Miracle-dz/UniFAR-FTUs huggingface dataset:
Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti‐myeloma activity in vitro and in vivo

This study investigated the cytotoxicity and mechanism of action of AS703026, a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma (MM). AS703026 inhibited growth and survival of MM cells and cytokine‐induced osteoclast differentiation more potently (9‐ to 10‐fold) than AZD6244. Inhibition of proliferation induced by AS703026 was mediated by G0‐G1 cell cycle arrest and was accompanied by reduction of MAF oncogene expression. AS703026 further induced apoptosis via caspase 3 and Poly ADP ribose polymerase (PARP) cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). Importantly, AS703026 sensitized MM cells to a broad spectrum of conventional (dexamethasone, melphalan), novel or emerging (lenalidomide, perifosine, bortezomib, rapamycin) anti‐MM therapies. Significant tumour growth reduction in AS703026‐ vs. vehicle‐treated mice bearing H929 MM xenograft tumours correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels in vivo. Moreover, AS703026 (<200 nmol/l) was cytotoxic against the majority of tumour cells tested from patients with relapsed and refractory MM (84%), regardless of mutational status of RAS and BRAF genes. Importantly, BMSC‐induced viability of MM patient cells was similarly blocked within the same dose range. Our results therefore support clinical evaluation of AS703026, alone or in combination with other anti‐MM agents, to improve patient outcome.
Healthy Human Subjects Have CD4+ T Cells Directed against H5N1 Influenza Virus1

It is commonly perceived that the human immune system is naive to the newly emerged H5N1 virus. In contrast, most adults have been exposed to influenza A H1N1 and H3N2 viruses through vaccination or infection. Adults born before 1968 have likely been exposed to H2N2 viruses. We hypothesized that CD4+ T cells generated in response to H1N1, H3N2, and H2N2 influenza A viruses also recognize H5N1 epitopes. Tetramer-guided epitope mapping and Ag-specific class II tetramers were used to identify H5N1-specific T cell epitopes and detect H5N1-specific T cell responses. Fifteen of 15 healthy subjects tested had robust CD4+ T cell responses against matrix protein, nucleoprotein, and neuraminidase of the influenza A/Viet Nam/1203/2004 (H5N1) virus. These results are not surprising, because the matrix protein and nucleoprotein of influenza A viruses are conserved while the neuraminidase of the H5N1 virus is of the same subtype as that of the circulating H1N1 influenza strain. However, H5N1 hemagglutinin-reactive CD4+ T cells were also detected in 14 of 14 subjects examined despite the fact that hemagglutinin is less conserved. Most were cross-reactive to H1, H2, or H3 hemagglutinin epitopes. H5N1-reactive T cells were also detected ex vivo, exhibited a memory phenotype, and were capable of secreting IFN-γ, TNF-α, IL-5, and IL-13. These data demonstrate the presence of H5N1 cross-reactive T cells in healthy Caucasian subjects, implying that exposure to influenza A H1N1, H3N2, or H2N2 viruses through either vaccination or infection may provide partial immunity to the H5N1 virus.
Neuromuscular fatigue after a ski skating marathon.

The aim of this study was to characterize neuromuscular fatigue in knee extensor muscles after a marathon skiing race (mean +/- SD duration = 159.7 +/- 17.9 min). During the 2 days preceding the event and immediately after, maximal percutaneous electrical stimulations (single twitch, 0.5-s tetanus at 20 and 80 Hz) were applied to the femoral nerve of 11 trained skiers. Superimposed twitches were also delivered during maximal voluntary contraction (MVC) to determine maximal voluntary activation (% VA). EMG was recorded from the vastus lateralis muscle. MVC decreased with fatigue from 171.7 +/- 33.7 to 157.3 +/- 35.2 Nm (-8.4%; p < 0.005) while % VA did not change significantly. The RMS measured during MVC and peak-to-peak amplitude of the compound muscle action potential (PPA) from the vastus lateralis decreased with fatigue by about 30% (p < 0.01), but RMS.PPA-1 was similar before and after the ski marathon. Peak tetanus tension at 20 Hz and 80 Hz (P(0)20 and P(0)80, respectively) did not change significantly, but P(0)20.P(0)80-1 increased (p < 0.05) after the ski marathon. Data from electrically evoked single twitches showed greater peak mechanical response, faster rate of force development, and shorter contraction time in the fatigued state. From these results it can be concluded that a ski skating marathon (a) alters slightly but significantly maximal voluntary strength of the knee extensors without affecting central activation, and (b) induces both potentiation and fatigue.
An Enzymatic Footprinting Analysis of the Interaction of 40S Ribosomal Subunits with the Internal Ribosomal Entry Site of Hepatitis C Virus

