Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK

Background: Azathioprine (AZA) is a common immunosuppressive drug used for relapse prevention in neuromyelitis optica (NMO). Objectives: The objective of this paper is to assess efficacy, tolerability and retention of AZA in a large NMO cohort. Methods: We conducted a retrospective review of medical records of 103 aquaporin-4 antibody-positive NMO and NMO spectrum disorder (NMOSD) patients treated with AZA. Results: This is the largest reported cohort of AQP4-Ab positive patients treated with AZA. Eighty-nine per cent (n = 92) had reduction in median annualised relapse rates from 1.5 (IQR 0.6–4.0) to 0 (IQR 0–0.27, p < 0.00005) with treatment. Sixty-one per cent (n = 63) remained relapse free at a median follow-up of 18 months. Neurological function improved or stabilised in 78%. At last follow-up, treatment was discontinued in 46% (n = 47). Of these, 62% (n = 29) were because of side effects, 19% (n = 9) because of death, 15% (n = 7) because of ongoing disease activity, and 2% (n = 1) because of pregnancy. Using Kaplan-Meyer curves, we estimate that 73%, 58%, 47% and 33% of patients will remain on AZA for longer than one, three, five and 10 years, respectively, after initiation of treatment. Conclusions: AZA is a modestly effective treatment for NMO. However, many patients discontinue AZA over time and this seems to reflect poor tolerability more than lack of efficacy.
Identical lesion morphology in primary progressive and relapsing–remitting MS –an ultrahigh field MRI study

Potential differences between primary progressive (PP) and relapsing–remitting (RR) multiple sclerosis (MS) have been controversially discussed. In this study, we compared lesion morphology and distribution in patients with PPMS and RRMS (nine in each group) using 7 T MRI. We found that gray and white matter lesions in PPMS and RRMS patients did not differ in their respective morphological characteristics (e.g. perivascular p = 0.863, hypointense rim p = 0.796, cortical lesion count p = 0.436). Although limited by a small sample size, our study results suggest that PPMS and RRMS, despite differences in disease course and clinical characteristics, exhibit identical lesion morphology under ultrahigh field MRI.
Resistance to Ceftazidime-Avibactam in Klebsiella pneumoniae Due to Porin Mutations and the Increased Expression of KPC-3

W e reported the ﬁrst clinical case of a ceftazidime-avibactam resistant KPC-3-producing Klebsiella pneumoniae (1), from a patient with no history of ceftazidime-avibactam therapy. We now present data documenting mechanisms of ceftazidime-avibactam resistance in this isolate. Whole-genome sequencing (WGS) was performed on two isolates: KP1245 (ceftazidime-avibactam MIC, 4 (cid:2) g/ml; from blood on hospital day 1; referred to as isolate 1 in our previous report [1]) and KP1244 (ceftazidime-avibactam MIC, 32 (cid:2) g/ml; from blood on hospital day 2; referred to as isolate 2 in our previous report [2]), using MiSeq (Illumina, San Diego, CA) and PacBio RSII (Menlo Park, CA) systems (2). The i n silico multilocus sequence type (ST) was ST258. Single nucleotide polymorphism (SNP) analysis revealed 17 SNPs between KP1245 and KP1244, indicating that the isolates were related but that signiﬁcant diversity existed in this patient (2). Nonsynonymous mutations are shown in Table 1; the most striking of these is in the OmpK36 porin gene. KP1244 contained a missense mutation predicted to encode a T333N mutation. Both isolates also harbored a mutation predicted to encode R191L in OmpK36 and had a nonfunctional OmpK35, due to a frameshift mutation that trun-cated the protein at amino acid 42, common to K.
Differential release of β‐chemokines in serum and CSF of patients with relapsing–remitting multiple sclerosis

Objective–β‐chemokines were recently demonstrated in active MS‐lesions. We tested whether MCP‐1 and RANTES can also be detected in CSF and serum of patients with MS and whether release is associated with inflammatory disease activity. Materials and methods– CSF and serum from 34 patients with newly diagnosed relapsing–remitting MS (RR‐MS), 17 patients with viral meningitis (VM) and 19 patients with non‐inflammatory neurological diseases (NIND) were investigated by ELISA. RR‐MS patients underwent lumbar puncture and Gd‐enhanced MRI examinations within 2 days. Results– MCP‐1 was strong intrathecally released in all patients. Compared to NIND CSF‐levels were increased in VM (P<0.001) and were decreased in RR‐MS (P<0.05). RANTES was only detected in serum in all patients. Levels were higher in VM and RR‐MS compared to NIND (P<0.05). A total of 14/34 RR‐MS patients exhibited active Gd‐enhancing lesions on MRI. They had lower MCP‐1 levels in CSF (P<0.001) and serum (P<0.05) and higher serum levels of RANTES (P<0.05) as compared to patients without active lesions. Conclusions– MCP‐1 and RANTES are differentially released during acute attacks of RR‐MS, which might reflect different immunregulatory roles of these β‐chemokines in RR‐MS.
Determination of the Duration of Antibacterial Efficacy following Administration of Gamithromycin Using a Bovine Mannheimia haemolytica Challenge Model

