Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of cholesteatomatous bone resorption with pamidronate disodium.

Bone destruction is known to be an important cause of complications in chronic cholesteatomatous otitis media. A strategy that blocks localized bone resorption may prevent the progression of the disease. The bisphosphonate drug pamidronate is known to inhibit bone resorption and has been used in the treatment of Paget's disease and osteoporosis. The aim of this study was to investigate the effect of pamidronate on the inhibition of bone resorption in cholesteatoma using a neonatal rat calvarial culture system. Radioactive calcium was subcutaneously injected into pregnant rats. Neonatal calvariae were harvested after i.p. injection of pamidronate disodium to neonatal rats and culture supernatants of cholesteatoma keratinocytes were then added to the calvarial culture media. Radioactive calcium release was measured using a beta-ray scintillation counter. The percentage of calcium release was significantly higher in cholesteatoma culture supernatant than in Dulbecco's modification of Eagle's medium. The percentage calcium release in cholesteatoma culture supernatant was significantly lower with the high dose of pamidronate than with the low dose. These results suggest that pamidronate can inhibit the bone resorption caused by cholesteatoma. This study suggests a possible application for pamidronate in the prevention of cholesteatomatous bone destruction.
Placental infection with human papillomavirus is associated with spontaneous preterm delivery.

BACKGROUND We sought to determine if human papillomavirus (HPV) infection of extravillous trophoblast cells reduces cell invasion and if placental infection is associated with adverse reproductive outcomes attributed to placental dysfunction. METHODS We conducted apoptosis and invasion assays using extravillous trophoblast (HTR-8/SVneo) cells that were transfected with a plasmid (pAT-HPV-16) containing the entire HPV-16 genome. In order to associate HPV infection with reproductive outcomes, we conducted a case-control study to detect HPV DNA in the extravillous trophoblast region of placentas from cases of spontaneous preterm delivery, severe pre-eclampsia requiring delivery at <37 weeks and controls who delivered at term. RESULTS Rates of apoptosis were 3- to 6-fold greater in transfected cells than in non-transfected cells or cells transfected with an empty plasmid. Invasion of transfected cells through extracellular matrices was 25-58% lower than that of the controls. HPV was detected more frequently in placentas from spontaneous preterm deliveries than in placentas from controls (P = 0.03). Identification of HPV in placentas from cases of pre-eclampsia was not significantly different to controls. CONCLUSIONS HPV infection of extravillous trophoblast induces cell death and may reduce placental invasion into the uterine wall. Thus, HPV infection may cause placental dysfunction and is associated with adverse pregnancy outcomes, including spontaneous preterm delivery.
Two Rare Variants Explain Association with Acute Myocardial Infarction in an Extended Genomic Region Including the Apolipoprotein(A) Gene

Relatively low numbers of kringle 4 type 2 repeats in apolipoprotein(a) and specific haplotypes of the SLC22A3‐LPAL2‐LPA region on chromosome 6 are associated with an increased risk of coronary disease. We examined the possibility that rs3798220 and rs10455872, short variations located in LPA [the apolipoprotein(a) gene], and related to the number of kringle 4 type 2 repeats, may serve as markers for the association between haplotypes and acute myocardial infarction. Genotypes were determined with TaqMan assays in a sample of 2136 cases and 1211 controls. The minor alleles of rs3798220 and rs10455872 were associated with increased risks (rs3798220‐C: adjusted OR 2.14, 95% CI, 1.37–3.33, P = 0.00080; rs10455872‐G: adjusted OR 1.74, 95% CI 1.36–2.24, P < 0.00001). After adjustments were made for potential confounders, none of nine polymorphisms included in a haplotype analysis were singly related to disease. Two risk haplotypes were identified; one (CCTTGTGTG; OR 1.25, 95% CI 1.08–1.45, P = 0.0022) was correlated with rs3798220‐C and the other (CCCTGGATC; OR 1.65, 95% CI 1.14–2.38, P = 0.0074) with rs10455872‐G. Thus, the findings allowed for a more precise definition of risk‐associated markers: specific nucleotides in LPA instead of standard haplotypes defined by noneffective variants from the extensive SLC22A3‐LPAL2‐LPA region.
Fast profiling of the integral metabolism of flavonols in the active fraction of Gossypium herbaceam L. using liquid chromatography/multi-stage tandem mass spectrometry.

