Miracle-dz/UniFAR-FTUs huggingface dataset:
Use and perceived relevance of health-related Internet sites and online contact with peers among young people with juvenile idiopathic arthritis.

OBJECTIVE To evaluate the frequency of use and relevance of health-related Internet (HRI) sites and online peer support groups and their association with demographic, disease-related and psychosocial variables in young people with JIA. METHODS In a cross-sectional study, 176 young people (10-27 years of age) with JIA were asked to complete a questionnaire. The frequency of using HRI sites (regarding information, medication use and aspects of JIA relating to social life), online peer contact and perceived relevance of HRI sites and online peer communication were determined. Associations with demographic variables, disease activity, medication, emotional behaviour and coping were also examined. RESULTS Seventy-one per cent of the 142 respondents had used the Internet to search for general information on JIA, but specific topics, such as medication, were searched for less often. Twenty-five per cent of respondents had visited a forum or had contacted peers online. The perceived relevance of HRI sites and online peer contact was rated low (median 2.0 and 1.0, respectively; scale 0-10). Apart from female gender (P < 0.01), none of the demographic and disease-related factors were associated with HRI site use. Coping styles, confrontation and reassuring thoughts were associated with increased HRI site use, but only in males. Internalizing and externalizing problem behaviour were not significantly associated. CONCLUSION The frequency of HRI site use among young people with JIA was less than expected and was considered of low relevance. HRI sites in their present form cannot replace traditional information as an additional source to increase knowledge.
A Multi-domain Fragment of Nogo-A Protein Is a Potent Inhibitor of Cortical Axon Regeneration via Nogo Receptor 1*

Nogo-A limits axon regeneration and functional recovery after central nervous system injury in adult mammals. Three regions of Nogo-A (Nogo-A-24, Nogo-66, and Nogo-C39) interact with the neuronal Nogo-66 receptor 1 (NgR1). Nogo-66 also interacts with a structurally unrelated cell surface receptor, paired immunoglobulin-like receptor (PirB). We show here that the other two NgR1-interacting domains, Nogo-A-24 and Nogo-C39, also bind to PirB with high affinity. A purified 22-kDa protein containing all three NgR1- and PirB-interacting domains (Nogo-22) is a substantially more potent growth cone-collapsing molecule than Nogo-66 for chick dorsal root ganglion neurons and mature cortical neurons. Moreover, Nogo-22 inhibits axon regeneration of mature cortical neurons in vitro more potently than does Nogo-66. Although all three NgR1-interacting domains of Nogo-A also interact with PirB, expression of PirB in mature cortical cultures is nearly undetectable. Consistent with a relatively minor role for PirB in mature cortical neurons, Nogo-22 inhibition of axon regeneration is abolished by genetic deletion of NgR1. Thus, NgR1 is the predominant receptor for Nogo-22 in regenerating cortical neurons.
The role of cFLIP in breast cancer stem cells

