Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Beryllium Disease and Glutathione Biosynthesis Genes

Objective: Because glutathione (GSH) has been reported to be increased in chronic beryllium disease (CBD) and is associated with immune modulation, associations between CBD and gene polymorphisms of the rate-limiting enzyme in GSH synthesis, glutamate cysteine ligase (GCL), were investigated. Glutamate cysteine ligase consists of a catalytic subunit (GCLC) and modifier subunit (GCLM). Methods: Patients with CBD, beryllium-sensitized subjects (BeS), and beryllium-exposed subjects without CBD were genotyped for the GCLC GAG trinucleotide repeat polymorphism (GCLC TNR), the GCLC-129 single nucleotide polymorphism (SNP), and the GCLM-588 SNP. Results: Results indicate that GCLC TNR genotype 7/7 is negatively associated with CBD (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.08–0.95) and the GCLM-588 C/C SNP genotype is associated with CBD susceptibility (OR = 3.07, 95% CI = 1.00–9.37). No differences were noted in the BeS group. Conclusions: This study suggests that GSH modulation may play a role in CBD pathogenesis, but not in sensitization to beryllium.
Electronic Nicotine Delivery Systems (“E-cigarettes”)

Background and Objectives Cigarette smoking is common among cancer patients and is associated with negative outcomes. Electronic nicotine delivery systems (“e-cigarettes”) are rapidly growing in popularity and use, but there is limited information on their safety or effectiveness in helping individuals quit smoking. Data Sources The authors searched PubMed, Web of Science, and additional sources for published empirical data on safety and use of electronic cigarettes as an aid to quit smoking. Review Methods We conducted a structured search of the current literature up to and including November 2013. Results E-cigarettes currently vary widely in their contents and are sometimes inconsistent with labeling. Compared to tobacco cigarettes, available evidence suggests that e-cigarettes are often substantially lower in toxic content, cytotoxicity, associated adverse effects, and secondhand toxicity exposure. Data on the use of e-cigarettes for quitting smoking are suggestive but ultimately inconclusive. Conclusions Clinicians are advised to be aware that the use of e-cigarettes, especially among cigarette smokers, is growing rapidly. These devices are unregulated, of unknown safety, and of uncertain benefit in quitting smoking. Implications for Practice In the absence of further data or regulation, oncologists are advised to discuss the known and unknown safety and efficacy information on e-cigarettes with interested patients and to encourage patients to first try FDA-approved pharmacotherapies for smoking cessation.
Activity Profile In Vitro of Micafungin against Spanish Clinical Isolates of Common and Emerging Species of Yeasts and Molds

ABSTRACT A collection of 2,278 isolates belonging to 86 different fungal species was tested with micafungin and eight other drugs using the EUCAST procedures. Micafungin was active against species of Candida and Aspergillus (even azole-resistant species) as well as Penicillium spp. , Scedosporium apiospermum, and Acremonium spp. It was inactive for species of Basidiomycota and Mucorales and for multiresistant species such as those of Fusarium.
The public release of hospital and physician mortality data in Pennsylvania. A case study.

OBJECTIVES Using the public reports of the Pennsylvania Health Care Cost Containment Council on coronary artery bypass graft surgery for 1990 to 1992 as a case study, the authors assess the sensitivity of results to the choice of data and statistical methodology. METHODS Using the Council's public-release data, surgical mortality and utilization were reanalyzed by standard linear models, empirical Bayes methods, Monte Carlo simulations, and hierarchical statistical models. RESULTS Statistical power calculations demonstrate that the annual volume of bypass surgery for many hospitals and for most surgeons is too small for meaningful mortality comparisons. The number of hospitals and physicians designated as mortality "outliers" in the Council's reports results in part from a failure to adjust critical P values for multiple comparisons. Hierarchical statistical models implemented by mixed effects logistic regression, by contrast, can detect true differences in performance without producing false outliers. Mortality analyses are sensitive to the choice of comorbidities used for severity adjustment of a mortality model. Small-area analyses indicate large differences in the rates of bypass surgery across Pennsylvania, with lower population-based rates of surgery associated with higher population-based inpatient mortality. CONCLUSIONS Analyses of mortality by operative procedure, rather than by patient diagnosis, should consider the potential for selection bias caused by the decision to elect surgery. The clinical and statistical issues of operative mortality are sufficiently complex to merit review by independent experts before public release of hospital and physician performance measures.
Anti-Factor Xa Assay Is a Superior Correlate of Heparin Dose Than Activated Partial Thromboplastin Time or Activated Clotting Time in Pediatric Extracorporeal Membrane Oxygenation*