ABSTRACT Hepatitis C virus translation is initiated on a ∼330-nucleotide (nt)-long internal ribosomal entry site (IRES) at the 5′ end of the genome. In this process, a 43S preinitiation complex (comprising a 40S ribosomal subunit, eukaryotic initiation factor 3 (eIF3), and a ternary [eIF2-GTP-initiator tRNA] complex) binds the IRES in a precise manner so that the initiation codon is placed at the ribosomal P site. This binding step involves specific interactions between the IRES and different components of the 43S complex. The 40S subunit and eIF3 can bind to the IRES independently; previous analyses revealed that eIF3 binds specifically to an apical half of IRES domain III. Nucleotides in the IRES that are involved in the interaction with the 40S subunit were identified by RNase footprinting and mapped to the basal half of domain III and in domain IV. Interaction sites were identified in locations that have been found to be essential for IRES function, including (i) the apical loop residues GGG266-268 in subdomain IIId and (ii) the pseudoknot. Extensive protection from RNase cleavage also occurred downstream of the pseudoknot in domain IV, flanking both sides of the initiation codon and corresponding in length to that of the mRNA-binding cleft of the 40S subunit. These results indicate that the 40S subunit makes multiple interactions with the IRES and suggest that only nucleotides in domain IV are inserted into the mRNA-binding cleft of the 40S subunit.
Heartbeat Classification Using Feature Selection Driven by Database Generalization Criteria

In this paper, we studied and validated a simple heart beat classifier based on ECG feature models selected with the focus on an improved generalization capability. We considered features from the RR series, as well as features computed from the ECG samples and different scales of the wavelet transform, at both avail able leads. The classification performance and generalization were studied using publicly available databases: the MIT-BIH Arrhythmia, the MIT-BIH Supraventricular Arrhythmia, and the St. Pe tersburg Institute of Cardiological Technics (INCART) databases. The Association for the Advancement of Medical Instrumentation recommendations for class labeling and results presentation were followed. A floating feature selection algorithm was used to obtain the best performing and generalizing models in the training and validation sets for different search configurations. The best model found comprehends eight features, was trained in a partition of the MIT-BIH Arrhythmia, and was evaluated in a completely disjoint partition of the same database. The results obtained were: global accuracy of 93%; for normal beats, sensitivity (S) 95%, positive predictive value (P+) 98%; for supraventricular beats, S 11%, P+ 39%; and for ventricular beats S 81%, P+ 87%. In order to test the generalization capability, performance was also evaluated in the INCART, with results comparable to those obtained in the test set. This classifier model has fewer features and performs better than other state-of-the-art methods with results suggesting better generalization capability.
Examining health literacy among urban African-American adolescents with asthma

Abstract Objective: This exploratory study assessed health literacy among urban African-American high school students to improve understanding of the association between adolescent health literacy and asthma. Methods: We conducted a secondary data analysis of the control group (n = 181) of the Puff City randomized controlled trial (2006–2010), a web-based intervention to promote asthma management among students, grades 9 through 12. A validated self-report 3-item health literacy screening instrument was completed at final online follow-up survey. Logistic regression was used to explore the association between health literacy, demographic characteristics, quality of life, asthma management, and health care utilization. Results: Multivariate analysis revealed that an overall inadequate health literacy score was associated with students who were more likely to be younger (OR 0.61; 95% CI 0.44–0.84), not on Medicaid (OR 0.36; 95% CI 0.17–0.76), have at least one hospitalization (OR 1.29; 95% CI 1.07–1.56); and a lower overall quality of life (OR 0.75; 95% CI 0.59–0.95). Those lacking confidence in filling out medical forms, needing help reading hospital materials, and having difficulty understanding written information were more likely to not have a rescue inhaler (OR 0.49; 95% CI 0.25–0.94), have one or more emergency visits (OR 1.21 95% CI 1.02–1.43), and one or more hospitalizations (OR 1.19; 95% CI 1.01–1.41), respectively. Conclusions: The findings indicate a significant association between inadequate health literary and suboptimal asthma management. It is important to advance understanding of adolescent health literacy, especially those at-risk, as they assume asthma self-management tasks and move toward independent adult self-care.
Directed evolution approach to a structural genomics project: Rv2002 from Mycobacterium tuberculosis

