Miracle-dz/UniFAR-FTUs huggingface dataset:
Guillain–Barré syndrome: An unusual presentation of West Nile virus infection

Article abstract West Nile fever is a mosquito-borne febrile illness seen in Africa, Asia, and Europe, but reported in North America only once. The recent outbreak in New York City represents the first time this virus has been detected in North America. West Nile virus usually causes mild symptoms, though rarely it can cause neurologic diseases, with a fatal outcome or permanent neurologic sequelae. We describe an elderly patient with West Nile virus infection who presented with Guillain–Barré syndrome.
Kinetic Analysis of Binding between Shiga Toxin and Receptor Glycolipid Gb3Cer by Surface Plasmon Resonance*

Shiga toxin (Stx) binds to the receptor glycolipid Gb3Cer on the cell surface and is responsible for hemolytic uremic syndrome. Stx has two isoforms, Stx1 and Stx2, and in clinical settings Stx2 is known to cause more severe symptoms, although the differences between the mechanisms of action of Stx1 and Stx2 are as yet unknown. In this study, the binding modes of these two isoforms to the receptor were investigated with a surface plasmon resonance analyzer to compare differences by real time receptor binding analysis. A sensor chip having a lipophilically modified dextran matrix or quasicrystalline hydrophobic layer was used to immobilize an amphipathic lipid layer that mimics the plasma membrane surface. Dose responsiveness was observed with both isoforms when either the toxin concentration or the Gb3Cer concentration was increased. In addition, this assay was shown to be specific, because neither Stx1 nor Stx2 bound to GM3, but both bound weakly to Gb4Cer. It was also shown that a number of fitting models can be used to analyze the sensorgrams obtained with different concentrations of the toxins, and the “bivalent analyte” model was found to best fit the interaction between Stxs and Gb3Cer. This shows that the interaction between Stxs and Gb3Cer in the lipid bilayer has a multivalent effect. The presence of cholesterol in the lipid bilayer significantly enhanced the binding of Stxs to Gb3Cer, although kinetics were unaffected. The association and dissociation rate constants of Stx1 were larger than those of Stx2: Stx2 binds to the receptor more slowly than Stx1 but, once bound, is difficult to dissociate. The data described herein clearly demonstrate differences between the binding properties of Stx1 and Stx2 and may facilitate understanding of the differences in clinical manifestations caused by these toxins.
Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial.

CONTEXT In patients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. OBJECTIVE To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, multicenter trial (2000-2001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors. INTERVENTIONS Adjusted-dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. MAIN OUTCOME MEASURES The primary end point was all strokes (ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0% per year according to the intention-to-treat model. RESULTS During 6405 patient-years (mean 20 months) of follow-up, 88 patients experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was within target during 68% of the treatment period. The primary event rate with ximelagatran was 1.6% per year and with warfarin was 1.2% per year (absolute difference, 0.45% per year; 95% confidence interval, -0.13% to 1.03% per year; P<.001 for the predefined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10% per year (95% confidence interval, -0.97% to 1.2% per year; P = .86). There was no difference between treatment groups in rates of major bleeding, but total bleeding (major and minor) was lower with ximelagatran (37% vs 47% per year; 95% confidence interval for the difference, -14% to -6.0% per year; P<.001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0% of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred. CONCLUSIONS The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.
Early Endoscopic Intervention Versus Early Conservative Management in Patients With Acute Gallstone Pancreatitis and Biliopancreatic Obstruction: A Randomized Clinical Trial

Objective:To test the hypothesis that early endoscopic intervention, performed on patients with acute gallstone pancreatitis and biliopancreatic obstruction, reduces systemic and local inflammation. Summary Background Data:The role of early endoscopic intervention, in the treatment of acute gallstone pancreatitis, remains controversial. Previous randomized trials have not focused on the subgroup of patients with clinical evidence of biliopancreatic obstruction. Methods:This single-center randomized clinical trial was performed between May 2000 and September 2005. Of 238 patients, admitted within 48 hours after the onset of acute gallstone pancreatitis, 103 with a distal bile duct measuring ≥8 mm combined with a total serum bilirubin ≥1.20 mg/dL, were randomized to receive either endoscopic retrograde cholangiopancreatography followed by endoscopic papillotomy for bile duct stones (EEI, n = 51) or early conservative management (ECM, n = 52). Patients with clinical evidence of coexisting acute cholangitis were excluded. Outcome measures included changes in organ failure score and computed tomography (CT) severity index during the first week after admission, incidence of local complications, and overall morbidity and mortality. Results:The incidence of bile duct stones at EEI was 72% and 40% of patients in the ECM group had persisting bile duct stones at elective biliary surgery. No significant differences were found between the EEI and ECM groups regarding changes in mean organ failure score (P = 0.87), mean CT severity index (P = 0.88), incidence of local complications (6% vs. 6%, P = 0.99), overall morbidity (21% vs. 18%, P = 0.80), and mortality (6% vs. 2%, P = 1). Conclusions:The present study failed to provide evidence that early endoscopic intervention reduces systemic and local inflammation in patients with acute gallstone pancreatitis and biliopancreatic obstruction. If acute cholangitis can be safely excluded, early endoscopic intervention is not mandatory and should not be considered a standard indication.
Dysregulation of microRNA‐204 mediates migration and invasion of endometrial cancer by regulating FOXC1

MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real‐time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti‐/pre‐miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR‐7, miR‐194 and miR‐449b, or overexpressing miR‐204, repressed migration, invasion and extracellular matrix‐adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR‐204, and two binding sites in the 3′‐untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR‐204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR‐204‐FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression‐ and metastasis‐related miRNAs offers a novel potential therapeutic strategy for the disease.
Growth hormone receptor abundance in tibial growth plates of uremic rats: GH/IGF-I treatment.

BACKGROUND Children with chronic renal failure (CRF) exhibit growth retardation and a disturbed growth hormone/insulin-like growth factor-I (GH/IGF-I) axis. Treatment of children with CRF with GH or GH/IGF-I can partially restore linear growth. The molecular basis for decreased longitudinal growth is not known but may involve an impaired action of GH. METHODS We used the growth-retarded uremic rat model to determine the abundance and distribution of GH receptors (GHRs) in the tibial epiphyseal growth plate and the influence of GH, IGF-I, or combined GH/IGF-I treatment. Pair-fed rats were used as the control. RESULTS While all treatment regimes increased body length and weight in both rat groups, only GH/IGF-I treatment increased the total growth plate width. This involved an increase in cell number in the hypertrophic zone, which could also be induced by IGF-I alone. Immunohistochemical analysis showed that uremic rats had decreased abundance of GHRs in the proliferative zone, and only GH/IGF-I therapy could overcome this decrease. These data thus suggest that growth retardation in uremic rats is, at least in part, due to a decrease in GHR abundance in chondrocytes of the proliferative zone of the tibial growth plate. This decreased GHR abundance can be overcome by combined GH/IGF-I therapy, thus enhancing generation and proliferation of hypertrophic zone chondrocytes and increasing growth-plate width. CONCLUSION These studies point to a mechanism for the growth retardation seen in children with CRF, and suggest that combined GH/IGF-I treatment may provide more effective therapy for these patients than GH alone.
Recurrence of Gestational Diabetes Mellitus

Objective: To assess the influence of several maternal and neonatal variables on the recurrence of gestational diabetes mellitus. Methods: A retrospective review was conducted on 90 of our patients whose index pregnancy was complicated by gestational diabetes mellitus and whose subsequent pregnancy was also managed at our institution. Results: Forty-seven women (52%) had a recurrence of gestational diabetes mellitus in their subsequent pregnancy. These 47 women had an increased body mass index (BMI) (32.8 ± 8.2 versus 28.9 ± 7.2 kg/m2; P <.03) and more large for gestational age (LGA) neonates (38 versus 14% P <.05) and more of them required insulin during their index pregnancy (38 versus 19% P <.05) than did those who did not have a recurrence of gestational diabetes mellitus. Women who developed a recurrence of gestational diabetes mellitus also had higher fasting (P <.05), 1-hour, 2-hour, and total glucose tolerance test values (P s .01) during their index pregnancy. Conclusion: Women with a history of gestational diabetes mellitus who have a BMI greater than 35 kg/m2, whose previous newborn was LGA, and who required insulin during their previous pregnancy are at increased risk for recurrence of gestational diabetes mellitus.
Hierarchical spectral clustering of MRI for global-to-local shape analysis: Applied to brain variations in Alzheimer's disease

In this paper a hierarchical brain segmentation from multiple MRIs is presented for a global-to-local shape analysis. The idea is to group voxels into clusters with high within-cluster and low between-cluster shape relations. Doing so, complementing voxels are analysed together, optimally wheeling the power of multivariate analysis. Therefore, we adapted hierarchical spectral clustering to volumetric image datasets. The outcome is a segmentation of the brain into regions at different levels of detail and anatomical overlap, which are tested in their ability to predict ADAS-cog (a score for cognitive function in Alzheimer's disease (AD) diagnosis) from brain shape. The results show a benefit for a global-to-local analysis compared to a typical voxel-based and whole brain-based analysis. Additionally, knowledge on brain variations in AD is perfectly confirmed and even elaborated on.
Corticostriatal connections of the superior temporal region in rhesus monkeys

