About 2%–5% of acute lymphoblastic leukemia (ALL) cases in pediatric patients are infants with an unfavorable prognosis because of high relapse probability. Early detection of the disease is, therefore, very important. Despite the fact that leukemia in twins occurs rarely, more attention has been paid to it in genetic studies. In the present study, through cytogenetic testing, a special case of concordant ALL in monozygotic twins was presented with different outcomes. In spite of an acceptable initial consequence to medical treatment in twins, in another brother (Twin B), early relapse was observed. In the cytogenetic study, both twins expressed t (4; 11) (q21; q23) while twin A expressed t (2; 7) (p10; q10). No cases have previously reported this mutation. Whether this translocation has a protective role for leukemia with mixed-lineage leukemia (MLL) gene rearrangement is still unclear. The difference in the translocation identified in the identical twins is also subject to further investigations. Full article

Background and Objective: Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis. Fibrin degradation products secondary to extravascular fibrin breakdown could contribute to the marked increase in D-Dimers during COVID-19. We sought to examine the prognostic value on lung injury of D-Dimers in non-critically ill COVID-19 patients without thrombotic events. Methods: This study retrospectively analysed hospitalized COVID-19 patients classified according to a D-Dimers threshold following the COVID-19 associated haemostatic abnormalities (CAHA) classification at baseline and at peak (Stage 1: D-Dimers less than three-fold above normal; Stage 2: D-Dimers three- to six-fold above normal; Stage 3: D-Dimers six-fold above normal). The primary endpoint was the occurrence of critical lung injuries on chest computed tomography. The secondary outcome was the composite of in-hospital death or transfer to the intensive care unit (ICU). Results: Among the 123 patients included, critical lung injuries were evidenced in 8 (11.9%) patients in Stage 1, 6 (20%) in Stage 2 and 15 (57.7%) in Stage 3 (p = 0.001). D-Dimers staging at peak was an independent predictor of critical lung injuries regardless of the inflammatory burden assessed by CRP levels (OR 2.70, 95% CI (1.50–4.86); p < 0.001) and was significantly associated with increased in-hospital death or ICU transfer (14.9 % in Stage 1, 50.0% in Stage 2 and 57.7% in Stage 3 (p < 0.001)). D-Dimers staging at peak was an independent predictor of in-hospital death or ICU transfer (OR 2.50, CI 95% (1.27–4.93); p = 0.008). Conclusions: In the absence of overt thrombotic events, D-Dimers quantification is a relevant marker of critical lung injuries and dismal patient outcome. Full article

In Antarctica, spectral mapping of altered minerals is very challenging due to the remoteness and inaccessibility of poorly exposed outcrops. This investigation evaluates the capability of Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) satellite remote sensing imagery for mapping and discrimination of phyllosilicate mineral groups in the Antarctic environment of northern Victoria Land. The Mixture-Tuned Matched-Filtering (MTMF) and Constrained Energy Minimization (CEM) algorithms were used to detect the sub-pixel abundance of Al-rich, Fe³⁺-rich, Fe²⁺-rich and Mg-rich phyllosilicates using the visible and near-infrared (VNIR), short-wave infrared (SWIR) and thermal-infrared (TIR) bands of ASTER. Results indicate that Al-rich phyllosilicates are strongly detected in the exposed outcrops of the Granite Harbour granitoids, Wilson Metamorphic Complex and the Beacon Supergroup. The presence of the smectite mineral group derived from the Jurassic basaltic rocks (Ferrar Dolerite and Kirkpatrick Basalts) by weathering and decomposition processes implicates Fe³⁺-rich and Fe²⁺-rich phyllosilicates. Biotite (Fe²⁺-rich phyllosilicate) is detected associated with the Granite Harbour granitoids, Wilson Metamorphic Complex and Melbourne Volcanics. Mg-rich phyllosilicates are mostly mapped in the scree, glacial drift, moraine and crevasse fields derived from weathering and decomposition of the Kirkpatrick Basalt and Ferrar Dolerite. Chlorite (Mg-rich phyllosilicate) was generally mapped in the exposures of Granite Harbour granodiorite and granite and partially identified in the Ferrar Dolerite, the Kirkpatrick Basalt, the Priestley Formation and Priestley Schist and the scree, glacial drift and moraine. Statistical results indicate that Al-rich phyllosilicates class pixels are strongly discriminated, while the pixels attributed to Fe³⁺-rich class, Fe²⁺-rich and Mg-rich phyllosilicates classes contain some spectral mixing due to their subtle spectral differences in the VNIR+SWIR bands of ASTER. Results derived from TIR bands of ASTER show that a high level of confusion is associated with mafic phyllosilicates pixels (Fe³⁺-rich, Fe²⁺-rich and Mg-rich classes), whereas felsic phyllosilicates (Al-rich class) pixels are well mapped. Ground truth with detailed geological data, petrographic study and X-ray diffraction (XRD) analysis verified the remote sensing results. Consequently, ASTER image-map of phyllosilicate minerals is generated for the Mesa Range, Campbell and Priestley Glaciers, northern Victoria Land of Antarctica. Full article

