Miracle-dz/UniFAR-FTUs huggingface dataset:
Research Paper: Implementation of Physician Order Entry: User Satisfaction and Self-Reported usage Patterns

OBJECTIVES To evaluate user satisfaction, correlates of satisfaction, and self-reported usage patterns regarding physician order entry (POE) in one hospital. DESIGN Surveys were sent to physician and nurse POE users from medical and surgical services. RESULTS The users were generally satisfied with POE (mean = 5.07 on a 1 to 7 scale). The physicians were more satisfied than the nurses, and the medical staff were more satisfied than the surgical staff; satisfaction levels were acceptable (more than 3.50) even in the less satisfied groups. Satisfaction was highly correlated with perceptions about POE's effects on productivity, ease of use, and speed. POE features directed at improving the quality of care were less strongly correlated with satisfaction. The physicians valued POE's off-floor accessibility most, and the nurses valued legibility and accuracy of POE orders most. Some features, such as off-floor ordering, were perceived to be highly useful and reported to be frequently used by the physicians; while other features, such as "quick mode'' ordering and personal order sets, received little self-reported use. CONCLUSIONS Survey of POE users showed that satisfaction with POE was good. Satisfaction was more correlated with perceptions about POE's effect on productivity than with POE's effect on quality of care. Physicians and nurses constitute two very different types of users, underscoring the importance of involving both physicians and nonphysicians in POE development. The results suggest that development efforts should focus on improving system speed, adding on-line help, and emphasizing quality benefits of POE.
A Simple and Rapid Method for the Determination of "free" Iron in Biological Fluids

We present a convenient method for determining "free" or non-protein-bound iron in biological fluids. The new method is based on the bathophenantroline method for determination of total serum iron, and comprises binding of iron by a chromogenic chelator (bathophenantroline-disulphonate, BPS), which is specific for ferrous iron. The ferrous complex of BPS absorbs strongly at 535 nm, and the detection limit is less than 1 w M in a sample size of 50 w l. The chelator does not liberate iron from either haemoglobin or transferrin. Interference from copper or zinc in concentrations up to 50 w M does not significantly disturb measurements. The main problem when measuring in blood plasma, the high and fluctuating background in the region around 535 nm, has been overcome through filtering techniques. Data from measurements of ferrous iron in microdialysate, cerebrospinal fluid, and blood plasma in different animal models and clinical conditions are presented as illustrative examples of the usefulness of the method. The method allows the determination of ferric, as well as ferrous, iron in the same sample.
Comparison of Immunohistochemistry, Acid-Fast Staining, and Cultivation for Detection of Mycobacterium Paratuberculosis in Goats

Forty-seven paired specimens of ileum and mesenterial lymph nodes from goats originating from 2 herds with paratuberculosis were investigated. Culture of the specimens for Mycobacterium paratuberculosis was compared with Ziehl-Neelsen staining and with immunohistochemical tests on paraffin-embedded tissue sections, using a M. paratuberculosis immune serum and an avidin-biotin-alkaline phosphatase method. Immunohistochemical techniques detected most positive samples and produced more clearly visible reactions than did acid-fast staining. Eighteen of 47 samples were positive by immunohistochemical methods, whereas 15 and 10 were positive for acid-fast staining and culture, respectively. Immunohistochemical techniques may represent a valuable adjunct to standard techniques for diagnosis of paratuberculosis in goats.
Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature

The last decade has seen a growing number of experiments aimed at systematically mapping the effects of mutations in different proteins, and of attempting to correlate their biophysical and biochemical effects with organismal fitness. While insightful, systematic laboratory measurements of fitness effects present challenges and difficulties. Here, we discuss the limitations associated with such measurements, and in particular the challenge of correlating the effects of mutations at the single protein level (“protein fitness”) with their effects on organismal fitness. A variety of experimental setups are used, with some measuring the direct effects on protein function and others monitoring the growth rate of a model organism carrying the protein mutants. The manners by which fitness effects are calculated and presented also vary, and the conclusions, including the derived distributions of fitness effects of mutations, vary accordingly. The comparison of the effects of mutations in the laboratory to the natural protein diversity, namely to amino acid changes that have fixed in the course of millions of years of evolution, is also debatable. The results of laboratory experiments may, therefore, be less relevant to understanding long‐term inter‐species variations yet insightful with regard to short‐term polymorphism, for example, in the study of the effects of human SNPs.
Harmonising the definition of refinement

