Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Primary Effusion Lymphoma Engraftment in Scid Mice by Morpholino Oligomers against Early Lytic Genes of Kaposi'S Sarcoma-Associated Herpesvirus

Background Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with several malignant diseases, including Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease. The objectives of this study were to investigate the use of peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) against KSHV early lytic genes and to assess their efficacy in severe combined immunodeficiency disease (SCID) mice against PEL engraftment. PPMOs are short, single-stranded DNA analogues that contain a backbone of morpholine rings and phosphorodiamidate linkages and have high delivery efficiency into cells. Methods PEL cells were treated with PPMOs against viral interferon regulatory factor 1 (vIRF-1) and expression of vIRF-1 was analysed. PPMOs against vIRF-1 and viral interleukin-6 (vIL-6) were evaluated against PEL cell engraftment in SCID mice. The PPMOs were incubated with BCBL-1 cells and then introduced into the peritoneal cavities of SCID mice, followed by 9 more doses of PPMOs administered at 2-day intervals. At weeks 3 and 9 after BCBL-1 delivery, peritoneal lavage was collected and the ratio of PEL cells among total cells was determined by flow cytometry analysis. Results Treatment of PEL cells with PPMOs against vIRF-1 led to a reduction of vIRF-1 expression in a dose-dependent manner. Reduction of vIRF-1 expression resulted in higher levels of cellular interferon regulatory factor 3 and of signal transducer and activator of transcription 1. SCID mice receiving a PPMO against vIL-6 had no engraftment of PEL cells and remained healthy throughout the 120-day study. Conclusions This study showed that PPMOs can be effective antiviral agents against KSHV. Blocking the expression of early lytic genes might be beneficial for the control of KSHV-associated malignant diseases.
Potentials of Digitally Sampling Scintillation Pulses in Timing Determination in PET

We investigate the potentials of digitally sampling scintillation pulses techniques for positron emission tomography (PET) in this paper, focusing on the determination of the event time. We have built, and continue building, a digital library of PET event waveforms generated with various combinations of photo-detectors and scintillator materials, with various crystal sizes. Events in this digital library are obtained at a high sampling of 20 GSps (Giga-samples per second) so that their waveforms are recorded with high accuracy. To explore the potential advantages of digitally sampling scintillation pulses, we employ a dataset in the above-mentioned library to evaluate two methods for digitizing the event pulses and linear interpolation techniques to analyze the resulting digital samples. Our results show that the two digitization methods that we studied can yield a coincidence timing resolution of about 300 ps FWHM when applied to events generated by a pair of LSO + PMT detector units. This timing resolution is comparable with that is achieved by the same detector pair with a constant fraction discriminator (CFD). As a benchmark, regular-time sampling (RTS) method, usually implemented with very fast traditional analog-to-digital converters (ADCs) for digitizing scintillation pulses, is not feasible for a multi-channel system like a PET system. Digitizing scintillation pulses with multi-voltage threshold (MVT) method could be implemented at a reasonable cost for a PET system. With digitized PET event samples, various digital signal processing (DSP) techniques can be implemented to determine event arrival time. Our results have therefore demonstrated the promising potentials of digitally sampling scintillation pulses techniques in PET imaging.
Strain Characteristics of  ${\hbox {CO}}_{2}$-Laser-Carved Long Period Fiber Gratings

Unique strain characteristics of long period fiber gratings (LPFG) fabricated by a focused CO2 laser beam carving periodic grooves on the fiber are investigated for the first time to our knowledge. Resonant wavelength, transmission attenuation, and polarization dependent loss (PDL) of the CO2-laser-carved LPFG are found to depend strongly on the tensile strain applied, and their strain sensitivities are dependent on the depth of grooves and/or the initial refractive index modulation. The average strain sensitivity of resonant wavelength for LPFG is increased by 229 times and is up to -102.89 nm/mepsiv by means of carving periodic grooves on the fiber. When a stretching force is applied to the LPFG, the resonant wavelength can "blue" shift by -11.84 nm, the absolute value of peak transmission attenuation and the maximum PDL can be increased by 25.913 and 26.535 dB, respectively. The CO2-laser-carved LPFG combines the features of the three types of LPFGs reported previously, i.e, the CO 2-laser-induced LPFGs without physical deformation, the corrugated LPFGs fabricated by hydrofluoric acid etching, and the microbend-induced LPFGs. The mechanisms of refractive index modulation in the CO2-laser-carved LPFGs under tensile strain are rather complicated and may be regarded as a combination of the stress-relaxation-, the groove-, the strain-, and the microbend-induced refractive index perturbations
A fast scan synthesizer-based microwave spectrometer

