Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonlinear PLS Integrated with Error-Based LSSVM and Its Application to NOX Modeling

This article presents a novel nonlinear partial least-squares (PLS) method to address a nonlinear problem with input collinearity in an industrial process. The proposed method integrates an inner least-squares support vector machine (LSSVM) function with an outer linear PLS framework. First, the input and output latent variables are extracted to eliminate the collinearity through PLS projection, and then LSSVM is used to construct nonlinear relation between each pair of latent variables. Moreover, a weight-updating procedure is incorporated to enhance the accuracy of prediction. Then, training and predicting algorithms based on modified nonlinear iterative partial least-squares (NIPALS) steps are also described in detail. The performance of the new method is also investigated with a benchmark data set. Finally, this approach is applied to a real industrial process to predict the NO x emissions of a coal-fired boiler. The root-mean-square errors (RMSEs) on the training and testing data decreased to only 12.6632 and 37.6609, respectively. Compared with the original linear PLS and other kinds of nonlinear PLS methods, a reduction of approximately 40.8―47.4% in the prediction errors is attained. The results reveal that the new approach is capable of modeling the nonlinear relation of NO x emissions with other process parameters and improving the prediction performance.
New Early Warning Score: EMS Off-Label Use in Out-of-Hospital Patients

Background: The National Early Warning Score (NEWS) is an assessment scale of in-hospital patients’ conditions. The purpose of this study was to assess the appropriateness of a potential off-label use of NEWS by the emergency medical system (EMS) to facilitate the identification of critical patients and to trigger appropriate care in the pre-hospital setting. Methods: A single centre, longitudinal, prospective study was carried out between July and August 2020 in the EMS service of Bologna. Home patients with age ≥ 18 years old were included in the study. The exclusion criterion was the impossibility to collect all the parameters needed to measure NEWS. Results: A total of 654 patients were enrolled in the study. The recorded NEWS values increased along with the severity of dispatch priority code, the EMS return code, the emergency department triage code, and with patients’ age (r = 0.135; p = 0.001). The aggregated value of NEWS was associated with an increased risk of hospitalization (OR = 1.30 (1.17; 1.34); p < 0.0001). Conclusion: This study showed that the use of NEWS in the urgent and emergency care services can help patient assessment while not affecting EMS crew operation and might assist decision making in terms of severity-code assignment and resources utilization.
Advances in 3D Printing for Tissue Engineering

Tissue engineering (TE) scaffolds have enormous significance for the possibility of regeneration of complex tissue structures or even whole organs. Three-dimensional (3D) printing techniques allow fabricating TE scaffolds, having an extremely complex structure, in a repeatable and precise manner. Moreover, they enable the easy application of computer-assisted methods to TE scaffold design. The latest additive manufacturing techniques open up opportunities not otherwise available. This study aimed to summarize the state-of-art field of 3D printing techniques in applications for tissue engineering with a focus on the latest advancements. The following topics are discussed: systematics of the available 3D printing techniques applied for TE scaffold fabrication; overview of 3D printable biomaterials and advancements in 3D-printing-assisted tissue engineering.
NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Simple Summary NLRP7 is the major gene responsible for recurrent hydatidiform mole (HM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). Among women with one HM (sporadic HM), about 1–9% develop a second mole (recurrent HM). While the association of biallelic mutations in NLRP7 with recurrent HM is well established, its role in the development and the immune tolerance of CC was unknown. The present work was conducted to investigate the direct involvement of NLRP7 in the development of CC and to provide evidences of its contribution in maternal immune tolerance. The study demonstrates that NLRP7 is directly involved in CC growth and downregulates the maternal immune response, thus fostering tumor growth and dissemination. Our study proposes that an increased expression of NLRP7 plays a significant role as a facilitator of CC growth, and therefore, NLRP7 should be categorized among important actors of CC development. The clinical relevance of NLRP7 in this rare female reproductive cancer highlights its therapeutic promise as a molecular target. Abstract The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.
Sialic Acids as Receptors for Pathogens

Carbohydrates have long been known to mediate intracellular interactions, whether within one organism or between different organisms. Sialic acids (Sias) are carbohydrates that usually occupy the terminal positions in longer carbohydrate chains, which makes them common recognition targets mediating these interactions. In this review, we summarize the knowledge about animal disease-causing agents such as viruses, bacteria and protozoa (including the malaria parasite Plasmodium falciparum) in which Sias play a role in infection biology. While Sias may promote binding of, e.g., influenza viruses and SV40, they act as decoys for betacoronaviruses. The presence of two common forms of Sias, Neu5Ac and Neu5Gc, is species-specific, and in humans, the enzyme converting Neu5Ac to Neu5Gc (CMAH, CMP-Neu5Ac hydroxylase) is lost, most likely due to adaptation to pathogen regimes; we discuss the research about the influence of malaria on this trait. In addition, we present data suggesting the CMAH gene was probably present in the ancestor of animals, shedding light on its glycobiology. We predict that a better understanding of the role of Sias in disease vectors would lead to more effective clinical interventions.
Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis

Bone marrow-derived mesenchymal stromal cells (MSCs) are major players in regenerative therapies for wound healing via their paracrine activity, mediated partially by exosomes. Our purpose was to test if MSC-derived exosomes could accelerate wound healing by enhancing the biological properties of the main cell types involved in the key phases of this process. Thus, the effects of exosomes on (i) macrophage activation, (ii) angiogenesis, (iii) keratinocytes and dermal fibroblasts proliferation and migration, and (iv) the capacity of myofibroblasts to regulate the turnover of the extracellular matrix were evaluated. The results showed that, although exosomes did not exhibit anti-inflammatory properties, they stimulated angiogenesis. Exposure of keratinocytes and dermal (myo)fibroblasts to exosomes enhanced their proliferation and migratory capacity. Additionally, exosomes prevented the upregulation of gene expression for type I and III collagen, α-smooth muscle actin, and MMP2 and 14, and they increased MMP13 expression during the fibroblast–myofibroblast transition. The regenerative properties of exosomes were validated using a wound healing skin organotypic model, which exhibited full re-epithelialization upon exosomes exposure. In summary, these data indicate that exosomes enhance the biological properties of keratinocytes, fibroblasts, and endothelial cells, thus providing a reliable therapeutic tool for skin regeneration.
Protective Effects of Oroxylin A on Retinal Ganglion Cells in Experimental Model of Anterior Ischemic Optic Neuropathy

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute vision loss in older people, and there is no effective therapy. The effect of the systemic or local application of steroids for NAION patients remains controversial. Oroxylin A (OA) (5,7-dihydroxy-6-methoxyflavone) is a bioactive flavonoid extracted from Scutellariae baicalensis Georgi. with various beneficial effects, including anti-inflammatory and neuroprotective effects. A previous study showed that OA promotes retinal ganglion cell (RGC) survival after optic nerve (ON) crush injury. The purpose of this research was to further explore the potential actions of OA in ischemic injury in an experimental anterior ischemic optic neuropathy (rAION) rat model induced by photothrombosis. Our results show that OA efficiently attenuated ischemic injury in rats by reducing optic disc edema, the apoptotic death of retinal ganglion cells, and the infiltration of inflammatory cells. Moreover, OA significantly ameliorated the pathologic changes of demyelination, modulated microglial polarization, and preserved visual function after rAION induction. OA activated nuclear factor E2 related factor (Nrf2) signaling and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1 (HO-1) in the retina. We demonstrated that OA activates Nrf2 signaling, protecting retinal ganglion cells from ischemic injury, in the rAION model and could potentially be used as a therapeutic approach in ischemic optic neuropathy.
How a Paleogenomic Approach Can Provide Details on Bioarchaeological Reconstruction: A Case Study from the Globular Amphorae Culture

Ancient human remains have the potential to explain a great deal about the prehistory of humankind. Due to recent technological and bioinformatics advances, their study, at the palaeogenomic level, can provide important information about population dynamics, culture changes, and the lifestyles of our ancestors. In this study, mitochondrial and nuclear genome data obtained from human bone remains associated with the Neolithic Globular Amphorae culture, which were recovered in the Megalithic barrow of Kierzkowo (Poland), were reanalysed to gain insight into the social organisation and use of the archaeological site and to provide information at the individual level. We were able to successfully estimate the minimum number of individuals, sex, kin relationships, and phenotypic traits of the buried individuals, despite the low level of preservation of the bone samples and the intricate taphonomic conditions. In addition, the evaluation of damage patterns allowed us to highlight the presence of “intruders”—that is, of more recent skeletal remains that did not belong to the original burial. Due to its characteristics, the study of the Kierzkowo barrow represented a challenge for the reconstruction of the biological profile of the human community who exploited it and an excellent example of the contribution that ancient genomic analysis can provide to archaeological reconstruction.
Redox and Anti-Inflammatory Properties from Hop Components in Beer-Related to Neuroprotection

Beer is a fermented beverage widely consumed worldwide with high nutritional and biological value due to its bioactive components. It has been described that both alcoholic and non-alcoholic beer have several nutrients derived from their ingredients including vitamins, minerals, proteins, carbohydrates, and antioxidants that make beer a potential functional supplement. Some of these compounds possess redox, anti-inflammatory and anticarcinogenic properties making the benefits of moderate beer consumption an attractive way to improve human health. Specifically, the hop cones used for beer brewing provide essential oils, bitter acids and flavonoids that are potent antioxidants and immune response modulators. This review focuses on the redox and anti-inflammatory properties of hop derivatives and summarizes the current knowledge of their neuroprotective effects.
Motor Cortical Activation Assessment in Progressive Multiple Sclerosis Patients Enrolled in Gait Rehabilitation: A Secondary Analysis of the RAGTIME Trial Assisted by Functional Near-Infrared Spectroscopy

