Miracle-dz/UniFAR-FTUs huggingface dataset:
A routine-qualified flow cytometric method for the identification of multiple sclerosis patients with a reduced therapeutic effectiveness of natalizumab

Abstract Background: Natalizumab-neutralizing antibodies (NABs) occur in 9% of natalizumab-treated multiple sclerosis (MS) patients. Loss of clinical and biological efficacy in patients with persisting NABs requires termination of natalizumab treatment. Because high-titer NABs are strongly associated with persistence of NABs, we investigated if determination of natalizumab saturation levels of α-4 integrins by flow cytometry has the potential to identify patients early with NABs. Methods: Cell-bound natalizumab and natalizumab saturation of α-4 integrins on T cells were detected by flow cytometry using a monoclonal anti-human IgG4 antibody. Peripheral blood mononuclear cells were enriched from venous blood collected at the start (baseline) and every 4 weeks immediately before subsequent infusions until up to 9 months from natalizumab-treated patients with NABs (n=4) and at the start and after 1 (n=15), 2 (n=14), 3 (n=9), 6 (n=7), and 9 months (n=3) from natalizumab-treated patients without NABs. Natalizumab saturation levels (in %) of T cells were determined by relating median fluorescence intensities (MFIs) of in vivo bound natalizumab to MFIs after in vitro incubation with saturating amounts of natalizumab. Determination of serum NABs was performed by ELISA. Results: In patients without NABs, the median natalizumab saturation level of T cells over 9 months was 75% (confidence interval of 95%: 72–78%). In two of the four patients with NABs, the natalizumab saturation level of T cells only reached approximately 50% after the first infusion and further declined to baseline levels with the second infusion. Low-titer NABs were measured after the first infusion and development of persistent high-titer NABs led to termination of natalizumab treatment after 6 months. In another two patients, the natalizumab saturation level of T cells was 74% and 68% after the first infusion, temporarily decreased to approximately baseline levels and re-increased after approximately 6 months. Transient NABs were detected after 2 and 3 months, which resolved after 5 and 6 months. Conclusions: Monitoring the natalizumab saturation level on T cells is a fast and reliable method to identify patients with a reduced treatment effect due to NABs. Both high- and low-titer NABs were equally effective in reducing cellular natalizumab saturation levels. We were able to show that monitoring the natalizumab saturation levels by flow cytometry, is a sensitive method for detecting a prolonged NAB-mediated reduced treatment effect because NABs are apparently effective longer than suggested by the detection limit of ELISA.
Rapid and simple detection of IFN‐neutralizing antibodies in chronic hepatitis C non‐responsive to IFN‐α

Different mechanisms have been proposed for the failure of interferon (IFN) therapy in patients with chronic hepatitis C and multiple sclerosis, for example, the presence of IFN‐neutralizing antibodies. In this study, a novel assay system based on the IFN‐inducible Mx‐promoter was used to detect IFN‐neutralizing antibodies in sera of patients with chronic hepatitis C. To monitor IFN bioactivity in IFN‐treated patients, a real‐time RT‐PCR for MxA gene expression in PBMCs was established. Using these two methods, patients with chronic hepatitis C virus (HCV) infection receiving IFN therapy and patients with treatment induced HCV clearance were monitored. Importantly, neutralizing anti‐IFN antibodies were detected in the sera of 3 of 38 chronically HCV‐infected patients who failed to respond to therapy but none in sera of patients who cleared HCV after IFN therapy. Interestingly, the presence of these antibodies correlated with the lack of MxA induction in PBMCs after initiation of IFN‐α therapy. Retrospective analysis of one patient's sera revealed that the anti‐IFN‐α antibodies had already developed after the first of four unsuccessful IFN therapies, suggesting that neutralizing antibodies may have contributed to the failure of previous IFN treatments. In summary, a novel screening assay was established that may be helpful for testing IFN non‐responders for the presence of clinically relevant anti‐IFN‐α antibodies and for selecting alternative IFN preparations not neutralized by these antibodies. J. Med. Virol. 78:74–82, 2006. © 2005 Wiley‐Liss, inc.
Monolithic Au/CeO2 nanorod framework catalyst prepared by dealloying for low-temperature CO oxidation