One of the serious bottlenecks in structural genomics projects is overexpression of the target proteins in soluble form. We have applied the directed evolution technique and prepared soluble mutants of the Mycobacterium tuberculosis Rv2002 gene product, the wild type of which had been expressed as inclusion bodies in Escherichia coli. A triple mutant I6T/V47M/T69K (Rv2002-M3) was chosen for structural and functional characterizations. Enzymatic assays indicate that the Rv2002-M3 protein has a high catalytic activity as a NADH-dependent 3α, 20β-hydroxysteroid dehydrogenase. We have determined the crystal structures of a binary complex with NAD+ and a ternary complex with androsterone and NADH. The structure reveals that Asp-38 determines the cofactor specificity. The catalytic site includes the triad Ser-140/Tyr-153/Lys-157. Additionally, it has an unusual feature, Glu-142. Enzymatic assays of the E142A mutant of Rv2002-M3 indicate that Glu-142 reverses the effect of Lys-157 in influencing the pKa of Tyr-153. This study suggests that the Rv2002 gene product is a unique member of the SDR family and is likely to be involved in steroid metabolism in M. tuberculosis. Our work demonstrates the power of the directed evolution technique as a general way of overcoming the difficulties in overexpressing the target proteins in soluble form.
Impact of GaN channel scaling in InAlN/GaN HEMTs

This paper studies the impact of GaN channel thickness scaling on the DC and RF performance of InAlN/GaN high electron mobility transistors (HEMTs) with 30–230 nm gate length. Thin GaN channels increase the charge confinement, which improves immunity to short-channel effects. However, as the channel thickness scales down, mobility degradation is observed due to additional interface and alloy scattering caused by the InGaN back barrier layer. Due to this higher interface scattering, the effective electron velocity decreases when thinning down the channel from 26 nm (ve=1.45 × 107 cm/s) down to 4 nm (ve=1.16 × 107 cm/s).
Multi-channel noise reduction for hands-free voice communication on mobile phones

Noise reduction technologies have been applied to enhance the intelligibility of voice communications. However, existing methods are vulnerable to complex non-stationary noisy conditions, which are commonly encountered in real world hands-free scenarios. Additionally, the existing methods do not fully take the advantage of the deployment of multi-channel microphone arrays on the burgeoning high-end mobile phones. In this paper, we propose a noise estimation method based on a hybrid of efficient single channel and globally optimized multi-channel microphone noise estimation using adaptive noise coherence models. Evaluation results on real-world recordings collected via a smartphone confirm its superior effectiveness to suppress the fast-varying noises compared to the state-of-the-art baseline methods.
8-Gb/s RGBY LED-Based WDM VLC System Employing High-Order CAP Modulation and Hybrid Post Equalizer

