Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced FK506 production in Streptomyces tsukubaensis by rational feeding strategies based on comparative metabolic profiling analysis

FK506, a widely used immunosuppressant, is produced by industrial fermentation processes using various Streptomyces species. However, the low titer becomes a bottleneck for its application and industrialization. It urgently required a full understanding of the biological mechanisms for FK506 overproduction. Towards this end, comparative metabolomics approach was employed to analyze metabolite concentrations difference of Streptomyces tsukubaensis cultivated in two media with low and high productivities. Initially, 98 intracellular metabolites were identified and 13 metabolites involved in five pathways were determined to be directly correlated with FK506 biosynthesis. Then in‐depth analysis elucidated how those key factors exerted influence on FK506 biosynthesis. Many previously unreported metabolites were shown to play an important role in FK506 biosynthesis and provided potential regulation points for external manipulation. Based on such key information, rationally designed feeding strategy was carried out. Results showed that the FK506 yield increased from 251 to 405 mg/L, whereas, by‐products FK520 and 37,38‐dihydro‐FK506 decreased by 31% and 39%, respectively, compared with the values of control. To our knowledge, it is the first study to apply the comparative metabolomics method to identify key metabolites to promote the FK506 production. The strategies developed here can easily be extended to titer improvement of other important microbial natural products and process optimization. Biotechnol. Bioeng. 2013;110: 2717–2730. © 2013 Wiley Periodicals, Inc.
Veinotonic effect, vascular protection, antiinflammatory and free radical scavenging properties of horse chestnut extract.

Horse chestnut extract (HCE), containing 70% escin, is the main active component of Veinotonyl 75. The aim of this work was to investigate pharmacological properties attempting to elucidate the efficacy of HCE in chronic venous insufficiency. Veinotonic and lymphagogue properties: HCE dose dependently contracts the canine saphenous isolated vein (cumulative doses 5 x 10(-8) to 5 x 10(-4) g/ml). Its action lasts more than 5 h. In the perfused canine saphenous vein, HCE (25-50 mg in bolus) increases the venous pressure of the normal vein and the pathological vein stenosed 8 days before, and the contractile response to noradrenaline is significantly potentiated. Moreover, during the perfusion in inverse direction of the blood stream, a clear contracting effect on the valves is also obtained with HCE. In the anaesthetized dog, HCE in situ improves the femoral vein compliance and opposes the venous distension obtained during clamping in a carotido-femoral perfusion with constant flow. In other respects, HCE significantly increases femoral venous pressure and flow, together with thoracic lymphatic flow, while respecting the arterial parameters (2.5 and 5 mg/kg i.v.). Vasculotropic action: HCE dose dependently diminishes the cutaneous capillary hyperpermeability induced either by injections of phlogistic agents as histamine and serotonin in the rat (100 to 400 mg/kg p.o.), or by an irritative agent (chloroform) application in the rabbit (50 to 300 mg/kg p.o. and 2.5 to 5 mg/kg i.v.). It significantly increases the vascular resistance in the guinea pig fed a scorbutigenic diet as measured by the petechia method (50 to 400 mg/kg p.o.). Antiedema and antiinflammatory properties: HCE decreases the formation of edemas induced in the rat's hind paw, one of lymphatic origin, the other of inflammatory origin (200 to 400 mg/kg p.o.). In an experimental model of pleurisy in the rat HCE suppresses plasmatic extravasation and leucocytes emigration into the pleural cavity (200 to 400 mg/kg p.o.; 1 to 10 mg/kg i.v.). It decreases the connective tissue formation in the subchronic model of inflammatory granuloma in the rat (400 mg/kg p.o. and 5-10 mg/kg s.c.). Antiradical mechanism of action both in vitro and in vivo: HCE dose dependently inhibits both enzymatic and non-enzymatic in vitro lipid peroxidation (5 x 10(-6) to 5 x 10(-4) g/ml). (ABSTRACT TRUNCATED AT 400 WORDS)
CEO Characteristics and Budgeting Practices in Emerging Market SMEs*

