Rare Case of a 20p13 Duplication Trisomy With Craniostenosis.

Duplication 20p or partial trisomy 20 is a rare chromosomal anomaly characterized by duplication of the short arm of chromosome 20, with various clinical abnormalities. Despite complete trisomy 20, which usually leads to prenatal death, partial trisomy 20 can manifest with variable phenotypes, from mild to severe manifestations. Here, we present a rare case of an 8-year-old boy diagnosed with trisomy 20, epilepsy with focal seizures of genetic origin, craniosynostosis, type 1 diabetes, and autism spectrum disorder. Duplication 20p is a complex diagnostic and presents a therapeutic challenge due to its diverse clinical manifestations. To succeed in the intricacy of such a unique and challenging case, a comprehensive clinical and genetic assessment must be performed.

Unconventional raw materials used in beer and beer-like beverages production: Impact on metabolomics and sensory profile.

Beer is the third most consumed beverage in the world, trailing only water and tea but ranking first among alcoholic beverages. In recent years, producers and researchers have shown a growing interest in brewing diversification and innovation, due to of the widespread consumption of beer. In order to create beers and beer-like products with unique and consumer-pleasing characteristics, the use of unconventional raw materials has become a subject of intensive research. The purpose of this paper is to identify, evaluate and summarize the findings of all relevant unconventional raw materials used in relevant scientific studies, as well as the effect on the metabolomics of beer and beer-like beverages.For the enhancement of beer characteristics, the production process may involve the use of an extremely diverse variety of unconventional raw materials that are not included on thelist of usual ingredients for the beer industry. However, the general trend is to use locally available ingredients as well as functional ingredients. Twoof the most studied functional characteristics involve phenolic compounds and antioxidant activity, which is why the fruit is by far the most commonly used adjunct category, as fruits are particularly important sources of polyphenols and antioxidants. Other uncommon adjuncts used in brewing includeplants, starch sources, spices or even propolis. Moreover, unconventional raw materials are used to enhance the sensory profile by create new characteristics such as new tastes and flavors, accentuation of the cooling sensation or even increasing acceptability among potential consumers, who do not appreciate traditional beers due to their specific characteristics.

The post-stroke young adult brain has limited capacity to re-express the gene expression patterns seen during early postnatal brain development.

The developmental origins of the brain's response to injury can play an important role in recovery after a brain lesion. In this study, we investigated whether the ischemic young adult brain can re-express brain plasticity genes that were active during early postnatal development. Differentially expressed genes in the cortex of juvenile post-natal day 3 and the peri-infarcted cortical areas of young, 3-month-old post-stroke rats were identified using fixed-effects modeling within an empirical Bayes framework through condition-specific comparison. To further analyze potential biological processes, upregulated and downregulated genes were assessed for enrichment using GSEA software. The genes showing the highest expression changes were subsequently verified through RT-PCR. Our findings indicate that the adult brain partially recapitulates the gene expression profile observed in the juvenile brain but fails to upregulate many genes and pathways necessary for brain plasticity. Of the upregulated genes in post-stroke brains, specific roles have not been assigned to Apobec1, Cenpf, Ect2, Folr2, Glipr1, Myo1f, and Pttg1. New genes that failed to upregulate in the adult post-stroke brain include Bex4, Cd24, Klhl1/Mrp2, Trim67, and St8sia2. Among the upregulated pathways, the largest change was observed in the KEGG pathway "One carbon pool of folate," which is necessary for cellular proliferation, followed by the KEGG pathway "Antifolate resistance," whose genes mainly encode the family of ABC transporters responsible for the efflux of drugs that have entered the brain. We also noted three less-described downregulated KEGG pathways in experimental models: glycolipid biosynthesis, oxytocin, and cortisol pathways, which could be relevant as therapeutic targets. The limited brain plasticity of the adult brain is illustrated through molecular and histological analysis of the axonal growth factor, KIF4. Collectively, these results strongly suggest that further research is needed to decipher the complex genetic mechanisms that prevent the re-expression of brain plasticity-associated genes in the adult brain.

Experimental Research on Wolfram Inert Gas AA1050 Aluminum Alloy Tailor Welded Blanks Processed by Single Point Incremental Forming Process.

