Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety of mycophenolate mofetil monotherapy in patients after liver transplantation.

BACKGROUND Due to the nephrotoxicity of calcineurin inhibitors (CNIs) mycophenolate mofetil (MMF) has become a promising immunosuppressive alternative in recent years. In several studies an improvement of renal function could be reached by introduction of MMF and withdrawal of CNIs but there is few known about the long-term effects of MMF on liver-, kidney- and bone marrow function. MATERIAL AND METHODS We therefore retrospectively reviewed 123 adult liver transplant patients who were successfully converted to MMF monotherapy without any acute rejection within the first three months of MMF monotherapy. RESULTS Serum levels of liver enzymes as well as white blood cells did not show any significant difference between the time of conversion and after 1 year but a significant reduction in serum creatinine could be evaluated (1.47 mg/dl vs. 1.54 mg/dl). In 59 patients liver biopsies were performed before and after introduction of MMF monotherapy. None displayed signs of chronic rejection during MMF monotherapy but there was a slight increase of the fat content of the liver (16.1% vs. 9.8%). CONCLUSIONS In conclusion after successful conversion to MMF monotherapy this regime is safe and effective and the long-term effects of MMF monotherapy on the liver tissue are minor. Furthermore renal function can be improved without considerable effects on the bone marrow.
Biased signaling pathways via CXCR3 control the development and function of CD4+ T cell subsets

Structurally related chemotactic cytokines (chemokines) regulate cell trafficking through interactions with 7‐transmembrane domain, G protein‐coupled receptors. Biased signaling or functional selectivity is a concept that describes a situation where a 7‐transmembrane domain receptor preferentially activates one of several available cellular signaling pathways. It can be divided into 3 distinct cases: ligand bias, receptor bias, and tissue or cell bias. Many studies, including those coming from our lab, have shown that only a limited number of chemokines are key drivers of inflammation. We have referred to them as “driver chemokines. ” They include the CXCR3 ligands CXCL9 and CXCL10, the CCR2 ligand CCL2, all 3 CCR5 ligands, and the CCR9 ligand CCL25. As for CXCR3, despite the proinflammatory nature of CXCL10 and CXCL9, transgenic mice lacking CXCR3 display an aggravated manifestation of different autoimmune disease, including Type I diabetes and experimental autoimmune encephalomyelitis. Recently, we showed that whereas CXCL9 and CXCL10 induce effector Th1/Th17 cells to promote inflammation, CXCL11, with a relatively higher binding affinity to CXCR3, drives the development of the forkhead box P3‐negative IL‐10high T regulatory 1 cell subset and hence, dampens inflammation. We also showed that CXCL9/CXCL10 activates a different signaling cascade than CXCL11, despite binding to the same receptor, CXCR3, which results in these diverse biologic activities. This provides new evidence for the role of biased signaling in regulating biologic activities, in which CXCL11 induces ligand bias at CXCR3 and receptor‐biased signaling via atypical chemokine receptor 3.
The effect of Hofmeister anions and protein concentration on the activity and stability of some immobilized NAD‐dependent dehydrogenases

The effect of several factors on the activity and stability of alcohol dehydrogenase, glyceraldehyde‐3‐phosphate dehydrogenase, and 20β‐hydroxysteroid dehydrogenase, both free and immobilized on CNBr‐activated Sepharose 4B, was investigated. Enzymes were im‐ mobilized under different conditions including various degrees of matrix activation, variable amounts of protein, in the presence, or in the absence of, additives (coenzymes, dithioth‐ reitol, salts). Activity recovery was in general satisfactorily high with 20β‐hydroxysteroid dehydrogenase, low with glyceraldehyde‐3‐phosphatedehydrogenase, and markedly linked to the concentration of immobilized protein with alcohol dehydrogenase. In the latter case the advantageous stabilizing effect of high enzyme concentrations was notably diminished by the parallel decrease of the effectiveness factor. The effect of high concentrations of anions of the Hofmeister series was examined. It was found that 1M phosphate and 0.5M sulfate dramatically stabilize both free and immobilized enzymes against inactivation by temperature and urea. Km, values of apolar substrates were considerably lowered by the two anions while Km values of polar substrates were not affected. In some cases Vmax values also were influenced by high concentrations of these anions. The present results appear of interest particularly in view of enzyme utilization for analytical as well as for preparative purposes.
Mitochondrial lipoic acid scavenging is essential for Plasmodium berghei liver stage development