Small and medium‐sized enterprises (SMEs) play an important role in the gross national product and employment in most emerging markets. However, little is known about their budgeting practices and, in particular, about the role of CEO characteristics for the adoption and extent of budget use. Drawing on a broad sample of manufacturing firms from Turkey, we shed light on the role of CEO characteristics for the adoption and extent of use of formal budgets. Our results suggest that apart from age and education, the CEO's openness to experience is an important factor for understanding budgeting practices in SMEs.
Evaluating the Quality and Readability of Internet Information Sources regarding the Treatment of Swallowing Disorders

The Internet has become a popular resource for patient education. The information it provides, however, is rarely peer-reviewed, and its quality may be a concern. Since the average American reads at an 8th grade level, the American Medical Association and the National Institutes of Health have recommended that health information be written at a 4th to 6th grade level. We performed a study to assess the quality and readability of online information regarding the treatment of swallowing disorders. A Google search for “swallowing treatment” was conducted. We studied the first 50 websites that appeared on the search engines results with the use of the DISCERN quality index tool, the Flesch Ease of Reading Score (FRES), and the Flesch-Kincaid Grade Level (FKGL) readability test. DISCERN is a validated 16-item questionnaire used to assess the quality of written health information; FRES and FKGL are used to assess readability. We classified the websites as either patient-targeted or professional-targeted sites, as well as either major or minor. The overall DISCERN score was 1.61 ± 0.61 (range: 1 to 5), the overall FRES was 39.1 ± 19.0 (range: 1 to 100), and the overall FKGL was 11.8 ± 3.4 (range: 3 to 12). As would be expected, patient-targeted websites had significantly higher FRES and significantly lower FKGL scores than did the professional-targeted websites (p = 0.01 and p = 0.04, respectively); there was no significant difference between the two in DISCERN scores. The major websites had significantly higher DISCERN scores than did the minor sites (p = 0.002); there were no significant differences in FRES and FKGL scores. We conclude that online information sources regarding the treatment of swallowing disorders were of sub optimal quality in that information was written at a level too difficult for the average American to easily understand. Also, the patient-targeted websites were written at a lower reading level, and the major websites contained a higher quality of information.
Relationship between the severity of β‐thalassaemia syndromes and the number of alleviating mutations

Abstract: Thalassaemia intermedia, defined as homozygous β‐thalassaemia in which patients are not transfusion‐dependent, covers a wide range of clinical severity. It may arise because one or more genetic factors ameliorate the otherwise severe phenotype of thalassaemia major. Exactly which and how many such mutations are necessary to produce a thalassaemia intermedia phenotype is incompletely understood, although such information would be useful both clinically and for prenatal diagnosis. We examined DNA from 28 patients with thalassaemia intermedia resident in London and 28 matched patients with thalassaemia major, for 3 types of genetic modifying factors, namely; mild β‐thalassaemia mutations, the upstream XmnI G‐gamma globin gene polymorphism, and α‐globin gene deletions. The results show that the number of alleviating mutations present has a large influence on the phenotype of patients with homozygous β‐thalassaemias. A single alleviating mutation was present in 56% of thalassaemia intermedia subjects compared with 26% of thalassaemia major subjects. Two alleviating mutations were present in 33% of thalassaemia intermedia subjects compared with 1 thalassaemia major subject. No patients with thalassaemia major had 3 alleviating mutations, in contrast to 11% of those with thalassaemia intermedia. Although the findings did not account for the full range of phenotypic variation, such information is of potential value both in the clinical management and the prenatal diagnosis of homozygous β‐thalassaemia.
Evaluation Of Macroprudential Policy On Credit Growth In Indonesia: Credit Registry Data Approach