The present paper aims to study the behavior of tailor welded blanks subjected to a single point incremental forming (SPIF) process from an experimental point of view. This process was chosen to deform truncated cone shapes of AA1050 aluminum alloy with different thicknesses. A uniaxial tensile test was performed to determine the mechanical characteristics of the alloy. Initial experimental tests implicated the use of variable wall angle parts which were processed on unwelded sheet blanks for determination of the behavior of the material and the forming forces. Afterwards, the wolfram inert gas (WIG) welding technique was used for joining two sheet blanks with different thicknesses either through one pass on one side, or by one pass on both sides. The conclusion of this paper indicates that one-sided welded blanks cannot be deformed successfully without fracture. In case of two-sided welded blanks, the results showed that the desired depth of 25 mm can be reached successfully. In case of the SPIF process, if welded blanks must be deformed, then the suitable method is to weld the blanks on both sides.

Two Spinning Black Holes Balanced by Their Synchronized Scalar Hair.

General relativity minimally coupled to a massive, free, complex scalar field, is shown to allow asymptotically flat solutions, nonsingular on and outside the event horizon, describing two spinning black holes (2sBHs) in equilibrium, with coaxial, aligned angular momenta. The 2sBHs configurations bifurcate from solutions describing dipolar spinning boson stars. The BHs emerge at equilibrium points diagnosed by a test particle analysis and illustrated by a Newtonian analog. The individual BH "charges" are mass and angular momentum only. Equilibrium is due to the scalar environment, acting as a (compact) dipolar field, providing a lift against their mutual attraction, making the 2sBHs (h)airborne. We explore the 2sBHs domain of solutions and its main features.

Eco-Design of Polymer Matrix Composite Parts: A Review.

This research presents a series of analyses related to the eco-design of polymer matrix composite parts, addressing various aspects of it. The main objective was to clarify the definition of ecological design, the benefits of its implementation and its importance in all stages of obtaining a product (design, manufacturing, recycling). Global environmental issues are presented, emphasizing the importance of adopting sustainable approaches in product design and manufacturing. Special attention is paid to the analysis of waste recycling technologies for polymer matrix composite materials. The analysis carried out identifies specific ecological design principles applicable to these materials and presents recent trends in the field. Relevant case studies are highlighted, demonstrating the benefits of ecological design in order to obtain sustainable products. Additionally, the conducted research allowed for finding answers to the questions "what", "why", "when" and "how" it is necessary to apply the principles of eco-design in the case of composite materials with a polymer matrix. In general, the research promotes eco-design as an indispensable strategy for sustainable and responsible production, inspiring companies to adopt these principles for the benefit of the environment and their business performance.

Exotic Compact Objects and the Fate of the Light-Ring Instability.

Ultracompact objects with light rings (LRs) but without an event horizon could mimic black holes (BHs) in their strong gravity phenomenology. But are such objects dynamically viable? Stationary and axisymmetric ultracompact objects that can form from smooth, quasi-Minkowski initial data must have at least one stable LR, which has been argued to trigger a spacetime instability; but its development and fate have been unknown. Using fully nonlinear numerical evolutions of ultracompact bosonic stars free of any other known instabilities and introducing a novel adiabatic effective potential technique, we confirm the LRs triggered instability, identifying two possible fates: migration to nonultracompact configurations or collapse to BHs. In concrete examples we show that typical migration (collapse) timescales are not larger than ∼10^{3} light-crossing times, unless the stable LR potential well is very shallow. Our results show that the LR instability is effective in destroying horizonless ultracompact objects that could be plausible BH imitators.

Vaccine mRNA Can Be Detected in Blood at 15 Days Post-Vaccination.

COVID-19 mRNA vaccines effectively reduce incidence of severe disease, hospitalisation and death. The biodistribution and pharmacokinetics of the mRNA-containing lipid nanoparticles (LNPs) in these vaccines are unknown in humans. In this study, we used qPCR to track circulating mRNA in blood at different time-points after BNT162b2 vaccination in a small cohort of healthy individuals. We found that vaccine-associated synthetic mRNA persists in systemic circulation for at least 2 weeks. Furthermore, we used transmission electron microscopy (TEM) to investigate SARS-CoV-2 spike protein expression in human leukemic cells and in primary mononuclear blood cells treated in vitro with the BNT162b2 vaccine. TEM revealed morphological changes suggestive of LNP uptake, but only a small fraction of K562 leukemic cells presented spike-like structures at the cell surface, suggesting reduced levels of expression for these specific phenotypes.

Multifield, Multifrequency Bosonic Stars and a Stabilization Mechanism.