Monolithic Au/CeO2 nanorod frameworks (NFs) with porous structure were prepared by dealloying melt-spun Al89.7Ce10Au0. 3 ribbons. After calcination in O2, a 3D Au/CeO2 NF catalyst with large surface area was obtained and used for low-temperature CO oxidation. The small Au clusters/nanoparticles (NPs) were in situ supported and highly dispersed on the nanorod surface, creating many nanoscale contact interfaces. XPS results demonstrated that high-concentration oxygen vacancy and Auδ+/Au0 co-existed in the calcined sample. The Au/CeO2 nanorod catalyst calcined at 400 °C exhibited much higher catalytic activity for CO oxidation compared with the dealloyed sample and bare CeO2 nanorods. Moreover, its complete reaction temperature was as low as 91 °C. The designed Au/CeO2 NF catalyst not only possessed extreme sintering resistance but also exhibited high performance owing to the enhanced interaction between the Au clusters/NPs and CeO2 nanorod during calcination.
Chiro-plasmonic refractory metamaterial with titanium nitride (TiN) core–shell nanohelices

Chiral metamaterials are obtained by assembling plasmonic elements in geometries with broken mirror symmetry, which can have promising applications pertaining to generation, manipulation and detection of optical polarisation. The materials used to fabricate this promising nanosystem, especially in the visible–NIR regime, are limited to noble metals such as Au and Ag. However, they are not stable at elevated temperatures and in addition, incompatible with CMOS technologies. We demonstrate that it is possible to develop a chiro-plasmonic system based on a refractory material such as titanium nitride (TiN) which does not have these disadvantages. The building block of our metamaterial is a novel core–shell helix, obtained by coating TiN over silica nanohelices. These were arranged in a regular two-dimensional array over cm-scale areas, made possible by the use of scalable fabrication techniques such as laser interference lithography, glancing angle deposition and DC magnetron sputtering. The measured chiro-optical response was extremely broadband (<500 nm to >1400 nm), and had contributions from individual, as well as collective plasmon modes of the interacting nanohelices, whose spectral characteristics could be easily controlled by varying the direction of the incident radiation.
Improving the photovoltaic performance of the all-solid-state TiO2 NR/CuInS2 solar cell by hydrogen plasma treatment

The interfacial properties of the heterojunction between p-type and n-type materials play an important role in the performance of the solar cell. In this paper, a p-type CuInS2 film was deposited on TiO2 nanorod arrays by spin coating to fabricate an all-solid-state solar cell and the TiO2 nanorod arrays were treated with hydrogen plasma(H:TiO2) to ameliorate the interfacial properties. The influence of the hydrogen plasma treatment on the performance of the solar cell was investigated. The short-circuit current density was obviously raised and the power conversion efficiency of the solar cell improved to 0.30%, which is three times that of solar cells without hydrogen plasma treatment. The enhancement of the performance is attributed to not only the enhancement of carrier separation and transport, but the reduction of the recombination of electrons and holes, which is caused by hydrogen plasma treatment.
Antiplatelet and Anticoagulant Prophylaxis and Postoperative Blood Loss in Cardiac Surgery: In Response

through and a strong enough heightened and fear for a needle (3). The present results suggest the possibility of anesthetizing the skin without pain, thereby preventing patients from developing needle phobia. BMI 43.4 (cid:3) 6.7 2 (range, 35–68) identify factors complicating direct laryngoscopy ET. measurements (neck circumference, mobility of the articulations of the cervical spine, the temporomandibular joints mobility, and width of mouth opening, sterno-mental distance, presence of edema of throat, crowding of the pharynx by the tongue, proceeding teeth) and Mallampati score were recorded. The direct laryngoscopy (Cormack scale) and the intubation conditions (Krieg scale) were estimated. Neither absolute obesity nor BMI associated with intubation difficulties: DI predicting factors were present in 19 (21.8%) patients; Cormack Class 3 and 4, 17 (19.5%) patients. Actual DI occurred in 4 (4.6%) patients, BMI 41.9–46.2 kg/m 2 ; in 2 of 4 patients, DI expected; 2 8 points. All MO patients with BMI (cid:6) 50 kg/m 2 intubated by first attempt.
Feasibility of tungsten functional paper in electron grid therapy: a Monte Carlo study

