Miracle-dz/UniFAR-FTUs huggingface dataset:
Long term azithromycin therapy in cystic fibrosis patients: a study on drug levels and sputum properties.

BACKGROUND Following reports on the treatment of diffuse panbronchiolitis (DPB), recent studies demonstrate that long term therapy with azithromycin (AZM) is effective in cystic fibrosis (CF) patients. However, the underlying mechanisms remain uncertain. Some macrolides, including AZM, display inhibition of virulence factors and other antipseudomonal effects at subinhibitory levels in vitro. OBJECTIVES Drug doses used for CF and DPB therapy were investigated to determine whether they achieve corresponding sputum drug levels in CF patients in vivo. METHODS In an open, prospective study, 14 CF patients with chronic Pseudomonas aeruginosa airway infection received 250 mg AZM either daily ('high dose') or twice weekly ('low dose') for 12 weeks. Viscoelasticity of sputum was assessed by magnetic microrheology. RESULTS AZM accumulated in sputum by two orders of magnitude over a period of four weeks. In the following steady state, median AZM concentrations in sputum were 9.5 microg/mL (0.6 to 79.3 microg/mL, interquartiles 1.4 to 33.4 microg/mL) and 0.5 microg/mL (range less than 0.1 [below detection level] to 5.2 microg/mL, interquartiles 0.2 to 1.4 microg/mL) in the high and low dose groups, respectively. Viscoelasticity improved in all patients but one. CONCLUSIONS The findings suggest that antipseudomonal activity has to be considered among the potential mechanisms of macrolide therapy. Further, viscoelasticity may be a valuable parameter in future clinical trials.
Assessing the Incidence and Efficiency of a Prominent Place Based Policy

This paper empirically assesses the incidence and efficiency of Round I of the federal urban Empowerment Zone (EZ) program using confidential microdata from the Decennial Census and the Longitudinal Business Database. Using rejected and future applicants to the EZ program as controls, we find that EZ designation substantially increased employment in zone neighborhoods and generated wage increases for local workers without corresponding increases in population or the local cost of living. The results suggest the efficiency costs of first Round EZs were relatively small.
The Relative Importance of Factors Influencing Tropical Cyclone Rapid Intensity Changes

Predicting rapid intensity changes in tropical cyclones (TCs) is a major challenge due to the influence of multiple competing processes within the vortex and in the TC environment. We present an empirical framework that quantifies the relative importance of the various factors that influence critical transitions in TC intensities. Our analysis of model simulations of recent TCs over the Bay of Bengal identifies the following variables within the vortex as the biggest influence on TC rapid intensity changes: the amplitudes of wave number 1 of 700‐ to 850‐mb horizontal moisture flux convergence and precipitation in the rainband region and the amplitude of wave number 0 of precipitation within the radius of maximum winds. Likewise, the most important environmental variables identified are the angle between the driest air and the shear vector and the magnitude of vertical wind shear. These findings provide guidance on guidance for future observational efforts and data assimilation into TC forecasting models.
Expression of CD45R0 (UCHL1) by CD4+ and CD8+ T cells as a sign of in vivo activation in infectious mononucleosis

CD4SR0 (UCHL1), a member of leucocyte common antigen family, is expressed largely on previously activated or memory T cells. We examined CD45R0 expression of T cell subpopulations in patients with Epstein‐Barr virus (EBV) induced infectious mononucleosis (IMN) as a sign of in vivo activation. Consistent with the notion that activated CD8+ T cells expand in acute IMN, the majority of CD8+ T cells in patients with acute IMN expressed CD45R0 to the similar extent to HLA‐DR expression. Most CD4+ T cells in these patients also demonstrated marked expression of CD45R0 as well as HLA‐DR antigens, compared with age‐matched controls. Expression of CD45R0 by CD4+ T cells in patients with acute IMN was more notable than their HLA‐DR expression. While predominant CD8+ T cells resulted in decreased percentages of CD4+ T cells, CD4+ T cells expressing CD4SR0 were shown to be significantly elevated in absolute number. The results suggest that both CD4+ and CD8+ T cells may be activated by stimulation with EBV infection. The appearance of two T cell subpopulations expressing CD4SR0 in acute IMN implies their immunoregulatory roles in the control of EBV‐infected cells.
From attention to memory along the dorsal-ventral axis of the medial prefrontal cortex: some methodological considerations

