Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of the Investigational Antifungal VT-1161 in Treating Naturally Occurring Coccidioidomycosis in Dogs

ABSTRACT Coccidioidomycosis can be a chronic, systemic fungal infection requiring long-term to lifetime medication. Thus, there is a need for improved antifungal agents with greater efficacy and reduced toxicity. VT-1161 has a low affinity for mammalian cytochromes and potently inhibits fungal CYP51 with proven efficacy in murine models of central nervous system (CNS) and respiratory coccidioidomycosis. Dogs experience coccidioidomycosis similar to humans and are a useful preclinical model for naturally occurring disease. Twenty-four client-owned dogs diagnosed with respiratory coccidioidomycosis based on radiography, serology, clinical signs, and clinicopathologic abnormalities were treated with a loading dose of VT-1161 for 14 days, followed by 46 days of a lower maintenance dose. Twelve dogs received a high dose (29 mg/kg loading, 6 mg/kg maintenance) and 12 received a low dose (10 mg/kg loading, 1.6 mg/kg maintenance). Response to treatment was assessed by calculating the reduction in disease scores at exit compared to disease scores at enrollment. Overall, 20 of 24 (83%) dogs had ≥50% reduction in enrollment disease scores at exit (P < 0.001), with no difference between the high- and low-dose groups (P = 0.66). Time-weighted average plasma concentrations for the high- and low-dose groups were 39 ± 5 μg/ml and 19 ± 2 μg/ml, respectively. In this open-label study, VT-1161 was efficacious for the treatment of respiratory coccidioidomycosis in naturally infected dogs. Combined with previously reported murine data, this finding supports the further development of VT-1161 for the treatment of coccidioidomycosis in humans.
Pharmacological management of psychiatric disorders in pregnancy complicated by diabetics

Abstract Pregnancy has been identified as a biological, psychological and social stressor that predisposes women to emergence/re-emergence of psychiatric disorders. Effective pharmacological treatment is available for various psychiatric disorders. However, management of psychiatric disorders during pregnancy requires careful selection of the pharmacotherapeutic agent. Management of psychiatric disorders in pregnancy among diabetics brings in an additional dimension. The psychotropic medicines have been found to impact blood glucose levels and can interfere with diabetes management. This article reviews the available evidence on the use of psychotropic medicines in antenatal women with diabetes.
Object-oriented software testing-some research and development

It is widely accepted that the OO paradigm will significantly increase software reusability, extendibility, interoperability, and reliability. This is also true for high assurance systems engineering, provided that the systems are tested adequately. Software testing is an important software quality assurance activity to ensure that the benefits of OO programming will be realized. OO software testing has to deal with new problems introduced by the powerful new features of OO languages. The objective of the article is to review some of the existing research in OO software testing, in particular, the research at the University of Texas at Arlington.
Managing Health Promotion: Developing Healthy Organizations and Communities

Ina Simnett Wiley, £14.99, pp 229 ISBN 0 471 95814 X Reviewing health in the Mersey region in 1984, I described health promotion as “any combination of health education and political, economic and organisational activity designed to improve or protect health through its effect on the human environment and on behaviour. ” At the time this definition attracted quite widespread support and of course since then we have had the rapid adoption of at least a ritual obeisance to the notion that health promotion is “a good thing. ” Health education departments have renamed themselves health promotion departments and those working in …
Isolation of Pseudomonas aeruginosa Coproducing Metallo-β-Lactamase SPM-1 and 16S rRNA Methylase RmtD1 in an Urban River

Pseudomonas aeruginosa (strain 48-1997A) producing Sao Paulo metallo-beta-lactamase (MBL)-1 (SPM-1) was described for the first time in 1997 and came from a 4-year-old leukemic girl in Sao Paulo, Brazil (15). Since then, SPM-1-producing P. aeruginosa has become endemic in Brazilian hospitals, being recurrently associated with outbreaks of nosocomial infection (8, 11, 12). More recently, the first reports of the MBL SPM-1 were described in Europe (14) and western Asia (GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"HM370523.1","term_id":"307949947","term_text":"HM370523.1"}}HM370523.1), denoting the potential for SPM-1 to become endemic worldwide (6). Unfortunately, carbapenem-resistant P. aeruginosa isolates carrying the SPM-1 enzyme have exhibited additional resistance to aminoglycosides, which has been mediated by a novel 16S rRNA methylase defined as RmtD (3), rendering ineffective a potent double-coverage regimen of a carbapenem plus an aminoglycoside and contributing to the emergence of panresistant phenotypes (3, 4). In this letter, we report the first environmentally isolated Pseudomonas aeruginosa carrying the blaSPM-1 and rmtD1 genes, providing additional data on the epidemiology of these genetic determinants of resistance.
Psychometrics and normative data for the Multiple Sclerosis Functional Composite: replacing the PASAT with the Symbol Digit Modalities Test

