Miracle-dz/UniFAR-FTUs huggingface dataset:
Left Atrial Strain: A Must or a Plus for Routine Clinical Practice?

Left atrial (LA) function has been the subject of study for many years.1 Interesting pathophysiological concepts have been described but to date, not many of these results have been translated into real clinical use and value.2 Doppler and volumetric approaches were the first methods used to assess LA function. More recently, speckle tracking echocardiography, initially developed for the left ventricle (LV), has been applied to assess LA deformation.3 Speckle tracking echocardiography–derived analysis of LA performance (namely LA strain) provides a window on all phases of LA function (reservoir, conduit, and booster pump; Figure) and has shown prognostic significance in different pathological conditions, and the results obtained with this method are not directly comparable to those obtained by volumetric approaches.4,5 If LA strain is to become accepted for assessment of LA performance, then a standardized methodology, common reference values, and the impact of different diseases on LA function need to be precisely described.6,7 Figure. Example of how to get …
Specificity Profiling of Dual Specificity Phosphatase Vaccinia VH1-related (VHR) Reveals Two Distinct Substrate Binding Modes*

Background: Factors that determine the in vivo substrate specificity of dual specificity phosphatases are currently unknown. Results: Specificity profiling of VHR through peptide library screening identified two distinct classes of peptide substrates, which bind to VHR in opposite orientations. Conclusion: VHR may act on a previously unrecognized class of protein substrates. Significance: The results should help identify new VHR substrates and elucidate its biological function. Vaccinia VH1-related (VHR) is a dual specificity phosphatase that consists of only a single catalytic domain. Although several protein substrates have been identified for VHR, the elements that control the in vivo substrate specificity of this enzyme remain unclear. In this work, the in vitro substrate specificity of VHR was systematically profiled by screening combinatorial peptide libraries. VHR exhibits more stringent substrate specificity than classical protein-tyrosine phosphatases and recognizes two distinct classes of Tyr(P) peptides. The class I substrates are similar to the Tyr(P) motifs derived from the VHR protein substrates, having sequences of (D/E/φ)(D/S/N/T/E)(P/I/M/S/A/V)pY(G/A/S/Q) or (D/E/φ)(T/S)(D/E)pY(G/A/S/Q) (where φ is a hydrophobic amino acid and pY is phosphotyrosine). The class II substrates have the consensus sequence of (V/A)P(I/L/M/V/F)X1–6pY (where X is any amino acid) with V/A preferably at the N terminus of the peptide. Site-directed mutagenesis and molecular modeling studies suggest that the class II peptides bind to VHR in an opposite orientation relative to the canonical binding mode of the class I substrates. In this alternative binding mode, the Tyr(P) side chain binds to the active site pocket, but the N terminus of the peptide interacts with the carboxylate side chain of Asp164, which normally interacts with the Tyr(P) + 3 residue of a class I substrate. Proteins containing the class II motifs are efficient VHR substrates in vitro, suggesting that VHR may act on a novel class of yet unidentified Tyr(P) proteins in vivo.
Ability of Nucleus Cochlear Implantees to Recognize Music

Eight adults with cochlear implants participated in experiments to test their ability to recognize music. Some subjects showed good ability to recognize songs that were sung with instrumental accompaniment but poor ability to recognize songs played on an electronic keyboard without verbal cues, indicating that they were recognizing the songs by verbal cues rather than by musical qualities such as tones and melodic intervals. This conclusion was strengthened by the finding that subjects were barely able to distinguish between songs with the same rhythm and pitch range, and they showed poor ability to discriminate musical intervals. (The closest discrimination was 4 semitones.) Subjects had good ability to distinguish among the synthesized sounds of various musical instruments played on the electronic keyboard. We speculate that subjects could distinguish the various musical instruments in the same way they distinguish among human voices using spectrographic patterns such as formants or maxima.
Aldosterone synthase -344c/t and angiotensin-converting enzyme I/D polymorphisms in Turkish hypertensive patients with normal coronary arteries