Distinctions along the dorsal-ventral axis of medial prefrontal cortex (mPFC), between anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) sub-regions, have been proposed on a variety of neuroanatomical and neurophysiological grounds. Conventional lesion approaches (as well as some electrophysiological studies) have shown that these distinctions relate to function in that a number behavioral dissociations have been demonstrated, particularly using rodent models of attention, learning, and memory. For example, there is evidence to suggest that AC has a relatively greater role in attention, whereas IL is more involved in executive function. However, the well-established methods of behavioral neuroscience have the limitation that neuromodulation is not addressed. The neurotoxin 6-hydroxydopamine has been used to deplete dopamine (DA) in mPFC sub-regions, but these lesions are not selective anatomically and noradrenalin is typically also depleted. Microinfusion of drugs through indwelling cannulae provides an alternative approach, to address the role of neuromodulation and moreover that of specific receptor subtypes within mPFC sub-regions, but the effects of such treatments cannot be assumed to be anatomically restricted either. New methodological approaches to the functional delineation of the role of mPFC in attention, learning and memory will also be considered. Taken in isolation, the conventional lesion methods which have been a first line of approach may suggest that a particular mPFC sub-region is not necessary for a particular aspect of function. However, this does not exclude a neuromodulatory role and more neuropsychopharmacological approaches are needed to explain some of the apparent inconsistencies in the results.
Duplex ultrasound for identifying renal artery stenosis: direct criteria re-evaluated

Background Renal artery duplex ultrasound (RADUS) is an established method for diagnosis of renal artery stenosis (RAS), but there is no consensus regarding optimal RADUS criteria. Purpose To define optimal cutoff values for RADUS parameters when screening for RAS using intra-arterial trans-stenotic pressure gradient measurement (PGM) as reference. Material and Methods The renal arteries of 58 consecutive patients evaluated for renovascular hypertension were examined by RADUS and PGM. Conclusive measurements with both methods were obtained in 76 arteries. Hemodynamically significant RAS was defined as PGM ≥15 mmHg and was found in 43 of the 76 arteries. RADUS parameters included renal artery peak systolic velocity (PSV) and the renal–aortic ratio (RAR) of flow velocities. Receiver operating characteristic curves (ROCs) and Youden’s index were used to calculate optimal RADUS criteria for RAS. Results When traditional RADUS criteria for RAS were used, with a combination of PSV ≥180 cm/s and RAR ≥3.5, the sensitivity was 62% and the specificity was 91%. When RADUS criteria were optimized for sensitivity, then RAR ≥2.6 alone resulted in a sensitivity of 89% and a specificity of 69%. Conclusion The RAR ≥2.6 is a more sensitive criterion than traditional RADUS criteria when screening patients with clinical suspicion of RAS.
Importance of the NCp7-like domain in the recognition of pre-let-7g by the pluripotency factor Lin28

The pluripotency factor Lin28 is a highly conserved protein comprising a unique combination of RNA-binding motifs, an N-terminal cold-shock domain and a C-terminal region containing two retroviral-type CCHC zinc-binding domains. An important function of Lin28 is to inhibit the biogenesis of the let-7 family of microRNAs through a direct interaction with let-7 precursors. Here, we systematically characterize the determinants of the interaction between Lin28 and pre-let-7g by investigating the effect of protein and RNA mutations on in vitro binding. We determine that Lin28 binds with high affinity to the extended loop of pre-let-7g and that its C-terminal domain contributes predominantly to the affinity of this interaction. We uncover remarkable similarities between this C-terminal domain and the NCp7 protein of HIV-1, not only in terms of primary structure but also in their modes of RNA binding. This NCp7-like domain of Lin28 recognizes a G-rich bulge within pre-let-7g, which is adjacent to one of the Dicer cleavage sites. We hypothesize that the NCp7-like domain initiates RNA binding and partially unfolds the RNA. This partial unfolding would then enable multiple copies of Lin28 to bind the extended loop of pre-let-7g and protect the RNA from cleavage by the pre-microRNA processing enzyme Dicer.
Variability in human milk composition: benefit of individualized fortification in very-low-birth-weight infants.

