Miracle-dz/UniFAR-FTUs huggingface dataset:
-Antitrypsin: A Marker of Intestinal Versus Systemic Inflammation in Pediatric Crohn’ s Disease?

Growth failure and malnutrition are major concerns in pediatric patients with frequent relapses of Crohn’s disease (CD). In search of an early, noninvasive marker of relapse, we prospectively examined the relationship between levels of fecal al-antitrypsin (ctl-AT) in comparison with other known inflammatory parameters and disease activity using a pediatric CD Activity Index (P-CDAI), as well as in relation to growth. Forty-two pediatric patients (29 M, 13 F, 7-16 years old, mean 12.8 years) with ileal or ileocolonic CD were prospectively examined at 4 monthly intervals over a 1 year period. Medmn (interquartile range) fecal ctl-AT values did not differ between children in clinical relapse (P-CDAI > 150, n = 10) compared with CD patients (n = 42) with quiescent disease [1.84 (3.67) mg/g versus 1.55 (3.97) mg/g, respectively, p = ns]. However, children with growth failure (n = 14) had a significantly higher fecal aI-AT [ 3.63 (5.65) mg/g] despite clinical remission [median P-CDAI 22 (72.5)] compared with those with normal growth [1.41 (1.66) mg/g, p = 0.021. Very high fecal a l -AT levels (A mg/g) were not associated with clinically active disease [median P-CDAT 23 (71 .5)]. Overall however, levels in CD were significantly higher than that of 17 pediatric control patients with diarrheal disorders unrelated to IBD [0.98 (1.21 ), p < 0.051. Fecal a l -AT seems therefore not to be a reliable marker of clinically evident disease activity, but was best correlated with chronic malnutrition and subclinical disease activity.
Prognostic factors of return to work after traumatic or non-traumatic acquired brain injury

Abstract Purpose: To investigate and to determine evidence of prognostic factors for return to work (RTW) after acquired brain injury (ABI). Method: A systematic literature search was conducted in PubMed (2008–2014), applying terms for ABI and RTW. In addition, studies published after 2003 of a previous review on the same topic were added. The methodological quality of the included studies was assessed and evidence was classified. Results: Twenty-seven studies were included. There is strong evidence that a high education level is positively associated with RTW after traumatic ABI; a low education level, unemployment and length of stay in rehabilitation are negatively associated, and a clear tendency has been deduced from the studies that conscious state in the Emergency Department is not associated with RTW. After non-traumatic ABI, there is strong evidence that independence in activities of daily living is positively associated with RTW and aetiology of stroke is not. Conclusions: This study confirms earlier findings that after both traumatic and non-traumatic ABI injury related factors in the Emergency Department are not associated with RTW. In addition, it provides further evidence that personal factors after traumatic ABI and activity-related factors after non-traumatic ABI are strongly associated with RTW. Implications for Rehabilitation We found strong evidence for a significant association between RTW and personal factors (education level, unemployment) after traumatic ABI, and activities of daily living (ADL) after non-traumatic ABI. We advise to focus on work-related activities during the RTW process besides ADL-training and pay attention to and support patients at risk for not returning to work.
Neuropsychological Profile of Children With Neurofibromatosis, Brain Tamor, or Both

Neurofibromatosis type 1, a common autosomal dominant genetic disorder, is associated with numerous physical and medical anomalies as well as an increased incidence of learning disability. Tumors of the central nervous system have been estimated to occur in 15%, but their contribution to neuropsychological status is unknown. This study examines the relative contribution of neurofibromatosis and brain tumor to the cognitive profile of children with neurofibromatosis. A comprehensive battery of neuropsychological and behavioral tests was administered to a group of 65 children with neurofibromatosis type 1. Fourteen were then matched on demographic variables with two other groups of children who had either a brain tumor in addition to neurofibromatosis or a brain tumor alone. The two brain tumor groups were also matched on tumor type, location, and therapy. Mean scores of the neurofibromatosis-brain tumor group were generally the lowest of the three groups; those of the brain tumor group were highest, and performance of the neurofibromatosis group was generally between the other two groups. These results suggest that neurofibromatosis is, by itself, associated with significant cognitive morbidity, but that the severity of the problems is increased somewhat if a brain tumor is also present. (J Child Neurol 1994;9:368-377).
Comparison of Amino Acid Positron Emission Tomographic Radiotracers for Molecular Imaging of Primary and Metastatic Brain Tumors