Objective: To assess the utility of activated clotting time, activated partial thromboplastin time, and anti-Factor Xa assay for the monitoring and dosing of heparin in pediatric patients requiring support with extracorporeal membrane oxygenation. Design: Retrospective chart review. Setting: PICU in a single, tertiary care, academic children’s hospital. Patients: Seventeen patients (age 1 d to 13.9 yr, median 0.83 yr) managed on pulmonary and cardiac extracorporeal membrane oxygenation between March 2010 and August 2012 by a single surgeon. Interventions: None. Measurements and Main Results: Twice daily measurements of anti-Factor Xa assay, activated clotting time, and activated partial thromboplastin time were determined from the same blood specimen. Data were analyzed using SAS system v9.2. Fourteen patients (82.4%) were successfully weaned from extracorporeal membrane oxygenation and 12 (70.6%) were discharged from the hospital. Pearson correlations were used to compare heparin dose and activated clotting time, activated partial thromboplastin time, and anti-Factor Xa assay. Analysis showed negative Pearson correlations in 11 of 17 patients between the activated clotting time and heparin, as compared with seven of 17 for activated partial thromboplastin time and only one for heparin and anti-Factor Xa assay. Only four patients had moderate to strong positive correlations between activated clotting time and heparin as compared with a moderate to strong positive correlation in 10 patients for anti-Factor Xa assay and heparin. Conclusions: The anti-Factor Xa assay correlated better with heparin dosing than activated clotting time or activated partial thromboplastin time. Activated clotting time has a poor correlation to heparin doses commonly associated with extracorporeal membrane oxygenation. In pediatric extracorporeal membrane oxygenation, anti-Factor Xa assay may be a more valuable monitor of heparin administration.
Immunohistochemical Observation of Pituitary Adenylate Cyclase–activating Polypeptide (PACAP) and Adenohypophysial Hormones in the Pituitary of a Teleost, Uranoscopus japonicus

Abstract A neuropeptide, pituitary adenylate cyclase–activating polypeptide (PACAP) has possible potency as a hypothalamic factor mediating the release of pituitary hormones, especially growth hormone (GH), in the fish pituitary. We used double-immunostaining to examine the relationship between PACAP nerve fibers and adenohypophysial hormone-producing cells in the pituitary of a teleost, the stargazer Uranoscopus japonicus, and enzyme immunoassay to determine the quantity of PACAP in the stargazer brain, in conjunction with the body mass and gonad somatic index (GSI) of fish. In adult stargazer, PACAP-like immunoreactive (PACAP-LI) nerve fibers and endings were identified in both the neurohypophysis and adenohypophysis in close proximity to pituitary cells containing immunoreactive hormones such as prolactin, somatolactin, the N-terminal peptide of proopiomelanocortin, and N-acetyl endorphin. PACAP-LI nerve fibers were also identified close to immunoreactive GH cells in the pituitary of young fish. The concentration of immunoreactive PACAP in whole brain ranged from 100 to 800 pmol/g wet weight, in fish with weighing 70–480 g. A negative correlation was found between the concentration of immunoreactive PACAP in the whole brain and body weight, but there was no relation between the former and GSI. These results suggest that PACAP may act as a hypophysiotropic factor in the stargazer pituitary.
Therapeutic Equivalence Requires Pharmaceutical, Pharmacokinetic, and Pharmacodynamic Identities: True Bioequivalence of a Generic Product of Intravenous Metronidazole