The MS Functional Composite (MSFC) is a continuous scale of neurological disability for patients with multiple sclerosis (MS). Cognition is represented by the Paced Auditory Serial Addition Test (PASAT), although the Symbol Digit Modalities Test (SDMT) has been proposed as a promising alternative. MSFC scores were calculated using either the PASAT or the SDMT with the following reference populations: National Multiple Sclerosis Society (NMSS) Task Force, 400 MS patients, and 100 normal controls. A subgroup of 115 patients was followed longitudinally, with a test—retest interval of 2.3 ± 1.2 years. Pearson correlations were calculated and analyses of variance (ANOVAs) were used to assess relationships among the MSFC components and composite scores, and differences in performance between patients and controls. Longitudinal changes were also assessed. Logistic regression was performed to determine which MSFC scores are most predictive of diagnosis, course, and work disability. All MSFCs had similar test—retest reliability and correlations with other measures including neurological disability, depression, and fatigue. The SDMT showed slightly better validity with respect to predicting diagnosis, course, and work disability, although the amount of variance accounted for was similar for each version of the MSFC. Our data, derived from a large sample of MS patients and normal controls, supports the validity of both PASAT and SDMT versions of the MSFC. Because the SDMT has slightly better predictive validity and has a relatively easier administration procedure, some clinicians and researchers may wish to replace the PASAT with the SDMT in future calculations of the MSFC using the calculation methods provided in this manuscript.
Integrating automatic verification of safety requirements in railway interlocking system design

A railway interlocking system (RIS) is an embedded system (namely a supervisory control system) that ensures the safe, operation of the devices in a railway station. RIS is a safety critical system. We explore the possibility of integrating automatic formal verification methods in a given industry RIS design flow. The main obstructions to be overcome in our work are: selecting a formal verification tool that is efficient enough to solve the verification problems at hand; and devising a cost effective integration strategy for such tool. We were able to devise a successful integration strategy meeting the above constraints without requiring major modification in the pre-existent design flow nor retraining of personnel. We run verification experiments for a RIS designed for the Singapore Subway. The experiments show that the RIS design flow obtained from our integration strategy is able to automatically verify real life RIS designs.
NDM-1-Producing Klebsiella pneumoniae Now in Turkey

The emergence of NDM producers among Gram-negative rods is being reported worldwide, with Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii being the main hosts for this resistance trait ([7][1]). Whereas the United Kingdom, India, and Pakistan have been identified as reservoirs
Learning more frequency components using P-type ILC with negative learning gain

In this paper, through the analysis on error contraction conditions in the frequency domain, it is found that a negative learning gain can be used in iterative learning control (ILC). The proper use of negative learning gain can increase the learnable frequency range. The conventional P-type learning control with both positive and negative gains is used over multichannel learnable bands. The design procedure is demonstrated via an example of robot joint control. Two channels, one uses a positive learning gain and the other a negative learning gain, substantially increase the frequency components to be learned by the P-type controller. Experimental results verify the effectiveness of using a negative learning gain.
Interleukin 18 Receptor 1 expression distinguishes patients with multiple sclerosis

Definition of dysregulated immune components in multiple sclerosis may help in the identification of new therapeutic targets. Deviation of the interleukin 18 receptor 1 (IL18R1) is of particular interest since the receptor is critical for experimental neuroinflammation. The objective of this study was to determine whether expression of IL18R1 varies between multiple sclerosis patients and controls, and to test genetic association of IL18R1 with multiple sclerosis. We used quantitative real-time PCR to assess mRNA levels of IL18R1 in cerebrospinal fluid and peripheral blood mononuclear cells of 191 patients with multiple sclerosis, 61 patients with clinically isolated syndrome and 168 controls having other neurological disorders. Association was tested in 2153 patients with multiple sclerosis and 1733 controls using 13 tagging single nucleotide polymorphisms within the IL18R1 gene. We found that patients with multiple sclerosis had increased IL18R1 mRNA expression in both cerebrospinal fluid cells (p < 0.05) and peripheral blood mononuclear cells (p < 0.05) compared with controls. Patients with clinically isolated syndrome had elevated levels compared with controls in cerebrospinal fluid cells (p < 0.001) but not in peripheral blood mononuclear cells. The gene was not associated to multiple sclerosis. We conclude that the increased expression of IL18R1 may contribute pathogenically to disease and is therefore a potential therapeutic target. The absence of a genetic association in the IL18R1 gene itself suggests regulation from other parts of the genome, or as part of the inflammatory cascade in multiple sclerosis without a prime genetic cause.
Intelligent PV Module for Grid-Connected PV Systems

