Miracle-dz/UniFAR-FTUs huggingface dataset:
Newly Synthesized Lignin Microparticles as Bioinspired Oral Drug-Delivery Vehicles: Flavonoid-Carrier Potential and In Vitro Radical-Scavenging Activity

The aim of the present study was to synthesize lignin microparticles, to evaluate their physicochemical, spectral, morphological and structural characteristics, to examine their encapsulation and in vitro release potential and behaviour towards the flavonoid morin in simulated physiological medium and to assess the in vitro radical-scavenging potential of the morin-loaded lignin microcarrier systems. The physicochemical, structural and morphological characteristics of alkali lignin, lignin particles (LP) and morin-encapsulated lignin microparticles (LMP) were determined based on particle size distribution, SEM, UV/Vis spectrophotometric, FTIR and potentiometric titration analyses. The encapsulation efficiency of LMP was 98.1%. The FTIR analyses proved that morin was successfully encapsulated in the LP without unexpected chemical reactions between the flavonoid and the heteropolymer. The in vitro release performance of the microcarrier system was successfully mathematically described by Korsmeyer–Peppas and the sigmoidal models outlining the general role of diffusion during the initial stages of the in vitro release process in simulated gastric fluid (SGF), and the predominant contribution of biopolymer relaxation and erosion was determined in simulated intestinal medium (SIF). The higher radical-scavenging potential of LMP, as compared to that of LP, was proven via DPPH and ABTS assays. The synthesis of lignin microcarriers not only provides a facile approach for the utilization of the heteropolymer but also determines its potential for the design of drug-delivery matrices.
Role of dermoscopy in detection of nailfold capillaroscopic changes in autoimmune connective tissue diseases

: Background: Nail fold capillaries abnormalities are characteristic in some autoimmune connective tissue diseases. Recently, handheld dermoscope can be used to detect these abnormalities. Aim of the study: To evaluate the nail fold capillaries pattern in different autoimmune connective tissue diseases using handheld dermoscope. Moreover, the relation between morphologic abnormalities and disease duration, activity, and severity were attempted. Patients and Methods: This cross-sectional study was carried out over a period of six months on patients presenting to outpatient clinics of Alexandria main University hospital diagnosed with autoimmune connective tissue diseases. Sixty-seven females were included and were further categorized according to their primary connective tissue diseases. Disease specific markers and disease activity were assessed. Capillaroscopy was performed using DermLite® DL4 pocket dermoscope. Results: The scleroderma pattern was detected in 100% of scleroderma and dermatomyositis, 71.4% of mixed connective tissue disease, 65.2 % of rheumatoid arthritis, and 52.9 % of systemic lupus erythematosus patients. There was a statistically significant relation between systemic lupus erythematosus disease activity index and abnormal morphology. There was no statistically significant relation between dermoscopic findings and any other disease activity markers, patients’ age, or disease duration. Conclusion/ recommendations: Dermoscopy is a helpful tool in assessment of nail fold capillaries abnormalities in autoimmune connective tissue diseases. Furthermore, in SLE patients, as abnormal morphology correlates with disease activity, dermoscopy could be a suitable screening test.
Emergence of OXA-484-Producing Klebsiella variicola in China