Scalar bosonic stars (BSs) stand out as a multipurpose model of exotic compact objects. We enlarge the landscape of such (asymptotically flat, stationary, everywhere regular) objects by considering multiple fields (possibly) with different frequencies. This allows for new morphologies and a stabilization mechanism for different sorts of unstable BSs. First, any odd number of complex fields, yields a continuous family of BSs departing from the spherical, equal frequency, ℓ-BSs. As the simplest illustration, we construct the ℓ=1 BSs family, that includes several single-frequency solutions, including even parity (such as spinning BSs and a toroidal, static BS) and odd parity (a dipole BS) limits. Second, these limiting solutions are dynamically unstable, but can be stabilized by a hybrid-ℓ construction: adding a sufficiently large fundamental ℓ=0 BS of another field, with a different frequency. Evidence for this dynamical robustness is obtained by nonlinear numerical simulations of the corresponding Einstein-(complex, massive) Klein-Gordon system, both in formation and evolution scenarios, and a suggestive correlation between stability and energy distribution is observed. Similarities and differences with vector BSs are anticipated.

Quantitative analyses of CD7, CD33, CD34, CD56, and CD123 within the FLT3-ITD/NPM1-MUT myeloblastic/monocytic bulk AML blastic populations.

The most frequent mutations in acute myeloid leukemia (AML) - FLT3-ITD and NPM1 - are associated with a specific immunophenotype. We evaluated the levels of surface antigens in an uninvestigated AML patient population according to the combination of FLT3-ITD/NPM1 mutations. Antigen levels were calculated as the geometric mean fluorescence index (MFI) ratio between myeloblasts or monoblasts/monocytes and a negative population for the specific antigen. In myeloblastic populations, FLT3-ITD cases presented CD7high MFI values (p < .001), while NPM1-MUT cases presented CD33high (p < .001), and CD34low (p < .001) MFI values. Within the monoblastic/monocytic populations, CD56high expression was observed only in the FLT3-WT/NPM1-MUT population (p=.003). The single common antigen expression between myeloblasts and monoblasts/monocytes was CD123high expression only within the FLT3-ITD/NPM1-MUT subgroup. Our results present a subtle influence of FLT3-ITD/NPM1 mutations upon antigen expression profiles in myeloblasts vs monoblasts/monocytes, and we described a novel correlation between the presence of NPM1 and CD56high values within bulk leukemic monoblasts/monocytes.

Traversable Wormholes in Einstein-Dirac-Maxwell Theory.

We construct a specific example of a class of traversable wormholes in Einstein-Dirac-Maxwell theory in four spacetime dimensions, without needing any form of exotic matter. Restricting to a model with two massive fermions in a singlet spinor state, we show the existence of spherically symmetric asymptotically flat configurations which are free of singularities, representing localized states. These solutions satisfy a generalized Smarr relation, being connected with the extremal Reissner-Nordström black holes. They also possess a finite mass M and electric charge Q_{e}, with Q_{e}/M>1. An exact wormhole solution with ungauged, massless fermions is also reported.

GW190521 as a Merger of Proca Stars: A Potential New Vector Boson of 8.7×10

Advanced LIGO-Virgo have reported a short gravitational-wave signal (GW190521) interpreted as a quasicircular merger of black holes, one at least populating the pair-instability supernova gap, that formed a remnant black hole of M_{f}∼142 M_{⊙} at a luminosity distance of d_{L}∼5.3 Gpc. With barely visible pre-merger emission, however, GW190521 merits further investigation of the pre-merger dynamics and even of the very nature of the colliding objects. We show that GW190521 is consistent with numerically simulated signals from head-on collisions of two (equal mass and spin) horizonless vector boson stars (aka Proca stars), forming a final black hole with M_{f}=231_{-17}^{+13} M_{⊙}, located at a distance of d_{L}=571_{-181}^{+348} Mpc. This provides the first demonstration of close degeneracy between these two theoretical models, for a real gravitational-wave event. The favored mass for the ultralight vector boson constituent of the Proca stars is µ_{V}=8.72_{-0.82}^{+0.73}×10^{-13} eV. Confirmation of the Proca star interpretation, which we find statistically slightly preferred, would provide the first evidence for a long sought dark matter particle.

Spin-Induced Scalarized Black Holes.

It was recently shown that a scalar field suitably coupled to the Gauss-Bonnet invariant G can undergo a spin-induced linear tachyonic instability near a Kerr black hole. This instability appears only once the dimensionless spin j is sufficiently large, that is, j≳0.5. A tachyonic instability is the hallmark of spontaneous scalarization. Focusing, for illustrative purposes, on a class of theories that do exhibit this instability, we show that stationary, rotating black hole solutions do indeed have scalar hair once the spin-induced instability threshold is exceeded, while black holes that lie below the threshold are described by the Kerr solution. Our results provide strong support for spin-induced black hole scalarization.

