were minimal and statistically insignificant.Conclusion. Patients without severe preoperative cognitive impairment presented with higher grade brain dysfunction in the form of increased theta activity at the frontal and parieto-occipital regions after combined CAE and CABG. A smaller decrease in theta power after surgery in patients with severe preoperative cognitive impairment, on the one hand, can indicate compensation after cerebral ischemia and resistance to hypoperfusion during on-pump cardiac surgery, and on the other, can be a manifestation of the ceiling effect and insufficiency of brain functional reserves.Основные положенияНаличие предоперационного умеренного когнитивного расстройства у пациентов, перенесших одномоментное вмешательство на каротидных и коронарных артериях, ассоциировано с выраженным послеоперационным увеличением тета-активности во фронтальных и парието-окципитальных отделах обоих полушарий. РезюмеЦель. Изучено влияние предоперационного когнитивного расстройства на изменения электрической активности головного мозга у больных, перенесших одномоментное вмешательство на каротидных и коронарных артериях.Материалы и методы. В исследовании участвовали 63 пациента, перенесших одномоментно каротидную эндартерэктомию и коронарное шунтирование с применением искусственного кровообращения. В зависимости от предоперационного состояния когнитивных функций участники разделены на три группы: без когнитивного расстройства (n = 17), с умеренным (n = 29) и тяжелым (n = 17) когнитивным расстройством. Электроэнцефалография высокого разрешения (62 канала, полоса пропускания 0,1–50,0 Гц, частота дискретизации 1 000 Гц) проведена за 3–5 дней и на 7–10-е сутки после вмешательства.Результаты. Установлено, что до операции у пациентов с тяжелым когнитивным расстройством показатели тета-активности во фронтальных отделах левого полушария были выше, чем у лиц без когнитивного расстройства и с умеренным когнитивным нарушением (p = 0,048). При этом после вмешательства у пациентов с умеренным когнитивным расстройством наблюдалось максимально выраженное увеличение тета-активности по сравнению с предоперационным уровнем во фронтальных и парието-окципитальных отделах коры левого и правого полушарий (p≤0,05). Тогда как у лиц с тяжелым когнитивным расстройством послеоперационные изменения тета-ритма были минимальны и не достигали статистической значимости.Заключение. Пациенты без тяжелых форм предоперационного когнитивного дефицита после одномоментного вмешательства на каротидных и коронарных артериях демонстрируют большую выраженность мозговой дисфункции по показателям тета-активности фронтальных и парието-окципитальных областей коры мозга. При этом меньшая выраженность изменений тета-ритма после операции у больных с тяжелым предоперационным когнитивным расстройством, с одной стороны, может быть индикатором компенсации хронической ишемии головного мозга и устойчивости к гипоперфузии при искусственном кровообращении, с другой – проявлением потолочного эффекта и недостаточности функциональных резервов

Effect of Carotid Stenosis Severity on Patterns of Brain Activity in Patients after Cardiac Surgery

Background: The negative effects of high-grade carotid stenosis on the brain are widely known. However, there are still insufficient data on the brain state in patients with small carotid stenosis and after isolated or combined coronary and carotid surgery. This EEG-based study aimed to analyze the effect of carotid stenosis severity on associated brain activity changes and the neurophysiological test results in patients undergoing coronary artery bypass grafting (CABG) with or without carotid endarterectomy (CEA). Methods: One hundred and forty cardiac surgery patients underwent a clinical and neuropsychological examination and a multichannel EEG before surgery and 7–10 days after surgery. Results: The patients with CA stenoses of less than 50% demonstrated higher values of theta2- and alpha-rhythm power compared to the patients without CA stenoses both before and after CABG. In addition, the patients who underwent right-sided CABG+CEA had generalized EEG “slowdown” compared with isolated CABG and left-sided CABG+CEA patients. Conclusions: The on-pump cardiac surgery accompanied by specific re-arrangements of frequency–spatial patterns of electrical brain activity are dependent on the degree of carotid stenoses. The information obtained can be used to optimize the process of preoperative and postoperative management, as well as the search for neuroprotection and safe surgical strategies for this category of patients

Establishment of a Pilot Newborn Screening Program for Spinal Muscular Atrophy in Saint Petersburg

Spinal muscular atrophy 5q (SMA) is one of the most common neuromuscular inherited diseases and is the most common genetic cause of infant mortality. SMA is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently developed drugs can improve the motor functions of infants with SMA when they are treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using a real-time PCR assay with dried blood spots (DBS) was performed from January 2022 through November 2022 in Saint Petersburg, which is a representative Russian megapolis. Here, 36,140 newborns were screened by the GenomeX real-time PCR-based screening test, and three genotypes were identified: homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns), and wild-type individuals (35,364 newborns). The disease status of all four newborns that screened positive for the homozygous SMN1 deletion was confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined the incidence of spinal muscular atrophy in Saint Petersburg to be 1 in 9035 and the SMA carrier frequency to be 1 in 47. In conclusion, providing timely information regarding SMN1, confirmation of disease status, and SMN2 copy number as part of the SMA newborn-screening algorithm can significantly improve clinical follow-up, testing of family members, and treatment of patients with SMA