ABSTRACT The antibacterial efficacy of gamithromycin administered once 1, 5, or 10 days prior to a challenge infection with Mannheimia haemolytica serotype A1 was evaluated. Forty calves were randomly allocated on day −11, restricted by body weight, to one of three treatment groups given gamithromycin at 6 mg/kg of body weight 10, 5, or 1 days before challenge or to an untreated control group. M. haemolytica A1 challenge infections were induced on day 0 by depositing 7.4 × 107 CFU at the bifurcation of the main bronchus using a bronchoscope. Clinical observations were made daily from the day of allocation to day 10, when necropsy was scheduled; three calves died or were euthanized in extremis on welfare grounds prior to scheduled necropsy. At necropsy the lungs were removed, pneumonic lesions were scored, and samples of lung tissue were cultured for M. haemolytica. The three groups of animals treated with gamithromycin before challenge had significantly lower lung M. haemolytica counts and fewer clinical signs of respiratory disease than did the saline-treated group. For most of the clinical parameters, the pattern of responses differed significantly (P < 0.05) between the gamithromycin-treated groups and the control group. There were no statistically significant differences between groups in the mean lung lesion scores, partly as a result of high individual variability, particularly within the control group. The administration of gamithromycin 1, 5, and 10 days prior to M. haemolytica A1 challenge resulted in a reduction in bacterial isolation from the lungs and a reduction in the severity of clinical disease.
A Real-Time Vision System for Nighttime Vehicle Detection and Traffic Surveillance

This paper presents an effective traffic surveillance system for detecting and tracking moving vehicles in nighttime traffic scenes. The proposed method identifies vehicles by detecting and locating vehicle headlights and taillights using image segmentation and pattern analysis techniques. First, a fast bright-object segmentation process based on automatic multilevel histogram thresholding is applied to effectively extract bright objects of interest. This automatic multilevel thresholding approach provides a robust and adaptable detection system that operates well under various nighttime illumination conditions. The extracted bright objects are then processed by a spatial clustering and tracking procedure that locates and analyzes the spatial and temporal features of vehicle light patterns, and identifies and classifies moving cars and motorbikes in traffic scenes. The proposed real-time vision system has also been implemented and evaluated on a TI DM642 DSP-based embedded platform. The system is set up on elevated platforms to perform traffic surveillance on real highways and urban roads. Experimental results demonstrate that the proposed traffic surveillance approach is feasible and effective for vehicle detection and identification in various nighttime environments.
Assessment of Fuel Cell Performance Under Different Air Stoichiometries and Fuel Composition

The behavior of fuel cells (FCs) at steady state and during transients is an important factor both for control tuning and for performance assessment. In the technical literature, few papers deal systematically with FC characterization. In this paper, the performance characterization of a proton exchange membrane (PEM) FC is carried out using an experimental analysis. The experimental activity has been conducted in a test station, properly designed and able to test PEM FC stacks in the range of 500-2000 W. The laboratory test facility is equipped with a National Instruments CompactDAQ real-time data acquisition and control system running a LabVIEW software. The bench commands two mass flow controllers, regulating both fuel flow and air flow which are commanded via two Recommended Standard 232 ports. The temperature of the FC is regulated via a fan operated by a brushless motor drive. An electronic load is connected to the FC terminals. The main operating parameters, such as the air stoichiometric ratio and fuel composition, have been varied and measured, and their influence on the PEM FC behavior has been investigated under both steady-state and transient conditions.
Switching Ripple Characteristics of Space Vector PWM Schemes for Five-Phase Two-Level Voltage Source Inverters—Part 2: Current Ripple

Flux harmonic distortion factors (HDFs) of two space vector pulse width modulation (SVPWM) schemes, aimed at sinusoidal output voltage generation with five-phase voltage source inverters, have been evaluated in Part 1 of this paper. Analytical considerations and numerical integration have been applied in order to determine the switching properties of the considered SVPWM methods. It has been shown that the SVPWM based on four large vectors leads to a considerably higher overall per-phase flux HDF than the method based on two large and two medium space vectors. The purpose of the second part of the paper is to relate flux HDFs to the current ripple and current total harmonic distortion and thus explore further switching characteristics of the two SVPWM techniques. The applied approach is based on simulation and experimentation, in conjunction with the subsequent fast Fourier transform of the waveforms, so that all the results for the ripple are obtained using a methodology completely different from the one in Part 1. Relationships that correlate the current ripple and the flux HDFs are established, and it is further shown that the current ripple can be easily calculated from the flux HDF values of Part 1 if the relevant leakage inductances of the two planes are known. Hence, the complete theory of Part 1 is fully verified by both simulation and experimentation. It is also shown that, in certain cases, the SVPWM based on four large vectors may lead to a smaller current ripple despite a considerably higher flux HDF.
Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease

ABSTRACT Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor β (TGF-β) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-β signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 104 trypomastigotes of T. cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-β signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration.
Evolving Gaits of a Hexapod Robot by Recurrent Neural Networks With Symbiotic Species-Based Particle Swarm Optimization

This paper proposes a new learning approach for evolving dynamic gaits of a hexapod robot. The controller that coordinates the leg movements consists of fully connected recurrent neural networks (FCRNNs). To automate the FCRNN parameter design, a symbiotic species-based particle swarm optimization (SSPSO) algorithm is proposed. There are multiple swarms in the SSPSO, where a swarm only optimizes the relevant parameters to a single node. The number of swarms is equal to the number of nodes in an FCRNN. The symbiotic behavior of particles from different swarms corresponds to the symbiotic structure of different nodes in an FCRNN. For a particle update, particles in different swarms update independently using a local version of particle swarm optimization (PSO) based on speciation. In each swarm, species are formed adaptively in each iteration according to both particle distance and performance. The design of FCRNNs using the SSPSO for temporal sequence generation and hexapod robot dynamic gait evolution for forward movement is conducted. For the latter, a multiple-FCRNN controller is first designed using a simulated hexapod robot. The designed controller is then successfully applied to a real hexapod robot gait control. The SSPSO is compared with the genetic algorithm and different PSO algorithms to verify its efficiency and effectiveness.
The Security-Welfare Relationship: Longitudinal Evidence from Taiwan

We investigate the security-welfare relationship in the case of Taiwan. Specifically, we analyze any possible longitudinal relationship between the government's allocations of dollars and personnel to the military on the one hand, and social welfare as measured by the physical quality of life index on the other. Our results show that the defense burden, whether operationalized in terms of the relative size of the island's military budget or in terms of the relative size of its military establishment, has played neither a major positive nor negative role in determining the changes in its social welfare. We have been unable to find statistically significant evidence of the defense burden influencing social welfare either directly or indirectly (through its effects on the growth of GNP per capita and on the government's welfare and education spending). These results suggest that Taiwan deviates from general cross-national patterns, and indicate the need for further investigation into why it has been relatively successful in dampening the widely suspected trade-offs between defense burden on the one hand, and economic growth and social welfare on the other.
Natalizumab for the prevention of post-partum relapses in women with multiple sclerosis

Objective: Our aim was to evaluate the impact of early redosing of natalizumab after delivery on the risk of post-partum relapses in six women with very active multiple sclerosis (MS). Methods: We undertook a retrospective analysis of data collected prospectively in the Lyon MS Cohort. Results: The annualized relapse rate (ARR) in the year before natalizumab treatment was 4.2 ±0.4, which decreased to 0.4 ±0.6 during the treatment period. The mean time between natalizumab withdrawal and onset of pregnancy was 9 months; one pregnancy was exposed to one infusion. The ARR between natalizumab withdrawal and onset of pregnancy was 1.8 ±0.7. Six relapses occurred before onset of pregnancy and seven during pregnancy. Natalizumab was restarted 7.8 days after delivery (between day 2 and 8 for five patients and on day 23 for one). Only one patient, who had restarted natalizumab 2 days after delivery, had a relapse 2 weeks later. The others five patients were relapse free after a mean of 14.2 ±9.1 months of follow-up. Conclusion: Despite a high risk of post-partum relapses, early redosing of natalizumab led to a complete disappearance of disease activity in all but one patient. These data suggest that natalizumab could be a good candidate for preventing early post-partum relapses.
Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue

Background: Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis, but its pathophysiological mechanisms are poorly understood. It is in particular unclear whether and how fatigue relates to structural and functional brain changes. Objective: We aimed to analyse the association of fatigue severity with basal ganglia functional connectivity, basal ganglia volumes, white matter integrity and grey matter density. Methods: In 44 patients with relapsing–remitting multiple sclerosis and 20 age- and gender-matched healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based morphometry was performed. Results: In comparison with healthy controls, patients showed alteration of grey matter density, white matter integrity, basal ganglia volumes and basal ganglia functional connectivity. No association of fatigue severity with grey matter density, white matter integrity and basal ganglia volumes was observed within patients. In contrast, fatigue severity was negatively correlated with functional connectivity of basal ganglia nuclei with medial prefrontal cortex, precuneus and posterior cingulate cortex in patients. Furthermore, fatigue severity was positively correlated with functional connectivity between caudate nucleus and motor cortex. Conclusion: Fatigue is associated with distinct alterations of basal ganglia functional connectivity independent of overall disability. The pattern of connectivity changes suggests that disruption of motor and non-motor basal ganglia functions, including motivation and reward processing, contributes to fatigue pathophysiology in multiple sclerosis.
Impact of parental multiple sclerosis on early childhood development: A retrospective cohort study

