Miracle-dz/UniFAR-FTUs huggingface dataset:
Cylindrical Microparticles Composed of Mesoporous Silica Nanoparticles for the Targeted Delivery of a Small Molecule and a Macromolecular Drug to the Lungs: Exemplified with Curcumin and siRNA

The transport of macromolecular drugs such as oligonucleotides into the lungs has become increasingly relevant in recent years due to their high potency. However, the chemical structure of this group of drugs poses a hurdle to their delivery, caused by the negative charge, membrane impermeability and instability. For example, siRNA to reduce tumour necrosis factor alpha (TNF-α) secretion to reduce inflammatory signals has been successfully delivered by inhalation. In order to increase the effect of the treatment, a co-transport of another anti-inflammatory ingredient was applied. Combining curcumin-loaded mesoporous silica nanoparticles in nanostructured cylindrical microparticles stabilized by the layer-by-layer technique using polyanionic siRNA against TNF-α was used for demonstration. This system showed aerodynamic properties suited for lung deposition (mass median aerodynamic diameter of 2.85 ± 0.44 µm). Furthermore, these inhalable carriers showed no acute in vitro toxicity tested in both alveolar epithelial cells and macrophages up to 48 h incubation. Ultimately, TNF-α release was significantly reduced by the particles, showing an improved activity co-delivering both drugs using such a drug-delivery system for specific inhibition of TNF-α in the lungs.
The Role of Therapeutic Plasma Exchange (TPE) in Multisystem Inflammatory Syndrome in Children (MIS-C)

Multisystemic inflammatory syndrome in children (MIS-C) is a new potentially life-threatening disease that is related to coronavirus disease 2019 (COVID-19). The aim of this study is to reveal the clinical and laboratory results of MIS-C and the role of therapeutic plasma exchange (TPE) in its treatment. Clinical, laboratory and radiological characteristics of the patients who were admitted to the pediatric ward and pediatric intensive care unit (PICU) of a tertiary hospital with a diagnosis of MIS-C between April 2020 and March 2021 were included in the study. Forty-one patients were admitted to our hospital with a diagnosis of MIS-C. Twenty-one (51.2%) patients were admitted to the PICU. Six patients needed invasive mechanical ventilation (14.6%), 10 patients (24.4%) TPE and 3 patients (7.3%) needed extracorporeal membrane oxygenation (ECMO). The patients were grouped according to need for PICU admission (Group 1: no need for PICU, Group 2: need for PICU admission). Group 2 had significantly higher levels of C-reactive protein (CRP), alanine aminotransferase (ALT), ferritin, D-dimer, pro-B type natriuretic peptide (pro BNP) and lactate (p < 0.05). Hyponatremia found to be an independent risk factor for inpatient MIS-C in the PICU. We think that dynamic laboratory trending is beneficial in determining the need for PICU admission and TPE may be effective in critically ill patients.
Atopic Dermatitis Treated Safely with Dupilumab during Pregnancy: A Case Report and Review of the Literature

Dupilumab is currently the only biologic treatment approved for moderate-to-severe atopic dermatitis. Though limited, available clinical data describing dupilumab use in pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Systemic treatment in pregnant women with atopic dermatitis is currently restricted to corticosteroids, cyclosporine A, and azathioprine. Atopic dermatitis often has a deleterious course in pregnancy which can cause substantial distress and significantly impact on global health and quality of life. We report a case of severe atopic dermatitis treated safely with dupilumab during pregnancy with no adverse maternal or fetal outcomes observed. Our case highlights that dupilumab use in pregnancy has its place but should always be preceded by careful assessment of the risks and benefits. Clinicians are encouraged to enroll their patients in relevant pregnancy registry studies to monitor outcomes in women exposed to dupilumab during pregnancy and lactation.
Characterization and Quantification of Selenoprotein P: Challenges to Mass Spectrometry

