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Techniques for Developing Reliable Machine Learning Classifiers Applied to Understanding and Predicting Protein:Protein Interaction Hot Spots.
Chen, J, Kuhn, LA, Raschka, S
Methods in molecular biology (Clifton, N.J.). 2024;:235-268
Abstract
With machine learning now transforming the sciences, successful prediction of biological structure or activity is mainly limited by the extent and quality of data available for training, the astute choice of features for prediction, and thorough assessment of the robustness of prediction on a variety of new cases. In this chapter, we address these issues while developing and sharing protocols to build a robust dataset and rigorously compare several predictive classifiers using the open-source Python machine learning library, scikit-learn. We show how to evaluate whether enough data has been used for training and whether the classifier has been overfit to training data. The most telling experiment is 500-fold repartitioning of the training and test sets, followed by prediction, which gives a good indication of whether a classifier performs consistently well on different datasets. An intuitive method is used to quantify which features are most important for correct prediction.The resulting well-trained classifier, hotspotter, can robustly predict the small subset of amino acid residues on the surface of a protein that are energetically most important for binding a protein partner: the interaction hot spots. Hotspotter has been trained and tested here on a curated dataset assembled from 1046 non-redundant alanine scanning mutation sites with experimentally measured change in binding free energy values from 97 different protein complexes; this dataset is available to download. The accessible surface area of the wild-type residue at a given site and its degree of evolutionary conservation proved the most important features to identify hot spots. A variant classifier was trained and validated for proteins where only the amino acid sequence is available, augmented by secondary structure assignment. This version of hotspotter requiring fewer features is almost as robust as the structure-based classifier. Application to the ACE2 (angiotensin converting enzyme 2) receptor, which mediates COVID-19 virus entry into human cells, identified the critical hot spot triad of ACE2 residues at the center of the small interface with the CoV-2 spike protein. Hotspotter results can be used to guide the strategic design of protein interfaces and ligands and also to identify likely interfacial residues for protein:protein docking.
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Coinfections and Superinfections Associated with COVID-19 in Colombia: A Narrative Review.
Dueñas, D, Daza, J, Liscano, Y
Medicina (Kaunas, Lithuania). 2023;(7)
Abstract
The COVID-19 pandemic has had significant impacts on healthcare systems around the world, including in Latin America. In Colombia, there have been over 23,000 confirmed cases and 100 deaths since 2022, with the highest number of cases occurring in females and the highest number of deaths in males. The elderly and those with comorbidities, such as arterial hypertension, diabetes mellitus, and respiratory diseases, have been particularly affected. Coinfections with other microorganisms, including dengue virus, Klebsiella pneumoniae, and Mycobacterium tuberculosis, have also been a significant factor in increasing morbidity and mortality rates in COVID-19 patients. It is important for surveillance systems to be improved and protocols to be established for the early detection and management of coinfections in COVID-19. In addition to traditional treatments, alternatives such as zinc supplementation and nanomedicine may have potential in the fight against COVID-19. It is also crucial to consider the social, labor, educational, psychological, and emotional costs of the pandemic and to address issues such as poverty and limited access to potable water in order to better prepare for future pandemics.
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Potential usefulness of Mediterranean diet polyphenols against COVID-19-induced inflammation: a review of the current knowledge.
Milton-Laskibar, I, Trepiana, J, Macarulla, MT, Gómez-Zorita, S, Arellano-García, L, Fernández-Quintela, A, Portillo, MP
Journal of physiology and biochemistry. 2023;(2):371-382
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Abstract
The Mediterranean diet is a dietary pattern typical of the populations living in the Mediterranean basin during the 50s-60s of the last century. This diet has demonstrated beneficial effects in the prevention of several pathologies such as cardiovascular diseases, metabolic syndrome, or several cancer types, at least in part, due to its antioxidant compounds. Since the COVID-19 pandemic started, different authors have been studying the effects of certain dietary habits on the presence of COVID-19 and its severity, and the Mediterranean diet is one of them. This review gathers data from studies supporting the potential usefulness of the main phenolic compounds present in the Mediterranean diet, based on their antioxidant and anti-inflammatory effects, as preventive/therapeutic agents against COVID-19. The current evidence supports the potential benefits that hydroxytyrosol, resveratrol, flavonols such as quercetin, flavanols like catechins, and flavanones on the order of naringenin could have on COVID-19. This is due to the increase in the synthesis and translocations of Nrf-2, which increases the activity of antioxidant enzymes and thus reduces ROS production, the scavenging of free radicals, and the suppression of the activity of MMP-9, which is involved in the cytokine storm, and the inhibition of NF-κB.