Macro-prudential policies have an essential role in mitigating the imbalances in the financial sector that stem from procyclical credit growth. This study aims to evaluate macro-prudential policy in mitigating risk on procyclical credit growth with a registry data approach. Structural Vector Autoregression (SVAR) analysis method is used to evaluate macro-prudential policy in influencing credit growth. The results show LTV instruments can reduce credit growth but not to procyclical mitigation. Dissimilar results in the implementation of CCB and GWM + LDR instruments are capable of procyclical credit mitigation. Policies that can be done by the central bank are the establishment of an early warning system in macro-prudential policy as well as strengthening of Countercyclical Buffer (CCB), Loan to Value (LTV) instruments and Minimum Reserve Requirement + Loan Funding Ratio (GWM + LFR) in capturing systemic risks from various sources which further strengthens the assessment and surveillance.DOI:10.15408/etk.v17i2. 7324
Learning from higher order relations

In a number of domains in computer vision, machine learning and psychology, it is common to model and analyze data in terms of pairwise interactions between data elements, that is, distances between pairs of points. A large variety of supervised and unsupervised algorithms exist for learning the structure of such data. However, it is not always the case that interactions between entities can be described in terms of pairs; often, higher order relations of size three and higher offer a more natural formulation. Consider the k-lines clustering problem, where the objective is to group data points in a d-dimensional vector space into k clusters where elements in each cluster are well approximated by a line. As every pair of data points trivially define a line, there does not exist a useful measure of similarity between pairs of points for this problem. However, it is possible to define measures of similarity over triplets of points that indicate how close they are to being collinear. Another example is the task of constructing an embedding obtained from psychometric experiments involving paired comparisons. A common paired comparison experiment is where subjects are shown three images--- X, Y and Z---and asked to report which of X or Y is more similar to Z. Here each observation is a triadic relation on the set of images. We refer to the problem of learning from such data-sets as higher order learning. In this dissertation we present solutions to two problems in higher order learning. The first is a new technique for clustering called Clique Averaging, in which we use a novel generative model for hypergraphs to construct a clustering algorithm that has better theoretical as well as empirical performance than existing algorithms. We show applications to illumination invariant clustering and k-subspace learning. The second is a new non-metric multi-dimensional scaling (MDS) algorithm for ordinal data, that is, data sets in which instead of the magnitude, only the relative or rank order of distances is known. We will show how this algorithm can be used to construct a perceptual space for reflectance.
A Case-Control Study on Excessive Daytime Sleepiness in Episodic Migraine

Migraine patients often complain of sleepiness, a problem that manifests both during and outside an attack, may impair the quality of life and can lead to potentially harmful situations. Findings from an uncontrolled study suggest that a high percentage of migraineurs experience excessive daytime sleepiness (EDS). We investigated EDS in a case-control study on 100 patients with episodic migraine and 100 age- and sex-matched healthy controls and also assessed sleep quality, anxiety and depression. Although it was found that EDS was more frequent in migraineurs than in controls (14% vs. 5%; odds ratio 3.1; 95% confidence interval 1.1–8.9), the frequency was lower than previously reported. EDS correlated with migraine disability, sleep problems and anxiety. EDS in patients with migraine probably stems from the full constellation of headache-sleep-affective symptoms resulting from the complex clinical burden of the disease.
Clinical drug‐drug interaction assessment of ivacaftor as a potential inhibitor of cytochrome P450 and P‐glycoprotein

Ivacaftor is approved in the USA for the treatment of cystic fibrosis (CF) in patients with a G551D‐CFTR mutation or one of eight other CFTR mutations. A series of in vitro experiments conducted early in the development of ivacaftor indicated ivacaftor and metabolites may have the potential to inhibit cytochrome P450 (CYP) 2C8, CYP2C9, CYP3A, and CYP2D6, as well as P‐glycoprotein (P‐gp). Based on these results, a series of clinical drug‐drug interaction (DDI) studies were conducted to evaluate the effect of ivacaftor on sensitive substrates of CYP2C8 (rosiglitazone), CYP3A (midazolam), CYP2D6 (desipramine), and P‐gp (digoxin). In addition, a DDI study was conducted to evaluate the effect of ivacaftor on a combined oral contraceptive, as this is considered an important comedication in CF patients. The results indicate ivacaftor is a weak inhibitor of CYP3A and P‐gp, but has no effect on CYP2C8 or CYP2D6. Ivacaftor caused non‐clinically significant increases in ethinyl estradiol and norethisterone exposure. Based on these results, caution and appropriate monitoring are recommended when concomitant substrates of CYP2C9, CYP3A and/or P‐gp are used during treatment with ivacaftor, particularly drugs with a narrow therapeutic index, such as warfarin.
Left atrial spontaneous echo contrast in patients with rheumatic mitral valve disease in sinus rhythm. Implication of an altered left atrial appendage function in its formation.