Background — The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure regulation, left ventricular and vascular structure. Some hypertensive patients develop left ventricular dilatation and heart failure symptoms while others are relatively less affected.The purpose of our study was to determine whether two major polymorphisms of RAAS are associated with echocardiographic left ventricular mass, function and dilatation in hypertensive patients with normal coronary arteries. Methods — A Turkish population of 88 patients with hypertension and normal coronary arteries were studied by echocardiography for left ventricular dimension, mass and function. Genotyping was performed for aldosterone synthase (CYP11B2) -344C/T polymorphism in 85, angiotensin-converting enzyme (ACE) I/D polymorphism in 88 patients. Left ventricular dimensions, mass and function indices, after adjustment for clinical covariates, were analysed by multiple regression according to genotypes. Results — None of the two genotypes studied predicted left ventricular dilatation, mass or function in hypertensive patients with normal coronary arteries. Conclusion — Neither ACE I/D nor CYP11B2 -344C/T polymorphisms were useful to predict left ventricular mass, function or dilatation in our hypertensive patients with normal coronary arteries.
Plasma NGAL similarly predicts acute kidney injury in sepsis and nonsepsis.

AIM Plasma NGAL is released in sepsis irrespective of acute kidney injury (AKI). The current study investigated the effect of sepsis on the diagnostic value of NGAL for AKI. MATERIALS & METHODS In 700 intensive care unit admissions, NGAL was measured at four time points (<24 h) following admission. RESULTS In total, 663 admissions were included in the final analysis, of which 80 patients had sepsis (12%). AKI occurred in 22% of the patients without and 66% with sepsis. NGAL levels were higher in non-AKI patients with sepsis compared with non-AKI patients without sepsis at all time points (p = 0.03 or lower). In patients with AKI a similar difference was observed (p < 0.001). The area under the curve for AKI was unaffected by the presence of sepsis (0.76 in sepsis vs 0.78 in nonsepsis; p = 0.72); however, the optimal test cutoff values were higher in the former. CONCLUSION Sepsis enhances the production of plasma NGAL in critically ill adult patients irrespective of the presence of AKI. However, the diagnostic test accuracy for AKI is unaffected by sepsis, although optimal cutoff values are elevated.
MJO Modulating the Activity of the Leading Mode of Intraseasonal Variability in South America

Intraseasonal (IS) variability in South America is efficiently described through the first empirical orthogonal function of filtered precipitation or outgoing longwave radiation (OLR) anomalies. In the 30–90-day band, the leading OLR pattern between October and April is a dipole with centers of action in the South Atlantic Convergence Zone (SACZ) and southeastern South America (SESA). The Madden Julian Oscillation (MJO) was shown to have an impact on the rainfall in South America, with greater influence during the austral warm season. The aim of this study is therefore to assess the modulation of the MJO in the activity of the leading pattern of variability in South America, named the 3090-Seasonal-Intraseasonal (SIS) pattern. It was found that the most intense periods of activity of the SIS pattern appear to be related to intense MJO events with coherent eastward propagation. Furthermore, positive 3090-SIS phases, associated with enhanced (inhibited) convection over the SESA (SACZ) region generally occur during MJO progression from the eastern Indian Ocean to the Western Pacific (i.e., Maritime Continent sector). On the contrary, negative 3090-SIS phases, associated with enhanced (inhibited) convection over SACZ (SESA) are observed when the MJO active phase locates between the Western Pacific and the western Indian Ocean (African sector). The 3090-SIS pattern modulation by the MJO opens the opportunity to develop skillful subseasonal prediction tools in South America.
Internal fixation of fractures and non-unions of the humeral shaft. Indications and results in a multi-center study.

