Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and tissue distribution studies of orally administered nanoparticles encapsulated ethionamide used as potential drug delivery system in management of multi-drug resistant tuberculosis

Sustained release nanoformulations of second line anti-tubercular drugs can help in reducing their dosing frequency and improve patient’s compliance in multi-drug resistant tuberculosis (MDR TB). The objective of the current study was to investigate the pharmacokinetics and tissues distribution of ethionamide encapsulated in poly (DL-lactide-co-glycolide) (PLGA) nanoparticles. The drug loaded nanoparticles were 286 ± 26 nm in size with narrow size distribution, and zeta-potential was −13 ± 2.5 mV. The drug encapsulation efficiency and loading capacity were 35.2 ± 3.1%w/w and 38.6 ± 2.3%w/w, respectively. Ethionamide-loaded nanoparticles were administered orally to mice at two different doses and the control group received free (unencapsulated) ethionamide. Ethionamide-loaded PLGA nanoparticles produced sustained release of ethionamide for 6 days in plasma against 6 h for free ethionamide. The Ethionamide was detected in organs (lung, liver, and spleen) for up to 5–7 days in the case of encapsulated ethionamide, whereas free ethionamide was cleared within 12 h. Ethionamide-loaded PLGA nanoparticles exhibited significant improvement in pharmacokinetic parameters, i.e. Cmax, tmax, AUC0–∞, AUMC0–∞, and MRT of encapsulated ethionamide as compared with free ethionamide. Drug in nanoparticles also exhibited a dose proportional increase in the AUC0–∞ values. The pharmacodynamic parameters such as AUC0–24/MIC, Cmax/MIC, and Time > MIC were also improved. PLGA nanoparticles of ethionamide have great potential in reducing dosing frequency of ethionamide in treatment of MDR TB.
Analyzing voltage ripple in variable-frequency DC/DC boost converter

Numerous variable-frequency (VF) EMI-reduction schemes have been proposed over the last decades. The aim of these VF or spread-spectrum techniques is to reduce both the measurable and effective undesirable electromagnetic noise of a switch mode power supply. Conducted RF-interference measurements have been reported in literature. However, low frequency output voltage ripple has been considered as a major problem in VF DC/DC converters and the majority of these papers do not consider this aspect of VF operation. Analysis of the output voltage ripple with four different VF techniques in six different configurations is made in this paper, and prototype measurements with a boost converter are presented.
Investigating the relationship between electron mobility and velocity in deeply scaled NMOS via mechanical stress

The importance of low-field mobility to the performance of deep-sub-100-nm bulk MOSFETs is not well understood. In this work, we investigate experimentally how effective electron mobility at low lateral electric fields relates to velocity in the MOSFET saturation regime, where lateral fields in the channel are high. For short (L/sub eff//spl ap/45 nm) NMOS devices, mobility is modified by externally applying uniaxial stress and the corresponding shifts in electron velocity are found to be significant.
Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion‐positive non–small cell lung cancer

The authors' previous study demonstrated that the B‐cell chronic lymphocytic leukemia/lymphoma (Bcl‐2)‐like 11 (BCL2L11) (Bim) deletion polymorphism was associated with poor clinical response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non–small cell lung cancer (NSCLC) with EGFR mutations. The objective of the current study was to investigate the impact of the Bim deletion polymorphism among patients with anaplastic lymphoma kinase (ALK)‐positive or ROS proto‐oncogene 1, receptor tyrosine kinase (ROS1)‐positive NSCLC who were treated with crizotinib.
Ergodic control of continuous-time Markov chains with pathwise constraints

We deal with unichain ergodic continuous-time controlled Markov chains with a denumerable state space, and unbounded reward and transition rates. We are concerned with finding control policies that maximize a sample-path average reward over the family of policies for which a certain pathwise average cost is below a given value with probability one. We illustrate our results with examples on the control of a queueing system and an epidemic process.
Perceptions of Family of Origin Among Lonely Adult Filipino Males With Schizophrenia: A Qualitative Analysis