Electron grid therapy is expected to be a valid treatment for bulky superficial tumors. It is difficult, however, to fit irradiation fields to bulky superficial tumor shapes for conventional electron grid therapy with a cerrobend grid collimator. In this study, we investigated whether a grid collimator using tungsten functional paper (TFP), with its radiation shielding ability, could be used for electron grid therapy. Dose distributions were measured using 9 MeV electron grid beams from a cerrobend grid collimator. For the simulation study, the same grid irradiation fields were shaped using a TFP grid collimator (thicknesses of 0.15, 0.3, 0.6, 0.9, and 1.2 cm) by laying them on a phantom. We then determined the dose distributions using Monte Carlo calculations and compared the cerrobend and TFP electron grid beams regarding dose distributions, including the depths of the maximum dose (dmax), 90% dose (d90), and 80% dose (d80), and the ratios of the doses in the areas with and without shielding (valley to peak ratios). The equivalent dosimetric thickness was obtained with the TFP grid collimator that was equivalent to the dose distribution of the cerrobend grid collimator. For the cerrobend electron grid beams, the dmax, d90, and d80 were 1.0, 2.1, and 2.5 cm, respectively, and the valley to peak ratios at those depths were 0.48, 0.66, and 0.73, respectively. The equivalent dosimetric thickness of TFP was 0.52 cm. The dmax, d90, and d80 for the 0.52 cm thick TFP electron grid beams were 1.1, 1.9, and 2.3 cm, respectively, and the valley to peak ratios at those depths were 0.49, 0.63, and 0.71, respectively. The TFP grid collimator flexibly delivered excellent dose distributions by simply attaching it to the patient’s skin. It could thus be used for electron grid therapy instead of the cerrobend grid collimator.
Genetic counselling: Predicting patient outcomes

Abstract With the rapid development of genetic testing, the demand for genetic counselling is increasing. Yet there is little known about what makes for effective or efficient genetic counselling. The aim of the current study is to determine the main factors influencing outcomes of genetic consultations. One hundred and thirty one routine consultations conducted in a regional genetics centre were audiotaped, transcribed and coded. The main predictors of outcome tested were pre-interview patient and counsellor expectations; pre-interview patient concerns; length of consultations; counsellor directiveness; and the extent to which social and emotional issues are addressed in the consultation. The main outcomes were the patient's view of the extent to which their expectations were met, their satisfaction with information provided, and concern about the problem they were referred with. Although there were six significant correlations between the process of consultation and outcome variables, multivariate analy.
Physical performance and body mass index in Swedish children and adolescents

Background: Physical fitness and overweight are both important health-related parameters. Reference data from a population are important for comparisons with children with impairments, different diseases, in habilitation or rehabilitation after injuries. Objective: The aim of the survey was to obtain reference data on physical performance in Swedish children and adolescents aged 10, 13 and 16 years. In addition, height and body mass were assessed and body mass index (BMI) was calculated. Design: In total, 2118 children and adolescents in 48 randomly selected schools in Sweden were invited and 1737 subjects participated. Testing procedures were similar to the Eurofit tests, but with some modifications. Results : Results show generally better performance in boys than in girls and increasing performance with age. BMI increased with age with only small differences between genders. Large variations were found within age and gender groups. Conclusions: The present study provides reference data on physical performance and body size in Swedish children and adolescents. The results from the present study may be used to compare performance and anthropometric data over time or between countries, to evaluate performance in different patient groups or to set goals for athletes. Keywords: cardiovascular; neuromuscular; paediatric; physical fitness; Sweden
Differential effects of methylphenidate and cocaine on GABA transmission in sensory thalamic nuclei

