Miracle-dz/UniFAR-FTUs huggingface dataset:
N epsilon-(carboxymethyl)lysine in blood from maintenance hemodialysis patients may contribute to dialysis-related amyloidosis.

BACKGROUND Recent studies demonstrated not only that advanced glycation end product could be found in amyloid tissue from patient with dialysis related amyloidosis, but also that amyloid beta2-microglobulin was modified with N(epsilon)-(carboxymethyl)lysine (CML). We wanted to determine if CML could be a biomarker in these patients. METHODS To raise polyclonal anti-carboxymethyllysine antibody, human serum albumin was carboxymethylated by glyoxylic acid and was immunized to rabbits as antigen. Carboxymethyllysine-hemoglobin (CML-Hb) levels were measured by the dot blotting method using this antibody. RESULTS The levels of CML-Hb were 6.68 +/- 3.10 nmol CML/mg Hb in nondiabetic hemodialysis patients (N = 70), 6.39 +/- 3.43 nmol CML/mg Hb in diabetic hemodialysis patient (N = 21), and 3.13 +/- 0.88 nmol CML/mg Hb in 47 healthy volunteers. For clinical signs of dialysis-related amyloidosis, 70 nondiabetic hemodialysis patients were scored according Gejyo's criteria. The CML-Hb levels in patients with a high amyloid score as well as a low amyloid score were significantly higher than in patients with negative amyloid score (8.89 +/- 3.53 nmol CMLmg Hb, 7.28 +/- 2.32 nmol CML/mg Hb vs. 5.11 +/- 2.09 nmol CML/mg Hb, P < 0.001, P < 0.05). Furthermore, the CML-Hb levels correlated significantly with serum values of the methylguanidine over creatinine ratio and hyaluronate. CONCLUSIONS We suggest that CML-Hb is increased in blood from patients on maintenance hemodialysis and is thus a potential biomarker of oxidative damage in these patients. Moreover, CML-modification of protein may play a pathogenic role in the development of dialysis related amyloidosis.
Erythropoietin Markedly Attenuates Brain Infarct Size and Improves Neurological Function in the Rat

Background The impact of epoetin beta (recombinant human erythropoietin) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) induced by distal left internal carotid artery occlusion was investigated. Methods Adult male Sprague-Dawley rats (n = 30) were categorized into group 2 (IS only) and group 3 (IS plus intraperitoneal erythropoietin 5000 IU/kg at 0, 12, and 24 hours after IS). Healthy Sprague-Dawley rats (n = 10) served as group 1. Results Analysis of brain tissues showed larger BIA in group 2 than in group 3 (P < 0.001). Corner test identified highest frequency of left turn in group 2 (P < 0.05). The mRNA expressions of Bax, caspase 3, interleukin 18, toll-like receptor 4, and plasminogen activator inhibitor 1 were highest, whereas Bcl-2 was lowest in group 2 (P < 0.05). Lower CXCR4 and stromal cell-derived factor 1 expressions were noted in group 2 than in group 3 (P < 0.01). Immunohistofluorescence staining showed lower expressions of CXCR4, stromal cell-derived factor 1, von Willebrand factor, and doublecortin with higher number of apoptotic nuclei in group 2 than in group 3 (P < 0.001). Immunohistochemical staining demonstrated lower cellular proliferation and number of small vessels with higher glial fibrillary acid protein expression in group 2 than in group 3 (P < 0.01). Conclusions Erythropoietin significantly limited BIA and improved sensorimotor dysfunction after acute IS.
Neuroprotective effect of nipradilol on axotomized rat retinal ganglion cells