Purpose The frequent and inappropriate use of antibiotics has caused a dramatic rise in the number, species, and degree of multi-drug resistant bacteria, making them more prevalent and difficult to treat. In this context, the aim of the present study was to characterize the OXA-484-producing strains isolated from a perianal swab of a patient by using whole-genome analysis. Patients and Methods In this study, carbapenemase-producing Klebsiella variicola was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), average nucleotide identity (ANI) and PCR. S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting were utilized to characterize the plasmid profiles of K. variicola 4717. In particular, WGS was performed to obtain genomic information on this clinical isolate, and assemble all the plasmids of the blaOXA-484-harboring strain. Results The antimicrobial susceptibility pattern of K. variicola 4717 revealed that it was resistant to a range of antibiotics, including aztreonam, imipenem, meropenem, ceftriaxone, cefotaxime, ceftazidime, levofloxacin, ciprofloxacin, piperacillin-tazobactam, methylene-sulfamer oxazole, amoxicillin-clavulanic acid, cefepime, and tigecycline. Its susceptibility to chloromycin was intermediate, while it was still susceptible to amikacin, gentamicin, fosfomycin, and polymyxin B. The presence of two companion plasmids, p4717_1 and p4717_2, together with a plasmid carrying the blaOXA-484 gene was observed. An in-depth investigation of p4717-OXA-484 uncovered that it is an IncX3-type plasmid and shares a similar segment encoded by IS26. Given the similar genetic background, it was conceivable that blaOXA-484 could have developed from blaOXA-181 through a series of mutations. Conclusion Herein, we described the first genome sequence of K. variicola strain harbouring the class D β-actamase blaOXA-484 in an Inc-X3-type plasmid. Our work also uncovered the genetic characterization of K. variicola 4717 and the importance of initiating antimicrobial detection promptly.
Erdheim–Chester Disease of the Breast: First Review and First Case of Isolated Severe Gynecomastia

(1) Introduction: Erdheim–Chester disease (ECD) is a life-threatening condition and often a diagnostic challenge. It has recently been classified as a hematopoietic tumour, and the cases of ECD reported in the literature has dramatically increased during the last 15 years. (2) Methods: We describe the case of a 57-year-old male patient with severe gynecomastia, with a detailed description of his diagnostic iter and consequent surgical operation. We provide the first systematic review of the literature of breast involvement in ECD, following PRISMA guidelines, including 13 studies and 16 patients. (3) Results: Our report resulted to be the first case of gynecomastia as a single clinical and imaging feature of ECD described in English literature. A total of 81.3% of patients included were female. Among them, 76.9% had unilateral and nodular presentation, while male patients presented bilateral heterogeneous breast enlargement. Globally, 87.5% expressed breast alterations as their first manifestations of ECD. Only 50% presented skeletal involvement. (4) Conclusion: The reported case represents a unique addition to the literature. We found two different patterns in ECD-related breast involvement between male and female patients, an unusual M/F ratio, and a lower rate of bone involvement. Breast involvement is frequently the first clinical feature; therefore, breast caregivers should be aware of this dangerous and most likely underestimated condition.
Efficient algorithm for localising 3-D narrowband multiple sources

The authors propose an efficient 3-D source localisation algorithm using three uniform linear subarrays. The proposed algorithm replaces the 3-D search required in conventional 3-D MUSIC with three 1D searches, and thus reduces the computational burden. An estimate of the 1-D incident angle obtained from a subarray under the far field assumption satisfies the nonlinear algebraic equation of the true source bearing angle, elevation angle, and range. The proposed algorithm estimates source location by solving three algebraic equations obtained from three subarrays. When comparing 3-D MUSIC spectra of the estimated source locations, the proposed algorithm is able to solve the pairing problem in localisation of multiple sources.
Effects of Apocynin, a NADPH Oxidase Inhibitor, in the Protection of the Heart from Ischemia/Reperfusion Injury

