Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased moxifloxacin utilization associated with an unrestricted addition to a drug reimbursement formulary: A population-based analysis.

OBJECTIVES To determine whether utilization of moxifloxacin, a broad-spectrum fluoroquinolone antibiotic, has changed since its addition to the British Columbia provincial formulary in 2009 and to determine whether utilization was guideline concordant. METHODS BC PharmaNet prescriptions for moxifloxacin from 2001 to 2010 were anonymously linked to associated Medical Services Plan fee-for-service practitioner claims for indication-specific analysis. Prescribing trends for adults ≥18 years of age were described using defined daily dose (DDD) per 1000 person-years. Monthly utilization rates were fit to a linear regression model that controlled for seasonal variation to examine the effect of the formulary addition. RESULTS Utilization rose more than sevenfold throughout the study period, from 21.3 DDD per 1000 person-years in 2001 to 163.3 DDD per 1000 person-years in 2010. Although the formulary addition was not associated with an immediate increase in utilization (7.5% [95% CI -4.4% to 20.9%]; P=0.226), it was associated with an overall increase in utilization of 2.1% (95% CI 1.3% to 3.0%; P<0.001) for every month after 2009. Overall, only 29% of moxifloxacin prescriptions could be linked to a diagnostic code that was considered to be guideline concordant. In more than one-half of moxifloxacin prescriptions, the patient had not used another antibiotic in the previous 90 days. Among moxifloxacin prescriptions in which another antibiotic had been used in the previous 90 days, 41.5% were prescriptions for an alternative fluoroquinolone. CONCLUSIONS The formulary addition was associated with a sustained increase in moxifloxacin utilization over time. Moxifloxacin is often prescribed to patients for indications that are not guideline concordant or to patients who have not previously received first-line antibiotics.
Distinct Habitats Select Particular Bacterial Communities in Mangrove Sediments

We investigated the relationship among environmental variables, composition, and structure of bacterial communities in different habitats in a mangrove located nearby to an oil exploitation area, aiming to retrieve the natural pattern of bacterial communities in this ecosystem. The T-RFLP analysis showed a high diversity of bacterial populations and an increase in the bacterial richness from habitats closer to the sea and without vegetation (S1) to habitats covered by Avicennia schaueriana (S2) and Rhizophora mangle (S3). Environmental variables in S1 and S2 were more similar than in S3; however, when comparing the bacterial compositions, S2 and S3 shared more OTUs between them, suggesting that the presence of vegetation is an important factor in shaping these bacterial communities. In silico analyses of the fragments revealed a high diversity of the class Gammaproteobacteria in the 3 sites, although in general they presented quite different bacterial composition, which is probably shaped by the specificities of each habitat. This study shows that microhabitats inside of a mangrove ecosystem harbor diverse and distinct microbiota, reinforcing the need to conserve these ecosystems as a whole.
Identification of AF-6 and Canoe as Putative Targets for Ras (*)

Ras (Ha-Ras, Ki-Ras, N-Ras) is implicated in the regulation of various cell functions such as gene expression and cell proliferation downstream from specific extracellular signals. Here, we partially purified a Ras-interacting protein with molecular mass of about 180 kDa (p180) from bovine brain membrane extract by glutathione S-transferase (GST)-Ha-Ras affinity column chromatography. This protein bound to the GTPS (guanosine 5′-(3-O-thio)triphosphate, a nonhydrolyzable GTP analog)•GST-Ha-Ras affinity column but not to those containing GDP•GST-Ha-Ras or GTPS•GST-Ha-Ras with a mutation in the effector domain (Ha-Ras). The amino acid sequences of the peptides derived from p180 were almost identical to those of human AF-6 that is identified as the fusion partner of the ALL-1 protein. The ALL-1/AF-6 chimeric protein is the critical product of the t (6:11) abnormality associated with some human leukemia. AF-6 has a GLGF/Dlg homology repeat (DHR) motif and shows a high degree of sequence similarity with Drosophila Canoe, which is assumed to function downstream from Notch in a common developmental pathway. The recombinant N-terminal domain of AF-6 and Canoe specifically interacted with GTPS•GST-Ha-Ras. The known Ras target c-Raf-1 inhibited the interaction of AF-6 with GTPS•GST-Ha-Ras. These results indicate that AF-6 and Canoe are putative targets for Ras.
Reye's syndrome.