Positron emission tomography (PET) is an imaging technology that can detect and characterize tumors based on their molecular and biochemical properties, such as altered glucose, nucleoside, or amino acid metabolism. PET plays a significant role in the diagnosis, prognostication, and treatment of various cancers, including brain tumors. In this article, we compare uptake mechanisms and the clinical performance of the amino acid PET radiotracers (L-[methyl-11C]methionine [MET], 18F-fluoroethyl-tyrosine [FET], 18F-fluoro-L- dihydroxy-phenylalanine [FDOPA], and 11C-alpha-methyl-L-tryptophan [AMT]) most commonly used for brain tumor imaging. First, we discuss and compare the mechanisms of tumoral transport and accumulation, the basis of differential performance of these radioligands in clinical studies. Then we summarize studies that provided direct comparisons among these amino acid tracers and to clinically used 2-deoxy-2[18F]fluoro-D-glucose [FDG] PET imaging. We also discuss how tracer kinetic analysis can enhance the clinical information obtained from amino acid PET images. We discuss both similarities and differences in potential clinical value for each radioligand. This comparative review can guide which radiotracer to favor in future clinical trials aimed at defining the role of these molecular imaging modalities in the clinical management of brain tumor patients.
Surgical treatment for secondary dystonia

Surgical therapy for the secondary dystonias is generally perceived to be less effective than for primary disease. However, a number of case reports and small open series have recently appeared describing quite favorable outcomes following surgery for some nonprimary dystonias. We discuss surgical treatment options for this group of diverse conditions, including tardive dystonia, dystonic cerebral palsy, and certain heredodegenerative diseases in which deep brain stimulation and ablative lesions of the posteroventral pallidum have been shown to be effective. Other types of secondary dystonia respond less well to pallidal surgery, particularly when anatomical lesions of the basal ganglia are prominent on preoperative imaging. For these conditions, central baclofen delivery and botulinum toxin denervation may be considered. With optimal medical and surgical care, some patients with secondary dystonia have achieved reductions in disability and pain that approach those documented for primary dystonia. © 2012 Movement Disorder Society
In vivo activation of CFTR-dependent chloride transport in murine airway epithelium by CNP

Kelley, Thomas J., Calvin U. Cotton, and Mitchell L. Drumm. In vivo activation of CFTR-dependent chloride transport in murine airway epithelium by CNP. Am. J. Physiol. 273 (Lung Cell. Mol. Physiol. 17): L1065–L1072, 1997. —Inhibitors of guanosine 38,58-cyclic monophosphate (cGMP)-inhibited phosphodiesterases stimulate Cl2 transport across the nasal epithelia of cystic fibrosis mice carrying the DF508 mutation [cystic fibrosis transmembrane conductance regulator (CFTR) (DF/DF)], suggesting a role for cGMP in regulation of epithelial ion transport. Here we show that activation of membrane-bound guanylate cyclases by C-type natriuretic peptide (CNP) stimulates hyperpolarization of nasal epithelium in both wild-type and DF508 CFTR mice in vivo but not in nasal epithelium of mice lacking CFTR [CFTR(2/2)]. With the use of a nasal transepithelial potential difference (TEPD) assay, CNP was found to hyperpolarize lumen negative TEPD by 6.1 6 0.6 mV in mice carrying wild-type CFTR. This value is consistent with that obtained with 8-bromoguanosine 38,58-cyclic monophosphate (6.2 6 0.9 mV). A combination of the adenylate cyclase agonist forskolin and CNP demonstrated a synergistic ability to induce Cl2 secretion across the nasal epithelium of CFTR(DF/DF) mice. No effect on TEPD was seen with this combination when used on CFTR(2/2) mice, implying that the CNP-induced change in TEPD in CFTR(DF/DF) mice is CFTR dependent.
The fiber-optic evanescent wave fluorescence sensor with a novel sensing architecture for determining penicillin G

