Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-Influenza Activity of the Ribonuclease Binase: Cellular Targets Detected by Quantitative Proteomics

Unpredictable influenza pandemics, annual epidemics, and sporadic poultry-to-human avian influenza virus infections with high morbidity and mortality rates dictate a need to develop new antiviral approaches. Targeting cellular pathways and processes is a promising antiviral strategy shown to be effective regardless of viral subtypes or viral evolution of drug-resistant variants. Proteomics-based searches provide a tool to reveal the druggable stages of the virus life cycle and to understand the putative antiviral mode of action of the drug(s). Ribonucleases (RNases) of different origins not only demonstrate antiviral effects that are mediated by the direct RNase action on viral and cellular RNAs but can also exert their impact by signal transduction modulation. To our knowledge, studies of the RNase-affected cell proteome have not yet been performed. To reveal cellular targets and explain the mechanisms underlying the antiviral effect employed by the small extra-cellular ribonuclease of Bacillus pumilus (binase) both in vitro and in vivo, qualitative shotgun and quantitative targeted proteomic analyses of the influenza A virus (IAV) H1N1pdm09-infected A549 cells upon binase treatment were performed. We compared proteomes of mock-treated, binase-treated, virus-infected, and virus-infected binase-treated cells to determine the proteins affected by IAV and/or binase. In general, IAV demonstrated a downregulating strategy towards cellular proteins, while binase had an upregulating effect. With the help of bioinformatics approaches, coregulated cellular protein sets were defined and assigned to their biological function; a possible interconnection with the progression of viral infection was conferred. Most of the proteins downregulated by IAV (e.g., AKR1B1, AKR1C1, CCL5, PFN1, RAN, S100A4, etc.) belong to the processes of cellular metabolism, response to stimulus, biological regulation, and cellular localization. Upregulated proteins upon the binase treatment (e.g., AKR1B10, CAP1, HNRNPA2B1, PFN1, PPIA, YWHAB, etc.) are united by the processes of biological regulation, cellular localization, and immune and metabolic processes. The antiviral activity of binase against IAV was expressed by the inversion of virus-induced proteomic changes, resulting in the inhibition of virus-associated processes, including nuclear ribonucleoprotein export (NCL, NPM1, Nup205, and Bax proteins involved) and cytoskeleton remodeling (RDX, PFN1, and TUBB) induced by IAV at the middle stage of single-cycle infection in A549 cells. Modulation of the immune response could be involved as well. Overall, it seems possible that binase exerts its antiviral effects in multiple ways.
Social network theory—an underutilized opportunity to align innovative methods with the demands of the opioid epidemic

ABSTRACT It has been almost 3 years since the opioid epidemic was declared a national public health emergency under federal law. Solutions have focused on supply-reduction strategies. These approaches, however, have failed to significantly curtail opioid overdose and related death. Demand for opioid use arising from social networks and environment is an important contributing factor to the current opioid epidemic. Adoption of existing underused methods is needed to drive further progress. This Perspective proposes the social contagion model as a promising framework through which to operationalize evaluation of the influence of social networks and environment in the opioid epidemic and argues for its greater application. Comparing the current epidemic with previous opioid epidemics reiterates the utility of the social contagion model. This model acknowledges social network influence on individual behavior. It leverages tools from epidemiology, permits evaluation of interpersonal influence, facilitates consideration of disproportionate and collateral effects, and overcomes limitations of traditional models and geographic assumptions inherent to many approaches surrounding the current opioid epidemic. Analyzing the opioid epidemic within a social contagion framework will enhance evaluation methods and enable the design of interventions to reflect the actual demands of the current crisis. If the influence of social networks and environment is not considered, the devastating toll of the opioid epidemic could grow.
Understanding the Fate of Almond (Prunus dulcis (Mill.) D.A. Webb) Oleosomes during Simulated Digestion

