Miracle-dz/UniFAR-FTUs huggingface dataset:
EVALUATION OF VANCOMYCIN INITIAL DOSING AND THE RESULTANT TROUGH LEVEL IN PAEDIATRIC PATIENTS

This study aims to examine the vancomycin initial dosing and the resultant trough level in paediatric patients. In this retrospective observational study, all therapeutic drug monitoring (TDM) records of paediatric patients admitted to Sabah Women and Children Hospital (SWACH) from January 2011 to September 2013 were reviewed and 116 patients without renal disease were included in the study. Of the total, 38.8% were neonates, 32.8% were infants and 28.4% were children. The majority of the patients were intensive care patients (69.0%) and the most common clinical indication for vancomycin was sepsis (44.8%). The four initial dosing regimens identified were 40 mg/kg/day (38.8%), 30 mg/kg/day (31.0%), 60 mg/kg/day (25.0%) and 45 mg/kg/day (5.2%). The distribution of initial dosing regimen was significantly different between the three age groups (p 20 mg/L) were 43.1% and 17.2% respectively. The distribution of trough level was significantly different between those who received ≤40 mg/kg/day and those who received >40 mg/kg/day (p=0.007). The proportions of those who achieved the target therapeutic range (10–20 mg/L) in the 2 dosing groups were 30.9% and 60.0% respectively. In conclusion, the study showed that the initial dosing of >40 mg/kg/day is more likely to achieve the target therapeutic range (10–20 mg/L) compared to the initial dosing of ≤40 mg/kg/day.
1992 ARRS Executive Council Award. Detection of deep venous thrombosis: prospective comparison of MR imaging with contrast venography.

OBJECTIVE Preliminary reports have described the use of MR imaging for the detection of deep venous thrombosis. However, no prospective study comparing MR imaging with contrast venography (the gold standard) has been reported. Accordingly, we performed a prospective, blinded study of the efficacy of MR imaging in 61 consecutive patients with clinically suspected deep venous thrombosis. In cases of disagreement, additional testing was performed to determine the diagnosis. SUBJECTS AND METHODS From June 1991 to February 1992, 61 patients with clinically suspected deep venous thrombosis were examined with venography and MR imaging. The average time between studies was 3 hr. In 21 of the 61 patients, the final diagnosis was deep venous thrombosis. RESULTS For detection of deep venous thrombosis in the pelvis, the sensitivity of MR imaging was 100% (9/9) with a 95% confidence interval of 72-100% and the specificity was 95% (52/55) with a 95% confidence interval of 85-99%. In the thigh, the sensitivity (16/16) and specificity (43/43) were both 100% with 95% confidence intervals of 83-100% and 93-100%, respectively. In the calf, the sensitivity was 87% (13/15) with a 95% confidence interval of 60-98% and the specificity was 97% (36/37) with a 95% confidence interval of 86-100%. CONCLUSION We found no statistically significant difference between MR imaging and contrast venography in the detection of deep venous thrombosis. This result suggests that MR imaging is at least as sensitive and specific as contrast venography in the detection of deep venous thrombosis.
Grid-connection strategies of the doubly-fed variable speed constant frequency wind power generators with/without load

It is pointed out in this paper that the connection between DFVSCF (doubly-fed variable speed constant frequency) wind power generator and the grid is flexible, which means that by excitation regulation, the stator output voltage can fulfill the condition of grid-connection and the generator can be safely connected to the grid at variable speed. Using the method of field-oriented vector control, the grid-connection principle of DFVSCF wind power generator was investigated in this paper, and two control strategies of the generator for grid-connection with load and without load were established based on stator flux oriented vector control technique. Finally, the experimental research was conducted, whose results verified the correctness and feasibility of the strategies proposed by this paper.
Conceptual Design and Characterization of Contractile Water Jet Thruster Using IPMC Actuator

