Miracle-dz/UniFAR-FTUs huggingface dataset:
Different amplification patterns of the human telomerase RNA gene in invasive cervical carcinomas and cervical intraepithelial neoplasia grade III

The aim of this study was to compare the amplification patterns of the human telomerase RNA gene (hTERC) in invasive cervical carcinomas (ICC) and cervical intraepithelial neoplasia grade III (CIN III) and to define their potential clinical implications. Cervical liquid‐based cytological (LBC) specimens were collected from 53 squamous cell carcinomas (SCC), 14 CIN III, and 20 normal controls. Copy numbers of the hTERC gene were measured by fluorescence in situ hybridization (FISH) using a dual‐color probe containing the hTERC probe and the control, chromosome 3 centromere‐specific probe (CSP3). Nucleus with abnormal FISH pattern for hTERC was observed in 0.94–90.65% of SCC cells and in 0–85.59% of CIN III cells. Using the threshold of 5.89%, the occurrence of hTERC amplification in SCC and CIN III was similar (90.6% vs. 85.7%, P = 0.630). However, the median percentage of cells with extra gains of hTERC (hTERC:CSP3 > 1) in SCC was higher than in CIN III (64.3% vs. 31.7%, P = 0.001). Among those cells, the 3:2 signal pattern was the leading pattern for both SCC and CIN III; high‐level amplification of hTERC was more common in SCC than in CIN III (60.9% vs. 48.9%, P = 0.002). In SCC, it was not found that extra gains of hTERC were associated with any clinicopathological parameters. Thus, hTERC amplification was common in cervical exfoliated cells from SCC and CIN III. More complex amplification patterns of hTERC were present in ICC. Clinical usefulness of hTERC amplification in LBC samples was limited in ICC. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
El mercado alternativo bursátil para empresas en crecimiento

El despegue del MAB parece no llegar nunca. A pesar del elevado numero de PYMEs que compone nuestro tejido empresarial, son minoria las que han acudido a este mercado bursatil como via alternativa de financiacion. El apoyo fiscal e institucional de las comunidades autonomas, la aceptacion de riesgos y una normativa favorable a la inclusion en fondos de inversion podrian ser algunas de las claves para su desarrollo definitivo
Accurate modeling of microwave structures using variable-fidelity response features

This paper describes a novel approach to low-cost, accurate modeling of microwave structures using response features. Computational efficiency of the proposed method originates from the less nonlinear dependence of the feature points on the designable parameters of the structure of interest than conventionally used responses (e.g., S-parameters vs. frequency). Further decrease of the surrogate model setup cost is obtained by exploiting variable-fidelity EM simulations that are blended together using co-kriging interpolation. Comprehensive verification and comparisons with benchmark techniques is provided.
Synergism of buthionine sulfoximine and melphalan against neuroblastoma cell lines derived after disease progression.

BACKGROUND Despite intensive-alkylator based regimens, >50% of patients with high-risk neuroblastoma (NB) die from recurrent disease that is probably due, in part, to acquired alkylator resistance. PROCEDURE Using buthionine sulfoximine (BSO)-mediated, glutathione (GSH) depletion to modulate melphalan (L-PAM) resistance, we examined six NB cell lines established after progressive disease following either standard chemotherapy, BSO/L-PAM therapy, or myeloablative therapy and autologous hematopoietic stem cell transplant (AHSCT). RESULTS Four of the six cell lines (three p53-nonfunctional and one p53-functional) showed high-level L-PAM resistance. CONCLUSIONS Fixed ratio analysis demonstrated BSO/L-PAM synergy (combination index >1) for all cell lines tested. In L-PAM-resistant cell lines, the minimal cytotoxicity observed for BSO combined with nonmyeloablative concentrations of L-PAM was markedly enhanced (>4 logs total cell kill) when BSO was combined with myeloablative concentrations of L-PAM. In alkylator-resistant NB, the optimal use of BSO may require dose escalation of L-PAM to levels requiring AHSCT.
Ultrastructural study of experimental cementum regeneration in rats.