Background: Almond kernels contain phytochemicals with positive health effects in relation to heart disease, diabetes and obesity. Several studies have previously highlighted that almond cell wall encapsulation during digestion and particle size are factors associated with these benefits. In the present study, we have characterized almond oleosomes, natural oil droplets abundant in plants, and we have investigated their integrity during simulated gastrointestinal digestion. Methods: Oleosomes were visualized on the almond seed surface by imaging mass spectrometry analysis, and then characterized in terms of droplet size distribution by dynamic light scattering and protein profile by liquid chromatography high-resolution tandem mass spectrometry analysis. Results: The almond oleosomes’ distribution remained monomodal after in vitro mastication, whereas gastric and duodenal digestion led to a bimodal distribution, albeit characterized mainly by a prevalent population with a droplet size decrease related to a rearrangement of the protein profile. Oleosins, structural proteins found in plant oil bodies, persisted unchanged during simulated mastication, with the appearance of new prunin isoforms after gastric and duodenal digestion. Conclusions: The rearrangement of the protein profile could limit lipid bioaccessibility. The data improve our understanding of the behavior of almond lipids during gastrointestinal digestion, and may have implications for energy intake and satiety imparted by almonds.
Modelling Foliar Penetration: Its Role in Optimising Pesticide Delivery

Abstract Rates of foliar uptake are often limited by slow cuticular penetration of active ingredients (ai). Rates of cuticular penetration have been modelled based on two processes, namely solute mobility in cuticles ( k *) and partitioning of ai or adjuvants between the formulation residue, and cuticular waxes ( K wxfr ). The model distinguishes between effects of ai and adjuvants on k* and on driving force of penetration, which is proportional to the product K wxfr C fr , the latter variable being the concentration of the ai in the formulation residue. Solute mobilities in cuticles varied greatly among species but for neutral ai it depended only on molar volumes and not on lipophilicity. Solute mobility decreased exponentially with increasing size of ai but size selectivity ( β ‘) was the same for cuticles from all plant species tested and also for extracted cuticles (polymer matrix). Differences in solute mobility among species were related to the term k* o , which represents the mobility of a hypothetical molecule having zero molar volume. While size selectivity did not change on extraction of cuticular waxes k* o increased by orders of magnitude depending on plant species. Evidence is presented showing that differences in solute mobility among species and higher solute mobility in extracted cuticles are related to the tortuosity factor. Crystalline waxes increase the lengths of the diffusion paths and decrease mobility in cuticles proportional to the tortuosity factor. Solute mobilities increased with increasing temperatures and it is argued that at 5 to 10 °C solute mobilities can become so low that significant penetration of ai is prevented. Rates of cuticular penetration can be manipulated by using appropriate adjuvants. The model distinguishes two adjuvant effects. Adjuvants which remain on the surface of the cuticles can serve as solvents and they affect driving forces via their effects on K wxfr and C fr . If these passive adjuvants are hygroscopic their effect on driving forces depends greatly on humidity. Active adjuvants are called accelerators. They are solvents as well, but in addition they penetrate into cuticles and increase solute mobility. These effects depend on type of accelerator, temperature, size of solutes, and plant species. Accelerators decrease viscosity of waxes which results in reduced size selectivity. Accelerators also reduce differences in solute mobility among plant species and penetration rates at low temperatures are greatly increased. By selecting the appropriate adjuvant, rates of foliar uptake can be manipulated and uniformity of biological responses of systemic ai can be improved, even under adverse environmental conditions.
Élaboration de particules de latex composites à base d'oxyde de cérium par polymérisation radicalaire en milieu aqueux dispersé