Breast tumours have intrinsic heterogeneity. The cancer stem cell hypothesis is currently challenging the notion that all cancer cells are equally malignant, suggesting that it is important to evaluate the efficacy of potential anti-cancer drugs by their ability to target the stem-like population. TRAIL is a cytotoxic agent the efficacy of which has been limited by a lack of patient stratification in clinical trials (Lemke 2014). In pre-clinical studies TRAIL has shown specificity towards mesenchymal-like breast cancer cell lines (Rahman et al. 2009) We show here that TRAIL is able to target the tumoursphere-forming population of four out of six breast cancer cell lines, including two epithelial-like lines, the bulk population of which is TRAIL-resistant. Furthermore, TRAIL also reduced the tumour-initiating capacity of the MCF-7 line. In addition, we have also investigated a paracrine mechanism of sensitising breast cancer cell lines to TRAIL. We have shown that a soluble factor produced by MDA-MB-231 cells, fibroblasts, and cancer-associated fibroblasts (CAFs) can sensitise both MCF-7 cells and SKBR3 tumoursphere-forming cells to TRAIL. Our data shows that cytoplasmic levels of Cellular FLICE-Like Inhibitory Protein (cFLIP) – a naturally occurring inhibitor of TRAIL’s cell toxicity effects- are lower in TRAIL-sensitive cells and suggest that tumoursphere populations are TRAIL-sensitive due to the re-localisation of cFLIP to the nucleus. We believe cFLIP is nuclear in stem-like cells due to a role as a promoter of the Wnt pathway. We have shown that inhibition of cFLIP by siRNA resulted in a reduction in both beta-catenin protein levels and Wnt-target gene transcription in both the MCF-7 and MDA-MB-231 breast cancer cell lines. We have also demonstrated a novel role for cFLIP as a promoter of bCSC maintenance. We have found that inhibition of cFLIP by shRNA decreased the self-renewal of tumoursphere-forming cells and also reduced colony formation. As TRAIL alone does not completely eradicate tumoursphere-forming or tumour-initiating cells in any breast cancer cell line, we believe our data are evidence of bCSC heterogeneity existing in terms of susceptibility to TRAIL. We propose a model of phenotypic heterogeneity within breast cancer cell lines and bCSCs whereby there exist two populations of cells which can be distinguished based on TRAIL susceptibility correlating with the known distinction of epithelial-like or mesenchymal-like status and our novel observation of cFLIP localisation. While these findings are currently restricted to cell lines, if confirmed in primary breast cancer cells, the clinical implication of our model is that although TRAIL alone is a potential therapy, a much more effective therapeutic strategy would be to also inhibit cFLIP, the consequences of which would not just be a sensitisation to TRAIL but also a reduction in Wnt signalling, and potentially a reduction in bCSC self-renewal and proliferation.
Isokinetic assessment and interpretation in paediatric populations: Why do we know relatively little?

Our understanding of the age and sex associated development in dynamic strength is based on a relatively small evidence base. This may be due in part to the proposed ethical difficulties in assessing paediatric populations combined with the expense associated with longitudinal studies. Despite this isokinetic testing of children has doubled in the last 5 years and has started to include data on clinical populations. A number of studies have demonstrated that isokinetic testing in children can be reliable given appropriate adaptations to equipment as well as the application of paediatric specific procedures, especially the inclusion of extensive habituation and familiarisation sessions. Data on the age and sex associated differences in dynamic strength are relatively consistent, indicating little sex differences up until the age of about 13/14 years. However changes in dynamic strength with age and maturation appear to be both muscle group and muscle action specific. Where comparisons of children of differing chronological or biological age are to be made appropriate allometric scaling techniques need to be employed to control for differences in body size. Studies on dynamic strength in children should begin to move away from descriptive studies and start to explore the mechanisms associated with the changes in strength, as well as applying findings to practical situations (for example injury prevention). More studies are needed on clinical populations to help to define decrements in dynamic strength and to help in applying appropriate strengthening programmes to enhance quality of life.
EFL materials in public school classrooms in Saudi Arabia: an investigation of the extent to which teachers engage in materials/textbooks development in order to design learning experiences to meet the needs of their students as an indicator of teacher autonomy

This study aims to investigate the ways in which EFL teachers in Saudi Arabia use, design, and evaluate their teaching materials, in a context where teachers are expected to use only the prescribed textbooks inside the classroom. The extent to which teachers supplement and adapt the set textbook is used as an indicator of their willingness and ability to adapt their teaching in response to the needs of the learners in their classrooms. Saudi teachers’ willingness and ability to take control of their personal teaching and learning in this way is investigated using Huang’s framework of autonomy. The study explores the different responses of the teachers in the study to the policy of the Ministry of Education regarding the use of the prescribed textbook and the extent to which through their use, design and evaluation of teaching materials, teachers are able to enhance their professionalism. Data was collected using classroom observations and semi-structured interviews of 6 male EFL (English as a Foreign Language) teachers in Saudi public schools and analysed using Narrative and Grounded theory approaches. The hybrid approach adopted for this study proved useful in uncovering much rich information about teachers’ perceptions about and use of the textbook and the implications of the extent to which they engaged in materials development in response to the needs of their students. The study revealed different perceptions and degrees of responsiveness to the need to adapt materials for the learners in the classroom. In some instances, whilst teachers described themselves as exercising autonomy the observation of classroom practice was not entirely consistent with such a perception. Conversely, some teachers were more proactive in the classroom than responses in interviews might suggest. The study builds on previous work into the trend for learners in EFL classrooms in Saudi Arabia to exercise more learner autonomy and the relationship between learner demands, the capacity of teachers to engage in materials development and teacher professionalism is examined. The study concludes that more research into providing scope for adaptation and variation in the use of textbooks in EFL in classrooms in Saudi Arabia could shed light on how institutional and personal constraints on teacher autonomy could be mediated without jeopardising the quality and consistency of learning and teaching.
Adherence to Antiretroviral Therapy: The Emerging Role of HIV Pharmacotherapy Specialists