BACKGROUND Preterm infants fed fortified human milk (HM) grow more slowly than those fed preterm formulas. These differences could be related to the variability in the macronutrient composition of expressed HM, resulting in inadequate nutrient intake in relation to the estimated needs of the preterm infants. OBJECTIVES The aim of this article was to show the variability in HM composition from an infant's own mother's milk (OMM) or pooled HM from the milk bank. The second objective was to evaluate the advantages of individual fortification on nutritional intakes over standard fortification. DESIGN The macronutrient composition of 428 OMM, 138 HM pools from single donors, 224 pools from multiple donors, and 14 pools from colostral milk was determined by using a mid-infrared analyzer. Individualized fortification was performed after analysis of the milk samples in 2 steps: adjustment of fat content up to 4 g/dL, followed by the addition of an HM fortifier to provide 4.3 g · kg(-1) · d(-1) according to the daily prescribed volume of feeding. Nutritional intakes resulting from the individualized fortification were compared with calculated intakes resulting from standard fortification (HM fortifier: 4 packets/dL). RESULTS The variability in contents of fat, protein, and energy was high for all types of HM samples. Compared with standard fortification, individual fortification significantly reduced the variability in nutritional intakes, allowing the maintenance of protein intake and the protein:energy ratio in the range of the nutritional recommendations. CONCLUSIONS The variability in expressed HM with respect to its protein and energy content is high. This variability persists after standard fortification, possibly resulting in under- or overnutrition. Because both over- and undernutrition confer risks in later development, individualized fortification optimizes protein and energy intake.
Genomic Risk Variants at 1p13.3, 1q41, and 3q22.3 Are Associated With Subsequent Cardiovascular Outcomes in Healthy Controls and in Established Coronary Artery Disease

Background— Genome-wide association studies have identified gene variants associated with coronary artery disease risk; however, whether they affect disease progression is largely unknown. This study investigated associations between polymorphisms at 1p13.3 (rs599839), 1q41 (rs17465637), and 3q22.3 (rs9818870) and cardiovascular outcomes in healthy volunteers and in patients with established heart disease. Methods and Results— Canterbury Healthy Volunteer study (HV) (n=1649), Coronary Disease Cohort Study (CDCS) (n=1797), and Post-Myocardial Infarction study (PMI) (n=906) participants (New Zealand), were genotyped for rs599839, rs9818870, and rs17465637. Associations between genotype and anthropometric characteristics, neurohormonal analysis, echocardiography, and clinical outcomes over medium-long-term follow-up (median HV, 5.9 years; CDCS, 3.7 years; PMI, 11.3 years) were tested. At 1p13.3, HV and CDCS participants carrying 1 or more rs599839 G allele had a lower prevalence of dyslipidemia (P⩽0.005) or lower levels of low-density lipoprotein (P=0.031) and total (P=0.004) cholesterol and/or less history of myocardial infarction (P⩽0.04) compared with AA participants. Moreover, CDCS and PMI AG/GG participants had better cardiac function as indicated by echocardiography (P⩽0.026), and fewer CDCS AG/GG participants were readmitted for a non-ST-segment elevation MI (P=0.012) during follow-up. The polymorphism at 1q41 (rs17465637) was associated with better cardiovascular outcomes in the HV (P=0.028) and PMI (P=0.008) cohorts, and 3q22.3 (rs9818870) was a predictor of death/admission in the HV cohort (P=0.045). Conclusions— These data suggest that coronary artery disease genomic risk variants at 1p13.3 and 1q41 are associated with subsequent clinical outcome in heart patients and confirm rs9818870 at 3q22.3 as a predictor of cardiovascular risk in individuals free of overt heart disease.
Coronary artery stenoses: detection with calcium scoring, CT angiography, and both methods combined.