Nous decrivons dans ce travail l’elaboration de latex nanocomposites a base d’oxyde de cerium en vue d’applications dans le domaine des revetements. Deux procedes originaux ont ete developpes afin de controler la morphologie des particules. Dans un premier temps, nous avons tire parti de la forte densite de charges des nanoparticules d’oxyde de cerium pour stabiliser des particules de latex obtenues par polymerisation en emulsion ou en miniemulsion « de Pickering ». Dans les deux cas, la reaction est conduite en presence des particules inorganiques et d’un agent complexant a caractere acide, l’acide methacrylique, en l’absence de tout tensioactif. Des particules de latex, decorees en surface par les nanoparticules d’oxyde de cerium ont ete ainsi synthetisees. Par la suite, une strategie qui consiste a utiliser des chaines de polymeres hydrophiles, reactivables (macro-agent RAFT) et prealablement adsorbees a la surface des nanoparticules d’oxyde de cerium a ete envisagee. Ces chaines polymeres comportant a la fois des fonctions carboxyliques et un groupe trithiocarbonate terminal sont capables de stabiliser la suspension colloidale des nanoparticules et de reamorcer la polymerisation en mode semi-continu permettant ainsi l’encapsulation de l’oxyde de cerium. Une optimisation visant a utiliser un procede batch a egalement ete evaluee. Quelle que soit la strategie employee, une attention toute particuliere a ete portee a la stabilite colloidale du milieu ainsi qu’a la cinetique de la reaction. La morphologie des particules composites a ete caracterisee par MET et cryo-MET et reliee aux conditions de modification de surface et de polymerisation
Hyperosmotic phase separation: Condensates beyond inclusions, granules and organelles

Biological liquid–liquid phase separation has gained considerable attention in recent years as a driving force for the assembly of subcellular compartments termed membraneless organelles. The field has made great strides in elucidating the molecular basis of biomolecular phase separation in various disease, stress response, and developmental contexts. Many important biological consequences of such “condensation” are now emerging from in vivo studies. Here we review recent work from our group and others showing that many proteins undergo rapid, reversible condensation in the cellular response to ubiquitous environmental fluctuations such as osmotic changes. We discuss molecular crowding as an important driver of condensation in these responses and suggest that a significant fraction of the proteome is poised to undergo phase separation under physiological conditions. In addition, we review methods currently emerging to visualize, quantify, and modulate the dynamics of intracellular condensates in live cells. Finally, we propose a metaphor for rapid phase separation based on cloud formation, reasoning that our familiar experiences with the readily reversible condensation of water droplets help understand the principle of phase separation. Overall, we provide an account of how biological phase separation supports the highly intertwined relationship between the composition and dynamic internal organization of cells, thus facilitating extremely rapid reorganization in response to internal and external fluctuations.
Pharmacodynamics of Posaconazole in Experimental Invasive Pulmonary Aspergillosis: Utility of Serum Galactomannan as a Dynamic Endpoint of Antifungal Efficacy

Aspergillus galactomannan antigenemia is an accepted tool for the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. Little is known, however, about the utility of this biomarker to assess the efficacy of antifungal therapies. The pharmacokinetics (PK) and pharmacodynamics (PD) of posaconazole in treatment and prophylaxis were investigated in the persistently neutropenic rabbit model of Aspergillus fumigatus IPA at doses between 2 and 20 mg/kg per day. ABSTRACT Aspergillus galactomannan antigenemia is an accepted tool for the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. Little is known, however, about the utility of this biomarker to assess the efficacy of antifungal therapies. The pharmacokinetics (PK) and pharmacodynamics (PD) of posaconazole in treatment and prophylaxis were investigated in the persistently neutropenic rabbit model of Aspergillus fumigatus IPA at doses between 2 and 20 mg/kg per day. Sparse plasma sampling was used to obtain PK data at steady state, and the serum galactomannan index (GMI), as a dynamic endpoint of antifungal response, was obtained every other day, in addition to conventional outcome parameters including survival and fungal tissue burden. Nonparametric PK/PD model building was performed using the Pmetrics package in R. A one-compartment model with linear elimination best described the PK of posaconazole. The PD effect of posaconazole exposure in plasma on the GMI in serum was best described by dynamic Hill functions reflecting growth and killing of the fungus. Through calculations of the area under the concentration-time curve from 0 to 24 h (AUC0–24) at steady state, the exposure-response relationship between posaconazole and the GMI for treatment followed a sigmoidal function with an asymptote forming above an AUC0–24 of 30 mg · h/liter. All prophylactic doses were able to control the fungal burden. A nonparametric population PK/PD model adequately described the effect of posaconazole in prophylaxis and treatment of experimental IPA. An AUC0–24 greater than 30 mg · h/liter was associated with adequate resolution of the GMI, which well supports previously suggested exposure-response relationships in humans.
[Expressions of ΔNp63α, DPC4/Smad4 and P21 in cervical squamous cell carcinoma an their clinical significance].