This paper presents the design, development and characterization of contractile water jet thruster (CWJT) for mini underwater robot. Instead of electric motor, this CWJT utilizes the Ionic Polymer Metal Composite (IPMC) as the actuator to generate the water jet. The main focus of this paper is to analyze the conceptual design of the proposed CWJT which would determine the thrust force value, jet flow behavior and actuator’s stress. Those thrust force and jet flow studies were carried out using Matlab/Simscape simulation software. The actuator stress had been analyzed using COSMOS simulation software. The results showed that there was no significant change for jet velocity at variable cross sectional nozzle area. However, a significant change was detected for jet velocity at different nozzle cross sectional area ratio which was up to 37%. The generated thrust force has proportional relation to the nozzle cross sectional area. Keywords—Contractile water jet thruster, IPMC actuator, Thrust force.
Regulation of NF-κB Activation in T Cells via Association of the Adapter Proteins ADAP and CARMA1

The adapter protein ADAP regulates T lymphocyte adhesion and activation. We present evidence for a previously unrecognized function for ADAP in regulating T cell receptor (TCR)–mediated activation of the transcription factor NF-κB. Stimulation of ADAP-deficient mouse T cells with antibodies to CD3 and CD28 resulted in impaired nuclear translocation of NF-κB, a reduced DNA binding, and delayed degradation and decreased phosphorylation of IκB (inhibitor of NF-κB). TCR-stimulated assembly of the CARMA1–BCL-10–MALT1 complex was substantially impaired in the absence of ADAP. We further identified a region of ADAP that is required for association with the CARMA1 adapter and NF-κB activation but is not required for ADAP-dependent regulation of adhesion. These findings provide new insights into ADAP function and the mechanism by which CARMA1 regulates NF-κB activation in T cells.
Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types

To determine whether the status of human‐papillomavirus (HPV) infection affects the clinical outcome of cervical carcinoma (CC), HPV genotype was prospectively determined in 94 consecutive CC cases subsequently followed for a median duration of 37.5 months. With a consensus PCR‐RFLP method of HPV genotyping, 81 (86.2%) cancers were positive for HPV DNA. They were classified, according to the phylogenic similarities, into HPV‐16‐related (type 16, n = 45; type 31, n = 2), HPV‐58‐related (type 58, n = 17; type 33, n = 3; type 52, n = 2) and HPV‐18‐related (type 18, n = 8; type 68, n = 1) groups, and analyzed in relation to clinical outcome. The following results were observed: (i) Type‐58‐related HPVs were more prevalent in the old age (older than the median age of 52) group than in the young age group (41% vs. 14.6%, p = 0.045); (ii) 63% (5/8) of patients with advanced stages (III and IV) were HPV‐negative, a figure much higher than that (9.3%, 8/84) of patients with early stages (stage I and II) (p = 0.002); (iii) the occurrence of adenocarcinoma or adenosquamous carcinoma was higher in the HPV‐18‐related group (50%) than in the HPV‐16‐related (33.3%) or the HPV‐58‐related (16.7%) groups (p = 0.024); (iv) the status of lymph‐node metastasis and tumor grade did not correlate with HPV status; (v) 5‐year survival rates were 90.2%, 80% and 74% for HPV‐58‐, HPV‐16‐ and HPV‐18‐related groups, respectively (p = 0.03, after adjustment for tumor stage); (vi) in comparison with the HPV‐16‐related group, the relative risk of death in the HPV‐58‐ and the HPV‐18‐related groups were 0.32 [95% CI, 0.07–1.49] and 1.87 [0.36–14.9] respectively. HPV genotype appears to affect the clinical behavior and outcome of cervical cancer. HPV‐58‐related types are prevalent in the older population, and appear to confer a favorable prognosis. Int. J. Cancer (Pred. Oncol.) 84:553–557, 1999. © 1999 Wiley‐Liss, Inc.
Neutrophilic urticarial dermatosis (NUD) indicating Cryopyrin‐associated periodic syndrome associated with a novel mutation of the NLRP3 gene

