Miracle-dz/UniFAR-FTUs huggingface dataset:
Myoinositol: The Bridge (PONTI) to Reach a Healthy Pregnancy

The use of folic acid in the periconceptional period can prevent about 70% of neural tube defects (NTDs). In the remaining cases, no medical prevention is available, and those conditions should be defined as folate-resistant NTDs. Rodent models suggest that some folate-resistant NTDs can be prevented by inositol (myoinositol and chiroinositol) supplementation prior to pregnancy. Should folic acid be combined with myoinositol periconceptional supplementation to reduce the overall risk of NTDs even in humans? Hereafter, we discuss the results from the PONTI study that strongly support both the effectiveness and safety of myoinositol periconceptional supplementation in preventing human NTDs. We further report on the largest case series of pregnancies treated with myoinositol and folic acid. At our institution, a sequential study during 12 years involved mothers at risk of fetal NTDs, and 29 babies from 27 pregnancies were born after periconceptional combined myoinositol and folic acid supplementation. No case of NTDs was observed, despite the high recurrence risk in the mothers. Taken together, those data suggest that periconceptional folic acid plus myoinositol can reduce both the occurrence and recurrence risks of NTDs in a greater number of cases than folic acid alone.
Xenin-25 Potentiates Glucose-dependent Insulinotropic Polypeptide Action via a Novel Cholinergic Relay Mechanism*

The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, “GIP/DT” animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the β-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in β-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM.
Interleukin‐18 and transforming growth factor‐beta 1 plasma levels in Alzheimer’s disease and vascular dementia

Inflammation has been involved in the development of dementia in cerebrovascular diseases. To investigate the cellular activation of the peripheral immune system in patients with Alzheimer’s disease (AD) and vascular dementia (VaD), we determined the presence of IL‐18 and TGF‐β1 in the plasma by using ELISA. The levels of IL‐18 and TGF‐β1 were significantly elevated in patients with AD and VaD compared to non‐demented, age‐matched subjects. We found an inverse correlation between the levels of IL‐18 and TGF‐β1 in AD patients. In VaD patients, the correlation between IL‐18 and TGF‐β1 reached a borderline positive value. Whereas, in the non‐demented, age‐matched subjects, a positive correlation between IL‐18 and TGF‐β1 levels was observed. These findings indicate that IL‐18 and TGF‐β1 elevation is associated with AD and VaD patients, confirming that the immune system might exert a remarkable role in the development and progression of neurodegenerative disorders. Moreover, as different modifications were detected in the patients affected by AD and VaD, we propose that IL‐18 and TGF‐ β1 plasma levels might represent possible differential biomarkers.
4-nitrophenyl phosphate--characterization of high-purity materials for measuring alkaline phosphatase activity in human serum.

We studied 53 lots of 4-nitrophenyl phosphate (I), obtained from 20 different commercial suppliers, and used this information to set specifications for it. Using these well-defined specifications, we classified 21 lots of I as "unacceptable," 26 lots as "borderline," and six as "acceptable. " All lots were shown to contain some 4-nitrophenol and inorganic phosphate. However, "acceptable" I had < 0.3 mmol of 4-nitrophenol and < 10 mmol of inorganic phosphate per mole of I. The mole concentration of I (based on disodium hexahydrate, formula weight 371) was determined by enzymic conversion to 4-nitrophenol in five lots of "acceptable" materials. The mole fraction of I ranged from 0.982 to 0.998. From these measurements and from estimates of impurities that absorb at 311 nm, as determined by liquid chromatography and spectrophotometry at other wavelengths, our best estimate of the molar absorptivity of I at 311 nm in 10 mmol/L NaOH at 25 degrees C was 9867 L x mol-1 x cm-1, with a total uncertainty of 76 L x mol-1 x cm-1. We recommend that I used in clinical laboratories for measurement of alkaline phosphatase activity in serum meet the specifications given in this paper: I content > 98%, maximum activity > 98% in comparative testing with other "acceptable" lots of I, and impurities not to exceed the values cited above.
Coverage in Wireless Sensor Networks