For a long time it was generally agreed that microwave PLL-spectrometers are rather complicated devices which allows to record molecular spectra rather slowly and in rather narrow frequency range. Therefore for full frequency range scan some alternative techniques were applied. There are two rather similar approaches: the so called RAD-3 spectrometer [1] and the Fast Scan Submillimeter Spectroscopic Technique (FASSST) spectrometer [2, 3]. Both these instruments based on application of BWO have essentially common feature: they do not use a phase-locked system for BWO frequency stabilization. Main advantage of both above-mentioned techniques is the possibility to obtain wide-range frequency scan. In addition FASSST spectrometer allows to record molecular spectra very rapidly. However the absence of phase-locked system leads to a principal disadvantage: both spectrometers provide rather low measurement accuracy. Typically, the uncertainties of the frequency determination of spectrometers without phase-locked system are about two orders of magnitude worse than those of PLL-spectrometers.
Playing the manic game. Interpersonal maneuvers of the acutely manic patient.

THE acutely manic patient, with his ability to create interpersonal havoc with family and therapist alike, can be one of the most challenging, taxing, and difficult of patients. It is our purpose to describe the character structure of the acutely manic patient, to define his patterns of interaction and communication, and to emphasize the impact these qualities have upon those around him. While previous studies have described the intrapsychic dynamics, pathogenesis, and character structure of patients suffering from manic-depressive psychoses, 1-5 the fashion with which the acutely manic patient deals with others, and the impact this has on them, has received sparse attention. Dooley 1 described patients with frequent manic attacks as being headstrong, selfsufficient, know-it-all types of people who will get the upper hand of the analyst. Gibson 2 noted that while manic-depressive individuals appear remarkably insensitive to interpersonal subtleties on a conscious level, they
Effect of drugs modulating serotonergic system on the analgesic action of paracetamol in mice

Objective: The underlying mechanisms for the analgesic action of paracetamol (PCT) are still under considerable debate. It has been recently proposed that PCT may act by modulating the Serotonin system. This study was conducted to verify the influence of Serotonin modulating drugs (buspirone, ondansetron, and fluoxetine) on the analgesic effect of PCT. Materials and Methods: Thirty adult albino mice were assigned to five groups: Normal saline, PCT, fluoxetine selective serotonin reuptake inhibitor (SSRI) + PCT, buspirone (5-HT1A Agonist) + PCT, and ondansetron (5HT3 antagonist) + PCT. Hot-plate and formalin test were used to determine pain threshold, tests being conducted 60 min after the last treatment. Statistical analysis was done using analysis of variance followed by Dunnet's test. Results: Coadministration of buspirone with PCT attenuated the antinociceptive activity of PCT (P < 0.001), whereas fluoxetine + PCT increased pain threshold in the hot-plate and formalin test (P = 0.0046). Analgesic effect of PCT was not affected by ondansetron in formalin models. It attenuated analgesic action of PCT in hot-plate test (P = 0.0137). Conclusion: The results suggest that 5-HT1 receptors could also be responsible for the analgesic effect of PCT. Also, higher analgesia is produced by co-administration of SSRI (fluoxetine) + PCT.
On the activation of soluble guanylyl cyclase by nitric oxide

