Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive analysis of neurobehavior associated with histomorphological alterations in a chronic constrictive nerve injury model through use of the CatWalk XT system.

OBJECT Neuropathic pain is debilitating, and when chronic, it significantly affects the patient physically, psychologically, and socially. The neurobehavior of animals used as a model for chronic constriction injury seems analogous to the neurobehavior of humans with neuropathic pain. However, no data depicting the severity of histomorphological alterations of the nervous system associated with graded changes in neurobehavior are available. To determine the severity of histomorphological alteration related to neurobehavior, the authors created a model of chronic constrictive injury of varying intensity in rats and used the CatWalk XT system to evaluate neurobehavior. METHODS A total of 60 Sprague-Dawley rats, weighing 250-300 g each, were randomly assigned to 1 of 5 groups that would receive sham surgery or 1, 2, 3, or 4 ligatures of 3-0 chromic gut loosely ligated around the left sciatic nerve. Neurobehavior was assessed by CatWalk XT, thermal hyperalgesia, and mechanic allodynia before injury and periodically after injury. The nerve tissue from skin to dorsal spinal cord was obtained for histomorphological analysis 1 week after injury, and brain evoked potentials were analyzed 4 weeks after injury. RESULTS Significant differences in expression of nerve growth factor existed in skin, and the differences were associated with the intensity of nerve injury. After injury, expression of cluster of differentiation 68 and tumor necrosis factor-α was increased, and expression of S100 protein in the middle of the injured nerve was decreased. Increased expression of synaptophysin in the dorsal root ganglion and dorsal spinal cord correlated with the intensity of injury. The amplitude of sensory evoked potential increased with greater severity of nerve damage. Mechanical allodynia and thermal hyperalgesia did not differ significantly among treatment groups at various time points. CatWalk XT gait analysis indicated significant differences for print areas, maximum contact maximum intensity, stand phase, swing phase, single stance, and regular index, with sham and/or intragroup comparisons. CONCLUSIONS Histomorphological and electrophysiological alterations were associated with severity of nerve damage. Subtle neurobehavioral differences were detected by the CatWalk XT system but not by mechanical allodynia or thermal hyperalgesia. Thus, the CatWalk XT system should be a useful tool for monitoring changes in neuropathic pain, especially subtle alterations.
Receptor status of tumor as prognostic factor in patients with bilateral breast cancer.

AIM To determine the receptor status of tumors as prognostic factor in development of bilateral breast cancer (BBC) and factor of prognosis of disease. PATIENTS AND METHODS 272 cases of BBC during the period from 1995 to 2011 in different oncological institutions of Ukraine have been analyzed. RESULTS Patients with metachronous BBC with positive status of hormone receptors (HR) of tumors have significantly better indices of overall and progression-free survival (three-years - 95%, five-years - 72%), than patients with HR-negative status (among them nobody has survived over 5 years). In patients with synchronous BBC, the receptor status of tumors has similar influence on the prognosis of survival. Nevertheless, indices of overall survival (65%) and progression-free survival (66%) in HR-positive patients were lower than that at metachronous BBC (overall survival and progression-free survival - 72%). CONCLUSIONS Synchronous breast cancer has more aggressive clinical course than metachronous one. It was determined significant influence of receptor status of tumors on the overall survival and progression-free survival in patients with BBC.
A Thermographic Study of Heat Generation During All Ceramic Preparation

Statement of problem: Saving pulp vitality is the great priority during all ceramic preparation.All ceramic preparation can cause pulpal lesionsif the temperature isn’t controlled.Purpose:The study was conducted to highlight two factors that may affect the heat generation during all ceramic preparation: 1Type of stone according to their abrasivenessgrit size (Fine , medium , Coarse). 2-Pattern of reduction (Continuous , Intermittent). Materials&Methods: Ninety freshly extracted sound,single rooted teeth was selected for this study and divided into two groups according to pattern of reduction (45 teeth for each group). Each group was subdivided into 3 subdivisions according to the type of stones used in the preparation. Copper-constantan thermocouple wire joined with digital thermometer used to measure the temperature rise in the pulp chamber at different places. Results: 1-The intermittent reduction produced lesser increase in tooth temperature and was statistical different than the increase of temperature of continuous reduction.2-The fine grit size stones produce the least temperature rise then the medium grit size stone then the coarse grit size.Conclusion: All ceramic preparation should be done as intermittent reduction using fine grit size rotary instruments with sufficient water coolant in the high-speed handpiece.
Low-density parity-check coding for impulse noise correction on power-line channels

