Miracle-dz/UniFAR-FTUs huggingface dataset:
A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and Challenges against Neurodegeneration

As life expectancy increases, dementia affects a growing number of people worldwide. Besides current treatments, phosphodiesterase 9 (PDE9) represents an alternative target for developing innovative small molecules to contrast neurodegeneration. PDE inhibition promotes neurotransmitter release, amelioration of microvascular dysfunction, and neuronal plasticity. This review will provide an update on natural and nature-inspired PDE9 inhibitors, with a focus on the structural features of PDE9 that encourage the development of isoform-selective ligands. The expression in the brain, the presence within its structure of a peculiar accessory pocket, the asymmetry between the two subunits composing the protein dimer, and the selectivity towards chiral species make PDE9 a suitable target to develop specific inhibitors. Additionally, the world of natural compounds is an ideal source for identifying novel, possibly asymmetric, scaffolds, and xanthines, flavonoids, neolignans, and their derivatives are currently being studied. In this review, the available literature data were interpreted and clarified, from a structural point of view, taking advantage of molecular modeling: 3D structures of ligand-target complexes were retrieved, or built, and discussed.
Antiviral treatment for hepatitis C is associated with a reduced risk of atherosclerotic cardiovascular outcomes: A systematic review and meta‐analysis

Hepatitis C virus infection (HCV) may be associated with a greater risk of cardiovascular disease (CVD), and the evidence for whether antiviral therapy for HCV could reduce the risk of CVD events is inconsistent. The aim of this meta‐analysis was to investigate the association between anti‐HCV treatment and the risk of CVD. We searched PubMed, EMBASE and Cochrane Library databases from inception to 20 August 2020. The pooled hazard ratio (HR) with 95% confidence interval (CI) of the risk of CVD events [any CVD, coronary artery disease (CAD) and stroke] was calculated using the random‐effects model. A total of eleven studies, including 309,470 subjects, were enrolled in this meta‐analysis. Among those, four studies reported on any CVD between anti‐HCV–treated and anti‐HCV–untreated patients, five studies reported on CAD, and five studies reported on stroke. Also, five studies reported on any CVD between patients with sustained virological response (SVR) and without SVR. Overall, antiviral therapy for HCV was associated with a reduced risk of any CVD (HR = 0.64, 95% CI: 0.50–0.83), CAD (HR = 0.73, 95% CI: 0.55–0.96) and stroke (HR = 0.74, 95% CI: 0.64–0.86). Besides, we found that SVR was associated with a significant decrease in any CVD compared with non‐SVR (HR = 0.74, 95% CI: 0.60–0.92). In conclusion, this meta‐analysis demonstrated that antiviral therapy for HCV was associated with a reduced risk of CVD events. In addition, the risk of CVD events was lower in individuals with SVR compared with those without SVR.
Success Rates of Monitoring for Healthcare Professionals with a Substance Use Disorder: A Meta-Analysis

In the past decades, monitoring programs have been developed for healthcare professionals with substance use disorders. We aimed to explore estimates of abstinence and work retention rates after participation in such monitoring programs. A literature search was performed using PubMed, Embase, PsycINFO, and CINAHL. Twenty-nine observational studies reporting on success rates (abstinence and work retention) of monitoring for healthcare professionals with a substance use disorder were included in the meta-analysis. Quality-effects models calculated pooled success rates and corresponding 95%-Confidence Intervals (CI), with subgroup analyses on monitoring elements and patient characteristics. Pooled success rates were 72% for abstinence (95%-CI = 63–80%) and 77% for work retention (95%-CI = 61–90%). Heterogeneity across studies was partly explained by the starting moment of monitoring, showing higher abstinence rates for studies that started monitoring after treatment completion (79%; 95%-CI = 72–85%) compared to studies that started monitoring with treatment initiation (61%; 95%-CI = 50–72%). About three-quarters of healthcare professionals with substance use disorders participating in monitoring programs are abstinent during follow-up and working at the end of the follow-up period. Due to selection and publication bias, no firm conclusions can be drawn about the effectiveness of monitoring for healthcare professionals with SUD.
Identification of Important N-Linked Glycosylation Sites in the Hemagglutinin Protein and Their Functional Impact on DC-SIGN Mediated Avian Influenza H5N1 Infection

