Integration of the Butina algorithm and ensemble learning strategies for the advancement of a pharmacophore ligand-based model: an in silico investigation of apelin agonists.

Introduction: 3D pharmacophore models describe the ligand's chemical interactions in their bioactive conformation. They offer a simple but sophisticated approach to decipher the chemically encoded ligand information, making them a valuable tool in drug design. Methods: Our research summarized the key studies for applying 3D pharmacophore models in virtual screening for 6,944 compounds of APJ receptor agonists. Recent advances in clustering algorithms and ensemble methods have enabled classical pharmacophore modeling to evolve into more flexible and knowledge-driven techniques. Butina clustering categorizes molecules based on their structural similarity (indicated by the Tanimoto coefficient) to create a structurally diverse training dataset. The learning method combines various individual pharmacophore models into a set of pharmacophore models for pharmacophore space optimization in virtual screening. Results: This approach was evaluated on Apelin datasets and afforded good screening performance, as proven by Receiver Operating Characteristic (AUC score of 0.994 ± 0.007), enrichment factor of (EF1% of 50.07 ± 0.211), Güner-Henry score of 0.956 ± 0.015, and F-measure of 0.911 ± 0.031. Discussion: Although one of the high-scoring models achieved statistically superior results in each dataset (AUC of 0.82; an EF1% of 19.466; GH of 0.131 and F1-score of 0.071), the ensemble learning method including voting and stacking method balanced the shortcomings of each model and passed with close performance measures.

Tannin Removal of Cashew Apple Juice by Powdered Gelatin Treatment and Its Utilization in Bacterial Cellulose Production.

In this study, cashew apple juice was treated with different levels of powdered gelatin (2%, 5%, and 10%) to remove tannins. The results showed that the addition of 5% gelatin removed 99.2% of condensed tannins while did not affect reducing sugars of juice. Subsequently, tannin-free cashew apple juice (CA) was aerobically fermented for 14 days with Komagataeibacter saccharivorans strain 1.1 (KS) and Gluconacetobacter entanii HWW100 (GE) in comparison with Hestrin-Schramm (HS) medium as control. The dry weight of bacterial cellulose (BC) obtained from the KS strain (2.12 and 1.48 g/L for CA and HS media, respectively) was higher than that from the GE strain (0.69 and 1.21 g/L for CA and HS media, respectively). Although GE showed low BC production yield, its viability in both media after 14-day fermentation was notable (6.06-7.21 log CFU/mL) compared to KS strain (1.90-3.30 log CFU/mL). In addition, the XRD and FT-IR analysis showed that there was no significant difference in the crystallinity and functional groups of BC films when cultured on CA and HS medium, while the morphology by SEM exhibited the phenolic molecules on the film surface. Cashew apple juice has been shown to be a viable and cost-effective medium for the BC production.

Pericarditis related to post-acute COVID infection: A case report and review of the literature.

Cardiovascular involvement has been described in acute and recovered COVID-19 patients. Here, we present a case of symptomatic pericarditis with persistent symptoms for at least six months after the acute infection and report 66 published cases of pericarditis in discharged COVID patients. Patient mean age ± SD was 49.7 ± 13.3 years, ranging from 15 to 75 years and 57.6% were female. A proportion of 89.4% patients reported at least one comorbidity, with autoimmune and allergic disorders, hypertension and dyslipidaemia, as the most frequent. Only 8.3% of patients experienced severe symptoms of acute COVID-19. The time between acute COVID and pericarditis symptoms varied from 14 to 255 days. Chest pain (90.9%), tachycardia (60.0%) and dyspnoea (38.2%) were the most frequent symptoms in post-acute pericarditis. A proportion of 45.5% and 87% of patients had an abnormal electrocardiogram and abnormal transthoracic ultrasound, respectively. Colchicine combined with non-steroidal anti-inflammatory drug (NSAID) or acetylsalicylic acid (aspirin) were prescribed to 39/54 (72%) patients. Of them, 12 were switched to corticosteroid therapy due to non-response to the first-line treatment. Only 6 patients had persisting symptoms and were considered as non-respondent to therapy.Our report highlights that pericarditis should be suspected in COVID-19 patients with persistent chest pain and dyspnoea when pulmonary function is normal. Treatment with non-steroidal anti-inflammatory and colchicine is usually effective but corticosteroids are sometimes required.