This paper considers the design of near capacity-achieving error correcting codes for a discrete multi-tone system in the presence of both additive white Gaussian noise and impulse noise. Impulse noise is one of the main channel impairments in the power-line channel. One way to combat impulse noise is to detect the presence of the impulses and to declare an erasure when an impulse occurs. In this paper, we propose a coding system based on irregular low-density parity-check (LDPC) codes and bit-interleaved coded modulation. We show that by carefully choosing the degree distribution of the irregular LDPC code, both the additive noise and the erasures can be handled in a single code. We show that the proposed system can perform close to the capacity of the channel and for the same redundancy is significantly more immune to the impulse noise than the existing methods based on an outer Reed-Solomon code.
Plasticity of memory for new learning in very old age: a story of major loss?

Longitudinal survivors of the Berlin Aging Study (N = 96, mean age = 84 years, range 75-101 years) were instructed and trained in a mnemonic skill to examine plasticity of episodic memory performance in very old age. Performance gains after mnemonic instruction were modest, and most individuals were unable to further enhance their performance during 4 sessions of mnemonic practice. Whereas the proportion of variance explained by measures from the broad fluid-ability domain (e.g., perceptual speed) increased with training, the proportion of variance explained by crystallized-ability domain (e.g., word knowledge) and sociobiographical variables decreased. Furthermore, prior 6-year longitudinal changes (loss) in perceptual speed predicted individual differences in plasticity. Results suggest that aging-induced biological factors are a prominent source of individual differences in cognitive plasticity in very old age.
Ligand design, synthesis and biological anti-HCV evaluations for genotypes 1b and 4a of certain 4-(3- & 4-[3-(3,5-dibromo-4-hydroxyphenyl)-propylamino]phenyl) butyric acids and 3-(3,5-dibromo-4-hydroxyphenyl)-propylamino-acetamidobenzoic acid esters

4-(4-[N-1-carboxy-3-(3,5-dibromo-4-hydroxyphenyl)-3-oxo-propylamino]phenyl)-4-oxo-butyric acid (V), 4-(3- & 4-[N-1-carboxy-3-(3,5-dibromo-4-hydroxyphenyl)-3-oxo-propylaminophenyl]-2-aryl-4-oxo-butyric acids (Xa–e) and 4-(2-alkyl-2-[N-3-(3,5-dibromo-4-hydroxyphenyl)-1-carboxy-3-oxo-propylamino]acetamido) benzoate esters (XVa–e) were designed, synthesized and biologically evaluated as anti-HCV for genotypes 1b and 4a. The design was based on their docking scores with HCV NS3/4A protease-binding site of the genotype 1b (1W3C), which is conserved in the genotype 4a structure. The docking scores predicted that most of these molecules have higher affinity to the HCV NS3/4A enzyme more than Indoline lead. These compounds were synthesized and evaluated for their cytopathic inhibitory activity against RAW HCV cell cultures of genotype 4a and also examined against Huh 5–2 HCV cell culture of genotype 1b, utilizing Luciferase and MTS assays. Compounds Xa and Xb have 95 and 80% of the activity of Ribavirin against genotype 4a and compounds XVa, XVb and XVd exerted high percentage inhibitory activity against genotype 1b equal 87.7, 84.3 and 82.8%, respectively, with low EC50 doses.
New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme

To date, the crystal structures of at least 12 human CYPs (1A2, 2A6, 2A13, 2C8, 2C9, 2D6, 2E1, 2R1, 3A4, 7A1, 8A1, and 46A1) have been determined. CYP2D6 accounts for only a small percentage of all hepatic CYPs (< 2%), but it metabolises ~25% of clinically used drugs with significant polymorphisms. CYP2D6 also metabolizes procarcinogens and neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, and indolealkylamines. Moreover, the enzyme utilizes hydroxytryptamines and neurosteroids as endogenous substrates. Typical CYP2D6 substrates are usually lipophilic bases with an aromatic ring and a nitrogen atom, which can be protonated at physiological pH. Substrate binding is generally followed by oxidation (5–7 å) from the proposed nitrogen-Asp301 interaction. A number of homology models have been constructed to explore the structural features of CYP2D6, while antibody studies also provide useful structural information. Site-directed mutagenesis studies have demonstrated that Glu216, Asp301, Phe120, Phe481, and Phe483 play important roles in determining the binding of ligands to CYP2D6. The structure of human CYP2D6 has been recently determined and shows the characteristic CYP fold observed for other members of the CYP superfamily. The lengths and orientations of the individual secondary structural elements in the CYP2D6 structure are similar to those seen in other human CYP2 members, such as CYP2C9 and 2C8. The 2D6 structure has a well-defined active-site cavity located above the heme group with a volume of ~540 å3, which is larger than equivalent cavities in CYP2A6 (260 å3), 1A2 (375 å3), and 2E1 (190 å3), but smaller than those in CYP3A4 (1385 å3) and 2C8 (1438 å3). Further studies are required to delineate the molecular mechanisms involved in CYP2D6 ligand interactions and their implications for drug development and clinical practice.
Strength and endurance of elite soccer players.

PURPOSE The major purpose of the present study was to examine whether there exists a relationship between preseasonal physiological tests and performance results in the soccer league. Further, it investigated maximal oxygen uptake and maximal strength in proportion to body mass for soccer players. A secondary aim was to establish some normative data of Norwegian elite soccer players. METHODS Two teams from the Norwegian elite soccer league participated in the study. RESULTS/CONCLUSION The present study supports previous investigations indicating a positive relationship between maximal aerobic capacity, physical strength, and performance results in the elite soccer league. It is concluded that for soccer players, maximal oxygen uptake should be expressed in relation to body mass raised to the power of 0.75 and maximal strength in relation to body mass raised to the power of 0.67, when the aim is to evaluate maximal aerobic capacity when running and strength capacity among players with different body mass. Midfield players had significantly higher maximal oxygen uptake compared with defense players using the traditional expression, mL x kg(-1) x min(-1), while no significant differences were found expressing maximal oxygen uptake either absolutely (L x min[-1]) or in relation to body mass raised to the power of 0.75 (mL x kg[-0.75] x min[-1]) among players grouped by position. There was a significant correlation (r = 0.61, P < 0.01) between squat IRM and vertical jump height. Vertical jump heights for defense and forward players were significantly higher compared with midfield players. Mean results from the laboratory test were 63.7 mL x kg(-1) x min(-1) or 188.6 mL x kg[-0.75] x min(-1) for maximal oxygen uptake, 150 kg or 8.0 kg x mb(-0.67) for 90 degrees squats, 79.9 kg or 4.4 kg x mb(-0.67) for bench press. Mean values of vertical jump height were 54.9 cm.
ARCHAEA‐ExPRESs targeting of α‐tubulin 4 mRNA: a model for high‐specificity trans‐splicing

Effectiveness of trans‐splicing‐mediated mRNA reprogramming depends on specificity and efficiency. We have previously developed a new strategy (ARCHAEA‐ExPRESs) that uses a tRNA endonuclease derived from Archaea and its natural substrate, the bulge‐helix‐bulge (BHB) structure. ARCHAEA‐ExPRESs provides increased specificity in functional targeting. In fact, this system is based on a double check, the base pairing and the formation of a BHB structure between the target mRNA and the targeting RNA. In this study, we demonstrate the high specificity of ARCHAEA‐ExPRESs by tagging the endogenous α‐tubulin 4 via trans‐splicing. α‐Tubulin 4 belongs to a gene family sharing high degree of nucleotide sequence homology. The formation of a perfect BHB structure between targeting RNAs and the isotype α‐tubulin 4 enables selective trans‐splicing. Most important, ARCHAEA‐ExPRESs functionality is conserved in vivo following transient expression of archaeal tRNA endonuclease in mouse liver. Production of the recombinant protein is strictly dependent on the expression of the archaeal endonuclease, and the efficiency of the system depends on the relative amount of the target and targeting mRNAs. These data prove the effectiveness of ARCHAEA‐ExPRESs in an endogenous highly demanding context and disclose the possibility to utilize this system in a variety of technological or therapeutic applications. —Deidda, G. , Rossi, N. , Putti, S. , Tocchini‐Valentini, G. P. ARCHAEA‐ExPRESs targeting of α‐tubulin 4 mRNA: a model for high‐specificity trans‐splicing. FASEB J. 24, 2976–2984 (2010). www.fasebj. org
Background Document for “Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2017-18 Influenza Season” Introduction