The most important recent development in our understanding of Reye's syndrome is the epidemiologic evidence linking this disease to aspirin in the United States. Assessment of epidemiologic issues of concern raised in prior studies did not explain the extremely high odds ratios observed in more recent studies. The observation of a dose-response relation between risk of Reye's syndrome and dose of aspirin ingested during the antecedent illness provides further supportive evidence for a causal link between Reye's syndrome and aspirin. Additional evidence for this association in the United States is provided by a marked decline in the use of aspirin among children in the United States, which has been accompanied by a dramatic decline in the incidence of Reye's syndrome. In contrast to experience in the United States, Reye's syndrome affecting primarily children aged 5-15 years has been relatively rare in Great Britain and Australia where acetaminophen rather than aspirin is the primary analgesic/antipyretic used. With the declining incidence of aspirin use in the United States, Reye's syndrome among children aged 5-15 years is becoming increasingly rare in the United States as well and, as in Great Britain and Australia, an increasing proportion of cases are being reported in children aged less than five years. Recent reports have suggested that many children younger than age five years who are thought to have the disease may be shown to have other metabolic disorders. (ABSTRACT TRUNCATED AT 250 WORDS)
Alkaline Phosphatase-To-Albumin Ratio as a Prognostic Indicator in Pancreatic Ductal Adenocarcinoma after Curative Resection

Background: The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains poor and the models for survival prediction in PDAC patients after curative resection are still limited. Preoperative alkaline phosphatase-to-albumin ratio (APAR), an original inflammation-based score, has been established to analyze the prognostic significance in PDAC. Therefore, in this study, we aim to formulate a valuable prognostic nomogram for PDAC following curative resection. Methods: A total of 354 patients with PDAC undergoing curative resection were retrospectively enrolled in this study. The prognostic value of APAR was analyzed in primary cohort containing 220 randomly selected PDAC patients with curative resection and prognostic nomogram incorporating APAR into the American Joint Commission on Cancer (AJCC) 8th edition was established to obtain superior discriminatory abilities. The predictive performance of APAR was further validated in another independent cohort of 134 PDAC patients. Results: Patients with higher serum APAR level were probable to sustain poorer overall survival (OS). Significant positive correlations were found between APAR and tumor site, and several serum biochemical indexes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), etc. The results of multivariate analysis showed, APAR was also identified as an independent prognostic indicator for OS in both primary and validation cohorts (P=0.004, P=0.038, respectively). Compared with the AJCC 8th edition, the nomogram consisting of APAR, pathological differentiation and the TNM staging system of AJCC 8th edition showed superior predictive accuracy for OS. All these results were further verified in the validation cohort. Conclusions: APAR can be considered as a novel independent prognostic biomarker for PDAC following curative resection. One more accurate and advanced predictive model will be achieved via the incorporation of APAR into nomogram.
Poly-vinyl alcohol hydrogel vascular models for in vitro aneurysm simulations: the key to low friction surfaces.

PURPOSE To develop a vessel model with poly-vinyl alcohol hydrogel (PVA-H) with low surface friction for in vitro simulations of vascular pathologies. MATERIALS AND METHODS Simulations of variable vascular pathologies were based on human vessel casts reproduced in wax. Constructions of vascular models were then obtained by lost wax techniques. As materials, liquid silicon or PVA in organic solvents were used. After solidification, the wax was drained by heating. Comparison of PVA-H with silicone models included evaluation of surface characteristics (friction coefficient), of visibility (transparence and compatibility with medical imaging techniques), and of stiffness (pulsatility of vascular lumen). Both model types were integrated in a circulation circuit allowing for flow simulations and testing with endovascular medical devices. RESULTS AND CONCLUSION Both model types were transparent and compatible with current medical imaging methods. PVA-H models exhibited much lower friction characteristics. PVA-H stiffness was closer to soft tissue when compared to silicone, allowing for pulsations during flow simulations.
Pharmacokinetics of Acyclovir and Its Metabolites in Cerebrospinal Fluid and Systemic Circulation after Administration of High-Dose Valacyclovir in Subjects with Normal and Impaired Renal Function

ABSTRACT Valacyclovir, the l-valyl ester prodrug of acyclovir (ACV), is widely prescribed to treat infections caused by varicella-zoster virus or herpes simplex virus. Rarely, treatment is complicated by reversible neuropsychiatric symptoms. By mechanisms not fully understood, this occurs more frequently in the setting of renal impairment. We characterized the steady-state pharmacokinetics of ACV and its metabolites 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8-hydroxy-acyclovir (8-OH-ACV) in cerebrospinal fluid (CSF) and the systemic circulation. We administered multiple doses of high-dose valacyclovir to 6 subjects with normal renal function and 3 subjects with chronic renal impairment (creatinine clearance [CrCl], ∼15 to 30 ml/min). Dosages were 2,000 mg every 6 h and 1,500 mg every 12 h, respectively. Indwelling intrathecal catheters allowed serial CSF sampling throughout the dosing interval. The average steady-state concentrations of acyclovir, CMMG, and 8-OH-ACV were greater in both the systemic circulation and the CSF among subjects with impaired renal function than among subjects with normal renal function. However, the CSF penetration of each analyte, reflected by the CSF-to-plasma area under the concentration-time curve over the 6- or 12-h dosing interval (AUCτ) ratio, did not differ based on renal function. Renal impairment does not alter the propensity for ACV or its metabolites to distribute to the CSF, but the higher concentrations in the systemic circulation, as a result of reduced elimination, are associated with proportionally higher concentrations in CSF.
Relationships with mother, teacher, and peers: unique and joint effects on young children's self-concept