Thirty-nine patients who had rheumatic mitral valve disease in sinus rhythm were studied to compare echocardiographic and hemodynamic characteristics between those with and without left atrial (LA) spontaneous echo contrast. Patients were divided into two groups according to the presence (group 1, n=17) or absence (group 2, n=22) of the echo contrast. Transthoracic echocardiography and transesophageal echocardiography were performed in all patients within 1 week of cardiac catheterization study. Group 1 patients (5 men and 12 women; mean age, 47.7 ± 13.1 years) showed smaller mitral valve area, greater transmitral valve pressure gradient, and absence of moderate to severe mitral regurgitation compared with group 2 patients (7 men and 15 women; mean age, 47.8 ± 14.3 years). There was no significant difference in LA dimension, left ventricular end-systolic and end-diastolic dimensions, or in left ventricular ejection fraction between the two groups of patients. Left atrial appendage function was studied with Doppler in 26 patients. Patients (n=10) with LA spontaneous echo contrast had significantly lower LA appendage ejection fraction (20.34 ± 10.76% vs 34.16 ± 13.13%; p
Implementation of a new clinical practice guideline regarding pain management during childhood vaccine injections.

OBJECTIVE To determine the impact of a multifaceted knowledge translation strategy for a new vaccination pain management guideline on public health immunizers' attitudes, beliefs and use of pain-relieving strategies during childhood vaccination. METHOD Using a randomized controlled pre-post study design, public health nurses (PHNs) at intervention sites received a multifaceted knowledge translation intervention about new pain management guidelines incorporated in the British Columbia Immunization Program Manual, including education, supplies and online support. Attitudes and beliefs of PHNs toward immunization pain and pain management, and use of pain-relieving strategies were compared for the intervention sites between the pre- and postimplementation phases. RESULTS A total of 516 children were immunized by 31 PHNs pre- and postimplementation in the intervention sites. Postimplementation, satisfaction and confidence with ability to manage pain and willingness to use newly recommended strategies were significantly more positive (P<0.05) in the intervention sites, and overall use of at least one newly recommended strategy increased from 49.8% preintervention to 77.6% postimplementation (P<0.001). CONCLUSION The knowledge translation intervention improved PHN immunizers' attitudes, beliefs and practices regarding paediatric vaccination pain management. Reducing pain may result in a better immunization experience for children, caregivers and immunizers.
Twenty-Year Trends of Authorship and Sampling in Applied Biomechanics Research

This study documented the trends in authorship and sampling in applied biomechanics research published in the Journal of Applied Biomechanics and ISBS Proceedings. Original research articles of the 1989, 1994, 1999, 2004, and 2009 volumes of these serials were reviewed, excluding reviews, modeling papers, technical notes, and editorials. Compared to 1989 volumes, the mean number of authors per paper significantly increased (35 and 100%, respectively) in the 2009 volumes, along with increased rates of hyperauthorship, and a decline in rates of single authorship. Sample sizes varied widely across papers and did not appear to change since 1989.
Risk Factors for Retinochoroiditis During the First 2 Years of Life in Infants With Treated Congenital Toxoplasmosis