Methylphenidate (MPH) is widely used to treat children and adolescents diagnosed with attention deficit/hyperactivity disorder. Although MPH shares mechanistic similarities to cocaine, its effects on GABAergic transmission in sensory thalamic nuclei are unknown. Our objective was to compare cocaine and MPH effects on GABAergic projections between thalamic reticular and ventrobasal (VB) nuclei. Mice (P18‐30) were subjected to binge‐like cocaine and MPH acute and sub‐chronic administrations. Cocaine and MPH enhanced hyperlocomotion, although sub‐chronic cocaine‐mediated effects were stronger than MPH effects. Cocaine and MPH sub‐chronic administration altered paired‐pulse and spontaneous GABAergic input differently. The effects of cocaine on evoked paired‐pulse GABA‐mediated currents changed from depression to facilitation with the duration of the protocols used, while MPH induced a constant increase throughout the administration protocols. Thalamic reticular nucleus GAD67 and VB CaV3.1 protein levels were measured using western blot to better understand their link to increased GABA release. Both proteins were increased by sub‐chronic administration of cocaine. MPH showed effects on GABAergic transmission that seems less disruptive than cocaine. Unique effects of cocaine on postsynaptic VB calcium currents might explain deleterious cocaine effects on sensory thalamic nuclei. These results suggest that cocaine and MPH produced distinct presynaptic alterations on GABAergic transmission.
Chapter 7.

Abstract College age students are in the midst of important psychosocial and neurobiological changes. The developmental fluidity of this period of life compels caution in diagnosing and treating depressive episodes, especially in discriminating between bipolar and non-bipolar depression. Treating college age students with depression requires adherence to four basic principles that guide treatment. We urge you to aim for diagnostic clarity, keep the developmental context in mind when making diagnoses and conducting treatment, establish clear aims for the pharmacologic intervention, and provide adequate resources to monitor treatment outcomes and respond rapidly to any untoward events.
Evaluation, validation, and modification of pictograms depicting potential side effects to medication

Abstract Rationale Health literacy and discordant languages are important barriers to communicating and educating patients about their treatment. Pictograms have shown to be an effective communication tool by increasing comprehension, information recall, and adherence. Objectives To evaluate, modify, and validate a set of pictograms that depict potential side effects to medication. Methods Children inpatient and outpatient were recruited at a Canadian pediatric hospital. Participants in Phase I completed a ‘guessability’ test in order to identify the best pictogram for 27 side effects. In Phase II, structured interview using ‘guessability’ and translucency questionnaires tested the comprehensibility of 28 side effects pictograms. Results Phase I: one hundred and six patients were enrolled and the best pictogram for each category was selected for Phase II. For the side effect ‘headache’, both pictograms achieved 100% of correct answer, so both of them were used in Phase II. For the pictogram ‘general pain 2’, 93.8% of the patients thought it was ‘back pain’, so we decided to use it as ‘back pain’ pictogram in Phase II. Phase II: sixty-seven patients were interviewed, we found that 11 out of 28 pictograms were not guessed correctly by 80% or more participants and six out of 28 pictograms did not achieve a score 5 or greater from 80% or more participants. We found a significant association between the comprehension of the pictogram ‘dizzy when getting up’ and taking three medications or more. Conclusion Sixteen pictograms were validated whereas 12 failed the validation. Five of them failed at both ‘guessability’ and translucency tests.
Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease

Alzheimer′s disease (AD) is the most common form of dementia in the elderly. Memory loss in AD is increasingly attributed to soluble oligomers of the amyloid‐β peptide (AβOs), toxins that accumulate in AD brains and target particular synapses. Glutamate receptors appear to be centrally involved in synaptic targeting by AβOs. Once bound to neurons, AβOs dysregulate the activity and reduce the surface expression of both N‐methyl‐d‐aspartate (NMDA) and 2‐amino‐3‐(3‐hydroxy‐5‐methyl‐isoxazol‐4‐yl)propanoic acid (AMPA) types of glutamate receptors, impairing signaling pathways involved in synaptic plasticity. In the extracellular milieu, AβOs promote accumulation of the excitatory amino acids, glutamate and d‐serine. This leads to overactivation of glutamate receptors, triggering abnormal calcium signals with noxious impacts on neurons. Here, we review key findings linking AβOs to deregulated glutamate neurotransmission and implicating this as a primary mechanism of synapse failure in AD. We also discuss strategies to counteract the impact of AβOs on excitatory neurotransmission. In particular, we review evidence showing that inducing neuronal hyperpolarization via activation of inhibitory GABAA receptors prevents AβO‐induced excitotoxicity, suggesting that this could comprise a possible therapeutic approach in AD.
PIGMENTED LINES IN RETROIRIDAL REGION OF ANTERIOR CAPSULE OF LENS