In this paper, we describe a specific fiber-optic evanescent wave (EW) fluorescence sensor with a naturally built-in high signal to noise ratio, including a novel sensing architecture. It includes two identical, low hydroxyl content, large core, multimode plastic-clad silica fibers that are positioned side to side, with a fiber for delivering incident exciting light and the other for receiving fluorescent light. By optimizing inclination of the incident fiber end-face, incident light illuminates perpendicularly receiving fiber after end-face reflection to excite fluorescent molecular in surrounding aqueous solution, and excited fluorescence couples into receiving fiber as the form of EW. Through increasing receiving fiber end-face's roughness, the total internal reflection of massive low-loss tunneling modes occurs on the end-face, providing a high signal to noise ratio without some filters in existence. Finally, by means of the fluorescence quenching analysis, we investigated the content determination of penicillin G on the fiber-optic evanescent wave sensing platform, and obtained corresponding standard working curve.
Models of synchronized hippocampal bursts in the presence of inhibition. I. Single population events.

1. We constructed model networks with 520 or 1,020 cells intended to represent the CA3 region of the hippocampus. Model neurons were simulated in enough detail to reproduce intrinsic bursting and the electrotonic flow of currents along dendritic cables. Neurons exerted either excitatory or inhibitory postsynaptic actions on other cells. The network models were simulated with different levels of excitatory and inhibitory synaptic strengths in order to study epileptic and other interesting collective behaviors in the system. 2. Excitatory synapses between neurons in the network were powerful enough so that burst firing in a presynaptic neuron would evoke bursting in its connected cells. Since orthodromic or antidromic stimulation evokes both a fast and a slow phase of inhibition, two types of inhibitory cells were simulated. The properties of these inhibitory cells were modeled to resemble those of two types of inhibitory cells characterized by dual intracellular recordings in the slice preparation. 3. With fast inhibition totally blocked, a stimulus to a single cell lead to a synchronized population burst. Thus the principles of our epileptic synchronization model, developed earlier, apply even when slow inhibitory postsynaptic potentials (IPSPs) are present, as apparently occurs in the epileptic hippocampal slice. The model performs in this way because bursting can propagate through several generations in the network before slow inhibition builds up enough to block burst propagation. This can occur, however, only if connectivity is sufficiently large. With very low connection densities, slow IPSPs will prevent the development of full synchronization. 4. We performed multiple simulations in which the fast inhibitory conductance strength was kept fixed at various levels while the strength of the excitatory synapses was varied. In each simulation, we stimulated either one or four cells. For each level of inhibition, the peak number of cells bursting depended sensitively on excitatory synaptic strength, showing a sudden increase as this strength reached a critical level. The critical excitation, which depended on the level of inhibition, corresponded to the level at which bursting can propagate from cell to cell at the particular level of inhibition. 5. We performed an analogous series of simulations in which the strength of excitatory synapses was held constant while the strength of fast inhibitory synapses was varied, stimulating a single neuron in each case. These simulations correspond to experiments that have been done in the hippocampal slice as low doses of picrotoxin are washed into a slice, gradually abolishing fast inhibition. (ABSTRACT TRUNCATED AT 400 WORDS)
Mechanism of Inhibition of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase by d4TTP: an Equivalent Incorporation Efficiency Relative to the Natural Substrate dTTP

ABSTRACT Among the clinically used nucleoside analogue inhibitors that target human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), there is little detailed mechanistic information on the interactions of 2′,3′-didehydro-2′,3′-dideoxythymidine-5′-triphosphate (d4TTP) with the enzyme · primer-template complex and how these interactions compare with those of the natural substrate, dTTP. Using a pre-steady-state kinetic analysis, we found that d4TTP was incorporated by HIV-1 RT just as efficiently as dTTP during both DNA- and RNA-dependent DNA synthesis. To our knowledge, these results represent the first observation of a 3′-modified nucleoside triphosphate analogue that has an incorporation efficiency comparable to that observed for the natural substrate during DNA synthesis by HIV-1 RT. This information provides a mechanistic basis for understanding the inhibition of HIV-1 RT by d4TTP as well as insight into the clinically observed lack of d4T resistance mutations in HIV-1 RT isolated from AIDS patients.
A molecular approach to comparative phylogeography of extant Malagasy lemurs