We address security and privacy problems for digital devices and biometrics from an information-theoretic optimality perspective to conduct authentication, message encryption/decryption, identification or secure and private computations by using a secret key. A physical unclonable function (PUF) provides local security to digital devices and this review gives the most relevant summary for information theorists, coding theorists, and signal processing community members who are interested in optimal PUF constructions. Low-complexity signal processing methods are applied to simplify information-theoretic analyses. The best trade-offs between the privacy-leakage, secret-key, and storage rates are discussed. Proposed optimal constructions that jointly design the vector quantizer and error-correction code parameters are listed. These constructions include modern and algebraic codes such as polar codes and convolutional codes, both of which can achieve small block-error probabilities at short block lengths, corresponding to a small number of PUF circuits. Open problems in the PUF literature from signal processing, information theory, coding theory, and hardware complexity perspectives and their combinations are listed to stimulate further advancements in the research on local privacy and security. Full article

There are >200 different types of human papilloma virus (HPV) of which >51 infect genital epithelium, with the ~14 of these classed as high-risk being more commonly associated with cervical cancer. During development of the disease, high-risk types have an increased tendency to develop a truncated non-replicative life cycle, whereas low-risk, non-cancer-associated HPV types are either asymptomatic or cause benign lesions completing their full replicative life cycle. HPVs can also be present as non-replicative so-called “latent” infections and they can also show superinfection exclusion, where cells with pre-existing infections with one type cannot be infected with a different HPV type. Thus, the HPV repertoire and replication status present in an individual can form a complex dynamic meta-community which changes with respect to both time and exposure to different HPV types. In light of these considerations, it is not clear how current prophylactic HPV vaccines will affect this system and the potential for iatrogenic outcomes is discussed in light of recent outcome data. Full article

The neuromuscular junction (NMJ) is at the crossroad between the nervous system (NS) and the muscle. Following neurotransmitter release from the motor neurons (MNs), muscle contraction occurs and movement is generated. Besides eliciting muscle contraction, the NMJ represents a site of chemical bidirectional interplay between nerve and muscle with the active participation of Schwann cells. Indeed, signals originating from the muscle play an important role in synapse formation, stabilization, maintenance and function, both in development and adulthood. We focus here on the contribution of the Glial cell line-Derived Neurotrophic Factor (GDNF) to these processes and to its potential role in the protection of the NMJ during neurodegeneration. Historically related to the maintenance and survival of dopaminergic neurons of the substantia nigra, GDNF also plays a fundamental role in the peripheral NS (PNS). At this level, it promotes muscle trophism and it participates to the functionality of synapses. Moreover, compared to the other neurotrophic factors, GDNF shows unique peculiarities, which make its contribution essential in neurodegenerative disorders. While describing the known structural and functional changes occurring at the NMJ during neurodegeneration, we highlight the role of GDNF in the NMJ–muscle cross-talk and we review its therapeutic potential in counteracting the degenerative process occurring in the PNS in progressive and severe diseases such as Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA). We also describe functional 3D neuromuscular co-culture systems that have been recently developed as a model for studying both NMJ formation in vitro and its involvement in neuromuscular disorders. Full article

This study aimed to develop and validate two predictive models of postpartum post-traumatic stress disorder (PTSD) risk using a retrospective cohort study of women who gave birth between 2018 and 2019 in Spain. The predictive models were developed using a referral cohort of 1752 women (2/3) and were validated on a cohort of 875 women (1/3). The predictive factors in model A were delivery type, skin-to-skin contact, admission of newborn to care unit, presence of a severe tear, type of infant feeding at discharge, postpartum hospital readmission. The area under curve (AUC) of the receiver operating characteristic (ROC) in the referral cohort was 0.70 (95% CI: 0.67–0.74), while in the validation cohort, it was 0.69 (95% CI: 0.63–0.75). The predictive factors in model B were delivery type, admission of newborn to care unit, type of infant feeding at discharge, postpartum hospital readmission, partner support, and the perception of adequate respect from health professionals. The predictive capacity of model B in both the referral cohort and the validation cohort was superior to model A with an AUC-ROC of 0.82 (95% CI: 0.79–0.85) and 0.83 (95% CI: 0.78–0.87), respectively. A predictive model (model B) formed by clinical variables and the perception of partner support and appropriate treatment by health professionals had a good predictive capacity in both the referral and validation cohorts. This model is preferred over the model (model A) that was formed exclusively by clinical variables. Full article