Lipoic acid is an essential cofactor for enzymes that participate in key metabolic pathways in most organisms. While in mammalian cells lipoylated proteins reside exclusively in the mitochondria, apicomplexan parasites of the genus Plasmodium harbour two independent lipoylation pathways in the mitochondrion and the apicoplast, a second organelle of endosymbiotic origin. Protein lipoylation in the apicoplast relies on de novo lipoic acid synthesis while lipoylation of proteins in the mitochondrion depends on scavenging of lipoic acid from the host cell. Here, we analyse the impact of lipoic acid scavenging on the development of Plasmodium berghei liver stage parasites. Treatment of P. berghei‐infected HepG2 cells with the lipoic acid analogue 8‐bromo‐octanoic acid (8‐BOA) abolished lipoylation of mitochondrial enzyme complexes in the parasite while lipoylation of apicoplast proteins was not affected. Parasite growth as well as the ability of the parasites to successfully complete liver stage development by merosome formation were severely impaired but not completely blocked by 8‐BOA. Liver stage parasites were most sensitive to 8‐BOA treatment during schizogony, the phase of development when the parasite grows and undergoes extensive nuclear division to form a multinucleated syncytium. Live cell imaging as well as immunofluorescence analysis and electronmicroscopy studies revealed a close association of both host cell and parasite mitochondria with the parasitophorous vacuole membrane suggesting that host cell mitochondria might be involved in lipoic acid uptake by the parasite from the host cell.
Splenic artery ligature associated with endoscopic banding for schistosomal portal hypertension.

AIM To propose a less invasive surgical treatment for schistosomal portal hypertension. METHODS Ten consecutive patients with hepatosplenic schistosomiasis and portal hypertension with a history of upper gastrointestinal hemorrhage from esophageal varices rupture were evaluated in this study. Patients were subjected to a small supraumbilical laparotomy with the ligature of the splenic artery and left gastric vein. During the procedure, direct portal vein pressure before and after the ligatures was measured. Upper gastrointestinal endoscopy was performed at the 30(th) postoperative day, when esophageal varices diameter were measured and band ligature performed. During follow-up, other endoscopic procedures were performed according to endoscopy findings. RESULTS There was no intra-operative mortality and all patients had confirmed histologic diagnoses of schistosomal portal hypertension. During the immediate postoperative period, two of the ten patients had complications, one characterized by a splenic infarction, and the other by an incision hematoma. Mean hospitalization time was 4.1 d (range: 2-7 d). Pre- and post-operative liver function tests did not show any significant changes. During endoscopy thirty days after surgery, a decrease in variceal diameters was observed in seven patients. During the follow-up period (57-72 mo), endoscopic therapy was performed and seven patients had their varices eradicated. Considering the late postoperative evaluation, nine patients had a decrease in variceal diameters. A mean of 3.9 endoscopic banding sessions were performed per patient. Two patients presented bleeding recurrence at the late postoperative period, which was controlled with endoscopic banding in one patient due to variceal rupture and presented as secondary to congestive gastropathy in the other patient. Both bleeding episodes were of minor degree with no hemodynamic consequences or need for blood transfusion. CONCLUSION Ligature of the splenic artery and left gastric vein with supraumbilical laparotomy is a promising and less invasive method for treating presinusoidal schistosomiasis portal hypertension.
Coherent campaigns? Campaign broadcast and social messaging