Ischemia and perfusion (I/R) induce inflammation and oxidative stress, which play a notable role in tissue damage. The aim of this study was to investigate the role of an NADPH oxidase inhibitor (apocynin) in the protection of the heart from I/R injury. Hearts isolated from Wistar rats (n = 8 per group) were perfused with a modified Langendorff preparation. Left ventricular (LV) contractility and cardiovascular hemodynamics were evaluated by a data acquisition program, and infarct size was evaluated by 2,3,5-Triphenyl-2H-tetrazolium chloride (TTC) staining. Furthermore, the effect of apocynin on the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and anti-inflammatory cytokine (IL-10) was evaluated using an enzyme linked immunosorbent assay (ELISA). Hearts were subjected to 30 min of regional ischemia, produced by ligation of the left anterior descending (LAD) coronary artery, followed by 30 min of reperfusion. Hearts were infused with apocynin before ischemia, during ischemia or at reperfusion. To understand the potential pathways of apocynin protection of the heart, a nitric oxide donor (S-nitroso-N-acetylpenicillamine, SNAP), nitric oxide blocker (N (gamma)-nitro-L-arginine methyl ester, L-Name), nicotinic acid adenine dinucleotide phosphate (NAADP) inhibiter (Ned-K), cyclic adenosine diphosphate ribose (cADPR) agonist, or CD38 blocker (Thiazoloquin (az)olin (on)e compound, 78c) was infused with apocynin. Antioxidants were evaluated by measuring superoxide dismutase (SOD) and catalase (CAT) activity. Apocynin infusion before ischemia or at reperfusion protected the heart by normalizing cardiac hemodynamics and decreasing the infarct size. Apocynin treatment resulted in a significant (p < 0.05) decrease in pro-inflammatory cytokine levels and a significant increase (p < 0.05) in anti-inflammatory and antioxidant levels. Apocynin infusion protected the heart by improving LV hemodynamics and coronary vascular dynamics. This treatment decreased the infarct size and inflammatory cytokine levels and increased anti-inflammatory cytokine and antioxidant levels. This protection follows a pathway involving CD38, nitric oxide and acidic stores.
Sustained Remission Off-Treatment (SROT) of TPO-RAs: The Burgos Ten-Step Eltrombopag Tapering Scheme

Background and Objectives: TPO-RAs (romiplostim/eltrombopag/avatrombopag) have broadly demonstrated high efficacy rates (59–88%), durable responses (up to three years) and a satisfactory safety profile in clinical trials. The effect of TPO-RAs is classically considered to be transient because platelet numbers usually dropped rapidly to baseline unless therapy was maintained. However, several groups have reported the possibility of successfully discontinuing TPO-RAs in some patients without further need for concomitant treatments. This concept is usually referred as sustained remission off-treatment (SROT). Materials and Methods: Unfortunately, we still lack predictors of the response to discontinuation even after the numerous biological, clinical and in vitro studies performed to study this phenomenon. The frequency of successful discontinuation is matter of controversy, although a percentage in the range of 25–40% may probably be considered a consensus. Here, we describe all major routine clinical practice studies and reviews that report the current position on this topic and compare them with our own results in Burgos. Results: We report our Burgos ten-step eltrombopag tapering scheme with which we have achieved an elevated percentage rate of success (70.3%) in discontinuing treatment. Conclusions: We hope this protocol may help successfully taper and discontinue TPO-RAs in daily clinical practice.
Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells

The androgen-dependent or -independent pathways are regarded as primary therapeutic targets for the neoplasm of the prostate. Mucosa-associated lymphoid tissue 1 (MALT1) acting as a paracaspase in the regulation of nuclear factor κB (NF-κB) signal transduction plays a central role in inflammation and oncogenesis in cancers. This study confirmed the potential linkages between androgen and NF-κB activation by inducing MALT1 in the androgen receptor-full length (ARFL)-positive LNCaP and 22Rv1 prostate cancer cells. Although androgen did not stimulate MALT1 expression in AR-null or ectopic ARFL-overexpressed PC-3 cells, the ectopic overexpression of the AR splicing variant 7 (ARv7) upregulated MALT1 to activate NF-κB activities in 22Rv1 and PC-3 cells. Since the nuclear translocation of p50 and p65 was facilitated by ARv7 to motivate NF-κB activity, the expressions of MALT1, prostate-specific antigen (PSA), and N-myc downstream regulated 1 (NDRG1) were therefore induced in ectopic ARv7-overexpressed prostate cancer cells. Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.
Transient wave propagation in a one dimensional partially saturated poroelastic column

Based on the theory of mixtures, a dynamic three phase model for partially saturated poroelasticity is established. This model is applied to a one‐dimensional unsaturated poroelastic column and an analytical solution in the Laplace domain is deduced. By using the Convolution Quadrature Method, the solution in the time domain is obtained. Using some widely distributed porous materials as rock, soil and sediment, the wave propagation behavior in terms of displacement and pore pressure is examined. By neglecting the viscosity of the fluid, assuming very large fluid permeabilities, the second and third compressional waves are identified. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Best ^{}-approximation of generalized biaxisymmetric potentials