In this paper, for the first time, we propose the use of a hybrid post equalizer in a high-order carrierless-amplitude-and-phase-modulation-based visible light communication (VLC) system. The hybrid equalizer consists of a linear equalizer, a Volterra-series-based nonlinear equalizer, and a decision-directed least mean squares equalizer to simultaneously mitigate the linear and nonlinear distortions of the VLC system. A commercially available red-blue-green-yellow light-emitting diode (RBGY LED) is utilized for four-wavelength multiplexing. By the hybrid equalizer, an aggregate data rate of 8 Gb/s is experimentally achieved over a 1-m indoor free-space transmission with the bit error rate (BER) below the 7% forward error correction (FEC) limit of 3.8 × 10-3. To the best of our knowledge, this is the highest data rate ever reported in high-speed VLC systems.
Comprehensive analysis of long non-coding RNA expression profiles in hepatitis B virus-related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common kinds of malignancies and is closely correlated with hepatitis B virus (HBV) infection. Recent evidence has proved that long non-coding RNAs (lncRNAs) are implicated in development and progression of cancer. However, the contributions of lncRNAs to HBV-related HCC remain largely unknown. Here, we comprehensively investigated lncRNA expression profiles in HBV-related HCC by annotating and analyzing microarray datasets. By analyzing 42 HCC tissue samples with different etiology (HBV-related, alcohol-related, and primary HCC) and 15 normal liver tissues, we identified 182 lncRNAs that were specifically differentially expressed in HBV-related HCC, namely HBV-related HCC specific lncRNAs(HH-lncRNAs). Using an online function annotation tool, we found these HH-lncRNAs were associated many oncogenes and immunity related biological processes. 6 candidate HH-lncRNAs were selected and further validated by quantitative real-time PCR analysis in a cohort of HCC tissue samples. Function of a candidate HH-lncRNAs, BAIAP2-AS1, was further predicted by co-expression network and gene set enrichment analysis. These findings provide insights into HH-lncRNAs and offer resource for further search of biomarkers and therapeutic targets of HBV-related HCC.
Evolution of fungal population and mycotoxins in sorghum silage

ABSTRACT Silage, one of the most important feed sources for cattle, is vulnerable to contamination by spoilage moulds and mycotoxins because ensilage materials are excellent substrates for fungal growth. The aim of this study was to identify the mycobiota of sorghum silages, to determine the presence of aflatoxins and fumonisins, and to correlate these results with physical parameters of the silage. A total of 275 samples of sorghum were collected from dairy farms in the south-west region of Uruguay were silage practices are developed. The presence of fungi was observed in all of the sorghum samples with values varying from 0.2 × 104 to 4085 × 104 UFC g−1. Significant difference were detected in the total number of fungi during the storage period; at six months there is a high risk of fungal spoilage. The most frequent genera isolated from sorghum samples were Penicillium (70%), Aspergillus (65%), Absidia (40%), Fusarium (35%), Paecilomyces (35%) and Alternaria, Cladosporium, Gliocadium and Mucor (30%). The toxigenic species most frequently found were Penicillium citrinum, Aspergillus flavus and Fusarium nygamai. Only two samples were contaminated by AFB1 with levels of 1 and 14 µg kg–1. Fumonisin was detected in 40% of freshly harvest samples with levels ranged from 533 µg kg–1 to 933 µg kg–1. The use of silo bags seems to be an effective tool to store sorghum. However, the presence of toxigenic fungi show that regular screening for mycotoxins levels in silages must be performed to avoid the exposure of animals to contaminated feed and the introduction of these compounds into the food chain.
Ureteroscopy in pregnant women for ureteral stone.

INTRODUCTION The occurrence of urolithiasis in pregnancy represents a challenge in both diagnosis and treatment of this condition, because it presents risks not only to the mother but also to the fetus. Surgical treatment may be indicated for patients with infection, persistent pain, and obstruction of a solitary kidney. We present our experience on the management of pregnant patients with ureteral calculi and a review of the literature. MATERIALS AND METHODS The charts of 19 pregnant patients with obstructive ureteral calculi were retrospectively reviewed. Gestational age ranged from 13 to 33 weeks. In all patients, ureteral stone was diagnosed on abdominal ultrasound. In regard to localization, 15 calculi were in the distal ureter, 3 in the proximal ureter, and 1 in the interior of an ureterocele. Calculi size ranged from 6 to 10 mm (mean, 8 mm). The following criteria were used to indicate ureteroscopy: persistent pain with no improvement after clinical treatment, increase in renal dilation, or presence of uterine contractions. Nine patients (47.3%) were submitted to ureteroscopy. All calculi (100%) were removed with a stone basket extractor under continuous endoscopic vision. None of the calculi demanded the use of a lithotriptor. RESULTS Nine patients (47.3%) treated with clinical measurements presented no obstetric complications and spontaneous elimination of the calculi. Nine patients (47.3%) submitted to ureteroscopy had no surgical complications. There was remission of pain in all cases after ureteroscopy and ureteral catheter placement. CONCLUSION The diagnosis and treatment of ureteral lithiasis in pregnant women present potential risks for the fetus and the mother. Conservative management is the first option, but ureteroscopy may be performed with safety and high success rates.
Cardiovascular risk factors, diet and lifestyle among European, South Asian and Chinese adolescents in Canada.