Purpose Despite the growing use of social media by politicians, especially during election campaigns, research on the integration of these media into broader campaign communication strategies remains rare. The purpose of this paper is to ask what the consequences of the transition to social media may be, specifically considering how Senate candidates’ use of a popular social network, Twitter, is related to their messaging via broadcast media in the form of campaign advertising, in terms of content and tone. Design/methodology/approach To address this research question, a unique data set combining every tweet (10,303) and every television ad aired (576,933 ad airings) by candidate campaigns for the US Senate during the 2010 campaign is created. Using these data, tweets and ads are analyzed for their references to issues as well as their overall tone. Findings Findings demonstrate that social messaging often resembles broadcast advertising, but that Twitter nonetheless occupies a unique place in modern campaigns in that its tone tends to be quite different than that of advertisements. Research limitations/implications This sheds light on a larger debate about whether online campaigning has produced a fundamental change in election practices or whether new media simply extend “campaigning as usual. ” Originality/value This study uses a novel data set, encompassing the complete universe of ads and tweets distributed by candidates for Senate in 2010.
Overexpression of histone variant H2A.1 and cellular transformation are related in N-nitrosodiethylamine-induced sequential hepatocarcinogenesis

Histones through a complex repertoire of non-allelic variants and their post-translational modifications regulate gene expression. Though alterations in histone-modifying enzymes and post-translational modifications of histones have been studied in cancer, expression of histone variants has not been clearly associated with dedifferentiation and malignant transformation of hepatocyte in vivo. In the present work, the pattern of variants of histones was investigated during N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. Our studies show for the first time in vivo overexpression of a major histone H2A variant H2A.1 and a decrease in H2A.2 at protein and mRNA levels by sodium dodecyl sulfate-Acetic acid-Urea-Triton (SDS-AUT) two-dimensional gel electrophoresis followed by matrix-assisted-laser desorption/ionization time-of-flight (TOF)/TOF mass spectrometry and reverse transcriptase-polymerase chain reaction analysis during sequential development of hepatocellular carcinoma (HCC). H2A.1 and H2A.2 are highly homologous, replication-dependent, non-allelic variants of histone H2A differing at only three amino acid positions. Our results of increase in proliferating cell nuclear antigen expression indicate that with increase in replicating population of transformed cells in HCC, H2A.1 expression increases, suggesting association of H2A.1 overexpression with hyper-proliferation of hepatocytes during cellular dedifferentiation and progressive transformation of normal liver to preneoplastic and neoplastic stages of HCC.
The effect of seated positioning quality on typical 6- and 7-year-old children's object manipulation skills.

OBJECTIVE The purpose of this study was to examine the effect of optimal seated positioning in individually fitted furniture versus suboptimal seated positioning in standard classroom furniture on typical 6- and 7-year-old children's object manipulation skills as measured by the In-hand Manipulation Test (IMT). METHOD An experimental research design was used to compare IMT performance of two groups of 20 children. One group was positioned in standard, too-large classroom furniture that did not support an optimal seated position, and one group was positioned optimally in furniture fitted to each child for tabletop activities, which allowed for hip flexion to 90 degrees, and foot placement on the floor, and the table to be at flexed elbow height. RESULTS Independent groups' t tests indicated that children who were optimally positioned performed significantly better (t = -2.77, df = 38, p < .01) than children who were tested in the too-large standard classroom furniture. The difference between groups was greater on the more difficult object manipulation items (t = -3.29, df = 38, p = .001) than on the easier items (t = -1.38, df = 38, p = .08). Age and gender may have differentially affected the results. CONCLUSION The study's results suggest that the fit of furniture relative to the child's size may have a significant impact on a young, typical child's object manipulation skills. Complex hand skills, such as those involving in-hand manipulation with stabilization, appear to be more affected by the quality of the child's seated position than are simpler, more well-established skills. Findings suggest that test administrators should strive to test young children in the most optimal seated position possible, particularly when the test involves complex hand skills. Further study is needed to assess the impact of the fit of furniture on hand skills in children with disabilities and on children's performance of other tasks.
Failure of IgG production due to a defect in the opening of the chromatin structure of Iγ1 region in a patient with IgG and IgA deficiency