Let F be a real-valued generalized biaxisymmetric potential (GBASP ) in V (p > 1) on 2, the open unit sphere about the origin. Convergence of a sequence of best harmonic polynomial approximates to F in Lp identifies those F that harmonically continue as entire function GBASP and determines their order and type. The analysis utilizes the Bergman and Gilbert Integral Operator Method to extend results from classical function theory on the best polynomial approximation of analytic functions of one complex variable. Introduction. Let F = F(x, y) be a real-valued regular solution to the generalized biaxially symmetric potential equation, (373.x2 + d2/dy2 + (2a + l)/xd/dx + (2ß + l)/yd/dy)F 0, a > ß > -1/2, (1) (a, ß) fixed in a neighborhood of the origin where the analytic Cauchy data, Fx(0, v) «■ Fy(x, 0) = 0, is satisfied along the singular lines. Such functions with even harmonic extensions are referred to as generalized biaxisymmetric potentials (GBASP), having local expansions of the form F(x,y)= 2 anR¡i'J'\x,y), n-0 R(«.ß\x,y) = (x2 + /Yfr*\{^ y2)/ i*2 + y2))/P^ß)d) (2) where P¡¡"S) are the Jacobi polynomials [1], [17]. Suitable limits of the parameters (a, /? ), after quadratic transformations [1] as necessary, produce various special functions from the R^a'ß). For example, a = ß = 0 gives the zonal harmonics so that F interprets as an axisymmetric potential on E3 and a = ß = -1/2 gives the even circular harmonics on E2 where the interpretation is F = Re/, / is real analytic. Further examples can be found in [1]. The Euler-Poisson-Darboux equation, arising in gas dynamics, is viewed in terms of equation (1) after a transformation [7, p. 223]. The F then suggest generalizations of analytic functions and have a variety of physical interpretations [4], [S], [7], [9]; also refer to the Method of Ascent [6]. Thus, of special interest are global properties characterizing solutions to this partial differential equation that are determined from local properties. Presented to the Society April 19, 1979; received by the editors March 21, 1979. AMS (MOS) subject classifications (1970). Primary 35J05, 25B05; Secondary 30A82, 30A66, 31B35.
Alignment Studies for Tungsten Near L3 Sub-Shell Threshold Via Theoretical, Experimental and Empirical Methods

Alignment studies are made for tungsten near L3 sub-shell threshold using theoretical, experimental and empirical approaches. Experimentally to measure alignment parameter, the angular distribution of L x-rays of tungsten (W-74) is measured in the angular range 0° to 120°, where maximum anisotropy is expected. The experimental measurements are performed in XRF laboratories of Raja Ramanna Center for Advanced Technology (RRCAT), Indore, India using a three-dimensional double reflection set-up. The weighted average of alignment values with 10% error comes 0.155 ± 0.009. Theoretically, the value of alignment parameter A 20 is calculated using non-relativistic dipole approximation in a point Coulomb potential and is found 0.151 at L3 threshold energy (10.676 keV). For empirical A 20 evaluations, IGELCS interpolated experimental LXRF cross-section σ*Lg (g = α, ) values of Mann et al with 8% reported errors are used along with the radiative decay rates. The comparison among theoretical, experimental and empirical values are similar and values being >0.1 at L3 threshold energy are certainly higher than the 5 to 8 percent uncertainties quoted in earlier experimental results.
Dynamics and optimal control of chemotherapy for low grade gliomas: Insights from a mathematical model

We discuss the optimization of chemotherapy treatment for low-grade gliomas using a mathematical model. We analyze the dynamics of the model and study the stability of solutions. The dynamical model is incorporated into an optimal control problem for which different objective functionals are considered. We establish the existence of optimal controls and give a detailed discussion of the necessary optimality conditions. Since the control variable appears linearly in the control problem, optimal controls are concatenations of bang-bang and singular arcs. We derive a formula of the singular control in terms of state and adjoint variables. Using discretization and optimization methods we compute optimal drug protocols in a number of scenarios. For small treatment periods, the optimal control is bang-bang, whereas for larger treatment periods we obtain both bang-bang and singular arcs. In particular, singular controls illustrate the metronomic chemotherapy.
Changes in Northern Hemisphere stratospheric variability under increased CO2 concentrations

