Miracle-dz/UniFAR-FTUs huggingface dataset:
Once-Weekly Micafungin Therapy Is as Effective as Daily Therapy for Disseminated Candidiasis in Mice with Persistent Neutropenia

ABSTRACT The effect of micafungin dose scheduling on the treatment of candidemia is unknown. Neutropenic mice with disseminated Candida glabrata infection were treated with single intraperitoneal micafungin doses of 0 to 100 mg/kg of body weight and sacrificed 7 days later. The maximal decline in kidney fungal burden was 5.8 log10 CFU/g. A 1-week pharmacokinetic-pharmacodynamic study revealed a micafungin serum half-life of 6.13 h. In mice treated with ≥50 mg/kg, there was maximal fungal decline without regrowth during the 1-week dosing interval. Next, doses associated with 34% (34% effective dose [ED34]) and 50% (ED50) of maximal kill were administered at one of three dose schedules: a single dose at t = 0, two equal doses at t = 0 and t = 3.5 days, and 7 equal doses daily. Some mice received a single dose of 100 mg/kg. Fungal burden was examined on days 1, 5, and 7. In mice treated with the ED34, microbial kill with the daily therapy initially lagged behind the intermittent doses but exceeded it by day 7. In mice treated with the ED50, daily and intermittent doses had equivalent day 7 effects. In mice treated with 100 mg/kg, there was no regrowth. The relative likelihoods that the area under the concentration-time curve/MIC ratio was linked to microbial kill versus peak concentration/MIC ratio or time above the MIC was 10.3 and 10,161.2, respectively. In all the experiments, no paradoxical increase in fungal burden was observed with high micafungin doses. However, only a single Candida isolate was tested. Regimens that simulated micafungin concentration-time profiles in patients treated with a single micafungin dose of 1,400 mg once a week demonstrated maximal fungal decline. Once-weekly micafungin therapy is as efficacious as daily therapy in a murine model of disseminated candidiasis.
Simultaneous degradation of organophosphorus pesticides and p-nitrophenol by a genetically engineered Moraxella sp. with surface-expressed organophosphorus hydrolase.

Moraxella sp. , a native soil organism that grows on p-nitrophenol (PNP), was genetically engineered for the simultaneous degradation of organophosphorus (OP) pesticides and p-nitrophenol (PNP). The truncated ice nucleation protein (INPNC) anchor was used to target the pesticide-hydrolyzing enzyme, organophosphorus hydrolase (OPH), onto the surface of Moraxella sp. , alleviating the potential substrate uptake limitation. A shuttle vector, pPNCO33, coding for INPNC-OPH was constructed and the translocation, surface display, and functionality of OPH were demonstrated in both E. coli and Moraxella sp. However, whole cell activity was 70-fold higher in Moraxella sp. than E. coli. The resulting Moraxella sp. degraded organophosphates as well as PNP rapidly, all within 10 h. The initial hydrolysis rate was 0.6 micromol/h/mg dry weight, 1.5 micromol/h/mg dry weight, and 9.0 micromol/h/mg dry weight for methyl parathion, parathion, and paraoxon, respectively. The possibility of rapidly degrading OP pesticides and their byproducts should open up new opportunities for improved remediation of OP nerve agents in the future.
Catecholamine support at the initiation of epoprostenol therapy in pulmonary arterial hypertension.