The lemurs of Madagascar provide an excellent model for exploring evolutionary diversification. This study investigates genetic divergence among most extant lemur taxa in relation to potential geographical boundaries to gene flow. For this purpose, ≈2,400 bp of mitochondrial DNA (part of the COIII gene; ND3, ND4L, and ND4 genes; and five tRNAs) were sequenced in a total of 131 lemurs from 5 families, 12 genera, 25 species, and 18 subspecies to reconstruct phylogenetic relationships among them. The comprehensive range of taxa makes this a particularly suitable molecular data set to examine lemur evolution. Those data clearly reveal that the Betsiboka River acts as an isolating barrier between populations of lemurs in north-western Madagascar. The Tsiribihina River similarly serves as a barrier to gene flow between northern and southern populations of lemurs in central western Madagascar, whereas the Mahavavy River does not seem to lead to genetic isolation of lemur populations. Several discrepancies among molecular data, current taxonomy, and geographic distribution along the western coast emerged. Examination of geographical distribution of the taxa concerned in comparison with distribution boundaries of other lemur taxa in that region yielded explanations for these inconsistencies. Eulemur fulvus and Eulemur mongoz are the only lemur taxa that also occur outside Madagascar, on the Comoro Islands. Genetic data show no significant differentiation between Malagasy and Comorian populations of these species, supporting the interpretation that both were introduced only recently to the Comoro Islands.
Respiratory outcomes, utilization and costs 12 months following a respiratory syncytial virus diagnosis among commercially insured late-preterm infants

Abstract Objectives: To determine, among a commercially-insured population of late-preterm infants, utilization of healthcare resources and costs during the 1 year following a diagnosis of respiratory syncytial virus lower respiratory infection (RSV LRI). Methods: Administrative claims for non-capitated, commercially-insured infants <1 year old were used to identify infants diagnosed with RSV LRI and unspecified bronchiolitis/pneumonia (UBP). Infants were stratified by the setting of diagnosis. Infants without evidence of RSV LRI or UBP were selected as a comparison group. Economic and clinical outcomes were analyzed descriptively using propensity score weighting and logged ordinary least squares models were used to examine the relationship between RSV and costs (adjusted to 2006 USD) incurred within 1 year of RSV LRI. Results: The majority of infants were 3 months or older at the time of RSV LRI or UBP diagnosis. The rate of wheezing was significantly greater for infants in the RSV LRI and UBP cohorts relative to the comparison group (p < 0.001). Infantile asthma rates were 6–9 times higher among RSV LRI and UBP infants than the comparison group. RSV LRI and UBP infants also had significantly more emergency department visits and outpatient visits than the comparison group. The marginal healthcare costs were significantly higher for RSV LRI inpatients ($24 027) and outpatients ($2703) infants than for the comparison group (all p < 0.001). Conclusion: Commercially insured late-preterm infants with RSV infection are at high risk for recurrent wheezing and infantile asthma during the 1-year period after the initial episode and impose a significant economic burden to the healthcare system.
Fine Mapping and Physical Characterization of Two Linked Quantitative Trait Loci Affecting Milk Fat Yield in Dairy Cattle on BTA26

Previously, a highly significant QTL affecting fat yield and protein yield and mapped to the bovine BTA26 chromosome has been reported to segregate in the French Holstein cattle population. To confirm and refine the location of this QTL, the original detection experiment was extended by adding 12 new families and genotyping 25 additional microsatellite markers (including 11 newly developed markers). Data were then analyzed by an approach combining both linkage and linkage disequilibrium information, making it possible to identify two linked QTL separated by 20 cM corresponding to ∼29 Mb. The presence of a QTL affecting protein yield was confirmed but its position was found to be more telomeric than the two QTLunderlying fat yield. Each identified QTL affecting milk fat yield was physically mapped within a segment estimated to be <500 kb. Two strong functional candidate genes involved, respectively, in fatty acid metabolism and membrane permeability were found to be localized within this segment while other functional candidate genes were discarded. A haplotype comprising the favorable allele at each QTL position appears to be overrepresented in the artificial insemination bull population.
Histologic Distribution of Hepatitis A, B, C, D, E, and G With Concomitant Cytokine Response in Liver Tissue