Patients with common variable immunodeficiency (CVID) display reduced levels of two or all three of the major immunoglobulin isotypes, and the deficiency is characterized by failure of B cells to differentiate into plasma cells in many cases. A patient (14 years old, female) showed normal serum IgM levels and low serum IgG and IgA levels, including low levels of all IgG subclasses. Northern blot analysis suggested that the patient's B cells may be defective at the immunoglobulin heavy chain isotype switch. The germ‐line Cγ1 transcript was amplified from cDNA of healthy controls by the addition of recombinant IL‐2 (rIL‐2) to pokeweed mitogen‐stimulated peripheral mononuclear cells or Staphylococcus aureus Cowan I (SAC)‐stimulated IgM‐producing lymphoblastoid cell lines (LCL) transformed by Epstein‐Barr virus, while it was not amplified from cDNA of the patient. In the Iγ1 region of LCL cultured with SAC plus rIL‐2, the inner cytosine in the 5′C‐C‐G‐G 3′sequence nearest the 3′site of the Iγ1 region, at least, was not completely unmethylated in the patient. Moreover, the DNase I hypersensitive site was not induced in the patient's LCL by SAC plus rIL‐2. These results indicate that the defects of the immunoglobulin heavy chain isotype switch in the patient's B cells are due to failure in the synthesis of germ‐line Cγ transcripts, and this may be caused by defects in opening of the chromatin structures of specific switch regions.
Scaled FitzHugh-Nagumo equations as building blocks for modelling dynamics adjusted to measurable biophysical data

We apply the method of scaling fitting of the FitzHugh-Nagumo equation to describe a circuit consisting of the two coupled neurons aimed to reproduce non-stationary EEG modulations of theta-rhythm emerging during a rat's run along a linear track. It is shown that such an approach allows a quantitative reproduction of recorded oscillations and, therefore, may be used for a further development of computational models describing the spatial navigation in a rat brain.
Regulation of p27 Degradation and S-Phase Progression by Ro52 RING Finger Protein

ABSTRACT Ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27 provides a powerful route for enforcing normal progression through the mammalian cell cycle. According to a current model, the ubiquitination of p27 during S-phase progression is mediated by SCFSkp2 E3 ligase that captures Thr187-phosphorylated p27 by means of the F-box protein Skp2, which in turn couples the bound substrate via Skp1 to a catalytic core complex composed of Cul1 and the Rbx/Roc RING finger protein. Here we identify Skp2 as a component of an Skp1-cullin-F-box complex that is based on a Cul1-Ro52 RING finger B-box coiled-coil motif family protein catalytic core. Ro52-containing complexes display E3 ligase activity and promote the ubiquitination of Thr187-phosphorylated p27 in a RING-dependent manner in vitro. The knockdown of Ro52 expression in human cells with small interfering RNAs causes the accumulation of p27 and the failure of cells to enter S phase. Importantly, these effects are abrogated by the simultaneous removal of p27. Taken together, these data suggest a key role for Ro52 RING finger protein in the regulation of p27 degradation and S-phase progression in mammalian cells and provide evidence for the existence of a Cul1-based catalytic core that utilizes Ro52 RING protein to promote ubiquitination.
A multiparameter model predicting in-hospital mortality in malignant cerebral infarction