Editor A 33-year-old female with a 30-year history of recurrent arthralgia, tendovaginitis and fever episodes presented to our institute for recalcitrant generalized urticarial lesions which started at the age of 29. Her diagnosis was chronic spontaneous urticaria. Extensive allergy testing and searches for infectious foci had been negative. She had fully recovered from herpes meningitis some years earlier. Urticae persisted for more than 24 h with a maximum in the evening. The patient reported itching, chronic fatigue and intermittent pain of the ankles and small joints. Extensive laboratory and technical tests were inconspicuous, except for a mild elevation of antinuclear antibodies (1 : 640). Punch biopsies were classified as unspecific urticae. Differential diagnoses included rheumatoid neutrophilic dermatitis, Sweet syndrome and systemic Lupus erythematosus (SLE). For treatment of the then favoured diagnosis SLE, the patient received methotrexate and hydroxychloroquine leading to a marginal improvement of arthralgia. The urticarial episodes with fatigue and intermittent fever, however, increased in frequency and intensity. All available treatments for urticaria including high-dose antihistamines, systemic corticosteroids and omalizumab were unsuccessful. Laboratory tests now showed an inflammatory reaction, pronounced during urticarial episodes, with neutrophilia, increased levels of alpha-1-globulin, and CRP. The patient was biopsied again and the old biopsies were reassessed. All specimens revealed the same histopathological pattern (Fig. 1). Based on recent literature the findings were now interpreted as neutrophilic urticarial dermatosis (NUD) as seen in Cryopyrin-associated periodic syndromes (CAPS) and Still’s disease. Subsequent genetic testing revealed a novel heterozygous c.1942G>T (p.Asp648Tyr) mutation in exon 3 of the NLRP3 gene, indicative of CAPS. The patient’s father, the sister of her father and one of her brothers were found to carry the same mutation (Fig. 2). The patient’s severe symptoms resolved within days upon initiation of daily anakinra injections. Several months later, the patient continues to be in full remission.
EGFR Mutations Compromise Hypoxia-Associated Radiation Resistance through Impaired Replication Fork–Associated DNA Damage Repair

EGFR signaling has been implicated in hypoxia-associated resistance to radiation or chemotherapy. Non–small cell lung carcinomas (NSCLC) with activating L858R or ΔE746-E750 EGFR mutations exhibit elevated EGFR activity and downstream signaling. Here, relative to wild-type (WT) EGFR, mutant (MT) EGFR expression significantly increases radiosensitivity in hypoxic cells. Gene expression profiling in human bronchial epithelial cells (HBEC) revealed that MT-EGFR expression elevated transcripts related to cell cycle and replication in aerobic and hypoxic conditions and downregulated RAD50, a critical component of nonhomologous end joining and homologous recombination DNA repair pathways. NSCLCs and HBEC with MT-EGFR revealed elevated basal and hypoxia-induced γ-H2AX–associated DNA lesions that were coincident with replication protein A in the S-phase nuclei. DNA fiber analysis showed that, relative to WT-EGFR, MT-EGFR NSCLCs harbored significantly higher levels of stalled replication forks and decreased fork velocities in aerobic and hypoxic conditions. EGFR blockade by cetuximab significantly increased radiosensitivity in hypoxic cells, recapitulating MT-EGFR expression and closely resembling synthetic lethality of PARP inhibition. Implications: This study demonstrates that within an altered DNA damage response of hypoxic NSCLC cells, mutant EGFR expression, or EGFR blockade by cetuximab exerts a synthetic lethality effect and significantly compromises radiation resistance in hypoxic tumor cells. Mol Cancer Res; 15(11); 1503–16. ©2017 AACR.
Multi-agent Polygon Formation using Reinforcement Learning

This work provides details a simulation experiment and analysis of Q-learning applied to multi-agent systems. Six agents interact within the environment to form hexagon, square and triangle, by reaching their specific goal states. In the proposed approach, the agents form a hexagon and the maximum dimension of this pattern is be reduced to form patterns with smaller dimensions. A decentralised approach of controlling the agents via Q-Learning was adopted which reduced complexity. The agents will be able to either move forward, backward and sideways based on the decision taken. Finally, the Q-Learning action-reward system was designed such that the agents could exploit the system which meant that they would earn high rewards for correct actions and negative rewards so the opposite.
Energy-efficient multiplication method for ECC in WSNs