ABSTRACT Animal models of infection have been used to demonstrate the therapeutic failure of “bioequivalent” generic products, but their applicability for this purpose requires the accurate identification of those products that are truly bioequivalent. Here, we present data comparing one intravenous generic product of metronidazole with the innovator product in a neutropenic mouse thigh anaerobic infection model. Simultaneous experiments allowed comparisons (generic versus innovator) of potency and the concentration of the active pharmaceutical ingredient (API), analytical chemistry (liquid chromatography/mass spectrometry [LC/MS]), in vitro susceptibility testing, single-dose serum pharmacokinetics (PK) in infected mice, and in vivo pharmacodynamics (PD) against Bacteroides fragilis ATCC 25825 in synergy with Escherichia coli SIG-1 in the neutropenic mouse thigh anaerobic infection model. The Hill dose-response model followed by curve-fitting analysis was used to calculate and compare primary and secondary PD parameters. The generic and the innovator products were identical in terms of the concentration and potency of the API, chromatographic and spectrographic profiles, MIC and minimal bactericidal concentrations (MBC) (2.0 mg/liter), and mouse PK. We found no differences between products in bacteriostatic doses (BD) (15 to 22 mg/kg of body weight per day) or the doses needed to kill 1 log (1LKD) (21 to 29 mg/kg per day) or 2 logs (2LKD) (28 to 54 mg/kg per day) of B. fragilis under dosing schedules of every 12 h (q12h), q8h, or q6h. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) was the best PD index to predict the antibacterial efficacy of metronidazole (adjusted coefficient of determination [AdjR2] = 84.6%), and its magnitude to reach bacteriostasis in vivo (56.6 ± 5.17 h) or to kill the first (90.8 ± 9.78 h) and second (155.5 ± 22.2 h) logs was the same for both products. Animal models of infection allow a thorough demonstration of the therapeutic equivalence of generic antimicrobials.
Adolescent subthreshold-depression and anxiety: psychopathology, functional impairment and increased suicide risk.

BACKGROUND Subthreshold-depression and anxiety have been associated with significant impairments in adults. This study investigates the characteristics of adolescent subthreshold-depression and anxiety with a focus on suicidality, using both categorical and dimensional diagnostic models. METHODS Data were drawn from the Saving and Empowering Young Lives in Europe (SEYLE) study, comprising 12,395 adolescents from 11 countries. Based on self-report, including Beck Depression Inventory-II (BDI-II), Zung Self-Rating Anxiety Scale (SAS), Strengths and Difficulties Questionnaire (SDQ) and Paykel Suicide Scale (PSS) were administered to students. Based on BDI-II, adolescents were divided into three groups: nondepressed, subthreshold-depressed and depressed; based on the SAS, they were divided into nonanxiety, subthreshold-anxiety and anxiety groups. Analyses of Covariance were conducted on SDQ scores to explore psychopathology of the defined groups. Logistic regression analyses were conducted to explore the relationships between functional impairments, suicidality and subthreshold and full syndromes. RESULTS Thirty-two percent of the adolescents were subthreshold-anxious and 5.8% anxious, 29.2% subthreshold-depressed and 10.5% depressed, with high comorbidity. Mean scores of SDQ of subthreshold-depressed/anxious were significantly higher than the mean scores of the nondepressed/nonanxious groups and significantly lower than those of the depressed/anxious groups. Both subthreshold and threshold-anxiety and depression were related to functional impairment and suicidality. CONCLUSIONS Subthreshold-depression and subthreshold-anxiety are associated with an increased burden of disease and suicide risk. These results highlight the importance of early identification of adolescent subthreshold-depression and anxiety to minimize suicide. Incorporating these subthreshold disorders into a diagnosis could provide a bridge between categorical and dimensional diagnostic models.
Functional and Structural Characterization of P[19] Rotavirus VP8* Interaction with Histo-blood Group Antigens

