Miracle-dz/UniFAR-FTUs huggingface dataset:
A Meta-analysis of Transient Elastography for the Detection of Hepatic Fibrosis

Objectives The use of transient elastography to assess liver stiffness measurement (LSM) has now become widely available for the diagnosis of liver fibrosis as a rapid, noninvasive test (it is still not approved for use in the United States). It has previously been showed as an accurate method of representing the state of liver fibrosis with concomitant evaluation of liver biopsy and the histologic scoring system METAVIR. We performed a meta-analysis to further assess its use in comparison with liver biopsy. Methods Studies from the literature were analyzed with a median liver stiffness value in kilopascal given for fibrosis stages according to histopathologic findings on biopsy and best discriminant cutoff levels in kilopascals for significant fibrosis (≥F2) and cirrhosis (F4). Results A total of 22 studies were selected comprising 4430 patients; chronic hepatitis C infection was the most common etiology of fibrosis. The pooled estimates for significant fibrosis (≥F2) measured 7.71 kPa (LSM cutoff value) with a sensitivity of 71.9% [95% confidence interval (CI): 71.4%-72.4%] and specificity of 82.4% (95% CI: 81.9-82.9%), whereas for cirrhosis (F4) the results showed a cutoff of 15.08 kPa with a sensitivity of 84.45% (95% CI: 84.2-84.7%) and specificity of 94.69% (95% CI: 94.3%-95%). Conclusions Further evaluation of transient elastography to assess LSM is required in prospective studies to potentially increase the sensitivity and establish its clinical utility.
The glycosomes of trypanosomes: number and distribution as revealed by electron spectroscopic imaging and 3‐D reconstruction

Computer‐aided 3‐D reconstruction of typanosomes from 0·35‐μm‐thick sections imaged on the Zeiss 902 electron microscope are being used to study the dynamics of cell organization. Segregation of glycolytic enzymes into glycosomes raises questions concerning the distribution and biogenesis of these organelles. Direct counts of glycosomes from Trypanosoma evansi indicate 30–40 per cell and for the closely related T. brucei, 65 per cell. These figures contrast with the estimates of others who have used model‐based morphometric methods to obtain a value of 230 per cell.
Affine Structure and Invariant Policies for Dynamic Programs

This paper studies a family of sequential decision processes whose affine structure is shown to imply that attention can be restricted to policies that select the same decision for all states. A sequence of n invariant policies (decisions) is shown to be optimal when the planning horizon is n epochs. When the planning horizon is infinite, added structure is imposed, and a stationary invariant policy is shown to be optimal. Computational methods and examples are included.
Effects of volcanism on tropical variability

The effects of large tropical volcanic eruptions on Indo‐Pacific tropical variability are investigated using 122 historical ensemble members from the Coupled Model Intercomparison Project 5. Radiative forcing due to volcanic aerosols in the stratosphere is found to increase the likelihood of a model climatic response that projects onto both the El Niño–Southern Oscillation and the Indian Ocean Dipole (IOD). Large eruptions are associated with co‐occurring El Niño and positive IOD events in the ensemble means that peak 6–12 months after the volcanic forcing peaks, marking a significant increase in the likelihood of each event occurring in the Southern Hemisphere (SH) spring/summer posteruption. There is also an ensemble mean La Niña‐like response in the third SH summer posteruption, which coincides with a significant increase in the likelihood of a La Niña occurring. Taken together with the initial cooling, this La Niña‐like response may increase the persistence of the cool global average surface temperature anomaly after an eruption.
Impact of nonphysician staffing on outcomes in a medical ICU.

BACKGROUND As the number of ICU beds and demand for intensivists increase, alternative solutions are needed to provide coverage for critically ill patients. The impact of different staffing models on the outcomes of patients in the medical ICU (MICU) remains unknown. In our study, we compare outcomes of nonphysician provider-based teams to those of medical house staff-based teams in the MICU. METHODS We conducted a retrospective review of 590 daytime (7:00 am-7:00 pm) admissions to two MICUs at one hospital. In one MICU staffed by nurse practitioners and physician assistants (MICU-NP/PA) there were nonphysicians (nurse practitioners and physicians assistants) during the day (7:00 am-7:00 pm) with attending physician coverage overnight. In the other MICU, there were medicine residents (MICU-RES) (24 h/d). The outcomes investigated were hospital mortality, length of stay (LOS) (ICU, hospital), and posthospital discharge destination. RESULTS Three hundred two patients were admitted to the MICU-NP/PA and 288 to the MICU-RES. Mortality probability model III (MPM(0)-III) predicted mortality was similar (P = .14). There was no significant difference in hospital mortality (32.1% for MICU-NP/PA vs 32.3% for MICU-RES, P = .96), MICU LOS (4.22 ± 2.51 days for MICU-NP/PA vs 4.44 ± 3.10 days for MICU-RES, P = .59), or hospital LOS (14.01 ± 2.92 days for MICU-NP/PA vs 13.74 ± 2.94 days for MICU-RES, P = .86). Discharge to a skilled care facility (vs home) was similar (37.1% for MICU-NP/PA vs 32.5% for MICU-RES, P = .34). After multivariate adjustment, MICU staffing type was not associated with hospital mortality (P = .26), MICU LOS (P = .29), hospital LOS (P = .19), or posthospital discharge destination (P = .90). CONCLUSIONS Staffing models including daytime use of nonphysician providers appear to be a safe and effective alternative to the traditional house staff-based team in a high-acuity, adult ICU.
Cytokine Storm may Play a Role in the Pathogenesis of HumanParechovirus Type 3-Associated Acute Encephalopathy in Neonates: A Case Report

Background: Human parechovirus type 3 (HPeV3) is an important cause of acute encephalitis in the neonatal and early infantile periods. Typical HPeV3-associated acute encephalitis paradoxically shows no cerebrospinal fluid (CSF) pleocytosis despite virus detection in CSF and diffuse deep white matter involvement of the corpus callosum on magnetic resonance images (MRI). Patient: An 8-day-old full-term infant was found to have HPeV3 infection of the central nervous system (CNS), which was confirmed using diffusion-weighted MRI showing poor diffusivity in the bilateral deep white matter and the corpus callosum without CNS pleocytosis, as seen in previously reported cases. Interestingly, this patient had extremely elevated serum ferritin and urinary beta-2-microglobulin levels, which indicated a surge of the cytokines tumor necrotizing factor alpha and interferon gamma. Conclusion: These findings suggest that the cytokine storm can promote the pathogenesis of white matter lesions in HPeV3-associated acute encephalopathy rather than direct infection of the brain.
CYTOTOXIC ACTIVITY OF PARIS QUADRIFOLIA EXTRACT AND ISOLATED SAPONIN FRACTIONS AGAINST HUMAN TUMOR CELL LINES

Steroidal saponins isolated from many plant species belonging to Monocotyledones display potent cytotoxic activity towards many human tumor cells. We examined the cytotoxic effects of crude Paris quadrifolia extract for the first time, testing isolated saponin-rich fractions against four different human cell lines using the [(3-(4,5dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was tested against human promyelocytic leukemia (HL-60) cells, human cervical adenocarcinoma (HeLa) cells and human breast cancer (MDA-MB-468) cells. Human skin fibroblasts were used as non-neoplastic control cells. Our results show significant activity of the weakly water-soluble solid residue and butanolic fraction against HL-60 and HeLa cells. The solid residue exerted cytotoxicity against all tested cell lines.
Pulsed Regimes of Erbium-Doped Fiber Laser Q-Switched Using Acousto-Optical Modulator

In this paper, we explore in details the operation regimes of an actively Q-switched erbium-doped fiber laser using a commercial acousto-optical modulator (AOM) and demonstrate that these regimes essentially depend on whether or not continuous-wave (CW) narrow-line lasing develops in the intervals when AOM is blocked. If such spurious CW lasing exists it always starts up within auxiliary low-Q cavity formed by an output coupler and weak reflections from AOM while the area where it occurs is limited by certain values of an active fiber's length and AOM's repetition rate. In the absence of spurious CW lasing (when shorter active fibers are used), the laser operates in the regime of “common” Q-switching where the shape of pulses can be easily managed by a proper waveform of the signal controlling the AOM's driver; pulse jittering in this regime is vastly negligible. In turn, when spurious CW lasing arises within the intervals when AOM is closed (this occurs at longer active fibers and at not too high AOM's repetition rates), the laser operates in the regime of SBS-induced pulsing where short and powerful pulses are released; pulse jittering in this case is perceptible and depends on AOM's repetition rate.
TALEN Knockout of the PSIP1 Gene in Human Cells: Analyses of HIV-1 Replication and Allosteric Integrase Inhibitor Mechanism

ABSTRACT HIV-1 utilizes the cellular protein LEDGF/p75 as a chromosome docking and integration cofactor. The LEDGF/p75 gene, PSIP1, is a potential therapeutic target because, like CCR5, depletion of LEDGF/p75 is tolerated well by human CD4+ T cells, and knockout mice have normal immune systems. RNA interference (RNAi) has been useful for studying LEDGF/p75, but the potent cofactor activity of small protein residua can be confounding. Here, in human cells with utility for HIV research (293T and Jurkat), we used transcription activator-like effector nucleases (TALENs) to completely eradicate all LEDGF/p75 expression. We performed two kinds of PSIP1 knockouts: whole-gene deletion and deletion of the integrase binding domain (IBD)-encoding exons. HIV-1 integration was inhibited, and spreading viral replication was severely impaired in PSIP1 −/− Jurkat cells infected at high multiplicity. Furthermore, frameshifting the gene in the first coding exon with a single TALEN pair yielded trace LEDGF/p75 levels that were virologically active, affirming the cofactor's potency and the value of definitive gene or IBD exon segment deletion. Some recent studies have suggested that LEDGF/p75 may participate in HIV-1 assembly. However, we determined that assembly of infectious viral particles is normal in PSIP1 −/− cells. The potency of an allosteric integrase inhibitor, ALLINI-2, for rendering produced virions noninfectious was also unaffected by total eradication of cellular LEDGF/p75. We conclude that HIV-1 particle assembly and the main ALLINI mechanism are LEDGF/p75 independent. The block to HIV-1 propagation in PSIP1 −/− human CD4+ T cells raises the possibility of gene targeting PSIP1 combinatorially with CCR5 for HIV-1 cure. IMPORTANCE LEDGF/p75 dependence is universally conserved in the retroviral genus Lentivirus. Once inside the nucleus, lentiviral preintegration complexes are thought to attach to the chromosome when integrase binds to LEDGF/p75. This tethering process is largely responsible for the 2-fold preference for integration into active genes, but the cofactor's full role in the lentiviral life cycle is not yet clear. Effective knockdowns are difficult because even trace residua of this tightly chromatin-bound protein can support integration cofactor function. Here, in experimentally useful human cell lines, we used TALENs to definitively eradicate LEDGF/p75 by deleting either all of PSIP1 or the exons that code for the integrase binding domain. HIV-1 replication was severely impaired in these PSIP1 knockout cells. Experiments in these cells also excluded a role for LEDGF/p75 in HIV-1 assembly and showed that the main ALLINI mechanism is LEDGF/p75 independent. Site-specific gene targeting of PSIP1 may have therapeutic potential for HIV-1 disease.
Clinical Analysis and Surgical Outcomes of 15 Cases of Cauda Equina Tumors

Objective: To evaluate the clinical results of gross total resection of cauda equina tumors. Patients and Methods: Between June 2007 and October 2011, 9 males and 6 females (mean age 37) diagnosed with intradural tumor in the region of the cauda equina were surgically treated at Suez Canal University Hospital. The neurological and functional states of each patient were evaluated according to the modified McCormick scale. Magnetic resonance imaging was used in diagnosis and follow-up. Results: The most common symptoms presented were pain (in 93.3%); weakness presented by 2 patients (13.3%), and incontinence by 1 patient (6.6%). Gross total resection (achieved in 13 patients = 86%) through a posterior approach. Surgical resection of these tumors led to significant alleviation of pre-operative symptoms. Conclusions: Cauda equina tumors generally carry a favorable prognosis: Most of these tumors are benign, and the aim of treatment is to restore function and prevent recurrences. The determining factors for optimal clinical results after surgery are a gross total resection of the tumor and good neurological condition before the operation.
On-line CORDIC algorithms

The CORDIC algorithms provide a fast way to calculate a number of basic arithmetic functions. A CORDIC calculation takes O(n) steps for a function, where n is the word length of the operands. The speed is limited by the carry propagation in the adders and the I/O throughput. Speed can be improved by introducing redundancy in the calculation circuitry and I/O throughput by doing I/O transfers while calculating. The latter is characteristic for the class of so-called online arithmetic. At the same time, the pin requirements are limited to a single digit per operand. The authors introduce a number of new algorithms that provide an online CORDIC implementation. <<ETX>>
Atomic Carbon Is a Temperature Probe in Dark Clouds