Ageing as a risk factor for cerebral ischemia: Underlying mechanisms and therapy in animal models and in the clinic.

Age is the only one non-modifiable risk of cerebral ischemia. Advances in stroke medicine and behavioral adaptation to stroke risk factors and comorbidities was successful in decreasing stroke incidence and increasing the number of stroke survivors in western societies. Comorbidities aggravates the outcome after cerebral ischemia. However, due to the increased in number of elderly, the incidence of stroke has increased again paralleled by an increase in the number of stroke survivors, many with severe disabilities, that has led to an increased economic and social burden in society. Animal models of stroke often ignore age and comorbidities frequently associated with senescence. This might explain why drugs working nicely in animal models fail to show efficacy in stroke survivors. Since stroke afflicts mostly the elderly comorbid patients, it is highly desirable to test the efficacy of stroke therapies in an appropriate animal stroke model. Therefore, in this review, we make parallels between animal models of stroke und clinical data and summarize the impact of ageing and age-related comorbidities on stroke outcome.

Evaluation of Commercial qPCR Kits for Detection of SARS-CoV-2 in Pooled Samples.

Due to the current pandemic, a global shortage of reagents has drawn interest in developing alternatives to increase the number of coronavirus tests. One such alternative is sample pooling. We compared commercial kits that are used in COVID-19 diagnostics in terms of their sensitivity and feasibility for use in pooling. In this preliminary study, we showed that pooling of up to 80 samples did not affect the efficacy of the kits. Additionally, the RNA-dependent RNA polymerase (RdRp) gene is a more suitable target in pooled samples than the envelope (E) gene. This approach could provide an easy method of screening a large number of samples and help adjust different governmental regulations.

FLT3-ITD DNA and mRNA levels in AML do not correlate with CD7, CD33 and CD123 expression.

INTRODUCTION: FLT3 internal tandem duplication (ITD) mutations are found in around 25% of all acute myeloid leukaemia (AML) cases and is associated with shorter disease-free and overall survival. Previous reports have shown that FLT3-ITD induces a specific phenotype in leukemic blasts, which is characterized by high levels of CD33 and CD123, and that expression of CD33 and CD123 is directly influenced by the DNA FLT3-ITD/wild-type FLT3 allelic ratio (AR). METHODS: A total of 42 FLT3-ITD and 104 FLT3-ITD-negative AML patients were analysed. Immunophenotyping data were used to calculate antigen expression levels as the ratio between the geometric mean fluorescence intensities (MFIs) of leukemic blasts and MFIs of negative lymphocyte populations. FLT3-ITD-DNA and RNA analysis was performed, under the same conditions, by capillary electrophoresis. RESULTS: Compared with the control group, the FLT3-ITD cohort presented significantly higher CD7, CD33 and CD123 levels. In order to assess the impact of FLT3-ITD abundance on antigen expression, the patients were grouped for each parameter into two cohorts using the following threshold values: (a) 0.5 for the AR, according to current AML guidelines; (b) 0.7 for the FLT3-ITD/FLT3-WT mRNA ratio (RR); and (c) 1.3 for the FLT3-ITD RR/AR ratio. We found higher values of CD33 for RR/AR ≥1.3, and no other statistical differences between CD7, CD33 and CD123 levels of the other FLT3-ITD groups. In terms of correlations between MFI values and FLT3-ITD parameters, we only observed a moderate interdependence between CD33 MFI and the RR/AR ratio, and a weak negative correlation between CD123 MFI and AR. CONCLUSION: FLT3-ITD mutations induce a specific antigen profile in AML blasts, and our data do not onfirm previous reports of FLT3-ITD AR influencing both CD33 and CD123 expression.

Versatile Biomaterial Platform Enriched with Graphene Oxide and Carbon Nanotubes for Multiple Tissue Engineering Applications.

Carbon-based nanomaterials, such as graphene oxide (GO) or carbon nanotubes (CNTs) are currently used in various medical applications due to their positive influence on biocompatibility, adhesion, proliferation, and differentiation, as well as their contribution to modulating cell behavior in response to nanomaterial substrates. In this context, in this study, novel flexible membranes based on cellulose acetate (CA) enriched with CNT and GO in different percentages were tested for their versatility to be used as substrates for soft or hard tissue engineering (TE), namely, for their ability to support human adipose-derived stem cells (hASCs) adhesion during adipogenic or osteogenic differentiation. For this purpose, differentiation markers were assessed both at gene and protein levels, while histological staining was performed to show the evolution of the processes in response to CA-CNT-GO substrates. Micro-CT analysis indicated porous morphologies with open and interconnected voids. A slightly lower total porosity was obtained for the samples filled with the highest amount of GO and CNTs, but thicker walls, larger and more uniform pores were obtained, providing beneficial effects on cell behavior and increased mechanical stability. The addition of 1 wt% GO and CNT to the biocomposites enhanced hASCs adhesion and cytoskeleton formation. The evolution of both adipogenic and osteogenic differentiation processes was found to be augmented proportionally to the GO-CNT concentration. In conclusion, CA-CNT-GO biomaterials displayed good properties and versatility as platforms for cell differentiation with potential as future implantable materials in TE applications.