Soluble guanylyl cyclase (sGC) is the major cellular receptor for the intercellular messenger nitric oxide (NO) and mediates a wide range of physiological effects through elevation of intracellular cGMP levels. Critical to our understanding of how NO signals are decoded by receptive cells and translated into a useful physiological response is an appreciation of the molecular and kinetic details of the mechanism by which NO activates sGC. It is known that NO binds to a haem prosthetic group on the receptor and triggers a conformational change that increases the catalysis of cGMP synthesis by several hundred-fold. The haem is covalently attached to sGC at His-105 of the β1 subunit, and it was thought previously that activation of sGC by NO occurs in two steps: binding of NO to the haem to form a biliganded state and then rupture of the bond to His-105 triggering an increase in catalytic activity. A recent investigation of the kinetics of sGC activation [Zhao, Y. , Brandish, P. E. , Ballou, D. P. & Marletta, M. A. (1999) Proc. Natl. Acad. Sci. USA, 96, 14753–14758], however, proposed an additional mechanism by which NO regulates sGC activity, namely, by influencing the rate of cleavage of the His-105 bond. The existence of a second (unidentified) NO-binding site on the enzyme was hypothesized and suggested to be fundamental to cellular NO-signal transduction. Here, we show that it is unnecessary to postulate any such additional mechanism because the results obtained are predicted by the simpler model of sGC activation with a single NO-binding event.
Th‐1 cytokines gene polymorphism in human brucellosis

Brucellosis is a worldwide zoonosis. Infection with Brucella species results in the activation of cell‐mediated immune response. The interaction between Th1and Th2 cytokines determines the outcome of disease. Production of each cytokine is in turn affected by genetic factors. In this study, we investigated the possible association between Th1 cytokines gene polymorphism and brucellosis. Different genotypes of TNF‐α, IFN‐γ and IL‐2 were determined by polymerase chain reaction–sequence‐specific primer in 47 patients with brucellosis and in 166 healthy controls. Allele frequencies of these genotypes were compared using the χ2 test. The results showed a significant difference in the TNF‐α genotype GG/GG in patients in comparison with controls (76.7% vs. 21%) (P = 0.001, OR = 12.42, 95%CI 5.7–27.7). There was no significant difference in the frequency distribution of the IFN‐γ genotypes between two groups. IL‐2 GG genotype at position −330 was about two times more common in cases than in controls, but the difference was not significant (10.6 vs. 4.6 P value = 0.09). This study shows that genetically low producers of TNF‐α are possibly susceptible to brucellosis and raise doubt about the role of gene polymorphism of INF‐γ in brucellosis which was demonstrated in previous studies. It seems that patients with brucellosis did not have a defect in producing IL‐2 with even a trend towards producing higher amounts of this cytokine.
Identification of Protein-Ligand Binding Sites by Sequence Information and Ensemble Classifier

Identifying protein-ligand binding sites is an important process in drug discovery and structure-based drug design. Detecting protein-ligand binding sites is expensive and time-consuming by traditional experimental methods. Hence, computational approaches provide many effective strategies to deal with this issue. Recently, lots of computational methods are based on structure information on proteins. However, these methods are limited in the common scenario, where both the sequence of protein target is known and sufficient 3D structure information is available. Studies indicate that sequence-based computational approaches for predicting protein-ligand binding sites are more practical. In this paper, we employ a novel computational model of protein-ligand binding sites prediction, using protein sequence. We apply the Discrete Cosine Transform (DCT) to extract feature from Position-Specific Score Matrix (PSSM). In order to improve the accuracy, Predicted Relative Solvent Accessibility (PRSA) information is also utilized. The predictor of protein-ligand binding sites is built by employing the ensemble weighted sparse representation model with random under-sampling. To evaluate our method, we conduct several comprehensive tests (12 types of ligands testing sets) for predicting protein-ligand binding sites. Results show that our method achieves better Matthew's correlation coefficient (MCC) than other outstanding methods on independent test sets of ATP (0.506), ADP (0.511), AMP (0.393), GDP (0.579), GTP (0.641), Mg2+ (0.317), Fe3+ (0.490) and HEME (0.640). Our proposed method outperforms earlier predictors (the performance of MCC) in 8 of the 12 ligands types.
Single‐Arm Study for the Characterization of Human Tissue Response to Injectable Poly‐L‐Lactic Acid