Selenoprotein P (SELENOP) is an emerging marker of the nutritional status of selenium and of various diseases, however, its chemical characteristics still need to be investigated and methods for its accurate quantitation improved. SELENOP is unique among selenoproteins, as it contains multiple genetically encoded SeCys residues, whereas all the other characterized selenoproteins contain just one. SELENOP occurs in the form of multiple isoforms, truncated species and post-translationally modified variants which are relatively poorly characterized. The accurate quantification of SELENOP is contingent on the availability of specific primary standards and reference methods. Before recombinant SELENOP becomes available to be used as a primary standard, careful investigation of the characteristics of the SELENOP measured by electrospray MS and strict control of the recoveries at the various steps of the analytical procedures are strongly recommended. This review critically discusses the state-of-the-art of analytical approaches to the characterization and quantification of SELENOP. While immunoassays remain the standard for the determination of human and animal health status, because of their speed and simplicity, mass spectrometry techniques offer many attractive and complementary features that are highlighted and critically evaluated.
Inositol Signaling in the Basidiomycete Fungus Schizophyllum commune

Intracellular signaling is conserved in eukaryotes to allow for response to extracellular signals and to regulate development and cellular functions. In fungi, inositol phosphate signaling has been shown to be involved in growth, sexual reproduction, and metabolic adaptation. However, reports on mushroom-forming fungi are lacking so far. In Schizophyllum commune, an inositol monophosphatase has been found up-regulated during sexual development. The enzyme is crucial for inositol cycling, where it catalyzes the last step of inositol phosphate metabolism, restoring the inositol pool from the monophosphorylated inositol monophosphate. We overexpressed the gene in this model basidiomycete and verified its involvement in cell wall integrity and intracellular trafficking. Strong phenotypes in mushroom formation and cell metabolism were evidenced by proteome analyses. In addition, altered inositol signaling was shown to be involved in tolerance towards cesium and zinc, and increased metal tolerance towards cadmium, associated with induced expression of kinases and repression of phosphatases within the inositol cycle. The presence of the heavy metals Sr, Cs, Cd, and Zn lowered intracellular calcium levels. We could develop a model integrating inositol signaling in the known signal transduction pathways governed by Ras, G-protein coupled receptors, and cAMP, and elucidate their different roles in development.
Predicting Long-Term Mortality in Patients with Angina across the Spectrum of Dysglycemia: A Machine Learning Approach

We aimed to develop and validate a model for predicting mortality in patients with angina across the spectrum of dysglycemia. A total of 1479 patients admitted for coronary angiography due to angina were enrolled. All-cause mortality served as the primary endpoint. The models were validated with five-fold cross validation to predict long-term mortality. The features selected by least absolute shrinkage and selection operator (LASSO) were age, heart rate, plasma glucose levels at 30 min and 120 min during an oral glucose tolerance test (OGTT), the use of angiotensin II receptor blockers, the use of diuretics, and smoking history. This best performing model was built using a random survival forest with selected features. It had a good discriminative ability (Harrell’s C-index: 0.829) and acceptable calibration (Brier score: 0.08) for predicting long-term mortality. Among patients with obstructive coronary artery disease confirmed by angiography, our model outperformed the Global Registry of Acute Coronary Events discharge score for mortality prediction (Harrell’s C-index: 0.829 vs. 0.739, p < 0.001). In conclusion, we developed a machine learning model to predict long-term mortality among patients with angina. With the integration of OGTT, the model could help to identify a high risk of mortality across the spectrum of dysglycemia.
Performance of Ground Granulated Blast-Furnace Slag and Coal Fly Ash Ternary Portland Cements Exposed to Natural Carbonation

Ternary Portland cements are new cementitious materials that contain different amounts of cement replacements. Ternary Portland cements composed of granulated blast-furnace slag (GBFS), coal fly ash (CFA), and clinker (K) can afford some environmental advantages by lowering the Portland cement clinker use. Accordingly, this is an opportunity to reduce carbon dioxide emissions and achieve net-zero carbon emissions by 2050. Furthermore, GBFS and CFA possess pozzolanic properties and enhance the mechanical strength and durability at later ages. Compressive strength and natural carbonation tests were performed in mortar and concrete. Cement-based materials made with GBFS and/or CFA presented a delay in the compressive strength development. In addition, they exhibited lower carbonation resistance than that of mortar and concrete made with plain Portland cements. Concrete reinforcement remains passive in common conditions; however, it could be corroded if the concrete pore solution pH drops due to the carbonation process. Service life estimation was performed for the ternary cements regarding the carbonation process. This information can be useful to material and civil engineers in designing concretes made with these ternary cements.
Promoting Mental Health of Nurses During the Coronavirus Pandemic: Will the Rapid Deployment of Nurses' Training Programs During COVID-19 Improve Self-Efficacy and Reduce Anxiety?