This document contains background material relevant to “Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2017-18 Influenza Season” (MMWR Recomm Rep 2017;66[no.RR-2]:120). The CDC/ACIP recommendations for use of influenza vaccines in various populations for the 2017-18 season, discussion of vaccines expected to be available, contraindications and precautions to vaccination, and relevant figures and tables may be found in the above-referenced MMWR document.
NMDA and dopamine D2L receptor interaction in human neuroblastoma SH‐SY5Y cells involves tyrosine kinase and phosphatase

BLOCKADE of N-methyl-D-aspartate (NMDA) receptors by the specific antagonists dizocilpine and (±)-3-(2-car-boxypiperazin-4-yl)-propyl-1-phosphonic acid on human neuroblastoma SH-SY5Y cells expressing human D2L receptors resulted in a significant increase in the density of D2L receptors. In order to understand the mechanism of dopamine D2L receptor induction following NMDA receptor blockade we used specific protein tyrosine kinase and phosphatase inhibitors to demonstrate their involvement in this interaction. The induction of dopamine D2L receptor was measured by radioreceptor binding assay. The density of the dopamine D2L receptor was increased to 109% by the inhibition of protein tyrosine kinase and prevented by the inhibition of phosphatase 1 or 2A. Inactivation of NMDA receptors might effect the phosphorylation-dephosphorylation states of the regulatory proteins and lead to the induction of the D2L receptor gene.
Mucin core proteins as differentiation markers in the gastrointestinal tract

The cloning and sequencing of epithelial mucin genes has converted the visually attractive art of mucin histochemistry into a precise scientific instrument for exploring the biological mechanisms underlying disorders of growth and differentiation. The sequence of nucleotides arranged in tandem repeats is specific to each mucin type. Serine and threonine are well represented within the variable nucleotide tandem repeat (VNTR) subdomains; these amino acids provide sites for O-glycosylation. The orchestration of enzymes required for post-translational modification (synthesis and assembly of carbohydrate chains) is complex and frequently fails to provide the diagnostic or experimental pathologist with specific probes for studying cellular differentiation. By contrast, the protein backbone shows a relatively restricted pattern of expression in tissues. `Second generation' monoclonal antibodies raised against synthetic peptide sequences obtained from the VNTR will detect specific MUC proteins in the course of their synthesis within rough endoplasmic reticulum. Antibodies will generally fail to react following posttranslational modification (without prior digestion) unless the selected synthetic peptide is from the relatively non-glycosylated C-terminal region or from the cytoplasmic tail in the case of transmembrane glycoproteins. The possibility that decreased, increased or inappropriate expression (in a neoplasm, say) may reflect defective glycosylation can be excluded by mRNA in-situ hybridization or Northern blotting. However, the expression patterns of several mucin genes in the normal gastrointestinal tract are now known and aberrant expression as shown by immunohistochemistry provides a useful guide to altered lineage differentiation. Nature of mucin core proteins in the gastrointestinal tract
Isolation of a novel iris-specific and leucine-rich repeat protein (oculoglycan) using differential selection.