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Frail2Fit study protocol: a feasibility and acceptability study of a virtual multimodal intervention delivered by volunteers to improve functional outcomes in older adults with frailty after discharge from hospital.
Meredith, SJ, Roberts, H, Grocott, MPW, Jack, S, Murphy, J, Varkonyi-Sepp, J, Bates, A, Lim, SER
BMJ open. 2023;(3):e069533
Abstract
INTRODUCTION Physical activity (PA) and replete nutritional status are key to maintaining independence and improving frailty status among frail older adults. In response to the COVID-19 pandemic, healthcare has increasingly turned to virtual modes of delivery and there is interest in the use of trained volunteers to deliver PA and nutrition interventions. We aim to evaluate the feasibility and acceptability of training hospital volunteers to deliver an online intervention, comprising exercise, behaviour change and nutrition support, to older people with frailty after discharge from hospital. METHODS We will use a quasi-experimental mixed methods approach. Hospital volunteers (n=6) will be trained to deliver an online, 3-month, multimodal intervention to frail (Clinical Frailty Scale ≥5) adults ≥65 years (n=30) after discharge from hospital. Feasibility will be assessed by determining the number of volunteers recruited, trained and retained at the end of the study; the proportion of intervention sessions delivered; participant recruitment, retention and adherence to the intervention. To determine the acceptability of the intervention, interviews will be conducted among a purposive sample of older adults, and volunteers. Secondary outcomes will include physical function, appetite, well-being, quality of life, anxiety and depression, self-efficacy for managing chronic disease and PA. Outcomes will be measured at baseline, 3 months and 6 months. ANALYSIS Descriptive statistics will be used to describe feasibility and adherence to the intervention. Secondary outcomes at baseline will be compared at 3 and 6 months. Interviews will be transcribed verbatim and analysed using thematic analysis. ETHICS AND DISSEMINATION Health Research Authority ethical approval was obtained on 30 May 2022 (reference: 22/WA/0155). Results will be disseminated through peer-reviewed journal articles, volunteer organisations, National Health Service communication systems and social media platforms. A toolkit will be developed to facilitate roll out of volunteer training. TRIAL REGISTRATION NUMBER NCT05384730.
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COVID-19 and coronary artery disease; A systematic review and meta-analysis.
Hajikhani, B, Safavi, M, Bostanshirin, N, Sameni, F, Ghazi, M, Yazdani, S, Nasiri, MJ, Khosravi-Dehaghi, N, Noorisepehr, N, Sayyari, S, et al
New microbes and new infections. 2023;:101151
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Abstract
BACKGROUND AND AIM Patients with underlying cardiovascular disorders such as coronary artery disease (CAD) are more prone to severe forms and multiple complications of COVID-19. The present systematic review and meta-analysis aimed to investigate the impact of CAD on patients with COVID-19. METHODS Main electronic databases, including Medline (via PubMed), EMBASE, and Web of Science, were carefully searched and reviewed for original research articles published between 2019 and 2021. One hundred nine studies that address CAD in patients with COVID-19 were selected and analyzed. RESULTS Following search and screening processes, 109 relevant publications were selected for analysis. The meta-analysis of prevalence studies indicated that the frequency of CAD among patients with COVID-19 was reported in 10 countries with an overall frequency of 12.4% [(95% CI) 11.1-13.8] among 20079 COVID-19 patients. According to case reports/case series studies, 50.9% of COVID-19 patients suffered from CAD. Fever was the most common symptom in these patients (47%); 36.5% also had hypertension. CONCLUSION The results obtained during the present study show that the simultaneous presence of COVID-19 and CAD, especially in men and elderly patients, can increase the risks and complications of both diseases. Therefore, careful examination of the condition of this group of patients for timely diagnosis and treatment is strongly recommended.
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Lobomycosis in a Post-Covid 19 Patient: A Case Report and Review of Literature.
Chavan, SS, Chandrashekhar, TN
Turk patoloji dergisi. 2023;(3):206-211
Abstract
AIM: To document a case of lobomycosis and to discuss its epidemiology & diagnosis. CASE REPORT A 53-year-old male presented with a history of nasal congestion, nasal discharge, and epistaxis following Covid 19 infection. On physical examination, there was necrotic slough in the nasal vestibule near the inferior turbinate. Scrapings and punch biopsy were taken from the lesion. Hematoxylin-eosin-stained sections showed necrotic and mucoid areas with mixed inflammatory cell infiltration and numerous budding yeasts 3- 7μm diameter in singles, and small clusters with single narrow based budding as well as multiple budding including sequential budding forming "chains of yeasts". A diagnosis of Lobomycosis was made. Yeasts of lobomycosis are often confused with other yeasts such as P. brasiliensis, Candida spp., B. dermatitidis, and Cryptococci, but characteristic 'sequential budding' with a 'chain of yeasts" aid in the final diagnosis. Demonstration of yeasts with characteristic chains either in tissue sections or in potassium hydroxide (KOH) preparation of scraped material, exudate, or exfoliative cytology is the mainstay in the diagnosis as the organisms are uncultivable in vitro in culture medium.
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Pulmonary recovery after COVID-19 - a review.
Sonnweber, T, Birgit, S, Weiss, G, Löffler-Ragg, J
Expert review of respiratory medicine. 2023;(6):447-457
Abstract
INTRODUCTION COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). As the respiratory tract is the primary site of infection and host-mediated inflammatory responses, pathologies and dysfunction of the respiratory system characterize the severe disease and are typically associated with the need for oxygen supply or even ventilator support. In survivors of severe COVID-19, computed tomography follow-up frequently reveals structural lung abnormalities, and one-third of individuals who were hospitalized during acute COVID-19 demonstrate persisting lung abnormalities for at least 12 months after disease onset. AREAS COVERED This review summarizes current evidence on pulmonary recovery after COVID-19, focusing on adult patients who suffered from COVID-19 pneumonia. EXPERT OPINION Severe COVID-19 is associated with a high frequency of persisting lung abnormalities at follow-up. The long-term consequences of these findings remain elusive and urge further evaluation to identify individuals at risk for COVID-19 long-term consequences.
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Therapeutically important bioactive compounds of the genus Polygonum L. and their possible interventions in clinical medicine.
Cherian, S, Hacisayidli, KM, Kurian, R, Mathews, A
The Journal of pharmacy and pharmacology. 2023;(3):301-327
Abstract
OBJECTIVES Increasing literature data have suggested that the genus Polygonum L. possesses pharmacologically important plant secondary metabolites. These bioactive compounds are implicated as effective agents in preclinical and clinical practice due to their pharmacological effects such as anti-inflammatory, anticancer, antidiabetic, antiaging, neuroprotective or immunomodulatory properties among many others. However, elaborate pharmacological and clinical data concerning the bioavailability, tissue distribution pattern, dosage and pharmacokinetic profiles of these compounds are still scanty. KEY FINDINGS The major bioactive compounds implicated in the therapeutic effects of Polygonum genus include phenolic and flavonoid compounds, anthraquinones and stilbenes, such as quercetin, resveratrol, polydatin and others, and could serve as potential drug leads or as adjuvant agents. Data from in-silico network pharmacology and computational molecular docking studies are also highly helpful in identifying the possible drug target of pathogens or host cell machinery. SUMMARY We provide an up-to-date overview of the data from pharmacodynamic, pharmacokinetic profiles and preclinical (in-vitro and in-vivo) investigations and the available clinical data on some of the therapeutically important compounds of genus Polygonum L. and their medical interventions, including combating the outbreak of the COVID-19 pandemic.