Recent improvements in affordable and efficient integrated electronic devices have a considerable impact on advancing the state of wireless sensor networks, which constitute the platform of a broad range of applications related to national security, surveillance, military, health care, and environmental monitoring. An important problem receiving increased consideration recently is the sensor coverage problem, centered around a fundamental question: How well do the sensors observe the physical space? The coverage concept is subject to a wide range of interpretations due to a variety of sensors and applications. Different coverage formulations have been proposed, based on the subject to be covered (area versus discrete points), sensor deployment mechanism (random versus deterministic) as well as other wireless sensor network properties (e.g. network connectivity and minimum energy consumption). In this article, we survey recent contributions addressing coverage problems in the context of static wireless sensor networks. We present various coverage formulations and their assumptions, as well as an overview of the solutions proposed.
Dialog state tracking, a machine reading approach using Memory Network

In an end-to-end dialog system, the aim of dialog state tracking is to accurately estimate a compact representation of the current dialog status from a sequence of noisy observations produced by the speech recognition and the natural language understanding modules. This paper introduces a novel method of dialog state tracking based on the general paradigm of machine reading and proposes to solve it using an End-to-End Memory Network, MemN2N, a memory-enhanced neural network architecture. We evaluate the proposed approach on the second Dialog State Tracking Challenge (DSTC-2) dataset. The corpus has been converted for the occasion in order to frame the hidden state variable inference as a question-answering task based on a sequence of utterances extracted from a dialog. We show that the proposed tracker gives encouraging results. Then, we propose to extend the DSTC-2 dataset with specific reasoning capabilities requirement like counting, list maintenance, yes-no question answering and indefinite knowledge management. Finally, we present encouraging results using our proposed MemN2N based tracking model.
The use of therapeutic massage as a nursing intervention to modify anxiety and the perception of cancer pain

The purpose of this exploratory study was to examine the effects of therapeutic massage (consisting of effleurage, petrissage, and myofascial trigger point therapy) on pain perception, anxiety, and relaxation levels in hospitalized patients experiencing significant cancer pain. Thirty minutes of therapeutic massage was administered on two consecutive evenings to nine hospitalized males diagnosed with cancer and experiencing cancer pain. The subjects' self-reports of pain and relaxation (measured by Visual Analogue Scales) as well as anxiety (measured by the Spielberger State Anxiety Inventory) were recorded before and immediately after the intervention. The objective physiologic measures of heart rate, respiratory rate, and blood pressure were obtained before, immediately after, and, finally, 10 min after the massage intervention. Massage therapy significantly reduced the subjects' level of pain perception (average = 60%) and anxiety (average = 24%) while enhancing their feelings of relaxation by an average of 58%. In addition to these subjective measures, all physiological measures (heart rate, respiratory rate, and blood pressure) tended to decrease from baseline, providing further indication of relaxation. In conclusion, although the exact mechanism is not known, therapeutic massage is a beneficial nursing intervention that promotes relaxation and alleviates the perception of pain and anxiety in hospitalized cancer patients.
Fast and Reliable Limit Analysis Approach for the Structural Assessment of FRP-Reinforced Masonry Arches

This contribution is devoted to assess the capability of a new upper-bound approach for the limit analysis of FRP-reinforced masonry arches by comparing it to both experimental tests and a number of existing numerical procedures. The approach is based on an idea previously presented by the Authors and relies on the representation of the geometry of both the arch and of FRP reinforcement through Non Uniform Rational B-Spline (NURBS) functions. This allows generating a rigid body assembly starting from the assigned geometry composed by very few elements which still provide an exact representation of the original shape. A homogenized kinematic formulation for the limit analysis of the obtained rigid blocks assembly is derived, which accounts for the main properties of masonry material. FRP material is included exploiting the Italian CNR Recommendations for the design of FRP based reinforcing interventions. The approach is capable of accurately predicting the load bearing capacity of masonry arches of arbitrary geometry, provided that the initial mesh is adjusted by means of a suitably devised Genetic Algorithm (GA) until the active interfaces among blocks (e.g. hinges) closely approximate the actual failure mechanism.
Group II mGluRs suppress hyperexcitability in mouse and human nociceptors

Abstract We introduce a strategy for preclinical research wherein promising targets for analgesia are tested in rodent and subsequently validated in human sensory neurons. We evaluate group II metabotropic glutamate receptors, the activation of which is efficacious in rodent models of pain. Immunohistochemical analysis showed positive immunoreactivity for mGlu2 in rodent dorsal root ganglia (DRG), peripheral fibers in skin, and central labeling in the spinal dorsal horn. We also found mGlu2-positive immunoreactivity in human neonatal and adult DRG. RNA-seq analysis of mouse and human DRG revealed a comparative expression profile between species for group II mGluRs and for opioid receptors. In rodent sensory neurons under basal conditions, activation of group II mGluRs with a selective group II agonist produced no changes to membrane excitability. However, membrane hyperexcitability in sensory neurons exposed to the inflammatory mediator prostaglandin E2 (PGE2) was prevented by (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC). In human sensory neurons from donors without a history of chronic pain, we show that PGE2 produced hyperexcitability that was similarly blocked by group II mGluR activation. These results reveal a mechanism for peripheral analgesia likely shared by mice and humans and demonstrate a translational research strategy to improve preclinical validation of novel analgesics using cultured human sensory neurons.
Differentiation of synovial CD‐105+ human mesenchymal stem cells into chondrocyte‐like cells through spheroid formation

Mesenchymal stem cells (MSCs) have the capacity to differentiate into several cell lineages, some of which can generate bone, cartilage, or adipose tissue. The presence of MSCs in the synovial membrane was recently reported. Data from comparative studies of MSCs derived from various mesenchymal tissues suggest that MSCs from synovial membranes have a superior chondrogenesis capacity. Previous chondrogenic differentiation studies have used the total population of MSCs, including cells with several MSC markers, such as CD44, CD90, CD105, or CD73. However the chondrogenic capacity of an individual population of MSCs has not been examined. Our aim was to study the chondrogenic capacity of the cellular MSC subset, CD105+, derived from synovial membrane tissues of patients with osteoarthritis (OA) and normal donors. The tissues were digested with a cocktail of collagenase/dispase and the isolated MSCs were seeded into plates. The subpopulation of CD105+‐MSCs was separated using a magnetic separator. The MSCs were then differentiated towards chondrocyte‐like cells using a specific medium to promote spheroid formation. Spheroids were collected after 14, 28, and 46 days in chondrogenic medium and stained with hematoxylin, eosin, Safranin O or Alcian blue to evaluate the extracellular matrix. Immunohistochemistry was performed to study collagen types I (COLI) and II (COLII) and aggrecan expression. Phenotypic characterization of the isolated CD105+‐MSCs shows that these cells are also positive for CD90 and CD44, but negatives for CD34 and CD45. In addition, this cellular subset expressed Sox‐9. Spheroids appeared after 7 days in culture in the presence of chondrogenic medium. Our studies show no differences between MSCs obtained from OA and normal synovial membranes during chondrogenesis. The morphological analysis of spheroids revealed characteristics typical of chondrocyte cells. The intensity of Safranin O, Alcian blue and aggrecan staining was positive and constant throughout the culture period. However, the intensity of COL2 staining was higher at 28 days (84.29 ± 0.1 U) than at 46 days (61.28 ± 01 U), while COL1 staining was not detected in any samples analyzed. These results were confirmed by reverse transcriptase‐polymerase chain reaction assays. We conclude that the cellular subset of CD105+‐MSCs has chondrogenic capacity. The study also show the similar chondrogenic capacity of CD105+‐MSCs cultured from normal and OA synovial membranes. J. Cell. Biochem. 108: 145–155, 2009. © 2009 Wiley‐Liss, Inc.
Multimodal Degradation Prognostics Based on Switching Kalman Filter Ensemble