Introduction The nursing profession is extremely demanding and stressful. Nurses have been facing a tremendous amount of fear and anxiety during the ongoing coronavirus disease 2019 (COVID-19) pandemic. General self-efficacy is considered one of the most influential factors that can modify the impact of anxiety on nurses' mental health. In this study, we aimed to determine the predictors of self-efficacy and anxiety among nurses during the current COVID-19 pandemic. Methods We conducted a cross-sectional survey involving 368 nurses working in a tertiary care hospital. The General Self-Efficacy scale (GSE) and Generalized Anxiety Disorder Scale-7 (GAD-7) were used for assessing self-efficacy and anxiety. The chi-square test followed by bivariate and multivariable regression analyses was performed to identify the determinants of self-efficacy and anxiety. Results The mean age of the nurses was 28.91 years (SD=3.68), with a mean working experience in the nursing field of 5.32 years (SD=2.48). The mean self-efficacy and anxiety scores were 32.19 (SD=4.53) and 3.82 (SD=2.87), respectively. Multivariable analysis showed that higher age (>30 years, p=.003), professional education acquired through a diploma course instead of a graduate degree (p<.001), and lack of training on handling COVID-19 patients (p=.003) were significant determinants of higher anxiety among nurses. Similarly, higher economic status (p=.001), sufficient COVID-19 training (p=.049), having family members tested positive for COVID-19 (p=.012), professional experience (≤5 years, p<0.001), and quarantine period (≤14 days, p=.002) were revealed to be independent determinants of a higher sense of self-efficacy among nurses during the COVID-19 pandemic. Conclusion Receiving adequate levels of training on COVID-19 plays a vital role in improving self-efficacy and reducing anxiety among nurses during the ongoing pandemic. Managing anxiety, increasing self-efficacy, and ensuring more exposure to COVID-19-related training may improve nurses' mental health and prepare them for fighting pandemics in a much better and more efficient manner.
Temporal Trends and Severity in Injury and Illness Incidence in the National Basketball Association Over 11 Seasons

Background: There is a paucity of current data describing injuries in professional basketball players. Utilizing publicly available injury data will allow for greater transparency for stakeholders to use the data as a shared resource to create future basketball injury prevention programs. Purpose: To describe injury and illness incidence, severity, and temporal trends in National Basketball Association (NBA) players. Among those who develop time-loss injury or illness, we estimated severity based on games missed because of injury or illness. Study Design: Descriptive epidemiology study. Methods: Publicly available NBA data were extracted through a reproducible computer-programmed process from the 2008 to 2019 seasons. Data were externally validated by 2 independent reviewers through other publicly available data sources. Injury and illness were calculated per 1000 athlete game-exposures (AGEs). Injury severity was calculated as games missed because of injury or illness. Injury and illness data were stratified by body part, position, severity (slight, minor, moderate, or severe), month, and year. Results: A total of 1369 players played a total of 302,018 player-games, with a total of 5375 injuries and illnesses. The overall injury and illness incidence was 17.80 per 1000 AGEs. The median injury severity was 3 games (interquartile range, 0-6 games) missed per injury. Overall, 33% of injuries were classified as slight; 26%, as minor; 26%, as moderate; and 15%, as severe. The ankle (2.57 injuries/1000 AGEs), knee (2.44 injuries/1000 AGEs), groin/hip/thigh (1.99 injuries/1000 AGEs), and illness (1.85 illnesses/1000 AGEs) had the greatest incidence of injury and illness. Neither injury or illness incidence nor severity was different among basketball playing positions. Injury incidence demonstrated increasing incremental trends with season progression. Injuries were similar throughout the 11-year reporting period, except for a substantial increase in the lockout-shortened 2012 season. Conclusion: The ankle and knee had the greatest injury incidence. Injury incidence was similar among basketball positions. Injury incidence increased throughout the season, demonstrating the potential relationship between player load and injury incidence.
Incidence and Risk Factors for Acute Kidney Injury during the Treatment of Methicillin-Sensitive Staphylococcus aureus Infections with Cloxacillin Based Antibiotic Regimens: A French Retrospective Study