RATIONALE Epoprostenol is a first-line therapy for patients with pulmonary arterial hypertension (PAH) in World Health Organization functional class IV who often have low cardiac output and hypotension. However, initiation of epoprostenol can cause hemodynamic collapse in these vulnerable patients. Inotropic agent support may prevent the hemodynamic instability caused by initiation of epoprostenol; however, a protocol for supportive therapy has not been established. OBJECTIVES To assess the reliability and prognostic effects of dobutamine and dopamine support at the initiation of epoprostenol therapy in patients with PAH. METHODS We initiated epoprostenol therapy in 71 patients with PAH. Hemodynamics at the initiation of epoprostenol were measured by right heart catheterization. We initiated dobutamine when a patient's mixed venous oxygen saturation was less than 60% or cardiac index was less than 2.0 L/min/m(2) or when right ventricular failure was clinically suspected. We initiated dopamine when a patient's systolic blood pressure was less than 90 mm Hg or urine volume was less than 20 ml/h. MEASUREMENTS AND MAIN RESULTS At the initiation of epoprostenol, dobutamine and/or dopamine were required to support 46 patients according to protocol. Eight patients died during the hospitalization and one patient received a living-donor lobar lung transplant after the initiation of epoprostenol therapy. Neither inotropic agent was an independent risk factor for short-term mortality (dobutamine: hazard ratio, 1.63; 95% confidence interval, 0.33-8.11; dopamine: hazard ratio, 0.22; 95% confidence interval, 0.03-1.70). Sixty-two patients were discharged for home infusion of epoprostenol. Transplant-free survival rates at 5 years were 80.0% for patients who did not require inotropic support at the start of epoprostenol and 76.6% for patients with who did require dopamine and/or dobutamine support (P = 0.45). CONCLUSIONS Temporary use of dobutamine and dopamine appears to be safe for hemodynamic support at the initiation of epoprostenol therapy for selected patients with PAH with low cardiac output and hypotension. The protocol presented here requires validation at other centers.
Local recurrences after curettage and cementing in long bone giant cell tumor

Background: Giant cell tumor of bone (GCT) is a benign lesion with great propensity for local recurrence. This study aimed to analyse the rates of local recurrence and its possible predisposing factors in Campanacci’s Grade III and II GCT of long bones following intralesional curettage and bone cementing. Materials and Methods: 32 cases of either sex with Campanacci’s Grade II (n= 14), and Grade III (n=18) with intact articular surface, operated between 1995 and 2007 in form of intralesional curettage and bone cementing were studied. All the cases were followed up for 2.5–12 years (mean, 6.5), after primary treatment. The mean age at operation was 32.4 years (range, 18.5–40 years). The proximal tibia was involved in 13 cases (40.6%), followed by distal femur (n=11)34.4% distal tibia (n=3) 9.4%, proximal femur (n=2) 3.2% and distal radius (n=3) 9.4%. Results: Eleven patients (34.4%) had local recurrence, of which eight were of Campanacci’s Grade III. The mean recurrence time was 14 months (range, 3-34 months). The two-year recurrence-free survivorship was 71.9% (n=23/32). Post-recurrence mean follow-up was 4.2 years (range, 2–6.5 years). Conclusion: We observed higher rate of local recurrence with Campanacci’s Grade III GCTs. We recommend selective use of this procedure in Grade III lesions, particularly with extensive soft tissue involvement.
Symptomatic carotid near‐occlusion with full collapse might cause a very high risk of stroke

The risk of early stroke recurrence amongst patients with symptomatic carotid near‐occlusion with and without full collapse is unknown. Therefore, the aim of this study was to analyse the 90‐day risk of recurrent ipsilateral ischaemic stroke in patients with symptomatic carotid near‐occlusion both with and without full collapse.
Two-Step Scheme for Rapid Identification and Differentiation of Legionella pneumophila and Non-Legionella pneumophila Species

ABSTRACT A rapid two-step scheme based on PCR amplification and enzymatic digestion analysis of a 226-bp fragment of the 16S rRNA gene was developed to identify the Legionella genus by PCR amplification and to differentiate the Legionella pneumophila and non-Legionella pneumophila species by enzymatic digestion analysis. Among 42 ATCC strains (16 strains of L. pneumophila and 26 strains of non-L. pneumophila) and 200 Legionella isolates from environmental water samples, including pools, rivers, lakes, and cooling towers in Guangdong province, 99.59% of L. pneumophila and non-L. pneumophila strains were correctly identified and differentiated by this scheme. The procedure of this two-step identification and differentiation scheme is simple and takes only about 4 h. These results suggest that this two-step scheme provides a simple and convenient method for the rapid identification and differentiation of L. pneumophila and non-L. pneumophila species.
Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization.