Background: Retinochoroiditis is the main complication of congenital toxoplasmosis. Its risk factors have rarely been investigated and were the object of this study. Methods: A retrospective study was conducted on 300 infants with congenital toxoplasmosis born between July 1, 1996 and December 31, 2002 and treated with pyrimethamine and sulfonamide for at least 12 months. Results of eye tests were collected up to 24 months. Risk factors associated with first retinochoroiditis were identified by univariate then multivariate analyses (Cox model). Results: One hundred forty-nine boys and 151 girls were included. Maternal infection dated from the first trimester in 34 cases, the second in 97 cases, and the last in 169 cases. At birth, 22 infants had cerebral calcifications. During the first 2 years of life, first retinochoroiditis was diagnosed in 36 infants (12%). In multivariate analysis, 3 factors were significantly associated with first retinochoroiditis before the age of 2 years: a delay of >8 weeks between maternal seroconversion and first treatment [hazard ratio, 2.54; 95% confidence interval (CI), 1.14–5.65], female gender (hazard ratio, 2.02; 95% CI, 1.01–4.1), and cerebral calcifications at birth (hazard ratio, 4.3; 95% CI, 1.9–10). There was no correlation between gestational age at the time of maternal infection and risk for retinochoroiditis. Conclusions: A delay of >8 weeks between maternal seroconversion and the beginning of treatment, female gender, and especially cerebral calcifications are risk factors for retinochoroiditis during the first 2 years of life in infants treated for congenital toxoplasmosis.
Long-term results of breast conservation therapy for breast cancer.

OBJECTIVE This study was done to determine the long-term outcome of breast conservation therapy (BCT) for patients with early-stage breast cancer during a period of treatment evolution at a single institution. SUMMARY BACKGROUND DATA Breast cancer treatment has evolved from extensive surgical extirpation of the breast to treatment options that conserve the breast. Prospective and retrospective studies have confirmed the efficacy of BCT and justify its use for many patients with early breast cancer, but there is no universally accepted consensus as to who benefits from more aggressive application of surgery or radiotherapy in BCT. Prognostic variables for breast cancer and information on factors that contribute to local recurrence help predict BCT results. Continued analysis of BCT still is necessary to improve patient outcome. METHODS Eighty-five patients treated with BCT (lumpectomy with adjuvant radiation therapy) at the Medical College of Virginia from 1980 to 1990 were identified. Clinicopathologic parameters and treatment details were analyzed for relationship to development of local recurrence, distant metastasis, and survival. Fisher's exact test was used for comparisons. Actuarial survival curves were plotted. The earlier treatment period (1980-1985) was compared with the later treatment period (1985-1990). RESULTS Median follow-up was 5 years. Actuarial overall survival was 83% at 5 years (69% at 10 years), and 5-year distant metastasis-free survival was 79%. The 5-year actuarial local recurrence rate was 6.6% (crude rate 10.6%, 9/85). Young patients (age < 40 years) were found to be at increased risk for local recurrence (24% < 40 years vs. 6% > or = 40 years, p < 0.05). Tumor margins < or = 3 mm were more frequently found, and lumpectomy site radiation boost was used increasingly from 1986 to 1990. Almost half of all local recurrences occurred after 5 years. CONCLUSIONS Survival and local recurrence rates were comparable to other series. Young patients were found to be at increased risk for local recurrence. Negative microscopic margins, even when close, can provide low local recurrence rates when adjuvant radiation therapy is administered.
Association Between Gender, Body Mass Index, and Ulnar Nerve Entrapment at the Elbow: A Retrospective Study

Introduction: Entrapment of the ulnar nerve is the second most common compression neuropathy in the upper extremity, but the etiology is multifactorial and still not clearly understood. The authors aimed to determine whether gender and body mass index (BMI) are risk factors for ulnar nerve entrapment (UNE) at the elbow. Methods: Results of electrodiagnostic studies performed on patients with UNE between January 2008 and February 2013 were examined retrospectively. Patients with BMI ⩽22 were considered slender, those with a BMI between 22 and 29, normal, and those with a BMI >29, overweight. The authors compared the data for patients with and without UNE. Results: A total of 622 subjects were studied; 295 were UNE cases (154 men, 141 women) and 327 were controls (110 men, 217 women). There was no difference between control and UNE groups in terms of BMI. In univariate analysis, age and gender are independent risk factors for UNE, but when included in a stepwise Cox regression model, only gender was a significant factor. Male gender was found to be a risk factor for UNE. Conclusions: Male gender is a risk factor for developing UNE, but age and BMI are not significant risk factors. Further studies which examine BMI and gender differences with data about occupational risk factors are required.