Purpose. To determine whether nipradilol, a new antiglaucoma drug, can protect retinal ganglion cells (RGCs) from secondary cell death caused by transection of the optic nerve (ON). Methods. The ON was transected 0.7mm from its exit from the eye in Sprague Dawley rats. Nipradilol (1 × 10 -8 – 10 -3 M), timolol, prazosin, or sodium nitroprusside (SNP)(1 × 10 -6 - 10 -4 M) was injected intravitreally fifteen-minutes before the ON transection. Control eyes received the same amount of phosphate buffered (PB). The RGCs were labeled retrogradely by placing gelfoam soaked in fluoro-gold (FG) on the stump of ON. RGCs density was determined by counting the FG-labeled RGCs in flat-mounted retinas 3 to 14 days post-transection. To determine whether the neuroprotective action of nipradilol was due to its NO-donor property, carboxy-PTIO, a NO-scavenger, or KT5832, a protein kinase G inhibitor, was injected with the nipradilol. Results. After ON transection, the number of surviving RGCs after intravitreal injection of 1 × 10 -4 M nipradilol was significantly higher than that following PB injection. This protective activity was dose-dependent. Neither timolol nor prazosin had a neuroprotective effect but SNP protected RGCs in a dose-dependent manner. Carboxy-PTIO and KT5832 decreased the neuroprotective effect of nipradilol. Conclusions. These results indicate that nipradilol has a possibility of neuroprotective effect on axotomized RGCs, and the effect depended mainly on its NO-donor property.
Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

CD4+ T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3+ regulatory T cell fates, the role of the T-bet–related transcription factor eomesodermin (Eomes) in CD4+ T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4+ T lymphocytes. We find that Eomes is readily expressed in activated CD4+ Th1 T cells in vivo. Eomes+ CD4+ T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4+ T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3+ cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4+ T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4+ T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4+ T cells. This enhanced capacity of Eomes-deficient CD4+ T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3+ cells. Our data identify a novel role for Eomes in CD4+ T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis.
Immunological evaluation of CTL precursor‐oriented vaccines for advanced lung cancer patients

Recent clinical trials of peptide vaccine for cancer patients have rarely resulted in tumor regression. One of the reasons for this failure could be an insufficient induction of anti‐tumor responses in these regimens, in which peptide‐specific memory cytotoxic T lymphocytes (CTLs) were not measured prior to vaccination. We investigated in this study whether pre‐vaccination measurement of peptide‐specific CTLs can provide any advantages in lung cancer patients receiving peptide vaccination with regard to safety and immunological responses. Ten patients with advanced lung cancer received vaccination with peptides under a regimen of CTL precursor‐oriented vaccination, in which pre‐vaccination peripheral blood mononuclear cells (PBMCs) were at first screened for reactivity in vitro to each of 14 peptides, followed by in vivo administration of only the reactive peptides. Profiles of the vaccinated peptides varied markedly among the 10 patients. This regimen was generally well‐tolerated, although local skin reactions, diarrhea, and colitis were observed in 8, 2, and 1 patient, respectively. Increased CTL responses against the immunized peptides and tumor cells were observed in the post‐vaccination PBMCs from 4 of 8 and 3 of 10 patients tested, respectively. Peptide‐specific IgG became detectable in post‐vaccination sera in 4 of 10 patients tested, and these 4 patients had a long progression‐free survival. Furthermore, the median survival time of 9 patients with non‐small cell lung cancer was 668.0±164.2 days. These results encourage further development of CTL precursor‐oriented peptide vaccination for lung cancer patients.
Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers

Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette‐related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing: (i) would be more active during exposure to cigarette‐related than neutral pictures; and (ii) would be less active to pleasant compared with cigarette‐related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole‐brain blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette‐related pictures. Whole‐brain analyses showed significantly larger BOLD responses during presentation of cigarette‐related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette‐related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette‐related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette‐related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli.
Dietary Cholesterol Enhances Pulmonary Eosinophilic Inflammation in a Murine Model of Asthma