DC-SIGN, a C-type lectin mainly expressed in dendritic cells (DCs), has been reported to mediate several viral infections. We previously reported that DC-SIGN mediated H5N1 influenza A virus (AIVs) infection, however, the important DC-SIGN interaction with N-glycosylation sites remain unknown. This study aims to identify the optimal DC-SIGN interacting N-glycosylation sites in HA proteins of H5N1-AIVs. Results from NetNGlyc program analyzed the H5 hemagglutinin sequences of isolates during 2004–2020, revealing that seven and two conserved N-glycosylation sites were detected in HA1 and HA2 domain, respectively. A lentivirus pseudotyped A/Vietnam/1203/04 H5N1 envelope (H5N1-PVs) was generated which displayed an abundance of HA5 proteins on the virions via immuno-electron microscope observation. Further, H5N1-PVs or reverse-genetics (H5N1-RG) strains carrying a serial N-glycosylated mutation was generated by site-directed mutagenesis assay. Human recombinant DC-SIGN (rDC-SIGN) coated ELISA showed that H5N1-PVs bound to DC-SIGN, however, mutation on the N27Q, N39Q, and N181Q significantly reduced this binding (p < 0.05). Infectivity and capture assay demonstrated that N27Q and N39Q mutations significantly ameliorated DC-SIGN mediated H5N1 infection. Furthermore, combined mutations (N27Q&N39Q) significantly waned the interaction on either H5N1-PVs or -RG infection in cis and in trans (p < 0.01). This study concludes that N27 and N39 are two essential N-glycosylation contributing to DC-SIGN mediating H5N1 infection.
Niobium Modification of Au/CeO2 for Enhanced Catalytic Performance over Benzene Combustion

A novel Au/Nb-CeO2 was obtained by loading Au to Nb-modified CeO2 adopting a thermal decomposition method. The modification effect of Nb on the physicochemical properties and performance of Au/CeO2 for benzene combustion was systematically clarified. The incorporated Nb species are found to be present in the two forms of highly-dispersed state and bulk NbOx into CeO2 lattice in the obtained Au/Nb-CeO2 catalyst. They greatly enlarged the BET surface area, improved the redox property, and strengthened the Au–support interaction. The addition of Nb also promotes catalytic performance of Au/CeO2, especially high-temperature performance: T90% decreases by ca. 40 °C and Au/Nb-CeO2 exhibits superior stability to Au/CeO2 at 230 °C. The slightly improved Au dispersion and redox properties resulted in the small increase on initial activity of Au/Nb-CeO2, but the large BET surface area and the strong Au–support interaction greatly promoted the high-temperature performance improvement of Au/Nb-CeO2 for benzene combustion reaction.
Dual Inhibition of Salmonella enterica and Clostridium perfringens by New Probiotic Candidates Isolated from Chicken Intestinal Mucosa

The poultry industry is the fastest-growing agricultural sector globally. With poultry meat being economical and in high demand, the end product’s safety is of importance. Globally, governments are coming together to ban the use of antibiotics as prophylaxis and for growth promotion in poultry. Salmonella and Clostridium perfringens are two leading pathogens that cause foodborne illnesses and are linked explicitly to poultry products. Furthermore, numerous outbreaks occur every year. A substitute for antibiotics is required by the industry to maintain the same productivity level and, hence, profits. We aimed to isolate and identify potential probiotic strains from the ceca mucosa of the chicken intestinal tract with bacteriocinogenic properties. We were able to isolate multiple and diverse strains, including a new uncultured bacterium, with inhibitory activity against Salmonella Typhimurium ATCC 14028, Salmonella Abony NCTC 6017, Salmonella Choleraesuis ATCC 10708, Clostridium perfringens ATCC 13124, and Escherichia coli ATCC 25922. The five most potent strains were further characterized for their probiotic potential (i.e., sensitivity to antibiotics and tolerance to gastrointestinal physicochemical conditions). Our analyzed lactobacilli strains exhibited some interesting probiotic features while being inhibitory against targeted pathogens.
Comparison of Smoothing Filters’ Influence on Quality of Data Recorded with the Emotiv EPOC Flex Brain–Computer Interface Headset during Audio Stimulation

