Miracle-dz/UniFAR-FTUs huggingface dataset:
Psycholinguistic profiling differentiates specific language impairment from typical development and from attention-deficit/hyperactivity disorder.

PURPOSE Practitioners must have confidence in the capacity of their language measures to discriminate developmental language disorders from typical development and from other common disorders. In this study, psycholinguistic profiles were collected from 3 groups: children with specific language impairment (SLI), children with attention-deficit/hyperactivity disorder (ADHD), and children with typical development (TD). The capacity of different language indices to successfully discriminate SLI cases from TD and ADHD cases was examined through response operating characteristics curves, likelihood ratios, and binary logistic regression. METHOD The Test of Early Grammatical Impairment (Rice & Wexler, 2001a), Dollaghan and Campbell's (1998) nonword repetition task, Redmond's (2005) sentence recall task, and the Test of Narrative Language (Gillam & Pearson, 2004) were administered to 60 children (7-8 years of age). RESULTS Diagnostic accuracy was high for all 4 psycholinguistic measures, although modest reductions were observed with the SLI versus ADHD discriminations. Classification accuracy associated with using the Test of Early Grammatical Impairment and the Sentence Recall task was equivalent to using all 4 measures. IMPLICATIONS Outcomes confirmed and extended previous investigations, documenting high levels of diagnostic integrity for these particular indices and supporting their incorporation into eligibility decisions, differential diagnosis, and the identification of comorbidity.
Transcriptional repressor snail and progression of human hepatocellular carcinoma.

PURPOSE Snail protein is a suppressive transcriptional factor of E-cadherin that mediates cell-to-cell adhesion, tumor progression, and metastases. We explored the expression and function of Snail and its family member Slug in human hepatocellular carcinoma (HCC) to identify its role in tumor progression. EXPERIMENTAL DESIGN AND RESULTS Transfection of Snail cDNA in Li-7, endogenous E-cadherin-positive human HCC cells, selectively induced the loss of E-cadherin protein expression. We then investigated the expression of Snail and Slug mRNA in 43 human tissue samples of HCC. Using in situ hybridization, Snail mRNA was determined to dominantly express in HCC cells, but not in bile duct cells, blood vessels or infiltrating leukocytes. The mRNA of Snail and Slug were quantified using real-time reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. Snail mRNA was overexpressed in 7 cases (16%) of HCC compared with adjacent noncancerous liver tissue. E-Cadherin protein expression determined in the same 43 cases by immunohistochemistry was significantly down-regulated in those cases with Snail mRNA overexpression (P = 0.04). The tumor and nontumor ratio of Snail mRNA independently correlated with tumor invasiveness (P = 0.04). However, Slug mRNA correlated with neither E-cadherin expression nor tumor invasiveness. CONCLUSIONS The data indicate that Snail both down-regulates E-cadherin expression and promotes the invasion in human HCC.
Fatal Head Injuries in Children Under the Age of 5 Years in Pretoria

AbstractThe incidence of fatal injuries in children has been reported to be highest among children aged 1 to 4 years. Major causes of head injury include road traffic accidents, falls, and intentional or inflicted injury (such as nonaccidental injury syndrome). This study reviewed the profile of children (under 5 years of age) who had been admitted to a large urban medicolegal mortuary (in Pretoria, the capital city of South Africa), after having suffered fatal head injuries. This study was conducted over a 5-year period (from January 2004 through December 2008), and a total of 107 cases were identified for inclusion. These cases constituted nearly a fifth of admissions in this age group. The male-to-female ratio was 56%:44%, and the peak age of injury was less than 1 year. Most head injuries were sustained in road traffic accidents (70%) followed by falls (10%) and other types of blunt force injuries (9%). Only 1 case of nonaccidental injury syndrome (child abuse) was found. The great majority of deaths were deemed to have been accidental in nature (91%) with 6 (6%) homicides. Urgent review pertaining to the use of child restraint devices and the safety of pedestrians is required, and the institution of childhood injury registers could aid in reducing childhood fatalities in South Africa.
Unsupervised Image Categorization by Hypergraph Partition