PURPOSE To identify and characterize genes expressed in the iris. METHODS A human adult iris cDNA library was constructed and subjected to a differential selection screen to identify genes preferentially expressed in iris or trabecular tissue versus those expressed in lymphoblasts. Selected cDNAs were partially sequenced. Novel cDNAs were chosen for further analysis. The cDNAs were localized within chromosomes using a radiation hybrid (RH) mapping panel. The tissue expression profile of each cDNA was found through computer-based searches. One novel cDNA was subjected to 5' rapid amplification of cDNA ends and Northern blot analysis. RESULTS Of 24 differentially selected clones, 14 cDNAs had homology to known genes, whereas the other 10 were previously uncharacterized cDNA clones. IR185 was one novel iris cDNA identified. Northern blot analysis with IR185 indicated that it is expressed in human fetal liver as a 2.7-kb transcript and in adult iris as a 1.6-kb transcript. Computer-based searches of public databases and reverse transcription-polymerase chain reaction experiments have determined that IR185 is also expressed in retina. RH mapping experiments have localized IR185 to the chromosomal interval 1q31-q32, near the loci for age-related degeneration (1q25-q31) and retinitis pigmentosa 12 (1q31-q32), and IR185 is in the region for posterior column ataxia with retinitis pigmentosa (1q31-q32). It has a 996-bp open reading frame encoding a putative protein with homology to the small leucine-rich proteoglycan (SLRP) family. The IR185 gene has been tentatively named oculoglycan. CONCLUSIONS Differential selection is a technique that has been useful in identifying genes specific to a variety of tissues. This is the first time this technique has been applied to the iris. Characterizing genes highly or uniquely expressed in the iris can assist in clarifying our understanding of iris function and lead to a better understanding of the molecular pathogenesis of ocular disease. IR185 is a tentative candidate for one eye disorder genetically localized to chromosome 1q31-q32.
Pre‐Transplant Inosine Monophosphate Dehydrogenase Activity is Associated with Clinical Outcome After Renal Transplantation

Mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase (IMPDH) activity, is usually administered as a standard dose of 1 g b.i. d. after renal transplantation. Because MMF dose reductions are associated with inferior outcome, we investigated pre‐transplant IMPDH activity, MMF dose reductions and outcome. IMPDH activity was determined in isolated peripheral mononuclear cells immediately prior to renal transplantation. We observed considerable inter‐individual variability in pre‐transplant IMPDH activity (9.35 ± 4.22 nmol/mg/h). Thirty of 48 patients (62.5%) with standard MMF dose (1 g b.i.d.) had dose reductions within 3 years post‐transplant; these patients also had significantly lower IMPDH activity. The area under the receiver‐operating characteristics curve (AUC‐ROC) for prediction of dose reduction within 6 months post‐transplant was 0.75 (95% CI, 0.61–0.89; p < 0.004). IMPDH activity above the cut‐off value, MMF dose reduction and age of recipient were significant contributors for the occurrence of acute rejection in the multivariate logistic regression. Patients with high IMPDH activity and MMF dose reduction had the highest rejection rate (81.8% vs. 36.4%; p < 0.01). Conclusion: Patients with low IMPDH activity experienced more complications of MMF therapy. High pre‐transplant IMPDH activity and MMF dose reductions were associated with rejection. Determination of IMPDH activity prior to transplantation may help to improve MMF therapy after renal transplantation.
Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients.

CONTEXT Adrenocortical carcinomas (ACC) are rare tumors with a poor prognosis. Few reports concerning large and homogeneous series are available. OBJECTIVE We aimed to determine the clinical characteristics and outcome of ACC and to identify prognostic factors. DESIGN AND SETTING This study is a descriptive and multivariate analysis of a cohort from a single endocrinology center. PATIENTS A total of 202 consecutive patients with ACC were studied. RESULTS The sex ratio (female to male) was 2.7. Mean age at diagnosis was 44 +/- 16 yr (range, 11-88 yr). We found that 154 patients (76%) had hypersecreting tumors [mostly cortisol and androgens (47%), cortisol alone (27%), or androgens alone (6%)] and 43 patients (21%) had metastases at diagnosis. At initial staging or during follow-up, 85 patients (42%) had liver metastases, 79 patients (39%) had lung metastases, and 20 patients had bone metastases (10%). The survival rate was 37% at 5 yr. Multivariate analysis identified the following independent prognostic factors associated with shorter survival: older age at diagnosis [hazard ratio (HR), 1.03; P < 0.0001], initial MacFarlane extension stages 3 (HR, 4.42; P = 0.005) and 4 (HR, 7.93; P < 0.0001), and cortisol hypersecretion (HR, 3.90; P < 0.0001). Treatment with 1,1-dichlorodiphenildichloroethane (o,p'DDD) in the 3 months after surgery increased the survival rate of patients with cortisol-secreting tumors (HR, 0.40; P = 0.04). CONCLUSION This study highlights the better prognosis of ACC diagnosed at a noninvasive local stage, the particularly poor prognosis of patients with cortisol-secreting tumors, and the beneficial effect of o,p'DDD therapy in this subgroup of patients.