Russell and Burch's Three Rs (replacement, reduction and refinement) remain the cornerstone for principles guiding humane experimental research. However, the concept of refinement has evolved considerably since its first inception and there have been numerous interpretations, some of which are regressive from the original definition. In this paper we examine the interpretations of refinement, and propose a harmonised progressive definition that is in line with changes in animal ethics and animal welfare science. Our definition should be applied to all aspects of refinement: those related to housing, husbandry and care, techniques used in scientific procedures, periprocedural care, health and welfare monitoring, and experimental design. We argue not only that the concept should include the avoidance or minimisation of adverse effects experienced at any time during the life of an animal destined for use in a laboratory, but also that it should be applied to the founder animals. Furthermore, we take a proactive stance and argue that refinement should include enhancing well-being through environmental enrichment. The acceptance and application of this new definition by legislative authorities and in guidelines would represent a significant step forward for animal welfare.
The Stefan Problem : Polar Exploration and the Mathematics of Moving Boundaries

A geophysicist and a mathematician are having coffee. The mathematician queries, “what are you working on these days? ” and the geophysicist responds, “I am studying the growth of ice. ” The mathematician says, “I see, the Stefan Problem! ”, to which his colleague says, “Oh, so you know about Stefan and Weyprecht? ”. “Certainly, Stefan must be a mathematician, but Weyprecht–who is Weyprecht? ” We are all keenly aware of the difficulties associated with understanding the subtle aspects of the problems that capture the attention of our colleagues in other disciplines even if those areas historically emerged from the same guiding principles. The disparity between the contemporary mathematical studies of “ice growth”, and its origins in polar exploration and Austrian science are the focus of this contribution. In physics, we know of Josef Stefan as an academic advisor to Ludwig Boltzmann in Vienna. The former is noted for having experimentally discovered, in 1879, the blackbody radiation law which relates the power/area of radiation emitted by an opaque body, PR, to the absolute temperature T through PR = σT , where σ = 5.6703×10−8 W m−2K−4 is now called Stefan’s constant. Boltzmann derived his advisor’s relation five years later from statistical mechanics, and it is now called the Stefan-Boltzmann law. This relation is, of course, also of great importance in polar science, allowing us to determine the surface temperature of sea ice by measurement of the emitted radiation, or vice versa. The seemingly banal phenomenon of the growth of a solid from a cooled boundary comes under the rubric of socalled Stefan problems. However, their rich nonlinear behavior, has attracted substantial mathematical interest (e.g. [1]), and their ubiquity in fields ranging from geology to metallurgy stimulates continual rediscovery of Stefan’s work, but rarely a scrutiny of its curious history. It not widely appreciated that Stefan’s interest in the thermodynamics of moving boundaries originated with field observations made during various nineteenth century polar expeditions. An interesting question of history concerns precisely which set of observations originally motivated Stefan’s consideration of the problem. The curiosity derives from Stefan’s pioneering paper of 1889, “Über einige Probleme der Theorie der Wärmeleitung” [2], which begins with a laconic description of the case to be treated:
Quality of life among adolescents with cerebral palsy: what does the literature tell us?

This review describes trends in quality of life (QOL) and health‐related quality of life (HRQOL) among adolescents with cerebral palsy (CP). Twenty original articles were identified by a structured search of multiple databases and grouped by design. Categories included descriptive cross‐sectional studies (n=8), measurement validation studies (n=9), and exploratory qualitative studies (n=3). Several trends were apparent. First, individuals with CP are reported to have decreased QOL and HRQOL compared with a normative population in some but not all areas of well‐being. Second, functional status measures such as the Gross Motor Function Classification System are reliable indicators of variations in physical function, but do not correlate consistently with psychosocial well‐being. Third, although adolescents with CP have different life issues than adults or children, limited research on factors associated with QOL and HRQOL has been described for this age range. We recommend that clinicians and researchers interested in assessing well‐being among adolescents with CP include participants from across the spectrum of motor impairment, allow adolescents to self‐report whenever possible, and assess adolescents independently, rather than including them with individuals from other age groups or clinical populations.
Additional Outcomes and Subgroup Analyses of NXY-059 for Acute Ischemic Stroke in the SAINT I Trial