We present a framework for unsupervised image categorization in which images containing specific objects are taken as vertices in a hypergraph and the task of image clustering is formulated as the problem of hypergraph partition. First, a novel method is proposed to select the region of interest (ROI) of each image, and then hyperedges are constructed based on shape and appearance features extracted from the ROIs. Each vertex (image) and its k-nearest neighbors (based on shape or appearance descriptors) form two kinds of hyperedges. The weight of a hyperedge is computed as the sum of the pairwise affinities within the hyperedge. Through all of the hyperedges, not only the local grouping relationships among the images are described, but also the merits of the shape and appearance characteristics are integrated together to enhance the clustering performance. Finally, a generalized spectral clustering technique is used to solve the hypergraph partition problem. We compare the proposed method to several methods and its effectiveness is demonstrated by extensive experiments on three image databases.
Evolution in changing environments: Modifiers of mutation, recombination, and migration

Significance Environmental variability is known to promote the evolution of mechanisms that increase phenotypic diversity. The evolution of recombination, mutation, and migration, which endow a population with the needed genetic and phenotypic variability, has been a focus of study in population genetics for more than five decades. Theoretical approaches have focused on conditions for the evolution of recombination, mutation, and migration when environments change periodically and with symmetric selection pressures. Here we extend these models to incorporate random and asymmetric selection. We compare and contrast how fluctuating selection affects the stable rates of these three evolutionary forces and highlight surprising similarities in their evolution under fluctuating selection. This study offers insights into the role of environmental duration, shape, and randomness in predicting the long-term evolutionary advantage of recombination, mutation, and migration. The production and maintenance of genetic and phenotypic diversity under temporally fluctuating selection and the signatures of environmental changes in the patterns of this variation have been important areas of focus in population genetics. On one hand, periods of constant selection pull the genetic makeup of populations toward local fitness optima. On the other, to cope with changes in the selection regime, populations may evolve mechanisms that create a diversity of genotypes. By tuning the rates at which variability is produced—such as the rates of recombination, mutation, or migration—populations may increase their long-term adaptability. Here we use theoretical models to gain insight into how the rates of these three evolutionary forces are shaped by fluctuating selection. We compare and contrast the evolution of recombination, mutation, and migration under similar patterns of environmental change and show that these three sources of phenotypic variation are surprisingly similar in their response to changing selection. We show that the shape, size, variance, and asymmetry of environmental fluctuation have different but predictable effects on evolutionary dynamics.
Treatment of Left Anterior Descending Coronary Artery Disease With Sirolimus-Eluting Stents

Background—Revascularization strategies often hinge on the presence and degree of left anterior descending coronary artery (LAD) stenosis. A decision for bypass surgery is often based on the durability of surgical LAD revascularization compared with percutaneous approaches. By decreasing restenosis, drug-eluting stents may have reduced the “reintervention gap” between surgery and percutaneous intervention, making the percutaneous route preferable. Methods and Results—Of the 1101 patients in the SIRIUS trial, 459 with an LAD stenosis were randomized to percutaneous intervention with either sirolimus-eluting or bare-metal stents. Baseline demographic, clinical, and angiographic data were obtained. Patients had 1-year clinical and 8-month angiographic follow-up. Baseline characteristics were similar in both groups. The majority of lesions were tubular type B lesions (69.7%) with a mean diameter of 2.73 mm and a mean length of 14.0 mm. The binary in-stent restenosis rate was 2% for the sirolimus stent group and 41.6% for the bare-metal arm (relative risk, 0.05; 95% CI, 0.02 to 0.1; P<0.001). One-year major adverse events (defined as cardiac death, Q-wave and non–Q-wave myocardial infarction, or target vessel revascularization) was decreased 59% in the sirolimus-stent group (9.8% versus 24.9%; relative risk, 0.39; 95% CI, 0.26 to 0.61; P<0.001). Subgroup analysis of 135 patients with proximal LAD lesions showed similar benefits. In-stent restenosis was 0 in the proximal LAD sirolimus-eluting group (n=67), compared with 38% in the bare-metal arm (n=68), and major adverse events demonstrated a similar trend, with a 50% decrease compared with control patients (10.4% versus 20.6%, P=NS). Conclusions—Sirolimus-eluting stents significantly decrease revascularization rates in LAD lesions. At 1 year, sirolimus-eluting stent revascularization rates are comparable to historic single vessel bypass surgery revascularization rates.
An interaction between the SRP receptor and the translocon is critical during cotranslational protein translocation

The signal recognition particle (SRP)–dependent targeting pathway facilitates rapid, efficient delivery of the ribosome–nascent chain complex (RNC) to the protein translocation channel. We test whether the SRP receptor (SR) locates a vacant protein translocation channel by interacting with the yeast Sec61 and Ssh1 translocons. Surprisingly, the slow growth and cotranslational translocation defects caused by deletion of the transmembrane (TM) span of yeast SRβ (SRβ-ΔTM) are exaggerated when the SSH1 gene is disrupted. Disruption of the SBH2 gene, which encodes the β subunit of the Ssh1p complex, likewise causes a growth defect when combined with SRβ-ΔTM. Cotranslational translocation defects in the ssh1ΔSRβ-ΔTM mutant are explained by slow and inefficient in vivo gating of translocons by RNCs. A critical function for translocation channel β subunits in the SR–channel interaction is supported by the observation that simultaneous deletion of Sbh1p and Sbh2p causes a defect in the cotranslational targeting pathway that is similar to the translocation defect caused by deletion of either subunit of the SR.
Thiazolidinedione drugs and cardiovascular risks: a science advisory from the American Heart Association and American College of Cardiology Foundation.

The purpose of this science advisory is to summarize the currently available data concerning thiazolidinediones and cardiovascular risk, with a focus on ischemic heart disease (IHD) events, and to provide practical recommendations to healthcare workers seeking to minimize the burden of cardiovascular disease (CVD) and other complications in their patients with type 2 diabetes mellitus. On May 21, 2007, the US Food and Drug Administration (FDA) released a safety alert concerning a possible increased risk of ischemic cardiovascular events in patients prescribed the thiazolidinedione rosiglitazone. This safety alert was prompted by the results of a large meta-analysis that reported that treatment with rosiglitazone resulted in a 43% increase in risk for myocardial infarction (MI) and a possible increase in risk for cardiovascular death.1 These data were particularly alarming because the metabolic effects of thiazolidinediones were widely presumed, although not proven, to reduce the risk for IHD. Subsequently, a number of additional reports using alternative meta-analytic techniques,2,3 new meta-analyses,4–10 recently published results of new clinical trials,11–15 and observational studies of both rosiglitazone and pioglitazone16–24 have provided variable evidence regarding an adverse cardiovascular effect of these agents. On November 14, 2007, after a specially convened FDA Advisory Panel meeting on July 30, 2007, the FDA decided not to withdraw rosiglitazone from the market. They issued new prescribing information that included a new boxed warning regarding the potential risk for myocardial ischemia, particularly in patients with heart disease taking nitrates, and in patients for whom rosiglitazone was added to established insulin therapy.25 Diabetes mellitus is increasing in prevalence in the United States and worldwide. An estimated 23.6 million people in the United States, 7.8% of the population, had diabetes in 2007, with more than 90% of cases being type 2 diabetes mellitus. Diabetes increases the risk of …
Isolation of urokinase by affinity ultrafiltration

A water‐soluble, ligand‐bound polymer has been synthesized for the purpose of isolation of urokinase, an important plasminogen activator. The affinity polymer was formed by copolymerizing N‐acryloyl‐m‐aminobenza‐midine and acrylamide in the absence of oxygen. An affinity ultrafiltration process was then developed for isolating urokinase from an artificial solution containing peroxidase and urokinase and from a crude urine source. The process yields were determined to be 86% and 49%, respectively. The recovered urokinase exhibited a specfic activity close to that of the highest commercial grade. This article also presents a new technique for assaying urokinase by coupling plasminogen with L‐benzoyl arginine‐p‐nitroanilide (L‐BAPNA), an inexpensive chromogenic substrate.
Neural Subtype Specification from Embryonic Stem Cells

One of the keys to using embryonic stem cells (ESCs) in brain research and potential application in neurological diseases is directed differentiation of neuronal and glial subtypes. This may be achieved by application of developmental principles in guiding cell lineage specification from naïve stem cells. Establishment of defined ESC differentiation models that recapitulate in vivo development, especially from human ESCs, will most likely provide a dynamic tool for dissecting molecular mechanisms underlying early embryonic development that is otherwise not readily obtainable. This is also a rational and realistic way of producing enriched populations of functional neurons and glia for pathological analyses as well as possible therapeutic applications.
The Qualification of Target Materials Using the Integral Theory of Impact

Abstract : A series of impact tests was conducted in the A.R. A.P. Impact Facility on a wide range of target materials. The penetration data obtained from these tests were used in conjunction with the simple code of the A.R. A.P. Integral Theory of Impact to evaluate two characteristic properties for each target material. One of these properties, E*p, represents the energy absorbed by the target during plastic deformation; the other, E*e is the elastic energy absorbed by the target. Knowledge of these two parameters is essential if one is to rationally design either a more effective armor system or a better penetrator. Coincident with the test program, a theory has been developed which relates these two properties to fundamental material properties which can be measured in static tests. This theory accounts for both strain-rate effects and material property changes due to shear heating. Because it clearly identifies the properties which most influence material response the theory can be used to identify candidate armor (or penetrator) materials.
Investigation of Boron Distribution in Martensitic 9% Cr Creep Resistant Steel

Chemical compositions of ferrite matrix and various other phases in a Fe - 0.17 wt. % C - 9.3 wt. % Cr - 1.55 wt. % Mo - 0.27 wt. % V - 0.015 wt. % N - 0.01 wt. % B creep resistant steel in as-received and crept conditions were analyzed with atom probe field ion microscopy. The results show the presence of some residual boron within the ferrite matrix. Analyses showed that boron was uniformly distributed within M23C6, M6C, MX, and Laves phases. Phosphor segregated to the M23C6 - ferrite matrix interface. The results are analyzed with thermodynamic calculations.
Thioredoxin Binding Protein-2 Regulates Autophagy of Human Lens Epithelial Cells under Oxidative Stress via Inhibition of Akt Phosphorylation

Oxidative stress plays an essential role in the development of age-related cataract. Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin (Trx), which deteriorates cellular antioxidant system. Our study focused on the autophagy-regulating effect of TBP-2 under oxidative stress in human lens epithelial cells (LECs). Human lens epithelial cells were used for cell culture and treatment. Lentiviral-based transfection system was used for overexpression of TBP-2. Cytotoxicity assay, western blot analysis, GFP/mCherry-fused LC3 plasmid, immunofluorescence, and transmission electronic microscopy were performed. The results showed that autophagic response of LECs with increased LC3-II, p62, and GFP/mCherry-LC3 puncta (P < 0.01) was induced by oxidative stress. Overexpression of TBP-2 further strengthens this response and worsens the cell viability (P < 0.01). Knockdown of TBP-2 attenuates the autophagic response and cell viability loss induced by oxidative stress. TBP-2 mainly regulates autophagy in the initiation stage, which is mTOR-independent and probably caused by the dephosphorylation of Akt under oxidative stress. These findings suggest a novel role of TBP-2 in human LECs under oxidative stress. Oxidative stress can cause cell injury and autophagy in LECs, and TBP-2 regulates this response. Hence, this study provides evidence regarding the role of TBP-2 in lens and the possible mechanism of cataract development.
Steady-state plasma and intrapulmonary concentrations of levofloxacin and ciprofloxacin in healthy adult subjects.