The mosquito Aedes aegypti transmits the virus that causes dengue, yellow fever, Zika and Chikungunya viruses, and in several regions of the planet represents a vector of great clinical importance. In terms of mortality and morbidity, infections caused by Ae. aegypti are among the most serious arthropod transmitted viral diseases. The present study investigated the larvicidal potential of seventeen cinnamic acid derivatives against fourth stage Ae. aegypti larvae. The larvicide assays were performed using larval mortality rates to determine lethal concentration (LC₅₀). Compounds containing the medium alkyl chains butyl cinnamate (7) and pentyl cinnamate (8) presented excellent larvicidal activity with LC₅₀ values of around 0.21–0.17 mM, respectively. While among the derivatives with aryl substituents, the best LC₅₀ result was 0.55 mM for benzyl cinnamate (13). The tested derivatives were natural compounds and in pharmacology and antiparasitic studies, many have been evaluated using biological models for environmental and toxicological safety. Molecular modeling analyses suggest that the larvicidal activity of these compounds might be due to a multi-target mechanism of action involving inhibition of a carbonic anhydrase (CA), a histone deacetylase (HDAC2), and two sodium-dependent cation-chloride co-transporters (CCC2 e CCC3). Full article

Accurate segmentation of retinal blood vessels is a key step in the diagnosis of fundus diseases, among which cataracts, glaucoma, and diabetic retinopathy (DR) are the main diseases that cause blindness. Most segmentation methods based on deep convolutional neural networks can effectively extract features. However, convolution and pooling operations also filter out some useful information, and the final segmented retinal vessels have problems such as low classification accuracy. In this paper, we propose a multi-scale residual attention network called MRA-UNet. Multi-scale inputs enable the network to learn features at different scales, which increases the robustness of the network. In the encoding phase, we reduce the negative influence of the background and eliminate noise by using the residual attention module. We use the bottom reconstruction module to aggregate the feature information under different receptive fields, so that the model can extract the information of different thicknesses of blood vessels. Finally, the spatial activation module is used to process the up-sampled image to further increase the difference between blood vessels and background, which promotes the recovery of small blood vessels at the edges. Our method was verified on the DRIVE, CHASE, and STARE datasets. Respectively, the segmentation accuracy rates reached 96.98%, 97.58%, and 97.63%; the specificity reached 98.28%, 98.54%, and 98.73%; and the F-measure scores reached 82.93%, 81.27%, and 84.22%. We compared the experimental results with some state-of-art methods, such as U-Net, R2U-Net, and AG-UNet in terms of accuracy, sensitivity, specificity, F-measure, and AUC${}_R{}_O{}_C$. Particularly, MRA-UNet outperformed U-Net by 1.51%, 3.44%, and 0.49% on DRIVE, CHASE, and STARE datasets, respectively. Full article

This paper investigates the asymptotical behavior of the equilibrium of linear classical duopolies by reconsidering the two-delay model with two different positive delays. In a two-dimensional analysis, the stability switching curves were first analytically determined. Numerical studies verified and illustrated the theoretical results. In the sensitivity analysis it was demonstrated that the inertia coefficient has a twofold effect: enlarges the stability region as well as simplifies the complicated dynamics with period-halving cascade. In contrary, the adjustment speed contracts the stability region and complicates simple dynamics with period-doubling bifurcation. In addition, for various values of ${\tau }_1$ and ${\tau }_2,$a wide variety of dynamics appears ranging from simple cycle via a Hopf bifurcation to chaotic oscillations. Full article