Background: Exposure to parental chronic illness is associated with several adverse developmental outcomes. Objectives: We examined the association between parental multiple sclerosis (MS) and childhood developmental outcomes. Methods: We conducted a population-based retrospective cohort study in Manitoba, Canada, using linked databases. The outcome was childhood development at 5 years of age, expressed as vulnerability (absent vs. present) on the Early Development Instrument (EDI). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results: Children with an MS parent (n=153) were similar to children of unaffected parents (n=876) on all EDI domains. However, mental health morbidity was more common among MS parents compared with non-MS parents 49.5% vs. 35.3%. Among MS parents, mental health morbidity was associated with children’s vulnerability on the social competence (OR, 5.73 [95% CI:1.11–29.58]) and emotional maturity (OR, 3.03 [95% CI:1.03–8.94]) domains. The duration of child’s exposure to parental MS was associated with vulnerability on the physical health domain (OR, 1.49 [95%CI:1.03–2.15]). Conclusion: Parental MS was not associated with adverse early childhood developmental outcomes. However, children of parents with mental health morbidity, and those with longer duration of exposure to parental MS, were at higher risk for early childhood developmental vulnerability.
Impact of neurological impairment, depression, cognitive function and coping on quality of life of people with multiple sclerosis: A relative importance analysis

Background: Determining the relative importance of factors that predict quality of life (QoL) in people with multiple sclerosis (MS) must be addressed through multiple regression metrics, e.g. relative weights, which are designed to solve colinearity problems. Objective: We aimed to compare disease variables, Expanded Disability Status Scale (EDSS), depressive symptomatology (BDI-FS), cognitive performance and coping in predicting MS patients’ QoL, using relative weights. Methods: We assessed 97 patients with MS, using the Functional Assessment of MS (FAMS) as the criterion. Results: EDSS predicted global and physical QoL domains, whereas BDI-FS predicted general contentment and global QoL. Conclusion: EDSS and BDI-FS are relevant determinants of QoL in people with MS.
Antimicrobial Resistance of Old and Recent Staphylococcus aureus Isolates from Poultry: First Detection of Livestock-Associated Methicillin-Resistant Strain ST398

ABSTRACT The susceptibilities of 12 antimicrobial agents for two collections of Staphylococcus aureus, isolated in the 1970s and in 2006 from poultry, were determined. For eight antibiotics, the percentage of resistance was significantly higher in the recent isolates. Ten recent isolates were methicillin resistant and had spa types t011 and t567, belonging to multilocus sequence type 398. This is the first report of “livestock-associated” methicillin resistant S. aureus from healthy poultry.
Characterization of the Global Stabilizing Substitution A77V and Its Role in the Evolution of CTX-M β-Lactamases

ABSTRACT The widespread use of oxyimino-cephalosporin antibiotics drives the evolution of the CTX-M family of β-lactamases that hydrolyze these drugs and confer antibiotic resistance. Clinically isolated CTX-M enzymes carrying the P167S or D240G active site-associated adaptive mutation have a broadened substrate profile that includes the oxyimino-cephalosporin antibiotic ceftazidime. The D240G substitution is known to reduce the stability of CTX-M-14 β-lactamase, and the P167S substitution is shown here to also destabilize the enzyme. Proteins are marginally stable entities, and second-site mutations that stabilize the enzyme can offset a loss in stability caused by mutations that enhance enzyme activity. Therefore, the evolution of antibiotic resistance enzymes can be dependent on the acquisition of stabilizing mutations. The A77V substitution is present in CTX-M extended-spectrum β-lactamases (ESBLs) from a number of clinical isolates, suggesting that it may be important in the evolution of antibiotic resistance in this family of β-lactamases. In this study, the effects of the A77V substitution in the CTX-M-14 model enzyme were characterized with regard to the kinetic parameters for antibiotic hydrolysis as well as enzyme expression levels in vivo and protein stability in vitro. The A77V substitution has little effect on the kinetics of oxyimino-cephalosporin hydrolysis, but it stabilizes the CTX-M enzyme and compensates for the loss of stability resulting from the P167S and D240G mutations. The acquisition of global stabilizing mutations, such as A77V, is an important feature in β-lactamase evolution and a common mechanism in protein evolution.