Background: Epidemiological studies have suggested that the dietary pattern may be associated with the prevalence of asthma. We previously reported that an increased intake of foods of animal origin was associated with the occurrence of allergic rhinitis and asthma in adolescents. Here we examined the effect of dietary cholesterol in a murine model of allergic pulmonary inflammation. Methods: Weanling C57BL/6 mice were fed a control diet containing 0.02% cholesterol or a diet supplemented with 1% or 2% cholesterol. Four weeks later the mice were sensitized with intraperitoneal ovalbumin (OVA) followed by OVA or saline inhalation 2 weeks later. OVA aerosol-induced inflammation was significantly enhanced by dietary supplementation of 1% or 2% cholesterol. Results: Among OVA-challenged mice, leukocyte numbers, particularly those of eosinophils, in the bronchoalveolar space increased by 3- to 5-fold with the cholesterol supplement. Among OVA aerosol-challenged mice, the levels of interleukin-5 and cysteinyl leukotrienes in the bronchoalveolar lavage fluid were significantly higher in those fed the 2% cholesterol diet compared with mice on the control diet. Conclusions: Dietary cholesterol may enhance pulmonary allergic inflammation.
Metabolic adaptation is not a major barrier to weight-loss maintenance

ABSTRACT Background The existence of metabolic adaptation, at the level of resting metabolic rate (RMR), remains highly controversial, likely due to lack of standardization of participants’ energy balance. Moreover, its role as a driver of relapse remains unproven. Objective The main aim was to determine if metabolic adaptation at the level of RMR was present after weight loss and at 1- and 2-y follow-up, with measurements taken under condition of weight stability. A secondary aim was to investigate race differences in metabolic adaptation after weight loss and if this phenomenon was associated with weight regain. Methods A total of 171 overweight women [BMI (kg/m2): 28.3 ± 1.3; age: 35.2 ± 6.3 y; 88 whites and 83 blacks] enrolled in a weight-loss program to achieve a BMI <25, and were followed for 2 y. Body weight and composition (4-compartment model) and RMR (indirect calorimetry) were measured after 4 wk of weight stability at baseline, after weight loss and at 1 and 2 y. Metabolic adaptation was defined as a significantly lower measured compared with predicted RMR (from own regression model). Results Participants lost, on average, 12 ± 2.6 kg and regained 52% ± 38% and 89% ± 54% of their initial weight lost at 1 and 2 y follow-up, respectively. Metabolic adaptation was found after weight loss (−54 ± 105 kcal/d; P < 0.001), with no difference between races and was positively correlated with fat-mass loss, but not with weight regain, overall. In a subset of women (n = 46) with data at all time points, metabolic adaptation was present after weight loss, but not at 1- or 2-y follow-up (−43 ± 119, P = 0.019; −18 ± 134, P = 0.380; and − 19 ± 166, P = 0.438 kcal/day respectively). Conclusions In overweight women, metabolic adaptation at the level of RMR is minimal when measurements are taken under conditions of weight stability and does not predict weight regain up to 2 years follow-up. The JULIET study is registered at https://clinicaltrials.gov/ct2/show/NCT00067873 as NCT00067873.
Ion transport characteristics of the murine trachea and caecum.