OBJECTIVE To investigate the expressions of ΔNp63α, DPC4/Smad4 and P21 in cervical squamous cell carcinomas and explore their implications in tumorigenesis, progression and prognosis of the malignancy. METHODS The expressions of ΔNp63α, DPC4/Smad4 and P21 were examined with immunohistochemistry in 100 specimens of cervical squamous cell carcinoma, 40 specimens of cervical intraepithelial neoplasia (CIN) and 40 specimens of normal cervical tissues to explore their associations with the occurrence, progression and prognosis of cervical squamous cell carcinoma. RESULTS The expressions of ΔNp63α and DPC4/Smad4 decreased and P21 expression increased significantly in the order of normal cervical tissue, CIN and cervical squamous cell carcinoma (P < 0.01), and their expressions were associated with the differentiation, clinical stages and lymph node metastasis of cervical squamous cell carcinoma (P < 0.01). The expression of ΔNp63α was positively correlated with the expression of DPC4/Smad4 (r=0.581, P < 0.05), and they were both negatively correlated with P21 expression (r=-0.449 and -0.254, respectively; P < 0.05). Kaplan-Meier survival analysis showed that patients with cervical squamous cell carcinoma positive for ΔNp63α and DPC4/Smad4 had a significantly higher 5-year survival rate than those negative for ΔNp63α and DPC4/Smad4 (P < 0.001); the patients positive for P21 had a significantly lower 5-year survival rate than the P21-negative patients (P < 0.005). CONCLUSIONS The expressions of ΔNp63α, DPC4/Smad4 and P21are related with the differentiation, invasion, lymph node metastasis, pTNM stage and prognosis of in cervical squamous cell carcinomas, suggesting their value as potential markers for prognostic evaluation of patients with cervical squamous cell carcinoma.
Comparison of short- and long-term effectiveness of ixekizumab and secukinumab in real-world practice

ABSTRACT Background: Although secukinumab and ixekizumab both act by inhibiting IL-17A, some scientific evidence suggests that there are differences in efficacy between the two agents. Objective: The aim of this study was to compare the short- and long-term effectiveness of ixekizumab and secukinumab in clinical practice. Methods: A retrospective study was conducted on a cohort of 245 psoriatic patients receiving secukinumab or ixekizumab during the period from September 2016 to December 2019. The proportion of patients achieving PASI75, PASI90, and PASI100 at weeks 12 and 24 was calculated. We recorded the 12- and 24-month drug survival as a measure to assess long-term effectiveness. Results: A higher proportion of patients in the secukinumab group achieved PASI75, 90, and 100 at 12 weeks. The Kaplan-Meier survival curve for any reason of discontinuation showed no differences between the two groups. Instead, the multivariate analysis for ineffectiveness, adjusted for potential confounders, showed a lower drug survival rate in the secukinumab group, with an adjusted HR of 2.57 (95% CI 1.05–6.28, p 0.038). Conclusion: This real-life study demonstrated that ixekizumab and secukinumab are both highly effective in short- and long-term treatment of psoriasis, even though few differences exist concerning speed of action and long-term effectiveness.
Behavioral economics of substance use: Understanding and reducing harmful use during the COVID-19 pandemic.