For accurate prognostics, users have to determine the current health of the system and predict future degradation pattern of the system. An increasingly popular approach toward tackling prognostic problems involves the use of switching models to represent various degradation phases, which the system undergoes. Such approaches have the advantage of determining the exact degradation phase of the system and being able to handle nonlinear degradation models through piecewise linear approximation. However, limitations of such existing methods include, limited applicability due to the discretization of predicted remaining useful life, insufficient robustness due to the use of single models and others. This paper circumvents these limitations by proposing a hybrid of ensemble methods with switching methods. The proposed method first implements a switching Kalman filter (SKF) to classify between various linear degradation phases, then predict the future propagation of fault dimension using appropriate Kalman filters for each phase. This proposed method achieves both continuous and discrete prediction values representing the remaining life and degradation phase of the system, respectively. The proposed framework is shown via a case study on benchmark simulated aeroengine data sets. The evaluation of the proposed framework shows that the proposed method achieves better accuracy and robustness against noise compared with other methods reported in the literature. The results also indicate the effectiveness of the SKF in detecting the switching point between various degradation modes.
Feeding Mechanics in Spinosaurid Theropods and Extant Crocodilians

A number of extant and extinct archosaurs evolved an elongate, narrow rostrum. This longirostrine condition has been associated with a diet comprising a higher proportion of fish and smaller prey items compared to taxa with broader, more robust snouts. The evolution of longirostrine morphology and a bulbous anterior rosette of premaxillary teeth also occurs in the spinosaurid theropod dinosaurs, leading to suggestions that at least some members of this clade also had a diet comprising a notable proportion of fish or other small vertebrates. Here we compare the rostral biomechanics of the spinosaurs Baryonyx walkeri and Spinosaurus c.f. S. aegyptiacus to three extant crocodilians: two longistrine taxa, the African slender-snouted crocodile Mecistops cataphractus and the Indian gharial Gavialis gangeticus; and the American alligator Alligator mississippiensis. Using computed tomography (CT) data, the second moments of area and moments of inertia at successive transverse slices along the rostrum were calculated for each of the species. Size-independent results tested the biomechanical benefits of material distribution within the rostra. The two spinosaur rostra were both digitally reconstructed from CT data and compared against all three crocodilians. Results show that African slender-snouted crocodile skulls are more resistant to bending than an equivalent sized gharial. The alligator has the highest resistances to bending and torsion of the crocodiles for its size and greater than that of the spinosaurs. The spinosaur rostra possess similar resistance to bending and torsion despite their different morphologies. When size is accounted for, B. walkeri performs mechanically differently from the gharial, contradicting previous studies whereas Spinosaurus does not. Biomechanical data support known feeding ecology for both African slender-snouted crocodile and alligator, and suggest that the spinosaurs were not obligate piscivores with diet being determined by individual animal size.
Functional expression of connexin57 in horizontal cells of the mouse retina