Despite the availability of 25 antiretroviral agents to treat HIV infection and the significant progresses made in the clinical pharmacology of HIV drugs, viral suppression and immune restoration remain problematic in a large number of HIV-infected persons. One of the main factors responsible for this partial therapeutic success is the difficulty patients have adhering consistently to antiretroviral therapy. Barriers to adherence are diverse and complex and evolve over time, complicating the monitoring of medication-taking behaviors. Consequently, multilevel interventions are often needed to address thoroughly adherence issues. Given the rapid and constant evolution of HIV treatments, innovative multidisciplinary programs integrating HIV pharmacotherapy specialists, as the “medication expert,” are being implemented. Because of his or her advanced knowledge of antiretrovirals, the HIV pharmacotherapy specialist is highly qualified to evaluate patients with complex regimens who are facing barriers to successful care and who need tailored interventions and long-term follow-up.
Genetic Susceptibility to Arsenic Exposure and Arsenical Skin Lesion Prevalence in Bangladesh

Genetic Susceptibility to Arsenic Exposure and Arsenical Skin Lesion Prevalence in Bangladesh Maria Argos Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. While arsenic is an established human carcinogen, a mode of action has yet to be determined for arsenic carcinogenesis. However, the oxidative stress and DNA repair pathways have been implicated in arsenic toxicity and have been hypothesized to underlie arsenic carcinogenesis. To date, few epidemiologic studies have evaluated genetic susceptibility to arsenical skin lesions based on single nucleotide polymorphisms (SNPs) in antioxidant enzyme or DNA repair genes. Utilizing crosssectional data from the 2000-2002 survey of the Health Effects of Arsenic Longitudinal Study (HEALS) for 610 prevalent arsenical skin lesion cases and 1,079 randomly selected controls, I evaluated the associations of SNPs in genes encoding antioxidant enzymes and DNA repair enzymes on skin lesion prevalence. I also evaluated potential interactions between the SNPS as well as SNP-environment interactions in determining skin lesion prevalence. In the first study of this dissertation (Chapter 2), I assessed the relationship between SNPs in antioxidant enzyme genes and skin lesion prevalence, as well as possible interactions of these associations on the additive scale by various environmental factors. There were no statistically significant associations between these SNPs (SOD2, rs4880; CAT, rs1001179; GPX1, rs1050450; and MPO, rs2333227) and skin lesion prevalence. Additionally, there was no evidence of additive interaction by arsenic
Évaluation des indications hors AMM chez des patients adultes traités par chimiothérapie anticancéreuse

Le but de notre travail etait d’evaluer la proportion d’ordonnances hors AMM, en termes d’indications, chez des patients adultes traites par chimiotherapie anticancereuse aux Hopitaux universitaires de Strasbourg. Les prescriptions de chimiotherapie administrees en hopital de jour ont ete analysees de maniere prospective par un pharmacien durant l’annee 2002. Les donnees concernant le type de cancer et l’indication de l’agent anticancereux ont ete recueillies et comparees au resume des caracteristiques du produit. Parmi les 6 168 prescriptions analysees (1 206 patients), 415 (6,7 %) presentaient un agent anticancereux utilise dans une indication hors AMM. Les prescriptions hors AMM etaient frequemment observees chez des patients atteints de cancers de la prostate hormonoresistants (57,6 % des ordonnances pour cette indication) et chez des patients atteints de tumeurs de la vessie (37,6 % des ordonnances). Aucune indication hors AMM n’a ete relevee chez des patients atteints de cancers colorectaux. Les agents anticancereux utilises le plus frequemment dans une indication hors AMM etaient le docetaxel (29,1 % des ordonnances) et l’oxaliplatine (23,6 %). En conclusion, l’utilisation d’agents anticancereux dans des indications hors AMM chez des patients adultes apparait peu frequente dans notre hopital.
A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H)

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disease characterized by progressive heterotopic endochondral osteogenesis with great‐toe malformations. A 617G > A (R206H) mutation of the activin A type 1 receptor gene (ACVR1) has been found in all previously reported patients with FOP. Thus, this is one of the most specific of all disease‐associated mutations. We report here on a 62‐year‐old man with slowly progressive FOP and a novel mutation in ACVR1. He developed difficulty in moving his shoulder since age 10 years due to contraction of the shoulder joint. The symptoms progressed slowly, and he could not walk at age 36 years and was bedridden at 55 years. He also showed rigid spine, baldness, sensorineural hearing loss, and hypodactyly accompanied by abnormal ectopic ossification. Analysis of ACVR1 and its cDNA revealed that the patient is heterozygous for a mutation, 1067G > A (G356D). Typing of SNPs located in the ∼0.5‐Mb region spanning ACVR1 and its neighbor genes suggested that 1067G > A is a de novo mutation. These results give a clue to better understanding of FOP as well as of the mild clinical symptoms in the patient. © 2008 Wiley‐Liss, Inc.
Hepatitis C Virus NS5B Protein Delays S Phase Progression in Human Hepatocyte-derived Cells by Relocalizing Cyclin-dependent Kinase 2-interacting Protein (CINP)*

Cell cycle dysregulation is a critical event in virus infection-associated tumorigenesis. Previous studies have suggested that hepatitis C virus NS5B modulates cell cycle progression in addition to participating in RNA synthesis as an RNA-dependent RNA polymerase. However, the molecular mechanisms have thus far remained unclear. In this study, a HepG2 Tet-On NS5B stable cell line was generated to confirm the effect of NS5B on the cell cycle. To better understand the role of NS5B in cell cycle regulation, yeast two-hybrid assays were performed using a human liver cDNA library. The cyclin-dependent kinase 2-interacting protein (CINP) was identified. The interaction between NS5B and CINP was further demonstrated by in vivo and in vitro assays, and their association was found to be indispensable for S phase delay and cell proliferation suppression. Further experiments indicated that NS5B relocalized CINP from the nucleus to the cytoplasm. Directly knocking down CINP by specific siRNA resulted in a significant alteration in the DNA damage response and expression of cell cycle checkpoint proteins, including an increase in p21 and a decrease in phosphorylated Retinoblastoma and Chk1. Similar results were observed in cells expressing NS5B, and the effects were partially reversed upon ectopic overexpression of CINP. These studies suggest that the DNA damage response might be exploited by NS5B to hinder cell cycle progression. Taken together, our data demonstrate that NS5B delays cells in S phase through interaction with CINP and relocalization of the protein from the nucleus to the cytoplasm. Such effects might contribute to hepatitis C virus persistence and pathogenesis.
FACTORES ASOCIADOS A MORTALIDAD POR NEUMONIA EN UN HOSPITAL DE TERCER NIVEL DE COLOMBIA

Objetivos: Determinar las variables asociadas con mortalidad por Neumonía Adquirida en la Comunidad (NAC) en hospital de Colombia Materiales y métodos: Estudio de corte transversal en pacientes mayores de 14 años con diagnóstico de NAC entre 1 enero 2010 y 30 marzo 2012. Se consideraron variables socio-demográficas, clínicas, paraclínicas y terapéuticas. Se hicieron análisis bivariados y multivariados con paquete estadístico SPSS-20.0 Resultados: De 297 casos con NAC, hubo predominio masculino (53,5%), edad promedio 56,3±22,4 años. El 22,6% de los casos murieron. Las variables ausencia de dolor pleurítico (OR:0,10; IC95%:0,040-0,292, p
Monozygotic twins discordant for trisomy 21 and maternal 21q inheritance: A complex series of events

