Miracle-dz/UniFAR-FTUs huggingface dataset:
Traumatic life events in bipolar disorder: impact on BDNF levels and psychopathology.

BACKGROUND There is evidence that vulnerability to depression and anxiety disorders is markedly increased by traumatic life events. While childhood abuse has been reported to be associated with poorer outcomes in bipolar disorder, little is known about the neurobiological basis underlying this association. The aim of this study was to ascertain whether bipolar patients who were exposed to a traumatic event or events (TE) have lower brain-derived neurotrophic factor (BDNF) levels and more severe psychopathology as indicated by increased comorbidity and other clinical features when compared to those who were not exposed to TE. METHODS One-hundred and sixty-three consecutively recruited bipolar outpatients were assessed by Structured Clinical Interview for DSM-IV (SCID) and standard protocol in order to evaluation psychopathology and clinical features. The reported TE was assessed using DSM-IV stem criteria for trauma (as defined by A1 and A2 criteria for trauma for post-traumatic stress disorder). Subjects were divided into 2 groups according to presence or absence of lifetime TE. The levels of BDNF, comorbidity and other clinical features were compared between groups. RESULTS After adjusting for confounders, results indicated that bipolar patients with a history of TE have alcohol abuse/dependence (p < 0.001), anxiety comorbidity, and lower levels of serum BDNF (p < 0.01) compared to those without a history of TE. There was no difference between the 2 groups in age of onset, presence of psychosis, other substance abuse and dependence, rapid cycling or suicide attempts. CONCLUSIONS Our findings suggest that TE are associated with significantly increased prevalence of alcohol and anxiety comorbidity as well as lower BDNF levels in bipolar patients. It is possible that a decrease in BDNF levels may account for increased comorbidity, but further prospective studies are required to confirm this.
Severe obstructive sleep apnea in loeys–dietz syndrome successfully treated using continuous positive airway pressure

Loeys–Dietz syndrome is a recently recognized connective tissue disorder characterized by severe craniofacial and skeletal abnormalities as well as arterial tortuosity with aggressive aneurysm formation. Marfan syndrome, a classic connective tissue disorder, is known to be associated with a risk of obstructive sleep apnea, but sleep‐related breathing disorders have not been previously documented in Loeys–Dietz syndrome. The propositus had the prototypic features of Loeys–Dietz syndrome with a de novo mutation in TGFBR2. He developed severe obstructive sleep apnea during his infancy. Continuous positive airway pressure was introduced at age 7 years and provided significant improvement in his nocturnal apnea and sleep apnea‐related symptoms, such as enuresis. Marfan syndrome is known to be associated with a high risk of sleep apnea because of its characteristic craniofacial and connective tissue abnormalities. Similarly, the severe craniofacial abnormalities in Loeys–Dietz syndrome may predispose patients to severe obstructive sleep apnea, even at a very young age. Despite the severity of obstructive sleep apnea in the propositus, the administration of continuous positive airway pressure was highly effective in alleviating his symptoms. In summary, severe obstructive sleep apnea was successfully treated using continuous positive airway pressure in a patient with Loeys–Dietz syndrome. Careful evaluation and aggressive intervention for the alleviation of obstructive sleep apnea is warranted in Loeys–Dietz syndrome. © 2013 Wiley Periodicals, Inc.
Methylation Levels of CADM1, MAL, and MIR124-2 in Cervical Scrapes for Triage of HIV-Infected, High-Risk HPV-Positive Women in Kenya

Objectives:To evaluate the value of cervical cell methylation markers in screening HIV-infected women also positive for high-risk human papillomavirus (hrHPV). Design:Cross-sectional and prospective. Methods:Two hundred forty-eight HIV-infected hrHPV-positive women enrolled in a cervical cancer screening study in Nairobi, Kenya, had colposcopy-directed biopsy and histological diagnoses. Exfoliated cervical cells were used to measure methylation levels of the CADM1, MAL, and MIR124-2 genes using quantitative methylation-specific polymerase chain reaction. Methylation levels were summarized as cycle threshold (Ct) ratios compared with the &bgr;-actin gene. Median Ct ratios were compared across histological diagnoses, with 95% confidence intervals calculated by bootstrapping. Methylation levels at 6 months were assessed in 128 women who remained hrHPV positive. Results:All 3 methylation markers showed significantly (P < 0.001) raised median Ct ratios in women with cervical intraepithelial neoplasia (CIN) grade 3 compared with women with a normal cervix. When markers were combined into a single test, the area under the receiver operating characteristic curve for prediction of CIN2 or worse (CIN2+) was 0.80. When the test was calibrated to have similar specificity, sensitivity of the combined tri-marker test for CIN2+ was comparable with cytology [atypical squamous cells of undetermined significance or worse] (89% and 95%, respectively) and superior to visual inspection with acetic acid (85% vs 70%) and HPV16/18 genotyping (65% vs 40%). Among women with no CIN2+ at baseline and persistent hrHPV at 6-month follow-up, MAL-m1 and MIR124-2 Ct ratios increased significantly. Conclusions:Methylation markers in combination with HPV testing may offer a full molecular screening strategy to the many HIV-infected women who are also hrHPV positive.
Evaluation on a Streptococcus suis vaccine using recombinant sao-l protein manufactured by bioreactors as the antigen in pigs.

Streptococcus suis (S. suis) can be classified into 33 serotypes based on the structure of capsular polysaccharides. Recent research indicated that a new surface protein designated as Sao (surface antigen one) reacts with 30 serotypes of convalescent-phase sera during S. suis infections, which makes Sao a good potential antigen for developing S. suis vaccines. The objectives of this study were to produce recombinant Sao-L protein (rSao-L) from a strain of S. suis serotype 2 by a prokaryotic expression system in bioreactors and to use rSao-L as the antigen for a S. suis vaccine in mouse and swine models. The antibody titres in mice and pigs immunized with rSao-L were significantly (P < 0.05) increased. After challenge with live S. suis serotype 1 bacteria, the anatomical lesions in pigs immunized with rSao-L were reduced by 60%. These data indicated that immunization with rSao-L can confer cross-serotype protection against S. suis. Moreover, percentages of CD8(+) and CD4(+) /CD8(+) double-positive T cells in immunized pigs were significantly higher than those of the control group (P < 0.01). Using bioreactors to produce rSao-L as the antigen for S. suis vaccines may broaden protective efficacy and reduce production costs.
Empathy Between Physician Assistant Students and Standardized Patients: Evidence of an Inflation Bias

Purpose Empathic communication with patients is an essential component of quality primary care. This study examines the ability of physician assistant (PA) students to communicate empathically in clinical interviews with standardized patients. Methods In their first year of training, PA students conducted 3 clinical interviews with standardized patients over a 6-month period in 2014, during the second half of their didactic year. Each interview was evaluated for empathy by 4 individuals: the students themselves, their standardized patients, their clinical instructors, and third-party observers. Results Students consistently rated their empathic abilities more favorably than did patients, clinical instructors, or observers, with mean differences ranging from 0.56 to 1.92 and averaging 1.09 on a 9-point scale. Students' evaluations were most dissimilar from those of patients (difference M = 1.12) and most similar to those of observers (difference M = 1.06). The assessments of all 4 raters varied over time: students rated themselves as significantly more empathic in April (time 2) than in July (time 3) of their didactic year. Patients rated students as significantly less empathic in January of the didactic year (time 1) than at time 2 and as significantly more empathic at time 2 than time 3. Instructors rated students as significantly less empathic at time 1 than at either time 2 or time 3. Finally, observers rated students as significantly more empathic at time 1 than at either time 2 or time 3. Conclusions PA students consistently overestimate their empathic abilities during their first year of training. Given the importance of empathy in clinical care, increased didactic efforts focused on developing and conveying empathy may be warranted in PA education.
Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors

The concept for cellular immunotherapy of solid tumors relies heavily on the capacity of class I MHC-restricted cytotoxic T lymphocytes (CTLs) to eliminate tumor cells. However, tumors often have managed to escape from the cytolytic machinery of these effector cells. Therefore, it is very important to chart the mechanisms through which this escape can occur. Target-cell killing by CTLs involves the induction of apoptosis by two major mechanisms: through death receptors and the perforin/granzyme B (GrB) pathway. Whereas tumors previously were shown to exhibit mechanisms for blocking the death receptor pathway, we now demonstrate that they also can resist CTL-mediated killing through interference with the perforin/GrB pathway. This escape mechanism involves expression of the serine protease inhibitor PI-9/SPI-6, which inactivates the apoptotic effector molecule GrB. Expression of PI-9 was observed in a variety of human and murine tumors. Moreover, we show that, indeed, expression results in the resistance of tumor cells to CTL-mediated killing both in vitro and in vivo. Our data reveal that PI-9/SPI-6 is an important parameter determining the success of T cell-based immunotherapeutic modalities against cancer.
The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase

We have previously shown that cells mutant for TOP3, a gene encoding a prokaryotic-like type I topoisomerase in Saccharomyces cerevisiae, display a pleiotropic phenotype including slow growth and genome instability. We identified a mutation, sgs1 (slow growth suppressor), that suppresses both the growth defect and the increased genomic instability of top3 mutants. Here we report the independent isolation of the SGS1 gene in a screen for proteins that interact with Top3. DNA sequence analysis reveals that the putative Sgs1 protein is highly homologous to the helicase encoded by the Escherichia coli recQ gene. These results imply that Sgs1 creates a deleterious topological substrate that Top3 preferentially resolves. The interaction of the Sgs1 helicase homolog and the Top3 topoisomerase is reminiscent of the recently described structure of reverse gyrase from Sulfolobus acidocaldarius, in which a type I DNA topoisomerase and a helicase-like domain are fused in a single polypeptide.
Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease.

BACKGROUND Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 microg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years. RESULTS Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the budesonide group, as compared with a decline of 81 ml per year in the placebo group (P<0.001). From nine months to the end of treatment, the FEV1 declined at similar rates in the two groups (P=0.39). Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising (P<0.001). Newly diagnosed hypertension, bone fractures, postcapsular cataracts, myopathy, and diabetes occurred in less than 5 percent of the subjects, and the diagnoses were equally distributed between the groups. CONCLUSIONS In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline.
Pharmacokinetic and pharmacodynamics evaluation of ceftobiprole medocaril for the treatment of hospital-acquired pneumonia

Introduction: Ceftobiprole is a cephalosporin with activity against methicillin-resistant Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa with a promising role in the treatment of hospital-acquired pneumonia (HAP). Cure rates, however, with ceftobiprole at the doses studied may be inferior to conventional treatment in the ventilator-acquired subset of HAP. Areas covered: Literature was sought using PubMed and through abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy (2006 – 2012) and the European Congress of Clinical Microbiology and Infectious Diseases (2007 – 2012). The authors used the search terms “ceftobiprole,” “BAL9141,” “RO63-9141,” “BAL5788,” and ‘RO5788. ” The article discusses the activity, mechanism of action, pharmacokinetics (PK), pharmacodynamics (PD), and clinical trials of ceftobiprole in HAP. The article also provides discussion of how PK/PD parameters play a role in the outcome of HAP treatment and how dosing in ventilator-associated pneumonia (VAP) should be reconsidered in light of altered PK/PD. Expert opinion: In patients with normal PK and non-VAP, ceftobiprole is effective for the treatment of HAP in the recommended doses, ceftobiprole is unlikely to achieve the desired PD targets when PK parameters are altered in VAP (e.g., increased volume of distribution and clearance). In these settings, off-label use at higher doses may overcome these limitations; but in the presence of alternative therapies, it cannot be currently recommended.
Contact-State Classification in Human-Demonstrated Robot Compliant Motion Tasks Using the Boosting Algorithm

Robot programming by demonstration is a robot programming paradigm in which a human operator directly demonstrates the task to be performed. In this paper, we focus on programming by demonstration of compliant motion tasks, which are tasks that involve contacts between an object manipulated by the robot and the environment in which it operates. Critical issues in this paradigm are to distinguish essential actions from those that are not relevant for the correct execution of the task and to transform this information into a robot-independent representation. Essential actions in compliant motion tasks are the contacts that take place, and therefore, it is important to understand the sequence of contact states that occur during a demonstration, called contact classification or contact segmentation. We propose a contact classification algorithm based on a supervised learning algorithm, in particular on a stochastic gradient boosting algorithm. The approach described in this paper is accurate and does not depend on the geometric model of the objects involved in the demonstration. It neither relies on the kinestatic model of the contact interactions nor on the contact state graph, whose computation is usually of prohibitive complexity even for very simple geometric object models.
Study on Semantic Similarity Computation in E-Commerce Semantic Search

Through the study on semantic similarity in e-commerce semantic search, this paper comes up with an approach for construction of upper-level ontology structure in the field of e-commerce and a new method for computation of semantic similarity between information content and concept node link distance. Semantic feature vectors of information from web pages are extracted by making use of the upper-level ontology structure and relevant feedback-based retrieval approaches. The semantic similarity relation between query conditions and document information is determined through the semantic feature vectors of documents and the similarity function which is based on the upper-level ontology structure, and this approach is applied in commercial information search.
Is the ℓ1-optimal lateral autopilot of PI type robust?

