Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals

Poor aqueous solubility of active compounds is a major issue in today’s drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future.
Understanding Malicious Accounts in Online Political Discussions: A Multilayer Network Approach

Online social media platforms play an important role in political communication where users can freely express and exchange their political opinion. Political entities have leveraged social media platforms as essential channels to disseminate information, interact with voters, and even influence public opinion. For this purpose, some organizations may create one or more accounts to join online political discussions. Using these accounts, they could promote candidates and attack competitors. To avoid such misleading speeches and improve the transparency of the online society, spotting such malicious accounts and understanding their behaviors are crucial issues. In this paper, we aim to use network-based analysis to sense influential human-operated malicious accounts who attempt to manipulate public opinion on political discussion forums. To this end, we collected the election-related articles and malicious accounts from the prominent Taiwan discussion forum spanning from 25 May 2018 to 11 January 2020 (the election day). We modeled the discussion network as a multilayer network and used various centrality measures to sense influential malicious accounts not only in a single-layer but also across different layers of the network. Moreover, community analysis was performed to discover prominent communities and their characteristics for each layer of the network. The results demonstrate that our proposed method can successfully identify several influential malicious accounts and prominent communities with apparent behavior differences from others.
Spatio-Temporal Distribution and Fixed-Precision Sampling Plan of Scirtothrips dorsalis (Thysanoptera: Thripidae) in Florida Blueberry

Simple Summary Scirtothrips dorsalis, chilli thrips, is an invasive insect species in Florida and an important foliar pest of blueberry. Sound knowledge of insect distribution within the field is needed to formulate accurate sampling methods. Fourteen blueberry fields were systematically sampled for chilli thrips during the summers of 2017 and 2018. Field counts were modeled in various spatial models and determined chilli thrips had temporally stable aggregated distribution. A fixed-precision sampling plan was developed for summer sampling, requiring seven and three sampling units (sampling unit = 10 young blueberry shoots) to estimate a nominal mean density of 20 chilli thrips with a precision of 25% and 40%, respectively. The sampling plan can be used to improve the timing of control measures and assess the effectiveness of these control measures. Abstract Scirtothrips dorsalis Hood is an invasive and foliar pest of Florida blueberry that reduces plant growth by feeding on new leaf growth. A sampling plan is needed to make informed control decisions for S. dorsalis in blueberry. Fourteen blueberry fields in central Florida were surveyed in 2017 and 2018 after summer pruning to determine the spatial and temporal distribution of S. dorsalis and to develop a fixed-precision sampling plan. A sampling unit of ten blueberry shoots (with four to five leaves each) was collected from one blueberry bush at each point along a 40 × 40 m grid. Field counts of S. dorsalis varied largely ranging from zero to 1122 adults and larvae per sampling unit. Scirtothrips dorsalis had aggregated distribution that was consistent within fields and temporally stable between summers, according to Taylor’s power law (TPL) (aggregation parameter, b = 1.57), probability distributions (56 out of 70 sampling occasions fit the negative binomial distribution), Lloyd’s index (b > 1 in 94% occasions), and Spatial Analysis by Distance IndicEs (31% had significant clusters). The newly developed fixed-precision sampling plan required 167, 42, seven, or three sampling units to estimate a nominal mean density of 20 S. dorsalis per sampling unit with a precision of 5%, 10%, 25%, or 40%, respectively. New knowledge on S. dorsalis distribution will aid in evaluating the timing and effectiveness of control measures.
Isomorph Invariance of Higher-Order Structural Measures in Four Lennard–Jones Systems

In the condensed liquid phase, both single- and multicomponent Lennard–Jones (LJ) systems obey the “hidden-scale-invariance” symmetry to a good approximation. Defining an isomorph as a line of constant excess entropy in the thermodynamic phase diagram, the consequent approximate isomorph invariance of structure and dynamics in appropriate units is well documented. However, although all measures of the structure are predicted to be isomorph invariant, with few exceptions only the radial distribution function (RDF) has been investigated. This paper studies the variation along isomorphs of the nearest-neighbor geometry quantified by the occurrence of Voronoi structures, Frank–Kasper bonds, icosahedral local order, and bond-orientational order. Data are presented for the standard LJ system and for three binary LJ mixtures (Kob–Andersen, Wahnström, NiY2). We find that, while the nearest-neighbor geometry generally varies significantly throughout the phase diagram, good invariance is observed along the isomorphs. We conclude that higher-order structural correlations are no less isomorph invariant than is the RDF.
Secondary Metabolism and Defense Responses Are Differently Regulated in Two Grapevine Cultivars during Ripening