BACKGROUND Injectable poly‐L‐lactic acid (PLLA) is a synthetic polymer indicated for the correction of facial wrinkles and folds. Animal studies have shown that implantation of PLLA stimulates collagen synthesis; human studies have been limited. OBJECTIVE To investigate human tissue response to injectable PLLA. METHODS AND MATERIALS In this exploratory single‐arm, open‐label study, 14 healthy subjects were administered injectable PLLA; punch biopsies at 3, 6, and 12 months were analyzed for qualitative and quantitative changes from baseline in collagen types I and III and assessed for inflammatory responses. RESULTS Quantitative and qualitative increases were observed for collagen types I and III at 3 and 6 months and were statistically significant for collagen type I at 3 and 6 months. Post hoc analyses at 12 months showed nominal collagen increases but were hindered by technical difficulties. The degree of inflammatory response was similar to baseline at 3, 6, and 12 months; all subjects were found to have no or mild inflammation after baseline. Adverse events were mild and among those reported previously. CONCLUSION Results of this study in humans found statistically significant stimulation of collagen type I with no or mild inflammatory response after administration of injectable PLLA.
Cytoreduction and Stem Cell Mobilization with a Regimen of Paclitaxel, Etoposide and Cyclophosphamide Followed by Autologous Transplantation Using a Preparative Regimen of Busulfan, Etoposide and Cyclophosphamide for Patients with Advanced Lymphoma

Forty-one patients with advanced Hodgkin’s disease or intermediate or high-grade lymphoma, after having received standard salvage chemotherapy, were treated with a nonablative high-dose regimen of paclitaxel, etoposide and cyclophosphamide (D-TEC) to optimally cytoreduce their disease and simultaneously mobilize peripheral blood stem cells. This regimen produced a response rate of 78% (35% complete and 43.2% partial response) and mobilized sufficient peripheral blood stem cells in 94% of the patients. Thirty-two of these patients then underwent autologous progenitor cell transplantation after ablative conditioning with busulfan, etoposide and cyclophosphamide. Actuarial overall survival at 61 months was 71.9% with an event-free survival (EFS) of 65.6%. Median EFS was 24.4 months. EFS of patients responsive to salvage chemotherapy was 75% at 61 months, compared to 33.3% at 51.4 months in patients resistant to salvage chemotherapy. EFS of patients with disease sensitive to D-TEC was 75% at 61 months compared to 0% at 13.1 months in patients resistant to D-TEC. In a multivariate analysis, the only significant parameter for transplant outcome was sensitivity to D-TEC (p = 0.016), but not sensitivity to standard salvage chemotherapy. Aggressive cytoreduction may permit even those patients who are resistant to standard salvage chemotherapy to become successful transplant candidates.
Economic appraisal of antidepressant pharmacotherapy: critical review of the literature and future directions

In the United States, an estimated $44 billion is expended annually for the treatment, morbidity, and mortality associated with depression. Domestic and international cost‐containment initiatives are mandating a demonstration of value for money defined in terms of a measurable health and/or financial outcome, and, in the case of medicines, attributable to a given expenditure for a given pharmacotherapeutic option. Recent pharmacotherapeutic advances in the treatment of depression have included the development of selective serotonin reuptake inhibitors (SSRIs), thereby providing an alternative to tricyclic antidepressants (TCAs). Herein, we review the pharmacoeconomic literature relative to antidepressant pharmacotherapy and identify issues for future inquiry. Depression and Anxiety, Volume 8, Supplement 1:121–127, 1998. © 1998 Wiley‐Liss, Inc.
Neural networks – a diagnostic tool in acute myocardial infarction with concomitant left bundle branch block

The prognosis of acute myocardial infarction (AMI) improves by early revascularization. However the presence of left bundle branch block (LBBB) in the electrocardiogram (ECG) increases the difficulty in recognizing an AMI and different ECG criteria for the diagnosis of AMI have proved to be of limited value. The purpose of this study was to detect AMI in ECGs with LBBB using artificial neural networks and to compare the performance of the networks to that of six sets of conventional ECG criteria and two experienced cardiologists. A total of 518 ECGs, recorded at an emergency department, with a QRS duration >120 ms and an LBBB configuration, were selected from the clinical ECG database. Of this sample 120 ECGs were recorded on patients with AMI, the remaining 398 ECGs being used as a control group. Artificial neural networks of feed‐forward type were trained to classify the ECGs as AMI or not AMI. The neural network showed higher sensitivities than both the cardiologists and the criteria when compared at the same levels of specificity. The sensitivity of the neural network was 12% (P = 0·02) and 19% (P = 0·001) higher than that of the cardiologists. Artificial neural networks can be trained to detect AMI in ECGs with concomitant LBBB more effectively than conventional ECG criteria or experienced cardiologists.
What is the best strategy to reduce the burden of occupational asthma and allergy in bakers?