Green removal of unpleasant volatiles from soapberry (Sapindus mukorossi) extracts by two-phase microbial fermentation fortified with pomelo peel waste.

Soapberry (Sapindus mukorossi Gaertn) is a popular woody plant in Vietnam, often used as a cleaning product due to its ability to wash, foam and emulsify due to high saponin content. In this study, the performance of fermentation by two microbial strains, namely Saccharomyces cerevisiae active dry yeast (ADY) and Levilactobacillus brevis lactic acid bacteria (LB) along with the addition of pomelo peel (flavedo) was evaluated during 15 days in terms of sugar removal, antioxidant and antibacterial activities, foaming power, volatile composition, and sensory acceptability. The results showed that the soluble solid content of original extracts experienced a significant decrease from 14.5% to a stable range of 9.4-11.0% until day 15 for all fermented samples, which correlated with a reduction by approximately 60% in reducing sugars (from 12.52 g L-1 to 4.77-6.56 g L-1). In addition, the saponin content of fermented extracts was in the range of 118.2-145.0 mg L-1 while antioxidant activities were extremely reduced after 15 days of fermentation. Increases in pomelo peel imparted fermented extracts with greater antibacterial activity against Staphylococcus aureus ATCC 6538, Proteus mirabilis ATCC 25933, and Candida albicans ATCC 10231, and LB had higher activity than ADY overall. Regarding the volatile profiles, two main compounds in the original extracts, including trilaurin (75.02%) and 1-dodecanoyl-3-myristoyl glycerol (24.85%), were completely removed and replaced by new alkanes, alkenes, alcohols, esters, and organic acids, and particularly d-limonene (86.34-95.31%) upon pomelo addition. Additionally, the foaming ability and stability of fermented extracts were also enhanced and there was clear distinction between fermented and unfermented samples using principal component analysis based on sensory liking data which showed consumers' preference towards fermented samples with a high percentage of pomelo peel.

Gelatin/carboxymethyl cellulose edible films: modification of physical properties by different hydrocolloids and application in beef preservation in combination with shallot waste powder.

In this work, a gelatin/carboxymethyl cellulose (CMC) base formulation was first modified by using different hydrocolloids like oxidized starch (1404), hydroxypropyl starch (1440), locust bean gum, xanthan gum, and guar gum. The properties of modified films were characterized using SEM, FT-IR, XRD and TGA-DSC before selecting of best-modified film for further development with shallot waste powder. SEM images showed that the rough or heterogeneous surface of the base was changed to more even and smooth depending on the hydrocolloids used while FTIR results demonstrated that a new NCO functional group non-existent in the base formulation was found for most of the modified films, implying that the modification led to the formation of this functional group. Compared to other hydrocolloids, the addition of guar gum into the gelatin/CMC base has improved its properties such as better color appearance, higher stability, and less weight loss during thermal degradation, and had minimal effect on the structure of resulting films. Subsequently, the incorporation of spray-dried shallot peel powder into gelatin/CMC/guar gum was conducted to investigate the applicability of edible films in the preservation of raw beef. Antibacterial activity assays revealed that the films can inhibit and kill both Gram-positive and Gram-negative bacteria as well as fungi. It is noteworthy that the addition of 0.5% shallot powder not only effectively decelerated the microbial growth but also destroyed E. coli during 11 days of storage (2.8 log CFU g-1) and the bacterial count was even lower than that of uncoated raw beef on day 0 (3.3 log CFU g-1).

SARS-CoV-2 Reinfection and Severity of the Disease: A Systematic Review and Meta-Analysis.

Since the discovery of SARS-CoV-2, changes in genotype and reinfection with different variants have been observed in COVID-19-recovered patients, raising questions around the clinical pattern and severity of primary infection and reinfection. In this systematic review, we summarize the results of 23 studies addressing SARS-CoV-2 reinfections. A total of 23,231 reinfected patients were included, with pooled estimated reinfection rates ranging from 0.1 to 6.8%. Reinfections were more prevalent during the Omicron variant period. The mean age of reinfected patients was 38.0 ± 6. years and females were predominant among reinfected patients (M/F = 0.8). The most common symptoms during the first and second infection were fever (41.1%), cough (35.7% and 44.6%), myalgia (34.5% and 33.3%), fatigue (23.8% and 25.6%), and headaches (24.4% and 21.4%). No significant differences of clinical pattern were observed between primary infection and reinfection. No significant differences in the severity of infection were observed between primary infection and reinfection. Being female, being a patient with comorbidities, lacking anti-nucleocapsid IgG after the first infection, being infected during the Delta and Omicron wave, and being unvaccinated were associated with a higher risk of reinfection. Conflicting age-related findings were found in two studies. Reinfection with SARS-CoV-2 suggests that natural immunity is not long-lasting in COVID-19 patients.