PURPOSE To investigate prospectively the relative accuracy of computed tomographic (CT) angiography, calcium scoring (CS), and both methods combined in demonstrating coronary artery stenoses by using conventional angiography as the reference standard. MATERIALS AND METHODS The study was approved by the institutional review board Human Research Ethics Committee, and all patients completed written informed consent. Fifty patients (40 men, 10 women) aged 62 years +/- 11 (+/- standard deviation) who were suspected of having coronary artery disease underwent both conventional coronary angiography and multisection coronary CT angiography with CS. Sensitivity and specificity of CS, CT angiography, and both methods combined in demonstrating luminal stenosis greater than or equal to 50% were determined for each arterial segment, coronary vessel, and patient. Receiver operating characteristic (ROC) curves were generated for CS prediction of significant stenosis, and the Mann-Whitney U test was used for comparison of CS between groups. RESULTS When used with segment-specific electrocardiographic phase reconstructions, CT angiography demonstrated stenosed segments with 79% sensitivity and 95% specificity. Mean calcium score was greater in segments, vessels, and patients with stenoses than in segments, vessels, and patients without stenoses (P < .001 for all); nine (16%) of 56 stenosed segments, however, had a calcium score of 0. The patient calcium score correlated strongly with the number of stenosed arteries (Spearman rho = 0.75, P < .001). CS was more accurate in demonstrating stenosis in patients than in segments (areas under ROC curve were 0.88 and 0.74, respectively). CT angiography, however, was more accurate than CS in demonstrating stenosis in patients, vessels, and segments. The sensitivity and specificity of CS varied according to the threshold used, but when the calcium score cutoff (ie, >150) matched the specificity of CT angiography (95%), the sensitivity of CS in demonstrating stenosed segments was 29% (compared with 79% for CT angiography). Combining CT angiography with CS (at threshold of 400) improved the sensitivity of CT angiography (from 93% to 100%) in demonstrating significant coronary disease in patients, without a loss of specificity (85%); this finding, however, was not statistically significant. CONCLUSION CT angiography is more accurate than CS in demonstrating coronary stenoses. A patient calcium score of greater than or equal to 400, however, can be used to potentially identify patients with significant coronary stenoses not detected at CT angiography.
Multi-objective autocalibration of SWAT model for improved low flow performance for a small snowfed catchment

ABSTRACT A reliable modelling framework needs to ensure that the model is simulating reality with limited uncertainty, thus enhancing its predictive ability. In the literature, hydrological model assessment using one or more metrics is reported to be inadequate when the river flow regime is required to be reproduced comprehensively. This research is aimed to: (a) calibrate the Soil and Water Assessment Tool (SWAT) based on the concept of multi-objective optimization by applying the Borg multi-objective evolutionary algorithm (MOEA); (b) apply hydrological signatures as objective functions; and (c) adopt a multi-metric approach for model evaluation. The SWAT model was coupled with a relatively newer and powerful Borg MOEA. The inclusion of hydrological signatures as objective functions along with the conventional statistical functions assisted in improving the performance for low flows by 135% in terms of volume efficiency and 65% for flow time series simulation.
Linking the High-Resolution Architecture of Modern and Ancient Wave-Dominated Deltas: Processes, Products, and Forcing Factors

Many thoughts and concepts used in this paper were initially developed as a result of work conducted with funding provided to the WAVE Consortium at the Australian School of Petroleum, University of Adelaide (RBA, BKV and JB). The consortium sponsors (Apache, BAPETCO, BHPBP, BG, BP, Chevron, ConocoPhillips, Nexen, OMV, Shell, Statoil, Todd Energy, and Woodside Energy) are thus thanked for making this work possible. We are indebted to journal reviewers Cornel Olariu and Howard Feldman, and to Associate Editor Janok Bhattacharya for numerous comments and suggestions that improved the clarity of the manuscript.
High Accuracy of Home-Based Community Rapid HIV Testing in Rural Malawi

Objective:To assess the performance of rapid HIV antibody tests when used as part of a home-based community wide counseling and testing strategy in northern Malawi. Design:A cross-sectional population survey of HIV infection, 2007 to 2008. Methods:Adults aged 15 years or older in a demographic surveillance area were counseled and then offered an HIV test at their home by government-certified counselors. Two initial rapid tests (Determine and Uni-Gold) were performed on all samples and a third, tie-breaker test (SD Bioline) used to resolve discordant results. All people who wanted to know were posttest-counseled and informed of their results with referral to local clinical services if found to be HIV-positive. Laboratory quality control comprised retesting all positive and every tenth negative venous blood sample collected. Results:A total of 10,819 adults provided venous blood samples for HIV testing, of whom 7.5% (813) were HIV-positive. The accuracy of the parallel testing strategy used was high with 99.6% sensitivity, 100.0% specificity, 99.9% positive predictive value, and 99.9% negative predictive value. Conclusion:Face-to-face rapid testing by health personnel with minimum training at the client's home performs well when used on a wide scale in the community setting.
Colon cancer surgery in patients operated on an emergency basis.