The present study examined two phases of experimental cementum regeneration at the ultrastructural level. Small fenestration wounds (1 mm in diameter) were made on the mesial root of mandibular first molars in 20 Lewis strain rats to remove cementum and periodontal ligament. The wounds were covered with sheets of Nucleopre filter, before replacing the extraorat flaps, to allow population of denuded roots by cells arising mainly from the adjacent periodontal ligament. The rats were sacrificed in two batches of 10 each to provide observation periods of 2 and 4 weeks. The specimens were processed for transmission electron microscopy. At 2 wk, fibroblasts exhibiting ultrastructural features suggestive of various stages of synthetic activity were seen in the wound and adjacent to denuded root surfaces which appeared irregular. At 4 wk, cementoid regeneration was seen with bundles of oriented collagen fibrils inserting into the cementoid matrix. A consistent finding at both observation periods was the presence of an electron-dense, granular zone between the cementum/collagen matrix and the denuded root surface. Contrary to previous reports, the electron-dense zone appeared bi-layered with collagen fibrils and filamentous material in the superficial layer. At both observation periods, synthetic activity and matrix organization were more advanced in areas away from the root surface (fibrillogenesis) compared to areas adjacent to the root surface (cementogenesis). The present findings suggest that some important cellular and molecular events, possibly regulatory in nature, occur during the early stages of cementum regeneration in rats.
Clinical management of catheter-related infections.

Central venous catheters represent a major source of nosocomial bloodstream infections, which cause considerable excess morbidity. It is currently unknown to what extent these infections contribute to mortality. Most catheter-related infections (CRIs) are caused by Gram-positive organisms (mainly coagulase-negative staphylococci). Definite diagnosis of CRI necessitates removal of the catheter in most cases. However, the recently described technique of differential time to positivity may allow diagnosis of CRI with the catheter left in place. Removal of the catheter has been standard clinical practice for the management of CRI in the past and is still recommended in many cases. In specific situations, such as infections of implanted catheters with coagulase-negative staphylococci, a trial of catheter salvage may be justified. In catheter-related bloodstream infection Staphylococcus aureus and Candida spp. , the catheter should be removed immediately, due to the high risk of metastatic infection and increased mortality. A clinical work-up for the detection of additional foci (including transesophageal echocardiography in S. aureus infections) is advisable in these cases. All CRIs should be treated with antibiotics to which the causative agent has been shown to be susceptible. In addition to systemic antimicrobial therapy, antibiotic lock therapy may be applied, especially in patients with implanted long-term catheters if catheter salvage is attempted.
Photoresponsive Fischer 344 Rats are Reproductively Inhibited by Melatonin and Differ in 2‐[125I] Iodomelatonin Binding from Nonphotoresponsive Sprague‐Dawley Rats

Many temperate‐zone species use photoperiod as an environmental cue to regulate reproductive timing. Strains of laboratory rats differ in their responsiveness to photoperiod, with the Fischer 344 (F344) strain being the most responsive known. F344 rats and closely related strains that differ in photoresponsiveness may be useful models to study the mechanisms and genetic basis for photoresponsiveness. We tested two hypotheses: (i) that melatonin mediates photoresponsiveness in F344 rats, as is the case in all other mammals tested, and (ii) that the location, abundance, or affinity of melatonin receptors, as estimated by the amount and location of binding of the radioligand 2‐[125I]‐iodomelatonin (IMEL) in the brain, might cause variation in photoresponsiveness among rat strains. Melatonin injections 1 h before lights off in a stimulatory photoperiod (L14 : D10) induced reproductive inhibition and reduced weight gain in a manner similar to short days of L8 : D16, while injections of ethanolic saline vehicle did not. Interestingly, melatonin injections administered during an inhibitory photoperiod (L10 : D14) caused greater inhibition of both reproduction and weight gain than short photoperiod alone. Pinealectomized F344 rats implanted subcutaneously with melatonin in a silastic capsule did not differ in testis size or body weight from controls with blank implants. The brains and pars tuberalis of the pituitary from photoresponsive F344 rats and nonphotoresponsive Harlan Sprague‐Dawley (HSD) rats were processed for autoradiography using IMEL. We found significantly higher specific IMEL binding in the anterior and posterior regions of the paraventricular nucleus of the thalamus (PVNt) and reuniens nucleus of the thalamus of F344 rats than in the same areas in HSD rats. There were no differences between strains in specific IMEL binding in the medial PVNt, anteroventral and anterodorsal nucleus of the thalamus, suprachiasmatic nucleus, or the pars tuberalis. These results indicate that melatonin mediates photoresponsiveness in F344 rats. In addition, they provide support for the hypothesis that F344 rats may be photoresponsive due to differences from other strains in the location, density, or affinity of melatonin receptors.
Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women.