Abstract The early identification of patients with large hemisphere infarctions (LHIs) at risk of fatal brain edema may result in better outcomes. A quantitative model using parameters obtained at admission may be a predictor of in-hospital mortality from LHI. This prospective study enrolled all patients with LHI involving >50% of the middle cerebral artery (MCA) admitted to our neurological intensive care unit within 48 hours of symptom onset. Early clinical and radiographic parameters and the baseline CHADS2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke [double weight]) were analyzed regarding their ability to predict patient outcomes. Seventy-seven patients with LHIs were identified, 33 (42.9%) with complete MCA infarction (CMCA), and 44 (57.1%) with incomplete MCA infarction (IMCA). The predictors of CMCA score included: >1/3 early hypodensity in computed tomography findings, hyperdense MCA sign, brain edema, initial National Institutes of Health Stroke Scale (NIHSS) score ≥17, and stroke in progression during the 1st 5 days of admission. The cutoff CMCA score was 2, with a sensitivity of 81.8% and specificity of 70.5%. Mortality score 1, used for predicting in-hospital mortality from LHI, included CMCA and CHADS2 scores ≥4 (sensitivity 100.0%, specificity 57.4%), and mortality score 2 included CMCA and CHADS2 scores ≥4, and NIHSS score ≥26, during the 1st 5 days (sensitivity 100.0%, specificity 91.7%). Patients qualifying for a mortality score of 2 were at high-risk of in-hospital mortality from LHI. These findings may aid in identifying patients who may benefit from invasive therapeutic strategies, and in better describing the characteristics of those at risk of mortality.
An in vivo model for load‐modulated remodeling in the rabbit flexor tendon

This study tested the hypothesis that eliminating in vivo compression to the wrap‐around, fibrocartilage‐rich zone of the flexor digitorum profundus tendon results in rapid depletion of fibrocartilage and changes in its mechanical properties, microstructure, extracellular matrix composition, and cellularity. The right flexor digitorum profundus tendons of 2.5‐3‐year‐old rabbits were translocated anteriorly to eliminate in vivo compression and shear to the fibrocartilage zone and, at 4 weeks after surgery, were compared with tendons that had sham surgery and with untreated tendons. The translocated tissue showed a significant increase in equilibrium strain under a compressive creep load (p < 0.05). The thickness and area of the fibrocartilage zone also decreased significantly (p < 0.05). The nuclear density decreased by 40% in the fibrocartilage zone (p < 0.005); however, nuclear shape and orientation were not significantly altered. Glycosaminoglycan content in the fibrocartilage zone was also depleted by 40% (p < 0.02). The tightly woven basket weave‐like mesh of collagen fibers in the zone appeared more loosely organized, suggesting matrix reorganization due to translocation. Moreover, immunoreactive type‐II collagen and link protein in the fibrocartilage zone also decreased. With use of this unique in vivo model, this research clearly elucidates how changing tissue function (by removing compressive forces) rapidly alters tissue form.
Troubles de la personnalité et troubles des conduites alimentaires : modèles théoriques et réalité clinique

Les definitions et les criteres diagnostiques des classifications internationales pour les troubles des conduites alimentaires (TCA) et les troubles de la personnalite (TP) et leurs modalites d'evaluation sont d'abord rappelees. Les etudes empiriques concernant la comorbidite entre TP et TCA sont ensuite resumees : les donnees de prevalence de la comorbidite entre TP et TCA - le retentissement de la comorbidite avec un TP sur la presentation clinique du TCA - les travaux portant sur l'impact du TP sur le devenir du TCA. Les principaux modeles theoriques de comorbidite entre TP et TCA sont exposes, avec les etudes empiriques en faveur ou en defaveur de l'un ou l'autre de ces modeles. Les prises en charge specifique des patients ayant un TCA et un TP comorbide sont detaillees. Nous cloturons les aspects theoriques concernant les TP et les TCA, en abordant une comorbidite tres frequente chez les TCA, la comorbidite avec un TP Borderline. Dans la derniere partie, nous presentons deux etudes que nous avons menees sur ce sujet : la premiere etude porte sur 100 patientes adultes hospitalisees consecutivement dans une unite specialisee TCA, et chez qui les diagnostics standardises de TP et l'evaluation des traits de personnalite ont ete realises - la deuxieme etude procede a l'inverse ; les TCA ont ete diagnostiques sur 85 patients adolescents ayant un TP Borderline, et le groupe avec TCA est compare au groupe sans TCA. Pour terminer, nous discutons les resultats obtenus dans le contexte de la litterature internationale, nous evoquons la poursuite de nos travaux et les perspectives de recherche dans ce domaine