Rationale Insight into the effectiveness of intervention strategies will help realise a decrease in the occupational disease burden from (allergic) respiratory diseases in the bakery population. Objectives To use a simulation model to assess the impact of different intervention strategies on the disease burden of the bakery population over time. Methods A recently developed dynamic population based model was used to prospectively evaluate the impact on disease burden resulting from different intervention strategies. We distinguished interventions based on exposure reductions for flour dust and fungal α-amylase, health surveillance combined with reduction in exposure, and pre-employment screening. Main Results The impact of most interventions on disease burden was limited, generally less than 50% for lower respiratory symptoms and disabling occupational asthma. Only the rigorous health surveillance strategy, identifying workers who are sensitised or report upper respiratory symptoms and decreasing their individual exposures by 90% shortly after diagnosis, resulted in a decrease of almost 60% in disease burden after 20 years. Conclusions This study demonstrates that different intervention strategies have substantially different impacts on the burden of disease. The time window during which changes occur differs considerably between strategies. This information can assist policy makers in their choice of intervention and gives guidance for achievable reductions in disease burden.
CTHRC1 activates pro-tumorigenic signaling pathways in hepatocellular carcinoma

CTHRC1 expression is involved in invasion and metastasis in various tumors. However, the molecules involved in its signaling pathways in hepatocellular carcinoma (HCC) remain elusive. The migration and invasion abilities of HCC cells stably expressing CTHRC1 were assessed in vitro and in vivo with a mouse model. Moreover, signaling pathways involved in invasion and metastasis were analyzed. CTHRC1 was abundantly expressed in HCC cell lines and HCC tissues. CTHRC1 was also detectable in the serum of HCC patients, compared with non-tumor controls. CTHRC1 mRNA was positively correlated with large tumor size (p <0.003), Edmondson differentiation grade (p <0.0001), microvessel invasion (p <0.05), intrahepatic metastasis (p <0.005), and HCC stage (AJCC, p <0.0001). Ectopic expression of CTHRC1 in HepG2 cells promoted cell migration and invasiveness in vitro, and promoted tumor metastasis in a lung metastasis mouse model. Knockdown of CTHRC1 by short hairpin RNA (shRNA) in HCC cells suppressed migratory and invasive abilities. Growth factor-mediated CTHRC1 expression promoted cancer cell invasiveness and metastasis through activation of CREB/Snail signaling, which induced EMT change and MMPs expression. Therefore, CTHRC1 and its downstream molecules may be potential therapeutic targets for HCC invasion and metastasis.
Rapamycin impairs HPD‐induced beneficial effects on glucose homeostasis

Rapamycin, which is used clinically to treat graft rejection, has also been proposed to have an effect on metabolic syndrome; however, very little information is available on its effects in lean animals/humans. The purpose of this study was to characterize further the effects of the continuous use of rapamycin on glucose homeostasis in lean C57BL6/J mice.
A semiautomatic saliency model and its application to video compression

This work aims to apply visual-attention modeling to attention-based video compression. During our comparison we found that eye-tracking data collected even from a single observer outperforms existing automatic models by a significant margin. Therefore, we offer a semiautomatic approach: using computer-vision algorithms and good initial estimation of eye-tracking data from just one observer to produce high-quality saliency maps that are similar to multi-observer eye tracking and that are appropriate for practical applications. We propose a simple algorithm that is based on temporal coherence of the visual-attention distribution and requires eye tracking of just one observer. The results are as good as an average gaze map for two observers. While preparing the saliency-model comparison, we paid special attention to the quality-measurement procedure. We observe that many modern visual-attention models can be improved by applying simple transforms such as brightness adjustment and blending with the center-prior model. The novel quality-evaluation procedure that we propose is invariant to such transforms. To show the practical use of our semiautomatic approach, we developed a saliency-aware modification of the x264 video encoder and performed subjective and objective evaluations. The modified encoder can serve with any attention model and is publicly available.