A method of fast profiling the constituents in an active herbal extract and their metabolites in biological fluids based on the combination of fragmentation behavior and metabolic pathways is described. The complementary information from fragmentation behavior and metabolic pathways helped not only to identify the structure of parent constituents and metabolites, but also to correlate metabolites back to their parent forms. An active fraction obtained from Gossypium herbaceam L. , named AB-8-2, and bile samples from rats administered it orally and intravenously were analyzed using high-performance liquid chromatography/multi-stage tandem mass spectrometry (HPLC-MSn) in a single chromatographic run. Fifty-eight flavonols comprising mixed sulfate, methyl, glucuronide and glycoside derivatives of quercetin or kaempferol were detected, including several groups of isomers. By contrasting the analytical results from AB-8-2 and from bile samples derived from different administration routes, a profile of the biotransformation of the flavonols in AB-8-2 was obtained. The results should be of benefit in targeting potential active ingredients in complex mixtures, such as herbs or their active extracts.
Nicotinamide N-methyltransferase enhances resistance to 5-fluorouracil in colorectal cancer cells through inhibition of the ASK1-p38 MAPK pathway

Nicotinamide N-methyltransferase (NNMT), which converts nicotinamide to 1-methylnicotinamide (1-MNA), is overexpressed in a variety of human cancers and serves as a potential anti-cancer target. In this study, we investigated the effect of NNMT on 5-fluorouracil (5-FU) sensitivity of colorectal cancer (CRC) cells, and the underlying mechanisms. Our results show that down-regulation of NNMT in CRC HT-29 cells diminishes 5-FU resistance, while over expression of NNMT in SW480 cells enhances it. NNMT reduces reactive oxygen species (ROS) production induced by 5-FU by increasing 1-MNA in CRC cells. The reduction in ROS leads to inactivation of the ASK1-p38 mitogen-activated protein kinase (MAPK) pathway, which reduces 5-FU-induced apoptosis. In vivo, NNMT attenuates 5-FU-induced inhibition of CRC tumor growth in nude mice. These observations suggest that NNMT and the 1-MNA it produces inhibit the ASK1-p38 MAPK pathway, resulting in increased CRC cell resistance to 5-FU.
Adolescent tibia vara: alternatives for operative treatment.

We reviewed the cases of fifteen obese patients (twenty-one extremities) who had had adolescent tibia vara and had been followed for at least two years. Of the nine patients (eleven extremities) who had been initially managed with lateral tibial hemiepiphyseodesis, eight (ten extremities) were skeletally mature at the time of the review (mean duration of follow-up, five years). The mechanical alignment was judged to be excellent in three of these ten extremities, fair in three, and poor in four. Excellent mechanical alignment was defined as a value within the reported normal range of 5 degrees of varus to 2 degrees of valgus. A poor result was defined as alignment that was more than 5 degrees outside the normal range. After secondary operative procedures, three of the extremities for which the result had been poor and one for which it had been fair had excellent alignment. Five of the nine patients had bilateral involvement. Two of them were managed with bilateral tibial hemiepiphyseodesis; two, with contralateral proximal tibial osteotomy; and one had a mild deformity on the contralateral side that was not treated. Six extremities in six patients (two of whom had a contralateral hemiepiphyseodesis) were managed primarily with proximal tibial osteotomy and were evaluated an average of seven years postoperatively. Two additional patients were managed with proximal tibial osteotomy because of residual varus deformity after the hemiepiphyseodesis. (ABSTRACT TRUNCATED AT 250 WORDS)
Topic models for image retrieval on large-scale databases

With the explosion of the number of images in personal and on-line collections, efficient techniques for navigating, indexing, labeling and searching images become more and more important. In this work we will rely on the image content as the main source of information to retrieve images. We study the representation of images by topic models in its various aspects and extend the current models. Starting from a bag-of-visual-words image description based on local image features, images representations are learned in an unsupervised fashion and each image is modeled as a mixture of topics/object parts depicted in the image. Thus topic models allow us to automatically extract high-level image content descriptions which in turn can be used to find similar images. Further, the typically lowdimensional topic-model-based representation enables efficient and fast search, especially in very large databases.
Dietary Influences on Blood Pressure: The Effect of the Mediterranean Diet on the Prevalence of Hypertension