This study explored the perceived family life experiences in the family of origin among 35 hospitalized lonely adult (range 27 to 44 years) Filipino males with schizophrenia during a period of remission of their overt psychotic features. Open-ended interview, checklists, and projective techniques were used to collect data. Together with an in-depth analysis of narratives, the responses of the lonely and the loneliest participants were compared by Mann—Whitney U nonparametric test of comparison. It was predicted in this study that individuals with schizophrenia with higher level of loneliness would be more likely to perceive their family life experiences negatively than the less lonely individuals with schizophrenia. Results showed that the degree of negative family experiences among the loneliest participants was significantly higher than the lonely participants. Moreover, a few participants regardless of the degree of loneliness positively viewed their family as united and close, interactive, affectionate and loving, kind and good, trustworthy, religious, morally good, complete, and supportive.
Pediatric tuberculosis: new guidelines and recommendations

Purpose of review To discuss the recommendations pertaining to infants, children, and adolescents in new and updated tuberculosis (TB) guidelines that have been published since 2010 – with emphasis on those from supranational organizations. Recent findings The main developments in the guidelines covered in this article are related to: novel diagnostics for TB infection, disease, and drug resistance; updated treatment regimens for childhood and drug-resistant TB (DR-TB); and primary and secondary prevention of TB disease in HIV-infected children and adolescents. Summary These new guidelines have significant implications for improving pediatric TB care. Regarding diagnosis, current interferon-gamma release assays should not replace tuberculin skin testing, but may be complementary; a polymerase chain reaction assay has been validated for detecting Mycobacterium tuberculosis and rifampicin resistance in microscopy-negative samples, especially in HIV-infected and DR-TB suspects; and a molecular line probe assay has been validated for detecting DR-TB in microscopy-positive samples and culture isolates in DR-TB suspects. With respect to treatment, there have been certain changes in the recent World Health Organization recommendations for certain clinical syndromes, for multidrug-resistant TB disease, and for HIV/TB disease. Concerning prevention, there are new screening algorithms for case finding, and new recommendations for treating HIV-infected children with presumed TB infection and with TB disease with treatment completed (i.e., secondary prophylaxis).
A quantitative comparison of functional and anti‐ischaemic effects of the phosphodiesterase‐inhibitors, amrinone, milrinone and levosimendan in rabbit isolated hearts

1 The functional and anti‐ischaemic effects of the phosphodiesterase (PDE)‐inhibitors, amrinone, milrinone and levosimendan, a new agent combining PDE‐inhibitory with calcium‐sensitizing properties, were investigated in rabbit isolated hearts (Langendorff, constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol l−1, 37°C). Anti‐ischaemic effects were studied in electrically‐driven hearts (200 beats min−1). Acute regional ischaemia was induced by ligature of a branch of the circumflex coronary artery and quantified from epicardial NADH‐fluorescence photography. 2 Cumulative concentration‐response curves in spontaneously beating hearts in the presence of isoprenaline (10−1 m), showed a higher inotropic and coronary vasodilator potency for levosimendan (EC50: 7 × 10−7 m) compared to milrinone (EC50: 7.7 × 10−6 m) or amrinone (EC50: 2 × 10−5 m). Although the maximal coronary dilator activity was similar for the three agents, the maximal inotropic and chronotropic effects were lower for levosimendan than for amrinone or milrinone (P < 0.05). 3 In regionally ischaemic hearts, milrinone (10−5 m) or levosimendan (5 × 10−6 m) similarly enhanced the left ventricular pressure (+15–20%) (P < 0.05) and the global coronary flow (+ 40–50%) (P < 0.05). The epicardial NADH‐fluorescence area was significantly diminished by milrinone or levosimendan (– 20–30%) (P < 0.05) and there was no significant difference between the anti‐ischaemic effects of either agent (P > 0.05). 4 It is concluded that amrinone and milrinone possess similar functional profiles in rabbit isolated hearts and a higher inotropic and chronotropic efficacy than levosimendan. At functionally equieffective concentrations, milrinone and levosimendan show similar anti‐ischaemic effects, related to an improvement of myocardial perfusion. The calcium‐sensitizing properties seem not to be relevant for cardioprotection by levosimendan at the concentration used.
Smoking Behavior Postmyocardial Infarction Among ENRICHD Trial Participants: Cognitive Behavior Therapy Intervention for Depression and Low Perceived Social Support Compared With Care as Usual

Introduction: Patients with cardiovascular disease who stop smoking lower their risk of subsequent morbidity and mortality. However, patients who have suffered a myocardial infarction (MI) are more likely to be depressed than the general population, which may make smoking cessation more difficult. Poor social support may also make smoking cessation more difficult for some patients. This study examines the effect of cognitive behavior therapy (CBT) for depression, low perceived social support or both on smoking behavior in post-MI patients. Methods: Participants were 1233 patients with a history of smoking enrolled in the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) trial who provided 7-day point-prevalence smoking behavior information at baseline and at two or more follow-up assessments. The ENRICHD trial enrolled post-MI patients with depression, low perceived social support or both. Participants were randomly assigned to either CBT intervention or usual care. We used mixed effects models to accommodate data from multiple smoking point-prevalence measures for each individual participant. Results: CBT did not significantly reduce post-MI smoking across all intervention patients with a history of smoking. However, CBT did reduce post-MI smoking among the subgroup of depressed patients with adequate perceived social support (OR, 0.68; 95% CI, 0.47–0.98). Conclusion: CBT for depression without more specific attention to smoking cessation may have little overall value as a strategy for helping post-MI patients refrain from smoking. However, use of CBT to treat depression may have the gratuitous benefit of reducing smoking among some post-MI patients. ENRICHD = Enhancing Recovery in Coronary Heart Disease Patients; MI = myocardial infarction; CBT = cognitive behavioral therapy; LPSS = low perceived social support; MDD = major depressive disorder; BDI = Beck Depression Inventory; OR = odds ratio.
Effects of red blood cells on hemostasis

BACKGROUND: Currently there is no sensitive laboratory test to establish the influence of red blood cells (RBCs) on hemostasis. As thromboelastography (TEG) measures hemostasis in whole blood, taking into account the interactions of all cellular elements, we used this instrument to investigate the role that RBCs play in hemostasis.
Automated lung nodule classification following automated nodule detection on CT: a serial approach.

We have evaluated the performance of an automated classifier applied to the task of differentiating malignant and benign lung nodules in low-dose helical computed tomography (CT) scans acquired as part of a lung cancer screening program. The nodules classified in this manner were initially identified by our automated lung nodule detection method, so that the output of automated lung nodule detection was used as input to automated lung nodule classification. This study begins to narrow the distinction between the "detection task" and the "classification task. " Automated lung nodule detection is based on two- and three-dimensional analyses of the CT image data. Gray-level-thresholding techniques are used to identify initial lung nodule candidates, for which morphological and gray-level features are computed. A rule-based approach is applied to reduce the number of nodule candidates that correspond to non-nodules, and the features of remaining candidates are merged through linear discriminant analysis to obtain final detection results. Automated lung nodule classification merges the features of the lung nodule candidates identified by the detection algorithm that correspond to actual nodules through another linear discriminant classifier to distinguish between malignant and benign nodules. The automated classification method was applied to the computerized detection results obtained from a database of 393 low-dose thoracic CT scans containing 470 confirmed lung nodules (69 malignant and 401 benign nodules). Receiver operating characteristic (ROC) analysis was used to evaluate the ability of the classifier to differentiate between nodule candidates that correspond to malignant nodules and nodule candidates that correspond to benign lesions. The area under the ROC curve for this classification task attained a value of 0.79 during a leave-one-out evaluation.
Comparison of Surgical versus Non-Surgical Treatment of Displaced 3- and 4-Part Fractures of the Proximal Humerus: A Meta-Analysis

ABSTRACT Purpose/Aim: This meta-analysis compares the clinical outcomes of surgical versus conservative treatment of displaced, 3- or 4-part, proximal humeral fractures. Materials and Methods: Medline, Cochrane, EMBASE, and Google Scholar were searched for studies published until October 2013, reporting functional outcomes of 3- or 4-part fractures of the proximal humerus in skeletally mature patients. Only randomized controlled trials were included. The treatments that were evaluated included non-surgical, open surgery, intramedullary pin, locking plate, arthroplasty, and minimally invasive surgical treatments. A meta-analysis was performed on the difference in functional outcomes and quality of life (QoL) between participants undergoing surgical versus non-surgical treatment. Results: Out of 254 participants in the studies who were analyzed, 127 were treated surgically. The difference in mean values of functional score showed similar results between surgical and non-surgical treatments (difference in mean values = 0.015, 95% CI = –0.232 to 0.261, p = .908). The difference in mean values of QoL showed that surgical treatment provided better post-operative QoL than non-surgical treatment (difference in mean values = 0.146, 95% CI = 0.052 to 0.240, p = .002). Conclusions: Surgical treatment of displaced, multi-fragment fractures of the proximal humerus did not improve shoulder functional outcome, based on the Constant–Murley Score, when compared with conservative and non-surgical treatments. However, health-related QoL was significantly improved with surgical treatment compared with conservative treatment.
Dissipative control for linear systems by static output feedback

In this article, the problem of static output-feedback dissipative control is investigated for linear continuous-time system based on an augmented system approach. A necessary and sufficient condition for stability and strict (Q,S,R)-dissipativity of the closed-loop system is established in terms of a matrix inequality with free parametrisation matrix. An equivalent characterisation with some slack matrices for numerical solvability is then proposed. Based on this, a necessary and sufficient condition for the existence of a desired controller is given, and a corresponding iterative algorithm is developed to solve the condition. The effectiveness of results developed in this article is demonstrated by some numerical examples.
Beaver ponds as habitat of amphibian communities in a central European highland

The Eurasian beaver Castor fiber, formerly occurred across the Palaearctic, but was nearly eradicated in the 19th century. Due to reintroductions in the 20th century, beaver populations are increasing and now extend into highland areas. Natural still waters are scarce in highlands of Central Europe. Therefore the question arises, "Are beaver ponds essential habitats for amphibians? ", especially since fishes, predators of amphibian larval stages, also inhabit beaver ponds. We investigated the amphibian fauna of one typical valley in the Eifel, that was colonized by beavers in 1981, and compared areas with and without beaver ponds. All anuran species of the region occupied beaver ponds, including species that were absent (Alytes obstetricans, Bufo bufo and Rana kl. esculenta )o r rare (Rana temporaria) in natural waters. Alytes obstetricans obviously benefited from pond construction and the removal of trees by beavers which leads to sunny plots along the slopes of the valley, crucial habitat for this species. The urodelans Salamandra salamandra, Triturus alpestris and Triturus helveticus were widely distributed in beaver ponds. Our results show clearly, that beaver altered landscapes offer high quality habitats for amphibians in our study area. Due to a considerable increase of habitat heterogeneity in impounded streams, the predator Salmo trutta was not able to extirpate the amphibian fauna. We conclude that the historic effects of beavers need to be considered for a proper understanding of patterns of amphibian distribution and habitat requirements in Central European Highlands. Furthermore, beaver-created landscapes will be of future relevance for conservation of endangered species, like Alytes obstetricans.
Diagnostic performance characteristics of architectural features revealed by high spatial-resolution MR imaging of the breast.