STUDY OBJECTIVE To determine the steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levofloxacin and ciprofloxacin. DESIGN Multiple-dose, open-label, randomized pharmacokinetic study. PARTICIPANTS Thirty-six healthy, nonsmoking adult subjects were randomized either to oral levofloxacin, 500 or 750 mg once daily for five doses, or ciprofloxacin, 500 mg q12h for nine doses. INTERVENTIONS Venipuncture, bronchoscopy, and BAL were performed in each subject at 4 h, 12 h, or 24 h after the last administered dose of antibiotic. MEASUREMENT AND RESULTS Mean plasma concentrations of levofloxacin and ciprofloxacin were similar to those previously reported. For once-daily dosing of levofloxacin, 500 mg, the mean (+/- SD) steady-state concentrations at 4 h, 12 h, and 24 h in ELF were 9.9 +/- 2.7 microg/mL, 6.5 +/- 2.5 microg/mL, and 0.7 +/- 0.4 microg/mL, respectively; AM concentrations were 97.9 +/- 80.0 microg/mL, 36.7 +/- 23.4 microg/mL, and 13.8 +/- 16.0 microg/mL, respectively. For levofloxacin, 750 mg, the mean steady-state concentrations in ELF were 22.1 +/- 14.9 microg/mL, 9.2 +/- 5.3 microg/mL, and 1.5 +/- 0.8 microg/mL, respectively; AM concentrations were 105.1 +/- 65.5 microg/mL, 36.2 +/- 26.1 microg/mL, and 15.1 +/- 2.0 microg/mL, respectively. The concentrations of ciprofloxacin at 4 h and 12 h in ELF were 1.9 +/- 0.9 microg/mL and 0.4 +/- 0.1 microg/mL, respectively; AM concentrations were 34.9 +/- 23.2 microg/mL and 6.8 +/- 5.9 microg/mL, respectively. The differences in the ELF concentrations of the two levofloxacin groups vs those of the ciprofloxacin group were significant (p < 0.05) at each sampling time. CONCLUSIONS Levofloxacin was more extensively distributed into intrapulmonary compartments than ciprofloxacin and achieved significantly higher steady-state concentrations in plasma and ELF during the 24 h after drug administration.
Risk of pneumonitis in cancer patients treated with immune checkpoint inhibitors: a meta-analysis

Background: A meta-analysis of the risk of pneumonitis associated with the use of immune checkpoint inhibitors in cancer patients has been conducted. Methods: Eligible publications included randomized trials of cancer patients on immune checkpoint inhibitors, describing events of all-grade and high-grade pneumonitis. Results: After exclusion of noneligible citations, a total of 11 clinical trials were eligible for the meta-analysis. The odds ratio was 3.96 [95% confidence interval (CI): 2.02–7.79; p < 0.0001] for all-grade pneumonitis and 2.87 (95% CI: 0.90–9.20; p = 0.08) for high-grade pneumonitis. Moreover, the odds ratio of all-grade pneumonitis with a nivolumab/ipilimumab combination versus ipilimumab monotherapy was 3.68 (95% CI: 1.59–8.50; p = 0.002) and, for high-grade pneumonitis, it was 1.86(95% CI: 0.36–9.53; p = 0.46). Subgroup analysis did not reveal a difference between lung cancer patients and other cancer patients in the risk of pneumonitis. Conclusions: Our analysis provided evidence that the use of immune checkpoint inhibitors is associated with an increased risk of all-grade pneumonitis compared with chemotherapy or placebo controls.
Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells

Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8+ T cells, we performed genome-wide analysis of DNA methylation, histone marking (acetylated lysine 9 in histone H3 and trimethylated lysine 9 in histone), and gene-expression profiles in naive, effector memory (EM), and terminally differentiated EM (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (e.g., KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8+ T cells, and that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8+ T cell maintenance and T cell terminal differentiation.