Most issues carried out about building integrated photovoltaic (PV) system performance show average losses of about 20%-25% in electricity production. The causes are varied, e.g., mismatching losses, partial shadows, variations in current-voltage (I-V) characteristics of PV modules due to manufacturing processes, differences in the orientations and inclinations of solar surfaces, and temperature effects. These losses can be decreased by means of suitable electronics. This paper presents the intelligent PV module concept, a low-cost high-efficiency dc-dc converter with maximum power point tracking (MPPT) functions, control, and power line communications (PLC). In addition, this paper analyses the alternatives for the architecture of grid-connected PV systems: centralized, string, and modular topologies. The proposed system, i.e., the intelligent PV module, fits within this last group. Its principles of operation, as well as the topology of boost dc-dc converter, are analyzed. Besides, a comparison of MPPT methods is performed, which shows the best results for the incremental conductance method. Regarding communications, PLC in every PV module and its feasibility for grid-connected PV plants are considered and analyzed in this paper. After developing an intelligent PV module (with dc-dc converter) prototype, its optimal performance has been experimentally confirmed by means of the PV system test platform. This paper describes this powerful tool especially designed to evaluate all kinds of PV systems
The Clinical Molecular Diagnostics Laboratory and Microsatellite Instability Testing of Colorectal Cancer

Identification of microsatellite instability (MSI) in colorectal cancer (CRC) patients can have prognostic, therapeutic, and family planning implications. MSI is a term that describes a shift in the length of microsatellite repeats because of mismatch repair gene deficiency secondary either to DNA methylation or genetic mutation. MSI testing is frequently performed on patients with suspected hereditary nonpolyposis CRC, and MSI is found in CRC samples from patients who eventually go on to be genotyped and confirmed to have Lynch syndrome. Other indications for MSI testing include prognosis determination, since MSI cancer patients do better than those with microsatellite stable cancers, and for chemotherapy selection, where some data indicate the lack of benefit to patients with microsatellite unstable CRCs treated with 5-Fluorouracil. During the histologic review of either a biopsy or a resection specimen, a pathologist's increased familiarity with the revised Bethesda criteria and awareness of the histopathological features commonly seen in colorectal tumors harboring MSI can increase the rate of clinically appropriate testing and improve patient care. Molecular analysis for MSI is performed routinely by a number of clinical laboratories on formalin-fixed paraffin-embedded tissue. Immunohistochemical stains can also be performed to assess for the absence of mismatch repair protein in a tumor cell. A representative case will be detailed to review the histology and the molecular data commonly observed in CRC showing MSI.
Task Characterization for an Effective Worker Targeting in Crowdsourcing

In the last decade, crowdsourcing (CS) has emergedas a very promising approach for obtaining services, feedbackor data from a large number of people connected through theInternet, in a short time and at a reasonable cost. CS has beenused in a large range of contexts, thus proving its versatility. However, the quality of the services or data provided by theworkers (the "crowd") is not guaranteed, and therefore mustbe verified. This verification usually results in additional timeand cost. We propose a novel approach of quality control incrowdsourcing that reduces, and in some cases eliminates, thisoverhead. Our approach uses a learning technique to characterizeand cluster tasks, and selects, within the available crowd, the mostreliable group of workers for a given type of tasks.
Design and Implementation of a Robust Current-Control Scheme for a PMSM Vector Drive With a Simple Adaptive Disturbance Observer

This paper introduces a robust current-control scheme for a permanent-magnet synchronous motor (PMSM) with a simple adaptive disturbance observer. The robust controller is realized by including an adaptive element in the reference-voltage-generation stage using the feedforward control. Due to the time-varying nature and the high-bandwidth property of the uncertainties in a practical PMSM drive system, the adaptive element is simply chosen as the estimated uncertainty function, which adaptively varies with different operating conditions. Subsequently, the frequency modes of the uncertainty function are embedded in the control effort, and a robust current-control performance is yielded. Furthermore, the inclusion of the estimated uncertainty function provides an efficient solution for torque-ripple minimization in PMSM drives. This is because the frequency modes of the disturbances to be eliminated, i.e., the flux harmonics, are included in the stable closed-loop system. To provide a high-bandwidth estimate of the uncertainty function, a simple adaptation law is derived using the nominal current dynamics and the steepest descent method. To guarantee the system's convergence and to properly tune the proposed observer, a stability analysis based on a discrete-time Lyapunov function has been used. Comparative evaluation experiments are presented to demonstrate the effectiveness of the proposed control scheme under different operating conditions.
Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