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Th1-dominant cytokine responses in kidney patients after COVID-19 vaccination are associated with poor humoral responses.
den Hartog, Y, Malahe, SRK, Rietdijk, WJR, Dieterich, M, Gommers, L, Geers, D, Bogers, S, van Baarle, D, Diavatopoulos, DA, Messchendorp, AL, et al
NPJ vaccines. 2023;(1):70
Abstract
Cytokines are regulators of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the contribution of cytokine-secreting CD4+ and CD8+ memory T cells to the SARS-CoV-2-specific humoral immune response in immunocompromised kidney patients is unknown. Here, we profiled 12 cytokines after stimulation of whole blood obtained 28 days post second 100 μg mRNA-1273 vaccination with peptides covering the SARS-CoV-2 spike (S)-protein from patients with chronic kidney disease (CKD) stage 4/5, on dialysis, kidney transplant recipients (KTR), and healthy controls. Unsupervised hierarchical clustering analysis revealed two distinct vaccine-induced cytokine profiles. The first profile was characterized by high levels of T-helper (Th)1 (IL-2, TNF-α, and IFN-γ) and Th2 (IL-4, IL-5, IL-13) cytokines, and low levels of Th17 (IL-17A, IL-22) and Th9 (IL-9) cytokines. This cluster was dominated by patients with CKD, on dialysis, and healthy controls. In contrast, the second cytokine profile contained predominantly KTRs producing mainly Th1 cytokines upon re-stimulation, with lower levels or absence of Th2, Th17, and Th9 cytokines. Multivariate analyses indicated that a balanced memory T cell response with the production of Th1 and Th2 cytokines was associated with high levels of S1-specific binding and neutralizing antibodies mainly at 6 months after second vaccination. In conclusion, seroconversion is associated with the balanced production of cytokines by memory T cells. This emphasizes the importance of measuring multiple T cell cytokines to understand their influence on seroconversion and potentially gain more information about the protection induced by vaccine-induced memory T cells.
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Coronavirus Disease 2019 and Hypertension: How Anti-hypertensive Drugs Affect COVID-19 Medications and Vice Versa.
Doostkam, A, Hosseinpour, A, Iravani, K, Malekmakan, L, Haghpanah, A, Masjedi, F, Karimi, Z, Rouzbeh, H, Roozbeh, J
Current drug safety. 2023;(2):125-137
Abstract
BACKGROUND As a medical problem, hypertension is one of the most common disorders in cardiovascular disease. High blood pressure has been identified as one of the most familiar risk factors for the ongoing COVID-19 pandemic. We planned to explore the possible interactions between anti-hypertensive agents and drugs targeting SARS-CoV-2 with broad investigations of these medications' mechanism of action and adverse effects. METHODS Two co-authors searched the electronic databases (PubMed, Scopus, and Google Scholar) to collect papers relevant to the subject. The keywords searched were angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II receptor blockers (ARBs), sympatholytic drugs (alpha-1 blockers, beta-blockers), vasodilators (calcium channel blockers, nitrates, and hydralazine), diuretics, chloroquine, hydroxychloroquine, lopinavir/ritonavir, remdesivir, favipiravir, interferons, azithromycin, anti-cytokine agents, glucocorticoids, anticoagulant agents, nitric oxide, and epoprostenol. RESULTS QT prolongation, arrhythmia, hypokalemia, hypertriglyceridemia are the most dangerous adverse effects in the patients on COVID-19 medications and anti-hypertensive drugs. CONCLUSION This review emphasized the importance of the potential interaction between drugs used against COVID-19 and anti-hypertensive agents. Therefore, caution must be exercised when these medications are being used simultaneously.