Early blood biomarkers to diagnose acute stroke could drastically reduce treatment delays. We investigated whether circulating small non-coding RNAs can serve as biomarkers to distinguish between acute ischemic stroke (IS), intracerebral hemorrhage (ICH) and stroke mimics (SM). In an ongoing observational cohort study, we performed small RNA-sequencing in plasma obtained from a discovery cohort of 26 patients (9 IS, 8 ICH and 9 SM) presented to the emergency department within 6 h of symptom onset. We validated our results in an independent dataset of 20 IS patients and 20 healthy controls. ICH plasma had the highest abundance of ribosomal and tRNA-derived fragments, while microRNAs were most abundant in plasma of IS patients. Combinations of four to five tRNAs yielded diagnostic accuracies (areas under the receiver operating characteristics curve) up to 0.986 (ICH vs. IS and SM) in the discovery cohort. Validation of the IS and SM models in the independent dataset yielded diagnostic accuracies of 0.870 and 0.885 to distinguish IS from healthy controls. Thus, we identified tRNA-derived fragments as a promising novel class of biomarkers to distinguish between acute IS, ICH and SM, as well as healthy controls. Full article

Substance use disorder (SUD) is a serious public health problem worldwide for which available treatments show limited effectiveness. Since the legalization of cannabis and the approval of cannabidiol (CBD) by the US Food and Drug Administration, therapeutic potential of CBD for the treatment of SUDs and other diseases has been widely explored. In this mini-review article, we first review the history and evidence supporting CBD as a potential pharmacotherapeutic. We then focus on recent progress in preclinical research regarding the pharmacological efficacy of CBD and the underlying receptor mechanisms on addictive-like behavior. Growing evidence indicates that CBD has therapeutic potential in reducing drug reward, as assessed in intravenous drug self-administration, conditioned place preference and intracranial brain-stimulation reward paradigms. In addition, CBD is effective in reducing relapse in experimental animals. Both in vivo and in vitro receptor mechanism studies indicate that CBD may act as a negative allosteric modulator of type 1 cannabinoid (CB1) receptor and an agonist of type 2 cannabinoid (CB2), transient receptor potential vanilloid 1 (TRPV1), and serotonin 5-HT_1A receptors. Through these multiple-receptor mechanisms, CBD is believed to modulate brain dopamine in response to drugs of abuse, leading to attenuation of drug-taking and drug-seeking behavior. While these findings suggest that CBD is a promising therapeutic candidate, further investigation is required to verify its safety, pharmacological efficacy and the underlying receptor mechanisms in both experimental animals and humans. Full article

Two poly(δ-valerolactone)/poly(ethylene-co-vinylalcohol)/beta-tricalcium phosphate (PEVAL/PDVAL/β-TCP) composites containing an equal ratio of polymer and filled with 50 and 70 wt% of β-TCP microparticles were prepared by the solvent casting method. Interconnected pores were realized using the salt leached technique, and the porosity of the resulted composites was evaluated by the scanning electron microscopy (SEM) method. The homogeneity of the hybrid materials was investigated by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The prepared materials’ SEM images showed interconnected micropores that respond to the conditions required to allow their uses as scaffolds. The porosity of each scaffold was determined from micro computed tomography (micro-CT) data, and the analysis of the mechanical properties of the prepared materials was studied through the stress-strain compressive test. The proliferation test results used human mesenchymal stem cells (MSCs) to grow and proliferate on the different types of prepared materials, reflecting that the hybrid materials were non-toxic and could be biologically acceptable scaffolds. The antibacterial activity test revealed that incorporation of amoxicillin in the specimens could inhibit the bacterial growth of S. aureus. The in vitro study of the release of amoxicillin from the PEVAL/PDVAL/amoxicillin and PEVAL/PDVAL/β-TCP/amoxicillin drug carrier systems in pH media 7.4, during eight days, gave promising results, and the antibiotic diffusion in these scaffolds obeys the Fickian model. Full article

Sorbus commixta is a valuable hardwood plant with a high economical value for its medicinal and ornamental qualities. The aim of this work was to investigate the effects of the iron (Fe) source and medium pH on the growth and development of S. commixta in vitro. The Fe sources used, including non-chelated iron sulfate (FeSO₄), iron ethylenediaminetetraacetic acid (Fe-EDTA), and iron diethylenetriaminepentaacetic acid (Fe-DTPA), were supplemented to the Multipurpose medium with a final Fe concentration of 2.78 mg·L⁻¹. The medium without any supplementary Fe was used as the control. The pH of the agar-solidified medium was adjusted to either 4.70, 5.70, or 6.70. The experiment was conducted in a culture room for six weeks with 25 °C day and night temperatures, and a 16-h photoperiod with a light intensity of 50 mmol·m⁻²·s⁻¹ photosynthetic photon flux density (PPFD). Both the Fe source and pH affected the growth and development of the micropropagated plants in vitro. The leaves were greener in the pH 4.70 and 5.70 treatments. The tissue Fe content decreased with the increase of the medium pH. The leaf chlorophyll content was similar between plants treated with FeSO₄ and those with Fe-EDTA. The numbers of the shoots and roots of plantlets treated with FeSO₄ were 2.5 and 2 times greater than those of the control, respectively. The fresh and dry weights of the shoot and the root were the greatest for plants treated with Fe-EDTA combined with pH 5.70. The calcium, magnesium, and manganese contents in the plantlets increased in the pH 5.70 treatments regardless of the Fe source. Supplementary Fe decreased the activity of ferric chelate reductase. Overall, although the plantlets absorbed more Fe at pH 4.70, Fe-EDTA combined with pH 5.70 was found to be the best for the growth and development of S. commixta in vitro. Full article