The ℓ1-optimal digital autopilot needed to control of the roll for an aircraft under an arbitrary unmeasured disturbances is addressed in this paper. This autopilot has to achieve a desired lateral motion control via minimizing the upper bound on the absolute value of the difference between the given and true roll angles. It is ensured by means of the two digital ℓ1-optimal controllers of PI type The main result consists in establishing the fact that this controller can be robust in the presence of parametric and nonparametric uncertainties.
EXPLORING THE SOCIOBIOLOGY OF PYOVERDIN‐PRODUCING PSEUDOMONAS

The idea that bacteria are social is a popular concept with implications for understanding the ecology and evolution of microbes. The view arises predominately from reasoning regarding extracellular products, which, it has been argued, can be considered “public goods. ” Among the best studied is pyoverdin—a diffusible iron‐chelating agent produced by bacteria of the genus Pseudomonas. Here we report the de novo evolution of pyoverdin nonproducing mutants, genetically characterize these types and then test the appropriateness of the sociobiology framework by performing growth and fitness assays in the same environment in which the nonproducing mutants evolved. Our data draw attention to discordance in the fit between social evolution theory and biological reality. We show that pyoverdin‐defective genotypes can gain advantage by avoiding the cost of production under conditions where the molecule is not required; in some environments pyoverdin is personalized. By exploring the fitness consequences of nonproducing types under a range of conditions, we show complex genotype‐by‐environment interactions with outcomes that range from social to asocial. Together these findings give reason to question the generality of the conclusion that pyoverdin is a social trait.
Infection assessment of totally implanted long-term venous access devices

Aim Comparison of catheter tip versus port content culture techniques to assess infection in totally implanted vascular access devices (TIVAD). Materials and methods Comparison of pocket swab, catheter-tip and port content cultures after removing the silicon puncture septum in a prospectively collected consecutive series of 102 TIVAD removed for clinical suspicion of infection, between May 2000 and March 2003. Results 102 totally implanted port-catheters in 98 patients, age ranging from 1 to 90 years (median 53 years), were removed 7 to 2616 days after insertion (median 210 days). Infection of the pocket surrounding the port was found in 21 cases, all proven by a positive culture of the pocket swab. Out of the remaining 81 cases without pocket infection, 32 had only a positive catheter tip culture, whereas 56 had a positive port content culture (p = 0.0002). Always the same microorganism was isolated in the 32 patients with positive catheter tip and port content cultures. The main organisms identified within TIVAD were Coagulase Negative Staphylococcus (CNS) (41 cases) and Candida sp (15 cases). Eight out of the 21 pocket infections were caused by Staphylococcus aureus. Conclusion In the presence of local signs of infection, taking cultures of the pocket surrounding the port is sufficient for diagnostic purposes. When infection is localized within the device only, port content cultures taken after removal of the silicon septum are more often positive than cultures of the catheter tip, and constitute therefore a more reliable tool for the assessment of TIVAD infection.
MuB is an AAA+ ATPase that forms helical filaments to control target selection for DNA transposition

Significance DNA transposons move from one genomic location to another using a transposase. A regulatory protein might assist in target selection and avoiding self-destruction. MuB is the regulatory protein of Mu transposon. Here we report that MuB is an AAA+ (ATPase associated with diverse cellular activities) ATPase and forms right-handed helical filaments around DNA. The helical parameters of MuB and DNA are mismatched and their interactions are nonuniform. We propose that enhanced ATP hydrolysis by MuB, induced by contacts with the MuA-transposon-end complex, leads to DNA deformation and bending at the MuB filament end, thus creating a favored target for transposition. MuB is an ATP-dependent nonspecific DNA-binding protein that regulates the activity of the MuA transposase and captures target DNA for transposition. Mechanistic understanding of MuB function has previously been hindered by MuB's poor solubility. Here we combine bioinformatic, mutagenic, biochemical, and electron microscopic analyses to unmask the structure and function of MuB. We demonstrate that MuB is an ATPase associated with diverse cellular activities (AAA+ ATPase) and forms ATP-dependent filaments with or without DNA. We also identify critical residues for MuB’s ATPase, DNA binding, protein polymerization, and MuA interaction activities. Using single-particle electron microscopy, we show that MuB assembles into a helical filament, which binds the DNA in the axial channel. The helical parameters of the MuB filament do not match those of the coated DNA. Despite this protein–DNA symmetry mismatch, MuB does not deform the DNA duplex. These findings, together with the influence of MuB filament size on strand-transfer efficiency, lead to a model in which MuB-imposed symmetry transiently deforms the DNA at the boundary of the MuB filament and results in a bent DNA favored by MuA for transposition.