Hypertension has long been recognized as a major risk factor for several common cardiovascular diseases. The World Health Organization reports that the number of people with hypertension worldwide is estimated at 600 million, while 3 million will die annually as a result of hypertension. There is evidence to support that several factors related to lifestyle habits may influence blood pressure levels. Among these, the beneficial effect of diet on human health, as well as on the control of hypertension, has been underlined in several studies. Moreover, adherence to a Mediterranean diet has been associated with reduced all‐cause mortality and, especially, coronary heart disease. The effect of this traditional diet on blood pressure levels has not been well understood and appreciated. This review summarizes the current understanding of the dietary influences on blood pressure control and the findings of observational and clinical studies that have evaluated the effect of the Mediterranean dietary pattern on the prevalence of chronic essential hypertension.
Autoformation en langues : quel guidage pour l'autonomisation ?

Dans le cadre de l'enseignement / apprentissage des langues en Master de didactique des langues a l'universite de Lille 3 sont proposes depuis deux ans des dispositifs d'autoformation guidee pour l'anglais, l'espagnol et le FLE. Ces dispositifs hybrides fonctionnent autour de plusieurs poles : un Centre de Ressources en Langues ou sont classees des ressources multimedia, des regroupements sous forme d'ateliers "apprendre a apprendre" et d'expression orale, une plateforme, lieu d'echanges et de travail collaboratif. Parallelement, des entretiens sont proposes aux etudiants a qui il est demande de rediger un journal d'apprentissage.Notre corpus est constitue de questionnaires remplis par les etudiants ayant participe au dispositif, croises avec les carnets de bord rediges au long de la formation. L'analyse des donnees semble aboutir a l'idee que l'autonomie ne se developpe pas dans toutes les activites de la meme maniere et surtout que l'on voit surgir differentes formes d'autonomie (autonomie generale, langagiere et d'apprentissage). Comment s'articulent ces elements constitutifs de l'autonomie ; la place qu'ils tiennent dans le dispositif est-elle fixe ou evolue-t-elle selon des etapes previsibles ? Nous avons essaye a partir de ces elements de faire surgir les tensions qui apparaissent entre guidage et autonomie. Ces notions semblent contradictoires en apparence, mais il apparait que certaines formes de guidage peuvent favoriser en fin de compte l'autonomie. Doit-on considerer qu'il s'agit alors d'un passage necessaire pour permettre ensuite de developper des strategies individuelles adaptees ? Notre objectif est de parvenir a comprendre selon quelle articulation ces elements doivent etre mis en place afin d'optimiser le dispositif d'autoformation.
Home based care and standard hospital care for patients with severe mental illness: a randomised controlled trial.

OBJECTIVE--To compare the efficacy of home based care with standard hospital care in treating serious mental illness. DESIGN--Randomised controlled trial. SETTING--South Southwark, London. PATIENTS--189 patients aged 18-64 living in catchment area. 92 were randomised to home based care (daily living programme) and 97 to standard hospital care. At three months' follow up 68 home care and 60 hospital patients were evaluated. MAIN OUTCOME MEASURES--Use of hospital beds, psychiatric diagnosis, social functioning, patients' and relatives' satisfaction, and activity of daily living programme staff. RESULTS--Home care reduced hospital stay by 80% (median stay six days in home care group, 53 days in hospital group) and did not increase the number of admissions compared with hospital care. On clinical and social outcome there was a non-significant trend in favour of home care, but both groups showed big improvements. On the global adjustment scale home care patients improved by 26.8 points and the hospital group by 21.6 points (difference 5.2; 95% confidence interval -1.5 to 12). Other rating scales showed similar trends. Home care patients required a wide range of support in areas such as housing, finance, and work. Only three patients dropped out from the programme. CONCLUSIONS--Home based care may offer some slight advantages over hospital based care for patients with serious mental illness and their relatives. The care is intensive, but the low drop out rate suggests appreciation. Changes to traditional training for mental health workers are required.
Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus

Activation and expansion of dengue virus‐specific T cells and abnormal liver functions in dengue patients have been documented. However, it remains to be determined whether T cells are involved in the pathogenic mechanism of dengue virus infection. In this study, immunocompetent C57BL/6 mice were employed to study dengue virus‐induced T cell activation. Mice were inoculated with 108 PFU dengue virus serotype 2 strain 16681 by the intravenous route. Dengue viral core RNA was detected by RT‐PCR in mouse serum, liver, spleen, and brain at different time points after infection. Splenic T cells were activated as evidenced by their expression of CD69 and O‐glycosylated CD43 at as early as day 3 after infection. Splenic T cell expression of O‐glycosylated CD43 and IFN‐γ production coordinately peaked at day 5. Coincided with the peak of splenic T cell activation was hepatic lymphocyte infiltration and elevation of liver enzymes. Flow cytometric analysis revealed the infiltrating CD8+ T cell to CD4+ T cell ratio was 5/3. After a second inoculation of dengue virus, hepatic T cell infiltration and liver enzyme levels increased sharply. The infiltrating hepatic CD8+ T cell to CD4+ T cell ratio increased to 5.8/1. A strong correlation was found between T cell activation and hepatic cellular infiltration in immunocompetent mice infected with dengue virus. The kinetics of liver enzyme elevation also correlated with that of T cell activation. These data suggest a relationship between T cell infiltration and elevation of liver enzymes. J. Med. Virol. 73:419–431, 2004. © 2004 Wiley‐Liss, Inc.
Muscle dysfunction in male hypogonadism

ABSTRACT Twenty‐eight consecutive male patients with primary and secondary hypogonadism (14 each) were evaluated clinically and electrophysiologically for muscle dysfunction. Although generalised muscle weakness was initially reported by only 9 patients, on direct questioning, it was recorded in 19. Objective weakness was found in 13 patients and it involved both the proximal and distal limb muscles. Quantitative electromyography showed evidence of myopathy in the proximal muscle in 25 patients, i.e., reduced MUP duration and amplitude with increased polyphasia in the deltoid and the gluteus maximus. There were no denervation potentials. None of the patients showed clinical neuropathy or NCV abnormalities. Thus, the profile of muscle involvement in hypogonadism closely simulates limb‐girdle muscular dystrophy and other endocrine myopathies. The incidence of muscle involvement was higher in secondary hypogonadism. Diminished androgens in primary hypogonadism and diminished growth hormone in the secondary hypogonadism are probably responsible for the myopathy.
In vivo replicative status and envelope heterogeneity of equine infectious anemia virus in an inapparent carrier

The distribution and replicative status of equine infectious anemia virus (EIAV) DNA in the tissues of a well-characterized inapparent carrier horse were established by using the PCR technique. The EIAV pol region could be amplified in all of the tissues tested, including the cerebellum and periventricular tissue, at concentrations approximately 10(5)-fold less than in the same tissue from an acutely infected horse. Further analysis of the EIAV genome, with primer pairs diagnostic for sequential stages of reverse transcription, suggests that EIAV DNA in the brain, liver, and lymph nodes was incompletely synthesized. The products of reverse transcription were found to diminish progressively during first-strand synthesis, while products indicative of second-strand synthesis were observed only in kidney and spleen DNA samples. Sequences specific for different regions of the envelope could not be amplified from any of the tissues of the inapparent carrier, suggesting that the envelope is highly variable and may be subject to extensive drift. Together, the data suggest that low levels of EIAV replication persist without causing clinical disease in an inapparent carrier.
Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations

Summary Aim: Investigation of the biodistribution and calculation of dosimetry of Ga-68-DOTATOCfor patients imaged in the routine clinical setting for diagnosis or exclusion of neuroendocrine tumours. Patients, methods: Dynamic PET/CT-imaging (Biograph 16) was performed over 20 min in 14 patients (8 men, 6 women) after injection of (112 ± 22) MBq 68Ga-DOTATOC followed by whole body 3D-acquisition (8 bed positions, 3 or 4 min each) 30 min p.i. and 120 min p.i. Urinary tracer elimination was measured and blood activity was derived non-invasively from the blood pool of the heart. The relevant organs for dosimetry were spleen, kidneys, liver, adrenals, urinary bladder and pituitary gland. Dosimetry was performed using OLINDA/ EXM 1.0 software and specific organ uptake was expressed as standardized uptake values (SUVs). Results: Rapid physiological uptake of the radiotracer could be demonstrated in liver, spleen and kidneys, adrenals and pituitary gland (mean SUVs were 6, 20, 16, 10, and 4, respectively). Radiotracer elimination was exclusively via urine (16% of injected dose within 2h); no redistribution could be observed. The spleen and the kidneys received the highest radiation exposure (0.24 mSv/MBq, 0.22 mSv/MBq resp.), mean effective dose yielded 0.023 mSv/MBq. Conclusion: 68Ga-DOTATOC is used extensively for diagnosis of somatostatin receptor positive tumours because it has several advantages over the 111In-labelled ligand. The derived dosimetric values are lower than first approximations from the biological data of OctreoScan. The use of CT for transmission correction of the PET data delivers radiation exposure up to 1 mSv (low dose).
Registered report: Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from "Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF" by Heidorn and colleagues, published in Cell in 2010 (Heidorn et al., 2010). The experiments to be replicated are those reported in Figures 1A, 1B, 3A, 3B, and 4D. Heidorn and colleagues report that paradoxical activation of the RAF-RAS-MEK-ERK pathway by BRAF inhibitors when applied to BRAFWT cells is a result of BRAF/CRAF heterodimer formation upon inactivation of BRAF kinase activity, and occurs only in the context of active RAS. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. DOI: http://dx.doi. org/10.7554/eLife.11999. 001
Early Reading Instruction for Children with Reading Difficulties

Several multiple-probe-across-participants design studies were employed to evaluate the effectiveness of a supplemental tutoring intervention using Read Well (Sprick, Howard, & Fidanque, 1998—2000). In Year 1, we conducted two studies with 7 first-, second-, and third-grade children (1 girl and 6 boys), who were classified as having learning disabilities, having attention-deficit disorder, or being English language learners and were identified by their teachers as poor readers. The results of the two studies indicated that 3 of the 5 children who received Read Well instruction showed improvement in passage fluency. Student performance on other measures of reading and comprehension was varied. Differences in student characteristics and in the amount of Read Well instruction received (2 to 7 weeks) seemed to account for the differences in performance. In Year 2, we implemented the same tutoring intervention for a longer duration (up to 16 weeks) and included 5 children in second and third grades (2 girls and 3 boys) with reading difficulties. Two of these children had previously participated in the Year 1 studies. The results indicated growth in reading, spelling, and comprehension for most children. Overall, the findings from Year 1 and 2 studies indicate the benefits of increased instructional intensity and duration for children who struggle with emerging reading skills.
Current pharmacotherapy for hepatitis B infection

Chronic infection with the hepatitis B virus (HBV) affects 350 million people worldwide, or approximately 5% of the global population, and commonly results in cirrhosis and hepatocellular carcinoma. Until recently, the only available treatment was injectable interferon alpha and response rates were suboptimal. Moreover, this expensive and toxic therapy had little applicability in the endemic regions of the world, i.e., Asia and Africa. The realisation that orally available nucleoside and nucleotide agents may effectively control this infection opened a new era in the management of chronic hepatitis B. Oral lamivudine recently became approved for treatment of hepatitis B worldwide. It is free of significant toxicity, improves liver histology and rapidly diminishes HBV DNA levels; lamivudine is expected to become the first-line therapy of choice. Nevertheless, the consistent emergence of lamivudine-resistant variants mandates the need to develop additional therapeutic agents. Adefovir dipivoxil, a nucleotide, and entecavir, a nucleoside agent, are promising new drugs that might eventually be used in combination with lamivudine and therefore reduce the incidence of drug resistance. There is a critical need to advance the research of hepatitis B antiviral agents so that effective combination therapies can become widely available.