Modification of microstructure and selected physicochemical properties of bacterial cellulose produced by bacterial isolate using hydrocolloid-fortified Hestrin-Schramm medium.

Bacterial cellulose (BC) is a biopolymer with applications in numerous industries such as food and pharmaceutical sectors. In this study, various hydrocolloids including modified starches (oxidized starch-1404 and hydroxypropyl starch-1440), locust bean gum, xanthan gum (XG), guar gum, and carboxymethyl cellulose were added to the Hestrin-Schramm medium to improve the production performance and microstructure of BC by Gluconacetobacter entanii isolated from coconut water. After 14-day fermentation, medium supplemented with 0.1% carboxymethyl cellulose and 0.1% XG resulted in the highest BC yield with dry BC content of 9.82 and 6.06 g/L, respectively. In addition, scanning electron microscopy showed that all modified films have the characteristic three-dimensional network of cellulose nanofibers with dense structure and low porosity as well as larger fiber size compared to control. X-ray diffraction indicated that BC fortified with carboxymethyl cellulose exhibited lower crystallinity while Fourier infrared spectroscopy showed characteristic peaks of both control and modified BC films.

Reinfections with Different SARS-CoV-2 Omicron Subvariants, France.

We describe 188 patients in France who were successively infected with different SARS-CoV-2 Omicron subvariants, including BA.1, BA.2, and BA.5. Time between 2 infections was <90 days for 50 (26.6%) patients and <60 days for 28 (14.9%) patients. This finding suggests that definitions for SARS-CoV-2 reinfection require revision.

Long-Term Persistence of Olfactory and Gustatory Disorders in COVID-19 Patients.

Smell and taste disorders are frequent symptoms during acute COVID-19 and may persist long after the resolution of the initial phase. This study aims to estimate the proportion and risk factors for smell and/or taste disorders at the onset of symptoms and their persistence after more than 6 months of follow-up in COVID-19 patients. We analyzed a prospective cohort of COVID-19 patients admitted to our institute in Marseille, France in early 2020. After being discharged from the hospital, patients with smell and/or taste disorders were contacted for a telephone interview. Logistic regression analysis was performed to determine the risk factors for smell and/or taste disorders. A total of 3,737 patients were included, of whom 1,676 reported smell and/or taste disorders at the onset of symptoms. Taste and/or smell disorders were independently associated with being younger and female, a lower likelihood of suffering from diabetes, cardiovascular diseases and cancer, a longer delay between the onset of symptoms and consultation, and non-severe forms of COVID-19 at admission. Of the 605 patients with smell and/or taste disorders who were followed-up, 154 (25.5%) reported the persistence of symptoms for more than 6 months. At the time of follow-up, being female, having a chronic respiratory disease and using angiotensin-converting enzyme inhibitors (ACEis) were factors independently associated with the persistence of smell and/or taste disorders. In conclusion, the long-term persistence of olfactory and gustative disorders is frequent among COVID-19 patients, notably affecting female patients and patients who suffered from chronic respiratory diseases before infection. The role of ACEis needs to be further evaluated in larger numbers of patients.

SARS-CoV-2 reinfection and COVID-19 severity.

SARS-CoV-2 reinfection rate is low. The relative severity of the first and second episodes of infection remains poorly studied. In this study, we aimed at assessing the frequency of SARS-CoV-2 reinfections and comparing the severity of the first and second episodes of infection. We retrospectively included patients with SARS-CoV-2 positive RT-PCR at least 90 days after clinical recovery from a COVID-19 episode and with at least one negative RT-PCR after the first infection. Whole genome sequencing and variant-specific RT-PCR were performed and clinical symptoms and severity of infection were retrospectively documented from medical files. A total of 209 COVID-19 reinfected patients were identified, accounting for 0.4% of positive cases diagnosed from 19 March 2020 to 24 August 2021. Serology was performed in 64 patients, of whom 39 (60.1%) had antibodies against SARS-CoV-2 when sampled at the early stage of their second infection. Only seven patients (3.4%) were infected twice with the same variant. We observed no differences in clinical presentation, hospitalization rate, and transfer to ICU when comparing the two episodes of infections. Our results suggest that the severity of the second episode of COVID-19 is in the same range as that of the first infection, including patients with antibodies.

Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review.

BACKGROUND: Long COVID-19 may affect patients after hospital discharge. AIMS: This study aims to describe the burden of the long-term persistence of clinical symptoms in COVID-19 patients. METHODS: We conducted a systematic review by using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. The PubMed and Google Scholar databases were searched for studies that included information on the prevalence of somatic clinical symptoms lasting at least 4 weeks after the onset of a PCR- or serology-confirmed diagnosis of COVID-19. The prevalence of persisting clinical symptoms was assessed and risk factors were described when investigated. Psychological symptoms and cognitive disorders were not evaluated in this study. RESULTS: Thirty-seven articles met the inclusion criteria. Eighteen studies involved in-patients only with a duration of follow-up of either less than 12 weeks, 12 weeks to 6 months, or more. In these studies, fatigue (16-64%), dyspnea (15-61%), cough (2-59%), arthralgia (8-55%), and thoracic pain (5-62%) were the most frequent persisting symptoms. In nineteen studies conducted in a majority of out-patients, the persistence of these symptoms was lower and 3% to 74% of patients reported prolonged smell and taste disorders. The main risk factors for persisting symptoms were being female, older, having comorbidities and severity at the acute phase of the disease. CONCLUSION: COVID-19 patients should have access to dedicated multidisciplinary healthcare allowing a holistic approach. Effective outpatient care for patients with long-COVID-19 requires coordination across multiple sub-specialties, which can be proposed in specialized post-COVID units.

Microencapsulation of roselle (Hibiscus sabdariffa L.) anthocyanins: Effects of drying conditions on some physicochemical properties and antioxidant activities of spray-dried powder.

Anthocyanins are important phytochemical compounds in nature that are of interest not only for their health benefits such as antioxidant, anti-inflammatory, and anti-carcinogenic properties, but also for their role in imparting attractive and characteristic color to food products. In this study, anthocyanins from hibiscus (Hibiscus sabdariffa L.) calyces were microencapsulated by spray-drying technique using maltodextrin as the carrier. The experiment was carried out in the full factorial design with two factors, namely inlet temperature (150, 160, and 170°C) and anthocyanin to maltodextrin mass ratio (1:50, 1:60, 1:70, 1:80, 1:90, and 1:100) with the aim of investigating the effect of spray drying conditions on phenolic content, anthocyanin, antioxidant activity, and color of spray-dried hibiscus powder. The results showed that increasing the carrier ratio significantly reduced the antioxidant content and their activities in the powder. However, the high level of carriers exhibited a protective effect in encapsulating anthocyanin compounds into the maltodextrin matrix, which was demonstrated by high encapsulation efficiency (>85%) observed in the samples prepared at a ratio of 1:100. It should be highlighted that although high temperature (170°C) reduced total anthocyanin concentration, it actually enhanced total phenolic content. In addition, the moisture content of the powder declined with increasing carrier ratio and inlet temperature, and it was found to be in the range of 5.57%-10.19% in the powder. With solubility greater than 93.71%, the total phenolic and total anthocyanin content of spray-dried hibiscus powder were 31.5-41.9 (mg gallic acid equivalent/g of dry powder) and 6.08-10.47 (mg cyanidin-3-glucoside/g of dry powder), respectively.

Comparison of Phytochemical Contents, Antioxidant and Antibacterial Activities of Various Solvent Extracts Obtained from 'Maluma' Avocado Pulp Powder.