The purpose of this study was to determine the frequency of infection by hepatitis A, B, C, D, E, and G in liver biopsy specimens from symptomatic patients and to correlate viral localization with the expression of interferon, interleukin 4, and tumor necrosis factor messenger RNA. Tissue biopsy specimens were taken from 78 patients as follows: 14 patients with transplants, 23 patients with cirrhotic livers, and 41 patients with chronic hepatitis. At least one of the hepatitis viruses was detected in 60 of 78 (77%) specimens; multiple infection was evident in 18 of 78 (23%) specimens. The overall incidence of the different viruses was as follows: 8% hepatitis A, 3% hepatitis B, 52% hepatitis C, 1% hepatitis D, 24% hepatitis E, 18% hepatitis G. Throughout each category, hepatitis C was the most common virus detected. No histologic variable correlated with either the percentage of infected hepatocytes per lobule or nodule or with the specific viral type. The cytokines localized to monocytes or lymphocytes adjacent to infected hepatocytes. These results demonstrate that viral infection is present in most biopsy specimens of patients with chronic hepatitis and liver transplants and that hepatitis C. E, and G account for most of the infections. The results also suggest that direct viral infection in conjunction with expression of different cytokines is important in the pathophysiology of viral-induced liver disease.
Monoclonal anti-CEA Antibody: Factors Affecting Localization in a Preclinical Study

131I-labelled anti-CEA monoclonal antibody was tested in an animal model to evaluate: influence of antibody type (whole versus F(ab’)2 fragments), administration route (i.v. versus i.p.), dose of tracer (100 μCi versus 1000 μCi), growth site (s.c. versus i.p.) and size of tumor. Athymic mice bearing CEA-producing human colon carcinoma (HT-29) or human melanoma as an irrelevant tumor (MeWo) received tracer and immunoscintigraphy and the localization ratios (LR) were compared. In HT-29 bearing animals F(ab’)2 fragments localized better than the whole antibody. The LR were higher after i.p. administration of the tracer, independently of the tumor characteristics or the injected dose. The highest values were achieved when the radioactivity remaining in the whole body was below 2% of the injected dose. The images were negative when the i.p. injected dose was low or tumor growth was i.p. but positive in the other conditions (i.v. administration, high tracer dose, s.c. tumor growth). In the animals bearing melanoma, images scored positive or negative when the tumor weight was respectively above or below 400 mg, but the LR were always low.
Structure‐based classification of FAD binding sites: A comparative study of structural alignment tools

A total of six different structural alignment tools (TM‐Align, TriangleMatch, CLICK, ProBis, SiteEngine and GA‐SI) were assessed for their ability to perform two particular tasks: (i) discriminating FAD (flavin adenine dinucleotide) from non‐FAD binding sites, and (ii) performing an all‐to‐all comparison on a set of 883 FAD binding sites for the purpose of classifying them. For the first task, the consistency of each alignment method was evaluated, showing that every method is able to distinguish FAD and non‐FAD binding sites with a high Matthews correlation coefficient. Additionally, GA‐SI was found to provide alignments different from those of the other approaches. The results obtained for the second task revealed more significant differences among alignment methods, as reflected in the poor correlation of their results and highlighted clearly by the independent evaluation of the structural superimpositions generated by each method. The classification itself was performed using the combined results of all methods, using the best result found for each comparison of binding sites. A number of different clustering methods (Single‐linkage, UPGMA, Complete‐linkage, SPICKER and k‐Means clustering) were also used. The groups of similar binding sites (proteins) or clusters generated by the best performing method were further analyzed in terms of local sequence identity, local structural similarity and conservation of analogous contacts with the FAD ligands. Each of the clusters was characterized by a unique set of structural features or patterns, demonstrating that the groups generated truly reflect the structural diversity of FAD binding sites. Proteins 2016; 84:1728–1747. © 2016 Wiley Periodicals, Inc.