This study tested the unique and joint effects of three significant relationships in young children's social lives, namely their relationships with mother, teacher, and peers, on three dimensions of self-concept (general, academic, and social). A sample of 113 children participated. Mother–child attachment quality was observed in preschool. In first grade, teacher ratings of teacher–child relationship quality, peer ratings of peer acceptance, and child reports of self-concept were administered. The results revealed domain-specific links between social relationships and self-concept dimensions. Specifically, academic self-concept related to teacher–child relationship quality, social self-concept to peer acceptance, and general self-concept to the quality of attachment to mother. Moreover, an indirect effect was revealed of earlier mother–child attachment quality on the academic dimension of self through its effect on current adult–child relationships in school. This way, the study uncovered the pathways through which significant social relationships shape the formation of young children's self-concept.
Do Private Firms Invest Differently than Public Firms? Taking Cues from the Natural Gas Industry

We study how listing status affects investment behavior. Theory offers competing hypotheses on how listing-related frictions affect investment decisions. We use detailed data on 74,670 individual projects in the U.S. natural gas industry to show that private firms respond less than public firms to changes in investment opportunities. Private firms adjust drilling activity for low capital-intensity investments. However, they do not increase drilling in response to new capital-intensive growth opportunities. Instead, they sell these projects to public firms. Our evidence suggests that differences in access to external capital are important in explaining the investment behavior of public and private firms.
High Prevalence of Serine Protease Inhibitor Kazal Type 1 Gene Variations Detected by Whole Gene Sequencing in Patients with Fibrocalculous Pancreatic Diabetes

Aim of Study: The aim is to study the prevalence and pattern of serine protease inhibitor Kazal type 1 (SPINK1) gene variations in patients with fibrocalculous pancreatic diabetes (FCPD) using whole gene sequencing. Materials and Methods: A total of 56 consecutive patients of FCPD were recruited for the study. Diagnosis of FCPD was based on the presence of diabetes mellitus in patients having chronic pancreatitis with radiological evidence of ductal calcifications, in the absence of other known causes for pancreatitis. Ethylenediaminetetraacetic acid samples were collected from all patients, and complete gene sequencing was performed for SPINK1 gene using Sanger technique. Results: Overall 35 patients (62.5%) were detected to have genetic alterations in SPINK1 gene. N34S polymorphism was seen in 23 participants (41.07%) out of which 3 were homozygous. N34S was seen to be in linkage disequilibrium with IVS1 − 37T>C (18/23) and IVS3-69insAAAA (19/23) polymorphisms. Seven patients (12.5%) had a 272 C>T 3'UTR polymorphism while one patient (1.8%) had a P55S polymorphism. Two patients (3.5%) had an IVS3 + 2T>C mutation which has been shown to be associated with loss of function of SPINK protein. Overall 48.2% of FCPD patients had genetic variations that were significant compared to the control population. There was no difference in anthropometric and biochemical parameters between those with or without SPINK1 gene variations. Conclusions: Variations in SPINK1 gene are frequently observed in FCPD. N34S polymorphism was the most common variation followed by intronic variations. Two patients had the pathogenic intronic IVS3 + 2T>C mutation. Whole gene sequencing of the SPINK1 gene enabled detection of an additional 7.1% of patients with significant SPINK1 gene variations as compared to targeted screening for the N34S variation.
Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial.

CONTEXT Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. OBJECTIVE To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. DESIGN, SETTING, AND PATIENTS This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. INTERVENTIONS Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. MAIN OUTCOME MEASURES The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. RESULTS No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91). CONCLUSION In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00091637.
Improving pulmonary vessel image quality with a full model-based iterative reconstruction algorithm in 80kVp low-dose chest CT for pediatric patients aged 0–6 years