Although avocado is a superfood rich in phytochemicals with high antioxidant activities, studies on the antibacterial properties of its pulp are limited, except for seed and peel portions. In this study, three types of solvent (acetone, methanol, and diethyl ether) were used to obtain the extracts from "Maluma" avocado pulp powder prepared by infrared drying. The extracts were analyzed for total polyphenols, phytopigments (total chlorophylls and carotenoids), antioxidant activities (ferric-reducing antioxidant power (FRAP), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays), and antibacterial activities against seven pathogens (Shigella sonnei ATCC 9290, Escherichia coli ATCC 8739, Salmonella typhi ATCC 6539, Vibrio parahaemolyticus ATCC 17802, Proteus mirabilis ATCC 25933, Staphylococcus aureus ATCC 6538, and Bacillus cereus ATCC 11778). The results showed that the acetone solvent could extract the highest polyphenols and chlorophylls with the highest antioxidant activity in terms of ABTS and DPPH assays. In contrast, diethyl ether exhibited the most significant content of carotenoids and FRAP values. However, the methanol extract was the best solvent, exerting the strongest antibacterial and meaningful antioxidant activities. For the bacterial activities, Gram-positive pathogens (Bacillus cereus and Staphylococcus aureus) were inhibited more efficiently by avocado extracts than Gram-negative bacteria. Therefore, the extracts from avocado powder showed great potential for applications in food processing and preservation, pharmaceuticals, and cosmetics.

Clinical outcomes in COVID-19 patients infected with different SARS-CoV-2 variants in Marseille, France.

OBJECTIVES: To compare the clinical and epidemiological aspects associated with different predominant lineages circulating in Marseille from March 2020 to January 2021. METHODS: In this single-centre retrospective cohort study, characteristics of patients infected with four different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were documented from medical files. The outcome was the occurrence of clinical failure, defined as hospitalization (for outpatients), transfer to the intensive care unit (inpatients) and death (all). RESULTS: A total of 254 patients were infected with clade 20A (20AS), 85 with Marseille-1 (M1V), 190 with Marseille-4 (M4V) and 211 with N501Y (N501YV) variants. 20AS presented a bell-shaped epidemiological curve and nearly disappeared around May 2020. M1V reached a very weak peak, then disappeared after six weeks. M4V appeared in July presented an atypical wave form for 7 months. N501YV has only recently appeared. Compared with 20AS, patients infected with M1V were less likely to report dyspnoea (adjusted odds ratio (OR) 0.50, p 0.04), rhinitis (aOR 0.57, p 0.04) and to be hospitalized (aOR 0.22, p 0.002). Patients infected with M4V were more likely to report fever than those with 20AS and M1V (aOR 2.49, p < 0.0001 and aOR 2.30, p 0.007, respectively) and to be hospitalized than those with M1V (aOR 4.81, p 0.003). Patients infected with N501YV reported lower rate of rhinitis (aOR 0.50, p 0.001) and anosmia (aOR 0.57, p 0.02), compared with those infected with 20AS. A lower rate of hospitalization was associated with N501YV infection compared with 20AS and M4V (aOR 0.33, p < 0.0001 and aOR 0.27, p < 0.0001, respectively). CONCLUSIONS: The four lineages have presentations that differ from one another, epidemiologically and clinically. This supports SARS-CoV-2 genomic surveillance through next-generation sequencing.

Screening of SARS-CoV-2 among homeless people, asylum-seekers and other people living in precarious conditions in Marseille, France, March-April 2020.

BACKGROUND: Surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among sheltered homeless and other vulnerable people might provide the information needed to prevent its spread within accommodation centres. METHODS: Data were obtained from 698 participants in different accommodation centres (411 homeless individuals, 77 asylum-seekers, 58 other people living in precarious conditions and 152 employees working in these accommodation centres) who completed questionnaires and had nasal samples collected between 26 March and 17 April 2020. SARS-CoV-2 carriage was assessed by quantitative PCR. RESULTS: We found a high acceptance rate (78.9%) for testing. Overall, 49 people (7.0%) were positive for SARS-CoV-2, including 37 homeless individuals (of 411, 9.0%) and 12 employees (of 152, 7.9%). SARS-CoV-2 positivity correlated with symptoms, although 51% of patients who tested positive did not report respiratory symptoms or fever. Among homeless people, being young (18-34 years) (odds ratio 3.83, 95% confidence interval 1.47-10.0, p = 0.006) and being housed in one specific shelter (odds ratio 9.13, 95% confidence interval 4.09-20.37, p < 0.001) were independent factors associated with SARS-CoV-2 positivity (rates of 11.4% and 20.6%, respectively). DISCUSSION: Symptom screening alone is insufficient to prevent SARS-CoV-2 transmission in vulnerable sheltered people. Systematic testing should be promoted.