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression in both animals and plants. By pairing to microRNA responsive elements (mREs) on target mRNAs, miRNAs play gene-regulatory roles, producing remarkable changes in several physiological and pathological processes. Thus, the identification of miRNA-mRNA target interactions is fundamental for discovering the regulatory network governed by miRNAs. The best way to achieve this goal is usually by computational prediction followed by experimental validation of these miRNA-mRNA interactions. This review summarizes the key strategies for miRNA target identification. Several tools for computational analysis exist, each with different approaches to predict miRNA targets, and their number is constantly increasing. The major algorithms available for this aim, including Machine Learning methods, are discussed, to provide practical tips for familiarizing with their assumptions and understanding how to interpret the results. Then, all the experimental procedures for verifying the authenticity of the identified miRNA-mRNA target pairs are described, including High-Throughput technologies, in order to find the best approach for miRNA validation. For each strategy, strengths and weaknesses are discussed, to enable users to evaluate and select the right approach for their interests. Full article

In this research, the effect of 2D and 3D Representative Volume Element (RVE) on the ductile damage behavior in single-phase (only ferrite) and dual-phase (ferrite and martensite) steels is analyzed. Physical and fitting parameters of the constitutive model for bcc-ferrite and bcc-martensite phases are adapted from the already published work. Crystal plasticity (CP) based numerical simulations without damage consideration are run and, later, ductile damage criteria for the ferrite phase is defined for all cases. The results of the non-damage (-nD-) and damage (-D-) simulations are compared to analyze the global and local differences of evolving stresses and strains. It is observed that for the same model parameters defined in all cases, damage initiation occurs at the overall higher global strain in the case of 3D compared to 2D. Based on statistical data analysis, a systematic comparison of local results is carried out to conclude that the 3D RVEs provide better quantitative and qualitative results and should be considered for such full phase simulations. Whereas 2D RVEs are simple to analyze and provide appropriate qualitative information about the damage initiation sites. Full article

The oxygen and nutrient-deprived tumor microenvironment is considered a key mechanism responsible for cancer resistance to chemotherapy. Methotrexate (MTX) is a widely incorporated chemotherapeutic agent employed in the treatment of several malignancies. However, drug resistance and systemic toxicity limit the curative effect in most cases. The present work aimed to design, synthesize, and biologically evaluate a novel glucose-methotrexate conjugate (Glu-MTX). Our study showed that Glu-MTX exerts an increased cytotoxic effect on cancer cells in comparison to MTX in hypoxia (1% O₂) and glucose starvation conditions. Furthermore, Glu-MTX was found to inhibit the proliferation and migration of cancer cells more effectively than MTX does. Our results demonstrate that the conjugation of MTX to glucose led to an increase in potency against malignant cells under oxygen and nutrient stress. The observations shed light on a potential therapeutic approach to overcome chemoresistance in cancer. Full article

The design, synthesis and characterization of new nanomaterials represents one of the most dynamic and transversal aspects of nanotechnology applications in the biomedical field. New synthetic and engineering improvements allow the design of a wide range of biocompatible nanostructured materials (NSMs) and nanoparticles (NPs) which, with or without additional chemical and/or biomolecular surface modifications, are more frequently employed in applications for successful diagnostic, drug delivery and therapeutic procedures. Metal-based nanoparticles (MNPs) including metal NPs, metal oxide NPs, quantum dots (QDs) and magnetic NPs, thanks to their physical and chemical properties have gained much traction for their functional use in biomedicine. In this review it is highlighted how the generation of reactive oxygen species (ROS), which in many respects could be considered a negative aspect of the interaction of MNPs with biological matter, may be a surprising nanotechnology weapon. From the exchange of knowledge between branches such as materials science, nanotechnology, engineering, biochemistry and medicine, researchers and clinicians are setting and standardizing treatments by tuning ROS production to induce cancer or microbial cell death. Full article