Pigmented lines on the lens were first described by Brueckner1in 1907. Vogt2referred to this condition as retroiridal pigmented lines on the anterior capsule of the lens and described 9 cases in his "Atlas. " Lugli3and Streiff4reported 5 and 3 cases respectively. Twenty-two cases in Geneva, Switzerland, were reported by Bischler.5As far as I can determine, this abnormality has never been described in the American or the English literature. The purpose of this report is to bring the condition to the attention of American ophthalmologists and to report 2 new cases, 1 of a soldier aged 27. His case is unique because in all previously reported cases the condition occurred in persons over 40 years of age. Pigmented lines in the retroiridal region of the anterior capsule of the lens occur nearly always bilaterally, although they may be more pronounced on one
Performance of three PCR methods targeting different regions of viral genome for the detection of TTV in Non A-E hepatitis, chronic B and C hepatitis and healthy blood donors

TT virus (TTV) was suggested to be the etiologic agent for non A-E hepatitis but this could not yet be proven due to high detection rates not only in hepatitis but also in healthy persons and sensitivity differences of PCR methods employed. The aim of this study was to evaluate TTV DNA positivity in non A-E hepatitis cases, chronic HBV and HCV hepatitis cases and healthy blood donors via PCR systems that target all regions of the viral genome used for viral detection. 23 non A-E hepatitis, 28 chronic HCV, 21 chronic HBV cases and 56 healthy blood donors were included in the study and evaluated by PCR protocols that target 5′-UTR, 3′-UTR and N22 (ORF1) regions. As a result, 3′-UTR and 5′-UTR PCR had comparable detection rates that were higher than N22 PCR. Differences in detection rates among study groups were not statistically significant for any PCR method. Hepatic enzyme levels of the patients were not correlated with the presence of TTV DNA. Detection rate was significantly higher for Non A-E hepatitis group when positivity rates from all methods were combined. These results suggest an alteration of viral genotypes in Non A-E hepatitis which might be associated with pathogenesis.
microRNA‐181a is involved in insulin‐like growth factor‐1‐mediated regulation of the transcription factor CREB1

microRNAs are a class of small non‐coding RNA molecules negatively regulating gene expression at post‐transcriptional level in many tissues including the central nervous system. cAMP response element binding protein (CREB) is a key nuclear factor highly expressed in hippocampal neurons on which many signal pathways converge. Recent studies have found that microRNA‐181a is rich in mature nerve cells, and bioinformatics analysis shows that the CREB1 mRNA 3′‐untranslated region (3′UTR) contains complementary sequence to the miR‐181a seed region. In this study, we investigated whether miR‐181a is a negative regulator for CREB1 expression in neurons. It was found that the expression of miR‐181a was negatively correlated with Insulin‐like growth factor‐1 (IGF‐1) and CREB1 in the Lewis rat hippocampus. miR‐181a bound to CREB1 mRNA through a specific binding site in the 3′UTR sequence. The expression of CREB1 in PC12 cells was down‐regulated by transfection with a miR‐181a mimic and up‐regulated by a miR‐181a inhibitor. A down‐regulated miR‐181a and an up‐regulated CREB1 were observed in IGF‐1‐stimulated PC12 cells. And miR‐181a inhibited dendritic growth of cultured hippocampus neurons. These suggest that miR‐181a is involved in IGF‐1‐regulated CREB1 expression by targeting its mRNA 3′UTR.