OBJECTIVE Our objective was twofold: to determine which architectural features revealed by high spatial-resolution MR imaging of the breast contribute to diagnostic accuracy and to evaluate the diagnostic performance characteristics of those architectural features. MATERIALS AND METHODS Eligible patients with suspicious mammographic or palpable findings or both underwent MR imaging. Ninety-three patients whose MR images revealed lesions that corresponded to the mammographically visible or palpable findings were included in the study. Patients were examined with sagittal T1-weighted spin-echo MR imaging, fat-saturated T2-weighted fast spin-echo MR imaging, and dynamically enhanced fat-saturated fast gradient-echo MR imaging. All patients underwent subsequent excisional biopsy or cyst aspiration. Lesions were identified initially by an experienced radiologist who was aware of the patient's clinical or mammographic information. Two radiologists who were unaware of the patients' histories and who had less experience in MR imaging of the breast then independently evaluated each lesion for the architectural-features and predicted each lesion's potential for malignancy. RESULTS Architectural features that were highly predictive of benign disease included smooth or lobulated borders (97-100%), the absence of mass enhancement (100%), and enhancement that was less than the enhancement of surrounding breast fibroglandular tissue (93-100%). Nonenhancing internal septations were specific for the diagnosis of fibroadenoma. Architectural features that were highly predictive of malignant disease included spiculated borders (76-88%) and peripheral rim enhancement in the presence of central lesion enhancement (79-92%). CONCLUSION Architectural features revealed by high spatial-resolution MR imaging of the breast can help distinguish benign from malignant disease.
Neural encoding of auditory temporal context in a songbird basal ganglia nucleus, and its independence of birds' song experience

Some of the most complex auditory neurons known are found in the songbird forebrain, throughout the ‘song system’, including its basal ganglia nucleus Area X. These cells are selective for the temporal order of the bird's own song (BOS): they typically respond strongly to BOS, but more weakly when the syllable sequence of BOS is played in reverse order (roBOS), indicating that they integrate auditory information over more than single syllables. Here, studying the zebra finch Area X, we found that order selectivity strongly depends on the mean syllable duration of individual songs, decreasing markedly as this duration approaches 150–200 ms. Simply segmenting the same songs differently, creating an increase in average syllable length towards 150 ms, caused a similar decrease in order selectivity. This suggests that song neurons integrate acoustic information over a relatively limited time window, predominantly less than 150 ms. We provided further support for this by showing that a significant fraction of Area X order selectivity was accounted for by the acoustic similarity between each BOS and roBOS, measured using cross‐correlation with fixed window sizes, but only when the correlation windows were at least 50 ms and no more than 200 ms long. All the same findings were evident in birds raised without tutor exposure, indicating that tutor learning has little effect on neural mechanisms underlying song temporal selectivity. Our results suggest that song‐selective neurons encode much of the temporal context of song using a short, constant time window that is conserved across differences in songs, birds and learning.
Nonmelanoma Skin Cancer: Is the Incidence Really Increasing among Patients Younger Than 40? A Reexamination Using 25 years of U.S. Outpatient Data

OBJECTIVE An increasing incidence of basal cell carcinomas and squamous cell carcinomas in patients younger than 40 years old diagnosed during years 1973 to 2003 was found in a recent population-based study in Olmsted County, Minnesota. We performed additional analyses using nationally representative patient samples to confirm these trends. STUDY DESIGN We analyzed a cross-sectional survey data on outpatient diagnoses, the National Ambulatory Medical Care Survey data from 1979 to 2003, for melanoma skin cancer. RESULTS A total of 4,100 office visits for nonmelanoma skin cancers were recorded, including 230 in patients younger than 40. Multivariate analysis indicated no significant increase in the number of office visits related to nonmelanoma skin cancer in younger patients [odds ratio (OR), 2.77; 95% CI, 0.75–10.26]. The mean age of office visits for nonmelanoma skin cancer did not change significantly. The ages of the office visit patients were 64.7 years and 69.02 years in the years 1979 and 2003, respectively. CONCLUSIONS Based on a representative sample of outpatient visit diagnoses, visits are not increasing for nonmelanoma skin cancer among patients 40 years and younger in the United States, albeit direct measurement of tumor incidence was not possible with this database.