This study aimed to determine cortical activation responses to two different rehabilitative programs, as measured through functional near-infrared spectroscopy (fNIRS). As a secondary analysis of the RAGTIME trial, we studied 24 patients with progressive multiple sclerosis (MS) and severe disability who were randomized to a regimen of robot-assisted gait training (RAGT) or overground walking (OW). Cortical activation during a treadmill walking task, assessed through fNIRS recordings from the motor and premotor cortexes (M1/PM), was calculated as the area under the curve (AUC) of oxyhemoglobin for each hemisphere and the total area (Tot-OxyAUC). Gait speed, endurance, and balance were also measured, along with five healthy control subjects. At baseline, Tot-OxyAUC during walking was significantly increased in MS patients compared to healthy people and was significantly higher for those with more severe disabilities; it was also inversely correlated with physical performance. After rehabilitation, significant opposite variations in Tot-OxyAUC were observed, with activity levels being increased after OW and decreased after RAGT (+242,080 ± 361,902 and −157,031 ± 172,496 arbitrary units, respectively; p = 0.002), particularly in patients who were trained at a lower speed. Greater reductions in the cortical activation of the more affected hemisphere were significantly related to improvements in gait speed (r = −0.42) and endurance (r = −0.44). Cortical activation, assessed through fNIRS, highlighted the brain activity in response to the type and intensity of rehabilitation.
Noise and Memristance Variation Tolerance of Single Crossbar Architectures for Neuromorphic Image Recognition

We performed a comparative study on the Gaussian noise and memristance variation tolerance of three crossbar architectures, namely the complementary crossbar architecture, the twin crossbar architecture, and the single crossbar architecture, for neuromorphic image recognition and conducted an experiment to determine the performance of the single crossbar architecture for simple pattern recognition. Ten grayscale images with the size of 32 × 32 pixels were used for testing and comparing the recognition rates of the three architectures. The recognition rates of the three memristor crossbar architectures were compared to each other when the noise level of images was varied from −10 to 4 dB and the percentage of memristance variation was varied from 0% to 40%. The simulation results showed that the single crossbar architecture had the best Gaussian noise input and memristance variation tolerance in terms of recognition rate. At the signal-to-noise ratio of −10 dB, the single crossbar architecture produced a recognition rate of 91%, which was 2% and 87% higher than those of the twin crossbar architecture and the complementary crossbar architecture, respectively. When the memristance variation percentage reached 40%, the single crossbar architecture had a recognition rate as high as 67.8%, which was 1.8% and 9.8% higher than the recognition rates of the twin crossbar architecture and the complementary crossbar architecture, respectively. Finally, we carried out an experiment to determine the performance of the single crossbar architecture with a fabricated 3 × 3 memristor crossbar based on carbon fiber and aluminum film. The experiment proved successful implementation of pattern recognition with the single crossbar architecture.
Three-Dimensional X-ray Imaging of β-Galactosidase Reporter Activity by Micro-CT: Implication for Quantitative Analysis of Gene Expression

Acquisition of detailed anatomical and molecular knowledge from intact biological samples while preserving their native three-dimensional structure is still a challenging issue for imaging studies aiming to unravel a system’s functions. Three-dimensional micro-CT X-ray imaging with a high spatial resolution in minimally perturbed naive non-transparent samples has recently gained increased popularity and broad application in biomedical research. Here, we describe a novel X-ray-based methodology for analysis of β-galactosidase (lacZ) reporter-driven gene expression in an intact murine brain ex vivo by micro-CT. The method relies on detection of bromine molecules in the product of the enzymatic β-galactosidase reaction. Enhancement of the X-ray signal is observed specifically in the regions of the murine brain where expression of the lacZ reporter gene is also detected histologically. We performed quantitative analysis of the expression levels of lacZ reporter activity by relative radiodensity estimation of the β-galactosidase/X-gal precipitate in situ. To demonstrate the feasibility of the method, we performed expression analysis of the Tsen54-lacZ reporter gene in the murine brain in a semi-quantitative manner. Human mutations in the Tsen54 gene cause pontocerebellar hypoplasia (PCH), a group of severe neurodegenerative disorders with both mental and motor deficits. Comparing relative levels of Tsen54 gene expression, we demonstrate that the highest Tsen54 expression is observed in anatomical brain substructures important for the normal motor and memory functions in mice.
Plasma Lutein, a Nutritional Biomarker for Development of Advanced Age-Related Macular Degeneration: The Alienor Study