Background: Cloxacillin has been associated with the occurrence of acute kidney injury (AKI). The incidence of this complication in the literature is low (2.5–3.5%) and probably underestimated, since most studies were done by selecting the presence of AKI in discharge codes. Objectives: The primary goal was to define the incidence of AKI in patients with a methicillin-sensitive Staphylococcus aureus infection treated with cloxacillin based antibiotic regimens. The secondary goals were to identify the risk factors associated with this complication and to describe the characteristics of AKI. Patients and methods: We carried out a retrospective study. The inclusion criteria were adult patients hospitalized in a medical department at the Le Mans Hospital between 1 July 2012 and 1 July 2019 with a diagnosis of methicillin-sensitive Staphylococcus aureus infection treated with cloxacillin. Results: One hundred twenty-three patients were included in the study. Forty-two patients (34.2%) developed AKI. In the multivariate analysis, age, the use of diuretics and the presence of endocarditis were independently associated with AKI. Age was associated with an OR of 4.38 (p = 0.002) for patients older than 75, being treated with diuretics was associated with an OR of 2.94 (p = 0.036) for loop diuretics and an OR of 3.05 (p = 0.027) for non-loop diuretics; type of infection was associated with an OR of 3.42 (p = 0.012) for endocarditis. Conclusions: The occurrence of AKI is frequent during cloxacillin based antibiotic regimens for methicillin-sensitive Staphylococcus aureus infections. Being older than 75, being treated with diuretics and the presence of endocarditis were the main risk factors for AKI in our population.
Direct Evidence for Viral Antigen Presentation during Latent Cytomegalovirus Infection

Murine models of cytomegalovirus (CMV) infection have revealed an immunological phenomenon known as “memory inflation” (MI). After a peak of a primary CD8+ T-cell response, the pool of epitope-specific cells contracts in parallel to the resolution of productive infection and the establishment of a latent infection, referred to as “latency. ” CMV latency is associated with an increase in the number of cells specific for certain viral epitopes over time. The inflationary subset was identified as effector-memory T cells (iTEM) characterized by the cell surface phenotype KLRG1+CD127−CD62L−. As we have shown recently, latent viral genomes are not transcriptionally silent. Rather, viral genes are sporadically desilenced in a stochastic fashion. The current hypothesis proposes MI to be driven by presented viral antigenic peptides encoded by the corresponding, stochastically expressed viral genes. Although this mechanism suggests itself, independent evidence for antigen presentation during viral latency is pending. Here we fill this gap by showing that T cell-receptor transgenic OT-I cells that are specific for peptide SIINFEKL proliferate upon adoptive cell transfer in C57BL/6 recipients latently infected with murine CMV encoding SIINFEKL (mCMV-SIINFEKL), but not in those latently infected with mCMV-SIINFEKA, in which antigenicity is lost by mutation L8A of the C-terminal amino acid residue.
Follow-Up Analysis of Pulmonary Function, Exercise Capacity, Radiological Changes, and Quality of Life Two Months after Recovery from SARS-CoV-2 Pneumonia