ABSTRACT Rotaviruses (RVs) of species A (RVA) are a major causative agent of acute gastroenteritis. Recently, histo-blood group antigens (HBGAs) have been reported to interact with human RVA VP8* proteins. Human P[19] is a rare P genotype of porcine origin that infects humans sporadically. The functional and structural characteristics of P[19] VP8* interaction with HBGAs are unknown. In this study, we expressed and purified the VP8* proteins of human and porcine P[19] RVs. In oligosaccharide and saliva binding assays, P[19] VP8* proteins showed obvious binding to A-, B-, and O-type saliva samples irrespective of the secretor status, implying broad binding patterns. However, they did not display specific binding to any of the oligosaccharides tested. In addition, we solved the structure of human P[19] VP8* at 2.4 Å, which revealed a typical galectin-like fold. The structural alignment demonstrated that P[19] VP8* was most similar to that of P[8], which was consistent with the phylogenetic analysis. Structure superimposition revealed the basis for the lack of binding to the oligosaccharides. Our study indicates that P[19] RVs may bind to other oligosaccharides or ligands and may have the potential to spread widely among humans. Thus, it is necessary to place the prevalence and evolution of P[19] RVs under surveillance. IMPORTANCE Human P[19] is a rare P genotype of porcine origin. Based on phylogenetic analysis of VP8* sequences, P[19] was classified in the P[II] genogroup, together with P[4], P[6], and P[8], which have been reported to interact with HBGAs in a genotype-dependent manner. In this study, we explored the functional and structural characteristics of P[19] VP8* interaction with HBGAs. P[19] VP8* showed binding to A-, B-, and O-type saliva samples, as well as saliva of nonsecretors. This implies that P[19] has the potential to spread among humans with a broad binding range. Careful attention should be paid to the evolution and prevalence of P[19] RVs. Furthermore, we solved the structure of P[19] VP8*. Structure superimposition indicated that P[19] may bind to other oligosaccharides or ligands using potential binding sites, suggesting that further investigation of the specific cell attachment factors is warranted.
Objective and subjective efficacy as well as tolerability of olanzapine in the acute treatment of 120 patients with schizophrenia spectrum disorders

The aim of the present study was to evaluate the objective and subjective efficacy as well as tolerability of olanzapine in acute treatment of schizophrenia spectrum disorders under naturalistic non-selective conditions. Inpatients with schizophrenia spectrum disorders, consecutively admitted over an 18-month period, treated with olanzapine, were included. Diagnoses were made according to ICD-10 criteria based on repeated clinical assessments. Efficacy and tolerability of olanzapine were assessed at baseline and at the end of inpatient acute treatment including Positive and Negative Symptom Scale (PANSS), Clinical Global Impression, subjective assessments, UKU and biological investigations. One hundred and twenty non-selected patients who met ICD-10 criteria for schizophrenia (73%), schizophreniform disorder (14%) or schizoaffective disorder (13%) were treated with olanzapine 15.3±5.2 mg/day. Baseline severity (PANSS total mean score 102.2) was higher compared to various admittance studies (PANSS total mean score 86–90). In 32% of patients (n=38), olanzapine treatment was discontinued, mainly because of inefficacy for positive (89%, n=34) and/or negative (95%, n=36) symptoms and/or because of adverse events (37%, n=14). Response rates as improvement in PANSS total score (after ≥3 weeks of treatment) of ≥20%, 30% or 40% were 68%, 55% and 35%, respectively. Response rates in post-hoc defined treatment resistant patients were not significantly different from non-refractory patients. Sedation (26%) was the most common side-effect, followed by weight gain (22%). With regards to subjective efficacy, 30% of the patients were not satisfied with the efficacy of olanzapine, while only 6% of the patients reported a not satisfying subjective tolerability. According to duration of olanzapine treatment, the results for patients, who remained in hospital, revealed a faster increase of weight compared to admittance studies (7 kg in 14 weeks versus 7 kg in 38 weeks). Olanzapine has been found to be effective and tolerable, also under naturalistic acute treatment conditions. Compared to previous double-blind admittance studies, patients had a higher severity of illness at entry and a lower ≥40% PANSS total score response rate. By contrast to previous results, mean dose of olanzapine was similar for multiple- and first-episode patients, and weight gain was more severe. The results underline the need of Phase IV studies for the assessment of clinical antipsychotic efficacy and tolerability.
Response to abomasal infusion of methionine of weaned dairy calves fed a complete pelleted starter ration based on by-product feeds.