Background Full model-based iterative reconstruction (MBIR) algorithm decreasing image noise and improving spatial resolution significantly, combined with low voltage scan may improve image and vessels quality. Purpose To evaluate the image quality improvement of pulmonary vessels using a full MBIR in low-dose chest computed tomography (CT) for children. Material and Methods This study was institutional review board approved. Forty-one children (age range, 28 days–6 years, mean age, 2.0 years) who underwent 80 kVp low-dose CT scans were included. Age-dependent noise index (NI) for a 5-mm slice thickness image was used for the acquisition: NI = 11 for 0–12 months old, NI = 13 for 1–2 years old, and NI = 15 for 3–6 years old. Images were retrospectively reconstructed into thin slice thickness of 0.625 mm using the MBIR and a conventional filtered back projection (FBP) algorithm. Two radiologists independently evaluated images subjectively focusing on the ability to display small arteries and diagnosis confidence on a 5-point scale with 3 being clinically acceptable. CT value and image noise in the descending aorta, muscle and fat were measured and statistically compared between the two reconstruction groups. Results The ability to display small vessels was significantly improved with the MBIR reconstruction. The subjective scores of displaying small vessels were 5.0 and 3.7 with MBIR and FBP, respectively, while the respective diagnosis confidence scores were 5.0 and 3.8. Quantitative image noise for the 0.625 mm slice thickness images in the descending aorta was 15.8 ± 3.8 HU in MBIR group, 57.3% lower than the 37.0 ± 7.3 HU in FBP group. The signal-to-noise ratio and contrast-to-noise ratio for the descending aorta were 28.3 ± 7.9 and 24.05 ± 7.5 in MBIR group, and 12.1 ± 3.7 and 10.6 ± 3.5 in FBP group, respectively. These values were improved by 133.9% and 132.1%, respectively, with MBIR reconstruction compared to FBP reconstruction. Conclusion Compared to the conventional FBP reconstruction, the image quality and diagnostic performance for pulmonary vessels was significantly improved by the MBIR reconstruction in low-dose chest CT in children.
[Bone metabolism markers in patients with Basedow-Graves disease].

Collagen type I is the main collagen type found in bones. Carboxyterminal propeptide, deriving and cleaved from procollagen type I (PICP) during collagen synthesis, is delivered into the blood, where it might represent an useful marker of bone formation similarly to osteocalcin. PICP, osteocalcin, alkaline phosphatase, serum and urinary calcium excretion were measured in 58 premenopausal females affected by Graves' disease and also 28 of them after attainment of euthyroidism by methimazole treatment to study these biochemical indices of bone remodelling before and after treatment. Before therapy PICP (mean +/- S.D.: 244.2 +/- 112.3 vs. 136.8 +/- 32.4 micrograms/l), osteocalcin (mean +/- S.D.: 17.8 +/- 6.7 vs. 7.5 +/- 2.7 micrograms/l) and other markers were significantly (p < 0.05) higher than sex and age matched controls (n = 24). Treatment induced a significant decrease of PICP, alkaline phosphatase, calcaemia and calciuria compared to pretreatment values, while osteocalcin did not significantly differ (mean +/- S. D.: 17.8 +/- 6.7 vs. 14.7 +/- 8.7 micrograms/l). These data suggest that hyperthyroidism due to Graves' disease causes an increase of serum levels of these markers, but further studies are necessary to asses the differences between PICP and osteocalcin as markers of osteoblast activity in hyperthyroidism.
Effect of a Previous Acute Angle Closure Attack on the Corneal Endothelial Cell Density in Chronic Angle Closure Glaucoma Patients

PurposeTo document the effect of a previous acute angle closure attack on the corneal endothelial cell density in chronic angle closure glaucoma (CACG) patients. MethodsConsecutive cases of CACG with patent peripheral iridotomy had their central corneal endothelial cell density measured by specular microscopy. The corneal endothelial cell density of those CACG eyes with a previous documented acute angle closure attack were compared with those eyes without such a history, to determine the effect of a previous acute angle closure attack on corneal endothelial cell density. ResultsFrom July 2003 to July 2005, a total of 52 CACG eyes of 52 patients fulfilling the study criteria were recruited. Thirteen eyes (25%) had a previous documented acute angle closure attack, whereas 39 eyes (75%) did not. The mean central corneal endothelial cell density ±1 standard deviation was 2271.7±312.9 (range, 1556 to 2661) cells/mm2 in those CACG eyes with previous acute angle closure, and 2570.0±429.9 (range, 1669 to 3861) cells/mm2 in those CACG eyes without previous acute angle closure (P<0.05, Student t test). A previous acute angle closure attack in a CACG eye correlates with a 11.6% reduction in corneal endothelial cell density, compared with a CACG eye without such a history. There were no statistically significant differences between the 2 groups in age, LogMAR visual acuity, intraocular pressure, number of glaucoma eye drops, vertical cup-to-disk ratio, mean deviation or pattern standard deviation in Humphrey automated perimetry (P>0.05). ConclusionsA previous acute angle closure attack correlates with a significantly reduced corneal endothelial cell density in CACG patients.
Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality

Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor and non‐motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality.