gebhart/patrepeval huggingface dataset:
Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants (2021)

Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years of age in Scotland presenting with epilepsies. We used two independent sources for case identification: clinical reporting and EEG record review. Capture-recapture methodology was then used to improve the accuracy of incidence estimates. Socio-demographic and clinical details were obtained at presentation, and 24 months later. Children were extensively investigated for aetiology. Whole genome sequencing was offered for all patients with drug-resistant epilepsy for whom no aetiology could yet be identified. Multivariate logistic regression modelling was used to determine associations between clinical features, aetiology, and outcome. Three hundred and ninety children were recruited over 3 years. The adjusted incidence of epilepsies presenting in the first 3 years of life was 239 per 100 000 live births [95% confidence interval (CI) 216-263]. There was a socio-economic gradient to incidence, with a significantly higher incidence in the most deprived quintile (301 per 100 000 live births, 95% CI 251-357) compared with the least deprived quintile (182 per 100 000 live births, 95% CI 139-233), χ2 odds ratio = 1.7 (95% CI 1.3-2.2). The relationship between deprivation and incidence was only observed in the group without identified aetiology, suggesting that populations living in higher deprivation areas have greater multifactorial risk for epilepsy. Aetiology was determined in 54% of children, and epilepsy syndrome was classified in 54%. Thirty-one per cent had an identified genetic cause for their epilepsy. We present novel data on the aetiological spectrum of the most commonly presenting epilepsies of early childhood. Twenty-four months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of an aetiology was the strongest determinant of both DRE and GDD. Aetiology was determined in 82% of those with DRE, and 75% of those with GDD. In young children with epilepsy, genetic testing should be prioritized as it has the highest yield of any investigation and is most likely to inform precision therapy and prognosis. Epilepsies in early childhood are 30% more common than previously reported. Epilepsies of undetermined aetiology present more frequently in deprived communities. This likely reflects increased multifactorial risk within these populations.
Photopatterned Polydiacetylene Images Using a DNA Bio-Photomask (2016)

We describe a novel strategy to fabricate a well-defined polydiacetylene (PDA) supramolecular pattern on polyvinylidene fluoride (PVDF) membrane utilizing a DNA bio-photomask. By focusing on that, the absorption spectrum of DNA molecules having a λmax at 260 nm overlaps with the wavelength at which the photopolymerization of the diacetylene monomer occurs, DNA molecules are used to define specific patterns on PVDF membranes coated with diacetylene lipids by shielding the applied 254 nm UV light and consequently preventing the photopolymerization of the lipids. As a result, the DNA-covered regions retain the original white color on the membrane while the regions uncovered by DNA molecules undergo the color change to blue through the photopolymerization by 254 nm UV irradiation. On the basis of the selective illumination through a DNA photomask, we precisely manufacture specific patterns using a microarray spotting method and also demonstrate the capability of this strategy to achieve a novel colorimetric DNA sensor without any complicated process.
Associations between neonatal hypoglycaemia and brain volumes, cortical thickness and white matter microstructure in mid-childhood: An MRI study (2022)

Neonatal hypoglycaemia is a common metabolic disorder that may cause brain damage, most visible in parieto-occipital regions on MRI in the acute phase. However, the long term effects of neonatal hypoglycaemia on the brain are not well understood. We investigated the association between neonatal hypoglycaemia and brain volumes, cortical thickness and white matter microstructure at 9-10 years. Children born at risk of neonatal hypoglycaemia at ≥ 36 weeks' gestation who took part in a prospective cohort study underwent brain MRI at 9-10 years. Neonatal hypoglycaemia was defined as at least one hypoglycaemic episode (at least one consecutive blood glucose concentration < 2.6 mmol/L) or interstitial episode (at least 10 min of interstitial glucose concentrations < 2.6 mmol/L). Brain volumes and cortical thickness were computed using Freesurfer. White matter microstructure was assessed using tract-based spatial statistics. Children who had (n = 75) and had not (n = 26) experienced neonatal hypoglycaemia had similar combined parietal and occipital lobe volumes and no differences in white matter microstructure at nine years of age. However, those who had experienced neonatal hypoglycaemia had smaller caudate volumes (mean difference: -557 mm<sup>3</sup>, 95% confidence interval (CI), -933 to -182, p = 0.004) and smaller thalamus (-0.03%, 95%CI, -0.06 to 0.00; p = 0.05) and subcortical grey matter (-0.10%, 95%CI -0.20 to 0.00, p = 0.05) volumes as percentage of total brain volume, and thinner occipital lobe cortex (-0.05 mm, 95%CI -0.10 to 0.00, p = 0.05) than those who had not. The finding of smaller caudate volumes after neonatal hypoglycaemia was consistent across analyses of pre-specified severity groups, clinically detected hypoglycaemic episodes, and severity and frequency of hypoglycaemic events. Neonatal hypoglycaemia is associated with smaller deep grey matter brain regions and thinner occipital lobe cortex but not altered white matter microstructure in mid-childhood.
The Efficiency of Muscle-Derived Cell-Mediated Bone Formation (2000)

The development of new clinically applicable methods for the delivery of bone morphogenic protein (BMP) is an area of intensive research. Cell-mediated gene therapy approaches are being explored as a potential delivery vehicle. Primary muscle-derived cells isolated from an adult mouse were transduced with an adenoviral-BMP-2 construct. These cells were injected into the triceps surae of severe combined immune deficient (SCID) mice where they induced heterotopic bone formation. BMP-2 expression by these muscle-derived cell constructs was measured in vitro to estimate in vivo BMP-2 delivery. In vitro expression of BMP-2 by 3 x l0(5) muscle-derived cells was 87.89 ng/72 h. These results suggest that the efficiency of muscle cell-based gene delivery of BMP-2 exceeds the direct delivery of recombinant BMP-2 protein.
Comparative genomics of Czech vaccine strains of Bordetella pertussis (2018)

Bordetella pertussis is a strictly human pathogen causing the respiratory infectious disease called whooping cough or pertussis. B. pertussis adaptation to acellular pertussis vaccine pressure has been repeatedly highlighted, but recent data indicate that adaptation of circulating strains started already in the era of the whole cell pertussis vaccine (wP) use. We sequenced the genomes of five B. pertussis wP vaccine strains isolated in the former Czechoslovakia in the pre-wP (1954-1957) and early wP (1958-1965) eras, when only limited population travel into and out of the country was possible. Four isolates exhibit a similar genome organization and form a distinct phylogenetic cluster with a geographic signature. The fifth strain is rather distinct, both in genome organization and SNP-based phylogeny. Surprisingly, despite isolation of this strain before 1966, its closest sequenced relative appears to be a recent isolate from the US. On the genome content level, the five vaccine strains contained both new and already described regions of difference. One of the new regions contains duplicated genes potentially associated with transport across the membrane. The prevalence of this region in recent isolates indicates that its spread might be associated with selective advantage leading to increased strain fitness.
[Acute paraffin oil pneumopathies. Apropos of a case in a fire-eater]. (1988)

A case of acute paraffin oil-induced pneumonia due to accidental inhalation by a fire-eater of kerdane, a petroleum derivative is reported. The symptoms and course of respiratory manifestations of acute paraffin oil poisoning are reviewed. The physical properties of the petroleum derivative inhaled account for the pathogenesis of the pneumonia. Pulmonary lesions, usually fully reversible, result from the joint effects of an inflammatory phase with exudate and a proliferative phase.
What's in a Name? Is Methicillin-Resistant Staphylococcus aureus Just Another S aureus When Treated With Vancomycin? (1989)

Methicillin-resistant Staphylococcus aureus (MRSA) strains, principally resistant to penicillinase-resistant penicillins and aminoglycosides, are increasingly common hospital isolates. We have examined the significance of MRSA colonization and infection in 1100 consecutively admitted, seriously burned patients in whom vancomycin was used to treat all staphylococcal infections. Colonization with S aureus (SA) was identified in 658 patients, in 319 of whom MRSA colonization was identified. Two hundred fifty-three SA infections occurred in 178 patients; of these infections, 58% were pulmonic and 38% were bacteremic. Methicillin-resistant SA infections occurred in 58 of the SA-infected patients. A severity index, based on multiple-regression analysis of mortality as a function of burn size and age in the study population, was used to estimate expected mortality. We demonstrated no measurable increase in mortality attributable to MRSA in this population of burned, SA-infected patients. The results question the clinical and economic value of added control practices, such as closing of units, refusal of transfer or admission, added isolation, treatment of carriers, furlough of colonized staff, and other expensive measures that are specifically directed at prevention of MRSA infections in critical care areas.
Direct echo PIV flow vector mapping on ultrasound DICOM images (2010)

Echo Particle Image Velocimetry (Echo PIV) has great potential as a non-invasive, simple-to-use hemodynamic vascular profiling technique. Results generated through the analysis of radio frequency (RF) data have shown to be accurate under in vitro and in vivo testing settings. However, most ultrasound (US) imaging systems do not provide RF data but provide image output using the DICOM standard. An important issue when analyzing DICOM-coded images using the Echo PIV method is how to reduce the effects of noise introduced during post-processing. In this work, a new Echo PIV analysis algorithm was developed to analyze DICOM images. In the algorithm, a quasi-linear transform first operates on the cross-correlation maps of each interrogation window, after which a modified ensemble average method is used to estimate time-averaged velocity field from multiple image pairs. This approach was validated against theory using measurements of fully developed laminar pipe flow, thus indicating that DICOM-image based Echo PIV is possible. We further demonstrate that the instantaneous velocity maps of certain pulsatile flow configurations were actually improved by the new method compared to the RF-based Echo PIV results.
Surface-Engineered Nanomaterials for Nanomedicine (2006)

An important feature of nanoparticles is the increased ratio of surface area to volume resulting in large percentage of the atoms on the surface, making them very reactive and offers opportunities to manipulate the properties through these surface atoms. For the most efficient use of nanoparticles in various applications, including biology and medicine, it is important to be able to manipulate the surface chemistry. This paper describes the synthesis and characterization of nanoparticles and the various surface engineering techniques that are utilized for optimizing their applications in nanomedicine.
1.3-$\mu$m InGaAlAs Short-Cavity DBR Lasers for Uncooled 10-Gb/s Operation With Low Drive Current (2006)

We present a novel 1.3-mum laser, a short-cavity distributed-Bragg-reflector (DBR) laser that enables uncooled, 10-Gb/s operation with low drive currents. The laser consists of a short InGaAlAs multiple-quantum-well active region butt-jointed to an InGaAsP-DBR region. A fabricated laser with a 75-mum active region demonstrated 100 degC, 10-Gb/s operation at a record low drive current of 14-mA peak-to-peak (mA <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p-p</sub> ) with an average output power of -3 dBm
Feasibility of Endoscopic Assessment and Treating to Target to Achieve Mucosal Healing in Ulcerative Colitis (2013)

Repeated assessment of endoscopic disease activity with adjustment of medical therapy to the target of MH is feasible in clinical practice in patients with ulcerative colitis, and seems to be of benefit.
First Complete Genome Sequence of TwoStaphylococcus epidermidisBacteriophages (2006)

Staphylococcus epidermidis is an important opportunistic pathogen causing nosocomial infections and is often associated with infections in patients with implanted prosthetic devices. A number of virulence determinants have been identified in S. epidermidis, which are typically acquired through horizontal gene transfer. Due to the high recombination potential, bacteriophages play an important role in these transfer events. Knowledge of phage genome sequences provides insights into phage-host biology and evolution. We present the complete genome sequence and a molecular characterization of two S. epidermidis phages, phiPH15 (PH15) and phiCNPH82 (CNPH82). Both phages belonged to the Siphoviridae family and produced stable lysogens. The PH15 and CNPH82 genomes displayed high sequence homology; however, our analyses also revealed important functional differences. The PH15 genome contained two introns, and in vivo splicing of phage mRNAs was demonstrated for both introns. Secondary structures for both introns were also predicted and showed high similarity to those of Streptococcus thermophilus phage 2972 introns. An additional finding was differential superinfection inhibition between the two phages that corresponded with differences in nucleotide sequence and overall gene content within the lysogeny module. We conducted phylogenetic analyses on all known Siphoviridae, which showed PH15 and CNPH82 clustering with Staphylococcus aureus, creating a novel clade within the S. aureus group and providing a higher overall resolution of the siphophage branch of the phage proteomic tree than previous studies. Until now, no S. epidermidis phage genome sequences have been reported in the literature, and thus this study represents the first complete genomic and molecular description of two S. epidermidis phages.
Side View Imaging for Three Dimensional Microflow Profile Reconstruction (2004)

A side view imaging system for three dimensional microflow profile reconstruction is successfully developed and demonstrated. Various types of microchannels are prepared and demonstrated to obtain side view images. By combining top view and side view data, the three-dimensional velocity and strain rate profiles are successfully reconstructed.
Low Heat Input Welding for Thin Steel Fabrication (2005)

As thinner members are used in marine construction, the use of conventional joining techniques result in significant angular and buckling distortion due to the inherent high heat input with these processes. Several low heat input alternatives, including laser beam, gas metal arc, and hybrid laser-arc welding are explored. The paper focuses on process development, real time distortion measurements and implementation of these processes.
Single-molecule protein folding: Diffusion fluorescence resonance energy transfer studies of the denaturation of chymotrypsin inhibitor 2 (2000)

We report single-molecule folding studies of a small, single-domain protein, chymotrypsin inhibitor 2 (CI2). CI2 is an excellent model system for protein folding studies and has been extensively studied, both experimentally (at the ensemble level) and theoretically. Conformationally assisted ligation methodology was used to synthesize the proteins and site-specifically label them with donor and acceptor dyes. Folded and denatured subpopulations were observed by fluorescence resonance energy transfer (FRET) measurements on freely diffusing single protein molecules. Properties of these subpopulations were directly monitored as a function of guanidinium chloride concentration. It is shown that new information about different aspects of the protein folding reaction can be extracted from such subpopulation properties. Shifts in the mean transfer efficiencies are discussed, FRET efficiency distributions are translated into potentials, and denaturation curves are directly plotted from the areas of the FRET peaks. Changes in stability caused by mutation also are measured by comparing pseudo wild-type CI2 with a destabilized mutant (K17G). Current limitations and future possibilities and prospects for single-pair FRET protein folding investigations are discussed.
Exploring how and why people use visualizations in casual contexts: Modeling user goals and regulated motivations (2012)

We present an artifact study that explores how people examine visual representations of data in non-work contexts, resulting in a proposed Promoter–Inhibitor Motivation Model of visualization use in casual contexts. We propose that user goals direct visualization use tasks, but the strength of user motivation is modified by promoting and inhibiting factors. Based on the duration and frequency of use for reported artifacts, we hypothesize that artifact use patterns depend on how promoters and inhibitors change over time, and we propose a six-stage model of artifact use. We hypothesize that the differences in how these artifacts were used ultimately reveals how promoters and inhibitors can be manipulated to promote frequent and long-duration visualization use. This model provides a cognitive framework for visualization designers and suggests new research directions.
NSAIDs increase survival in the Sandhoff disease mouse: Synergy with N‐butyldeoxynojirimycin (2004)

The GM2 gangliosidoses are caused by incomplete catabolism of GM2 ganglioside in the lysosome, leading to progressive storage and a neurodegenerative clinical course. An inflammatory response (microglial activation, macrophage infiltration, oxidative damage) has been found to be a consequence of GM2 storage in the brain, although it remains unclear whether this contributes to pathogenesis or disease progression. In this study, we treated Sandhoff disease mice with nonsteroidal antiinflammatory drugs (indomethacin, aspirin, and ibuprofen) and antioxidants (L-ascorbic acid and alpha-tocopherol acetate). The treated mice lived significantly longer than untreated littermates (12-23%, p <0.0001) and showed a slower rate of disease progression (p <0.001). When aspirin treatment was combined with substrate reduction therapy, synergy resulted (11%, p <0.05) with a maximum improvement of 73% in survival (p <0.00001). This study demonstrates that inflammation contributes to disease progression and identifies antiinflammatory and antioxidant therapies as a potential adjunctive approach to slow the clinical course of this and related disorders.
36. Translation of an Adenovirus-Based Cocaine Vaccine dAd5GNE to a Clinical Trial (2016)

dAd5GNE, an anti-cocaine vaccine based on a disrupted serotype 5 adenovirus gene transfer vector covalently conjugated to the cocaine analog GNE, evokes high titers of high affinity anti-cocaine antibodies that prevent cocaine from reaching its cognate receptor in the CNS. dAd5GNE has been shown to be effective in preclinical efficacy studies in mice, rats and nonhuman primates. In order to translate dAd5GNE to the clinic, this study focused on optimizing the choice of adjuvant, timing of vaccination regimen and dose. Adjuvant. To evaluate vaccine formulation, the adjuvants Adjuplex and Alum were assessed at a fixed dose to identify the formulation that evoked the fastest and highest titer response. BALB/c mice vaccinated with dAd5GNE/Adjuplex demonstrated high serum anti-cocaine antibody titers (>5×105) after a single administration while animals vaccinated with dAd5GNE/Alum required multiple injections to achieve high titers, and mice vaccinated with dAd5GNE/PBS plateaued at a lower titer. Therefore, a formulation based on the Adjuplex adjuvant was chosen for the clinical protocol. Timing. The measurement of titer half-life in nonhuman primates following individual vaccinations at variable intervals was used to inform the timing between vaccine boosts. The anti-cocaine antibody titer half-life in 8 dAd5GNE/Adjuplex vaccinated nonhuman primates was assayed regularly over the course of 1 yr and the titer half-life was calculated following each administration. The average half-life for all animals was 4.0 ± 0.2 wk. Continued cocaine use did not impact the titer half-life. These results indicate that a 4 wk interval for vaccinations is necessary to maintain the high titer anti-cocaine antibody levels. Dose. We measured the dose response in mice to provide the baseline for a phase I/II clinical trial and identified the range of doses that bracket the anticipated minimum effective dose and maximum tolerated dose. Doses from 0.04-40 μg of the vaccine were evaluated in BALB/c for the capacity to evoke antibody titers and to minimize access of radiolabelled cocaine to the CNS. Doses at and above 4 µg produced high anti-cocaine antibody titers above the threshold for efficacy (>5×105) which substantially reduced cocaine levels in the brain (p<0.0001 vs PBS). Using a modified weight adjusted dose from these results, the vaccine doses to be evaluated in the clinical trial were determined to be 100 to 1000 µg. The results of these studies combine to provide the specifications for critical vaccine design parameters required to translate the anti-cocaine vaccine to evaluation in a clinical trial. Based on these specifications the FDA has allowed the Adjuplex-formulated dAd5GNE vaccine to proceed to clinical study with a monthly vaccination regimen in recovering cocaine addicts.