Vitis vinifera ‘Nebbiolo’ is one of the most important wine grape cultivars used to produce prestigious high-quality wines known throughout the world, such as Barolo and Barbaresco. ‘Nebbiolo’ is a distinctive genotype characterized by medium/high vigor, long vegetative and ripening cycles, and limited berry skin color rich in 3′-hydroxylated anthocyanins. To investigate the molecular basis of these characteristics, ‘Nebbiolo’ berries collected at three different stages of ripening (berry pea size, véraison, and harvest) were compared with V. vinifera ‘Barbera’ berries, which are rich in 3′,5′-hydroxylated anthocyanins, using transcriptomic and analytical approaches. In two consecutive seasons, the two genotypes confirmed their characteristic anthocyanin profiles associated with a different modulation of their transcriptomes during ripening. Secondary metabolism and response to stress were the functional categories that most differentially changed between ‘Nebbiolo’ and ‘Barbera’. The profile rich in 3′-hydroxylated anthocyanins of ‘Nebbiolo’ was likely linked to a transcriptional downregulation of key genes of anthocyanin biosynthesis. In addition, at berry pea size, the defense metabolism was more active in ‘Nebbiolo’ than ‘Barbera’ in absence of biotic attacks. Accordingly, several pathogenesis-related proteins, WRKY transcription factors, and stilbene synthase genes were overexpressed in ‘Nebbiolo’, suggesting an interesting specific regulation of defense pathways in this genotype that deserves to be further explored.
Change Point Analysis for Detecting Vaccine Safety Signals

It is important to detect signals of abrupt changes in adverse event reporting in order to notice public safety concerns and take prompt action, especially for vaccines under national immunization programs. In this study, we assessed the applicability of change point analysis (CPA) for signal detection in vaccine safety surveillance. The performances of three CPA methods, namely Bayesian change point analysis, Taylor’s change point analysis (Taylor-CPA), and environmental time series change point detection (EnvCpt), were assessed via simulated data with assumptions for the baseline number of events and degrees of change. The analysis was validated using the Korea Adverse Event Reporting System (KAERS) database. In the simulation study, the Taylor-CPA method exhibited better results for the detection of a change point (accuracy of 96% to 100%, sensitivity of 7% to 100%, specificity of 98% to 100%, positive predictive value of 25% to 85%, negative predictive value of 96% to 100%, and balanced accuracy of 53% to 100%) than the other two CPA methods. When the CPA methods were applied to reports of syncope or dizziness following human papillomavirus (HPV) immunization in the KAERS database, Taylor-CPA and EnvCpt detected a change point (Q2/2013), which was consistent with actual public safety concerns. CPA can be applied as an efficient tool for the early detection of vaccine safety signals.
3DP Printing of Oral Solid Formulations: A Systematic Review

Three-dimensional (3D) printing is a recent technology, which gives the possibility to manufacture personalised dosage forms and it has a broad range of applications. One of the most developed, it is the manufacture of oral solid dosage and the four 3DP techniques which have been more used for their manufacture are FDM, inkjet 3DP, SLA and SLS. This systematic review is carried out to statistically analyze the current 3DP techniques employed in manufacturing oral solid formulations and assess the recent trends of this new technology. The work has been organised into four steps, (1) screening of the articles, definition of the inclusion and exclusion criteria and classification of the articles in the two main groups (included/excluded); (2) quantification and characterisation of the included articles; (3) evaluation of the validity of data and data extraction process; (4) data analysis, discussion, and conclusion to define which technique offers the best properties to be applied in the manufacture of oral solid formulations. It has been observed that with SLS 3DP technique, all the characterisation tests required by the BP (drug content, drug dissolution profile, hardness, friability, disintegration time and uniformity of weight) have been performed in the majority of articles, except for the friability test. However, it is not possible to define which of the four 3DP techniques is the most suitable for the manufacture of oral solid formulations, because the selection is affected by different parameters, such as the type of formulation, the physical-mechanical properties to achieve. Moreover, each technique has its specific advantages and disadvantages, such as for FDM the biggest challenge is the degradation of the drug, due to high printing temperature process or for SLA is the toxicity of the carcinogenic risk of the photopolymerising material.
Sperm Cholesterol Content Modifies Sperm Function and TRPV1-Mediated Sperm Migration

Transient receptor potential channels-vanilloid receptor 1 (TRPV1) regulates thermotaxis in sperm-oriented motility. We investigated the role of membrane cholesterol (Chol) on TRPV1-mediated human sperm migration. Semen samples were obtained from five normozoospemic healthy volunteers. Sperm membrane Chol content, quantified by liquid chromatography-mass spectrometry, was modified by incubating cells with 2-hydroxypropyl-ß-cyclodextrin (CD) or the complex between CD and Chol (CD:Chol). The effect on sperm migration on a 10 μM capsaicin gradient (CPS), a TRPV1 agonist, was then investigated. Motility parameters were evaluated by Sperm Class Analyser. Intracellular calcium concentration and acrosome reaction were measured by staining with calcium orange and FITC-conjugated anti-CD46 antibody, respectively. TRPV1-Chol interaction was modelled by computational molecular-modelling (MM). CD and CD:Chol, respectively, reduced and increased membrane Chol content in a dose-dependent manner, resulting in a dose-dependent increase and reduction of sperm migration in a CPS gradient. MM confirmed a specific interaction of Chol with a TRPV1 domain that appeared precluded to the Chol epimer epicholesterol (Epi-Chol). Accordingly, CD:Epi-Chol was significantly less efficient than CD:Chol, in reducing sperm migration under CPS gradient. Chol inhibits TRPV1-mediated sperm function by directly interacting with a consensus sequence of the receptor.
The Impact of Seasonality in Pasture-Based Production Systems on Milk Composition and Functionality

Seasonal calving, pasture-based dairy systems are widely practiced in countries with a temperate climate and plentiful rainfall such as Ireland and New Zealand. This approach maximizes milk production from pasture and, consequently, is a low-cost, low-input dairy production system. On the other hand, the majority of global milk supply is derived from high input indoor total mixed ration systems where seasonal calving is not practiced due to the dependence on ensiled silages, grains and concentrated feeds, which are available year-round. Synchronous changes in the macro and micronutrients in milk are much more noticeable as lactation progresses through early, mid and late stages in seasonal systems compared to non-seasonal systems—which can have implications on the processability and functionality of milk.
Deletion of Superoxide Dismutase 1 Blunted Inflammatory Aortic Remodeling in Hypertensive Mice under Angiotensin II Infusion

Superoxide dismutase (SOD) is an enzyme that catalyzes the dismutation of two superoxide anions (O2·−) into hydrogen peroxide (H2O2) and oxygen (O2) and is generally known to protect against oxidative stress. Angiotensin II (AngII) causes vascular hypertrophic remodeling which is associated with H2O2 generation. The aim of this study is to investigate the role of cytosolic SOD (SOD1) in AngII-induced vascular hypertrophy. We employed C57/BL6 mice (WT) and SOD1 deficient mice (SOD1−/−) with the same background. They received a continuous infusion of saline or AngII (3.2 mg/kg/day) for seven days. The blood pressures were equally elevated at 1.5 times with AngII, however, vascular hypertrophy was blunted in SOD1−/− mice compared to WT mice (WT mice 91.9 ± 1.13 µm versus SOD1−/− mice 68.4 ± 1.41 µm p < 0.001). The elevation of aortic interleukin 6 (IL-6) and phosphorylation of pro-inflammatory STAT3 due to AngII were also blunted in SOD1−/− mice’s aortas. In cultured rat vascular smooth muscle cells (VSMCs), reducing expression of SOD1 with siRNA decreased AngII induced IL-6 release as well as phosphorylation of STAT3. Pre-incubation with polyethylene glycol (PEG)-catalase also attenuated phosphorylation of STAT3 due to AngII. These results indicate that SOD1 in VSMCs plays a role in vascular hypertrophy due to increased inflammation caused by AngII, probably via the production of cytosolic H2O2.
The Latest Research on RT-QuIC Assays—A Literature Review

The misfolding of proteins such as the prion protein, α-synuclein, and tau represents a key initiating event for pathogenesis of most common neurodegenerative disorders, and its presence correlates with infectivity. To date, the diagnosis of these disorders mainly relied on the recognition of clinical symptoms when neurodegeneration was already at an advanced phase. In recent years, several efforts have been made to develop new diagnostic tools for the early diagnosis of prion diseases. The real-time quaking-induced conversion (RT–QuIC) assay, an in vitro assay that can indirectly detect very low amounts of PrPSc aggregates, has provided a very promising tool to improve the early diagnosis of human prion diseases. Over the decade since RT–QuIC was introduced, the diagnosis of not only prion diseases but also synucleinopathies and tauopathies has greatly improved. Therefore, in our study, we summarize the current trends and knowledge of RT–QuIC assays, as well as discuss the diagnosis of neurodegenerative diseases using RT–QuIC assays, which have been updated in recent years.
Proton Transport in Cancer Cells: The Role of Carbonic Anhydrases

Intra- and extracellular pH regulation is a pivotal function of all cells and tissues. Net outward transport of H+ is a prerequisite for normal physiological function, since a number of intracellular processes, such as metabolism and energy supply, produce acid. In tumor tissues, distorted pH regulation results in extracellular acidification and the formation of a hostile environment in which cancer cells can outcompete healthy local host cells. Cancer cells employ a variety of H+/HCO3−-coupled transporters in combination with intra- and extracellular carbonic anhydrase (CA) isoforms, to alter intra- and extracellular pH to values that promote tumor progression. Many of the transporters could closely associate to CAs, to form a protein complex coined “transport metabolon”. While transport metabolons built with HCO3−-coupled transporters require CA catalytic activity, transport metabolons with monocarboxylate transporters (MCTs) operate independently from CA catalytic function. In this article, we assess some of the processes and functions of CAs for tumor pH regulation and discuss the role of intra- and extracellular pH regulation for cancer pathogenesis and therapeutic intervention.
Atheroprotective Properties of Costus spicatus (Jacq.) Sw. in Female Rats

Background: Costus spicatus (Jacq.) Sw. is a medicinal species frequently prescribed for the treatment of cardiovascular diseases. This study aims to evaluate the effects of this species against the development of atherosclerosis. Methods: First, an anatomical study of the C. spicatus leaves was performed. Then, the extract (ESCS) was obtained and submitted to phytochemical analysis. Female rats were treated with a single dose of ESCS (2000 mg/kg) to assess acute toxicity. Other groups of female rats received an atherogenic diet for 60 days. After 30 days, the animals were treated orally with ESCS (30 and 300 mg/kg), rosuvastatin (5 mg/kg), or vehicle once daily for 30 days. Serum lipids oxidized low-density lipoprotein, soluble adhesion molecules, interleukins 1β and 6, and markers of renal and liver function were measured. Renal function, blood pressure, electrocardiography, and vascular reactivity were also evaluated. Arteries, heart, liver, and kidney were also collected to evaluate the tissue redox state and histopathological analysis. Results: Prolonged treatment with ESCS induces significant hypolipidemic and antioxidant effects, that prevent endothelial dysfunction and modulated the local inflammatory process, reducing the evolution of the atherosclerotic disease. Conclusions: This study provides a scientific basis for the popular use of C. spicatus for the treatment of atherosclerosis.
Semi-Synthesis of Small Molecules of Aminocarbazoles: Tumor Growth Inhibition and Potential Impact on p53

The tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. Small molecules that bind and stabilize those mutants may represent effective anticancer drugs. Herein, we report the tumor cell growth inhibitory activity of carbazole alkaloids and amino derivatives, as well as their potential activation of p53. Twelve aminocarbazole alkaloids were semi-synthesized from heptaphylline (1), 7-methoxy heptaphylline (2), and 7-methoxymukonal (3), isolated from Clausena harmandiana, using a reductive amination protocol. Naturally-occurring carbazoles 1–3 and their amino derivatives were evaluated for their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles 1–3 showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline (1) the most promising in all the investigated cell lines. However, compound 1 also showed growth inhibition against non-tumor cells. Conversely, semi-synthetic aminocarbazole 1d showed an interesting growth inhibitory activity in tumor cells expressing both wild-type and mutant p53, exhibiting low growth inhibition on non-tumor cells. The yeast assay showed a potential reactivation of mutant p53 by heptaphylline derivatives, including compound 1d. The results obtained indicate that carbazole alkaloids may represent a promising starting point to search for new mutp53-reactivating agents with promising applications in cancer therapy.
Predictive Factors for Severe Maternal Morbidity in Brazil: A Case-Control Study

The maternal mortality or "maternal near miss" ratio in Brazil reflects the socioeconomic indicators as well as the healthcare quality in some areas of this country, pointing out fragile points in the health services. The aim of this study was to estimate the association of diverse variables related to pregnancy and the occurrence of Near Miss in a population of women who were cared in public maternity wards in Brazil. A case-control study was performed. The association between variables and outcomes was verified through a chi-square test. A multiple analysis was carried out, producing odds ratio (OR) estimates with values of p≤0.25 in the univariate model. The results point to the following risk factors for Severe Maternal Morbidity: non-white (<0.001, OR 2.973), family income of up to two minimum wage salaries (<0.001; OR 2.159), not having a partner (<0.001, OR 2.694), obesity (<0.001, OR 20.852), not having received pre-natal care (<0.001, OR 2.843), going to less than six prenatal appointments (<0.001, OR 3.498), undergoing an inter-hospital transfer (<0.001, OR 24.655), and the absence of labor during admission (<0.001, OR 25.205). Although the results vary, the incidence of women with potential life-threatening complications is high in Brazil, which reinforces the need to universalize more complex interventions as well as coverage of primary care. The presence of precarious socio-economic indicators and unqualified obstetric care were risk factors for Severe Maternal Morbidity.