We performed ninety-six internal-fixation procedures for fracture or non-union of the humeral shaft in eighty-four patients, with a mean follow-up of 32.6 months (range, three months to fourteen years). The primary indications for operative intervention included humeral shaft fracture in a patient with multiple trauma, non-union, inadequate reduction of a humeral shaft fracture by closed methods, pathological humeral-shaft fracture, and progressive radial-nerve palsy. Methods of internal fixation included compression plates and screws and intramedullary Kuntscher nails or Rush rods. The use of an AO/ASIF compression plate or interfragmentary lag screws with an AO/ASIF neutralization plate in twenty-seven multiply-injured patients resulted in a union rate of 100 per cent and generally good motion of the shoulder and elbow. Five multiply-injured patients also obtained good results through fixation by a modified Hackethal technique using two Rush rods. The use of intramedullary Kuntscher nails resulted in a rate of union of 91 per cent in eleven multiply injured patients. Ten patients with non-union of a humeral shaft fracture had an 80 per cent rate of union with the use of an AO/ASIF compression plate. The use of a Kuntscher nail in eleven patients with non-union resulted in a rate of union of only 73 per cent and frequently caused subacromial impingement. Fractures of the humeral shaft that had had an inadequate reduction by closed means or were associated with progressive radial-nerve palsy were best managed by a compression plate or the modified Hackethal technique. (ABSTRACT TRUNCATED AT 250 WORDS)
A Precision Pseudo Resistor Bias Scheme for the Design of Very Large Time Constant Filters

In this brief, a novel pseudo resistor bias scheme capable of achieving improved performances against process parameter variations is presented. The use of a matched structure allows for achieving a simulated statistical variation <inline-formula><tex-math notation="LaTeX">$\sigma/\mu$</tex-math></inline-formula> one order of magnitude better than conventional bias schemes proposed in the literature. The entire circuit was designed to be able to emulate a tunable resistor whose resistance could be digitally set in the range of 400 <inline-formula><tex-math notation="LaTeX">$\text{M}\Omega$</tex-math></inline-formula>–90 <inline-formula><tex-math notation="LaTeX">$\text{G}\Omega$</tex-math></inline-formula>. The design of a very low frequency bandpass filter (BPF) for biopotential recording was also covered as a suitable application. The tunability offered by the bias scheme was employed, in this case, to realize a high-pass cutoff frequency variable in the range of 10 Hz–2 kHz. An integrated circuit including eight acquisition channels, each of which is composed of the designed BPF and a conventional 10-bit analog-to-digital converter, was finally realized in a CMOS 0.35-<inline-formula><tex-math notation="LaTeX">$\mu\text{m}$</tex-math></inline-formula> process. The chip was successfully tested showing a measured <inline-formula><tex-math notation="LaTeX">$\sigma/\mu$</tex-math></inline-formula> variation of the high-pass cutoff frequency equal to 0.13 when different channels on the same die are considered.
Respiratory Chain of a Pathogenic Fungus, Microsporum gypseum: Effect of the Antifungal Agent Pyrrolnitrin

Pyrrolnitrin has been reported to inhibit Bacillus megaterium primarily by forming complexes with phospholipids and to block electron transfer of Saccharomyces cerevisiae between succinate or reduced nicotinamide adenine dinucleotide (NADH) and coenzyme Q. We found that pyrrolnitrin inhibited respiration of conidia of Microsporum gypseum. In mitochondrial preparations, pyrrolnitrin strongly inhibited respiration and the rotenone-sensitive NADH-cytochrome c reductase. The rotenone-insensitive NADH-cytochrome c reductase, the succinate-cytochrome c reductase, and the reduction of dichlorophenolindophenol by either NADH or succinate were inhibited to a lesser extent. However, the activity of cytochrome oxidase was not affected by pyrrolnitrin. The extent of reduction of flavoproteins by NADH and succinate, measured at 465 - 510 nm, was unaltered; however, the reduction of cytochrome b, measured at 560 - 575 nm, was partially inhibited by pyrrolnitrin. The level of totally reduced cytochrome b was restored with antimycin A. We, therefore, concluded that the primary site of action of this antifungal antibiotic is to block electron transfer between the flavoprotein of the NADH-dehydrogenase and cytochrome b segment of the respiratory chain of M. gypseum.
Effects of Light and CO on the Survival of a Marine Ammonium-Oxidizing Bacterium during Energy Source Deprivation

The chemolithotrophic ammonium-oxidizing bacterium Nitrosomonas cryotolerans responds uniquely to nutrient deprivation by lowering its endogenous respiration and anabolic processes to undetectable levels during starvation, thus appearing to enter a dormant state. To ascertain whether this state protects the cells from further stresses (as seen with endospore-forming bacteria), the starved cells were subjected to two known inhibitors, CO and light. It was found that long-term-starved cells were less resistant than freshly starved cells to light inhibition. Both long-term-starved cells and freshly starved cells were unaffected by CO.
Distribution of [14C]labeled purines in the mouse. A whole body autoradiographic assessment of purine metabolism in mammals.