Background and Purpose— NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke. We conducted analyses on additional end points and sensitivity analyses to confirm our findings. Methods— We randomized 1722 patients with acute ischemic stroke to a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours of stroke onset. The primary outcome was disability at 90 days, as measured by the modified Rankin Scale (mRS), a 6-point scale ranging from 0 (no residual symptoms) to 5 (bed-bound, requiring constant care). Additional and exploratory analyses included mRS at 7 and 30 days; subgroup interactions with final mRS; assessments of activities of daily living by Barthel index; and National Institutes of Health Stroke Scale (NIHSS) neurological scores at 7 and 90 days. Results— NXY-059 significantly improved the distribution of the mRS disability score compared with placebo at 7, 30, and 90 days (Cochran-Mantel-Haenszel test P=0.002, 0.004, 0.038, respectively; 90-day common odds ratio 1.20; 95% CI, 1.01 to 1.42). The benefit was not attributable to any specific baseline characteristic, stratification variable or subgroup interaction. Neurological scores were improved at 7 days (odds ratio [OR], 1.46; 95% CI, 1.13, 1.89; P=0.003) and the Barthel index was improved at 7 and 30 days (OR, 1.55; 95% CI, 1.22, 1.98; P<0.0001; OR, 1.27; 95% CI, 1.01, 1.59; P=0.02). Conclusions— NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. Benefit on neurological scores and activities of daily living was detectable early but not significant at 90 days; however, our trial was underpowered to measure effects on the neurological examination. The benefit on disability is not confounded by interactions and is supported by other outcome measures.
Treatment of HCV infection by targeting microRNA.

BACKGROUND The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen is a locked nucleic acid-modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 in a highly stable heteroduplex, thereby inhibiting its function. METHODS In this phase 2a study at seven international sites, we evaluated the safety and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection. The patients were randomly assigned to receive five weekly subcutaneous injections of miravirsen at doses of 3 mg, 5 mg, or 7 mg per kilogram of body weight or placebo over a 29-day period. They were followed until 18 weeks after randomization. RESULTS Miravirsen resulted in a dose-dependent reduction in HCV RNA levels that endured beyond the end of active therapy. In the miravirsen groups, the mean maximum reduction in HCV RNA level (log10 IU per milliliter) from baseline was 1.2 (P=0.01) for patients receiving 3 mg per kilogram, 2.9 (P=0.003) for those receiving 5 mg per kilogram, and 3.0 (P=0.002) for those receiving 7 mg per kilogram, as compared with a reduction of 0.4 in the placebo group. During 14 weeks of follow-up after treatment, HCV RNA was not detected in one patient in the 5-mg group and in four patients in the 7-mg group. We observed no dose-limiting adverse events and no escape mutations in the miR-122 binding sites of the HCV genome. CONCLUSIONS The use of miravirsen in patients with chronic HCV genotype 1 infection showed prolonged dose-dependent reductions in HCV RNA levels without evidence of viral resistance. (Funded by Santaris Pharma; ClinicalTrials.gov number, NCT01200420.).
Predictive value of epigenetic alterations in head and neck squamous cell carcinoma

Head and neck cancer collectively describes malignant tumors originating from the mucosal surface of the upper aerodigestive tract. These tumors pose a great threat to public health because of their high incidence and mortality. Traditional risk factors are tobacco and alcohol abuse. More recently, infection by high-risk types of human papilloma virus (HPV) has been identified as an additional risk factor, especially for oropharyngeal squamous cell carcinoma (OPSCC). Moreover, HPV-positive OPSCC is considered a distinct tumor entity with an improved clinical outcome compared to HPV-negative OPSCC. Epigenetic alterations act as key events in the pathogenesis of cancer and are of special interest for basic and translational oncology because of their reversible nature. This review provides a comprehensive summary of alterations of the epigenome in head and neck squamous cell carcinoma (HNSCC) with a focus on the methylome (hypomethylation and hypermethylation) and its predictive value in the evaluation of pathologic states and clinical outcome, or monitoring response rates to certain therapies.
Sperm Motility Is Lost In Vitro as a Consequence of Mitochondrial Free Radical Production and the Generation of Electrophilic Aldehydes but Can Be Significantly Rescued by the Presence of Nucleophilic Thiols1

ABSTRACT The prolonged incubation of human spermatozoa in vitro was found to induce a loss of motility associated with the activation of mitochondrial reactive oxygen species generation in the absence of any change in mitochondrial membrane potential. The increase in mitochondrial free radical production was paralleled by a loss of protein thiols and a concomitant rise in the formation of 4-hydroxynonenal, an electrophilic product of lipid peroxidation that was found to directly suppress sperm movement. These results prompted a search for nucleophiles that could counteract the action of such cytotoxic aldehydes, as a means of ensuring the long-term survival of spermatozoa in vitro. Four nucleophilic compounds were consequently assessed (penicillamine, homocysteine, N-acetylcysteine, and mercaptosuccinate) in three species (human, rat, and horse). The results of this analysis revealed drug and species specificity in the manner in which these compounds affected sperm function, with penicillamine conferring the most consistent, effective support. This prosurvival effect was achieved downstream of mitochondrial reactive oxygen species generation and was associated with the stabilization of 4-hydroxynonenal generation, the preservation of sperm thiols, and a reduction in 8-hydroxy-2′-deoxyguanosine formation. Theoretical calculations of Fe-S and Cu-S bond distances and corresponding binding energies suggested that the particular effectiveness of penicillamine may, in part, reflect the ability of this nucleophile to form stable complexes with transition metals that catalyze lipid peroxidation. The practical implications of these findings were indicated by the effective preservation of equine spermatozoa for 8 days at ambient temperature when the culture medium was supplemented with penicillamine.
Design and analysis of MEMS piezoresistive SiO2 cantilever-based sensor with stress concentration region for biosensing applications