Off-the-shelf, consumer-grade EEG equipment is nowadays becoming the first-choice equipment for many scientists when it comes to recording brain waves for research purposes. On one hand, this is perfectly understandable due to its availability and relatively low cost (especially in comparison to some clinical-level EEG devices), but, on the other hand, quality of the recorded signals is gradually increasing and reaching levels that were offered just a few years ago by much more expensive devices used in medicine for diagnostic purposes. In many cases, a well-designed filter and/or a well-thought signal acquisition method improve the signal quality to the level that it becomes good enough to become subject of further analysis allowing to formulate some valid scientific theories and draw far-fetched conclusions related to human brain operation. In this paper, we propose a smoothing filter based upon the Savitzky–Golay filter for the purpose of EEG signal filtering. Additionally, we provide a summary and comparison of the applied filter to some other approaches to EEG data filtering. All the analyzed signals were acquired from subjects performing visually involving high-concentration tasks with audio stimuli using Emotiv EPOC Flex equipment.
Uremia Coupled with Mucosal Damage Predisposes Mice with Kidney Disease to Systemic Infection by Commensal Candida albicans

Infections are the second major cause of mortality in patients with kidney disease and accompanying uremia. Both vascular access and non–access-related infections contribute equally to the infection-related deaths in patients with kidney disease. Dialysis is the most common cause of systemic infection by Candida albicans in these patients. C. albicans also reside in the gastrointestinal tract as a commensal fungus. However, the contribution of gut-derived C. albicans in non–access-related infections in kidney disease is unknown. Using a mouse model of kidney disease, we demonstrate that uremic animals showed increased gut barrier permeability, impaired mucosal defense, and dysbiosis. The disturbance in gut homeostasis is sufficient to drive the translocation of microbiota and intestinal pathogen Citrobacter rodentium to extraintestinal sites but not C. albicans. Interestingly, a majority of uremic animals showed fungal translocation only when the gut barrier integrity is disrupted. Our data demonstrate that uremia coupled with gut mucosal damage may aid in the translocation of C. albicans and cause systemic infection in kidney disease. Because most of the individuals with kidney disease suffer from some form of gut mucosal damage, these results have important implications in the risk stratification and control of non–access-related opportunistic fungal infections in these patients.
Temporal proximity to the elicitation of curiosity is key for enhancing memory for incidental information

Curiosity states benefit memory for target information, but also incidental information presented during curiosity states. However, it is not known whether incidental curiosity-enhanced memory depends on when incidental information during curiosity states is encountered. Here, participants incidentally encoded unrelated face images at different time points while they anticipated answers to trivia questions. Across two experiments, we found memory enhancements for unrelated faces presented during high-curiosity compared with low-curiosity states, but only when presented shortly after a trivia question. This suggests processes associated with the elicitation of curiosity—but not sustained anticipation or the satisfaction of curiosity—enhance memory for incidental information.
A review of the impact and potential of intermittent aeration on continuous flow nitrifying activated sludge

Intermittent aeration of activated sludge plants (ASPs) is a potential strategy that may help deliver reduced operational costs while providing an adequate effluent quality. This review paper critically assesses the implications of temporary turning aeration off in continuous flow nitrifying ASPs, including impact on dissolved oxygen concentrations, process biology and operational parameters. The potential savings and pitfalls of the approach are further illustrated through an example scenario. Findings from this review indicate rapid dissolved oxygen depletion times of 1–60 minutes and a significant reduction of nitrification rates from 0.12 to less than 0.04 g NH4-N/g VSS/d. Further negative impacts include a potential increase in nitrous oxide emissions from 0.07% to 27% N2O-N per mole of NH4-N oxidized; enhanced filamentous bacteria growth; a noticeable increase in effluent turbidity developing within one hour of air supply interruption; and, if no mechanical mixing is in place, risk of mixed liquor suspended solids settling in the bioreactor within short times (23–53 min). However, the potential savings in terms of aeration costs could amount to 33%–45% if instrumentation adequacy and impact on process biology and carbon equivalent emissions are excluded from the economic analysis. Further research on the areas of nitrous oxide emissions and the use of hybrid systems to provide resilience and robustness to the intermittent operation of continuous flow nitrifying ASPs is recommended.
Do truth-telling oaths improve honesty in crowd-working?