OBJECTIVE to study the epidemiological profile of patients with colorectal cancer operated on an emergency basis at the Bonsucesso Federal Hospital. METHODS this is a retrospective study of patients operated between January 1999 and December 2012. We analyzed the following variables: age, gender, clinical data, TMN staging, tumor location, survival and types of surgery. RESULTS we evaluated 130 patients in the study period. The most frequent clinical picture was intestinal obstruction, in 78% of cases. Intestinal perforation was the surgical indication in 15%. The majority (39%) of the patients had advanced TNM staging, compared with 27% in the initial stage. There were 39 deaths (30%) documented in the period. The most common tumor site was the sigmoid colon (51%), followed by the ascending colon (16%). The curative intent was performed in most cases, with adjuvant treatment being performed in 40% of the patients. Distant metastases were found in 42% of the patients and 10% had documented disease recurrence. Disease-free survival at two and five years was 69% and 41%, respectively. CONCLUSION there was a high mortality rate and a low survival rate in colorectal cancer patients operated on urgently.
Evaluating State-of-the-Art Object Detector on Challenging Traffic Light Data

Traffic light detection (TLD) is a vital part of both intelligent vehicles and driving assistance systems (DAS). General for most TLDs is that they are evaluated on small and private datasets making it hard to determine the exact performance of a given method. In this paper we apply the state-of-the-art, real-time object detection system You Only Look Once, (YOLO) on the public LISA Traffic Light dataset available through the VIVA-challenge, which contain a high number of annotated traffic lights, captured in varying light and weather conditions. ,,,,,,The YOLO object detector achieves an AUC of impressively 90.49% for daysequence1, which is an improvement of 50.32% compared to the latest ACF entry in the VIVAchallenge. Using the exact same training configuration as the ACF detector, the YOLO detector reaches an AUC of 58.3%, which is in an increase of 18.13%.
Budesonide nasal irrigations in the postoperative management of chronic rhinosinusitis

Nasal steroids play an important role in the postoperative management of patients with chronic rhinosinusitis (CRS). However, commercially available nasal steroid sprays may not deliver adequate amounts of medication to the entire postoperative sinus cavity. The off‐label use of budesonide nasal irrigation (BNI) theoretically solves this problem by delivering concentrated steroid solution through a high‐pressure, high‐volume system. Several studies have attested to the safety of BNI, but there are very few reports of its efficacy.
RNA Interference against Platelet-Derived Growth Factor Receptor α mRNA Inhibits Fibroblast Transdifferentiation in Skin Lesions of Patients with Systemic Sclerosis

Objective To down-regulate expression of mRNA for the platelet-derived growth factor receptor (PDGFR)-α, block the signalling pathway of PDGF and its receptor, and study their influence on fibroblast transdifferentiation to myofibroblasts in systemic sclerosis (SSc). Methods Fibroblasts from skin lesions of SSc patients and health adult controls were cultured in vitro, and α-smooth muscle actin (α-SMA) expression was determined by immunocytochemistry. Both groups of fibroblasts were stimulated with PDGF-AA, transforming growth factor β1 (TGF-β1), and costimulated with PDGF-AA and TGF-β1, then PDGFR-α and α-SMA mRNA and protein expression were detected with RT-PCR and WB respectively. Three pairs of siRNAs targeting different PDGFR-α mRNA sequences were synthesized for RNAi. SSc and control fibroblasts were transfected with PDGFR-α siRNA; stimulated with PDGF-AA; and assessed for PDGFR-α and α-SMA mRNA and protein expression. Results Although the fibroblasts from both groups had similar morphology, the SSc skin lesions had significantly more myofibroblasts than control skin lesions. PDGF-AA stimulation, TGF-β1 stimulation, and costimulation significantly up-regulated PDGFR-α and α-SMA mRNA and protein expression in SSc fibroblasts compared to control (P<0.05), and costimulation had the strongest effects (P<0.05). All three pairs of siRNAs suppressed PDGFR-α mRNA and protein expression (P<0.05), but siRNA1495 had the highest gene-silencing efficiency (P<0.05). PDGFR-α siRNA attenuated the effects of PDGF-AA through up-regulating PDGFR-α and α-SMA mRNA and protein expression and inhibiting fibroblast transdifferentiation to myofibroblasts in SSc (P<0.05). Conclusions PDGFR-α over-expression in SSc fibroblasts bound PDGF-AA more efficiently and promoted fibroblast transdifferentiation, which was enhanced by TGF-β1. PDGFR-α siRNA down-regulated PDGFR-α expression, blocked binding to PDGF-AA, and inhibited fibroblast transdifferentiation to myofibroblasts.