PURPOSE To identify novel genomic regions of interest in acute myeloid leukemia (AML) with complex karyotypes, we applied comparative genomic hybridization to microarrays (array-CGH), allowing high-resolution genome-wide screening of genomic imbalances. PATIENTS AND METHODS Sixty AML cases with complex karyotypes were analyzed using array-CGH; parallel analysis of gene expression was performed in a subset of cases. RESULTS Genomic losses were found more frequently than gains. The most frequent losses affected 5q (77%), 17p (55%), and 7q (45%), and the most frequent genomic gains 11q (40%) and 8q (38%). Critical segments could be delineated to genomic fragments of only 0.8 to a few megabase-pairs of DNA. In lost/gained regions, gene expression profiling detected a gene dosage effect with significant lower/higher average gene expression levels across the genes located in the respective regions. Furthermore, high-level DNA amplifications were identified in several regions: 11q23.3-q24.1 (n = 7), 21q22 (n = 6), 11q23.3 (n = 5), 13q12 (n = 3), 8q24 (n = 3), 9p24 (n = 2), 12p13 (n = 2), and 20q11 (n = 2). Parallel analysis of gene expression in critical amplicons displayed overexpressed candidate genes (eg, C8FW and MYC in 8q24). CONCLUSION In conclusion, a large spectrum of genomic imbalances, including novel recurring changes in AML with complex karyotypes, was identified using array-CGH. In addition, the combined analysis of array-CGH data with gene expression profiles allowed the detection of candidate genes involved in the pathogenesis of AML.
Cellular immunity to the P6 outer membrane protein of nontypeable Haemophilus influenzae

Cellular immunity to nontypeable Haemophilus influenzae in a population of 10 healthy, immune adults was determined by measuring lymphocyte blast transformation and antibody secretion in response to the P6 outer membrane protein. P6 (200 microliters/ml) induced lymphocyte blast transformation that peaked on day 10 of incubation. The peak induction of antibody-secreting cells occurred on day 8 of incubation. In comparison with the response to tetanus toxoid stimulation, the peak lymphocyte blast transformation response to P6 was reduced (mean counts per minute +/- standard error of the mean [SEM], 3,457 +/- 503 versus 9,414 +/- 1,464; P = 0.0051) and delayed (mean days +/- SEM, 10.3 +/- 0.4 versus 8.4 +/- 0.5; P = 0.0169); however, P6 was a better stimulus of antibody secretion from lymphocytes, particularly antibody of the immunoglobulin M (IgM) class (mean peak numbers of antibody-secreting cells per 10(5) peripheral blood mononuclear cells +/- SEM: IgG, 85 +/- 29 versus 42 +/- 16 [P = 0.0469]; IgM, 81 +/- 20 versus 25 +/- 7 [P = 0.0125]; IgA, 24 +/- 8 versus 16 +/- 6 [P = 0.0526]). Thus, lymphocytes from immune individuals recognize P6 of nontypeable H. influenzae as an immunogen. These data provide a basis for future studies with otitis-prone children who fail to develop a normal antibody response to P6 antigen (N. Yamanaka and H. Faden, J. Pediatr. 122:212-218, 1993).
Analysis of Thermal Stabilizing Interactions in Mesophilic and Thermophilic Adenylate Kinases from the GenusMethanococcus *

Adenylate kinases (ADKs) from four closely related methanogenic members of the Archaea (the mesophileMethanococcus voltae (MVO), the thermopileMethanococcus thermolithotrophicus (MTH), and the extreme thermopiles Methanococcus igneus (MIG) andMethanococcus jannaschii (MJA)) were characterized for their resistance to thermal denaturation. Despite possessing between 68 and 81% sequence identity, the methanococcal ADKs significantly differed in their stability against thermal denaturation, with melting points ranging from 69 to 103 °C. The high sequence identity between these organisms allowed regions of the MVO and MJA ADKs to be exchanged, producing chimeric ADKs with significantly altered thermal stability. Up to a 20 °C increase or decrease in stability was achieved for chimeric ADKs, whereas 88% of the original protein sequence was maintained. Based on our previous structural modeling studies, we conclude that cooperative interactions within the hydrophobic protein core play an integral role in determining the differences in structural stability observed between the methanococcal ADKs. From comparisons of the effects of temperature on protein unfolding and optimal enzymatic activity, we also conclude that thermostability and enzymatic temperature optima are influenced differently by molecular modifications and thus that the protein flexibility required for activity and stability, respectively, is not unconditionally linked within the methanococcal ADKs.
Smart electricity meter data analytics: A brief review