In order to evaluate circulating purines in mammals systemically, mice received intravenous injections of [‘4C]labeled purines and their incorporation into tissues was assessed by whole-body autoradiography with the aid of metabolic inhibitors, reference purines and pyrimidines and a few biochemical confirmations. The results of this work clearly showed that the incorporation of purines is tissue-specific and possibly related to the functions of the organs. Adenosine was incorporated into tissues of the so-called energetic type, into tissues having high vascularity such as the heart and lung, and into erythrocytes. Nearly all of the incorporation of inosine occurred only after its conversion to hypoxanthine. Hypoxanthine was incorporated not only into the kidney but also into peripheral tissues such as bone marrow, lymph node, thymus, intestinal mucosa and submaxillary gland that rapidly synthesize nucleic acids and have at least a partial requirement for hypoxanthine supplied from other tissues by way of erythrocytes. Xanthine and successive metabolites were not retained by tissues but were rapidly metabolized and excreted. This gross survey of purine uptake from the systemic circulation provides a way of assessing the relative importance of systemic salvage of circulating purines among different tissues in an animal body. The whole-body autoradiographic technique has been shown to furnish systemic information on biochemical processes relating to purine metabolism that occur throughout the animal body. The technique itself offers a wide potential for the study of other systemic biochemical phenomena in vivo.
Epidemiology and demographics of prostatitis

Summary. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a multifactorial problem affecting men of all ages and demographics. Currently, there is a relative dearth of epidemiological information on CPPS. It is clear that patients with CPPS have a dismal quality of life and many have benefited only minimally from empiric, goal‐directed therapy. Long‐term follow‐up of the CPPS cohort will answer important questions about the natural and treated history of this syndrome. Similarly, ongoing and future studies will provide community‐based and prevalence estimates for CPPS, morbidity rates for men with CPPS, and the rates of symptom improvement and symptom deterioration for these men, as well as the probability of benefits and harm from different treatments. Although men with CP routinely receive anti‐inflammatory and antimicrobial therapy, recent studies suggest that leucocyte and bacterial counts do not correlate with severity of symptoms. These findings suggest that factors other than leucocytes and bacteria contribute to the symptoms associated with CPPS. The probability of benefits and harm from different treatments for CPPS, and reliable and valid measures to define these outcomes are eagerly awaited.
Dietary intake is associated with human chronotype as assessed by both morningness–eveningness score and preferred midpoint of sleep in young Japanese women

We analyzed the association between dietary intake and chronotype as assessed by both Morningness–Eveningness Questionnaire (MEQ) score and preferred midpoint of sleep in 112 young Japanese women. Dietary intake was assessed by a brief, self-administered diet history questionnaire. A lower MEQ score (evening-type tendency) showed a significant association with a lower energy-adjusted intake of protein, calcium, magnesium, zinc, vitamins (D, riboflavin, and B6), and vegetables, and with a higher intake of noodles. Furthermore, a later midpoint of sleep showed a significant association with a lower energy-adjusted intake of protein, cholesterol, potassium, calcium, magnesium, zinc, vitamins (D, riboflavin, B6, and B12), soy, fish and shellfish, and eggs, and with a higher intake of noodles, bread, and confections. These data suggest that evening chronotype is associated with inadequate dietary habits such as low vitamin and mineral intakes.
Excitatory interneurons dominate sensory processing in the spinal substantia gelatinosa of rat