This study explores whether an oath to honesty can reduce both shirking and lying among crowd-sourced internet workers. Using a classic coin-flip experiment, we first confirm that a substantial majority of Mechanical Turk workers both shirk and lie when reporting the number of heads flipped. We then demonstrate that lying can be reduced by first asking each worker to swear voluntarily on his or her honor to tell the truth in subsequent economic decisions. Even in this online, purely anonymous environment, the oath significantly reduced the percent of subjects telling “big” lies (by roughly 27%), but did not affect shirking. We also explore whether a truth-telling oath can be used as a screening device if implemented after decisions have been made. Conditional on flipping response, MTurk shirkers and workers who lied were significantly less likely to agree to an ex-post honesty oath. Our results suggest oaths may help elicit more truthful behavior, even in online crowd-sourced environments.
A MODEL FOR DIFFUSION of SODIUM IN GREEN OLIVES AT DIFFERENT TEMPERATURES and LYE CONCENTRATIONS

A diffusion model for a composite flat plate, consisting of a thin skin of thickness δ, and a thicker flesh of thickness L, with constant flesh and skin effective diffusion coefficients (D F and D S ) was successfully adjusted to the experimental data obtained during the debittering of green olives variety Arauco (also known as Criolla) at 15C, 20C and 25C and lye concentrations of 1.50%, 2.25% and 3.00% of NaOH. The D F values ranged between 1.64 x 10 -10 and 9.20 x 10 -10 m 2 /s, and increased with increasing temperature and lye concentration. The D S values ranged between 1.27 × 10 -12 and 5.63 × 10 -12 m 2 /s, and also increased with increasing lye concentration and temperature. Activation Energies (Ea) of diffusion in the flesh and the skin were evaluated with an Arrhenius-type relationship. The Ea values for the flesh were 93.2, 72.7 and 64.8 kJ/mol, and 92.7, 91.46 and 33.67 for the skin for lye concentrations of 1.50%, 2.25% and 3.00%, respectively.
Factors Associated with Refusal or Discontinuation of Treatment in Patients with Bladder Cancer: A Cohort Population-Based Study in Taiwan

Cancer treatment causes adverse effects that lead to refusal or discontinuation of treatment. The purposes of this study were to identify 1) the factors associated with and 2) the reasons for refusing and discontinuing treatment in patients with bladder cancer (BC). We conducted a retrospective cohort study in patients diagnosed with BC in Taiwan from 1 January 2014 to 30 June 2019 using a linked cancer registry database. Of the 1247 BC patients in the study cohort, 2.1% reported refusing treatment. Patients with less education and those diagnosed at cancer stage II–IV were more likely to refuse treatment. The major reason for refusing treatment was “patient or the family considered patient’s poor physical condition (chronic disease or unstable systemic disease), difficulty in enduring any condition likely to cause physical discomfort from disease treatment”. A total of 4.3% of BC patients reported discontinuing treatment. Patients not living in the northern region of Taiwan and those diagnosed at cancer stage II–IV were more likely to terminate treatment before completion. The major reason given for discontinuing treatment was inconvenient transportation. Sufficient social resources and supportive care can help BC patients cope with the physical and psychological burden of treatment.
Facial Imitation Improves Emotion Recognition in Adults with Different Levels of Sub-Clinical Autistic Traits