We have mapped the C I 3P1 → 3P0 line at 492 GHz in three molecular clouds immersed in weak ultraviolet radiation fields, TMC-1, L134N, and IC 5146. In all three clouds, the C I peak T ~ 1 K, with very small dispersion. The spatial C I distribution is extended and rather smooth. The J = 2 → 1 transitions of CO isotopomers were observed at the same angular resolution as C I. The C I peak T is typically one-third of the peak T of 13CO J = 2 → 1, and the C I emission is usually more extended than emission in 13CO or C18O J = 2 → 1. The C I line width is close to the 13CO J = 2 → 1 line width, larger than the C18O J = 2 → 1 line width and smaller than the 12CO J = 2 → 1 line width. The shapes of these lines occasionally differ significantly, probably because of the combined effects of differing opacities and the physical separation of the line-forming regions. The uniformity of the C I peak T is remarkable for a line in the Wien portion of the Planck function and indicates a very uniform excitation temperature. This uniformity is best explained if the line is opaque and thermalized. If so, the C I line probes kinetic temperature in clouds exposed to low-ultraviolet fluxes. This conclusion has significant implications for the thermal balance in such clouds. At AV ≃ 2, these clouds have a remarkably constant temperature from place to place and from cloud to cloud (7.9 ± 0.8 K). Photodissociation region models of clouds immersed in the mean interstellar radiation field tend to predict stronger lines than we see, but this may be an artifact of assumptions about the temperature.
eakness Is the Primary Contributor to Finger Impairment in hronic Stroke

Objective: To assess the relative contributions of several neuologic and biomechanic impairment mechanisms to overall finger nd hand impairment in chronic hemiparetic stroke survivors. Design: Repeated-measures design. Setting: Clinical research laboratory. Participants: Thirty stroke survivors with chronic hemipaesis. Fifteen subjects had severe hand motor impairment and 5 had moderate impairment, as measured with the ChedokecMaster Stroke Assessment. Interventions: Not applicable. Main Outcome Measures: The biomechanic factors stiffness nd resting flexion torque, together with the neurologic factors pasticity, strength, and coactivation, were quantified by using a ustom hand manipulator, a dynamometer, and electromyographic ecordings. Both passive and active rotations of the metacarpohalangeal joints of the fingers were examined. Results: Although subjects in the severely impaired group xhibited statistically greater passive stiffness and resting exion torque than their moderately impaired counterparts P . 05), the overall effect of these biomechanic changes apeared small in relation to the deficits attributable to neurologic hanges such as spasticity and, especially, weakness. In fact, eakness in grip strength and isometric extension accounted or the greatest portion of the variance between the 2 groups 2 . 40 and 2 . 23, respectively). Conclusions: Thus, deficits in hand motor control after troke seem to derive mainly from weakness, which may be ttributable to the loss of descending corticospinal pathway ctivation of motoneurons.
Obesity and asthma: association or epiphenomenon?

OBJECTIVE To relate obesity and asthma by comparing gender, age, initial classification of asthma, clinical control, basal forced expiratory volume in one second (FEV1) and forced expiratory flow between 25 and 75% (FEF25-75%) with rates of body mass index (BMI) in asthmatic adolescents. METHODS Cross-sectional study involving 120 asthmatics patients (1.9 male: 1 female) with a mean age of 14.1 years (9 to 20.1 years of age), classified according to asthma severity and control, and evaluated by spirometry using their basal FEV1 and FEF25-75%. The data were described by frequency, mean and standard deviation or median and range and analyzed by ANOVA, unpaired t test, Fischer's exact test, Kruskal-Wallis and Pearson's correlation, considering significant p<0.05. RESULTS There was no difference between gender in relation to the initial classification and the level of asthma control; 91.7% (100 cases) received initial classification as persistent and 106 cases (88.3%) were partially or totally controlled. There was no statistical difference between controlled patients and the others in relation to BMI. No significant correlations were found between zBMI and FEV1 and between zBMI and FEF25-75%, analyzing all patients and only patients with overweight or obese. CONCLUSIONS In this study, no significant correlation was found between overweight/obesity and asthma using clinical, anthropometric and spirometric parameters.
Wiskott–Aldrich syndrome protein – dynamic regulation of actin homeostasis: from activation through function and signal termination in T lymphocytes