Corticostriatal connections of auditory areas within the supratemporal plane and in rostral and caudal portions of the superior temporal gyrus were studied by the autoradiographic anterograde tracing technique. The results show that the primary auditory cortex has limited projections to the caudoventral putamen and to the tail of the caudate nucleus. In contrast, the second auditory area within the circular sulcus has connections to the rostral and the caudal putamen and to the body of the caudate nucleus and the tail. The association areas of the superior temporal gyrus collectively have widespread corticostriatal projections characterized by differential topographic distributions. The rostral part of the gyrus projects to ventral portions of the head of the caudate nucleus and of the body and to the tail. In addition, there are connections to rostroventral and caudoventral portions of the putamen. The mid‐portion of the gyrus projects to similar striatal regions, but the connections to the head of the caudate nucleus are less extensive. Compared with the rostral and middle parts of the superior temporal gyrus, the caudal portion has little connectivity to the tail of the caudate nucleus. It projects more dorsally within the head and the body and also more dorsally within the caudal putamen. These differential patterns of corticostriatal connectivity are consistent with functional specialization at the cortical level. J. Comp. Neurol. 399:384–402, 1998. © 1998 Wiley‐Liss, Inc.
Roles of Host Species, Geographic Separation, and Isolation in the Seroprevalence of Jamestown Canyon and Snowshoe Hare Viruses in Newfoundland

ABSTRACT California serogroup viruses, including Jamestown Canyon virus (JCV) and snowshoe hare virus (SSHV), are mosquito-borne members of the Bunyaviridae family and are endemic across North America. These arboviruses are potential pathogens which occasionally cause neuroinvasive disease in humans and livestock. A neutralization assay was used to document JCV and SSHV seroprevalence using blood collected from a variety of domestic and wildlife host species. These species were sampled in an island setting, Newfoundland, which contains diverse ecoregions, ecological landscapes, and habitats. Seroprevalence rates for each virus differed significantly among host species and within certain species across different geographic areas. JCV was significantly associated with large mammals, and SSHV was significantly associated with snowshoe hares. Seroprevalence rates in the 5 species of animals tested for prior exposure to JCV ranged from 0% in snowshoe hares to 64% in horses. Seroprevalence rates for SSHV ranged from less than 1% in bovines to 55% in all snowshoe hares. The seroprevalence of SSHV differed significantly (P < 0.05) among hares occupying the discrete habitats of watersheds separated by 14 to 35 km. Cattle on farms in boreal forest landscapes displayed significantly higher JCV seroprevalence (P < 0.001) than those on farms located in seacoast landscapes. Lifelong geographic isolation of cattle to insular Newfoundland was associated with significantly lower JCV seroprevalence (P < 0.01) than that for cattle which had lived off-island.
Opposing Effects of Ubiquitin Conjugation and SUMO Modification of PCNA on Replicational Bypass of DNA Lesions in Saccharomyces cerevisiae

ABSTRACT The Rad6-Rad18 ubiquitin-conjugating enzyme complex of Saccharomyces cerevisiae promotes replication through DNA lesions via three separate pathways that include translesion synthesis (TLS) by DNA polymerases ζ (Polζ) and Polη and postreplicational repair mediated by the Mms2-Ubc13 ubiquitin-conjugating enzyme and Rad5. Here we report our studies with a proliferating cell nuclear antigen (PCNA) mutation, pol30-119, which results from a change of the lysine 164 residue to arginine. It has been shown recently that following treatment of yeast cells with DNA-damaging agents, the lysine 164 residue of PCNA becomes monoubiquitinated in a Rad6-Rad18-dependent manner and that subsequently this PCNA residue is polyubiquitinated via a lysine 63-linked ubiquitin chain in an Mms2-Ubc13-, Rad5-dependent manner. PCNA is also modified by SUMO conjugation at the lysine 164 residue. Our genetic studies with the pol30-119 mutation show that in addition to conferring a defect in Polζ-dependent UV mutagenesis and in Polη-dependent TLS, this PCNA mutation inhibits postreplicational repair of discontinuities that form in the newly synthesized strand across from UV lesions. In addition, we provide evidence for the activation of the RAD52 recombinational pathway in the pol30-119 mutant and we infer that SUMO conjugation at the lysine 164 residue of PCNA has a role in suppressing the Rad52-dependent postreplicational repair pathway.
A Live, Attenuated Bordetella pertussis Vaccine Provides Long-Term Protection against Virulent Challenge in a Murine Model