1. The basic defect in cystic fibrosis relates to abnormalities of ion transport in affected tissues, such as the respiratory and gastrointestinal tracts. The identification of the cystic fibrosis gene has enabled studies on the production of a cystic fibrosis transgenic mouse to be undertaken. Knowledge of normal ion transport will be necessary for the validation of any such animal model. We have therefore characterized selected responses of the murine trachea and caecum mounted in 'mini' Ussing chambers under open-circuit conditions. 2. Basal values for the trachea were: potential difference, 1.1 mV (SEM 0.2; n = 18); equivalent short-circuit current, 20.4 microA/cm2 (3.6); conductance, 18.2 mS/cm2 (1.7). Corresponding values for the caecum were: potential difference, 0.7 mV (0.1; n = 18); equivalent short-circuit current, 11.0 microA/cm2 (1.6); conductance, 14.5 mS/cm2 (1.4). 3. Amiloride (10 mumol/l) produced a significant (P less than 0.001) fall in potential difference of 43.0% (5.7) in the trachea, but had no significant effect in the caecum. 4. Subsequently, one of three protocols was used to assess the capacity of either tissue for chloride secretion. Addition of a combination of forskolin (1 mumol/l) and zardaverine (10 mumol/l) produced rises in the potential difference of 873% (509) in the trachea and 399% (202) in the caecum. Both A23187 (10 mumol/l) and phorbol dibutyrate (10 nmol/l) increased tracheal potential difference by 350% (182) and 147% (47), respectively. Neither had a significant effect in the caecum. 5. Subsequent addition of bumetanide caused a fall in the stimulated potential difference of between 39.8% and 71.7%, depending on secretagogue and tissue type. (ABSTRACT TRUNCATED AT 250 WORDS)
Behavioural and Cognitive Psychotherapy: A Descriptive Review (2000 to July 2016)

Background: The Behavioural and Cognitive Psychotherapy (BCP) Journal is the main academic publication of the British Association for Behavioural and Cognitive Psychotherapies. It publishes empirical studies, reviews and theoretical papers, brief reports and single cases. Aim: To describe the main areas of interest and focus in BCP papers. Method: All the papers published in BCP from 2000 to July 2016 were analysed. A categorization procedure was followed with 813 contributions in six main areas: main author country; main author gender; kind of contribution; kind of therapeutic approaches; kind of samples; kind of focus/topic. Results: Although the journal's scope is international, first authors tend to come from English-speaking countries. Since 2009, females contribute more than males. Empirical studies surpass theoretical studies and reviews, while the main therapy denomination is cognitive behavioural therapy. Variability of samples is wide, and ranges from analogues to main disorders. Finally, the main focus of papers is to study change and psychopathology, therapists’ training and improvement of CBT. Conclusion: Given the total number of categorized papers, it can be tentatively assumed that they could exemplify some main areas of interest and evolvement in the cognitive and behavioural field.
Exploring Automatic Feature Selection for Transition-Based Dependency Parsing

alisis de dependencias, MaltOptimizer, MaltParser Abstract: In this paper we investigate automatic techniques for nding an opti- mal feature model in the case of transition-based dependency parsing. We show a comparative study making a distinction between search algorithms, validation and decision rules demonstrating at the same time that using our methods it is possible to come up with quite complex feature specications which are able to provide bet-
Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C.

BACKGROUND The standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated sofosbuvir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection. METHODS We provided open-label treatment to eight groups of patients. A total of 40 previously untreated patients with HCV genotype 2 or 3 infection were randomly assigned to four groups; all four groups received sofosbuvir (at a dose of 400 mg once daily) plus ribavirin for 12 weeks. Three of these groups also received peginterferon alfa-2a for 4, 8, or 12 weeks. Two additional groups of previously untreated patients with HCV genotype 2 or 3 infection received sofosbuvir monotherapy for 12 weeks or sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks. Two groups of patients with HCV genotype 1 infection received sofosbuvir and ribavirin for 12 weeks: 10 patients with no response to prior treatment and 25 with no previous treatment. We report the rate of sustained virologic response 24 weeks after therapy. RESULTS Of the 40 patients who underwent randomization, all 10 (100%) who received sofosbuvir plus ribavirin without interferon and all 30 (100%) who received sofosbuvir plus ribavirin for 12 weeks and interferon for 4, 8, or 12 weeks had a sustained virologic response at 24 weeks. For the other patients with HCV genotype 2 or 3 infection, all 10 (100%) who received sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks had a sustained virologic response at 24 weeks, as did 6 of 10 (60%) who received sofosbuvir monotherapy. Among patients with HCV genotype 1 infection, 21 of 25 previously untreated patients (84%) and 1 of 10 with no response to previous therapy (10%) had a sustained virologic response at 24 weeks. The most common adverse events were headache, fatigue, insomnia, nausea, rash, and anemia. CONCLUSIONS Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection. (Funded by Pharmasset and Gilead Sciences; ClinicalTrials.gov number, NCT01260350.).
Additional evidence that the sympathetic nervous system regulates the vessel wall release of tissue plasminogen activator