This paper uses finite element method to obtain the optimal performance of piezoresistive microcantilever sensor by optimizing the geometrical dimension of both cantilever and piezoresistor. A 250 mum times 100 mum times 1 mum SiO2 cantilever integrated with 0.2 mum thick Si piezoresistor was used in this study. The sensor performance was measured on the basis of displacement sensitivity and surface stress sensitivity. The resulting maximum displacement value is about 0.7 nm for an applied load of 250 pN. A comparison between polySi and SiO2 cantilever has been carried out which shows the latter gives higher displacement for the same applied load. The sensor sensitivity was investigated by varying cantilever thickness as well as piezoresistor thickness. Simulation results show that the cantilever sensitivity is maximum when both the cantilever and the piezoresistor thicknesses are at minimum. Simulations were also conducted on the effects of incorporating various stress concentration region (SCR) designs at the bottom of the cantilevers. Cantilevers with incorporated stress concentration regions shows improved sensitivity over the cantilever without SCR. The cantilever with a rectangular shaped SCR extended up to the edge of the cantilever width yields a maximum Mises stress of 0.73 kPa compares to the other designs. For the same design, the cantilever with minimum SCR thickness of 0.2 mum yields maximum stress which results in maximum sensitivity.
Estimating the distribution of the window period for recent HIV infections: A comparison of statistical methods

In the past few years a number of antibody biomarkers have been developed to distinguish between recent and established Human Immunodeficiency Virus (HIV) infection. Typically, a specific threshold/cut‐off of the biomarker is chosen, values below which are indicative of recent infections. Such biomarkers have attracted considerable interest as the basis for incidence estimation using a cross‐sectional sample. An estimate of HIV incidence can be obtained from the prevalence of recent infection, as measured in the sample, and knowledge of the time spent in the recent infection state, known as the window period. However, such calculations are based on a number of assumptions concerning the distribution of the window period. We compare two statistical methods for estimating the mean and distribution of a window period using data on repeated measurements of an antibody biomarker from a cohort of HIV seroconverters. The methods account for the interval‐censored nature of both the date of seroconversion and the date of crossing a specific threshold. We illustrate the methods using repeated measurements of the Avidity Index (AI) and make recommendations about the choice of threshold for this biomarker so that the resulting window period satisfies the assumptions for incidence estimation. Copyright © 2010 John Wiley & Sons, Ltd.
The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes

Mitochondrial respiratory chain (RC) disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA) replication, transcription, and translation, require nuclear-encoded genes. In the past decade, a growing number of syndromes associated with dysfunction of mtDNA translation have been reported. This paper reviews the current knowledge of mutations affecting mitochondrial aminoacyl tRNAs synthetases and their role in the pathogenic mechanisms underlying the different clinical presentations.
Conditional Genetic Interactions of RTT107, SLX4, and HRQ1 Reveal Dynamic Networks upon DNA Damage in S. cerevisiae

The DNA damage response (DDR) is a dynamic process that is crucial for protecting the cell from challenges to genome integrity. Although many genome-wide studies in Saccharomyces cerevisiae have identified genes that contribute to resistance to DNA-damaging agents, more work is needed to elucidate the changes in genetic interaction networks in response to DNA lesions. Here we used conditional epistatic miniarray profiling to analyze the genetic interaction networks of the DDR genes RTT107, SLX4, and HRQ1 under three DNA-damaging conditions: camptothecin, hydroxyurea, and methyl methanesulfonate. Rtt107 and its interaction partner Slx4 are targets of the checkpoint kinase Mec1, which is central to the DDR-signaling cascades. Hrq1 recently was identified as a novel member of the RecQ helicase family in S. cerevisiae but is still poorly characterized. The conditional genetic networks that we generated revealed functional insights into all three genes and showed that there were varied responses to different DNA damaging agents. We observed that RTT107 had more genetic interactions under camptothecin conditions than SLX4 or HRQ1, suggesting that Rtt107 has an important role in response to this type of DNA lesion. Although RTT107 and SLX4 function together, they also had many distinct genetic interactions. In particular, RTT107 and SLX4 showed contrasting genetic interactions for a few genes, which we validated with independently constructed strains. Interestingly, HRQ1 had a genetic interaction profile that correlated with that of SLX4 and both were enriched for very similar gene ontology terms, suggesting that they function together in the DDR.