ABSTRACT Despite successful mass vaccination programs, whooping cough remains a significant cause of neonatal mortality. Immunity induced by current vaccines wanes in adolescence, requiring additional immunizations to prevent resurgence. There is a need for a new generation of vaccines capable of conferring long-lasting immunity from birth. Recently, a live, attenuated whooping cough vaccine, BPZE1, has been developed. Here, an established murine immunization model was used to examine the induction and longevity of immunological memory. In this predictive model, BPZE1 conferred a level of protection against virulent bacterial challenge comparable to that conferred by recovery from prior infection, up to 1 year after immunization. One year after immunization with BPZE1, a pertussis-specific persistent response, with high levels of gamma interferon (IFN-γ), could be detected from spleen cells restimulated with inactivated Bordetella pertussis. BPZE1 induced low levels of interleukin-17 (IL-17) and no IL-10 or IL-5. BPZE1 immunization induced long-lasting, efficacious memory B-cell and specific antibody responses dominated by IgG2a, which were boosted by subsequent challenge. Finally, the antibody induced by BPZE1 was functionally relevant and could clear a virulent B. pertussis infection in antibody-deficient mice following passive transfer. This study suggests that BPZE1 is capable of conferring a high level of long-lived effective protection against virulent B. pertussis.
Terminations of pregnancy in the European Union

Please cite this paper as: Gissler M, Fronteira I, Jahn A, Karro H, Moreau C, Oliveira da Silva M, Olsen J, Savona‐Ventura C, Temmerman M, Hemminki E, the REPROSTAT group. Terminations of pregnancy in the European Union. BJOG 2011; DOI: 10.1111/j.1471‐0528.2011. 03189.x.
Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy*

Background: Carbohydrate metabolism during decidualization is unknown. Results: Decidual cells undergo glycolysis upon progesterone signals, and the undifferentiated stromal cells consume lactate for proliferation. Inhibition of glycolysis or lactate flux could compromise decidual development. Conclusion: Warburg-like glycolysis and lactate communication play critical roles during decidualization. Significance: Our study will be valuable for understanding the mechanism underlying decidualization. Decidualization is an essential process of maternal endometrial stromal cells to support pregnancy. Although it is known that enhanced glucose influx is critical for decidualization, the underlying mechanism in regulating glucose metabolism in decidua remains insufficiently understood. Here, we demonstrate that aerobic glycolysis-related genes and factors are all substantially induced during decidualization, indicating the existence of Warburg-like glycolysis in decidua. In vitro, progesterone activates hypoxia-inducible factor 1α (Hif1α) and c-Myc through Pi3k-Akt signaling pathway to maintain aerobic glycolysis in decidualizing cells. Knocking down of pyruvate kinase M2 (Pkm2) attenuates the induction of decidual marker gene. Decidual formation in vivo is also impaired by glycolysis inhibitor 3-bromopyruvate. Besides, lactate exporter monocarboxylate transporter 4 (Mct4) is induced in newly formed decidual cells, whereas lactate importer Mct1 and proliferation marker Ki-67 are complementarily located in the surrounding undifferentiated cells, which are supposed to consume lactate for proliferation. Hif1α activation is required for lactate-dependent proliferation of the undifferentiated cells. Inhibition of lactate flux leads to compromised decidualization and decelerated lactate-dependent proliferation. In summary, we reveal that Warburg-like glycolysis and local lactate shuttle are activated in decidua and play important roles for supporting early pregnancy.
Effet de l'intensité du traitement sur la composition élémentaire et la durabilité du bois traité thermiquement : développement d'un marqueur de prédiction de la résistance aux champignons basidiomycètes

Le traitement thermique est une methode appropriee pour la valorisation d'essences europeennes peu durables. Les modifications chimiques en resultant conferent au bois une meilleure stabilite dimensionnelle et durabilite aux attaques fongiques, alors que les proprietes mecaniques diminuent plus ou moins. Le verrou actuel de ce procede reste la grande difficulte a produire a l'echelle industrielle un produit de qualite constante (durabilite, stabilite dimensionnelle, couleur). Ces difficultes sont dues a l'heterogeneite du materiau et des conditions de traitement realise generalement par convexion. La mise au point d'un pilote de traitement thermique par conduction permettant une mesure en dynamique de la perte de masse a ete realisee pour optimiser la conduite du traitement, mieux comprendre les reactions de thermodegradation et developper un outil de controle de la qualite du bois traite. Les resultats obtenus, realises dans des conditions de traitement proches des conditions industrielles, indiquent un effet important de l'essence de bois traitee sur les cinetiques de perte de masse observees, les feuillus etant generalement plus sensibles a la thermodegradation que les resineux. Il a ensuite ete etabli une forte correlation entre le niveau de thermodegradation du bois estime a partir de sa perte de masse et l'augmentation de sa durabilite aux champignons basidiomycetes. L'analyse fine et la comprehension des mecanismes reactionnels intervenant durant le traitement ont permis de mettre en evidence un lien direct entre la composition elementaire du bois et la perte de masse due aux reactions de thermodegradation, permettant egalement de predire la durabilite aux attaques fongiques. Le taux de carbone, d'oxygene ou encore le rapport O/C peuvent de ce fait etre consideres comme des marqueurs pertinents permettant de controler la qualite du bois traite thermiquement.