The use of smart meters have been increased in many countries across the globe. Smart meters are not only used for measurement of electricity consumption but also used for the measurement of gas and water consumption. The smart meter is an integral part of the smart grid system and its use incurs benefits to people in various aspects such as social, economic and environmental. The smart meters' main functionality is measuring, capturing and transforming data related to usage or consumption of electricity, gas or water and events such as meter status and power quality. Such functionality encounters many data related issues such as the volume of data, the speed of collecting data and complexity. To gain the hidden insights and knowledge from such data we require the advanced data analytical tools and technologies. This paper provides a brief review of tools and technologies used in smart electricity meter data analytics as well as a comprehensive survey of several key analytical applications and techniques and tools used in those applications.
Surgical Correction of Scoliosis by In Situ Contouring: A Detorsion Analysis

Study Design. A detorsion analysis of the scoliosis surgical correction by means of in situ contouring technique (ISC). Objective. To describe the technique of ISC. To measure the vertebral and intervertebral axial rotation in thoracic and lumbar curves and their correction obtained by ISC. Summary and Background Data. The vertebral and intervertebral axial rotation allows to evaluate the severity of the curves. However, the intervertebral axial rotation is barely studied and the vertebral axial rotation is a controversial point of the surgical correction. Methods. Twenty patients with thoracic and lumbar scoliosis were operated on with ISC. Vertebral axial rotation at the apex and the sum of intervertebral axial rotations all along the curve were computed before and after surgery from the three-dimensional stereoradiographic reconstruction of the spine and the pelvis. All the measurements were made in the standing position. Results. Correction of the axial rotation was obtained at the apex of both thoracic and lumbar curves of idiopathic and degenerative scoliosis. The mean values of correction (in terms of axial rotation) were 8° to 19° (62%–67%). The percentage of correction of the sum of intervertebral axial rotations all along the curve, proposed as a “detorsion index” (preoperative − postoperative/preoperative), was found at 57% to 92%. No significant differences were found for the correction (in terms of axial rotation and detorsion) between idiopathic and degenerative curves. Conclusions. The axial rotation was measured in clinics on standing patients with scoliosis from three-dimensional stereoradiographic reconstruction and demonstrated a reliable detorsion obtained by ISC.
Multicentre aneurysm screening study (MASS): cost effectiveness analysis of screening for abdominal aortic aneurysms based on four year results from randomised controlled trial

Abstract Objective:To assess the cost effectiveness of ultrasound screening for abdominal aortic aneurysms. Design: Primary analysis: four year cost effectiveness analysis based directly on results from a randomised controlled trial in which patients were individually allocated to invitation to ultrasound screening (intervention) or to a control group not offered screening. Secondary analysis: projection of the data, based on conservative assumptions, to indicate likely cost effectiveness at 10 years. Setting:Four centres in the United Kingdom. Screening delivered in primary care settings with follow up and surgery offered in the main hospitals Participants: Population based sample of 67 800 men aged 65-74 years. Main outcome measures:Mortality from and costs (screening, follow up, elective and emergency surgery) related to abdominal aortic aneurysm; cost per life year gained. Results:Over four years there were 47 fewer deaths related to abdominal aortic aneurysms in the screening group than in the control group, but the additional costs incurred were £2.2m. After adjustment for censoring and discounted at 6% the mean additional cost of the screening programme was £63.39 ($97.77, €100.48) (95% confidence interval £53.31 to £73.48) per patient. The hazard ratio for abdominal aortic aneurysm was 0.58 (0.42 to 0.78). Over four years the mean incremental cost effectiveness ratio for screening was £28 400 (£15 000 to £146 000) per life year gained, equivalent to about £36 000 per quality adjusted life year. After 10 years this figure is estimated to fall to around £8000 per life year gained. Conclusions:Even at four years the cost effectiveness of screening for abdominal aortic aneurysms is at the margin of acceptability according to current NHS thresholds. Over a longer period the cost effectiveness will improve substantially, the predicted ratio at 10 years falling to around a quarter of the four year figure.
Differentiation of the maize subgenomes by genome dominance and both ancient and ongoing gene loss