BACKGROUND There is a paucity of data on the efficacy of nitrofurantoin for the treatment of acute uncomplicated cystitis in regimens shorter than 7 days. Evidence-based use of this drug is increasingly important as trimethoprim-sulfamethoxazole resistance among uropathogens increases. METHODS To assess the efficacy of nitrofurantoin vs trimethoprim-sulfamethoxazole, 338 women aged 18 to 45 years with acute uncomplicated cystitis were randomized to open-label treatment with either trimethoprim-sulfamethoxazole, 1 double-strength tablet twice daily for 3 days, or nitrofurantoin, 100 mg twice daily for 5 days. Clinical cure 30 days after therapy was the main outcome measure. Secondary outcomes included clinical and microbiological cure rates 5 to 9 days after therapy and, for trimethoprim-sulfamethoxazole-treated women, clinical cure stratified by the trimethoprim-sulfamethoxazole susceptibility of the uropathogen. RESULTS Clinical cure was achieved in 79% of the trimethoprim-sulfamethoxazole group and in 84% of the nitrofurantoin group, for a difference of -5% (95% confidence interval, -13% to 4%). Clinical and microbiological cure rates at the first follow-up visit were also equivalent between the 2 groups. In the trimethoprim-sulfamethoxazole arm, 7 of 17 women (41%) with a trimethoprim-sulfamethoxazole-nonsusceptible isolate had a clinical cure compared with 84% of women with a trimethoprim-sulfamethoxazole-susceptible isolate (P < .001). CONCLUSION A 5-day course of nitrofurantoin is equivalent clinically and microbiologically to a 3-day course of trimethoprim-sulfamethoxazole and should be considered an effective fluoroquinolone-sparing alternative for the treatment of acute cystitis in women.
A Novel Haptic Interface for Navigation in Large Volume Environments

Haptic interfaces can provide highly realistic interaction with objects within their workspace, but the task of interacting with objects over large areas or volumes is made difficult by the limits of interface travel. This paper details the development of a custom haptic interface for navigating a large virtual environment (a simulated supermarket), and investigation into different control methods which allow for haptic interaction over extremely large workspaces
The effects of Salvia officinalis L. on granulosa cells and in vitro maturation of oocytes in mice

Background: Salvia officinalis L. has been used since ancient times but there are little data about effects of this herb on normal reproductive cells. Objective: To investigate the toxicity effects of Salvia officinalis L. on granulosa cells (GCs) and maturation of oocytes. Materials and Methods: GCs and oocytes were extracted from superovulated ovaries of immature mice. The cells were treated with concentrations of 10, 50, 100, 500, and 1000 μg/ml of Salvia officinalis hydroalcoholic extracts and compared with the control culture. Bioviability, chromatin condensation, estradiol and progesterone concentrations, lipid synthesis, apoptosis, and alkaline phosphatase activity of GCs were measured. In vitro maturation of oocytes by determination of different maturation stages of oocytes including germinal vesicle, germinal vesicle breaks down, and metaphase II were examined. Results: The results revealed that 500 and 1000 μg/ml concentrations of Salvia officinalis L. were toxic. The most of the GCs were in the early stages of apoptosis in 100 μg/ml treated culture and cell death happened with 500 μg/ml treatment. Progesterone concentration was reduced in 100 μg/ml and higher doses but estradiol concentration and alkaline phosphatase showed opposite effects. The lipid droplets content of GCs reduced significantly in all groups especially in 500 and 1000 μg/ml. Finally, oocyte’s nucleus and cytoplasm showed a high level of condensation, and meiosis rate reduced in all treated cultures. Conclusion: Our findings suggested that higher dose of Salvia officinalis hydroalcoholic extracts inhibits, oocyte maturation, GCs bioviability, proliferation, and secretion.
Functional Integration Between Brain Regions at Rest Occurs in Multiple-Frequency Bands