OBJECTIVE The authors previously reported that adult South Asian immigrants to Canada have an increased risk of cardiovascular disease (CVD) compared to their European and Chinese counterparts. It is unknown whether these ethnic differences also exist among adolescents, and whether they are related to diet and lifestyle. The objective of the present study was to assess the prevalence of CVD risk factors among apparently healthy adolescents in the three largest ethnic population groups in Canada (European, South Asian and Chinese). METHODS A cross-sectional study among secondary school students in the Greater Toronto Area was undertaken. A total of 203 adolescents from 62 GTA secondary schools were recruited (48% Europeans, 35% Chinese and 18% South Asians) with a mean age of 17.3±1 years; 72% were female. RESULTS Similar to adults, South Asian adolescents have increased rates of CVD risk factors compared with their European and Chinese peers, including higher prevalence of low high-density lipoprotein levels (P=0.001), high triglycerides (P=0.006) and high triglyceride/high-density lipoprotein levels (P<0.001), despite no significant differences in dietary intake among the ethnic groups. European adolescents had higher rates of self-reported intensity of physical activity (P=0.002) than their Chinese or South Asian peers. CONCLUSIONS Similar to adult data, South Asian adolescents have comparably higher rates of CVD risk factors compared with their European or Chinese peers, which could partly be attributed to lower physical activity in South Asian adolescents. Whether the findings in these selected samples of healthy adolescents can be generalized to their respective populations requires further validation.
Mycophenolate Mofetil for the Treatment of Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology. Despite advances in understanding the pathophysiology underlying this disorder, no effective medical therapy has been identified for halting disease progression. The aim of this investigation was to determine the safety and estimated efficacy of mycophenolate mofetil (MMF) for the treatment of PSC. Thirty patients with PSC received MMF 1 g daily to a maximum of 3 g daily for 1 yr. Liver tests were determined at 3-month intervals with the Mayo risk score calculated at baseline and at the end of therapy. Twenty-three (77%) patients completed 1 yr of therapy. Significant but clinically marginal improvement in serum alkaline phosphatase level after 1 yr of therapy was observed (1135 ± 581 U/L vs 912 ± 463 U/L, p = 0.02). No other significant changes in liver biochemistries or Mayo risk score was observed. Seven patients (23%) discontinued MMF due to adverse events possibly related to therapy. Adverse reactions resolved spontaneously or with dose reduction in 10 (33%) patients. One patient developed pancreatitis, bacterial cholangitis, and sepsis during the eighth month of MMF therapy. No patient developed cytopenia on therapy. In conclusion, MMF does not appear to have clinically important benefits for PSC despite being tolerated by most patients. The results of this pilot study do not support further study of MMF as a single agent in the treatment of PSC.
Improving the provision of driving advice on discharge after abdominal surgery

Abstract Ensuring the safety of patients is a vital duty of a doctor. It is their responsibility to advise patients about activity limitations on discharge from hospital. This study aims to assess the current provision of driving advice for patients after abdominal surgery and institute improvements to this provision of information in North Bristol NHS Trust. A preliminary questionnaire ascertained current doctor’s knowledge regarding limitations of driving postoperatively and whether information was communicated to patients. Baseline retrospective data were collected from electronic discharge summaries to determine documentation of advice provision. Educational interventions were introduced, followed by data collection after each intervention. Initial questionnaires demonstrated poor knowledge amongst doctors and a lack of provision of driving advice postoperatively. After multiple educational interventions, the provision of driving advice on electronic discharge summaries increased from 0% (0) at baseline to 75% (9). Initially, the provision of driving advice postoperatively was poorly documented for inpatients undergoing abdominal surgery; following multiple educational interventions, the provision of written advice improved. Future plans include the introduction of prewritten sentences onto the electronic discharge summaries to facilitate ease of information provision and a reaudit in 12 months.