It is established that sympathetic neurons can synthesize, transport and store tissue plasminogen activator (t-PA) within axon terminals in the smooth muscle of vessel walls. Moreover, sympathetic excitations (e.g. physical and mental stress) are known to induce an acute release of t-PA into the circulation. However, relatively little is known about the nature and extent of sympathetic nervous system involvement in the release process per se. We inquired whether a chemical sympathectomy will alter the release of t-PA into the blood, and the intrinsic release of stored t-PA from isolated whole vessel explants. A long-term sympathectomy was induced in adult Sprague–Dawley rats by injection of guanethidine during a 5-week course. The destruction of ganglion neurons and vessel wall axons was verified immunohistochemically. t-PA release was assayed as the free activity in hind limb plasma and explant culture medium. Following sympathectomy: (i) the basal t-PA activity in plasma was 70% less than controls (2.92 ± 1.96 versus 9.33 ± 1.72 IU/ml;P ⩽ 0.001); (ii) the acute release from isolated vessels induced by bradykinin or phenylephrine was comparably reduced; and (iii) the greatest reductions occurred in densely innervated small vessel explants. The results provide new support for an autonomic regulation of neural t-PA release into the vessel wall matrix and blood of densely innervated thin-walled microvessels.
Production of platelet-activating factor by neuronal cells in the rat brain with cold injury

Abstract The production and localization of platelet-activating factor (PAF) in the brain following focal brain injury were examined. Immunofluorescent staining was used to detect PAF in the rat brain with cold-induced local brain injury. After cold injury, immediate-early PAF staining was observed within the cold lesion followed later by immunoreactivity in the ipsilateral white matter. PAF immunoreactivity was also clearly seen both in cortical neurons adjacent to the cold lesion and in the ipsilateral hippocampus which showed delayed neuronal degeneration. The data suggest that PAF synthesis occurs in the neuronal cells in the perilesional area and hippocampus as well as within the cold lesion site during the early stages of cold-induced brain injury. PAF expression may contribute to the onset and progression of further brain damage, such as delayed axotomy and delayed neuronal loss. [Neurol Res 2001; 23: 605-611]
Emergence of Multifunctional Oxygenase Activities by Random Priming Recombination*

Biphenyl dioxygenase (Bph Dox) is responsible for the initial dioxygenation of biphenyl. The large subunit (BphA1) of Bph Dox plays a crucial role in determination of substrate specificity of biphenyl-related compounds including polychlorinated biphenyls (PCBs). Functional evolution of Bph Dox ofPseudomonas pseudoalcaligenes KF707 was accomplished by random priming recombination of the bphA1 gene, involving two rounds of in vitro recombination and mutation followed by selection for increased activity in vivo. Evolved Bph Dox acquired novel and multifunctional degradation capabilities not only for PCBs but also for dibenzofuran, dibenzo-p-dioxin, dibenzothiophene, and fluorene, the compounds scarcely attacked by the original KF707 Bph Dox. The modes of oxygenation were angular and lateral dioxygenation for dibenzofuran and dibenzo-p-dioxin, sulfoxidation for dibenzothiophene, and mono-oxygenation for fluorene. These enzymes also exhibited enhanced degradation abilities for PCB congeners, retaining 2,3-dioxygenase activity and gaining 3,4-dioxygenase activity, depending on the chlorine substitution of PCB congeners. Further mutation analysis revealed that the amino acid at position 376 in BphA1 is significantly involved in the acquisition of multifunctional oxygenase activities and mode of oxygenation.