Studies of resting-state fMRI have shown that blood oxygen level dependent (BOLD) signals giving rise to temporal correlation across voxels (or regions) are dominated by low-frequency fluctuations in the range of ∼ 0.01-0.1 Hz. These low-frequency fluctuations have been further divided into multiple distinct frequency bands (slow-5 and -4) based on earlier neurophysiological studies, though low sampling frequency of fMRI (∼ 0.5 Hz) has substantially limited the exploration of other known frequency bands of neurophysiological origins (slow-3, -2, and -1). In this study, we used resting-state fMRI data acquired from 21 healthy subjects at a higher sampling frequency of 1.5 Hz to assess the presence of resting-state functional connectivity (RSFC) across multiple frequency bands: slow-5 to slow-1. The effect of different frequency bands on spatial extent and connectivity strength for known resting-state networks (RSNs) was also evaluated. RSNs were derived using independent component analysis and seed-based correlation. Commonly known RSNs, such as the default mode, the fronto-parietal, the dorsal attention, and the visual networks, were consistently observed at multiple frequency bands. Significant inter-hemispheric connectivity was observed between each seed and its contra lateral brain region across all frequency bands, though overall spatial extent of seed-based correlation maps decreased in slow-2 and slow-1 frequency bands. These results suggest that functional integration between brain regions at rest occurs over multiple frequency bands and RSFC is a multiband phenomenon. These results also suggest that further investigation of BOLD signal in multiple frequency bands for related cognitive processes should be undertaken.
Primary structure and functional properties of an epithelial K channel.

Expression cloning in Xenopus oocytes was used to identify a clone for a renal K channel. The clone, named ROMK2, was obtained from a cDNA library constructed in the plasmid vector pSPORT using size-selected poly(A)+ RNA from whole rat kidney. ROMK2 consists of 1,837 nucleotides, with an open reading frame of 1,116 bases predicted to code for a 372-amino acid peptide. The clone appears to be a splice variant of a recently reported K channel (ROMK1) from rat renal outer medulla (Ho, K.H., C.G. Nichols, W.J. Lederer, J. Lytton, P.M. Vassilev, M.V. Kanazirska, and S.C. Hebert. Nature Lond. 362: 31-37, 1993). Northern blot analysis indicates that ROMK2 is expressed in renal cortex, medulla, and papilla. Expression in other tissues appears to be much lower. The functional properties of the channel as measured in Xenopus oocytes indicate its close relationship to ROMK1 and more distant relationship to the inward rectifier K channel (IRK1) (Kubo, Y, T.J. Baldwin, Y. N. Jan, and L. Y. Jan. Nature Lond. 362: 127-133, 1993). The inward conductance of the channel is a saturable function of external K, with a half-maximal conductance at <5 mM. The selectivity sequence for ion permeability based on reversal potential measurements was K > Rb > NH4 > Na, Li. The conductance to Rb was only one-half that to K. Extracellular Ba2+ and Cs+ blocked the channel in a voltage-dependent manner. The high sensitivity of Cs+ block to voltage is consistent with the channel's operating as a multi-ion pore. The channel was blocked by high concentrations (100 microM) of glibenclamide. It did not appear to be blocked by extracellular Na+ or tetraethyl-ammonium ion. Patch-clamp measurements indicated a single-channel conductance of 30 pS in the presence of 110 mM K and high open probability that was weakly dependent on voltage. This channel may be involved in maintaining the membrane potential of renal cells and/or mediating renal K secretion.
Proven Epstein–Barr encephalitis with negative EBV‐DNA load in cerebrospinal fluid after allogeneic hematopoietic stem cell transplantation in a child with acute lymphoblastic leukemia