We used computer-based automatic expression analysis to investigate the impact of imitation on facial emotion recognition with a baseline-intervention-retest design. The participants: 55 young adults with varying degrees of autistic traits, completed an emotion recognition task with images of faces displaying one of six basic emotional expressions. This task was then repeated with instructions to imitate the expressions. During the experiment, a camera captured the participants’ faces for an automatic evaluation of their imitation performance. The instruction to imitate enhanced imitation performance as well as emotion recognition. Of relevance, emotion recognition improvements in the imitation block were larger in people with higher levels of autistic traits, whereas imitation enhancements were independent of autistic traits. The finding that an imitation instruction improves emotion recognition, and that imitation is a positive within-participant predictor of recognition accuracy in the imitation block supports the idea of a link between motor expression and perception in the processing of emotions, which might be mediated by the mirror neuron system. However, because there was no evidence that people with higher autistic traits differ in their imitative behavior per se, their disproportional emotion recognition benefits could have arisen from indirect effects of imitation instructions
Antibiotic-Associated Adverse Events in Hospitalized Children.

BACKGROUND Antibiotic-associated adverse events (AEs) in hospitalized children have not been comprehensively characterized. METHODS We conducted a retrospective observational study of children hospitalized at The Johns Hopkins Hospital receiving ≥24 hours of systemic antibiotics. Consensus regarding antibiotic-associated AE definitions was established by 5 infectious diseases specialists prior to data collection. Two physicians reviewed potential AEs and determined whether they were more likely than not related to antibiotics after comprehensive manual chart review. Inpatient and post-discharge AEs were identified using the Epic Care Everywhere network. AEs evaluated from the initiation of antibiotics until 30 days after antibiotic completion included gastrointestinal, hematologic, hepatobiliary, renal, neurologic, dermatologic, cardiac, myositis, vascular access device-related events, and systemic reactions. Ninety-day AEs included Clostridioides difficile infections, multidrug-resistant organism infections, and clinically significant candidal infections. The impact of AEs was categorized as necessitating additional diagnostic testing, changes in medications, unplanned medical encounters, prolonged or new hospitalizations, or death. RESULTS Among 400 antibiotic courses, 21% were complicated by at least one AE and 30% occurred post-discharge. Each additional day of antibiotics was associated with a 7% increased odds of an AE. Of courses complicated by an AE, 66% required further intervention. Hematologic, gastrointestinal, and renal AEs were the most common, accounting for 31%, 15%, and 11% of AEs, respectively. AEs complicated 35%, 35%, 19%, and 18% of courses of piperacillin-tazobactam, tobramycin, ceftazidime, and vancomycin, respectively. CONCLUSIONS More than 1 in 5 courses of antibiotics administered to hospitalized children are complicated by AEs. Clinicians should weigh the risk of harm against expected benefit when prescribing antibiotics.
Idiopathic CD4 T Cell Lymphocytopenia: A Case of Overexpression of PD-1/PDL-1 and CTLA-4

Idiopathic CD4 T cell lymphocytopenia (ICL) is a rare entity characterized by CD4 T cell count of <300 cells/mm3 along with opportunistic infection for which T cell marker expression remains to be fully explored. We report an ICL case for which T lymphocyte phenotype and its costimulatory molecules expression was analyzed both ex vivo and after overnight stimulation through CD3/CD28. The ICL patient was compared to five healthy controls. We observed higher expression of inhibitory molecules PD-1/PDL-1 and CTLA-4 on CD4 T cells and increased regulatory T cells in ICL, along with high activation and low proliferation of CD4 T cells. The alteration in the expression of both the costimulatory pathway and the apoptotic pathway might participate to down-regulate both CD4 T cell functions and numbers observed in ICL.
FTIR Spectroscopic Studies of Kerogen and Its Pyrolysates from Selected Egyptian Oil Shales

Abstract Pyrolysis of kerogen, isolated from the main producing mines of oil shales (Abu-Shegeili, El-Beida, El-Nakheil, and Abu-Tundub) in the Red Sea area, were studied to investigate their potential as fuel substituents. Kerogen was subjected to dry pyrolysis at different temperatures ranging between 300°C and 550°C. The oil yield shows a progressive increase to reach a maximum at 450°C. El-Nakheil oil shale gave the highest oil yield, while Abu-Shigeili exhibited the lowest amount of oil. The isolated kerogen, pyrolysate, and residual materials were subjected to FTIR spectroscopy to give valuable information about chain length, degree of branching, and degree of substitutions of aromatic structure of kerogen and its pyrolysates.