We report on a monochorionic/diamniotic twin pregnancy discordant for trisomy 21. Amniocentesis (at ${\rm 13}{\raise0.5ex\hbox{$\scriptstyle {\rm 5}$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle {\rm 7}$}}$ weeks) was performed following ultrasound signs of hydrops and cystic hygroma in twin 1 (T1). Prenatal karyotype showed non‐mosaic trisomy 21 in T1 (47,XX,+21[7]), and low‐grade mosaic trisomy 21 in twin 2 (T2) (47,XX,+21[2]/46,XX[19]). Post mortem examination of fetal skin, kidneys and lungs confirmed trisomy 21 in T1 (47,XX,+21[548]) and the placenta (47,XX,+21[200]). T2 had a normal karyotype (46,XX[648]). Analysis of microsatellite polymorphisms in multiple samples from the placenta, hand, lungs, kidneys and the umbilical cords of both twins confirmed monozygosity for all loci tested, and trisomy 21 in T1. Unexpectedly, T1 and T2 inherited different maternal alleles for markers of the most distal 4 Mbp of 21q. At least four successive events are needed to explain the genetic status of both twins and include maternal MI premature chromatids separation or maternal II meiotic nondisjunction and post‐zygotic events such as, chromosome rescue, nondisjunction, an/or recombination. © 2008 Wiley‐Liss, Inc.
Quantitative measurement of 18F-FDG PET/CT uptake reflects the expansion of circulating plasmablasts in IgG4-related disease

Objective [18F]Fluorodeoxyglucose (18F-FDG) PET/CT is increasingly used to assess organ involvement and response to treatment in IgG4-related disease (IgG4-RD), but clear correlations between 18F-FDG uptake and disease activity have not been established yet. We aimed to correlate the intensity and distribution of 18F-FDG uptake with validated clinical, serological and immunological parameters of IgG4-RD activity. Methods Twenty patients with active IgG4-RD underwent a baseline 18F-FDG PET/CT. Ten patients repeated 18F-FDG PET/CT after immunosuppressive treatments. 18F-FDG tissue uptake was measured using the standardized uptake value corrected for the partial volume effect (PVC-SUV) and the total lesion glycolysis (TLG) with (TLGtot+ln) and without (TLGtot-ln) lymph nodes. Disease activity was assessed by means of clinical parameters [IgG4-RD Responder Index (RI)], serological (ESR and CRP) and immunological (serum IgG4 and circulating plasmablasts) biomarkers. The enhanced liver fibrosis score was exploited as a biomarker for fibroblast activation. Results Thirteen (65%) patients had two or more organs affected by IgG4-RD. All patients had active IgG4-RD as defined by a median IgG4-RD RI value of 9 (range 6-15; normal < 3). Serum IgG4 and plasmablasts were elevated in 85% of patients. Circulating plasmablasts positively correlated with PVC-SUV (P = 0.027), inversely correlated with TLGtot-ln (P = 0.023) and did not correlate with TLGtot+ln (P > 0.05). No statistically significant correlation was found between PVC-SUV or TLG and IgG4-RD RI, ESR, CRP, serum IgG4 or enhanced liver fibrosis score (P > 0.05). Clinical response to immunosuppressive therapies was associated with a consensual reduction of circulating plasmablasts, PVC-SUV, TLGtot+ln and TLGtot-ln values (P < 0.05 for all comparisons). Conclusions 18F-FDG uptake of IgG4-RD lesions reflects immunological perturbations of the B cell compartment rather than fibroblast activation and extracellular matrix deposition. Conventional biomarkers of disease activity, namely IgG4-RD RI, ESR, CRP and serum IgG4 levels, do not appear to correlate with the radiometabolic activity of IgG4-RD lesions. In light of our results PET/CT represents a reliable instrument for assessing IgG4-RD activity, although lymph-node uptake deserves careful interpretation.