Three abomasal infusion trials were to determine the first-limiting amino acid for nitrogen retention of postweaned Holstein bull calves fed a starter ration based on cereal by-product feeds. Ration ingredients contributed the following percentages of total amino acids: wheat middlings 38, brewer's grains 24, hominy feed 21, oat hulls 10, distiller's grains 6, and molasses 1. Dry matter of the pelleted ration contained 13 to 14% crude protein and . 23 to . 26% sulfur. Each trial was a replicated 4 x 4 Latin square with 9-day periods. Calves were weaned at 4 wk and infusions initiated at 5 to 6 wk of age. Abomasal infusion of the 10 essential amino acids, an isonitrogenous quantity of an equimolar mixture of alanine, asparagine, glutamate, glycine, and serine, or an isocaloric quantity of glucose indicated that essential amino acid(s) rather than nonspecific nitrogen or energy was limiting protein synthesis. Quadratic responses in urine nitrogen excretion and retained nitrogen occurred when 0, . 3, . 6, and 1.2 g L-methionine/kg starter ration were infused. Greatest responses occurred with . 6 g methionine, which increased retained nitrogen 11 and 19% and decreased urine nitrogen 7 and 10%. The relationship between infused methionine and plasma methionine was linear. Infusions in all trials had no effect on digestibility of energy and nitrogen.
Handwriting in Children With ADHD

Objective: Children with ADHD–combined type (ADHD-CT) display fine and gross motor problems, often expressed as handwriting difficulties. This study aimed to kinematically characterize the handwriting of children with ADHD using a cursive letter l’s task. Method: In all, 28 boys (7-12 years), 14 ADHD-CT and 14 typically developing (TD), without developmental coordination disorder (DCD) or comorbid autism, wrote a series of four cursive letter l’s using a graphics tablet and stylus. Results: Children with ADHD-CT had more inconsistent writing size than did TD controls. In addition, ADHD-CT symptom severity, specifically inattention, predicted poorer handwriting outcomes. Conclusion: In a sample of children with ADHD-CT who do not have DCD or autism, subtle handwriting differences were evident. It was concluded that handwriting might be impaired in children with ADHD in a manner dependent on symptom severity. This may reflect reports of underlying motor impairment in ADHD.
Gene Delivery to Muscle

The delivery of genes to skeletal muscle by myoblast implantation, DNA injection, or viral transduction has therapeutic applications for human neuromuscular and systemic disorders, many of which are now represented by transgenic or “knockout” mouse models. This unit describes the isolation and retroviral transduction of mouse myoblasts, the injection of myoblasts and plasmid DNA into mouse muscle, and histological methods for analyzing the recipient muscle. A procedure describing the injection of plasmid DNA into muscle with or without electric charge is also included.
Meikin‐associated polo‐like kinase specifies Bub1 distribution in meiosis I

In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono‐orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP‐C during meiosis I, recruits Plo1 (polo‐like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1. Consequently, in contrast to the transient kinetochore localization of mitotic Bub1, meiotic Bub1 persists at kinetochores until anaphase I. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization and cohesion protection at centromeres by cooperating with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Furthermore, molecular genetic analyses show a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin that is important for establishing meiosis‐specific chromosome segregation. We provide evidence that the meiosis‐specific Bub1 regulation is conserved in mouse.
Characterization of the complete mitochondrial genome of the Grey-backed Shrike, Lanius tephronotus (Aves: Passeriformes): The first representative of the family Laniidae with a novel CAA stop codon at the end of cox2 gene

The complete Grey-backed Shrike mitochondrial genome has been sequenced to be 16,820 bp in length, consisting of 37 encode genes: 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. In addition, a single control region was also observed. Compared with other reported Passeriformes mtgenome sequences, three bases CAA were detected at the end of Lanius tephronotus cox2 gene with the downstream adjacent base T. The first base of CAA probably occurred C to U transcript editing event resulting in a normal stop codon UAA.
Coordinated control of multiple unicycles for escorting and patrolling task based on a cyclic pursuit strategy

This paper investigates the coordinated control problem of multiple unicycles for the escorting and patrolling task with respect to a moving target unicycle. The topology of the sensor graph results from a cyclic pursuit strategy and it may dynamically change with the positions of unicycles. A controller for each escort unicycle is developed by using the information from local sensing. It is shown that with the proposed control law, all escort unicycles can globally converge to orbiting around the target in a common circle with desired radius and maintaining evenly spaced along the circle. Finally, the simulation results of an example verify effectiveness of the proposed controller.