The actin cytoskeleton network forms a key link between T‐cell antigen receptor (TCR) stimulation and T‐cell effector functions, providing a structural basis for T‐cell morphological changes and signal transduction. Accumulating evidence positions the Wiskott–Aldrich syndrome protein (WASp), a scaffolding protein that promotes actin polymerization, at the center of actin cytoskeleton‐dependent T‐cell function. During the past decade, we and others have utilized multidisciplinary technologies, including live‐cell imaging, biochemical, and biophysical analyses, to gain insight into the mechanisms by which WASp and other cytoskeletal proteins control actin homeostasis. Following TCR engagement, WASp is rapidly activated and recruited to TCR microclusters, as part of multiprotein complexes, where it promotes actin remodeling. Late in the activation process, WASp is internalized and eventually degraded. In this review, we describe the dynamic interactions of WASp with signaling proteins, which regulate its activation and recruitment to the TCR and to actin‐rich sites. Finally, we present the molecular mechanism of WASp downregulation. Some of the signaling proteins that mediate WASp activation eventually lead to its degradation. Thus, we focus here on the regulation of WASp expression and function and the mechanisms whereby they control actin machinery and T‐cell effector functions.
Harmonic generation by an intense laser pulse in neutral and ionized gases

Reported are the results of a harmonic generation experiment in a simple gas (hydrogen) using 1-ps, 1- mu m laser pulses with a range of intensities extending from below to far above the laser ionization saturation threshold. The scaling with intensity above saturation of the third harmonic generated by a single laser-pulse in a filled gas cell is observed not to fit with a simple model that takes into consideration volume ionization effects alone. In another experiment, a pump-probe type, an upper limit on the conversion efficiency of third-harmonic generation in a preformed plasma is determined. It is found to be in agreement with the efficiency predicted by a relativistic harmonic generation theory. >
Ca2+ and voltage inactivate Ca2+ channels in guinea‐pig ventricular myocytes through independent mechanisms.

1. L‐type Ca2+ currents and Ca2+ channel gating currents were studied in isolated guinea‐pig ventricular heart cells using the whole‐cell patch‐clamp technique, in order to investigate the mechanism of Ca(2+)‐dependent inactivation. The effect of altering the intracellular Ca2+ concentration ([Ca2+]i) on these currents was studied through photorelease of intracellular Ca2+ ions using the photolabile Ca2+ chelators DM‐nitrophen and nitr‐5. 2. We found that step increases in [Ca2+]i produced by photorelease could either increase or decrease the L‐type Ca2+ current. Specifically, Ca2+ photorelease from DM‐nitrophen almost exclusively caused inactivation of the Ca2+ current. In contrast, Ca2+ photorelease from nitr‐5 had a biphasic effect: a small, rapid inactivation of the Ca2+ current was followed by a slow potentiation. These two Ca(2+)‐dependent processes seemed to differ in their Ca2+ dependence, as small Ca2+ photoreleases elicited potentiation without a preceding inactivation, whereas larger photoreleases elicited both inactivation and potentiation. 3. The mechanism of the Ca(2+)‐dependent inactivation of Ca2+ channels was explored by comparing the effects of voltage and photoreleased Ca2+ on the Ca2+ current and the Ca2+ channel gating current. Voltage was found to reduce both the Ca2+ current and the gating current proportionally. However, Ca2+ photorelease from intracellular DM‐nitrophen inactivated the Ca2+ current without having any effect on the gating current. 4. The dephosphorylation hypothesis for Ca(2+)‐dependent inactivation was tested by applying isoprenaline to the cells before eliciting a maximal rise of [Ca2+]i (maximal flash intensity, zero external [Na+]i). Isoprenaline could completely prevent Ca(2+)‐dependent inactivation under these conditions, even when [Ca2+]i rose so high as to cause an irreversible contracture of the cell. 5. We concluded from these experiments that voltage and Ca2+ ions inactivate the L‐type Ca2+ channel through separate, independent mechanisms. In addition, we found that Ca(2+)‐dependent inactivation does not result in the immobilization of gating charge, and apparently closes the Ca2+ permeation pathway through a mechanism that does not involve the voltage‐sensing region of the channel. Furthermore, we found that Ca(2+)‐dependent inactivation is entirely sensitive to beta‐adrenergic stimulation. These facts suggest that either Ca(2+)‐dependent inactivation results from Ca(2+)‐dependent dephosphorylation of the Ca2+ channel, or that Ca(2+)‐dependent inactivation is modulated by protein kinase A.