The robustness of stratospheric circulation changes under increased concentrations of carbon dioxide are investigated using the Met Office HadSM3‐L64 model. Equilibrium climate change simulations employing forcing of two and four times pre‐industrial CO2 are presented, with particular focus on the temperature response of the Arctic lower stratosphere during Northern Hemisphere winter. High CO2 loading provides the ability to attain the statistical significance of any response, typically a problem given the large component of interannual variability common to the region. In response to CO2, the expected global stratospheric cooling is modified by an anomalous dynamical warming of the Arctic winter lower stratosphere. This warming is shown to be associated with an increase in frequency of stratospheric sudden warming (SSW) events. At four times pre‐industrial CO2, the frequency of SSW events per year is doubled with respect to the control simulation. Further, by comparing winters with and without SSW events, it is shown that the warming of the lower stratosphere cannot be achieved without the presence of a frequency modulation of SSW events. Copyright © 2010 Royal Meteorological Society and Crown Copyright.
Almost contact structures and curvature tensors

We determine an orthogonal decomposition of the vector space of some curvature tensors on a co-Hermitian real vector space, in irreducible components with respect to the natural induced representation of c U(n)xl. One of the components is used to introduce a Bochner curvature tensor on a class of almost co-Hermitian manifolds (or almost contact metric manifolds), called C(ά) -manifolds, containing e.g. co-Kahlerian, Sasakian and Kenmotsu manifolds. Other applications of the decomposition are given.
Anti-Angiogenic Activity of Drugs in Multiple Myeloma

Simple Summary The “angiogenic switch” contributes to the transition from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM), sustaining disease progression and drug resistance. In this review, we describe the anti-angiogenic activity of drugs employed in clinical settings for the management of MM patients providing important information on their pharmacological profile and on the molecular mechanisms responsible for their direct and indirect anti-angiogenic effect. Abstract Angiogenesis represents a pivotal hallmark of multiple myeloma (MM) that correlates to patients’ prognosis, overall survival, and drug resistance. Hence, several anti-angiogenic drugs that directly target angiogenic cytokines (i.e., monoclonal antibodies, recombinant molecules) or their cognate receptors (i.e., tyrosine kinase inhibitors) have been developed. Additionally, many standard antimyeloma drugs currently used in clinical practice (i.e., immunomodulatory drugs, bisphosphonates, proteasome inhibitors, alkylating agents, glucocorticoids) show anti-angiogenic effects further supporting the importance of inhibiting angiogenesis from potentiating the antimyeloma activity. Here, we review the most important anti-angiogenic therapies used for the management of MM patients with a particular focus on their pharmacological profile and on their anti-angiogenic effect in vitro and in vivo. Despite the promising perspective, the direct targeting of angiogenic cytokines/receptors did not show a great efficacy in MM patients, suggesting the need to a deeper knowledge of the BM angiogenic niche for the design of novel multi-targeting anti-angiogenic therapies.
Methods in molecular biogeography: The case of New Caledonia

To examine the different methods currently used in molecular biogeography. Methods of interpreting evolution in space (ancestral‐area algorithms) always find a centre of origin for a group in the region of a paraphyletic basal grade, although regionally restricted basal grades can also be generated by simple vicariance. Current analyses of the timeline of evolution are usually based on the conversion of fossil‐calibrated ages (minimum clade ages) into maximum clade ages by imposing arbitrary, subjective priors. Thus, methods of analysing both space and time in evolution are flawed in theory. They are also inefficient in practice, as indicated by recent papers on the history of the New Caledonian biota, examined here as a case‐study. Work using current methods has left the phenomena as unexplained ‘conundrums’ and ‘enigmas’.