Background and objective: According to the World Health Organization (WHO), more than 100 million people have already recovered from SARS-CoV-2 infection. Therefore, it is imperative to understand the possible outcomes of COVID-19. The aim of our study was to evaluate pulmonary function, exercise capacity, residual radiological changes, and health-related quality of life (HRQoL) at follow-up in a cohort of SARS-CoV-2 pneumonia survivors. Materials and Methods: Patients with SARS-CoV-2 infection and radiologically confirmed lung injury, with no chronic lung disease prior to this infection, were included in the study. Patients’ evaluation 2 months after their discharge from hospital included spirometry (FVC, FEV1, FEV1/FVC), determination of lung volume (TLC, VC, RV) and diffusing capacity of lung for carbon monoxide (DLCO, adjusted for hemoglobin), 6-Minute Walk Test (6MWT), chest CT scan, and 36-Item Short Form General Health Survey (SF-36). Results: Fifty-one patients (25 men, 26 women) were included. The mean age was 56 years (SD-11,72). Eighteen patients (35.3%) had experienced moderate COVID-19, 21 (41.2%) severe COVID-19, and 12 (23.5%) were critically ill. The mean follow-up visit time after the discharge from hospital was 60 days (SD-17). Pulmonary function at follow-up was impaired in 24 (47.2%) patients. Reduced lung volume was observed in 15 (29.4%) patients, DLCO reduction in 15 (29.4%) patients, and only one patient displayed obstruction. Twelve patients out of 51 (12/51, 27.3%) showed reduced physical capacity in the 6 MWT, and 3/51 (9.1%) showed desaturation, with SO2 < 90%. Different levels of abnormality were found in 49/51 (96,1%) patients on follow-up chest CT; the median radiological score was 10.9 (SD ± 8.87, possible maximal score, 25). Ground-glass opacity was the most common radiological feature, found in 45 (88.2%) patients. The SF-36 scores demonstrated a reduction in health status across all domains, with the lowest scores for limitations in social activities because of physical problems, vitality, and general health. Conclusion: In the group of COVID-19 pneumonia survivors 2 months after hospital discharge, residual changes in the lungs on chest CT and in lung function and reduced physical and HRQoL status were found in a significant number of patients. To evaluate COVID-19 long-term consequences, a longer follow-up period is needed.
Factors Predicting Ictal Quality in Bilateral Electroconvulsive Therapy Sessions

In electroconvulsive therapy (ECT), ictal characteristics predict treatment response and can be modified by changes in seizure threshold and in the ECT technique. We aimed to study the impact of ECT procedure-related variables that interact during each session and might influence the seizure results. Two hundred and fifty sessions of bilateral ECT in forty-seven subjects were included. Seizure results were evaluated by two different scales of combined ictal EEG parameters (seizure quality index (SQI) and seizure adequacy markers sum (SAMS) scores) and postictal suppression rating. Repeated measurement regression analyses were performed to identify predictors of each session’s three outcome variables. Univariate models identified age, physical status, hyperventilation, basal oxygen saturation, days between sessions, benzodiazepines, lithium, and tricyclic antidepressants as predictors of seizure quality. Days elapsed between sessions, higher oxygen saturation and protocolized hyperventilation application were significant predictors of better seizure quality in both scales used in multivariate models. Additionally, lower ASA classification influenced SQI scores as well as benzodiazepine use and lithium daily doses were predictors of SAMS scores. Higher muscle relaxant doses and lower applied stimulus intensities significantly influenced the postictal suppression rating. The study found several modifiable procedural factors that impacted the obtained seizure characteristics; they could be adjusted to optimize ECT session results.
Secondary Metabolite Production Potential of Mangrove-Derived Streptomyces olivaceus

Mangroves are intertidal extreme environments with rich microbial communities. Actinobacteria are well known for producing antibiotics. The search for biosynthetic potential of Actinobacteria from mangrove environments could provide more possibilities for useful secondary metabolites. In this study, whole genome sequencing and MS/MS analysis were used to explore the secondary metabolite production potential of one actinobacterial strain of Streptomyces olivaceus sp. , isolated from a mangrove in Macau, China. The results showed that a total of 105 gene clusters were found in the genome of S. olivaceus sp. , and 53 known secondary metabolites, including bioactive compounds, peptides, and other products, were predicted by genome mining. There were 28 secondary metabolites classified as antibiotics, which were not previously known from S. olivaceus. ISP medium 2 was then used to ferment the S. olivaceus sp. to determine which predicted secondary metabolite could be truly produced. The chemical analysis revealed that ectoine, melanin, and the antibiotic of validamycin A could be observed in the fermentation broth. This was the first observation that these three compounds can be produced by a strain of S. olivaceus. Therefore, it can be concluded that Actinobacteria isolated from the mangrove environment have unknown potential to produce bioactive secondary metabolites.