Wireless sensor networks (WSN's)are highly resource constrained and require energy efficient and strong cryptographic techniques to ensure secure connectivity. Elliptic Curve Cryptography (ECC) is a very popular public key cryptography technique due to the extremely complex and difficult Elliptic Curve Discrete Logarithm Problem (ECDLP), it relies upon. In this paper, a technique for speeding up point multiplication, a fundamental operation involved in ECC, is presented. Specifically, the computation cost of the width-w Non-Adjacent Form (NAF) method of point multiplication is drastically reduced by employing a mixed coordinate system to perform the basic point doubling and addition operations. This paper demonstrates that this technique results in a reduction of about 62% in the number of field multiplications required when compared to the traditional techniques for elliptic curve point multiplication.
Differential Requirement of DNA Replication Factors for Subtelomeric ARS Consensus Sequence Protosilencers in Saccharomyces cerevisiae

The establishment of silent chromatin requires passage through S-phase, but not DNA replication per se. Nevertheless, many proteins that affect silencing are bona fide DNA replication factors. It is not clear if mutations in these replication factors affect silencing directly or indirectly via deregulation of S-phase or DNA replication. Consequently, the relationship between DNA replication and silencing remains an issue of debate. Here we analyze the effect of mutations in DNA replication factors (mcm5-461, mcm5-1, orc2-1, orc5-1, cdc45-1, cdc6-1, and cdc7-1) on the silencing of a group of reporter constructs, which contain different combinations of “natural” subtelomeric elements. We show that the mcm5-461, mcm5-1, and orc2-1 mutations affect silencing through subtelomeric ARS consensus sequences (ACS), while cdc6-1 affects silencing independently of ACS. orc5-1, cdc45-1, and cdc7-1 affect silencing through ACS, but also show ACS-independent effects. We also demonstrate that isolated nontelomeric ACS do not recapitulate the same effects when inserted in the telomere. We propose a model that defines the modes of action of MCM5 and CDC6 in silencing.
Utilization of poly(methyl methacrylate) - Carbon nanotube and polystyrene-Carbon nanotube in situ polymerized composites as masterbatches for melt mixing

Carbon nanotubes (CNTs) were melt mixed directly or by using an in situ polymerized masterbatch into a matrix polymer, polystyrene (PS) or poly(methyl methacrylate) (PMMA). The mechanical properties of the composites were mostly determined by the amount of CNTs, and not by the use of directly melt mixed CNTs or the use of the masterbatch. In contrast, the electrical resistivity of the composites was dependent on the manner in which the CNTs were added to the matrix polymer. When there was increased interfacial adhesion between the components, as for PS and the CNTs, the use of directly melt mixed CNTs gave better resistivity results. Without strong interactions between the CNTs and the matrix, as with PMMA and CNTs, the use of a tailored masterbatch had a significant effect on properties of the final composites. The molecular weight and viscosity of masterbatches can be varied and when the PMMA-masterbatch had optimized viscosity with respect to the PMMA matrix, electrical resistivity of the final composites decreased noticeably.
'It's more scary not to know': a qualitative study exploring the information needs of patients with systemic lupus erythematosus at the time of diagnosis.

OBJECTIVES To identify the information needs of patients newly diagnosed with systemic lupus erythematosus (lupus), to inform the design of a future education package. METHODS Focus groups were conducted in seven rheumatology centres in the UK with 43 purposively selected participants. Data were subjected to thematic inductive analysis. RESULTS The first major theme, 'Impact of early information', describes how for many individuals information was scant and, as most had little prior knowledge of lupus, the information was difficult to absorb, leaving them with feelings of fear and confusion. 'Information received versus information sought' (theme 2) describes how few participants felt they had received clear, consistent information. For most, information was felt to be insufficient, forcing them to seek it elsewhere, which, if unsuitable, resulted in further distress. 'Early education needs' (theme 3) reflects that patients would rather be informed of potential problems than remain naïve. Patients felt that receiving a comprehensive information pack as an adjunct to verbal information from their clinician would be helpful, along with rapid access to knowledgeable professionals when they were ready to ask questions about their lupus. CONCLUSIONS Participants stated information and support currently provided at diagnosis is inadequate for their needs. They would like detailed information, provided through a variety of formats. Crucially this should be supported by professionals and available at whatever point in the patient's journey they want to access such discussions . The challenge is for health professionals to meet these needs in the most beneficial and cost effective way.
Enterotoxigenic Escherichia coli virulence factors and vaccine approaches