Behavioral economic research demonstrates that alcohol and drug consumption is (a) an inverse function of constraints on access to the substance and (b) a direct function of constraints on access to alternative rewards. Physical distancing interventions and economic consequences of the COVID-19 pandemic have resulted in unprecedented reductions in many of the constraints on substance use and in critical evolutionarily salient sources of alternative reward, such as social interaction, physical activity, leisure activities and hobbies, and academic and occupational pursuits. Thus, behavioral economics suggests that the pandemic and necessary public health response have created a "perfect storm" for exacerbation of individual-level and population-level substance use problems and also points to multilevel intervention strategies. We summarize this perspective and research by highlighting 3 critical behavioral processes that will influence drug and alcohol consumption. First, the sudden absence of many effective constraints on substance use (work, school, community, or service obligations) will reduce the actual and perceived cost of use. Second, physical distancing measures will reduce the availability, and increase the cost, of many rewarding substance-free activities and commodities. Third, increased uncertainty around current and future events increases discounting of delayed rewards. These effects will be especially pernicious among populations with existing health disparities. Next, we outline interventions suggested by behavioral economics to mitigate the impact of COVID-19 on substance use that are aimed at increasing perceived costs of use; increasing access to substance-free activities, including treatment; and lengthening the timeframe for behavioral allocation and altering environmental contexts to promote healthy choices. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Microwave Bone Imaging: A Preliminary Investigation on Numerical Bone Phantoms for Bone Health Monitoring

Microwave tomography (MWT) can be used as an alternative modality for monitoring human bone health. Studies have found a significant dielectric contrast between healthy and diseased human trabecular bones. A set of diverse bone phantoms were developed based on single-pole Debye parameters of osteoporotic and osteoarthritis human trabecular bones. The bone phantoms were designed as a two-layered circular structure, where the outer layer mimics the dielectric properties of the cortical bone and the inner layer mimics the dielectric properties of the trabecular bone. The electromagnetic (EM) inverse scattering problem was solved using a distorted Born iterative method (DBIM). A compressed sensing-based linear inversion approach referred to as iterative method with adaptive thresholding for compressed sensing (IMATCS) has been employed for solving the underdetermined set of linear equations at each DBIM iteration. To overcome the challenges posed by the ill-posedness of the EM inverse scattering problem, the L2-based regularization approach was adopted in the amalgamation of the IMATCS approach. The simulation results showed that osteoporotic and osteoarthritis bones can be differentiated based on the reconstructed dielectric properties even for low values of the signal-to-noise ratio. These results show that the adopted approach can be used to monitor bone health based on the reconstructed dielectric properties.
Emotional loneliness is associated with a risk of dementia in a general Japanese older population: the Hisayama Study.

OBJECTIVES To investigate the association of loneliness and its component subscales with the risk of dementia in a general Japanese older population. METHOD A total of 1,141 community-dwelling Japanese residents aged ≥65 years without dementia were prospectively followed up for a median 5.0 years. We evaluated any loneliness and its component subscales-namely, social and emotional loneliness-by using the 6-Item de Jong Gierveld Loneliness Scale. Cox proportional hazards models were used to estimate hazard ratios (HRs) of each loneliness type on the risk of dementia controlling for demographic factors, lifestyle factors, physical factors, social isolation factors, and depression. RESULTS During the follow-up, 114 participants developed dementia. The age- and sex-adjusted incidence rate of dementia was significantly greater in participants with any loneliness and emotional loneliness than those without. The multivariable-adjusted HRs (95% confidence intervals) of participants with any loneliness and emotional loneliness on incident dementia were 1.61 (1.08-2.40) and 1.65 (1.07-2.54), respectively, as compared to those without. However, there was no significant association between social loneliness and dementia risk. In subgroup analyses of social isolation factors, excess risks of dementia associated with emotional loneliness were observed in participants who had a partner, lived with someone, or rarely communicated with relatives or friends, but such association was not significant in participants who had no partner, lived alone, or frequently communicated with friends or relatives. DISCUSSION The present study suggested that loneliness, especially emotional loneliness, was a significant risk factor for the development of dementia in the general older population in Japan.