ABSTRACT Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = −0.66, P = 0.04) and acid-fast bacilli (R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens.
Small-Plasmid-Mediated Antibiotic Resistance Is Enhanced by Increases in Plasmid Copy Number and Bacterial Fitness

ABSTRACT Plasmids play a key role in the horizontal spread of antibiotic resistance determinants among bacterial pathogens. When an antibiotic resistance plasmid arrives in a new bacterial host, it produces a fitness cost, causing a competitive disadvantage for the plasmid-bearing bacterium in the absence of antibiotics. On the other hand, in the presence of antibiotics, the plasmid promotes the survival of the clone. The adaptations experienced by plasmid and bacterium in the presence of antibiotics during the first generations of coexistence will be crucial for the progress of the infection and the maintenance of plasmid-mediated resistance once the treatment is over. Here we developed a model system using the human pathogen Haemophilus influenzae carrying the small plasmid pB1000 conferring resistance to β-lactam antibiotics to investigate host and plasmid adaptations in the course of a simulated ampicillin therapy. Our results proved that plasmid-bearing clones compensated for the fitness disadvantage during the first 100 generations of plasmid-host adaptation. In addition, ampicillin treatment was associated with an increase in pB1000 copy number. The augmentation in both bacterial fitness and plasmid copy number gave rise to H. influenzae populations with higher ampicillin resistance levels. In conclusion, we show here that the modulations in bacterial fitness and plasmid copy number help a plasmid-bearing bacterium to adapt during antibiotic therapy, promoting both the survival of the host and the spread of the plasmid.
Anti-Epstein–Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel

Background: Elevated Epstein–Barr virus (EBV) antibody titers are risk factors for multiple sclerosis (MS), but the strength and consistency of this association are not well characterized. Objectives: The objectives of this study were to determine whether this association is confounded by vitamin D or modified by gender or race, and the usefulness of EBV nuclear antigen (EBNA) antibodies as a marker for MS. Methods: We conducted a prospective study among US military personnel. Antibody titers against EBV antigens were measured in serum samples from 222 individuals who developed MS and 444 age, sex, and race/ethnicity matched controls. Conditional logistic regression was used to estimate relative risks. Results: MS risk increased with increasing titers of anti-EBNA complex (p < 10−9) and anti-EBNA-1 (p = 5.8 × 10−9) titers. MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers <20 (95% confidence interval [CI] 9.6–136), and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 <20 (95% CI 2.6–23). These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels. Areas under the receiver operating characteristic (ROC) curves were 0.67 for EBNA complex and 0.65 for EBNA-1. Conclusions: Serum titers of pre-onset anti-EBNA antibodies are strong, robust markers of MS risk and could be useful in an MS risk score.
Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens

ABSTRACT Trials to test new drugs currently in development against tuberculosis in humans are impractical. All animal models to prioritize new regimens are imperfect, but nonhuman primates (NHPs) infected with Mycobacterium tuberculosis develop active tuberculosis (TB) disease with a full spectrum of lesion types seen in humans. Serial 2-deoxy-2-[18F]-fluoro-d-glucose (FDG) positron emission tomography (PET) with computed tomography (CT) imaging was performed on cynomolgus macaques during infection and chemotherapy with individual agents or the four-drug combination therapy most widely used globally. The size and metabolic activity of lung granulomas varied among animals and even within a single animal during development of disease. Individual granulomas within untreated animals had highly local and independent outcomes, some progressing in size and FDG uptake, while others waned, illustrating the highly dynamic nature of active TB. At necropsy, even untreated animals were found to have a proportion of sterile lesions consistent with the dynamics of this infection. A more marked reduction in overall metabolic activity in the lungs (decreased FDG uptake) was associated with effective treatment. A reduction in the size of individual lesions correlated with a lower bacterial burden at necropsy. Isoniazid treatment was associated with a transient increase in metabolic activity in individual lesions, whereas a net reduction occurred in most lesions from rifampin-treated animals. Quadruple-drug therapy resulted in the highest decrease in FDG uptake. The findings of PET-CT imaging may provide an important early correlate of the efficacy of novel combinations of new drugs that can be directly translated to human clinical trials.