Enterotoxigenic Escherichia coli (ETEC) is recognized as one of the major causes of infectious diarrhea in developing countries. Worldwide, the incidence of ETEC infections is estimated to result in 650 million cases of diarrhea and 380,000 deaths in children under 5 years of age. ETEC is also an important cause of travelers’ diarrhea in people traveling to endemic regions of the world. Although ETEC is an uncommon cause of infections in the USA, there have been 14 reported outbreaks of ETEC in the USA and seven on cruise ships over the 20-year period between 1975 and 1995. ETEC strains are comprised of a large number of serotypes that produce a variety of colonization factors and enterotoxins. On infection, ETEC first establishes itself by adhering to the epithelium of the small intestine via one or more colonization factor antigens or coli surface proteins. Once established, ETEC expresses one or more enterotoxin(s), which results in the production of secretory diarrhea. While the need for an efficacious, easily administered vaccine is great, there are currently no licensed ETEC vaccines available for use in endemic countries or for US travelers.
Human platelet heparanase: purification, characterization and catalytic activity.

Heparan sulphate (HS) is an important component of the extracellular matrix (ECM) and the vasculature basal lamina (BL) which functions as a barrier to the extravasation of metastatic and inflammatory cells. Platelet-tumour cell aggregation at the capillary endothelium results in activation and degranulation of platelets. Cleavage of HS by endoglycosidase or heparanase activity produced in relatively large amounts by the platelets and the invading cells may assist in the disassembly of the ECM and BL, and thereby facilitate cell migration. Using a recently published rapid, quantitative assay for heparanase activity towards HS [Freeman, C. and Parish, C.R. (1997), Biochem. J., 325, 229-237], human platelet heparanase has now been purified 1700-fold to homogeneity in 19% yield by a five column procedure, which consists of concanavalin A-Sepharose, Zn2+-chelating-Sepharose, Blue A-agarose, octyl-agarose and gel filtration chromatography. The enzyme, which was shown to be an endoglucuronidase that degrades both heparin and HS, has a native molecular mass of 50 kDa when analysed by gel filtration chromatography and by SDS/PAGE. Platelet heparanase degraded porcine mucosal HS in a stepwise fashion from a number average molecular mass of 18.5 to 13, to 8 and finally to 4.5 kDa fragments as determined by gel filtration analysis. Bovine lung heparin was degraded from 8.9 to 4.8 kDa while porcine mucosal heparin was degraded from 8.1 kDa to 3.8 and finally to 2.9 kDa fragments. Studies of the enzyme's substrate specificity using modified heparin analogues showed that substrate cleavage required the presence of carboxyl groups, but O- and N-sulphation were not essential. Inhibition studies demonstrated an absolute requirement for the presence of O-sulphate groups. Platelet heparanase was inhibited by heparin analogues which also inhibited tumour heparanase, suggesting that sulphated polysaccharides which inhibit tumour metastasis may act to prevent both tumour cell and platelet heparanase degradation of endothelial cell surface HS and the basal laminar.
Systematic pipeline for the analysis of microRNA-gene interactions in active and latent TB infection

Tuberculosis (TB) is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic-the so-called latent TB infections (LTBI), with a 10% lifetime chance of progressing to active TB. Several gene expression studies have compared healthy controls versus active TB or LTBI patients. The results vary due to diverse genetic background, study designs, and the inherent complexity of the disease process. Thus, developing a sensitive and efficient method for the detection of LTBI is both crucial and challenging. Our objective was to establish an efficient and cost-effective pipeline for gene and microRNA expression profiling in TB and LTBI. We attempted to investigate the interaction between these two types of molecular signatures as biomarkers for a more sensitive and specific differentiation among active TB, LTBI, and healthy individuals. Following our systematic pipeline, we have uncovered novel differences specific to the Taiwanese population. Differentially expressed microRNAs and their interactions with the corresponding target genes will serve as potential molecular signatures to enhance our understanding of the underlying mechanisms of TB and facilitate the development for a more sensitive diagnostic assay for LTBI.