Horizontal cells are interneurons of the vertebrate retina that exhibit strong electrical and tracer coupling but the identity of the channel‐forming connexins has remained elusive. Here we show that horizontal cells of the mouse retina express connexin57 (Cx57). We have generated Cx57‐deficient mice by replacing the Cx57 coding region with a lacZ reporter gene, expressed under control of the endogenous Cx57 promoter. These mice were fertile and showed no obvious anatomical or behavioural abnormalities. Cx57 mRNA was expressed in the retina of wild‐type littermates but was absent from the retina of Cx57‐deficient mice. Previously reported results that the Cx57 gene was very weakly expressed in several other mouse tissues turned out to be unspecific. Cx57 mRNA is abundantly expressed in the retina and weakly in the thymus of adult mice but absent in all other adult tissues tested, including brain. Furthermore, Cx57 is expressed in embryonic kidney at E16.5 to E18.5 days post‐conception, as indicated by the pattern of lacZ expression. Within the retina, lacZ signals were assigned exclusively to horizontal cells based on co‐localization with cell‐type‐specific marker proteins. Microinjection of Neurobiotin into horizontal cells of isolated retinae revealed less than 1% of tracer coupling in Cx57‐deficient retinae compared with wild‐type controls. Cx57 is the first connexin identified in mammalian horizontal cells and the first connexin whose expression is apparently restricted to only one type of neuron.
The size distribution of galaxies in the Sloan Digital Sky Survey

We use a complete sample of about 140,000 galaxies from the Sloan Digital Sky Survey (SDSS) to study the size distribution of galaxies and its dependence on their luminosity, stellar mass, and morphological type. The large SDSS database provides statistics of unprecedented accuracy. For each type of galaxy, the size distribution at given luminosity (or stellar mass) is well described by a log-normal function, characterized by its median ¯
Microglia change from a reactive to an age-like phenotype with the time in culture

Age-related neurodegenerative diseases have been associated with chronic neuroinflammation and microglia activation. However, cumulative evidence supports that inflammation only occurs at an early stage once microglia change the endogenous characteristics with aging and switch to irresponsive/senescent and dystrophic phenotypes with disease progression. Thus, it will be important to have the means to assess the role of reactive and aged microglia when studying advanced brain neurodegeneration processes and age-associated related disorders. Yet, most studies are done with microglia from neonates since there are no adequate means to isolate degenerating microglia for experimentation. Indeed, only a few studies report microglia isolation from aged animals, using either short-term cultures or high concentrations of mitogens in the medium, which trigger microglia reactivity. The purpose of this study was to develop an experimental process to naturally age microglia after isolation from neonatal mice and to characterize the cultured cells at 2 days in vitro (DIV), 10 DIV, and 16 DIV. We found that 2 DIV (young) microglia had predominant amoeboid morphology and markers of stressed/reactive phenotype. In contrast, 16 DIV (aged) microglia evidenced ramified morphology and increased matrix metalloproteinase (MMP)-2 activation, as well as reduced MMP-9, glutamate release and nuclear factor kappa-B activation, in parallel with decreased expression of Toll-like receptor (TLR)-2 and TLR-4, capacity to migrate and phagocytose. These findings together with the reduced expression of microRNA (miR)-124, and miR-155, decreased autophagy, enhanced senescence associated beta-galactosidase activity and elevated miR-146a expression, are suggestive that 16 DIV cells mainly correspond to irresponsive/senescent microglia. Data indicate that the model represent an opportunity to understand and control microglial aging, as well as to explore strategies to recover microglia surveillance function.
Survey of Salmonella serovars in broilers and laying breeding reproducers in East of Algeria.

BACKGROUND Avian salmonellosis affects the poultry industry in underdeveloped and in developed countries. The aim of this study was to identify the most common Salmonella serovars in broilers and laying breeding reproducers in Eastern Algeria according to the ISO 6579 method. METHODOLOGY A total of 294 samples were obtained from two flocks of 10,000 broilers and laying breeding reproducers. Samples included livers and spleens, drag swabs of bottom boxes of young chickens, cloacal swabs, and faecal samples of chickens. Additional samples were also taken from water, feed and dusty surfaces. RESULTS AND CONCLUSIONS Only the cloacal swabs, poultry faeces and samples from dusty surfaces were positive for Salmonella Typhimurium and Salmonella Livingstone with a detection rate of 12% and 1.6% respectively. The results showed evidence of legislative failure regarding biosafety within the poultry industry in the area of Batna, Eastern Algeria.