Lutein and zeaxanthin may lower the risk of age-related macular degeneration (AMD). We evaluated the associations of plasma lutein and zeaxanthin with the incidence of advanced AMD in the Alienor study (Antioxydants Lipides Essentiels Nutrition et Maladies Oculaires). Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006–2008). The present study included 609 participants with complete ophthalmologic and plasma carotenoids data. Examinations were performed every two years over an eight-year period (2006 to 2017). Plasma lutein and zeaxanthin were determined at baseline from fasting blood samples using high-performance liquid chromatography. Cox proportional hazard models were used to assess associations between plasma lutein, zeaxanthin, and their (total cholesterol (TC) + triglycerides (TG)) ratios with AMD. Among the 609 included participants, 54 developed advanced incident AMD during a median follow-up time of 7.6 years (range 0.7 to 10.4). Participants with higher plasma lutein had a reduced risk for incident advanced AMD in the fully adjusted model (HR = 0.63 per 1-SD increase (95% CI, 0.41–0.97), p = 0.03). A similar association was observed using the lutein/(TC + TG) ratio (HR = 0.59 (95% CI, 0.39–0.90), p = 0.01). No associations were evidenced for other carotenoids. Higher plasma lutein was associated with a 37% reduced risk of incident advanced AMD.
Influence of the Alkali Treatment of Flax and Hemp Fibers on the Properties of PHBV Based Biocomposites

This study assessed the impact of alkali treatment of hemp and flax fibers on mechanical properties (determined by means of the uniaxial tensile test, impact tensile strength test and hardness test), processing properties (the course of the extrusion and injection process) and usable properties (shrinkage of molded pieces, degree of water absorption) of biocomposites on the base of poly (3-hydroxybutyric-co-3-hydroxyvaleric acid) (PHBV) biopolymer. For this purpose, 1 mm of length flax and hemp fibers was surface-modified by means of aqueous solution of NaOH (sodium hydroxide) with concentrations of 2%, 5% and 10%. The composites were made using the extrusion technology. The test specimens were produced by injection molding technology. In total, eight types of biocomposites with modified and non-modified fibers were produced, and each biocomposite contained the same filler content (15 wt.%). Their properties were compared in some cases with pure PHBV polymer. In the case of biocomposites filled with hemp fibers, it was noted that an increase of the alkalizing solution concentration improved most of the tested properties of the obtained biocomposites. On the other hand, in the case of flax fibers, there was a significant decrease in most of the mechanical properties tested for the composite containing fibers etched by 10% NaOH solution. The obtained results were verified by examining fibers and the destroyed specimens with a scanning electron microscope (SEM) and an optical microscope, which confirmed, especially, the significant geometry changes of the flax fibers etched by 10% NaOH solution. This procedure also resulted in a significant change of processing properties—a composite of this fiber type required about 20 °C lower temperature during the extrusion and injection molding process in order to obtain the right product. These results lead to the important conclusion that for each filler of the plant-origin and polymer matrix, the fiber alkalization method should be selected individually in order to improve the specific properties of biocomposites.
Novel Sequence Types of Listeria monocytogenes of Different Origin Obtained in the Republic of Serbia

Listeria monocytogenes, the causative agent of listeriosis, is amongst the major food-borne pathogens in the world that affect mammal species, including humans. This microorganism has been associated with both sporadic episodes and large outbreaks of human listeriosis worldwide, with high mortality rates. In this study, the main sequence types (STs) and clonal complexes (CCs) were investigated in all of the 13 L. monocytogenes strains originating from different sources in the Republic of Serbia in 2004–2019 and that were available in the BIGSdb-Lm database. We found at least 13 STs belonging to the phylogenetic lineages I and II. These strains were represented by ST1/ST3/ST9 of CC1/CC3/CC9, which were common in the majority of the European countries and worldwide, as well as by eight novel STs (ST1232/ST1233/ST1234/ST1235/ST1238/ST1236/ST1237/ST1242) of CC19/CC155/CC5/CC21/CC3/CC315/CC37, and the rare ST32 (clonal complex ST32) and ST734 (CC1), reported in the Republic of Serbia, the EU, for the first time. Our study confirmed the association of CC1 with cases of neuroinfection and abortions among small ruminants, and of CC3 and CC9 with food products of animal origin. The strains isolated in 2019 carried alleles of the internalin genes (inlA/inlB/inlC/inlE) characteristic of the most virulent strains from the hypervirulent CC1. These findings demonstrated the genetic relatedness between L. monocytogenes strains isolated in the Republic of Serbia and worldwide. Our study adds further information about the diversity of the L. monocytogenes genotypes of small ruminants and food products, as the strain distribution in these sources in Serbia had not previously been evaluated.