Ancient tetraploidies are found throughout the eukaryotes. After duplication, one copy of each duplicate gene pair tends to be lost (fractionate). For all studied tetraploidies, the loss of duplicated genes, known as homeologs, homoeologs, ohnologs, or syntenic paralogs, is uneven between duplicate regions. In maize, a species that experienced a tetraploidy 5–12 million years ago, we show that in addition to uneven ancient gene loss, the two complete genomes contained within maize are differentiated by ongoing fractionation among diverse inbreds as well as by a pattern of overexpression of genes from the genome that has experienced less gene loss. These expression differences are consistent over a range of experiments quantifying RNA abundance in different tissues. We propose that the universal bias in gene loss between the genomes of this ancient tetraploid, and perhaps all tetraploids, is the result of selection against loss of the gene responsible for the majority of total expression for a duplicate gene pair. Although the tetraploidy of maize is ancient, biased gene loss and expression continue today and explain, at least in part, the remarkable genetic diversity found among modern maize cultivars.
Olfactory ensheathing cell membrane properties are shaped by connectivity

Olfactory ensheathing cells (OECs) have been repeatedly implicated in mediating plasticity, particularly in situ in the olfactory nerve in which they support the extension of olfactory sensory neuron (OSN) axons from the olfactory epithelium to the olfactory bulb (OB). OECs are specialized glia whose processes surround OSN axon fascicles within the olfactory nerve and across the OB surface. Despite their purported importance in promoting axon extension, and following transplants, little is known about either morphology or biophysical properties of OECs in situ. In particular, cell–cell interactions that may influence OEC function are largely unexplored. Here, we studied OEC connectivity and morphology in slice preparations, preserving tissue structure and cell–cell interactions. Our analyses showed that OECs form a matrix of cellular projections surrounding axons, unique among glia, and express high levels of connexin‐43. Lucifer Yellow injections revealed selective dye coupling among small subgroups of OECs. Two types of OECs were biophysically distinguished with whole‐cell voltage‐clamp recordings: (1) with low‐input resistance (Ri), linear current profiles, and frequently dye coupled; and (2) with high Ri, nonlinear current profiles, and infrequent dye coupling. Pharmacological blockade of gap junctions changed OEC membrane properties such that linear OECs became nonlinear. Double recordings indicated that the appearance of the nonlinear current profile was associated with the loss of electrical coupling between OECs. We conclude that the diversity of OEC current profiles can be explained by differences in gap‐junction connectivity and discuss implications of this diversity for OEC influences on axon growth and excitability. © 2009 Wiley‐Liss, Inc.
The syndrome concept: history and statistical operationalizations

Synopsis A historical analysis of the syndrome concept shows that this term has been used in many different ways, ranging from clinical experience to records of coinciding symptoms. However, there seems to be broad agreement on the use of the word ‘syndrome’ in daily practice. If empirical–mathematical methods are applied in syndrome detection, however, a precise operation-alization of the syndrome concept is needed. Traditional procedures have often used models more dictated by methodological considerations than derived from the field of application, i.e. psychiatric syndromatology. An alternative approach, Boolean factor analysis, is presented in this paper. This relatively new method is illustrated by means of the analysis of a small artificial sample with a known structure. As a point of reference, traditional methods (factor analysis, cluster analysis, and multidimensional scaling) are also briefly discussed. It is demonstrated that they all share a deficiency of information about inter-group structure. In contrast, Boolean factor analysis uses a syndromic definition which builds on the basic notion of concurrent symptoms. Moreover, this approach can easily be understood by clinicians.
Exercise and cardiac regulation: what can electrocardiographic time series tell us?

Electrocardiographic (ECG) monitoring allows temporal analysis of cardiac rhythm. We are usually interested in the variability of two components of the ECG: RR interval (a surrogate marker of cardiac interval) and QT interval (the duration of ventricular depolarization/repolarization). Quantification of RR rhythm, called heart rate variability (HRV) analysis, reflects the cardiac influences of the autonomic nervous system. QT variability provides insight regarding the risk of ventricular arrhythmia, and is at least partially independent of HRV. In this review, we consider the analysis of ECG time series during physical exercise. Our objectives were to show the variety of methods that can be used to characterize these time series data and to demonstrate “normal” changes in these characteristics during exercise and recovery. Attaining a comprehensive understanding of cardiac electrical conduction changes during exercise is not straightforward: analysis methods are numerous and results require careful interpretation. However, we recommend that assessment of both HRV and QT properties yields the most valuable information, the utility of which can be appreciated from the viewpoints of the athlete (e.g. providing feedback on the cardiac effects of training), the clinician (assisting in cardiovascular screening and exercise therapy evaluation) and the exercise physiologist (providing data for physiological process modelling).