Substantia gelatinosa (SG, lamina II) is a spinal cord region where most unmyelinated primary afferents terminate and the central nociceptive processing begins. It is formed by several distinct groups of interneurons whose functional properties and synaptic connections are poorly understood, in part, because recordings from synaptically coupled pairs of SG neurons are quite challenging due to a very low probability of finding connected cells. Here, we describe an efficient method for identifying synaptically coupled interneurons in rat spinal cord slices and characterizing their excitatory or inhibitory function. Using tight‐seal whole‐cell recordings and a cell‐attached stimulation technique, we routinely tested about 1500 SG interneurons, classifying 102 of them as monosynaptically connected to neurons in lamina I–III. Surprisingly, the vast majority of SG interneurons (n= 87) were excitatory and glutamatergic, while only 15 neurons were inhibitory. According to their intrinsic firing properties, these 102 SG neurons were also classified as tonic (n= 49), adapting (n= 17) or delayed‐firing neurons (n= 36). All but two tonic neurons and all adapting neurons were excitatory interneurons. Of 36 delayed‐firing neurons, 23 were excitatory and 13 were inhibitory. We conclude that sensory integration in the intrinsic SG neuronal network is dominated by excitatory interneurons. Such organization of neuronal circuitries in the spinal SG can be important for nociceptive encoding.
Identification of Essential Residues of Human RL-Fucosidase and Tests of Its Mechanism †

Fucosylated glycoconjugates have critical roles in biological processes, but a limited availability of R-L-fucosidase has hampered research on this human enzyme (h-Fuc) at a molecular level. After overexpressing h-Fuc in Escherichia coli as an active form, we investigated the catalytic function of this recombinant enzyme. Based on sequence alignment and structural analysis of close homologues of h-Fuc, nine residues of glutamate and aspartate in h-Fuc were selected for mutagenic tests to determine the essential residues. Among the mutants, D225N, E289Q, and E289G lost catalytic activity significantly; their kcat values are 1/5700, 1/430, and 1/340, respectively, of that of the wild-type enzyme. The Brønsted plot for kcat/Km for the E289G mutant is linear with lg ) -0.93, but that for kcat is biphasic, with lg for poor substrates being -0.88 and for activated substrates being -0.11. The small magnitude of lg for the activated substrates may indicate that the rate-limiting step of the reaction is defucosylation, whereas the large magnitude of the latter lg value for the poor substrates indicates that the rate-limiting step of the reaction becomes fucosylation. The kinetic outcomes support an argument that Asp225 functions as a nucleophile and Glu289 as a general acid/base catalyst. As further evidence, azide significantly reactivated D225G and E289G, and 1H NMR spectral analysis confirmed the formation of -fucosyl azide and R-fucosyl azide in the azide rescues of D225G and E289G catalyses, respectively. As direct evidence to prove the function of Glu289, an accumulation of fucosyl-enzyme intermediate was detected directly through ESI/ MS analysis. Fucose-containing carbohydrates are involved in such critical physiological activities as oncogenesis (1, 2), blood coagulation cascade and clot dissolution (3-5), and hostmicrobial interactions (6, 7). R-L-Fucosidases (EC 3.2.1.51) are responsible for the removal of L-fucosyl residues from the nonreducing end of glycoconjugates. A severe deficiency of R-L-fucosidase causes fucosidosis that can produce mental and motor retardation (8). Several pathological conditions including inflammation (4, 9), cancer (10-12) and cystic fibrosis (13, 14) are also related to an atypical activity of R-L-fucosidase. Human R-L-fucosidases (h-Fuc) are thus of substantial interest because abnormal fucosidase activity in serum was shown to serve as a diagnostic marker of early colorectal (2, 12) and hepatocellular cancers (10, 15). A treatment of R-L-fucosidase to breast cancer cells also showed impairment of the interaction between these tumor cells and their microenvironment, which might consequently modulate
Strategic R%D internationalisation in developing Asian countries - the Italian experience

Increasingly over the last two decades, companies not only produce and sell, but also develop goods and services outside their home countries. Rapidly becoming the rule rather than the exception, these firms undertake significant R%D activities at different locations abroad. The phenomenon is especially visible in the developing Asian countries, whose markets are becoming extremely attractive to foreign firms while their workforces and infrastructural R%D capacities and competencies themselves progressively favour R%D. The aim of this paper is to show R%D internationalisation activities of firms from Italy in Asian developing countries. Using a dataset of 500 Italian firms with international R R%DD units, as well as interviews, we researched whether companies follow a knowledge augmenting or knowledge sourcing strategy. The results show a positive relation between the choice to settle R%D units in Asia and the sale of innovative products in Asia, concluding that firms follow a knowledge exploiting strategy, establishing their whole innovation value chain to developing Asian countries.