Spontaneously Scalarized Kerr Black Holes in Extended Scalar-Tensor-Gauss-Bonnet Gravity.

We construct asymptotically flat, spinning, regular on and outside an event horizon, scalarized black holes (SBHs) in extended scalar-tensor-Gauss-Bonnet models. They reduce to Kerr BHs when the scalar field vanishes. For an illustrative choice of nonminimal coupling, we scan the domain of existence. For each value of spin, SBHs exist in an interval between two critical masses, with the lowest one vanishing in the static limit. Non-uniqueness with Kerr BHs of equal global charges is observed; the SBHs are entropically favoured. This suggests that SBHs form dynamically from the spontaneous scalarization of Kerr BHs, which are prone to a scalar-triggered tachyonic instability, below the largest critical mass. Phenomenologically, the introduction of BH spin damps the maximal observable difference between comparable scalarized and vacuum BHs. In the static limit, (perturbatively stable) SBHs can store over 20% of the spacetime energy outside the event horizon; in comparison with Schwarzschild BHs, their geodesic frequency at the ISCO can differ by a factor of 2.5 and deviations in the shadow areal radius may top 40%. As the BH spin grows, low mass SBHs are excluded, and the maximal relative differences decrease, becoming of the order of a few percent for dimensionless spin j≳0.5. This reveals a spin selection effect: non-GR effects are only significant for low spin. We discuss if and how the recently measured shadow size of the M87 supermassive BH constrains the length scale of the Gauss-Bonnet coupling.

Spontaneous Scalarization of Charged Black Holes.

Extended scalar-tensor Gauss-Bonnet (ESTGB) gravity has been recently argued to exhibit spontaneous scalarization of vacuum black holes (BHs). A similar phenomenon can be expected in a larger class of models, which includes, e.g., Einstein-Maxwell scalar (EMS) models, where spontaneous scalarization of electrovacuum BHs should occur. EMS models have no higher curvature corrections, a technical simplification over ESTGB models that allows us to investigate, fully nonlinearly, BH scalarization in two novel directions. First, numerical simulations in spherical symmetry show, dynamically, that Reissner-Nordström (RN) BHs evolve into a perturbatively stable scalarized BH. Second, we compute the nonspherical sector of static scalarized BH solutions bifurcating from the RN BH trunk. Scalarized BHs form an infinite (countable) number of branches and possess a large freedom in their multipole structure. Unlike the case of electrovacuum, the EMS model admits static, asymptotically flat, regular on and outside the horizon BHs without spherical symmetry and even without any spatial isometries, which are thermodynamically preferred over the electrovacuum state. We speculate on a possible dynamical role of these nonspherical scalarized BHs.

Targeting CD36 as Biomarker for Metastasis Prognostic: How Far from Translation into Clinical Practice?

Metastasis requires cellular changes related to cell-to-cell and cell-to-matrix adhesion, immune surveillance, activation of growth and survival signalling pathways, and epigenetic modifications. In addition to tumour cells, tumour stroma is also modified in relationship to the primary tumour as well as to distant metastatic sites (forming a metastatic niche). A common denominator of most stromal partners in tumour progression is CD36, a scavenger receptor for fatty acid uptake that modulates cell-to-extracellular matrix attachment, stromal cell fate (for adipocytes, endothelial cells), TGFß activation, and immune signalling. CD36 has been repeatedly proposed as a prognostic marker in various cancers, mostly of epithelial origin (breast, prostate, ovary, and colon) and also for hepatic carcinoma and gliomas. Data gathered in preclinical models of various cancers have shown that blocking CD36 might prove beneficial in stopping metastasis spread. However, targeting the receptor in clinical trials with thrombospondin mimetic peptides has proven ineffective, and monoclonal antibodies are not yet available for patient use. This review presents data to support CD36 as a potential prognostic biomarker in cancer, its current stage towards achieving bona fide biomarker status, and knowledge gaps that must be filled before further advancement towards clinical practice.