We report a case of EBV encephalitis in a seven‐yr‐old child with Ph+ ALL. Two months after an allogeneic HSCT from his HLA mismatched mother, the patient showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood and CSF PCR analyses were negative for the most common viruses involved in immunocompromised patients including EBV. A cerebral biopsy was performed, which showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis performed on brain tissue was positive only for the EBV genome, while extensive investigations for other viral infections were negative. The patient's neurological symptoms rapidly worsened and he died two months later. This case report suggests that in patients presenting neurological and radiological signs of encephalitis after an HSCT, an EBV involvement should be considered, even in the absence of CSF and blood PCR virus detection.
Testing for soil-transmitted helminth transmission elimination: Analysing the impact of the sensitivity of different diagnostic tools

In recent years, an increased focus has been placed upon the possibility of the elimination of soil-transmitted helminth (STH) transmission using various interventions including mass drug administration. The primary diagnostic tool recommended by the WHO is the detection of STH eggs in stool using the Kato-Katz (KK) method. However, detecting infected individuals using this method becomes increasingly difficult as the intensity of infection decreases. Newer techniques, such as qPCR, have been shown to have greater sensitivity than KK, especially at low prevalence. However, the impact of using qPCR on elimination thresholds is yet to be investigated. In this paper, we aim to quantify how the sensitivity of these two diagnostic tools affects the optimal prevalence threshold at which to declare the interruption of transmission with a defined level of confidence. A stochastic, individual-based STH transmission model was used in this study to simulate the transmission dynamics of Ascaris and hookworm. Data from a Kenyan deworming study were used to parameterize the diagnostic model which was based on egg detection probabilities. The positive and negative predictive values (PPV and NPV) were calculated to assess the quality of any given threshold, with the optimal threshold value taken to be that at which both were maximised. The threshold prevalence of infection values for declaring elimination of Ascaris transmission were 6% and 12% for KK and qPCR respectively. For hookworm, these threshold values are lower at 0.5% and 2% respectively. Diagnostic tests with greater sensitivity are becoming increasingly important as we approach the elimination of STH transmission in some regions of the world. For declaring the elimination of transmission, using qPCR to diagnose STH infection results in the definition of a higher prevalence, than when KK is used.
Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection

OBJECTIVES:Needle liver biopsy has been shown to have a high rate of sampling error in patients with diffuse parenchymal liver diseases. In these cases, the sample of liver tissue does not reflect the true degree of inflammation, fibrosis, or cirrhosis, despite an adequate sample size. The aim of this study was to determine the rate and extent of sampling error in patients with chronic hepatitis C virus infection, and to assess the intraobserver variation with the commonly used scoring system proposed by Scheuer and modified by Batts and Ludwig.METHODS:A total of 124 patients with chronic hepatitis C virus infection underwent simultaneous laparoscopy-guided biopsies of the right and left hepatic lobes. Formalin-fixed paraffin-embedded sections were stained with hematoxylin and eosin and with trichrome. The slides were blindly coded and randomly divided among two hepatopathologists. Inflammation and fibrosis were scored according to the standard grading (inflammation) and staging (fibrosis) method based on the modified Scheuer system. Following the interpretation, the slides were uncoded to compare the results of the right and left lobes. Fifty of the samples were blindly resubmitted to each of the pathologists to determine the intraobserver variation.RESULTS:Thirty of 124 patients (24.2%) had a difference of at least one grade, and 41 of 124 patients (33.1%) had a difference of at least one stage between the right and left lobes. In 18 patients (14.5%), interpretation of cirrhosis was given in one lobe, whereas stage 3 fibrosis was given in the other. A difference of two stages or two grades was found in only three (2.4%) and two (1.6%) patients, respectively. Of the 50 samples that were examined twice, the grading by each pathologist on the second examination differed from the first examination in 0% and 4%, and the staging differed in 6% and 10%, respectively. All observed variations were of one grade or one stage.CONCLUSIONS:Liver biopsy samples taken from the right and left hepatic lobes differed in histological grading and staging in a large proportion of chronic hepatitis C virus patients; however, differences of more than one stage or grade were uncommon. A sampling error may have led to underdiagnosis of cirrhosis in 14.5% of the patients. These differences could not be attributed to intraobserver variation, which appeared to be low.